Mapping the fascicular morphology and organization of the human sciatic nerve via high-resolution MicroCT imaging

Abstract

Abstract Implanted neuroprostheses can restore standing and walking after spinal cord injury and somatosensation after limb loss. Yet current approaches often fail to reliably activate hamstring muscles crucial for upright stability and mobility or to target afferent fibers for sensory restoration. We developed a novel methodology using high-resolution micro-computed tomography (microCT) to visualize and track fascicle groups innervating distinct hamstring muscles along the human sciatic nerve. Bilateral sciatic nerves were dissected and excised from an embalmed human cadaver, annotated with branch target names, and stained with phosphotungstic acid before undergoing microCT scanning at 11.4 μm isotropic resolution. Images were segmented with a 3D U-Net convolutional neural network. Segmentation results were used to quantify morphological metrics and track fascicular organization along ~ 25 cm of the nerve. MicroCT reconstructions were validated against histological cross sections. Gross dissection revealed matched proximal-to-distal branching between left and right sciatic nerves: branch to long head of the biceps femoris (lhBF), branch to hamstring part of the adductor magnus and semimembranosus (HAM/SM), and branch to semitendinosus (ST). All branches originated medially and followed an inferomedial trajectory. Branch-free lengths of the sciatic exhibited asymmetry, especially between the lumbosacral roots to the first branch (5.5 cm left vs. 1.5 cm right) and lhBF to the HAM/SM branch (9.0 cm left vs. 16.5 cm right). MicroCT analysis revealed bilateral symmetry in fascicle diameters (~ 0.4 mm) and total fascicle counts (~ 83) but asymmetry in hamstring-innervating fascicle counts (left ~ 7, right ~ 9). The 3D fascicular maps revealed that hamstring fascicles clustered in the anteromedial portion of the sciatic nerve cross section. As a combined group, hamstring-innervating fascicles (ST, HAM/SM, lhBF) remained separate from non-hamstring fascicles for up to 15.9 cm proximal to their branch points. Our microCT-based method enables efficient, high-resolution 3D mapping of fascicular organization within large, complex peripheral nerves such as the sciatic nerve, overcoming previous technical limitations. This methodology provides baseline high-resolution anatomical maps of sciatic fascicular organization. These data offer essential geometric inputs for future computational modeling and provide hypotheses for testing electrode placement and selective activation strategies in future studies.