To assess the striatal volumes of early manifest Huntington disease (HD) patients to establish volumetric parameters for safe, MRI-guided, convection-enhanced delivery (CED) of gene therapy.

Selective neuronal loss in the striatum is an integral part of the neuropathology of HD.  The delivery of specific drug volumes to the striatum in HD must account for poroelastic modeling, atrophic changes, and neurosurgical trajectories to safely transduce neurons in the striatum.

Volumetric MRI were acquired on a 3.0T scanner on 20 anonymous patients with early manifest HD. The putamen and caudate nuclei for each patient were profiled using software with a build-in tool for auto-segmentation. The software implements the active appearance model methodology and uses a multi-atlas of brain features defined in a series of T1 and T2 MRI scans. Real-time volume of distribution (V_d) and volume of infusion (V_i) data from non-human primates (NHPs) were used to estimate a scale-up factor for human CED of gene therapy.

The mean volume of the putamen was 3.11±0.54 cm³ (mean±SD) and 2.93±0.60 cm³ without the lenticulostriate and perivascular spaces. The volume of the entire caudate was 2.24 ±0.36 cm³.  An infusion of 100 microliters with a V_d/V_i=2.0 filled two-thirds of the caudate and putamen in the NHPs. A factor of 5 achieved the same filling by CED into human the caudate head and putamen. Despite the generalized cortical and striatal atrophy evident in HD patients, simulated surgical planning showed the feasibility to deliver gene therapy safely to both the caudate and putamen.