In Vivo High-Resolution MR Imaging of Neuropathologic Changes in the Injured Rat Spinal Cord
T. Webera,b,
M. Vroemenb,d,
V. Behra,
T. Neubergera,
P. Jakoba,
A. Haasea,
G. Schuiererc,
U. Bogdahnb,
C. Fabera and
N. Weidnerb
a Department of Physics, EP5 (Biophysics), University of Würzburg, Würzburg, Germany
b Department of Neurology, University of Regensburg, Bezirksklinikum Regensburg, Regensburg, Germany
c Institute for Neuroradiology, Bezirksklinikum Regensburg, Regensburg, Germany
d Department of Urology, Technical University, Munich, Germany
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Fig 1. In vivo MR imaging of intact spinal cord at 17.6T. Panels A and B show sagittal scans through the thoracic spinal cord (section thickness, 239 µm; FOV, 40 x 30 mm; in-plane resolution, 156 x 117 µm; TR,  200 milliseconds, depending on heart rate; TE, 4.4 milliseconds). Panels C and D display axial scans through the thoracic spinal cord (section thickness, 500 µm; FOV, 17.7 x 35.5 mm; in-plane resolution, 69 x 69 µm; TR and TE, as above). Scale bar, 2 mm. A, A more lateral sagittal scan depicts primarily white matter (lower signal intensity) with some longitudinally oriented more hyperintense structure, reflecting the gray matter of the lateral ventral horn. CSF appears hyperintense, vertebral bodies are hypointense. B, Most of the spinal cord parenchyma displayed here represents gray matter (hyperintense) surrounded by white matter tracts (hypointense) in a paramedian sagittal scan through the spinal cord. C, An axial scan through the thoracic spinal cord allows the clear distinction between the typical butterfly appearance of the spinal cord gray matter and the surrounding hypointense white matter. Also of note, spinal roots can be clearly identified at this level. D, A subsequent scan more caudally shows the spinal cord in cross-section away from the spinal root entry zone.
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Fig 2. Axial ex vivo MR imaging scans of contused rat spinal cord. Axial sections of ex vivo MR imaging show microscopy grade visualization of morphologic changes in the injured rat spinal cord 4 weeks after contusion injury at midthoracic level (2D multisection spin-echo; section thickness, 300 µm; FOV, 6 x 6 mm; in-plane resolution, 23 x 23 µm; TE, 7.5 milliseconds; TR, 2 seconds). Scale bar, 1 mm. Panels A–L show consecutive sections in the rostral-caudal direction. In rats the dorsal columns contain not only ascending proprioceptive projections, which are located in the dorsal half of the dorsal column. The crossed corticospinal tract projects in the ventral half of the dorsal columns, unlike humans, where most corticospinal axons are located in the lateral columns. A–F, In sections rostral to the contusion site, the spinal cord morphology is still maintained with a clear differentiation of white and gray matter. Note the hypointensity in the dorsal part of the dorsal columns (arrowheads) identical to ascending proprioceptive projections. G–I, At the lesion center, the spinal cord diameter is reduced and gray and white matter can no longer be separated. Hypointensities located in the center (G) reflect hemosiderin deposits. J–L, Caudal to the lesion, the gray-white matter contrast is preserved. Both in rostral and caudal scans (B–D and J–L) hyperintense signals are found in the dorsal columns consistent with cystic defects (see also Fig 3). Hypointensities in axial scans rostral to the lesion correspond to ascending sensory projections, whereas in caudal scans they represent the area of the corticospinal tract (J–L, arrowheads).
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Fig 3. Sagittal ex vivo MR imaging scans of contused rat spinal cord and corresponding histology. Midthoracic contusion injury 4 weeks postlesioning; same specimen as Fig 2 (2D multisection spin-echo; section thickness, 208 µm; FOV, 20 x 6 mm; in-plane resolution, 23 x 78 µm; TE, 7.5 milliseconds; TR, 2 seconds). Scale bar, 2 mm. A–D, Ex vivo MR imaging scans from lateral to medial. E–H, Corresponding Nissl-stained sections. I–L, Corresponding GFAP immunostained sections. M–P, Corresponding collagen type III immunostained sections. Homogenous hyperintensities at the injury center (A) correspond to cystic lesion defects in histologic sections (E, I, and M). In other sections. mixed hypo-/hyperintensities in the lesion center (B and C, arrows) are associated either with cystic lesion defects, hemosiderin deposits, or fibrotic scar formation (F, N, G, and O, arrows). A hypointensity following the path of the dorsal corticospinal tract caudal to the lesion—corresponding to hypointensities in the dorsal columns in axial MR images (Fig 2)—is highlighted by arrowheads (B).
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Fig 4. Sagittal in vivo MR imaging scans of contused rat spinal cord and corresponding histology. In vivo MR imaging in adult rats at 2 and 8 weeks after thoracic contusion injury displays signal intensity changes, which parallel the ex vivo MR imaging data (2D multisection gradient-echo; A–C, section thickness, 311 µm; FOV, 30 x 30 mm; in-plane resolution, 117 x 117 µm; TE, 4.4 milliseconds; TR, 200 milliseconds, depending on heart rate; D–F, section thickness, 300 µm; FOV, 40 x 25 mm; in-plane resolution, 156 x 98 µm; TE, 3.7 milliseconds; TR, 200 milliseconds, depending on heart rate). Scale bar A–F, 5 mm; G–O, 1 mm. Consecutive sagittal MR images are shown at 2 weeks (A–C) and 8 weeks (D–F) postinjury with corresponding histologic Nissl (G–I) and Prussian-blue (J–L) –stained sections, and sections processed for ED1 immunohistochemistry (macrophages, monocytes; M–O), all from the same animal. Arrows in A and B highlight the site of the impact. Hypointensities along ascending and descending axon projections in the dorsal columns (B and E) correlate with hemosiderin deposits (K) rather than macrophage/monocyte infiltration (O; respective areas are indicated by arrowheads). These changes increase from 2 weeks (C) until 8 weeks (G) postinjury. The clear reduction in cord diameter over time (B vs E and C vs F) corresponds to the atrophy seen in histologic sections (G–O).
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Fig 5. Axial in vivo MR imaging scans of contused rat spinal cord. In vivo MR axial scans in adult rats 6 weeks postinjury (2D multisection gradient-echo; section thickness, 370 µm; FOV, 20 x 20 mm; in-plane resolution, 78 x 78 µm; TE, 4.2 milliseconds; TR, 200 milliseconds, depending on heart rate). Scale bar, 2 mm. Scans rostral to the contusion (A–C), at the lesion center (D–G), and caudal to the lesion (H). The clear differentiation between white and gray matter disappears over subsequent sections. At the lesion center, hypointensities are surrounded by hyperintensities, which are less pronounced toward the cord surface (E and F). The dorsal aspect of the spinal cord at the lesion site appears more homogenously hyperintensive, most likely representing cystic changes (D and E, arrowheads). Signs of atrophy are present in the dorsolateral spinal cord (E and F).
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