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Int J Mol Sci. 2019 Feb 12;20(3). pii: E776. doi: 10.3390/ijms20030776.

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

Author information

1
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK. m.j.thrippleton@ed.ac.uk.
2
Edinburgh Imaging, University of Edinburgh, Edinburgh EH16 4TJ, UK. m.j.thrippleton@ed.ac.uk.
3
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK. gordon.blair@ed.ac.uk.
4
Edinburgh Imaging, University of Edinburgh, Edinburgh EH16 4TJ, UK. gordon.blair@ed.ac.uk.
5
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK. M.Valdes-Hernan@ed.ac.uk.
6
Edinburgh Imaging, University of Edinburgh, Edinburgh EH16 4TJ, UK. M.Valdes-Hernan@ed.ac.uk.
7
UK Dementia Research Institute at the University of Edinburgh, London W1T 7NF, UK. M.Valdes-Hernan@ed.ac.uk.
8
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK. andi@mingsze.com.
9
Edinburgh Imaging, University of Edinburgh, Edinburgh EH16 4TJ, UK. andi@mingsze.com.
10
Edinburgh Imaging, University of Edinburgh, Edinburgh EH16 4TJ, UK. scott.semple@ed.ac.uk.
11
Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK. scott.semple@ed.ac.uk.
12
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK. fergus.doubal@ed.ac.uk.
13
Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK. alexvesey@gmail.com.
14
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK. ian.marshall@ed.ac.uk.
15
Edinburgh Imaging, University of Edinburgh, Edinburgh EH16 4TJ, UK. ian.marshall@ed.ac.uk.
16
Edinburgh Imaging, University of Edinburgh, Edinburgh EH16 4TJ, UK. d.e.newby@ed.ac.uk.
17
Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK. d.e.newby@ed.ac.uk.
18
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK. joanna.wardlaw@ed.ac.uk.
19
Edinburgh Imaging, University of Edinburgh, Edinburgh EH16 4TJ, UK. joanna.wardlaw@ed.ac.uk.
20
UK Dementia Research Institute at the University of Edinburgh, London W1T 7NF, UK. joanna.wardlaw@ed.ac.uk.

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.

KEYWORDS:

MRI; USPIO; cerebral small vessel disease; ferumoxytol; inflammation; relaxometry

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