Spring 2012

_________

Vol. III No. 2

UIC Bioengineering Student Journal

UBSJ

University of

Illinois at Chicago

Bioengineering Student Journal

Spring 2012 Vol. III No. 2

CHIEF EDITOR

Carson Ingo

EDITORS Cierra M. Hall

Benjamin L. Schwartz

REVIEWERS Lara Ansari

Helen Ashaye Aimee Bobko

Nikhil Bommakanti Rudhram Gajendran

Mina Khalil Noman A. Khan

Andre Paredes Rachna Parwani

Dan Yu Julia Zelenakova

COVER ARTIST Lara Ansari

FACULTY ADVISOR Professor Richard L. Magin

Contact: bioejour@uic.edu

phone: (312) 996 – 2335 fax: (312) 996 - 5921 UIC Bioengineering Student Journal

Department of Bioengineering, University of Illinois at Chicago, Science & Engineering Offices (SEO), Room 218 (M/C 063)

UBSJ IS A UNIVERSITY OF ILLINOIS AT CHICAGO BIOENGINEERING

STUDENT PUBLICATION

UIC Bioengineering Student Journal Spring 2012

Vol. III No.2

Contents

Foreword

i

TAILORING THE RF PULSE: A SURVEY OF PULSE SHAPE EFFECTS

ON MAGNETIZATION WITH FOCUS ON RECT AND SINC PULSES

Lara Ansari

1

THE ROLE AND IMPACT OF ULTRASOUND GUIDED

TECHNOLOGY FOR REGIONAL ANESTHESIA PLACEMENT

Aimee Bobko

6

A REVIEW OF APPLICATIONS USING CURRENT MRI TECHNOLOGIES

Noman Ali Khan

12

BASICS OF MAGNETOENCEPHALOGRAPHY AND ITS

APPLICATIONS AS AN EXPERIMENTAL TOOL

Vu Nguyen

17

MEDICAL SIMULATIONS OF INTRATHECAL MORPHINE

FOR PAIN CONTROL AND MANAGEMENT

Jamie M. Stewart

21

APPLICATION OF NUCLEAR MAGNETIC

RESONANCE IN POROUS MEDIA

Dan Yu

26

VIEWING INTERVERTEBRAL DISC PROPERTIES OF

RODENT ANIMALS THROUGH MORPHOLOGY AND MRI

Julia Zelenakova

32

Call For Papers

37

Image Credits 38

i

Foreword

I am very lucky to have been a part of the editorial board of this journal, a wholly student-driven

publication that demonstrates the caliber of instruction and atmosphere of cooperation within the

department of Bioengineering at the University of Illinois at Chicago. Publications in peer-

reviewed journals are the coin of the realm in Academia, so it behooves bioengineering students

to hone this craft just as they would, e.g. mathematical analysis. The rigorous review process

each author must navigate—and which each reviewer must exact—has made for invaluable

practice in both scientific writing and the critiquing thereof. To my knowledge, a publication of

this nature is rare among engineering programs in American universities, highlighting the role

UIC has played in leading the charge of bringing the discipline of bioengineering the formal

recognition it now enjoys globally. It is my wish that our work—writing, editing, reviewing—

will inspire students to contribute their time and effort to future issues of this journal that it may

become an even brighter example of the good science we do here. Finally, I hope that this

journal serves, in part, as the face of UIC Bioengineering. Prospective students will see not only

the vast ocean of knowledge open to them, but that their learning and growth as engineers is

recognized and celebrated by our community. Prospective faculty, by reading the UBSJ, will see

a department that engenders cooperation among researchers, instructors, and students, alike. My

deep thanks go to all the students who have helped to make this issue a reality. We are all now

part of something larger than ourselves and our sum.

Benjamin L. Schwartz

Editor

1

TAILORING THE RF PULSE: A SURVEY OF PULSE SHAPE EFFECTS

ON MAGNETIZATION WITH FOCUS ON RECT AND SINC PULSES Lara Ansari

lansar2@uic.edu

Abstract Radiofrequency (RF) pulse design is an active research focus for many engineers and scientists

studying MRI and its advancement. Particularly, the shape of the RF pulse is of vast importance to

the reconstruction of images in k-space using Fourier Tansforms (FT), as well as the optimization

of signal transduction and correction of magnetic field inhomogeneities for high-field applications.

In this paper, a brief overview of the different types of RF pulses and algorithms commonly used

today are introduced, highlighting the RECT and SINC pulse shapes in both their physical

interactions with the magnetization vector, as well as their respective mathematical descriptions.

An overview of the basic factors influencing RF pulse design and the considerations taken when

concerned with high magnetic field applications is also presented here. The concept of Specific

Absorption Rate (SAR) is addressed as a clinical example of the importance of diversity in RF

pulse tailoring methods, as certain design algorithms such as the Shinnar-LeRoux (SLR)

algorithm for arbitrary tip angles and the design of more specific pulse shapes can influence SAR.

Programming applications such as MATLAB are discussed in their relevance to the advancement

of the field, and reference to Amir Stricker’s work in designing an RF pulse design toolkit for

MATLAB is presented. This paper is predominantly concerned with basic RF pulse shape effects

on magnetization of spins due to the variable characteristics of the pulse shape itself—and thus

the basis for customized tailoring of RF pulses with SLR, though the discussion here is not

concerned with the explanation of the SLR algorithm or other means of shaping RF pulses beyond

the RECT or SINC forms.

Keywords: RF Pulses, pulse sequences, SLR Algorithm, SINC, RECT, pulse shaping, SAR,

MATLAB, nuclear induction, frequency profiling, FWHM

1. Introduction

When a patient is subjected to a homogeneous,

constant magnetic field, B0, the net magnetization of

the protons aligned in his body lies upon the z-axis in

the direction of the field (assuming the +z-axis points

head-to-toe of the patient, the +x-axis left-to-right,

and the +y-axis back-to-front).

In order to communicate with these protons in

precession and generate a response in the form of an

―echo‖ capable of being detected by the receiving

radiofrequency coil, a pulsed magnetic field must be

applied in order to perturb the proton spins such that

they are forced out of their equilibrium state at the

precessing (Larmor) frequency. Due to this

perturbation, the protons are forced to return to

equilibrium while releasing the energy absorbed

during their original deflection from the z-axis. This

energy in the form of a radiofrequency wave can then

be received by the detecting radiofrequency coil.

If energy in the radiofrequency region of the

electromagnetic spectrum is released as the protons

are returned to equilibrium, the communicating

pulsed magnetic field must be carried by a

radiofrequency pulse.

A radiofrequency (RF) pulse can be described by the

following characteristics [4]:

(1) Its pulse amplitude – A1(t)

(2) Its pulse envelope – E1(t)

(3) The pulse carrier frequency – ω1

(4) The pulse duration – τ

Each RF pulse characteristic is vital to the

communication of information that allows one to

manipulate the net magnetization of multiple nuclei

precessing in a constant magnetic field, such as that

within the patient previously mentioned.

The RF Envelope is a slowly varying function in the

time domain with respect to the carrier frequency,

and comprises the shape of the radiofrequency pulse

[1]. It is a result of filtering the RF waveform in order

Tailoring the RF Pulse: A Survey of Pulse Shape Effects on Magnetization—L. Ansari

2

to restrict its effective bandwidth between two

frequency boundaries.

The RF pulsed waveform generated by the actual RF

coil of the MRI hardware is a higher-frequency

―carrier‖ waveform that modulates (or multiplies) the

RF envelope waveform. This RF carrier frequency is

what is set to the proton’s Larmor frequency, with an

offset of ±Δf, the pulse bandwidth, and is what allows

only select protons comprising a specific slice

location to respond to the RF pulse. The pulse

duration can be described as the pulse width, and is

measured in units of seconds.

Another parameter that may characterize an RF pulse

is in terms of the flip angle (α) it is capable of

inducing in the net magnetization vector from

equilibrium [2]. Flip angle is also a parameter

affected by the RF pulse shape, as it can be calculated

as the area contained beneath the RF pulse envelope.

Equation 1, below, illustrates this in terms of E1(t)

(the pulse envelope), A1(t) (the pulse amplitude), τ

(the pulse duration), and a constant, γ, known as the

gyromagnetic ratio [1,3]:

α = γ = γ A1(t) (1)

The flip angle is represented as the integral of the RF

envelope over a pulse duration of d , multiplied by

the gyromagnetic ratio. From equation 1 it is evident

that the amplitude, A1(t)—or the magnitude of the

pulsed magnetic field at time t for small

approximations of α and , also written as B1(t)—

varies the flip angle directly. This is another manner

in which the shape of an RF pulse determines the

manipulations of the magnetization vector,

illustrating the importance of proper RF pulse

selection and RF pulse design.

The basis and need for RF pulse ―tailoring‖, or

customization, such as by means of methods like the

Shinnar-Leigh-LeRoux (SLR) algorithm, are

presented in this paper through the explanation of

basic RECT and SINC pulse applications and effects

on image characteristics in MRI, as well as through

the acknowledgement of more clinical considerations

such as SAR, and corrections in high-field

applications.

2. Basic Pulses

RF Pulse shaping, tailoring, and manipulating all

simply refer to designing the RF pulse envelope in

such a way as to allow the RF pulse to selectively

excite spins [4] in an effective and anticipated

manner.

Basic pulse shapes include the RECT and SINC

waveforms, SINC being the more commonly used as

opposed to RECT. For applications not requiring

customizability of RF pulses, such as in imaging in

low-fields (clinical field ranges up to 3T), selection

of a common RF pulse such as SINC, Gaussian, or

truncated-SINC can be sufficient to invoke a proper

image for diagnostic purposes.

However, more advanced methods that are intended

for optimizing an RF pulse under highly specific or

more unique cases (such as for field inhomogeneities)

might require design algorithms such as SLR.

The following sections introduce the RECT and

SINC pulses.

2.1 RECT Pulse

The RECT pulse is simply a hard RF pulse with few

practical applications on its own in diagnostic

imaging. Figure 1, below, shows a basic RECT pulse.

Often it is replaced with other ―windowed‖ pulse

shapes such as a half-sine pulse, or even a simple

ramp-shaped RF pulse such as the TRAP pulse, in

order to compensate for waveform discontinuities

often resulting in low-fidelity signals from RF

amplifiers in MRI or other electronic hardware [1].

Figure 1. Representation of a RECT pulse in the time

domain; although it may also be represented in the

frequency domain with preservation of rectangular form.

Aside from the discontinuities dictated by the

mathematical characterization of the RECT pulse, it

is also an infrequently used RF pulse in diagnostic

imaging due to its deficiencies in spatial and spectral

selectivity, arising from its mathematical description.

Yet despite the RECT pulse’s limited use in MRI, it

is often employed in NMR for assessment of

chemical structure. Because RECT RF pulses often

Tailoring the RF Pulse: A Survey of Pulse Shape Effects on Magnetization—L. Ansari

3

interact with the magnetization vector in the absence

of a gradient magnetic field, and because of their

possibility of being applied with exceedingly short

pulse durations (and thus very broad bandwidth in the

frequency domain), multiple spins with varying

resonance frequencies may be influenced—a trait that

is exploited in NMR of chemical structures [3].

2.1.1 Mathematical Description

Equation 2 [1], below, is the mathematical

representation of the RECT function, for which it can

be seen that for time values of t less than half the

pulse width in the time domain (T), RECT is equal to

1—corresponding to an ―on‖ edge pulse—and for t

greater than half the pulse width in the time domain,

RECT is equal to 0—corresponding to an ―off‖ edge

pulse.

(2)

The frequency-domain representation of the RECT

pulse is the SINC pulse, meaning that the SINC pulse

is thus the Fourier Transform (FT) of the RECT pulse.

The frequency-domain representation of the RECT

pulse is shown below in equation 3 [1].

(3)

It is now understood why the excitation bandwidth of

the RECT pulse is so broad for very small pulse

widths; for example, in NMR, in order to yield

quantitative data for chemical structures of interest, it

is important to have as uniform an excitation profile

as possible elicited from the species under study. This

means that as much of the full frequency bandwidth

(or pulse width, T) of the RECT pulse must be able to

fit within the central peak of the SINC profile in the

frequency domain as possible. The only way to

accomplish this is with shorter pulse widths in the

time domain.

2.2 SINC Pulse

Much more applicable to a variety of applications

than the RECT pulse, the SINC--or sin(x)/(x)--pulse

is a soft pulse form consisting of one large central

peak, bounded by a series of smaller decreasing lobes

on either side. A SINC function is shown in Figure 2.

The central peak of the SINC pulse is always twice as

wide as all other lobes and much higher in amplitude

[1].

Figure 2. A SINC pulse in the time domain, with central

peak and two negative and two positive neighboring lobes.

SINC pulses are particularly convenient to use for

small flip angle excitation (α < 90o), as the slice

profile for a small-angle SINC pulse is more

approximately uniform, and is thus considered more

selective using the small-angle approximation than

when trying to use a SINC pulse for α greater than

90o.

2.2.1 Mathematical Description

The shape (RF envelope, E1(t) or B1(t)), of the RF

SINC pulse is given below in Equation 4 [1]:

(

4)

Where: A = Peak amplitude at t = 0

t0 = Width of each side lobe

NL = Number of zeros toward -∞

NR = Number of zeros toward +∞

Because the Fourier Transform of the SINC pulse is

the RECT pulse, this implies that the most uniform

slice profile (or representation in the frequency

domain) can be achieved for a SINC function with

infinitely many ―zeros‖ on the plot of the SINC

function versus time (infinite values of NL and NR).

This is represented in the mathematical description of

the SINC pulse if one notes the domain over which

the nonzero portion of the function is defined.

Time (ms)

B1

Tailoring the RF Pulse: A Survey of Pulse Shape Effects on Magnetization—L. Ansari

4

Simply, the greater the number of lobes on the SINC

pulse function, the more ideal the rendered slice

profile becomes, and thus the more spatially selective

the RF pulse for a particular slice.

Physically, this corresponds to unrealistically long

pulse duration, however, resulting in impractically

long echo (TE) and repetition (TR) times. Normally a

SINC pulse is truncated when used in the clinical

setting, and this is achieved by only allowing the

SINC peak and several neighboring lobes remain to

form the RF envelope [1,3]. Truncating the

neighboring lobes from the positive side of the SINC

function results in shorter TE.

3. Design Considerations

A study conducted by Wang et al. [7] observed that

different RF pulse shapes do have an impact on

certain factors such as flip angle, spatial uniformity,

and slice profile. The authors of the study also

mention the importance of matching the RF pulse

profile with the particular field mapping (flip-angle

mapping) procedure of interest.

RF pulse shaping is important for being able to

correct for inhomogeneities in the static magnetic

fields of high-field (5T-7T) applications. A SINC

pulse is not necessarily always the most ideal

waveform to use, particularly concerning large flip-

angle purposes for angles greater than 90o, since

varying flip angles are more likely to occur on a

greater scale for the same slice under this condition.

