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. B₁-insensitive R₁ measurement was evaluated in vitro. Twelve participants with history of minor stroke were scanned at 3-T MRI including structural imaging, and R₁ and R₂* 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 R₁ and R₂* were measured in white matter (WM), deep grey matter (GM), white matter hyperintensity (WMH) and stroke lesion regions. R₁ measurements were accurate across a wide range of values. R₁ (p < 0.05) and R₂* (p < 0.01) mapping detected increases in relaxation rate in all tissues immediately post-USPIO and at 24⁻30 h. R₂* returned to baseline at one month. Blood-normalised R₁ and R₂* 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 R₂* than for R₁ mapping. R₁ and R₂* changes were correlated at 24⁻30 h (p < 0.01). MRI relaxometry permits quantitative evaluation of USPIO uptake; R₂* appears to be more sensitive to USPIO than R₁. 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.