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Brain hypoxia mapping in acute stroke: Back-to-back T2′ MR versus 18F-fluoromisonidazole PET in rodents

Accepted version
Peer-reviewed

Type

Article

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Authors

Jensen-Kondering, U 
Ejaz, S 
Sawiak, SJ 
Carpenter, TA 

Abstract

Background

Mapping the hypoxic brain in acute ischemic stroke has considerable potential for both diagnosis and treatment monitoring. PET using (18)F-fluoro-misonidazole (FMISO) is the reference method; however, it lacks clinical accessibility and involves radiation exposure. MR-based T2' mapping may identify tissue hypoxia and holds clinical potential. However, its validation against FMISO imaging is lacking. Here we implemented back-to-back FMISO-PET and T2' MR in rodents subjected to acute middle cerebral artery occlusion. For direct clinical relevance, regions of interest delineating reduced T2' signal areas were manually drawn.

Methods

Wistar rats were subjected to filament middle cerebral artery occlusion, immediately followed by intravenous FMISO injection. Multi-echo T2 and T2* sequences were acquired twice during FMISO brain uptake, interleaved with diffusion-weighted imaging. Perfusion-weighted MR was also acquired whenever feasible. Immediately following MR, PET data reflecting the history of FMISO brain uptake during MR acquisition were acquired. T2' maps were generated voxel-wise from T2 and T2*. Two raters independently drew T2' lesion regions of interest. FMISO uptake and perfusion data were obtained within T2' consensus regions of interest, and their overlap with the automatically generated FMISO lesion and apparent diffusion coefficient lesion regions of interest was computed.

Results

As predicted, consensus T2' lesion regions of interest exhibited high FMISO uptake as well as substantial overlap with the FMISO lesion and significant hypoperfusion, but only small overlap with the apparent diffusion coefficient lesion. Overlap of the T2' lesion regions of interest between the two raters was ∼50%.

Conclusions

This study provides formal validation of T2' to map non-core hypoxic tissue in acute stroke. T2' lesion delineation reproducibility was suboptimal, reflecting unclear lesion borders.

Description

Keywords

positron emission tomography, cerebral ischemia, MRI, brain imaging, stroke, 18F-fluoro-misonidazole

Journal Title

International Journal of Stroke

Conference Name

Journal ISSN

1747-4930
1747-4949

Volume Title

12

Publisher

SAGE Publications
Sponsorship
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Medical Research Council (G0600986)
Medical Research Council (G0500874)
Medical Research Council (G0600986/1)
This study was funded by an EU Grant (EUSTROKE Health-F2-2008-2022131). DJW was funded by an MRC collaborative grant (G0600986), RM by the NIHR Cambridge Biomedical Research Centre, and UJK by a fellowship from the Deutsche Forschungsgemeinschaft (Je 598/1-1).