Specific Absorption Rate (SAR) is also of concern in

the clinical environment, as RF pulses contribute to

the irradiation of patients due to heat given off by the

RF coil. Because it is the RF transmitting coil that is

exposing the patient to dissipated heat, SAR doses

are administered anywhere that is in range of the RF

coil, and in quantities proportional to the amplitude

of the transmitted RF pulse [2].

SLR-based MRI systems have replaced most SINC

systems [1], since the flexibility and tailoring

capabilities allow SLR to correct for field

inhomogeneities, adjust peak RF pulse amplitudes to

better prevent SAR, and generate more ideal

waveforms designed to excite slice profiles unique to

a specific application.

4. Pulse Modeling and MATLAB Simulating and designing RF pulses in MATLAB is

an indispensible activity for anyone interested in the

generation of novel RF pulse design; whether it is for

the pursuit of improved models and algorithms, or

simply just out of personal interest in the field.

A project published by Amir Stricker [7] shares the

code for producing one’s own RF pulse design and

simulation toolkit for MATLAB. Note that Amir

Stricker’s work was published in 2001, likely for the

2001 version of MATLAB, and thus special attention

must be given to commands which may require to be

modified for later versions of MATLAB.

Amir Stricker’s function toolkit implements the SLR

algorithm to design pulses, and does not provide

―template‖ pulses such as for Gaussian, SINC, or

RECT functions of the common type.

The reader is referred to [7] for demonstrations of the

toolkit’s capabilities. They are not presented in this

paper, as it would require an explanation of the SLR

algorithm, which is not fully within the context of the

discussion presented here.

5. Conclusion

Characteristics of the RF pulse waveform directly

influence the excitation profiles of the irradiated

slices of interest. RF pulses can be described by four

distinct characteristics; A1(t), the pulse amplitude;

E1(t), the pulse envelope; ω1, the pulse carrier

frequency; and τ , the pulse width. These essential

components of a pulsed signal manipulate the

interactions between MRI technician and proton

spins, therefore providing a means by which to

communicate with—and receive cooperation from –

the magnetized protons subjected to uniform

magnetic fields.

For this reason, RF pulse design and simulation is a

viable field, producing such mechanisms as the SLR

Algorithm for tailoring the RF pulse to better suit any

signaling application. Analysis of the slice profiles

for RECT and SINC pulse forms reveal the spectral

and spatial excitations that the pulse is capable of,

however, these two basic pulses are hardly as flexible

as more rigorous pulse shaping methods such as SLR.

MATLAB is a useful tool in aiding in the

visualization of multiple pulse forms with highly

variable properties. In the future, the author would

like to contribute another paper detailing more

personal experiences with user-defined MATLAB

functions and the publication of her own updated RF

design toolkit, much like Amir Stricker’s work

presented here.

Tailoring the RF Pulse: A Survey of Pulse Shape Effects on Magnetization—L. Ansari

5

6. References

1. Bernstein, Matt A., Kevin Franklin. King, and

Xiaohong Joe. Zhou. Handbook of MRI Pulse

Sequences. Amsterdam: Academic, 2004. Print.

2. Bottomley, P. A., Redington, R. W., Edelstein,

W. A., and Schenck, J. F. 1985. Estimating

radiofrequency power deposition in body NMR

imaging. Magn. Reson. Med. 2:336-349. Print.

3. Claridge, Timothy D. W. High Resolution NMR

Techniques in Organic Chemistry. Amsterdam

[u.a.: Elsevier, 2006. Print.

4. Epstein, Charles L. "A Lecture on Selective RF-

pulses in MRI." University of Pennsylvania,

Philadelphia. Reading.

5. Gershenzon, Naum I., David F. Miller, and

Thomas E. Skinner. "The Design of Excitation

Pulses for Spin Systems Using Optimal Control

Theory: With Application to NMR

Spectroscopy." Optimal Control Applications

and Methods 30.5 (2009): 463-75. Print.

6. Khalifa, A. A., AB M. Youssef, and Y. M.

Kadah. "Optimal Design of RF Pulses with

Arbitrary Profiles in Magnetic Resonance

Imaging." Engineering in Medicine and Biology

Society, 2001 3: 2296-299. Print.

7. MATLAB Tools for RF Pulse Design and

Simulations:

http://amirschricker.org/pubs/proj_rfpulse.pdf

8. Smith, Nadine, and Andrew Webb. Introduction

to Medical Imaging: Physics, Engineering and

Clinical Applications. Cambridge, UK:

Cambridge UP, 2011. Print.

9. Wang, Jinghua, Weihua Mao, Maolin Qiu,

Michael B. Smith, and R. Todd Constable.

"Factors Influencing Flip Angle Mapping in

MRI: RF Pulse Shape, Slice-select Gradients,

Off-resonance Excitation, AndB0

Inhomogeneities." Magnetic Resonance in

Medicine 56.2 (2006): 463-68. Print.

6

THE ROLE AND IMPACE OF ULTRASOUND GUIDED TECHNOLOGY

FOR REGIONAL ANESTHESIA PLACEMENT Aimee Bobko

abobko2@uic.edu

Abstract Regional anesthesia is used to decrease pain observed near a specific surgical site. By placing the

anesthetics near nerves responsible for the sensory information of the desired area, temporary

sensory loss can occur; this is called an anesthetic block [4]. In order for the anesthetic to be

injected and placed, locating the correct nerve is essential. Initially, it was required for the block

to be placed in blindly which introduces a higher risk for nerve damage to the patient and

increases the chance for block failure [3]. In the late 1970s, ultrasound technology was applied to

this procedure to allow for real time imaging [2]. The main purpose of using ultrasound for this

procedure was for improved nerve identification and localization. Studies have shown that

ultrasound guided anesthetic blocks typically have a 94% success rate of sensory loss in the right

area compared to the 79% success rate of sensory loss with the blind technique [1]. Using

ultrasound includes other advantages such as less pain medication consumption and fewer needle

insertions into the body [1]. As a result, this technology has revolutionized the field of regional

anesthesia and has become a common practice throughout surgical units across the country [4].

This technique is a great example of advancing medical care through the use of real time imaging

to improve treatment. This application also emphasizes that patient specific treatments are

becoming more favorable as it is now better understood that each person’s anatomy is slightly

different [4]. Taking this fact into consideration produces more successful care as physicians can

tailor specified patient plans. Medicine can become more exact and certain. The ultrasound

guided technology with regional anesthesia placement serves an important role in healthcare

today and is continuing to advance patient care.

Keywords: Ultrasound, Anesthesia, Medical Imaging

1. Introduction

The interest in the use of regional anesthesia began in

1884 with the discovery of local anesthetic properties

in cocaine [2]. As more anesthetics were discovered

and improved, there was an increasing trend to move

towards the use of regional anesthetics blocks in

conjugation with certain surgical procedures such as

foot or ankle surgery. Blocks started to gain rapid

popularity in the 1970s and 1980s when there was a

large concern about analgesia, pain experienced after

undergoing surgery [2]. A regional anesthetic block

consists of incremental doses of an anesthetic through

a perineural catheter [1]. This catheter is placed near

nerves close to or leading towards the surgical site.

By placing the anesthetics near nerves responsible for

the sensory information of the desired area,

temporary sensory loss can occur; this is called an

anesthetic block [4]. The purpose of regional

anesthesia is to decrease the pain observed near the

surgical site and in some cases, to avoid the use of

general anesthesia.

The most important aspect of implementing this

application is placing the anesthetic in the proper

location to ensure proper function while avoiding

nerve damage. Traditionally, this procedure was

performed blindly without visualization of the nerve

for anesthetic placement, and usually, only with the

help of electrical stimulation technology, which

produces an indirect indication of location through

muscle twitches around the desired area. Hence, this

produced a problem with respect to the inability to

confidently receive the precise nerve location [4].

Figure 1. This figure shows a typical set-up of an

ultrasound guided regional anesthesia block with a

computer screen nearby for the clinician to get a good

visualization of the region underneath the transducer on the

patient’s body prior to needle insertion [6].

The Role and Impact of Ultrasound Guided Technology for Regional Anesthesia Placement—A. Bobko

7

Due to its ability to produce a real-time image of

identifiable structures below the skin, ultrasound

technology has been applied to fulfill this role to

assist clinicians in their placements of regional nerve

blocks, as seen in Figure 1. The images give an

accurate idea of the location and direction of the

nerves [4]. This is especially useful in accounting for

the varied anatomy of each individual patient [4]. By

having a more accurate guide for anesthetic

placement, more precise movements and control of

the needle during the procedure are obtained, as seen

in Figure 2 [8]. The spread of the anesthetic

throughout the visualized region can also be assessed

for accuracy [8]. This leads to more properly placed

blocks which will reduce pain greater more

effectively than a block placement with electrical

stimulation. With less pain experienced, patients do

not have to use as much pain medication and their

overall satisfaction is greater.

Common areas in which ultrasound has been found to

be useful include procedures involving venous

access, epidural space identification, and

identification of nerve plexuses for nerve blocks [4].

Ultrasound guided regional anesthesia placement in

particular is an excellent example of the results

obtained through the use of a combination of

technology.

2. Evolution of Technology

2.1 Electrical Stimulation

Prior to the 1970s, electrical stimulation was the

major form of guidance utilized for peripheral nerve

blocks [2]. The electrical stimulation technology

utilizes an electrical current for short intervals to

induce a muscular twitch response [1]. In order to

first locate the desired nerve, a needle is inserted into

the body, which will subsequently be replaced by the

catheter. In order to ensure the needle is in the

appropriate location and near the correct nerves,

electrical stimulation elicits a response from the

muscles which the needle is currently affecting. For

example, if a block for ankle surgery is desired,

twitches of the surrounding ankle muscles would be

needed to ensure the anesthesia would travel to the

correct location. Often, there is a large distance from

the block placement to the affected surgical area. As

a result, it is essential for a clinician to have through

knowledge of the anatomy of these regions [8].

This method is associated with several risks. Since

this procedure offers the clinician no visual

assistance, the needle insertion is performed almost

blind creating a situation where uncertainty plays a

role in a block placement. As a result, even when

used by experienced clinicians, electrical stimulation

outcomes cannot be reliable [4]. Without the

assistance of visual cues, there can also be a higher

risk of punctured blood vessels and nerve damage

[8]. Furthermore, specific structural landmarks that

may be relied on with electrical stimulation can be

skewed by factors such as obesity or varying patient

anatomy, resulting in a more difficult block

placement. This method illustrates a less than ideal

environment for the placement of regional

anesthetics.

2.2 Ultrasound

Figure 2. Shows a close up view of the approach a clinician

takes to make the needle insertion as part of the procedure

for regional anesthesia placement. The clinician has placed

the transducer over the site where they predict a desired

nerve plexus is located. The clinician will be able to see

this plexus as they guide the needle into the correct position

[7].

As mentioned previously, ultrasound offers an

opportunity to obtain some visual guidance as a way

for clinicians to place blocks with more success.

Thomas Bendtsen demonstrated this claim in a study

where sensory blockade success, pain medication

consumption, needle passes (the number of times the

needle was inserted and withdrawn from the body)

and patient satisfaction where measured in 100

patients [1]. This study found that the patients who

received the ultrasound guided nerve block had a

success rate of 94% which is much higher compared

to that of the electrical stimulation group with a

success rate of only 79% [1]. This demonstrates that

greater sensory blocks can be obtained with the use

of an ultrasound guide. Bendtsen was looking at

nerve blocks specifically with the popliteal sciatic

nerve and considered sensory block to be achieved

when there was sensory loss in both the tibial and

common peroneal regions [1]. In addition to the

success rate of the ultrasound guided block, this study

The Role and Impact of Ultrasound Guided Technology for Regional Anesthesia Placement—A. Bobko

8

proved that the ultrasound treatment group had a

reduced need for morphine pain medication

consumption. This group required a median of 18mg

compared to the median 34mg of the electrical

stimulation treatment group [1]. The decreased

amount of pain medication indicates a larger effect of

the block in terms of successfully decreasing the

amount of pain in the surgical area. In terms of

needle passes, where the needle may need to be

withdrawn from the body and reinserted due to

misplacement, there was also a difference between

the two groups. In the ultrasound group, there was a

median of one pass versus a median of two passes for

the electrical stimulation group [1]. Fewer needle

passes means less chance of nerve damage as well as

quicker and more accurate needle placement. Patient

satisfaction was also measured on a scale of 1-10 in

this study. In the ultrasound group, there was a

median patient satisfaction number of 9. The

electrical stimulation group had a median patient

satisfaction number of 8 [1]. The slight difference in

patient satisfaction shows that patients in the

ultrasound category felt happier with the outcomes of

their overall treatment. In this study, the ultrasound

procedure fared better in each degree of

measurement.

N.S. Sandhu also conducted a similar study with 126

patients who underwent ultrasound guided

infraclavicular brachial plexus blocks [8]. His results

indicated that 90.4% of the block only procedures did

not require any additional anesthetic [8]. This high

success rate gives insight into the decreased degree of

speculation and subsequent failure associated with

the ultrasound guided procedure.

A combination of ultrasound technology and

electrical stimulation can be used to further ensure

the location of the needle in relation to desired nerves

[3]. The electrical stimulation confirms the proper

needle placement that was determined through

ultrasound use. This can lead to an even higher

success rate for the blocks. The specific technique of

the ultrasound method will be discussed in the

following section.

3. Technique and Image Quality

The technique of an ultrasound guided regional

anesthesia block begins with the insertion of a needle

and the tip being led towards the appropriate

neurovascular bundle, which can be seen on an

adjacent ultrasound imaging screen. The image is

generated through sound transmission and reflection

through the transducer. Sound is able to pass through

the fluids which make up the soft tissues [4]. This is

why fluids are displayed in black color on the

resulting image [4]. The materials composing the

actual soft tissue reflect a portion of the sound back

towards the transducer, making them a lighter color.

Once the needle is in place, test injections of the local

anesthetic can be conducted. These injections should

only be 1-2ml, just to see if the spread of the

anesthesia is occurring in the correct direction [3]. If

not, the needle will need to be moved [4]. Once in the

correct position, the appropriate dose of local

anesthesia can be injected and visualized.

An essential component of this procedure is the need

for needle visibility on the ultrasound image screen,

as seen in Figure 3. The visibility depends on the

echogenicity of the needle in comparison to the

echogenicity of the surrounding tissue [5].

Echogenicity refers to the ability to reflect a portion

of the ultrasound wave back [5]. If there is only a

small difference between the echogenicities, the

visibility will be poor [5].

Figure 3. This image is a short axis ultrasound scan of the

musculocutaneous nerve in the axilla. The needle tip can be

visualized along with the local anesthetic that has just been

injected (arrowheads). After the injection, the needle can be

seen displaced from the nerve [3].

Human tissue has a high echogenicity, resulting in a

less than ideal needle visibility [5]. The needle’s

echogenicity is determined by its angle of insertion to

the ultrasound beam, quality of the needle, and

needle gauge [3]. The needle begins to become less

visible at steep angles and more visible with larger

gauged needles. The larger needle can be seen more

easily due to its size and stiffness. [3]

The nerve viewing planes are also important to

ensure correct needle and anesthetic spread images.

