1. Introduction Material and Methods Result 2: Evolution of the lesion Result 1: DTI can map the injured spinal cord Conclusion J. Cohen-Adad 1, H. Leblond 1, H. Delivet-Mongrain 1, M. Martinez 1, J. Provencher 1, C. Hurst 2, H. Benali 3, S. Rossignol 1 The study of chronic spinal cord lesion (SCI) of cats may help understand plastic changes by identifying the importance of specific spinal pathways [1]. Experimental or clincial mechanical or traumatic lesions can induce unpredictable secondary damage that have to be identified beyound the acute stage because they may alter the potential for sensori-motor function recovery. One goal of in vivo neuroimaging is therefore the detection of neurodegenerative processes after SC injury. Non-invasive examination of white matter fibers in the living SC can be conducted using magnetic resonance diffusion tensor imaging (DTI). Here we used advanced acquisition and processing methods [2,3] to image the SC of cats before and after partial injury. We notably show that: High-resolution DTI can map the lesioned spinal cord Tractography-based DTI can detect degeneration and/or demyelination in spinal pathways Cat model of partial spinal cord injury Experiments were conducted in accordance with the Ethical Committee of the Université de Montréal. Unilateral hemisections were performed in adult cats (N=12) at T10-11 [1]. Cats were imaged before injury (intact) 3 days after injury (D3) and 21 days after injury (D21). High spatial and angular resolution dMRI acquisition Images were acquired on a 3T scanner (Siemens Medical Systems) using phased array coils and a spin echo EPI sequence. Parameters were: sagittal orientation, 128×128 matrix, TR/TE = 9500/109 ms, respiratory-gating, iPAT=3. Slice thickness was enhanced to 1 mm using super-resolution methods [4], enabling a spatial resolution of 1.5x1.5x1 mm 3. Distortion correction One challenge of dMRI of the spinal cord is the presence of distortions induced by susceptibility artifacts. In this study, distortions were efficiently corrected using the reversed gradients method as implemented in [5]. 1.5 mm 1* mm 1.5 mm 64 directions b = 1000 s/mm 2 Angular resolution Spatial resolution Same coronal slice in one injured cat showing T2-weighted EPI (top) and FA map (bottom). FA can detect white matter abnormalities not seen in T2 T2 FA References Outcomes. We propose a framework to visualize and to quantify in vivo the integrity of spinal cord pathways using DTI tractography. Application in SC injured cats showed that DTI metrics can detect degeneration/demyelination of ascending fibers caudal to the lesion, and of descending fibers rostral to the lesion, consistent with the known existence of Wallerian degeneration following axonal injury [6]. The interest here is that these changes can be seen only with these metrics since T2 images are not sensitive enough. Perspective. Next step is to use this framework to compare DTI metrics and choose the best biomarkers to white matter pathologies such as Wallerian degeneration and axonal necrosis. One ultimate goal is to show whether DTI metrics are sensitive to white matter plasticity after various interventions. Contact: jcohen@nmr.mgh.harvard.edu EMERGENCY NUMBER: +1 857 544 6110jcohen@nmr.mgh.harvard.edu 1 GRSNC, Department of Physiology, Université de Montréal, QC, Canada ; 2 Unité de Neuroimagerie Fonctionnelle, CRIUGM, Université de Montréal, Montreal, QC, Canada ; 3 INSERM U678, Université Paris 6, France Result 3: Detection of degeneration AnatomicEPI rawEPI corrected Axonal injury after partial spinal lesion in cats detected in vivo using diffusion tensor imaging 468.7 a: Coronal views of FA maps at various depths of the spinal cord. Decrease of FA in the dorsal-left aspect at T11 is consistent with the known location of the lesion (red arrow). b: Axial PD-TSE at 360x360 μm resolution centered on the lesion. c: Histological slice centered on the lesion. The lesion has been delineated on the anatomical image and histology with dashed line. The spinal cord is delineated on the anatomical image with continuous line. Orientation is indicated as L: Left, R: Right, C: Caudal, D: Dorsal and V: Ventral. Group results of quantitative tractography showing mean FA along the dorsal, ventral, right and left aspect of the spinal cord for the Intact (left), D3 (middle) and D21 (right) state. The mean FA across quadrants is shown in thick blue line. Lower FA is noticeable on the dorsal aspect rostrally to the lesion (red arrow), and on the left aspect caudally to the lesion (green arrow). These trends are both observed at D3 and D21 and may be associated with degeneration of ascending fibers rostral to the lesion, and of descending fibers caudally to the lesion. Group Analysis Quantification of FA in various quadrants of the cord, rostrally, at the epicenter and caudally to the lesion. The rostral area is defined between -45 mm and -15 mm from the lesion (~T8-T10). The epicenter area is defined between -3 mm and +3 mm from the lesion (T11). The caudal area is defined between +15 mm and +45 mm from the lesion (~T13-L1). Standard error represents variability across cats. Unpaired Student’s t-tests have been conducted between each condition. Levels of statistical significance are referred to as *: P<0.05; **: P<0.01 and ***: P<0.001. At lesion epicenter, FA is significantly different between the intact and both D3 and D21 conditions in the dorsal and left quadrants of the cord, whereas significant change is observed in the ventral and right quadrants only between the Intact and D21 conditions. Interestingly, FA is significantly reduced on the dorsal aspect caudally to the lesion and on the left quadrant rostrally to the lesion, which strongly supports the detection of Wallerian degeneration in these areas. Quantitative tractography To accurately quantify DTI/QBI metrics along the cord, tractography was used to isolate dorsal and ventrolateral pathways. Then, metrics were registered with respect to the lesion location and averaged across cats. ROI selection DORSAL LEFT Selective tractography Quantify metrics along tracts FA Lesion Sensory Motor