Assessing Complementary Information on Stroke Effects

PET and MRI have been used to study stroke in small animal models, examining changes in water diffusion and glucose metabolism.  Ischemic events produce a cascade of rapidly evolving physiological changes1 , including a reduction in cerebral blood flow (CBF) and cerebral blood volume (CBV), that can be highly individualized in certain animal models, creating data interpretation challenges when animals are imaged sequentially. With instruments capable of simultaneous PET/MRI acquisition researchers can assess complimentary information about the evolution of injury and the effect of interventions such as neuroprotective compounds.

MRI has been used extensively to monitor water diffusion changes in stroke patients, quantified by the apparent diffusion coefficient (ADC) using diffusion weighted imaging (DWI). PET provides complimentary information, and has been used to evaluate changes in glucose metabolism in rat models.

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(A) Coronal and transverse slice of an animal showing [18F]FDG uptake. The PET image is overlaid and fused to an anatomical MRI image. The PET data is summed across all frames. (B) In the same animal, [18F]FDG time activity curve for the contralateral hemisphere (blue) and the ipsilateral hemisphere (red).
(A) Coronal and transverse slice of an animal showing [18F]FDG uptake. The PET image is overlaid and fused to an anatomical MRI image. The PET data is summed across all frames. (B) In the same animal, [18F]FDG time activity curve for the contralateral hemisphere (blue) and the ipsilateral hemisphere (red).

Benefits of Simultaneous PET/MRI to Observe Heterogenous Changes During Brain Injury

Recently a group of researchers from the University of California, Davis and Genentech demonstrated successful multi-modal evaluation of the time course of a hypoxic challenge in mouse models of cerebral hypoxia-ischemia2. The extent of brain injury is variable in these models3, and along with the speed of ischemic changes, make a strong argument for simultaneous PET/MRI acquisition in small-animal stroke research.

In most animals, [18F]FDG PET images fused with anatomical MRI images showed reduced uptake in the occluded side relative to the non-occluded side, although this was not true in all cases likely due to animal variability. Executing sequential imaging studies and relying on software co-registration techniques would require the assumption that animal physiology has not significantly changed between imaging sessions; a potential pitfall given the rapid progression of ischemic brain injury.4 Simultaneous PET/MRI instrumentation can arm researchers with a new, powerful tool for multi-modal investigation into physiological changes during stroke and the effectiveness of novel interventional strategies.

(A) Time activity curves of contralateral (solid) and ipsilateral (dotted) hemisphere [18F]FDG uptake – shown on the same axis are examples of an unexpected [18F]FDG time activity curve (blue) and animal death at the end of H2 (at 45 min, green). (B) Ghosting artifacts.
(A) Time activity curves of contralateral (solid) and ipsilateral (dotted) hemisphere [18F]FDG uptake – shown on the same axis are examples of an unexpected [18F]FDG time activity curve (blue) and animal death at the end of H2 (at 45 min, green). (B) Ghosting artifacts.
(A) An example of parametric ADCz maps acquired at baseline and through post-hypoxia. (B) %L-R difference in ADCz from baseline to post-hypoxia. Asterisks indicate a significant difference compared to baseline value. (C) An example of an EPI-DWI acqusition.
(A) An example of parametric ADCz maps acquired at baseline and through post-hypoxia. (B) %L-R difference in ADCz from baseline to post-hypoxia. Asterisks indicate a significant difference compared to baseline value. (C) An example of an EPI-DWI acqusition.

Related

Fox MS, Palmer VL, Schellenberg G, Sparkes R, Thiessen JD. Characterization of an MRI-Compatible Pre-Clinical Insert with First Results Imaging a Rat Model of Stroke. WMIC 2018 World Molecular Imaging Congress, Seattle WA, USA, September 12-15, 2018.

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