J007 Neuroimaging-guided automated trajectory planning for direct neurotherapeutics delivery for Huntington’s disease
Year: 2024
Type: conference-paper
Abstract: Background Convection-enhanced Delivery (CED) allows for administration of neurotherapeutic agents into the striatum to target the neurodegenerative process in Huntington’s Disease (HD).1 2 Cortical and striatal atrophy can limit the safety and accuracy of possible surgical trajectories. Neuroimaging-guided computer-assisted trajectory planning can aid in optimising delivery, by ensuring the maximum volume of distribution (Vdmax) within the target and minimising disruption to critical tissues. Aims Using imaging-based framework, investigate how progressive cortical and striatal atrophy affects CED planning in HD. Methods T1-weighted MRI images of pre-manifest HD patients were acquired on 3T scanner. Segmentation was performed as follows: (a) skull using SimNIBS charm,3 (b) cortex, ventricles, brainstem using FreeSurfer,4 (c) subcortical nuclei with FSL FIRST.5 Volumes were calculated using SamSeg.6 All possible trajectories to three targets (anterior caudate, anterior putamen, posterior putamen) on both hemispheres were evaluated. Trajectories were excluded: (1) from contralateral hemisphere, basal skull, eloquent cortex, sulcal surfaces, (2) within 2 mm of non-target nuclei, ventricles, and non-entry cortex. Estimation of Vdmax per trajectory was performed. Results Data analysing trajectories to the right anterior putamen in three subjects with various degrees of atrophy are presented (putamen/total intracranial volume: 0.0058;0.0028;0.0025) (figure 1). With increasing atrophy, the number of valid trajectories decreased (8:7:1), shortest trajectory became longer (58;62;64mm), Vdmax decreased (1.12;0.67;0.49mls). Conclusions Progressive atrophy limits trajectory options for CED. Our results raise the question regarding the timing of CED in disease evolution. The methods presented here will be applied to a larger cohort of HD patients for a more in-depth analysis. References Tabrizi SJ, Estevez-Fraga C, van Roon-Mom WMC, et al. Potential disease-modifying therapies for Huntington’s disease: lessons learned and future opportunities. Lancet Neurol. 2022;21(7):645-658. doi:10.1016/S1474-4422(22)00121-1 Bobo RH, Laske DW, Akbasak A, Morrison PF, Dedrick RL, Oldfield EH. Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci U S A. Mar 15 1994;91(6):2076-80. doi:10.1073/pnas.91.6.2076. Puonti O, Van Leemput K, Saturnino GB, Siebner HR, Madsen KH, Thielscher A. Accurate and robust whole-head segmentation from magnetic resonance images for individualized head modeling. Neuroimage, 2020;219:117044. Fischl, B. ‘FreeSurfer.’ Neuroimage 62.2 2012:774-781. Patenaude B, Smith SM, Kennedy DN, Jenkinson M. A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage. 2011;56(3):907-922. doi:10.1016/j.neuroimage.2011.02.046. Puonti O, Iglesias JE, Van Leemput K. Fast and sequence-adaptive whole-brain segmentation using parametric Bayesian modeling. Neuroimage. 2016;143:235-249. doi:10.1016/j.neuroimage.2016.09.011.
Institutions: University Hospital of Wales, Cardiff University
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4402374371