The needle is better seen in comparison with the

surrounding tissues in the transverse direction [4].

Also, these blocks are usually performed by short

axis imaging [3]. This allows for good visualization

The Role and Impact of Ultrasound Guided Technology for Regional Anesthesia Placement—A. Bobko

9

of nerves and resolution of surrounding barriers [3].

Also, if the transducer moves somewhat, the nerves

will still be visible [3]. It is imperative to ensure the

clearest combination of needle and tissue structures

in the resulting image.

Frequency of the ultrasound beam is also another

aspect of the image affecting the quality. The

frequency is decided based on the needed range of

depth and resolution [4]. The general trend is that

high frequencies will only allow short tissue depths

and produce high resolution, which is seen in Figure

4. Inversely, low frequencies waves will allow for

deep tissue penetration but produce low resolution.

Common needed nerve depth is between 3-7cm,

which can be reached with high frequency ultrasound

waves with decent image quality [3]. However, there

have been current advances in technology that have

been able to distinguish between nerves and other

various structures at low frequencies [3].

The most efficient mode of ultrasound for this

procedure is cross-sectional B-mode, since images

show a slice of tissue and are the easiest to interpret

for clinicians [4]. As a result, in real time, the needle

location and any local structures can be seen.

Figure 4. This figure shows ultrasound scans of the median

nerve of the forearm, which is labeled by the yellow arrow,

at five different depths. As the depth increases, the nerve

becomes visually smaller and more difficult to see. This

illustrates the importance of choosing appropriate image

settings with ultrasound for a desired nerve [9].

Usually, a built-in caliper allows for measurements

such as the depth and length of various structures

such as nerves to be measured [3]. A lot of these

aspects contribute to creating an image that will be

most helpful to guide clinicians as they look to ensure

they have achieved the correct position to insert

anesthetics into the body. Although ultrasound does

not allow for a clear direct image, the reflection of

the sound waves creates a good enough visual aid

with low safety risks that is able to serve the needed

role well enough.

4. Advantages and Disadvantages

4.1 Advantages

There are many advantages to the ultrasound guided

method which is why it has become increasingly

popular in its use. As discussed earlier, there has been

evidence from studies which show that higher

success rates can be achieved from the use of

ultrasound in regional anesthetic placement [1]. This

can be concluded from measurements of the high

degree of sensory loss, lower pain medication

consumption, fewer needle passes, and higher patient

satisfaction, specifically in comparison to the

electrical stimulation technique [1]. In addition, one

of the most advantageous features of ultrasound

technology in this application is being able to move

and relocate the needle after the initial dispersion of

anesthetic without necessarily removing or

withdrawing the needle from the body [3]. By being

able to recognize and correct the misplacement on the

ultrasound image screen, this greatly helps avoid

complications [4]. It allows for faster placement and

less risk of nerve damage or block failure.

Furthermore, something electrical stimulation is

incapable of achieving but ultrasound can is able to

perform a successful block on patients with

amputated distal upper extremities [8]. It is important

that this treatment protocol offers the opportunity to

better reach patient populations that were not able to

be accessible before.

In terms of image visualization, ultrasound is more

useful than other medical imaging modalities.

Ultrasound equipment is smaller and more easily

transported compared to other imaging technology

available in addition to creating acceptable

resolution, depth distance, and structure identification

[4]. Nerves are identified by moving the image along

the path of the nerve which is often in a slanted

direction. This is difficult to achieve with other

imaging technologies such as medical resonance

The Role and Impact of Ultrasound Guided Technology for Regional Anesthesia Placement—A. Bobko

10

imaging (MRI) [3]. Thus, ultrasound has many

factors that contribute to its success in this role.

4.2 Disadvantages

However, along with the many advantages of the

technology, there are also several disadvantages with

the technique as well. First there is a definite need for

more training to be able to utilize and perform the

technique successfully. It is important for clinicians

to understand not only how to operate the machinery

but also how to work with ultrasound and anesthetics

in combination to recognize correct nerves and

proper placement. In order to be able to make these

recognitions, clinicians often have to fight the less

than perfect needle visibility produced by the

technology. Since living human tissue has high

background echogenicity, the needle can be difficult

to identify [5]. This problem must be treated with

care because not being able to correctly see the

needle can lead to mistakenly puncturing structures

and causing damage. In addition, another factor to

consider is that the nerves can be displaced from their

usual positions. This displacement that moves nerves

can be caused by light pressure from the ultrasound

probe, needle advancement through the tissues, or

even the anesthetic as it distributes in the body [3].

The correct identification of nerves is needed

throughout the entire procedure in order to produce a

successful block in the right area.

Since image quality is such a high priority, it is

necessary to avoid any factors that may distort the

image through items such as shadows. As a result, air

bubbles which cause shadowing have to be evaded as

well as bicarbonate containing solutions since they

can produce carbon dioxide which would disrupt the

image clarity [4]. Another factor in image quality is

the resolution and the ability to distinguish between

structural components. Currently, there is a limit to

the resolution of the image due in part to nerve size.

At this time, the smallest nerves that can be

distinguished in an image are 2mm in diameter [3].

Most nerves for regional blocks can be seen in the

generated image; however, if this limit could be

lowered, success in the procedure would most likely

increase further.

Low image quality prevents accurate interpretation

by clinicians. These interpretations are on an

individual scale and can vary between clinicians [4].

As a result, there is still a portion of this procedure

that requires educated guessing and decision making.

Another limiting factor that needs to be considered is

the time and intensity of exposure of the body to the

ultrasound waves. Despite the increased safety of

ultrasound’s non-ionizing radiation, these waves can

have a high enough energy to cause heating and

damage to tissues [4]. In order to avoid this, the

clinician must have knowledge about the settings for

ultrasounds as well as the effects the waves can have

under certain circumstances.

Futhermore, other limiting factors of the ultrasound

technology include space and cost. There is the high

cost of the ultrasound equipment which could deter

performing the procedure. However, this would be a

onetime cost that could become very cost effective

with the amount of patients who could utilize this

treatment as well as the time that could be saved by

investing in a more precise method [8]. In addition to

the cost of the equipment, space in hospitals is also

needed in order to perform this procedure. Specific

rooms need to be allocated in hospitals as ―block

rooms‖ where the necessary equipment could be

permanently situated [3]. This could be a problem if a

hospital does not have any additional space to make

available.

Other disadvantages that may be in the realm of this

method’s protocol include that in some cases, it may

be easier to give general anesthesia rather than

regional anesthesia, there may lack of anatomical

knowledge by clinicians needed for this technique,

and there could also be a lack of knowledge by the

clinicians regarding the benefits and uses of regional

anesthesia [3]. These disadvantages emphasize the

need for extensive training in order to combat these

typical limiting factors of this procedure.

5. Conclusion

Ultrasound guided regional anesthesia placement has

revolutionized the field of regional anesthesia by

allowing for clinicians to be able to see a real time

image of their anesthetic placement. Being able to

have this picture greatly alleviates much of the

guesswork that previously went into this application.

This can be seen in the difference of success rates of

sensory blocks with 94% for the ultrasound group

and 79% for the electrical stimulation group. These

differences as well as the differences in pain

medication consumption, number of needle passes,

and degree of patient satisfaction, show how

ultrasound has advanced the medical treatment of this

procedure. The ultrasound guided blocks are

achieving their purpose by decreasing the amount of

pain experienced by a patient post-operatively.

Since the late 1970’s, ultrasound has been utilized in

this procedure, and now, it has become a rather

The Role and Impact of Ultrasound Guided Technology for Regional Anesthesia Placement—A. Bobko

11

routine component with the procedure in surgical

units across the country [4]. As a result of its high

use, it would not be surprising to see ultrasound

machines being incorporated as a key component on

anesthesia machines in operating rooms in the future

[3]. This demonstrates the increasing role medical

imaging is playing in health care today. There is a

growing need for clinicians to be able to have a real

time image of what is going on beneath the skin, and

ultrasound is becoming the preferred imaging

modality to do so. With real time imaging, medicine

is achieving a higher degree of precision and

confidence.

Currently, clinicians are finding the procedure to be

particularly useful in patients with different and

difficult anatomies [3]. The integration of this

technique into their practice is allowing them to gain

a better sense of how to approach the treatment of

these patients and to gain a better idea of how to

move forward with a treatment plan. Clinicians have

also been finding this procedure to be useful with

children who share a high degree of anatomic

variation among one another [4]. This procedure is

also very useful since a child’s nerves are rather

superficial, making them easy to access through this

technique [4]. These examples illustrate the

importance of the new trend of individualized

medicine. Since each person’s anatomy is slightly

varied, ultrasound is allowing clinicians to account

for this by displaying images that demonstrate that

not every individual’s nerve plexuses are in the exact

same location [4]. Individualized medicine is

allowing for the treatment of each patient more

successfully because clinicians are working a plan

that is specified to the structures within the anatomy

of a specific patient, which is ultimately leading to

better results.

There are many current research investigations that

are hoping to improve ultrasound technology for

regional anesthesia placements further in the future.

It is hoped that one day this technique could be used

to access traditionally difficult nerves or nerves that

cannot be easily located [4]. There is also a goal to

achieve clearer imaging of smaller and deeper nerves

[3]. Another aspect being tested is the use of color

encoded echoes which could lead to better image

visibility. This could assist with the identification of

the needle, structural components, and anesthetic [3].

Additionally, the improvement of needle

echogenicity is being examined to see if the effects of

material modifications through the use of procedures

such coating can attain better visibility [3]. All of

these factors could eventually lead to large advances

in the field of regional anesthesia as well as the

medical field as a whole.

Ultrasound guided regional anesthesia placement is a

good example of a time when imaging can be used in

a functional role to assist with procedures. It has had

a large impact thus far and will continue to do so.

6. References 1. Bendtsen, Thomas, Thomas Nielsen, Claus

Rohde, Kristian Kibak, and Frank Linde.

Ultrasound Guidance Improves a Continuous

Popliteal Sciatic Nerve Block When Compared

With Nerve Stimulation. Regional Anesthesia

and Pain Medicine. 36.2: 181-184, 2011.

2. Brown, T.C.K. History of Pediatric Regional

Anesthesia. Pediatric Anesthesia. 22.1: 3-9,

2011.

3. Gray, Andrew. Ultrasound-guided Regional

Anesthesia: Current State of the Art.

Anesthesiology. 104: 68-73, 2006.

4. Gupta, Prashant, Kumkum Gupta, Amit

Dwivedi, and Manish Jain. Potential Role of

Ultrasound in Anesthesia and Intensive Care.

Anesthesia Essays and Researches. 5.1: 11-19,

2011.

5. Hocking, Graham. Simon Hebard, and

Christopher Mitchell. A Review of the Benefts

and Pitfalls of Phantoms in Ultrasound-Guided

Regional Anesthesia. Regional Anesthesia and

Pain Medicine. 36.2: 162-170, 2011.

6. Philips. 2011. Regional Anesthesia and Pain

Medication Products. 21 Nov. 2011. <http://ww

w.healthcare.philips.com/de_de/products/ultraso

und/categories/regional_anesthesia.wpd.>.

7. Romdhane, Kamel, Adel Zorkani, Maizar

Khalaf, and Safwan Jandali. Introduction to the

Ultrasound Guided Regional Anesthesia. The

Internet Journal of Health. 5:2, 2007.

8. Sandhu, N.S. and L.M. Capan. Ultrasound-

guided infraclavicular brachial plexus block.

British Journal of Anasthesia. 89.2: 254-259,

2002.

9. USRA. Scanning Technique – Machine Settings.

20008. Ultrasound for Regional Anesthesia. 21

Nov. 2011 <http://ww w.usra.ca/ugt_st_ms_io>.

12

A REVIEW OF APPLICATIONS USING CURRENT MRI TECHNOLOGY Noman Ali Khan Nkhan26@uic.edu

Abstract Magnetic Resonance Imaging is one of the most informative diagnostic imaging tools. Since the

scanning process does not expose the patient to ionizing radiation it is one of the safest imaging

technologies, which should be taken advantage of. One of the future benefits of MRI is the ability

to monitor intracellular drug delivery. Another future application of MRI is to examine metabolic

function of the brain. Not only is the number of MRI applications evolving but the method for

capturing these images is evolving as well. Structural and functional MRI’s are being integrated.

Spatial resolution of obtained images has greatly increased with MRI. With other imaging

techniques which are used for diagnostics, there are not many quantative functions. However

there are new research studies which evaluate the possibility of quantitative functional MRI. Not

only is MRI being used in medical applications it is also being used in lie detection and even

marketing. This article will not only explain these applications and processes but also assess the

validity of these technologies and provide an insight on the usefulness of each application.

Keywords: MRI, UIC, Bioengineering, Lie Detection, Future Technologies, fMRI, marketing

1. Background

Magnetic Resonance Imaging (MRI) is a diagnostic

tool mainly used by radiologists and other

professionals in the medical field. There are many

more applications for MRI, which are discussed later

in this paper. The first one-dimensional magnetic

resonance image was reported by Herman Carr in the

1950‟s. Later on, Paul Lauterbur developed a

technique to construct two and three-dimensional

MRI images. The first MRI cross sectional image of

a mouse brain was documented in 1974. Peter

Mansfield enhanced MRI technology to reduce the

amount of time it took in order to generate an image

as well as increase the quality of the image. Both

Lauterbur and Mansfield won the 2003 Nobel Prize

for their “discoveries concerning magnetic resonance

imaging” [3].

Figure 1. An image of a typical MRI machine with coils

inside the “MRI ring” and a table for the patient to lie on

during the exam [7].

According to Textbook of Medical Physiology, the

human body consists of approximately 57% water

[1]. Since each water molecule contains two protons

in the form of hydrogen, MRI takes advantage of that

by applying a magnetic field to these molecules and

aligning them with the magnetic field direction. An

RF pulse is initiated temporarily to create an

electromagnetic field. The photons of this field move

according to the resonance or Larmour frequency,

which allows them to be absorbed by the protons that

in return will flip its spinning direction. When the

field is turned off the energy absorbing protons

subsequently return to their original states releasing

energy, which is detected by the scanner as an

electromagnetic signal. The image itself is

determined by applying more gradient fields to the

scan. Through solenoids a current is passed which

will vary the magnetic field according to the position

of the patient. This position can be predicted using

the inverse Fourier transform. The Fourier transform

converts the mathematical results into an image,

which can be later used for diagnostic purposes [3].

There are some major advantages of MRI: no

ionizing radiation, images can be captured in any 2-D

or 3-D plane, very good soft tissue contrast, images

are produced with inconsequential penetration

effects, and a spatial resolution of 1mm can be

acquired. There are also some disadvantages of MRI

which includes: time to acquire an MR image is

longer than x-ray or ultrasound images, patients with

certain metallic implants are unable to undergo a

scan, and it is relatively more expensive than x-ray or

ultrasound [7]. Since MRI is so expensive, most

A Review of Applications Using Current MRI Technology—N. Ali Khan

13

hospitals are not able to afford as many MRI

machines as x-ray machines, which means that more

people may need to wait on a waiting list to receive a

scan. MRI already takes a long time to obtain, and

with the lack of machinery it could affect the patient,

who will be the one that pays for it, in time and

money. Although this is an unfortunate drawback the

spatial resolution and safety of MRI overcomes the

cost, which may be why there are over 10 million

MRI‟s prescribed every year [7].

