Akbar, MA

Cohen-Adad, J

Curt, A

Fehlings, M

Freund, P

Gandini Wheeler-Kingshott, CAM

Samson, R

Seif, M

Stutters, J

English

UCL Discovery

Inves�ga�on of DTI parameters in the cor�cospinal tract: from cervical cord to motor cortexRebecca Sara Samson , Jon Stu�ers , Muhammad Ali Akbar , Julien Cohen-Adad , Armin Curt , Michael Fehlings , Patrick Freund , Maryam Seif , and Claudia Angela Gandini Wheeler-Kingsho�Queen Square MS Centre, Department of Neuroinflamma�on, UCL Queen Square Ins�tute of Neurology, University College London, London, United Kingdom, Ins�tute of Medical Science, University of Toronto,Toronto, ON, Canada, NeuroPoly Lab, Ins�tute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada, Func�onal Neuroimaging Unit, CRIUGM, Université de Montréal, Montreal, QC, Canada,Spinal Cord Injury Center Balgrist, University of Zurich, Zurich, Switzerland, Krembil Research Ins�tute (Krembil), University Health Network, Toronto, ON, Canada, Department of Neurophysics, Wellcome Trust Centrefor Neuroimaging, UCL Queen Square Ins�tute of Neurology, University College London, London, United Kingdom, Max Planck Ins�tute for Human Cogni�ve and Brain Sciences, Leipzig, Germany, Department of Brainand Behavioural Sciences, University of Pavia, Pavia, Italy, Brain MRI 3T Centre, IRCCS Mondino Founda�on, Pavia, ItalySynopsisWe have explored diffusion tensor imaging (DTI) metrics along the cor�cospinal tract (CST) from the cervical cord to the motor cortex, measured using separate whole brain and cervical cord DTI protocols in healthysubjects at two different sites. We have also explored sensi�vity to disease in pa�ents with cervical spondylo�c myelopathy (CSM), and spinal cord injury (SCI). Several studies have looked either at brain or cervicalcord separately, which makes it difficult to learn about possible interac�ons between brain and cord. Here, we combine brain and cord measurements and examine how the CST is affected in CSM and SCI.Introduc�onThe cor�cospinal tract (CST) is a white ma�er (WM) motor pathway star�ng at the cerebral cortex that terminates on lower motor neurons and interneurons in the spinal cord, controlling movements of the limbs andtrunk .There are two divisions of the CST; lateral, which crosses the midline in the cord, and controls the limbs and digits, and ventral, which controls the trunk muscles, and stays on the same side of the body.Quan�ta�ve MRI metrics in the CST are expected to be affected by cord pathology, including mul�ple sclerosis, amyotrophic lateral sclerosis, cervical spondylo�c myelopathy (CSM), and spinal cord injury (SCI) .Diffusion Tensor Imaging (DTI) provides several indices thought to be sensi�ve to �ssue microstructural abnormali�es. These are the frac�onal anisotropy (FA), mean diffusivity (MD), and axial and radial diffusivi�es (ADand RD) and can be related to specific aspects of �ssue damage/repair, e.g. demyelina�on and axonal damage. Several studies have examined either the brain or the cord CST separately. Here we characterise brain andcord measurements obtained from separate cord and brain DTI protocols, but during the same scanning session, in healthy controls (HC) and CSM/SCI pa�ents, acquired as part of a mul�-centre study involving twodifferent clinical sites.MethodsMRI Acquisi�on:At two sites the following subjects were scanned using a 3T Siemens Skyra Fit (Siemens Healthineers, Erlangen, Germany), with a 16-channel head and neck coil:Site 01: 4 HC [2F, age 37.5±14.6 years (mean ± standard devia�on (SD))], 1 CSM (F, 71), 1 SCI (F, 44);Site 02: 5 HC (1F, 47.0±10.3), 10 CSM (4F, 55.3±11.4).The same whole brain and cervical cord (covering levels C2-C5) DTI protocols were performed at both sites; acquisi�on parameters are given in Figure 1.Image Analysis:1 1 2 3,4 5 2,6 5,7,8 51,9,101 23 45 6 78 91012https://submissions.mirasmart.com/ISMRM2019/ViewSubmission.aspx...1 of 5 07/11/2018, 14:49Brain DTI data were co-registered to MNI space prior to running TractSeg (an automa�c WM segmenta�on tool) . The subject-specific CST obtained using TractSeg was used to mask DTI parameter maps, es�mated usingCamino  (also in MNI space), and subsequently downsampled to give 5mm segments in the foot/head direc�on, from the bo�om of the pons upwards.Similarly, cord DTI data were transformed to the PAM50 template space , and the CST obtained using the spinal cord toolbox  (version 3.2.0) was used to mask DTI parameter maps, also downsampled to give 5mmsec�ons along the foot/head direc�on.In the cord, the le� ventral and right lateral CST, and similarly right ventral and le� lateral CST were combined. Between-group whole brain/cord CST differences were tested via one-way ANCOVA (using IBM SPSS forWindows, v22.0), with age and gender included as covariates.ResultsExample single slice brain and cord images for a HC are shown in Figure 2.Mean parameter values measured along the CST in the foot/head direc�on are plo�ed in Figures 3 (HC both sites) and 4 (HC and CSM site 02).Whole cord and brain CST