Advanced MRI methods in diagnostics of spinal cord pathology

Advanced MRI methods in diagnostics of spinal cord pathology Stanisław Kwieciński Department of Magnetic Resonance

MR IMAGING LAB MRI /MRS IN BIOMEDICAL RESEARCH ON HUMANS AND ANIMAL MODELS IN VIVO Equipment: 4.7T/31cm MRI, 8.5T MR Microscope, Animal Lab, access to clinical 1.5T MRI Diffusion Rat Injured Spinal Cord Genomic Mouse Heart Diffusion Tensor Imaging & fmri of spinal cord on humans and rats to develop methods of early diagnostics of injury. MRI of heart pathology on Transgenic mouse model. 31 P MRS in human skeletal muscle physiology. MRI in pharmacy to monitor the disintegration processes of drug tablets MRI in Dentistry in vitro on extracted teeth. MRI/MRS Physics and Technology: sequence design, software and hardware: gradient coils, RF-coils and probes Human spinal cord

Spinal Cord Imaging why so important? Spinal cord injuries are main factor of permanent disability affecting population as a result of communication, work or sport accidents. Outgrowth and regeneration of injured nerve fibers is possible Early diagnosis of pathologies such as Alzheimer, 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 Medium T1 (ms) T2 (ms) GM WM CSF 1200 1010 3120 100 90 160

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 Anisotropy ADC Apparent Diffusion Coeficient...)

Diffusion Tensor D D D D = αβ D D D D D D xx xy xz yx yy yz zx zy zz Matrix, S e -b D It fully describes molecular mobility along each direction and correlation among these directions Quantitative analysis: FA = {3[(λ 1 - λ ) 2 + (λ 2 - λ ) 2 + (λ 3 - λ ) 2 ]} / {2[(λ 12 + λ 22 +λ 32 )]} ADC = λ Where λ = Trace/3 = (λ 1 + λ 2 + λ 3 )/3 λ 1, λ 2, λ 3 : eigenvalues of a diffusion tensor

We have started with RATS Sagital projection Axial projection T2 T2 DTI ADC ADC [mm^2/s ] DTI 4.7T Bruker, bore: 30 cm tadc Slice 1 WM Testing neuroprotecive drugs 0.0014 0.0012 0.001 0.0008 0.0006 0.0004 0.0002 0 1 24 48 168 time [h] Reference (normal) Injured with drug Injured without drug

We have continued with HUMANS Images from 1.5T clinical system T2 DTI ADC FA

Cervical Thoracic Spine FA and ADC Sagittal plane Spinal segment Cervical Thoracic Lumbar FA [%] Entire Cord 61 ± 5 55 ± 7 32 ± 3 ADC x 10-3 [mm 2 /s] Entire Cord 0.78 ± 0.06 0.77 ± 0.06 1.06 ± 0.29 FA ADC 8 volunteers

DTI measurements in axial projections VHR AF VHL C5 PF FA FA in GM & WM - voluntie rs FA 1 0,8 0,6 0,4 0,2 VHR VHL PF 0 C3 C4 C5 C6 0 1 2 3 4 5 6 7 8 9 Slice numbe r AF Localizer

Patient No.1 Shot wound (10 years after) 0.66 36 0.86 0.80 0.78 0.76 0.86 1.25 0.82 0.81 35 43 40 37 26 13 35 37 T2 DWI ADC [x10-3 mm 2 /s] ADC - healthy volunteer: 0.78 ± 0.06 FA [% ] FA - healthy volunteer: 61 ±5

Patient No.2 Gym accident C5/C6 dislocation 0.94 58 0.83 0.92 0.60 0.55 0.80 1.11 1.18 66 58 42 32 40 41 38 CT T2 Before surgery After surgery ADC [x10-3 mm 2 /s ] ADC - healthy volunteer: 0.78 ± 0.06 FA [% ] FA - healthy volunteer: 61 ±5

Going further - biexponential diffusion A f S=A f exp(-b D f ) + A s exp(-b D s )

Vector Maps Spinal Structure 1 st eigenvector 2 nd eigenvector λ 1 Collateral Fibers λ 2 λ 3 Diffusion Ellipsoid λ 1 >λ 2 >λ 3 Craniocaudal Fibers Cajal et al, Histology of the Nervous System

Fiber tracking in the spinal cord

Spinal fmri Task 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. 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 Activation area stimulation www.driesen.com/dermatomes_of_the_human_body.htm

Stimulation paradigm block design 30sec. On / 30sec. Off Motor task: Fist clenching Thermal stimulation: Ice bag Electric stimulation: 3-9mA, freq. 8Hz

Results Motor task Fist clenching Axial slices

fmri study on RATS

Simultaneous spinal and brain fmri Spinal cord Brain Mean signal change 4 3,5 3 2,5 2 1,5 1 0,5 0-0,5 brain spinal cord paradigm -1 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 Image number REST1 STIM1 REST2 STIM2 REST3

Conclusions DTI and fmri are 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