2. Current MRI Applications

There are several companies, which manufacturing

MRI machines. The machines these companies

produce are mainly used in hospital or clinical

settings. Some of these companies include: Fonar,

General Electric Healthcare, Hitachi Medical

Systems, Odin Medical Technologies, Philips

Medical Systems, Siemens, and Toshiba.

One of the current supremacies of MRI technology is

the ability to see more clearly into musculoskeletal

tissues. Because of the high spatial resolution of

MRI, even fine details in the structure are easily

displayed. For example, MRI may be used to detect

symptoms of rheumatoid arthritis in the wrists and

knees [7].

Another current use of MRI is to diagnose diseases in

soft tissues. One example is the diagnosis of liver

cancer using MRI. Using a contrast agent,

metastases, which are the most common form liver

tumors, may be visible. Other diseases that may be

diagnosed because of MRI include cirrhosis,

haemochromatosis and haemolytic anemia, hepatic

adenoma, as well as other focal and diffuse liver

diseases [7].

There are quite a few neurological applications for

MRI. Some of the diseases that are diagnosed

through MRI include: meningioma, lymphoma,

schwannoma, astrocytoma, glioblastomas, and

vasogenic or cytotoxic edema. One of the main

neurological diseases that are diagnosed through

MRI is a stroke. Strokes occur when there is a

blood clot in one of the blood vessels in the brain.

This blood clot leads to the failure of a

sodium/potassium pump which will cause

cytotoxic edema. Since certain therapies must be

administered after a stroke, an early detection is

essential. Alzheimer‟s and Huntington‟s diseases

may also be diagnosed using MRI. However, they are much more difficult to diagnose since the

symptoms of these two diseases lead to white

matter lesions similar to that of normal aging [7].

MRI angiography is essential in observing the

blood flow through the body and its organs. Using

this technique, fine details of the blood vessel

structure in the brain can be detected. The images

of blood vessels from MRI can be used to evaluate

a stenosis or aneurysms. Another use for MRI

angiography is in the cardiac tissue, specifically

the heart. The heart can be imaged to show the

four stages of the cardiac cycle. Abnormalities

such as left anterior descending coronary artery

disease, which is the most common cause of heart

attacks, may be detected using MRI angiography.

Figure 2. On the left shows the MRI angiogram of the brain

with maximum intensity. The left image shows the details

acquired using MRI angiogram [7].

Functional MRI (fMRI) is used in order to examine,

which parts of the brain are used for certain activities.

Oxygenation of certain parts of the brain during these

tasks such as speech, sensory motion, and other tasks

allows fMRI to display them. Although fMRI is used

in research more than in clinical applications, it is

used in some clinical applications such as the pre-

surgical planning. Here a surgery may be planned

using fMRI in order to avoid critical areas of the

brain, which may be necessary for tasks such as

speaking and sensory motion [7].

3. Diagnostic MRI Enhancements

In order to diagnose amyotrophic lateral sclerosis

(ALS) a team of researchers at Oxford used a

combined fMRI as well as structural MRI to see if it

would have any diagnostic value. Twenty-Five

patients who were diagnosed with sporadic ALS were

chosen for the study as well as fifteen control

subjects. Images were taken using a 3T Siemens Trio

scanner. This scanner includes a twelve channel head

coil and has met guidelines set by the 2010

Neuroimaging Symposium in ALS. The subjects

A Review of Applications Using Current MRI Technology—N. Ali Khan

14

went through a T1-weighted, diffusion weighted and

resting state fMRI. A three-dimensional whole brain

T1-weighted MRI scan was also acquired with

specific time/echo, flip angle, and spatial resolution.

Subjects were kept awake for the scans but were

instructed to keep their eyes closed [8].

Figure 3. A diagram of structural and fMRI overlaid each

other which shows white matter damage commonly

associated with ALS [8].

The results for this study showed that by using this

novel approach to integrate structural and functional

MRI the researchers found connectivity between the

two in ALS subjects which was not found in the

control group. This connectivity is essentially an

“ALS cerebral signature” which could be a potential

method for early detection of ALS. There were a few

drawbacks to this study including not being able to

image “mild cognitive impairment”; however, there

is great potential in combining structural and

functional MRI and this study has displayed some of

that potential [8].

Another diagnostic MRI enhancement is the study

involving using fMRI as a quantative diagnostic tool.

FMRI has greatly increased the potential of MRI, by

allowing researchers to qualitatively asses brain

function. However, it has not been able to give

quantative results that may be used for diagnostic

purposes. This research paper shows that fMRI can

be quantified into showing cerebral blood flow,

cerebral blood volume, and oxygen metabolism in the

brain as a quantative result. Quantative fMRI has

already shown a linear relationship between cerebral

blood flow and oxygen metabolism in the brain. One

of the main challenges for fMRI to be used in a

clinical setting is the lack of adoption in

pharmacological research studies, and individual

patient evaluations. If there were an accurate

methodology for interpreting the results of an fMRI

so that it may be used for these types of uses, it could

have a plethora of clinical applications [6].

4. Future MRI Applications

One of the future applications of MRI is the

possibility of specific drug delivery imaging. The

goal of this specific study is to “strengthen future

nanomedicine research by improving our ability to

design sensitive „targeted cell-shuttle‟ type nano-

probes for monitoring drug delivery and therapy”.

The way MRI fits in this study is that it is used to

capture the images of the cells. These cells receive

this drug and the researcher evaluates whether the

MRI is able to accurately image the nano-probes and

specific drugs that are being introduced into the cells.

The study uses a 14T magnetic field strength using a

10mm micro-imaging coil. This study proves that

MRI is able to image this nanoparticle system. In the

future this discovery could lead to more

breakthroughs in cancer biology and drug delivery

[5].

The use of magnetic resonance spectroscopy (MRS)

has a great deal of useful applications. It is able to

show the amount of a substance in an MR image. For

example it can determine the amount of lactate or

lipids within a certain organ such as the brain. It can

also be used to determine the metabolic profiles of

tumors. One of the main uses of MRS is to diagnose

various disorders including: brain tumors,

neurodegenerative disorders, metabolic

encephalopathy, ischemia, hypoxia, and white matter

diseases. Another possible use of MRS is to diagnose

Parkinson‟s disease. By investing the metabolic

profiles of patients with Parkinson‟s it is able to

detect pathogenic markers of the disease which could

help in early diagnosis. Because of the great clinical

potential of MRS and especially its effect on

evaluating metabolic processes it is a future

breakthrough in MRI applications [2].

Figure 4. An MRS image which shows the image as well as

the amount of each compound, slightly increased lactate

and lipids are present here [2].

A Review of Applications Using Current MRI Technology—N. Ali Khan

15

5. Non-Medical MRI Applications

Aside from clinical uses of MRI there are many other

uses including marketing research as well as possible

lie detection.

In marketing, MRI is being used in order to

determine whether a consumer is interested in a

product. This product is placed with other products,

ideas, and pictures in order to stimulate a response

from the consumer‟s brain directly using fMRI.

Below is a graph which shows how attentive

someone is when they are shown pictures of different

things. There is a very noticeable change when the

person is shown a plant versus a bottle of Coca-Cola.

Figure 5. A chart which displays the attention index during

a series of advertisements shown to members of this study

group [9]. The peaks indicate increased attention and

troughs are decreased attention.

Although this research is controversial it is difficult

to say that it has no value as research at all. There is

some basis to say that it does provide useful

information to potential product manufacturers. For

example, there is a direct correlation to using EEG or

MEG to determine if an advertisement has been

remembered or not, which would be of great value to

marketing companies. However, it is difficult to

gauge whether a consumer had a specific emotional

response. More research is necessary, and the

researchers of this particular study stated that

companies which employ this method of marketing

need to publish their results. However, this may be

difficult due to the competition, which would also

have the results as well [9].

Another application for MRI may be lie detection. In

a recent study published by the journal of Behavioral

Sceience and the Law, 333 undergraduate students

served as “jurors” in a mock trial where they had to

evaluate fMRI as a possible lie detection criterion in

a court case. The following chart shows that most

jurors did believe that fMRI is accurate in lie

detection.

Figure 6. A graph of jurors‟ guilty responses when each

method of lie detection was claimed to asses the guilt of the

defendant. FMRI has the highest validity of guilt prediction

[4].

Although this research study is quite thorough in

determining the value of fMRI in the minds of many

jurors, it did not assess the validity of fMRI as lie

detection technology itself. More research studies are

needed in order to determine whether MRI

technology is an accurate method in detecting lies.

However, this research proves that if fMRI results are

ever admitted into court as evidence it will most

likely have a very influential impact in the minds of

jurors [4].

6. References

1. Guyton, Arthur C. (1991). Textbook of Medical

Physiology (8th ed.). Philadelphia: W.B.

Saunders. p. 274. ISBN 0-7216-3994-11.

2. Hall, Hélène, Sandra Baena, Carina Dahlberg,

René Zandt, Vladimir Denisov, and Deniz Kirik.

"Magnetic Resonance Spectroscopic Methods for

the Assessment of Metabolic Functions in the

Diseased Brain." Current Topics in Behavioral

Neuroscience (2011): 1-30. 11 Nov.2011

3. "Magnetic Resonance Imaging." Wikipedia, the

Free Encyclopedia. Web. 05 Dec. 2011.

<http://en.wikipedia.org/wiki/Magnetic_resonan

ce_imaging>.

4. McCabe, David P., Alan D. Castel, and Matthew

G. Rhodes. "The Influence of FMRI Lie

Detection Evidence on Juror Decision-making."

Behavioral Sciences and the Law 29 (2011):

566-77. 29 July 2011. Web.2011.

A Review of Applications Using Current MRI Technology—N. Ali Khan

16

5. Mitra, Rajendra N., Mona Doshi, Xiaolei Zhang,

Jessica C. Tyus, Niclas Bengtsson, Steven

Fletcher, Brent Page, James Turkson, Andre J.

Gesquiere, Patrick T. Gunning, Glenn A. Walter,

and Swadeshmukul Santra. "An Activatable

Multimodal/multifunctional Nanoprobe for

Direct Imaging of Intracellular Drug Delivery."

Biomaterial (2011): 1-9. 24 Oct. 2011.

Web.2011

6. Pike, G. B. "Quantitative Functional MRI:

Concepts, Issues and Future Challenges."

NeuroImage (2011): 1-7. Print.

7. Smith, Nadine, and Andrew Webb. "Magnetic

Resonance Imaging (MRI)." Introduction to

Medical Imaging: Physics, Engineering and

Clinical Applications. Cambridge, UK:

Cambridge UP, 2011. 204-73. Print.

8. Turner, Martin R., Gwenaëlle Douaud, Nicola

Filippini, Steven Knight, and Kevin Talbot.

"Integration of Structural and Functional

Magnetic Resonance Imaging in Amyotrophic

Lateral Sclerosis." Brain (2011): 1-10. 10 Nov.

2011. Web.2011.

9. Vecchiato, Giovanni, Laura Astolf, Fabrizio V.

Fallani, Jlenia Toppi, Fabio Aloise, Francesco

Bez, Daming Wei, Wanzeng Kong, Jounging

Dai, Febo Cincotti, Donatella Mattia, and Fabio

Babiloni. "On the Use of EEG or MEG Brain

Imaging Tools in Neuromarketing Research."

Computational Intelligence and N (2011): 1-12.

28 June 2011. Web.2011.

17

BASICS OF MAGNETOENCEPHALOGRAPHY AND ITS

APPLICATIONS AS AN EXPERIMENTAL TOOL Vu Nguyen

Nguyen14@uic.edu

Abstract Magnetoencephalography (MEG) is a new novel noninvasive method used to measure the magnetic flux

associated with the electrical current occurring naturally in the brain. The location of the magnetic flux is

caused by the action potential of neurons during synaptic transmission. By locating the sites of the active

neurons, MEG is able to identify and visualize brain activity with superior temporal and spatial resolution

compared to functional magnetic resonance imaging (fMRI). MEG imaging technique can be used to study

many properties of the working human brain, including spontaneous activity and signal processing after

stimulation. Also, MEG the only imaging technique today that can record brain function in millisecond

interval provides doctors and researchers real time information on brain activities. This paper provides a

survey of this current technology assessing the basic physical theories behind the technology. Sections in

this paper include the description of instrumentations including the construction of the main detector in

MEG, the superconducting quantum interference devices (SQUIDs), data analysis and interpretation.

Finally, several current experiments on brain functions using MEG method and its future applications in

clinical settings are discussed.

Keywords: Magnetoencephalography, SQUID, Electroencephalography

1. Introduction

The human brain is the most complex structure

known to man consisting of more than 10 billion

neurons in a vast network of signaling that handles

hundreds of billions of synapses [1]. During brain

activity, the intracellular currents are produced within

the network creating a weak magnetic field that

forms regular distributions on the surface of the head

where they can be recorded by sensitive

magnetometers.

Magnetoencephalography is a novel noninvasive

method of functional brain imaging. The

technology’s functions are to record the magnetic

flux across the head surface, estimate the locations of

neuronal activity, and project the signals onto an MRI

image of the brain.

The magnitude of the magnetic field that a MEG

measurement is in the range of pico-Tesla which is

millions times smaller than the magnetic field

generated by the Earth [5]. The only detector capable

of such a small field is the superconducting quantum

interference devices (SQUID). A SQUID

magnetometer is coupled to the brain magnetic fields

by combinations of superconducting coils called flux

transformer. The MEG signals are detected by the

magnetometer and converted into information on the

current distribution of the brain through series of

mathematical models which are briefly discussed in

later section.

Along with MEG imaging technique, many imaging

methods of the human brain are available today [3].

Methods such as X-ray imaging, single-photon-

emission computed tomography (SPECT), positron-

emission tomography (PET), and MRI provide

precise anatomical structures of the brain without

opening the skull, but exposed the subjects to

ionizing radiation, x-rays, and strong magnetic fields

[1]. Electroencephalography (EEG) is a

complimentary noninvasive imaging method with

MEG that similarly measures the neuronal activity of

the brain with the resolution of milliseconds.

Present studies and experiments have explored vast

knowledge of how the brain functions, yet the

fundamental questions of how the brain processes

information still remain unclear [1]. MEG technique,

as a result, can be used to investigate changes in brain

reaction to external stimuli and localize brain regions

involved with language functions [4]. In this review,

the physiology of the brain and the mathematical

aspect are being accessed along with the SQUID

instrumentation. Finally, the paper will survey the

current experiments and developments of clinical

applications using MEG.

