MRI Relaxometry for Quantitative Analysis of USPIO Uptake in Cerebral Small Vessel Disease

A protocol for evaluating ultrasmall superparamagnetic particles of iron oxide (USPIO) uptake and elimination in cerebral small vessel disease patients was developed and piloted. B-1-insensitive R-1 measurement was evaluated in vitro. Twelve participants with history of minor stroke were scanned at 3-T MRI including structural imaging, and R-1 and R-2* mapping. Participants were scanned (i) before and (ii) after USPIO (ferumoxytol) infusion, and again at (iii) 24-30 h and (iv) one month. Absolute and blood-normalised changes in R-1 and R-2* were measured in white matter (WM), deep grey matter (GM), white matter hyperintensity (WMH) and stroke lesion regions. R-1 measurements were accurate across a wide range of values. R-1 (p < 0.05) and R-2* (p < 0.01) mapping detected increases in relaxation rate in all tissues immediately post-USPIO and at 24-30 h. R-2* returned to baseline at one month. Blood-normalised R-1 and R-2* changes post-infusion and at 24-30 h were similar, and were greater in GM versus WM (p < 0.001). Narrower distributions were seen with R-2* than for R-1 mapping. R-1 and R-2* changes were correlated at 24-30 h (p < 0.01). MRI relaxometry permits quantitative evaluation of USPIO uptake; R-2* appears to be more sensitive to USPIO than R-1. Our data are explained by intravascular uptake alone, yielding estimates of cerebral blood volume, and did not support parenchymal uptake. Ferumoxytol appears to be eliminated at 1 month. The approach should be valuable in future studies to quantify both blood-pool USPIO and parenchymal uptake associated with inflammatory cells or blood-brain barrier leak.