mean parameter values are given in Figure 5.Intra-site CoVs were 0.86-7.36% and 3.65-13.6% in site 01 brain and cord respec�vely, and 1.18-2.41% and 6.53-25.1% in site 02 respec�vely. Inter-site CoVs ranged from 1.11-8.28% in the brain and 4.86-19.6% in thecord.At site 01, right brain CST MD was increased in CSM and SCI (p<0.05). In the cord, le� MD and RD were reduced in CSM and increased in SCI (p<0.05), compared to HC.At site 02, right brain AD was reduced in CSM (p<0.05), and in the cord right FA was reduced in CSM (p<0.05), compared to HC.Discussion and ConclusionsWe established a pipeline to extract the CST profile from the cervical spinal cord to the brain in standard space. Qualita�vely, the profiles of all DTI parameters along both CSTs followed very similar pa�erns, whencomparing HC across sites or CSM and HC at site 02 (figures 3 and 4). However, some differences may be appreciated indica�ng areas where subjec�ve variability may be higher, e.g. near the cortex.The higher DTI parameters observed in the cord compared to the brain could be due to the much lower b-value (500smm ) used in the cord protocol . Cord parameters were also more variable, possibly due to the lowerSNR of the protocol.Altera�ons of DTI parameters at different levels along the CST in CSM pa�ents can be seen in figure 4. Sta�s�cally significant changes were observed between CSM and SCI and HC when comparing averaged brain or cordCST, demonstra�ng the sensi�vity of CST metrics to pathology; however this data is part of a larger ongoing mul�-centre study, which is expected to strengthen these findings.AcknowledgementsThis study was funded by INSPIRED (a spinal cord imaging grant funded by the Interna�onal Spinal Research Trust, Wings for Life, and CHNF). Funding was also received from the MS Society of the UK (grant reference77/2018), and the Department of Health’s NIHR Biomedical Research Centres funding scheme (NIHR BRC UCLH/UCL High Impact Ini�a�ve-BW.mn.BRC10269). Addi�onally, this project has received funding from theEuropean Union's Horizon 2020 research and innova�on programme under the grant agreement No 681094, and is supported by the Swiss State Secretariat for Educa�on, Research and Innova�on (SERI) under contractnumber 15.0137. We would also like to thank all the par�cipants of the study.References[1] Kolb, B. & Whishaw, I. Q. (2009). Fundamentals of human neuropsychology: Sixth edi�on. New York, NY: Worth Publishers;[2] Gandini Wheeler-Kingsho�, CAM et al Neuroimage 84:1082-93 (2014);345 6-2 7https://submissions.mirasmart.com/ISMRM2019/ViewSubmission.aspx...2 of 5 07/11/2018, 14:49[3] Wasserthal J et al. NeuroImage Volume 183: 239-253 (2018);[4] Cook, PA et al. Proc ISMRM p2759 (2006);[5] De Leener B et al&shy;. NeuroImage 165 :170-79 (2018);[6] De Leener B et al NeuroImage 45 (Pt A):24-43 (2017) ;[7] Hui ES et al. Neuroimage 49(3): 2366-74 (2010).FiguresFigure 1: Acquisi�on parameters for brain and reduced field-of-view (using zoomit) cervical cord DTI protocols.Figure 2: Single slice example HC images and parameter maps for the brain (top), displayed coronally, and cord (bottom), displayed axially. From left to right: b=0, b=0 with CST overlaidhttps://submissions.mirasmart.com/ISMRM2019/ViewSubmission.aspx...3 of 5 07/11/2018, 14:49(right in red, left in blue), AD, FA, MD, RD. Colour bar units are m s  (except for FA which is a ratio).Figure 3: HC average CST DTI parameter values from both sites plotted as a function of position from the cervical cord upwards in 5mm sections (note the gap between cord and brain atthe brainstem level). Arrows indicate C2 cervical cord level, and error bars are standard errors. The left ventral and right lateral cord CST were paired with left brain and vice versa, sincethe lateral portions of the CST cross over at the level of the medulla/brainstem, whereas the ventral portions do not.2 -1https://submissions.mirasmart.com/ISMRM2019/ViewSubmission.aspx...4 of 5 07/11/2018, 14:49Figure 4: Site 02 CST DTI parameter values plotted as a function of position from the cervical cord upwards in 5mm sections (note the gap between cord and brain at the brainstem level).Arrows indicate C2 cervical cord level, and error bars are standard errors. The left ventral and right lateral cord CST were paired with left brain and vice versa, since the lateral portions ofthe CST cross over at the level of the medulla/brainstem, whereas the ventral portions do not.Figure 5: Brain or cord parameters over all CST levels (mean ±SD) for each site and subject group; *= p<0.05 compared to HC. Units are m s  (except for FA which is a ratio).2 -1https://submissions.mirasmart.com/ISMRM2019/ViewSubmission.aspx...5 of 5 07/11/2018, 14:49

Investigation of DTI parameters in the corticospinal tract: from cervical cord to motor cortex

https://discovery.ucl.ac.uk/id/eprint/10068967/1/RSamson_ISMRM_2019.pdf

Investigation of DTI parameters in the corticospinal tract: from cervical cord to motor cortex

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