2. Physiological basics of the neuronal

signals

Glial cells and neurons are the building blocks of the

brain. The glial cells are used for structural support

and neurons are the information processing units

Basics of Magnetoencephalography and its Applications as an Experimental Tool—V. Nguyen

18

which are the main focus in this section. A neuron

(Fig. 1) consists of a cell body as a controlling center,

dendrites to receive signals from other cells, and the

axon which carries the signal from the cell body to

other cells. The MEG signals are caused by

synapses from by the firing of an action potential at

the axon hillock [1]. As a consequence, the ion

pumps are activated resulting in the flow of charged

K+, Na

+, and Cl

- ions that would change the

membrane potential.

Figure 1. A neuron with its soma (body) with dendrites and

axons used to receive and carry signal from and toward the

soma. The three types of synapses during the firing of an

action potential [1].

The strength of the signal across neurons is

dependent on the permeability of the membrane to K+

and Na+

ions. An action potential is initiated when

voltage at the axon hillock reaches the firing

threshold. The change in potential triggers the

neighboring neurons like a domino effect. The

synaptic current flow is the source of the EEG and

MEG signals.

3. Mathematical Model of the

Electromagnetic Fields

This section briefly discusses about the origin of the

magnetic field being measure and the mathematical

model used to interpret the phenomenon. The MEG

signals measured can be fully described by a model

of simple current dipole in which the magnetic field

arose from (Fig 2).

On the macroscopic scale, the Maxwell’s equations

(Equation 1-4) and the continuity equation (Equation

5) can be used to calculate the electric field E and the

magnetic field B:

Figure 2: Current contours of the human head with the

magnetic flux flowing in and out of the head which are

indicated by the ―-‖ and ―+‖, respectively [3].

0

E (1)

t

BE

(2)

0 B (3)

t

EJB 0

0

(4)

tJ

(5)

where J is the total current density and ρ is the charge

density. The detailed derivation can be obtained

from Hamalainen.M et al [1].

The model of the current dipole is described as the

forward problem where as the magnetic field can be

easily calculated provided the knowledge of current

dipole and a realistic volume conductor model is

present. On the other hand, in a realistic research

case, the locations and strength of the currents in the

brain have to be estimated given the magnetic. This

inverse problem has no unique solution since each

magnetic field has an infinite number of possible

interpretations which was proven by German

physicist Helmholtz. Several methods using

probabilistic approach to estimate the location of the

brain currents can be further explored from

Hamalainen et al [2].

4. MEG Signal Detector and

Instrumentations

This section reviews in detail the instrumentations

necessary in MEG imaging including the mechanism

of the SQUID detector, noise reduction, and signal

processing. MEG is composed of a complex network

Basics of Magnetoencephalography and its Applications as an Experimental Tool—V. Nguyen

19

of many devices used to detect and analyze the

magnetic flux signal. A complete schematic of MEG

instrumentation system is shown in Fig 3:

Figure 3: Schematic of the entire MEG instrumentation [5].

4.1 Environmental Noises and Solutions

In the laboratory environment where MEG machines

are usually located, there are many sources of

magnetic noise with the magnitude several times

stronger than the biomagnetic signals to be measured

[1]. Magnetic noises are generated from electric

equipments, biological artifacts generated from the

smallest source of movements inside the subject’s

body such as blinking, muscle contractions, and

cardiac activity.

As a result, all devices and materials that may

interfere with the MEG have to be removed from the

environment and the subject. The most effective way

to reduce external disturbances is to measure MEG

signals in a magnetically shielded room. There are

currently four different methods that are used to

insulate a room from the external magnetic

disturbances: ferromagnetic shielding, eddy-current

shielding, active compensation, and the recently

introduced high temperature superconducting

shielding. Another method used in conjunction with

the shielded room is the flux transformer

configurations shown in Fig 4. A more detailed

description of how these configuration works can be

further explained by Hamalainen.M et al [1].

Figure 4: Several arrangements of the flux transformers. (a)

magnetometer; (b) series planar gradiometer; (c) parallel

planar gradiometer; (d) symmetric series axial gradiometer;

(e) asymmetric series axial gradiometer; (f) symmetric

parallel axial gradiometer; and (g) second-order series axial

gradiometer [1].

4.2 Superconducting Quantum Interference Devices

The only sensor on the market today sensitive enough

to detect the minute MEG signals is the SQUID [5].

The most popular types of SQUID are direct current

(dc) and radio frequency (rf) SQUID. Most modern

MEG instrumentations use dc SQUID due to more

sensitive detections and simpler electronic readouts

[5]. The dc SQUID is made up of a thin film of

superconducting loop, interrupted by two Josephson

junctions (Fig 5). Modern SQUIDs use materials

made up from the refractory metals due to their

outstanding resistance to heat and wear.

Figure 5: Simplified structure of a planar thin film dc

SQUID [1].

The rate of mapping the magnetic field can be

increased by integrating a multi-channel

magnetometer into the MEG system. The review by

Hamalainen.M et al [1] provides several examples of

multi-channel SQUID system used in experimental

applications.

4.3 Signal Analysis

The goals of MEG are to enhance the signal-to-noise

ration of the electrophysiological signals and to

locate the incoming signal. The detected signal is

averaged to enhance the signal-to-noise ratio.

Several quantitative methods are designed to analyze

the MEG signals, such as, time-amplitude analysis,

coherence analysis, forward and inverse solutions [5].

A typical result includes the bypassed filtered data,

the magnetic field distribution, and most importantly,

the estimated solution of the inverse problem. Proper

design of the MEG software is of equal importance

that has to display the analyzed data in such a way

that can be observed by the operating personnel.

Basics of Magnetoencephalography and its Applications as an Experimental Tool—V. Nguyen

20

5. Compliments Systems of MEG

MRI imaging system provides accurate images of the

brain anatomy. When used concurrently with MEG,

the locations of the magnetic field sources can be

compared with actual anatomical structure (Fig 6).

Figure 6. The combination of MEG and MRI imaging

techniques on a patient’s skull. The white dot shows the

location of the current dipole superimposed on an MRI

image [1].

Additionally, electroencephalography (EEG) has the

same working mechanism as MEG but provide

complimentary information regarding the volume

current of the brain. Consequently, the combination

of EEG and MEG can create significant

improvements in modeling the conductivity of the

brain.

6. MEG Imaging in Experimental

Research

MEG is one of the preferred methods used to

investigate how the brain reacts to various stimuli. It

is also the only imaging method that can reveal brain

function within milliseconds intervals; study by

Wheeles, J et al [4] has shown that MEG can be used

to localize brain areas involved in key language

functions. Using data obtained from MEG signals,

the team investigates the validity and reliability of

various tasks that can be used to identify the frontal

lobe areas involved in expressing language functions.

Several other studies at Helsinki University examines

how the human brain, specifically the auditory and

visual cortex reacts when evoked by different

external stimuli.

7. Conclusion

The human brain is the most complex structure

known to man consists of billions of neurons with an

equivalent number of synapses. MEG is one of the

emerging imaging techniques that are capable of

providing accurate location of the magnetic field

generated during brain activity. This paper has

surveyed the functional and structural make-up of the

MEG system. Even though there are many obstacles

in localizing brain activity based on the magnetic

field, better estimations in the future can minimize

this effect greatly. Many experiments and research

have shown the practicality and reliability of MEG as

an experimental tool assisting researchers to study

many aspects of how the brain works. In the near

future, MEG imaging has a great potential to be used

in many clinical applications.

8. References

1. Hamalainen.M et al. Magnetoencephalography-

theory, instrumentation, and applications to

noninvasive studies of the working human brain.

Rev. Mod. Phys., Vol. 65, No. 2: 413-497. 1993.

2. Hamalainen, M. S., H. Haario, and M. S.

Lehtinen."Interferences about sources of

neuromagnetic fields using Bayesian parameter

estimation‖ Technical Report TKK-F-A620.

1987

3. Lutken, B. Magnetoencephalography and its

Achilles’ heel. Journal of Physiology - Paris

97:641-658. 2003.

4. Wheeles, J et al. Assessing normal brain

function with magnetoencephalograph.

International Congress Series 1232. 519–534.

2002.

5. Vrba, J, and Robinson, S. Signal Processing in

Magnetoencephalography. METHODS 25, 249–

271. 2001.

21

MEDICAL SIMULATIONS OF INTRATHECAL MORPHINE FOR PAIN

CONTROL AND MANAGEMENT Jaimie M. Stewart Jstewa6@uic.edu

Abstract Intrathecal drug delivery is used for administering drugs to the central nervous system by

injecting into the cerebrospinal fluid. It is more efficient than oral and intravenous because it

requires less of the drug and allows drugs composed of macromolecules to bypass the blood brain

barrier. Additionally, certain drugs have greater therapeutic effect when administered

intrathecally because they are able to reach their specific binding site in the brain and spinal

canal. The infusion, distribution, and binding of morphine to the μ-opioid receptors were

investigated. The purpose of morphine is to treat chronic pain. Current treatments with morphine

are not patient specific and either result in over dosage or repeated dosage to achieve the desired

therapeutic effect. First, the intrathecal injection of morphine in the spine using a 3-dimensional

computational model created from patient images of the spine investigated the species transport of

morphine. Second, the intrathecal injection of morphine in an axial section of the lumbar region of

the spinal cord and spinal canal using a 2-dimensional computation model also created from a

patient image investigated binding, reaction rates, and kinetics of morphine.

Keywords: Morphine, Intrathecal, Spinal Cord, Spinal Canal, μ-opioid Receptors,

Cerebrospinal Fluid

1. Introduction

1.1 The μ-opioid Receptors

The typical μ-opioid receptor agonist is the opium

alkaloid morphine; μ (mu) refers to morphine. These

receptors can exist either presynaptically or

postsynaptically depending upon the cell types. The

μ-opioid receptors exist generally presynaptically in

the gray matter, and in the superficial dorsal horn of

the spinal cord, more specifically in the laminae I-III

[7]. μ-opioid receptors are found in numerous areas

throughout the body such as the external plexiform

layer of the olfactory bulb, the nucleus accumbens, in

numerous layers of the cerebral cortex, in certain

nuclei of the amygdala, and in the intestinal tract

[9,17].

1.2 Morphine

Morphine is a potent opioid analgesic used to relieve

severe pain. Morphine can be administered into the

body in various ways such as orally, rectally,

subcutaneously, intravenously, epidurally, and

intrathecally [3]. Toxicity of morphine can occur if

the patient has either an allergic reaction or has

overdosed. Symptoms that may allude to morphine

toxicity include respiratory depression, hypotension,

circulatory failure, comatose, and death [3]. Pain is

eliminated by morphine binding to receptors located

on neuronal cell membranes. This binding activates

the presynaptic action of opioids. Ca++ channels

reduce Ca++ entry, or indirectly by increasing the

outward K+ current, thus shortening repolarization

time and the duration of the action potential and

inhibiting neurotransmitter release. This inhibits pain

signals to be sent to the brain and allows the flow of

dopamine [6]. Figure 2 displays this action.

Figure 2. Morphine binding action [6]

Figure 1. Autoradiograms of axial sections of lumbar

regions (L2 and L4) that represent a distribution of

opiate receptors (light spaces) [7]

Medical Simulations of Intrathecal Morphine for Pain Control and Management—J. Stewart

22

Figure 4. 3D mesh of spine created from MRI data [13]

1.3 Intrathecal delivery

Intrathecal delivery of morphine is the best method of

drug transport in comparison to the other ways

morphine can be distributed. For example, if

morphine was taken orally only 40% to 50% of the

dose would reach the central nervous system.

Therefore, more of the drug would have to be

administered orally to obtain the same level of effect,

as a smaller dose of intrathecal delivery would

transport. This chronic administration increases the

chances of the patient overdosing. Additionally,

morphine crosses the blood-brain barrier, but it does

not cross it easily due to poor lipid solubility, protein

binding, fast conjoinment with glucuronic acid, and

ionization. Intrathecal delivery also allows for a drug

to pass the blood-brain barrier, therefore making

morphine’s bypass through the barrier easier than is

administered in an alternate way [17].

1.4 Computation of Morphine Binding Drug

Action

It is assumed that morphine reaction kinetics is a

second order reversible reaction, which agrees with

the following equation [16].

This equation presents the theory that there are a

limited number of receptors that morphine can bind

to and that this reaction is reversible allowing the

morphine to unbind from the receptor. The reaction

constants ka and kb govern the rate at which this

occurs. From this, a two second order curves are

expected as shown in figure 3.

2. Methods

2.1 Transport Model

2.1.1 Literature Data for Species Transport

Five patients, 3 males and 2 females with intractable

pain due to cancer were treated with 2 mg morphine

hydrochloride in 2ml of saline solution, both isobaric

and hyperbaric solutions were administered in

different patients, this paper will focus on isobaric

solutions. The isobaric solution was injected slowly

for 1 minute into the subarachnoid space (L5-S1) via

spinal needle. The CSF samples were collected at the

T10 level and measured using high performance

liquid chromatography analysis [5].

2.1.2 Three-Dimensional Spine

A computational mesh of the spine was created from

actual patient magnetic resonance imaging (MRI),

shown in figure 4. The mesh of the spinal canal was

created in Ansys [2]. The mesh is discretized into

633790 cells and is scaled at a length of 0.71 meters,

which is the average length of the male vertebral

column [11]. The spinal cord is not included in this

mesh, because this model is solely investigating

species transport in the CSF and CSF velocity.

Figure 3. Graphical representation of morphine

binding action, governed by constants ka and

kb

Medical Simulations of Intrathecal Morphine for Pain Control and Management—J. Stewart

23

Figure 6. Velocity at Ventral C4

2.1.3 Species Transport

In this model, a finite volume method integrating the

Navier Stokes, continuity, and the species transport

equations were used to conduct simulations. Water,

the bulk fluid, is assumed to be a Newtonian fluid,

because it resists compression and retains constant

viscosity. For the species transport, it is assumed that

there are no reactions, no radiation, and no heat

production. Additionally the size of the needle used

for injection is assumed to be 1 mm in diameter.

For the investigation of the species of drug transport

a three-dimensional simulation is selected. The

velocity of injection was calculated to be 1.0452e-05

m/s of 2.0 ml of mixture at a constant velocity over 1

minute.

2.1.4 Equations and Numerical Methods

The commercial software, Fluent [3], is used to

conduct the simulations. Fluent utilizes the Navier

Stokes equation (2), the continuity equation (3) and

the species transport equation (4). The Navier Stokes

equation describes the motion of fluid, the continuity

equation is a conservation equation for

incompressible flow, and the species transport

equation is a diffusion equation.

Equations (2)-(4) are solved using the finite volume

method in Fluent. It utilizes the numerical algorithm,

Semi-Implicit Method for Pressure-Linked equations

(SIMPLE) algorithm [15]. The algorithm initially

guesses for the pressure field, and then solves the

Navier Stokes equation for a velocity field. The

pressure and velocity gradients are used to compute

mass fluxes at each face, using the continuity

equation. The algorithm updates the pressure fields

and then corrects the previously computed mass

fluxes. This process is repeated iteratively until the

solution attained is within the specified convergence

criteria [14]

.

