Perfluorocarbon Enhanced Glasgow Oxygen Level Dependent (GOLD) magnetic resonance metabolic imaging identifies the penumbra following acute ischemic stroke

Deuchar, G. A., Brennan, D., Holmes, W. M. , Shaw, M., Macrae, I. M. and Santosh, C. (2018) Perfluorocarbon Enhanced Glasgow Oxygen Level Dependent (GOLD) magnetic resonance metabolic imaging identifies the penumbra following acute ischemic stroke. Theranostics, 8(6), pp. 1706-1722. (doi: 10.7150/thno.21685)

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The ability to identify metabolically active and potentially salvageable ischaemic penumbra is crucial for improving treatment decisions in acute stroke patients. Our solution involves two complementary novel MRI techniques (Glasgow Oxygen Level Dependant (GOLD) Metabolic Imaging), which when combined with a perfluorocarbon (PFC) based oxygen carrier and hyperoxia can identify penumbra due to dynamic changes related to continued metabolism within this tissue compartment. Our aims were (i) to investigate whether PFC offers similar enhancement of the second technique (Lactate Change) as previously demonstrated for the T2*OC technique (ii) to demonstrate both GOLD metabolic imaging techniques working concurrently to identify penumbra, following administration of Oxycyte® (O-PFC) with hyperoxia. Methods: An established rat stroke model was utilised. Part-1: Following either saline or PFC, magnetic resonance spectroscopy was applied to investigate the effect of hyperoxia on lactate change in presumed penumbra. Part-2; rats received O-PFC prior to T2*OC (technique 1) and MR spectroscopic imaging, which was used to identify regions of tissue lactate change (technique 2) in response to hyperoxia. In order to validate the techniques, imaging was followed by [14C]2-deoxyglucose autoradiography to correlate tissue metabolic status to areas identified as penumbra. Results: Part-1: PFC+hyperoxia resulted in an enhanced reduction of lactate in the penumbra when compared to saline+hyperoxia. Part-2: Regions of brain tissue identified as potential penumbra by both GOLD metabolic imaging techniques utilising O-PFC, demonstrated maintained glucose metabolism as compared to adjacent core tissue. Conclusion: For the first time in vivo, enhancement of both GOLD metabolic imaging techniques has been demonstrated following intravenous O-PFC+hyperoxia to identify ischaemic penumbra. We have also presented preliminary evidence of the potential therapeutic benefit offered by O-PFC. These unique theranostic applications would enable treatment based on metabolic status of the brain tissue, independent of time from stroke onset, leading to increased uptake and safer use of currently available treatment options.

Item Type:Articles
Additional Information:This work was supported by an award from Scottish Enterprise, Proof of Concept (POC 8-LSM019).
Glasgow Author(s) Enlighten ID:Deuchar, Dr Graeme and Macrae, Professor Mhairi and Brennan, Dr David and Santosh, Dr Celestine and Holmes, Dr William and Shaw, Dr Martin
Authors: Deuchar, G. A., Brennan, D., Holmes, W. M., Shaw, M., Macrae, I. M., and Santosh, C.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Theranostics
Publisher:Ivyspring International Publisher
ISSN (Online):1838-7640
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Theranostics 8(6):1706-1722
Publisher Policy:Reproduced under a Creative Commons License

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