Abstract
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.
Highlights
Cerebral small vessel disease (SVD) accounts for 20–25% of strokes and increases the risk of cognitive impairment, disability and dementia
As far as we are aware, no studies have employed ultrasmall superparamagnetic particles of iron oxide (USPIO) contrast agents to study SVD. These particles, which have T1, T2 and T2* shortening effects, have several benefits compared with gadolinium-based contrast agents: (i) a large T2* effect due to the superparamagnetic nature of the contrast agent, (ii) they may often be used in patients with renal failure, for whom gadolinium-based agents are contraindicated [7], (iii) slow rates of extravasation and elimination facilitate convenient MR angiography at high resolution and steady-state cerebral blood volume (CBV) measurement [8], and (iv) phagocytosis by macrophages, which concentrate in inflamed tissue, provides an imaging marker of inflammation [9], for example in abdominal aortic aneurysm [10] and myocardial infarction [11]
We developed and evaluated an magnetic resonance imaging (MRI) relaxometry protocol for assessing USPIO uptake in patients with cerebral SVD
Summary
Cerebral small vessel disease (SVD) accounts for 20–25% of strokes and increases the risk of cognitive impairment, disability and dementia. As far as we are aware, no studies have employed ultrasmall superparamagnetic particles of iron oxide (USPIO) contrast agents to study SVD These particles, which have T1, T2 and T2* shortening effects, have several benefits compared with gadolinium-based contrast agents: (i) a large T2* effect due to the superparamagnetic nature of the contrast agent, (ii) they may often be used in patients with renal failure, for whom gadolinium-based agents are contraindicated [7], (iii) slow rates of extravasation and elimination facilitate convenient MR angiography at high resolution and steady-state cerebral blood volume (CBV) measurement [8], and (iv) phagocytosis by macrophages, which concentrate in inflamed tissue, provides an imaging marker of inflammation [9], for example in abdominal aortic aneurysm [10] and myocardial infarction [11]. Since inflammatory uptake typically occurs over a longer period than the MRI examination, multiple examinations are required and quantitative analysis based on signal changes is impractical
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