2.2 Binding Model

2.2.1 Lumbar Axial Section of Spinal Cord

and Spinal Canal

In this study, a finite volume method integrating the

Navier Stokes, continuity, species transport

equations, and reaction kinetics was used to conduct

first order steady state simulations by directing

variables of a species distribution in reactive zones in

an experimental setup which serves as a simplified

model for an axial lumbar section of the spinal cord

and canal. The mesh of the axial section of the

lumbar spinal cord and canal is discretized into

38782 cells. The sites of reaction in the right and left

dorsal horns were meshed finer for higher accuracy

of simulation results. In figure 5 the mesh is

displayed.

3. Results

3.1 Simulation of Three-Dimensional Spine

In figure 6 the velocity at the C4 ventral section was

measured and plotted. This data presented a

sinusoidal wave. This is representative of one cardiac

cycle for 1 second.

Figure 5. Mesh of axial lumbar section of spinal cord and

canal derived from actual patient image [4,14]

Medical Simulations of Intrathecal Morphine for Pain Control and Management—J. Stewart

24

Figure 8. Morphine distribution along the spine

for 15, 30, and 60 seconds [1]

Figure 7. Morphine distributions over time in the spine

at L2 over 1.65 seconds in the CSF [3]

Morphine was injected at L5-S1 of the spine. In figure

7 the distribution of morphine in the spine at L2 is

shown in the time span of 1.65 seconds.

Figure 8 displays the percentage of morphine

distributed along the spinal cord for 15, 30 and 60

seconds. Morphine peaks at approximately 20% of

morphine after length of injection.

3.2 Simulation of Lumbar Axial Section of

Spinal Cord and Spinal Canal

An initial mass fraction of morphine was set to be a

fixed value. This was repeated for five steady state

simulations with initial mass fractions of morphine of

0.01, 0.05, 0.1, 0.15, and 0.2. The right and left

dorsal horns were set as reactive zones to display

morphine binding. Figure 9 displays the mass

fraction of bound morphine vs. the initial fixed mass

fraction of morphine from the steady state simulation.

This graph shows the amount of bound morphine

found in the right and left dorsal horns depending on

the amount of morphine that is in the CSF. Figure 10

illustrates the contours of the mass fraction morphine

and bound morphine. The volume-average of bound

morphine for the left dorsal horn was 3.6987942e-05

and was 6.005871e-05 for the right dorsal horn.

4. Discussion

The morphine distribution displayed over time at L2

does not change drastically due to the short amount

distribution time, and the fact that the mesh is 3-

dimensional, fewer incidences of dispersion is

expected. Literature states that only 3.8% of

morphine enters the spinal cord when adminstered

intrathecally [12]. The data in figure 10 is

approximately this amount until a mass fraction of

0.2 is injected, this validates that amounts over 0.2

mass fraction are toxic and a physican would not

adminster this amount. The velocity plot shown in

figure 6 is the convective CSF flow field. The flow

dynamics of CSF flow were accounted for by

pulsations that were set by boundary conditions. The

Figure 10. Fixed Mass Fraction of Morphine 0.01:

Contours of the Mass Fraction Morphine (a) and the

Contours of “Morx” (Bound Morphine) (b) [3]

Figure 9. Mass Fraction of Bound Morphine

VS. Fixed Mass Fraction of Bound Morphine

Medical Simulations of Intrathecal Morphine for Pain Control and Management—J. Stewart

25

curve is 10 times larger than clinical data, but this

error can be accounted for in scaling.

5. Conclusion

Pulsatile flow affects the CSF flow field and the

dispersion of morphine in the spinal canal. Receptor

kinetics plays an important role in the uptake of

morphine. The initial concentration of morphine in

the system will determine the amount of morphine

that will bind to the receptors, however, there are not

unlimited receptors in the dorsal horns, and therefore

saturation of the receptors is expected to occur.

Future work includes building a global model that

would compute infusion, distribution, binding, and

downstream cellular events. More specific modeling

conditions including permeability of tissues in the

spine such as the pia membrane, and approximation

of μ-opioid receptors in the cord.

6. Acknowledgements

This work was supported by the Laboratory for

Product and Process Design. The author would like

express her deepest gratitude to Ying Hsu and Dr.

Andreas Linninger for their invaluable guidance,

support, and time in making this project possible.

7. References

1. A.D.A.M. The Anatomy of the Spine.

Photograph. Http://www.adamimages.com/.

2011.

2. ANSYS® Academic Research, Release 13.0,

Help System, Coupled Field Analysis Guide,

ANSYS, Inc.

3. ANSYS® Fluent, Release 6.3.26, Help System,

2ddp, ANSYS, Inc

4. ANSYS® Gambit, Release 2.3.16, Help System,

ANSYS, Inc.

5. Caute, B., B. Monsarrat, C. Gouarderes, J.C.

Verdie, Y. Lazorthes, J. Cros, and R. Bastide.

Csf morphine levels after lumbar intrathecal

administration of isobaric and hyperbaric

solutions for cancer pain. Pain. 141-46. 1988.

6. Chahl, L.A., Opioids: mechanism of action.

Australian Prescriber. 19:63-65. 1996.

7. Faull, R., and J. Villiger. Opiate receptors in the

spinal cord: a detailed anatomical study

comparing the autoradiographic localization of

[3H] diprenorphine binding sites with the

laminar pattern of substance P, myelin and nissl

staining. Neuroscience. 395-407. 1987.

8. DeCasteo L., Meynadier J., and Zenz M.

Regional Opioid Analgesia. The Netherlands:

Kluwer Academic Publishers. 23-26. 1991.

9. GetData Graph Digitizer. Digitize Graphs and

Plots. Vers. 2.24. 2011.

10. Gray, H. Anatomy of the Human

Body. Philadelphia; Lea & Febiger, 2000, 1396

pp.

11. Hanna, M. H., S. J. Peat, M. Woodham, A.

Knibb, and C. Fung. "Analgesic efficacy and csf

Pharmacokinetics of intrathecal morphine-6-

glucuronide: comparison with morphine. British

Journal of Anesthesia. 547-50. 1990.

12. Manx Pain Clinic. Spine01-MRI for Website.

Photograph. Http://www.manxpainclinic.com/us

erimages/spine01-MRI%20for%20website.jpg.

2010.

13. Overney, G. Exploration of human brain tissue.

Micscape Magazine. 84. 2002.

14. Pantakar, S.V., Numerical heat transfer and fluid

flow, Hemisphere Publishing Corporation,

United States, p126-p135. 1980.

15. Raffa, R.B., Porreca, F., Cowan, A., Tallarida,

R.J., Morphine-receptor dissociation constant

and the stimulus-effect relation for inhibition of

gastrointestinal transit in the rat. European

Journal of Pharmacology. 11-16. 1982.

16. Schreiter, A., Gore C., Roques, B.P., Stein, H,

and Machelska, H. Pain control by prevention of

opioid peptide degradation in peripheral

inflamed tissue. European Journal of Pain 13.

89. 2009.

17. Smith, H.S., Deer, T.R., Taats, P.S., Singh, V.,

Sehgal, N., Cordner, H.. Intrathecal drug

delivery. Pain Physician. 89-104. 2008.

26

APPLICATION OF NUCLEAR MAGNETIC RESONANCE IN POROUS

MEDIA Dan Yu

dyu23@uic.edu

Abstract Nuclear magnetic resonance (NMR) is now widely used as a tool to study the structure of porous

media system, molecular dynamics, and fluid transport and various processes occurring in them.

There are many types of such systems and an understanding of the spatial distribution of fluids

and their diffusion and flow with these structures is important in a variety of contexts. Examples

can be found in the reservoir rocks and aquifers of the oil and water industries, in biological

tissues and in many other naturally occurring or man-made systems. Typically the measured NMR

properties of molecules in the probed fluid reflect the internal dimensions and geometries of these

structures. This technique can determine characteristics such as the porosity and pore size

distribution, the permeability, the water saturation, the wettability, etc. This paper introduces the

basic theory in the process of using NMR to study porous media, and also a novel method called

NMR Cryoporometry which is developed to determine media pore size and pore size distributions

of porous materials. An application of NMR in porous media is also presented in this paper, which

is the development of the NMR well logging device for measuring nuclear magnetic properties of

fluids in underground porous sediments. NMR is an effective and quantitative method to monitor

the distribution of fluids and flow in porous media, particularly helpful in fields such as well

logging in which it is hardly accessible to sampling.

Keywords: NMR, porous media, permeability, NMR Cryoporometry, well logging

1. Introduction

Flow of fluids through porous media is involved in

many processes in biological and geological areas,

including microscopic and macroscopic researches.

For example, the transfer of gases to blood within the

lung and through organ tissues occurs in porous

media. As another example in a larger scale process,

the flow of water and the flow of petroleum in

underground geological formation are closely

associated with properties of porous media, too. This

is important to help extract petroleum. Even though

these processes are quite different, they share many

characteristics. They involve large expanses in

porous material, which are commonly hard to access

by direct sampling. These processes are considered

important, so researchers strive to design and control

of these flow processes in porous media [11].

1.1 Advantage of Nuclear Magnetic

Resonance

Various of methods used to gain information of

properties and fluid states in the porous media, such

as optical, ultrasonic, and x-ray methods. They all

can be used to visualize fluid saturations and flow

patterns and provide useful information. But all of

these methods have obvious limitations. Nuclear

magnetic resonance provides many exciting new and

effective opportunities for probing fluid states and

flows within porous media to obtain quantitative

information. It is not only an effective method but

also a non-invasive method which is sensitive to

molecular-level events within fluids, and with nuclear

magnetic resonance imaging, fluid states and

properties can be spatially resolved.

1.2 The Basic Idea and Limits of NMR Used

in Porous Media

It is often desired to simulate the flow of fluids in

porous media to design and control processes. Such

simulations require suitable mathematic models that

can describe various fluid states, and various porous

media properties within the models [5].

Many of the issues in modeling flow in porous media

are basically the same in different applications,

except that the terminology is often different.

By detecting the signals from the fluid phase, NMR

imaging is used to acquire information of properties

of flow in porous material. Protons are most

commonly nuclei chosen to be observed. The primary

challenge of NMR imaging in fluid-saturated porous

systems is that the transverse relaxation is too fast.

When the transverse relaxation time is smaller than

the minimum time needed to acquire image data from

Application of Nuclear Magnetic Resonance in Porous Media—D. Yu

27

excitation of the spin system, some relaxation will

have occurred before data are acquired, which will

cause difficulty in quantification of porosity and fluid

saturation. Furthermore, some fluid may not be

observed by NMR, due to its small pore size. This

means NMR has its limitation in detecting fluids that

reside in extremely small pores [5].

1.3 NMR Imaging in Underground Geological

Formations

The essential challenge for successfully applying

NMR in porous media is how to explicate the signals

measured by NMR. That means it is important to find

out the useful properties, which describes the storage

and flow in porous media, from the NMR

measurements [11].

There are a lot of porous media that are studied by

researchers. For example, NMR experiments can be

conducted in well pores to obtain information about

underground geological formations, which has

further increased interest in using NMR to

characterize fluids and flow in porous media. A

considerable effort has been made to study on these

porous media, but it is limited by the lack of means

for observing fluid states within porous media. In this

paper I will elaborate on those methods which are

applied to underground geological formations.

2. Methods

There are are basically two relaxation processes for

fluids in porous media. The first one is called T1

relaxation, which describes the decay of the excited

nuclear spin system associated with the fluid

molecules to thermal equilibrium with its

surroundings (the lattice). Experimentally, this spin-

lattice relaxation process, is the return of the

macroscopic nuclear magnetization to its equilibrium

after a perturbation. The second process is called T2

relaxation, which describes the decay of the spin

system to internal equilibrium. Experimentally, this

spin-spin relaxation process involves the decay to

zero of the magnetization perpendicular to the

external magnetic field [11].

Below I choose some of the most important processes

occurring in porous media when using NMR to

measure and study the properties of the porous media.

2.1 Relaxation Process

Through the modification of the relaxation properties

of the fluid inside the solid phase, we can obtain

physicochemical information on porous media, such

as pore size, wettability, permeability or surface

properties. Moreover, NMR can also use pulsed

gradient techniques to measure and visualize the

diffusion and flow in porous media. The

susceptibility contrast between the fluid and the solid

phases, however, is usually very strong in rocks, and

consequently a significant line-broadening is

observed. Thus, spin-echo methods must be used, and

in some cases more specialized solid-state methods

are necessary [6].

2.2 Diffusion in Porous Media

There are two basic models used in porous media,

which are called microscopic model and macroscopic

model. In this case, microscopic models are chosen.

Because microscopic models can be used to display

the relationship between pore structural features and

responses measured by nuclear magnetic resonance

experiments.

No matter which mechanism of relaxation is

considered, the enhanced relaxation associated with

surfaces is commonly modeled by giving a different

relaxation rate to the region near the solid surfaces

than to the bulk fluid. As a result, the signal

measured by NMR turns out to be proportional to the

total spin magnetization throughout the sample. This

depends on many factors, and the most essential one

is the interaction of molecular diffusion of the spins

with the geometry of the porous media [11].

2.3 Surface-Limited and Diffusion-Limited

Regimes

The relaxation will be enhanced in the pore-grain

interface in porous media. If the magnetic relaxation

occurs at the surface, the nuclear magnetization in a

pore is uniform. In this case, the magnetization decay

in the pore depending on the surface-to-volume ratio

of the pore instead of depending on the pore shape.

This is called the 'fast diffusion' or 'surface-limited'

regime [8].

In the opposite, if the magnetic relaxation occurs at

the grain surface, when pores are large or surface

relaxation is strong. In this case, the magnetization

decay depends on the shape of the pore and the

magnetization in the pore is not uniform. This is

called 'slow diffusion' or 'diffusion-limited' regime

[8].

Application of Nuclear Magnetic Resonance in Porous Media—D. Yu

28

2.4 Line Broadening

As we know, the NMR spectrum for fluid regarding

to one signal resonance frequency is Lorentzian in

shape, and has a width of few hertz. However, when

fluids in porous media interact with solid surfaces,

the line widths will rise, which is ranging from 102 to

104 Hz. Also the transverse relation rate will be faster

[11].

The spectrum also has relationships with some

properties in porous media. It has been observed that

the transverse relaxation time decreases as the fluid

saturation is lowered. Another experiment shows that

the spectral width increases with decreasing water

saturation. In fact, the inhomogeneous line

broadening in porous media (rocks) is mainly due to

the variations of magnetic susceptibility [11].

However, this line-broadening dependence result in

limitation of resolution in NMR, because the

resolution cannot exceed this fundamental parameter.

Moreover, the line broadening can also be used to

detect fractures in porous media. If there are fractures,

it will lead to significantly broadened line shapes,

because resonance frequencies of the fractures and

porous matrix are shifted by different amounts [11].

