In Vivo High-Resolution MR Imaging of Neuropathologic Changes in the Injured Rat Spinal Cord

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 × 6 mm; in-plane resolution, 23 × 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).

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 × 6 mm; in-plane resolution, 23 × 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).

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 × 30 mm; in-plane resolution, 117 × 117 μm; TE, 4.4 milliseconds; TR, ∼200 milliseconds, depending on heart rate; D–F, section thickness, 300 μm; FOV, 40 × 25 mm; in-plane resolution, 156 × 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).