Fig. 3: Effects of gene therapy on non-lesional white matter microvascular function.
a Theoretical relationship between the imaging parameters capillary transit time heterogeneity (CTH) and mean transit time (MTT, an overall tissue perfusion marker) regarding the oxygen saturation of the perfused tissue. Flow disturbances in the capillary system lead to a mismatch between MTT and CTH (quantifiable as increased relative transit time heterogeneity = RTH). The microvascular flow delay results in increased oxygen extraction in the capillary bed (ΔSO2) indicating a reduction in vascular efficacy. This affects the relaxation curves from MRI gradient- and spin-echo signals and forms a reduced relative vortex area (VA). b Mean RTH in corresponding NAWM of HEM and controls without ALD (CON, n = 7). Data are expressed as mean ± SD; the P values were determined by two-tailed unpaired students’ t tests. c Mean RTH in distant normal-appearing white matter (NAWM) in CALD patients (n = 13) before (PRE) and 2Y post gene therapy (GT) and baseline to 2Y follow-up visit in age-matched hemizygotes without CALD (HEM, BL vs. 2Y, n = 11). Data are expressed as mean ± SD; the P values were determined by two-tailed paired and unpaired students’ t tests. d Same comparisons as in (b) for mean VA (n = 7). Data are expressed as mean ± SD; the P values were determined by two-tailed unpaired students’ t tests. e Same comparisons as in c for mean VA (n = 10–9). Data are expressed as mean ± SD; the P values were determined by two-tailed paired and unpaired students’ t tests. f Representative T2-weighted (T2W) images of distant NAWM and corresponding RTH and VA maps in a CALD patient PRE and 2Y post GT and an untreated HEM boy of same age without CALD at baseline and 2 years later. Source data are provided as a Source Data file.
