Advanced MRI methods in diagnostics of spinal cord

pathology

Stanisław KwiecińskiDepartment of Magnetic Resonance

MR IMAGING LABMR IMAGING LABMRI /MRS IN BIOMEDICAL RESEARCH MRI /MRS IN BIOMEDICAL RESEARCH

ON HUMANS AND ANIMAL MODELS ON HUMANS AND ANIMAL MODELS IN VIVOIN VIVO

Equipment: 4.7T/31cm MRI, 8.5T MR Microscope, AnimalLab, access to clinical 1.5T MRI

Diffusion Tensor Imaging & fMRI of spinal cord on humans and rats to develop methods of earlydiagnostics of injury.MRI of heart pathology on Transgenic mouse model.31P MRS in human skeletal muscle physiology.MRI in pharmacy to monitor the disintegration processes of drug tabletsMRI in Dentistry in vitro on extracted teeth.MRI/MRS Physics and Technology:sequence design, software and hardware: gradient coils, RF-coils and probes

GenomicGenomic Mouse HeartMouse Heart

HumanHuman spinal cordspinal cord

DiffusionDiffusion Rat Rat Injured Spinal CordInjured Spinal Cord

Spinal Cord Imaging – why so important ?

• Spinal cord injuries are main factor of permanentdisability affecting population as a result of communication, work or sport accidents.

• Outgrowth and regeneration of injured nerve fibersis possible

• Early diagnosis of pathologies such asAlzheimer, Sclerosis Multiplex, tumors,venous malformations ...

Major Nerve Pathways

of a spinal cord

www.paraplegic-online.com

What MRI Physicist can offer ?

To develop a non-invasive, quantitative method of EARLY COMPLETE DIAGNOSTICS of the spinal cord injuries , white matter diseases and other spinal cord pathologies in humans in vivo based on

MR diffusion tensor imaging (DTI)

and

functional MRI (fMRI)

Problems with Spinal Cord Imaging

• Size and shape

• Environment (various tissues, bones, CSF ) poor magnetic field homogeneity caused by susceptibility differences

• Motional artefacts (breathing, swallowing, beating heart, pulsating CSF)

Image from www.vilenski.org/science/humanbody

Grey and White Matter in Spinal Cord

1603120CSF

901010WM

1001200GM

T2 (ms)T1 (ms)Medium

Why Diffusion Imaging ?• Diffusion provides unique indicator of tissue

microstructure (natural contrast !!!)

• Diffusional parameters change immediately after injury

• Diffusion attributes allow „fiber tracking“

Extracting information from Diffusion Imaging:

• Images

• Vector Maps

• Quantitative Analysis (FA – Fractional AnisotropyADC – Apparent Diffusion Coeficient...)

Diffusion Tensor S ∼ e-b⋅D

DD D DD D DD D D

xx xy xz

yx yy yz

zx zy zz

αβ =

,

Matrix

It fully describes molecular mobility along each direction and correlation among these directions

Quantitative analysis:FA = √{3[(λ1- ⟨λ⟩ )2 + (λ2- ⟨λ⟩ )2 + (λ3- ⟨λ⟩ )2]} / √{2[(λ1

2 + λ22 +λ3

2)]}

ADC = ⟨λ⟩

Where ⟨λ⟩ = Trace/3 = (λ1 + λ2 + λ3)/3

λ1 , λ2 , λ3 : eigenvalues of a diffusion tensor

We have started with RATSSagital projection Axial projection

T2T2

DTIDTI

4.7T Bruker, bore: 30 cm

tADC Slice 1 WM

00.00020.00040.00060.0008

0.0010.00120.0014

1 24 48 168

time [h]

ADC

[mm

^2/s

] Reference (normal)

Injured with drug

Injured without drug

Testing neuroprotecive drugs

ADC

We have continued with HUMANS Images from 1.5T clinical system

T2 DTI ADC FA

Cervical – Thoracic Spine FA and ADC Sagittal plane

8 volunteersFA ADC

1.06 ± 0.2932 ± 3Lumbar

0.77 ± 0.0655 ± 7Thoracic

0.78 ± 0.0661 ± 5Cervical

ADC x 10-3 [mm2/s] Entire Cord

FA [%]

Entire CordSpinal

segment

DTI measurements in axial projections

FA in GM & WM - voluntie rs

0

0,2

0,4

0,6

0,8

1

0 1 2 3 4 5 6 7 8 9

S lice numbe r

FA

VHR

VHL

P F

AFC3 C4 C5 C6

Localizer

FA

C5

VHR VHLAF

PF

Patient No.1 Shot wound (10 years after)

0.66

0.86

0.80

0.78

0.76

0.861.250.820.81

36

35

43

40

37

26133537

T2 DWI ADC [x10-3mm2/s]ADC - healthy volunteer:

0.78 ± 0.06

FA [% ]FA - healthy volunteer:

61 ±5

Patient No.2 Gym accident C5/C6 dislocation

ADC [x10-3mm2/s ]ADC - healthy volunteer:

0.78 ± 0.06

FA [% ]FA - healthy volunteer:

61 ±5

0.94

0.83

0.92

0.60

0.550.80

1.11

1.18

58

66

58

42

3240

41

38

CTBefore surgery

T2After surgery

Going further - biexponential diffusion

Af

+ As⋅exp(-b⋅Ds) S=Af⋅exp(-b⋅Df)

Vector Maps ⇒ Spinal Structure1st eigenvector 2nd eigenvector

Diffusion Ellipsoid

λ1

λ3λ2

λ1>λ2>λ3Cajal et al, Histology of the Nervous System

Craniocaudal Fibers

Collateral Fibers

Fiber tracking in the spinal cord

The grey matter of the spinal cord has a high density of neuron cell bodies and high capillary density. When spinal cord neurons are activated, hemodynamic effects, comparable to those in the brain should take place.

Spinal fMRI

Task

neuron activation

inflow of oxygenated blood

Decrease of deoxygenated blood level (paramagnetic) BOLD effect

Local change of proton density SEEP effect

Change of signal intensity

Spinal cord fMRI study: aims

• Determine whether fMRI signal can be measured on a 1.5T / 3T clinical MR systems and on 9T research system

• Determine whether the fMRI signal can be spatially localized to particular anatomical locations

• To verify intra-subject reproducibility

Dermatomes of a human body

stimulation

Activation area

www.driesen.com/dermatomes_of_the_human_body.htm

Stimulation paradigmblock design 30sec. On / 30sec. Off

Motor task: Fist clenching

Thermal stimulation: Ice bag

Electric stimulation: 3-9mA, freq. 8Hz

Results – Motor task

Fist clenching

Axialslices

fMRI study on RATS

Simultaneous spinal and brain fMRI

Spinal cord Brain

-1

-0,5

0

0,5

1

1,5

2

2,5

3

3,5

4

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31Image number

REST1 STIM1 REST2 STIM2 REST3

Me

an

sig

na

l c

ha

ng

e

bra in

spina l cord

paradigm

Conclusions

DTI and fMRIare powerful tools enabling

complete diagnosis of spinal cord injury and pathology

in the near future

Thank you for your attention

Acknowledgment to our scientific collaborators in the field of spinal MRI

M.Konopka, M.Hartel, Diagnostic Imaging Centre „HELIMED”, Katowice, Poland

B.Tomanek, P.Stroman, Institute for Biodiagnostics, Calgary, Alberta, Canada

S.Kollias, P.Summers, Institute of Neuroradiology, University Hospital Zurich, Switzerland