Utility of thalamic nuclei segmentation in targeted delivery of gene therapy using intrathalamic injections in Tay-Sachs disease patients

Motivation: Clinical outcomes from gene therapy treatment of Tay-Sachs disease patients using bilateral intrathalamic injections in the brain are unknown. Goal(s): We will perform a retrospective analysis on Tay-Sachs patients that received bilateral intrathalamic injections and identify the thalamic nuclei regions that intersect with the adeno-associated virus (AAV) vector distribution. Approach: We will use a histogram-based polynomial synthesis method to synthesize white-matter nulled images from standard T1 images to improve intrathalamic contrast prior to multi-atlas segmentation and reconstruct them with the AAV vector distribution overlay in 3D to precisely identify the target delivery regions within the thalamus. Impact: This study will advance precision targeting of intrathalamic injections in Tay-Sachs gene therapy that can provide insights into AAV vector distribution within the thalamus, refine delivery techniques, improve clinical outcomes, and inspire new questions about targeted therapy in neurodegenerative disorders.