Applications of MRI inApplications of MRI in Biomedical Engineeringa Biomolecular Engineering Perspective

Johannes LeisenGeorgia InstituteInstitute ofof Technologynology,Georgia InstituteInstitute ofof Technologynology,

Department of Biomedical Engineering, School of Chemistry

Safetyy

http://www.metrasens.com/images/safety1.jpg

No lose ferrous items:‐wallets‐cell phonescell phones‐lose change‐ jewelry (some)‐ hair‐pins

www.topmedicalsupply.com/plastic‐mri‐warning‐.

p‐ implants‐ …

Magnetic Resonance ImagingMagnetic Resonance Imaging

* Physical Principles a very brief historical perspective

*Applications of MRI in Biomedical Engineeringa Biomolecular Engineering Perspective

NMR Spectroscopy NMR Relaxometry• Solution NMR• Solid State NMR• …

•Solution NMR• Solid State NMR• Low Resolution NMR

MR

… Low Resolution NMR• …

MR(Nuclear Magnetic Resonance)

(N)MR‐Imaging (MRI)• Clinical MRI

Diffusion NMR• DOSY (solutions)

• Functional MRI• Engineering• NMRMicroimaging

( )• PFG (materials)• q‐space (porous materials)• DTI (MRI)• NMR Microimaging

• …• DTI (MRI)• …

Edward Mills Purcell (1912‐1997)Felix Bloch (1905‐1983)

Wikipedia com Wiki diWikipedia.com

Noble Price in Physics, 1955. 

Wikipedia.com

First NMR signals of waterFirst NMR signals of water

Bloch, F., Hansen, W. W. and Packard, M. Phys. Rev.70, 474–485 (1946);

Bloch, F., Hansen, W. W. and Packard, M. Phys. Rev.70, 474–485 (1946);

NMR Experiment

http://www.fotosearch.com/ART435/aa041117/http://www.graphicsfactory.com/

rf sender                                          sample                                    rf receiver

ω=γ (1 σ) Bω=γ (1‐σ) B0

ω=γ (1‐σ) B0 σ: Chemical Shift

First NMR signals of water

Bloch, F., Hansen, W. W. and Packard, M. Phys. Rev.70, 474–485 (1946);

First NMR signals of ethanol (1951)g ( )

CH CH OHCH3‐CH2‐OH

http://www‐bioc.rice.edu/bios576/nmr/nmr.html

Richard Ernst  (1933‐ )  Paul Lauterbur (1929‐2007)

Fourier‐Transform NMR,http://nobelprize.org

http://nobelprize.org Back‐Projection MRIMultidimensional NMR, and MRI

1991 Noble Prize in Chemistry

p p g

2003 Noble Prize in Medicine

1991 Noble Prize in Chemistry

MRI Experiment

http://www.fotosearch.com/ART435/aa041117/http://www.graphicsfactory.com/

rf sender                                          sample                                    rf receiver

inhomogenous magnetic fieldω(x)=γ (1‐σ) B0(x)

NMR Imaging with Linear Magnetic Field G diGradients

NMR Spectroscopy NMR Imaging

Bo + GxGx = ∂Bz/∂x

ωo = γ(1-σo)Bo ωo = γ(1-σo)(Bo+x·G x)

yz

Boy

z

x x

ωω12

Back ProjectionBack Projection

Paul Lauterbur, Nature 242, 1973

18951895First X‐ray taken of a human(the hand of Röntgen’s wife)

Wilhelm Röntgen (1845 – 1923)1901: first Nobel Price in Physics

http://www.magnet.fsu.edu

Magnetic Resonance Imaging

+ 3D imaging of opaque objects is possible+ 3D imaging of opaque objects is possible+ non‐destructive / non‐invasive (ideal for the study of time dependent phenomena)+ well defined contrast (selective detection of fluids, study of physico‐chemical properties)

‐moderate spatial resolutionli i d i i i‐ limited sensitivity

‐ only for liquid or “soft” samplesl f d i d i l‐ only for non‐conducting and non‐magnetic samples

Clinical MRI

Medicine:

Source: www.cmiv.liu.se

Veterinary MRIVeterinary MRI

http:/www.advancedveterinarycare.net/mri.asp

Applications of MRI in Biomedical Applications of MRI in iomedicalEngineering

a Biomolecular Engineering Perspective

Molecular Imaging ?

http://www.keck.bioimaging.wisc.edu/symposium2005

Molecular Imaging:Localization of Specific Moleculesp

www.nature.com

Imaging of Molecules

The Resolution of MRIThe Resolution of MRI

Example:hi h l ti MRI fhigh resolution MRI of a mouseField of View  = 22 mm256x256 Voxel.

=> (In plane) resolution ≈ 86 μm 

Technical/Physical Limitations:• Sensitivity• Sensitivity• Diffusion Effects

MRI of Single Cells?MRI of Single Cells?

Paramecium:‐immobilized (dead?)

i ti 8h‐measuring time: 8h

MRI of Molecules?MRI of Molecules?

Degen C L et al. PNAS 2009;106:1313-1317

However, 

Magnetic Resonance Spectroscopy can tell us aMagnetic Resonance Spectroscopy can tell us a lot about molecules

Example: 13C DEPT135 spectrum of Strychnine

MRS: Detecting BiochemistryVolume Selective Spectroscopy

Most of the MRI signal in biological tissuecomes fromWater,comes from Water, butis it possible to use (highly sensitive) probe molecules?probe molecules?

(1)MRI with hyperpolarized nuclei H S TM

(difficult technology, limited lifetime of hyperpolarization)

(2) 19F MRI 

HyperSenseTMwww.oxford‐instruments.com

(~3/4 the sensitivity of 1H but no biological background) www.bioe.umd.edu

(3) Contrast Agents/ Overlay:  1H – 19F images

Contrast AgentsInfluence the MRI signal of  1H nuclei in surrounding water. g

apod.nasa.gov

Super Paramagnetic Iron Oxide (SPIO)Super Paramagnetic Iron Oxide (SPIO) Nanoparticle: affects surrounding magnetic field

Superparamagnetic Iron Oxide Nanoparticles

c: Sheng Tong/GT‐BME

U f SPIO f C ll T kiUse of SPIOs for Cell Tracking

Sequential in vivo MRI images, obtained at a field strength of 4.7 T, of a rat brainafter transplantation of oligodendroglial progenitor cells containing SPIOs (dark areas,because of the negative contrast of the transplanted cells) These images were obtainedbecause of the negative contrast of the transplanted cells). These images were obtainedsix weeks after stem cell transplantation.(Bulte, J. W., et al., Nat. Biotechnol. (2001) 19 (12), 1141.)

Targeting of SPIOs

Clustering of SPIOs leads to enhanced(negative) contrast.( g )

future devices for medical diagnostics 

/spectrum.ieee.org/biomedical/diagnostics/bedside‐cancer‐detectorCopyright:

(courtesy: Sheng Tong/GT‐BME)

OutlookThere is much more Applications of MRI in Biomedical Engineering

• MRI of Bioreactors with cultured cells• Cardiac models (in vitro and in vivo)• Development and Testing of Implants etc.evelopment and Testing of Implants etc.• Testing of Biomedical Products and Devices• Study of Anatomical Preparations• Phenotyping of Transgenic Species• Phenotyping of Transgenic Species• Biomechanical Studies• …

Succesful Biomedical Engineering leads often to Preclinical Studies,where MRI is also gaining importance.g g p