Yang, P.-F. | bioRxiv Science

bioRxiv2025

Detection of Region-specific Fiber Damage within Injured Spinal Cord Using Advanced Diffusion MRI

This study aimed to evaluate diffusion parameters derived from diffusion tensor imaging (DTI) and spherical mean technique (SMT) for detecting region-specific, fine-grained tissue damage and white matter (WM) tract disruptions following spinal cord injury (SCI). Diffusion MRI data were acquired from the cervical spinal cord of monkeys before and after a unilateral dorsal column lesion at the C5 level, using a 9.4T scanner. Parametric maps derived from DTI and SMT effectively detected regional fiber damage around 16 weeks post-injury. Post-mortem silver staining served as the ground truth for assessing region-specific fiber damage. Diffusion MRI maps aligned well with histological measures and captured the severity of WM damage at the lesioned segment (in an order of dorsal > ventral > lateral WM tracts) and along the dorsal column tract across segments (in an order of lesion center > rostral > caudal). Among the diffusion parameters, fractional anisotropy (FA), axonal volume fraction (Vax), radial diffusivity (RD), and extra axonal transverse diffusivity (Dex) showed most significant changes at and around the lesion site where severe tissue damage occurred. FA, Vax, and axial diffusivity (AD) exhibited marked changes in dorsal column proximal to the lesion center, where moderate axonal damage occurred. Additionally, AD and FA showed the greatest sensitivity (true positive rate) and specificity (true negative rate) to mild fiber disruption and demyelination in regions distal to the lesion. Overall, FA provided the highest sensitivity and specificity for detecting fiber degeneration and demyelination, while Vax demonstrated the strongest spatial correlation with histologic markers of regional fiber damage. The combination of DTI and SMT thus offers reliable biomarkers for assessing SCI.

neuroscience↗

bioRxiv2023

Small volume blood-brain barrier opening in macaques with a 1 MHz ultrasound phased array

Focused ultrasound blood-brain barrier (BBB) opening is a promising tool for targeted delivery of therapeutic agents into the brain. The volume of opening determines the extent of therapeutic administration and sets a lower bound on the size of targets which can be selectively treated. We tested a custom 1 MHz array transducer optimized for cortical regions in the macaque brain with the goal of achieving small volume openings. We integrated this device into a magnetic resonance image guided focused ultrasound system and demonstrated twelve instances of small volume BBB opening with average opening volumes of 59 {+/-} 37 mm3 and 184 {+/-} 2 mm3 in cortical and subcortical targets, respectively. We developed real-time cavitation monitoring using a passive cavitation detector embedded in the array and characterized its performance on a bench-top flow phantom mimicking transcranial BBB opening procedures. We monitored cavitation during in-vivo procedures and compared cavitation metrics against opening volumes and safety outcomes measured with FLAIR and susceptibility weighted MR imaging. Our findings show small BBB opening at cortical targets in macaques and characterize the safe pressure range for 1 MHz BBB opening. Additionally, we used subject-specific simulations to investigate variance in measured opening volumes and found high correlation (R2 = 0.8577) between simulation predictions and observed measurements. Simulations suggest the threshold for 1 MHz BBB opening was 0.53 MPa. This system enables BBB opening for drug delivery and gene therapy to be targeted to more specific brain regions.

bioengineering↗