Dataset Information

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

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

SUBMITTER: Thrippleton MJ

PROVIDER: S-EPMC6387454 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Thrippleton Michael J MJ Blair Gordon W GW Valdes-Hernandez Maria C MC Glatz Andreas A Semple Scott I K SIK Doubal Fergus F Vesey Alex A Marshall Ian I Newby David E DE Wardlaw Joanna M JM

International journal of molecular sciences 20190212 3

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 ...[more]

PMID: 30759756

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Project description:Highlights • RISH harmonization is applicable to multicentre dMRI of elderly subjects with SVD.• Harmonization removes site-differences in dMRI metrics in matched controls.• Associations between dMRI metrics and SVD markers in patients are preserved.• Harmonized scans can be pooled to into a single large dataset to increased power. Objectives Acquisition-related differences in diffusion magnetic resonance imaging (dMRI) hamper pooling of multicentre data to achieve large sample sizes. A promising solution is to harmonize the raw diffusion signal using rotation invariant spherical harmonic (RISH) features, but this has not been tested in elderly subjects. Here we aimed to establish if RISH harmonization effectively removes acquisition-related differences in multicentre dMRI of elderly subjects with cerebral small vessel disease (SVD), while preserving sensitivity to disease effects. Methods Five cohorts of patients with SVD (N = 397) and elderly controls (N = 175) with 3 Tesla MRI on different systems were included. First, to establish effectiveness of harmonization, the RISH method was trained with data of 13 to 15 age and sex-matched controls from each site. Fractional anisotropy (FA) and mean diffusivity (MD) were compared in matched controls between sites using tract-based spatial statistics (TBSS) and voxel-wise analysis, before and after harmonization. Second, to assess sensitivity to disease effects, we examined whether the contrast (effect sizes of FA, MD and peak width of skeletonized MD - PSMD) between patients and controls within each site remained unaffected by harmonization. Finally, we evaluated the association between white matter hyperintensity (WMH) burden, FA, MD and PSMD using linear regression analyses both within individual cohorts as well as with pooled scans from multiple sites, before and after harmonization. Results Before harmonization, significant differences in FA and MD were observed between matched controls of different sites (p < 0.05). After harmonization these site-differences were removed. Within each site, RISH harmonization did not alter the effect sizes of FA, MD and PSMD between patients and controls (relative change in Cohen’s d = 4 %) nor the strength of association with WMH volume (relative change in R2 = 2.8 %). After harmonization, patient data of all sites could be aggregated in a single analysis to infer the association between WMH volume and FA (R2 = 0.62), MD (R2 = 0.64), and PSMD (R2 = 0.60). Conclusions We showed that RISH harmonization effectively removes acquisition-related differences in dMRI of elderly subjects while preserving sensitivity to SVD-related effects. This study provides proof of concept for future multicentre SVD studies with pooled datasets.

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Dataset Information

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

Publications

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

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