3. Results Using NMR in porous media, we can obtain

quantitative information, about pore size,

permeability and wettability. In this section, several

essential properties of porous media associated with

well logging are discussed in the first part. Also a

new NMR technique for measuring pore size is

briefly introduced. Lastly, the application to well

logging and the recent progress in this field are

briefly discussed.

3.1 NMR Permeability

Permeability is a very important property which is

essential in research and also industry associated with

porous media, such as well logging. Permeability is

the ability of fluids to flow through the rocks. The

higher the permeability, the easier it is to extract oil

and gas from the well.

NMR is typically used to measure permeability for

fluid typing and to obtain formation porosity. The

common approach is based on the model proposed by

Brownstein and Tarr [4]. They have shown that, in

the fast diffusion limit, given by the expression:

(1)

where ρ is the surface relaxivity of pore wall

material, r is the radius of the spherical pore and D is

the bulk diffusivity.

For a single pore, the magnetic decay as a function of

time is described by a single exponential:

(2)

where M0 is the initial magnetization and the

transverse relaxation time T2 is given by:

(3)

S / V is the surface-to-volume ratio of the pore, T2b is

bulk relaxation time of the fluid that fills the pore

space, and ρis the surface relaxation strength. When

the pores are small or the ρ is large, the bulk

relaxation time is small and the equation can be

simplified by:

(4)

In fact, real rocks should contain different types of

pores which have different sizes. These pores are

connected with narrow and small pore "throats"

which restrict interpore diffusion. But if we neglect

the influence of these "throats", we can consider

every pore as a distinct and independent pore and the

magnetization with each pore decays independently.

The decay can be represented by:

(5)

where ai is the volume fraction of pores of size i that

decays with relaxation time T2.

3.2 Wettability

The wettability conditions contain two or more

different fluid phases, which determine the

microscopic fluid distribution in pore network.

Nuclear magnetic resonance is effective and sensitive

to wettability, because the solid surface has strong

Application of Nuclear Magnetic Resonance in Porous Media—D. Yu

29

effect on promoting magnetic relaxation of the

saturating fluid.

There has been a long history of researchers

measuring wettability. The idea of using NMR to

measure wettability was first presented by Brown and

Fatt in 1956 [3]. Their theory is built on a hypothesis

that the movements of molecules are slower in bulk

liquid than at the solid-liquid interface. In this solid-

liquid interface the diffusion coefficient is reduced,

corresponding to a zone of higher viscosity. In this

higher viscosity zone, the magnetically aligned

protons can more easily transfer their energy to their

surroundings. Thus, the magnitude of this effect

depends upon the wettability characteristics of the

solid with respect to the liquid in contact with the

surface [7].

3.3 NMR Cryoporometry

NMR Cryoporometry (NMRC) is a recent technique

for measuring total porosity and pore size

distributions. It is based on the Gibbs-Thomson effect:

small crystals of a liquid in the pores melt at a lower

temperature than the bulk liquid. The melting point

depression is inversely proportional to the pore size.

This technique is well connected with gas adsorption

to measure pore sizes [9].

In a Cryoporometry measurement, some amount of

liquid is imbibed into the porous media (sample), and

the sample cools until all the liquid is frozen. Then it

warms slowly while measuring the quantity of the

liquid that has melted. This process is similar to DSC

thermoporosimetry, except that it has a higher

resolution. Because the signal detection does not rely

on transient heat flows, and the measurement can be

made discretionarily slowly. It is especially suitable

for those pores whose diameters range from 2 nm-2

µm.

As the fact that in many cases, the T2 relaxation time

in a frozen material is much shorter than that in

mobile material, Nuclear Magnetic Resonance is

suitable for using as a convenient method of

measuring the quantity of liquid that has melted, as a

function of time.

This technique is also suitable to experiment on

structural resolution in spatially dependent pore size

distribution [10], and dynamic information of the

liquid [1].

3.4 Application in Well Logging

Well logging measurements are always considered to

be quite complicated. But it is widely admitted that

the main target is the measurement of geophysical

properties under the surface of rocks. There are many

properties useful for well logging, such as

permeability, porosity and fluid content.

To introduce the definition of these properties,

porosity is the proportion of fluid-filled space within

rocks. It is this space which contains the oil and gas.

Permeability is the ability of fluids to flow through

rocks. The higher the porosity, the higher the possible

oil and gas content of rocks. The higher the

permeability, the easier for the oil and gas to flow

toward the well bore.

Beyond just the porosity and permeability, various

logging measurements allow the interpretation of

what kinds of fluids are in the pores—oil, gas, brine.

Moreover, the logging measurements can also be

used to study the mechanical properties of the rock

formations. These researches are important, because

these properties can be used to determine what kind

of damage (such as erosion) will possibly happen

during oil and gas production.

3.4.1 Small-scale instrumentation for nuclear

magnetic resonance of porous media

Researchers have been making an effort to design

instruments that can be used in porous media for a

long time, and develop small-scale nuclear magnetic

resonance instruments that are mobile and can be

moved into the site of the object, such as well pore of

an oil well. The analysis was originally restricted by

the inferior homogeneity of the magnets. But today

portable and mobile magnets are available for all

kinds of NMR measurements, including relaxometry,

imaging and spectroscopy in two types of geometries

(figure 1) [2].

These small-scale instruments are built with

permanent magnets, so the magnetic field strengths

are low. These low-field instruments come with

closed magnets and open magnets. The former

surrounds the sample, and the latter one is exposed to

the object and acquires NMR signal from a sensitive

volume outside the magnet and inside the object.

Currently these small-scale NMR instruments are

used for porosity analysis, describing of diesel

particulate filters, the determination of the moisture

content from grey concrete, and also new approaches

to analyze the pore space and moisture migration in

soil [2].

Application of Nuclear Magnetic Resonance in Porous Media—D. Yu

30

Figure 1. Instruments for small-scale NMR and for large-scale NMR [2].

This principle has been pioneered in well-logging

NMR and become popular for materials testing

with the invention of the NMR-MOUSE [2].

4. Discussion

Flows in the porous media are important in many

biological and geological processes. But sometimes

the sample is not accessible, so researchers make

much effort to design such instruments and in order

to measure and control the processes happened in

these media.

NMR in porous media is based on microscopic and

macroscopic mathematical models. It measures

several main properties of porous media to reflect

internal properties so we can predict what kind of

process (or sometimes damage) will happen during

industrial processes, such as production of oil and gas

from reservoir rocks. This greatly helps in specific

industry fields.

5. Conclusion

This paper briefly describes the process of using

nuclear magnetic resonance as a tool to study the

structure of porous media systems. Compared to

other techniques, such as sonic or x-ray, NMR turns

out to be an effective and quantitative method to

monitor the distribution of fluids and flow in porous

media, even though NMR also has its limitations, like

resolution.

NMR provides a suitable way to measure the porous

media that is hardly accessible for sampling. This

makes NMR widely applied in fields such as

measuring oil and gas in reservoir rocks. During the

experiment, researchers put NMR instruments in the

sample instead of taking the sample to the NMR

instruments, which is a revolutionary method in

measuring and monitoring properties in porous media.

6. References

1. Alnaimi, S.M. Binary liquid mixtures in porous

solids. Journal of Chemical Physics. 120 (5):

2075-2077, 2004

2. Blümich, F. C., M. D. et al. Small scale-

instrumentation for nuclear magnetic resonance

of porous media. New Journal of Physics.13

(2011) 015003 (15pp)

3. Brown, Fatt. Measurements of fractional

wettability of oil fields' rocks by the nuclear

magnetic relaxation method. Society of

Petroleum Engineers. Fall Meeting of the

Petroleum Branch of AIME, 14-17 October

1956, Los Angeles, California

Application of Nuclear Magnetic Resonance in Porous Media—D. Yu

31

4. Brownstein K.R., Tarr C.E. Importance of

classical diffusion in NMR studies of water in

biological cells. Physical Review A. 19 (6): 2446,

1979

5. Chang, A.T. Watson. NMR imaging of fluids

and flow in porous media. Experimental

Methods in the Physcial Sciences. 35: 387-423

6. Guillot. MRI of oil/water in rocks. Encyclopedia

of Spectroscopy and Spectrometry. p. 1380-1387,

1999

7. Howard J.J. Quantitative estimates of porous

media wettability from proton NMR, Magnetic

resonance imaging. 16 (5–6): 529, 1998

8. Kleinberg. Well logging. Encyclopedia of

Magnetic Resonance. 2007.

9. Mitchell J, Webber J. B. W., Strange J. H.

Nuclear Magnetic Resonance Cryoporometry,

Physics Reports, 461 (1): 1–36, 2008

10. Strange, J.H. Spatially resolved pore size

distributions by NMR. Measurement Science

and Technology. 8 (5): 555-561, 1997

11. Watson, C. T. Philip Chang. Characterizing

porous media with NMR methods. Progress in

Nuclear Magnetic Resonance Spectroscopy. 31:

343-386, 1997

32

VIEWING INTERVERTEBRAL DISC PROPERTIES OF RODENT

ANIMALS THROUGH MORPHOLOGY AND MRI Julia Zelenakova jzelen4@uic.edu

Abstract Rodents are popular laboratory animals used for investigation of intervertebral disc disease and

other spine related disabilities. Rodents have well-characterized skeleton, although it possesses a

smaller cancellous bone to total bone mass ratio, when compared to human skeleton. Similarly,

the rodent intervertebral disc consists of the nucleus pulposus (NP) surrounded by the annulus

fibrosus (AF). Disc provides acceptable resemblance in terms of morphology, cellularity,

biochemistry and biomechanical properties. It is possible to observe the changes in signal

intensity when comparing a control group of animals with a group that shows signs of disc

degeneration. Nevertheless, different stages of disc degeneration and the structures of the

intervertebral disc itself can be recognized using fast spin echo sequences. T1 and T2 relaxation

times are recorded to distinguish between regions of the spine motion segment. Structures such us

the nucleus pulposus, annulus fibrosus, cartilaginous endplates and the vertebral bodies are able

to be displayed with excellent soft tissue contrast and high spatial resolution. It is more difficult to

acquire diffusion tensor imaging data to quantify variations in water diffusion, due to microscopic

structures of collagen fibers and the overall size of the disc. It is necessary to understand the

animal disc features and use previously obtained knowledge as a foundation for diagnostics of the

degenerative disc disease pathways and its progression in humans.

Keywords: Intervertebral Disc, MRI, Rodent, Disc Degeneration Disease, Nucleus Pulposus,

Annulus Fibrosus

1. Introduction

Rodents have interacted with the human population

for decades and are mostly known for disease

spreading and crop destruction. Although their

reputation among the general public has not

improved over the years, they have become very

popular in the research society. Small animal rodent

models are widely used to conduct physiological and

biochemical research studies. Rats have been

domesticated as first mammals for being tireless,

their compact size, breeding habits, short lifespan,

and their personality features. Rodents become

addicted to drugs, alcohol and other substances

similarly as humans, and their system can absorb and

eliminate several drugs at comparable rates. The

Food and Drug Administration usually requires

rodent animal studies as a foundation to preclinical

investigation. Rodents comprise up to 95% of all

laboratory animals used for research purposes. [1, 2]

Orthopaedic research is among the many fields that

have adopted rodent mammals as its research model

for biochemical, morphological and biomechanical

analysis. Several hundred papers have fully examined

the properties of specific bones and cooperation of

musculature within the whole skeleton. Particularly

large interest has been given to the investigation of

the spine [1,2,4,7]. Both skeletally immature and

mature animal models are used for specific aims,

such as whether examined changes are related to

adolescent bone growth, or if they are related to fully

mature bone. However, animal models are not limited

to only the investigation of bone properties, but also

soft tissue components. Using animal models is

necessary in order to gain insight in elementary

mechanisms and to evaluate new treatment strategies.

They have shown importance particularly in

investigation of intervertebral disc degeneration

disease. Several requirements must be met in order to

proceed with animal models, such as inducing the

degeneration of the disc. In order to mimic the state

of progression as it occurs in humans, the animal

intervertebral disc model should be validated in terms

of morphology, cellularity, biochemistry and

biomechanical properties. Nevertheless, animals

studied for specific findings need to possess the same

characteristics in their group to avoid any other

influences on the studied matter. Comparison of the

animal intervertebral disc model to the human

intervertebral disc needs to be properly optimized in

order to draw conclusions for our findings.

Spontaneous recovery should not occur while the

evaluation of our tested animal models is ongoing,

and all treatments to the intervertebral disc need to be

reproducible and reliable during modeling procedures

for inducing animal disc degeneration.

Viewing Intervertebral Disc Properties of Rodent Animals through Morphology and MRI—J. Zelenakova

33

2. Similarities and Deviations between

Rodent and Human IVD Anatomy

Reversal of disc degeneration disease has yet to be

discovered. Rodent animal models are widely used to

study the role of therapeutic treatment and surgical

procedures in order to halt the occurrence of

degenerative disc disease. Animal species are

evaluated, measured and compared with each other in

order to find a valuable animal model for exploration

of intervertebral disc chronic disorder.

Figure 1. Representative axial cross section from human,

rat tail and lumbar and mouse tail and lumbar intervertebral

disc. [5]

The human intervertebral disc consists of the annulus

fibrosus and the nucleus pulposus, and it is connected

to adjacent vertebral bodies with cartilagenous

endplates. This basic morphological structure of the

intervertebral disc is shared with most other animal

species. It is reasonable to suggest that establishing

animal models for examining the intervertebral disc

would be a great opportunity to learn about how to

preserve the function of the human disc and possibly

how to treat degenerative disc disorders, which occur

in the majority of the global adult population.

However, the availability of the tissue, the decreased

variability between subjects compared with humans,

and the feasibility to perform in vivo experiments is

relevant for successful study, as the animal models

are often criticized for being irrelevant to the human

situation.

2.1 Cellular Composition of Rodent and

Human Intervertebral Disc

All animals that model disc degeneration have

insufficiencies in their comparability to humans. One

of them is the difference in size of the intervertebral

disc, where the small size of the rodent disc affects

the diffusion process important for oxygenation and

nutrient supply of cartilage. The human intervertebral

disc lacks notochordal cells at the age of skeletal

maturity, whereas in the animal disc the notochordal

cells are present, even during the post-adolescent

period of their lifespan. This is a crucial difference

between the human and animal disc because it is

affects the progression of degeneration and

regeneration of the disc. Notochordal cells are

believed to modify disc matrix synthesis, and their

presence influences the cell viability and nutrition of

the disc and affects proteoglycan content in the

nucleus pulposus. Proteoglycan fragmentation is

usually the starting indication of human disc

degeneration and it can be mimicked by injections of

different degrading enzymes that affect

proteoglycans. This is one of the methods of how disc

degeneration can be induced in the rodent animal

model. When the nucleus pulposus starts to lose

proteoglycans, it is losing its water binding capacity,

and changes in the mechanical properties are

followed by alterations of biochemical factors.

Similarly with humans, a common pathway of

increasing intervertebral disc degeneration takes

place, where alterations in the nucleus pulposus and

the anulus fibrosus occur.

