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

1
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK
2
Edinburgh Imaging, University of Edinburgh, Edinburgh EH16 4TJ, UK
3
UK Dementia Research Institute at the University of Edinburgh, Edinburgh EH16 4SB, UK
4
Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(3), 776; https://doi.org/10.3390/ijms20030776
Received: 14 December 2018 / Revised: 29 January 2019 / Accepted: 1 February 2019 / Published: 12 February 2019
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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. View Full-Text
Keywords: cerebral small vessel disease; MRI; ferumoxytol; USPIO; inflammation; relaxometry cerebral small vessel disease; MRI; ferumoxytol; USPIO; inflammation; relaxometry
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Thrippleton, M.J.; Blair, G.W.; Valdes-Hernandez, M.C.; Glatz, A.; Semple, S.I.K.; Doubal, F.; Vesey, A.; Marshall, I.; Newby, D.E.; Wardlaw, J.M. MRI Relaxometry for Quantitative Analysis of USPIO Uptake in Cerebral Small Vessel Disease. Int. J. Mol. Sci. 2019, 20, 776.

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