Other signs of degenerative disc disease are loss of

disc height and signal intensity on T2-weighted

magnetic resonace images, histologic and

macroscopic changes, and biochemical and gene

expression pattern modifications. Researchers are

trying to induce these cascades in the rodent animal

models as well as in other animal species to learn

about the progression of the disc diseases, by

attempting to follow the pathways of its progression.

2.2 Morphological Composition of Rodent

and Human Intervertebral Disc

Several disc types were investigated in comparison to

the human disc in terms of cost, availability, and time

constraints. Lumbar disc geometry for the rat and

mouse were evaluated, as well as tail disc geometry

for both rodent species. Their geometrical properties

were normalized and compared with humans. The

representative axial cross section of the rat tail, rat

lumbar, mouse tail and lumbar intervertebral disc is

shown on the Figure 1.[5]. The human intervertebral

disc is noted for its kidney-like shape, and both

rodent species differ from this shape.

The tail intervertebral disc of both species has a

circular cross-section and its shape is unlike the

human one. Tail disc models have been often used

Viewing Intervertebral Disc Properties of Rodent Animals through Morphology and MRI—J. Zelenakova

34

because of its excellent when surgical procedures are

required in the studies. Tail models are also preferred

when biomechanical loads are applied on the

intervertebral disc to measure mechanical properties

of both healthy and degenerative disc. Numerous in

vivo studies use external fixators that can easily be

attached to the tails of both rodent species. Future

investigations are needed to confirm that using the

rodent tail disc provides a valid comparison to the

anatomy and function of the human disc.

Unfortunately, there is still a general lack of

comparative data with respect to the human disc.

Analog animal models are evaluated by vertebral

body anatomy, biomechanics, size, cost, disc

geometry, biochemistry, cellularity and others.

Table 1. Normalized Parameters of the Disc to the Area, as

well as to the Lateral and Antero-Posterior Width [5]

Height Lateral

width

AP

Width

Area

Human 0.202 1.0 0.665 0.553

Rat L 0.161 1.0 0.753 0.609

Mouse L 0.169 1.0 0.674 0.535

Rat T 0.288 1.0 1.067 0.834

Mouse T 0.198 1.0 1.083 0.813

One of these studies focused on the comparison of

disc anatomies across animal species and compared

the rat lumbar and tail anatomy as well as mouse

lumbar and tail anatomy. It showed a comprehensive

evaluation of rodent disc geometry, axial cross

sections, shape and position of the nucleus pulposus.

Relative disc height for the rodent species has been

also collected. All obtained parameters were

normalized and compared with human lumbar disc

geometry, see Figure 2. The scaled dimensions

collected are summarized for the rodent species in the

Table 1 [5] and can further be used for mechanical

testing protocols and finite element models.

The geometry of the animal disc must be taken into

consideration when analyzing collected mechanical

data. Interesting findings show that the mouse tail

normalized disc height is the only species within 10%

of the human disc. The normalized disc height is

larger in the rat tail than the human, and the rest of

the species seems to have a smaller normalized disc

height. Human lumbar disc anterior-posterior width is

most closely matched within 10 to 15% by the mouse

and rat lumbar discs. The mouse and rat tail discs

have a large normalized anterior-posterior width

when compared to human disc, because of the

circular shape of the intervertebral discs in the tail.

[3, 6] Validation for the mouse and rat disc as an

animal model of the human disc provides correlations

between lumbar spine properties and rodent lumbar

spine models. The differences between lumbar and

tail intervertebral disc need additional examination in

order to select the appropriate model for the human

disc.

Figure 2. Schematic view of IVD cross-section, defining

geometric parameters of IVD. Disc LW and Disc AP-W are

disc width in lateral and antero-posterior direction,

respectively. Nucleus LW and Nucleus AP-W are nucleus

pulposus lateral and antero-posterior widths, respectively.

After normalizing parameters across the rodent

species, several ratios were taken into account: the

disc height scaled by lateral width, the AP width

scaled by lateral width, and the nucleus pulposus area

scaled by disc area. Overall deviation from human

geometry for these parameters is the following:

mouse lumbar (12%), rat lumbar (15%), mouse tail

(18%) and rat tail (46%) [3]. It can be noted that

using the rat tail disc model for comparison with the

human disc might not be the best idea.

2.3 Posture Differences between Rodent and

Human Intervertebral Disc

Another limitation of using rodent animal disc

models is that most of the animals used for spine

research are quadruped. Whether the horizontal

position of the animal spine can be an adequate

model of the vertical human spine position from the

biomechanical point of view can be questioned.

Because of the horizontal vs. vertical positions of the

spine, there is subsequently a difference in terms of

mechanical load that animal and human spine

experience. It can be seen in the behavior of the

animal bone, and it corresponds morphologically to

the different directions of trabeculae formation as in

humans. Bone needs to withstand the physiological

and mechanical loads that are necessary to control the

posture of either a quadruped or bipedal spine, so as a

consequence its structure will be affected. This

phenomenon is described by Wolff’s law. Due to

additional tensile forces from muscles and ligaments,

quadrupeds experience more axial compression on

their spine. [8]

Viewing Intervertebral Disc Properties of Rodent Animals through Morphology and MRI—J. Zelenakova

35

Figure 3. Rat Skeleton [10]

In order to direct the quadruped posture, the rodent

spine is mainly loaded by axial compression. This is

why trabeculae in a rodent’s vertebral body are found

to be in the horizontal direction between the superior

and inferior endplates. Differences in bipedal and

quadruped posture of humans and rodents

respectively are causing differences in the bone

structures of the vertebrae between the species. The

density of the vertebrae of humans is lower than that

of rodent vertebrae, signifying that the quadruped

posture has to sustain higher axial compression

stresses than the upright human posture. As a result,

the rodent vertebrae will absorb most of the axial

compression and its intervertebral disc will

experience a smaller amount of compression force.

Figure 4. Human Skeleton [11]

Rodent vertebral bodies are longer when compared to

human ones, so this results in a smaller rodent disc

height when normalized and compared to humans.

Therefore, there are some restrictions on the

transferability of the outcome from rodent animal

experiments to the human situation. The rodent

skeleton consists of 6 lumbar vertebrae and 12 caudal

(tail) vertebrae (see Figure 3). And the shape of

rodent vertebra resembles human vertebral bodies,

though posterior spine elements differ in angle

orientation as well as in size and shape. Even if it is

accepted that quadruped animal spines are

experiencing different loads from those in the upright

human spine (see Figure 4), several studies show

remarkable resemblance in geometry, demonstrating

that quadruped and bipedal spines must be loaded in

a similar way.

3. Monitoring Rodent IVD through

Magnetic Resonance Imaging

It is possible to observe the changes in signal

intensity when comparing a control group of animals

with a group that shows signs of disc degeneration.

Nevertheless, different stages of disc degeneration

and the structures of the intervertebral disc itself can

be recognized using fast spin echo sequences [6,9].T1

and T2 relaxation times are recorded to distinguish

between regions of the spine motion segment.

Structures such us the nucleus pulposus, annulus

fibrosus, cartilaginous endplates and the vertebral

bodies are able to be displayed with excellent soft

tissue contrast and high spatial resolution.

Figure 5. Cross-section of the rat IVD using 9.4T magnet at

UIC, using 5mm coil

The T2-weighted image in Figure 5 represents a

cross-sectional area of rat lumbar L2 healthy disc. It

is displaying different structures of the rodent

intervertebral disc; such as annulus fibrosus and

nucleus pulposus using 9.4T magnet at the NMR

facility of UIC. In this image you can clearly

distinguish these structures of the disc. Along the

perimeter of the disc are fiber layers that form the

annulus fibrosus. Near the middle of the disc, the

Viewing Intervertebral Disc Properties of Rodent Animals through Morphology and MRI—J. Zelenakova

36

fibers are being replaced by gellous structures in the

transitional zone. The center of the rat disc is formed

by the nucleus pulposus, and it has approximately

80% to 95% content of the water. It is a gel-like

substance and it acts as a shock absorber for the

spine. Traces in the green color are representing

annulus fibrosus portions of the disc, the yellow trace

located in the center, is the representative of the

nucleus pulposus. Special preparation of the rat disc

specimen was done by carefully dissecting the rat

intervertebral disc from the spinal column, cutting off

posterior elements and dissecting vertebral bodies in

order to fit the disc into a 5mm coil used for

Magnetic Resonance Imaging. It is more difficult to

acquire diffusion tensor imaging data to quantify

variations in water diffusion, due to microscopic

structures of collagen fibers and the overall size of

the disc.

4. Conclusion

Rodents are popular laboratory animals used for

investigation of intervertebral disc disease and other

spine related disabilities. Rodents have well-

characterized skeleton, although it possesses a

smaller cancellous bone to total bone mass ratio,

when compared to human skeleton. Similarly, the

rodent intervertebral disc consists of the nucleus

pulposus surrounded by the annulus fibrosus, and

provides acceptable resemblance in terms of

morphology, cellularity, biochemistry and

biomechanical properties. Choosing appropriate

methods to fully explore the properties of the rodent

intervertebral disc, will give us a powerful tool for

future analysis of human disc pathologies.

Limitations for radiological data collections

presented in this paper include the size of the imaged

structures, where both rodent species are quite small.

This paper reviews deviations in morphology

structures between human and rodent intervertebral

discs, and demonstrates the close similarities between

the two. The process of disc degeneration involves

alterations in structural proteins within the

extracellular matrix including collagens and

proteoglycans, which can be displayed radiologically

as well as histologically. Previous studies have used

animal models to mimic human degenerative disc

disease, and this trend will continue in the future,

especially due to cost effectiveness, vailability and

lifespan of the animal. Immunohistochemical,

biomechanical and radiological analysis will help

explore the animal intervertebral disc, so it can be a

better tool for future investigation of human disc

degeneration disease.

5. References

1. Clause, B. T. The Wistar Rat as a Right Choice:

Establishing Mammalian Standards and the Ideal

of a Standardized Mammal. J. Hist. Biol,, 26(2):

329-349, 1993

2. Trull F. L., B. Rich. More Regulation of

Rodents., Science 284(5419):1463, 1999

3. Elliott, D. M. and Sarver J. J. Young Investigator

Award Winner: Validation of the Mouse and Rat

Disc as Mechanical Models of the Human

Lumbar Disc. Spine 29 (7): 713–72, 2004

4. Gruber H. et al. The Sand Rat Model for Disc

Degeneration: Radiologic Characterization of

Age-Related Changes. Spine 27(3):230–234,

2002

5. O’Connell, G. et al. Comparison of Animals

Used in Disc Research to Human Lumbar Disc

Geometry. Spine 32(3): 328-333, 2007

6. Pfirrmann, C. W., A. Metzdorf, M. Zanetti, J.

Hodler, and N. Boos. Magnetic Resonance

Classification of Lumbar Intervertebral Disc

Degeneration. Spine 26(17): 1873-1878, 2001

7. Singh, K. et al. Animal models for human disc

degeneration. The Spine Journal 5:267S–279,

2005

8. Smit, T. H. The use of a quadruped as an in vivo

model for the study of the spine - biomechanical

considerations. Eur Spine J 11 :137–144, 2002

9. Sobajima, S. et al. A Slowly Progressive and

Reproducible Animal Model of Intervertebral

Disc Degeneration Characterized by MRI, X-

Ray, and Histology. Spine 30(1):15-24, 2005

10. ―Rat Skeleton.‖ Carolina Biological Supply

Company. Web. February 2012.

<http://www.carolina.com/text/pdf/owls/ratskelet

on.pdf>

11. ―Vertebral Column.‖ Spineuniverse. Web. 20

Sept. 2011.

<http://www.spineuniverse.com/anatomy/vertebr

al-column>.

37

CALL FOR ARTICLES - FALL 2012

Mission The mission of the journal is to develop the art of scientific writing among students.

Students may submit articles that discuss original research or review research published

elsewhere. This allows students to hone their writing skills without being limited by a

lack of a data to present. The journal also provides students with an opportunity to be

involved as editors and reviewers. This gives students an overall appreciation of the

processes involved in disseminating scientific findings. The journal finally serves to

expose the reader to current trends in the bioengineering spectrum.

Scope Completed research projects are not necessary for publication. Articles are intended to

document research accomplishments to date. It is expected that many of the articles that

appear in the journal will later be expanded to full-length studies and published

elsewhere. Publication in the UBSJ will not preclude later publication of the results in a

more complete presentation. Submissions can range from original research articles and

technical reviews to book reviews relevant to bioengineering. Letters to the editor are

also welcome.

Submission Process & Guidelines

We have setup a Bioengineering Student Journal Blackboard site to streamline

submissions and make the process as transparent as possible.

1. Single author.

2. The student must be a current UIC Bioengineering undergraduate/graduate student.

3. Only review and research articles may be submitted.

4. Appropriate credit must be cited and permission must be given when applicable.

5. Papers are typically around 4-6 pages long and must be formatted according the

template available on Blackboard.

6. The criteria of acceptance shall be based on volume of papers received, relevance,

subject mastery, organization, appropriate documentation etc.

7. Please refrain from submitting any material that might involve copyright restrictions.

This journal is for learning purposes only. Papers already submitted elsewhere, in-press,

or already published may not be resubmitted here.

8. All submissions will be peer reviewed and the author will be informed in advance if

their article is selected for publication.

9. Submissions are to be made as both .doc and .pdf files. The files shall be named in the

following format:

AuthorName_AuthorLastName_AbbreviatedArticleTitle_VersionMonthDate

If you have any questions please contact:

bioejour@uic.edu

38

FRONT

“Broken Knee, X-ray”. Image courtesy of © Zephyr/Science Photo Library/Corbis (royalty-

free, license obtained).

SEM of a Neuron Cell. Image courtesy of ACM at the University of Illinois at Urbana-

Champaign, part of the Sigbio group project. URL:

<http://www.acm.uiuc.edu/sigbio/project/nervous/micro_info/ct_neuron.html>.

Gene Sequencing Plot. Image courtesy of M. F McDermott, et. al., from “Germline Mutations

in the Extracellular Domains of the 55 kDa TNF Receptor, TNFR1, Define a Family of

Dominantly Inherited Autoinflammatory Syndromes.” Cell 97 (1999): 133-144.

Action Potential Plot. Image courtesy of Sharanya Arcot Desai et. al., from “Improving

impedance of implantable microwire multi-electrode arrays by ultrasonic electroplating of

durable platinum black.” Frontiers in Neuroengineering 3 (2010).

BACK

Cell-Stained Images a-f. Image courtesy of W. Boesmans, et. al., from ”Brain-derived

neurotrophic factor amplifies neurotransmitter responses and promotes synaptic communication

in the enteric nervous system.” Neurogastroenterology 57 (2007): 314-322.

Protein Subunits 3D Image. Image courtesy of the University of Texas Health Science Center

at San Antonio.

Blood Flow Dynamics in Vessels. Image courtesy of Fernando Calamante, et. al., from

“Estimation of bolus dispersion effects in perfusion MRI using image-based computational fluid

dynamics”.

bioe.uic.edu