Brain PET imaging of stroke

Vedashree Meher, M.Sc

Stroke is a clinical syndrome, so-named due to the sudden onset of symptoms caused by reduced blood supply, oxygen and nutrients to the brain. Stroke is a second leading cause of death and a major contributor of long-term disabilities globally (Katan & Luft, 2018). There are two types of strokes: hemorrhagic and ischemic. Hemorrhagic strokes account for 10-15% of all strokes and are caused by ruptured vessels from aneurysms, weakened vessel walls or arteriovenous malformations, where blood seeps into or around the brain causing swelling and increased intracranial pressure. Ischemic strokes account for 85% of all strokes and are usually caused by thromboemboli that block cerebral vessels. These thromboemboli can form in-situ or can travel from either the carotid artery (arterial embolus) or the heart (cardioemboli) and dislodge in one of the intracranial arteries. Regardless of the type of stroke, hypoperfusion and hypoxia subsequently causes necrosis. Other molecular mechanisms that contribute to brain damage include excitotoxity, edema, microglial activation, blood brain barrier disruption and increased intracranial pressure (Kuriakose & Xiao, 2020). The imaging clinical modalities commonly used in stroke include:

NCCT – identifies the type of stroke (excludes hemorrhagic stroke in the hyperacute stroke phase), identifies calcification, NCCT can show edema with mass effect and defined margins in the subacute stroke phase. Furthermore, large infarctions from the treatment could sometimes occur which can then be evaluated through NCCT scoring system (ASPECTS).

CT – advantages include fast attainment of images, less sensitive to motion, high resolution images.

CTA – using an IV contrast agent, this modality can identify vessel thrombosis, vascular malformations, dissections, vasculitis and aneurysms.

CT perfusion – identifies brain parenchymal enhancement

  • CT modalities except for NCCT, all require exposure to ionization radiation and an iodinated contrast agent. Risks of nephrotoxicity should be considered especially for renal artery stenosis in azotemic patients (Fisher & Olin, 2006).

PET – has been an asset for its diagnostic applications in oncology, radiology and brain imaging. For ischemic brain damage, PET can identify the extent of the metabolically active penumbra by measuring cerebral blood flow (CBF) using [15O]H2O radiotracers  and cerebral metabolic rate using [18 F]FDG radiotracers. Penumbra identified via PET is more accurate than perfusion weighted imaging (Catana et al., 2012). However, stand-alone PET scanners have limitations with spatial resolution, sensitivity, attenuation and scatter correction. Furthermore, PET studies for cerebral blood flow and oxygen consumption are time consuming and not feasible for acute ischemic stroke patients (Heiss, 2016). Additionally, [15O]H2O PET radiotracer has a very short half-life making it challenging (Miller-Thomas & Benzinger, 2017).

MRI – including contrast-enhanced MRI, perfusion-weighted imaging, diffusion weighted imaging and functional MRI, provide additional information to assess various metabolic and physiologic parameters such as blood supply, perfusion, edema and functional activation, respectively. MRI is more sensitive than CT. The typical multi-modal MRI protocol consists of T2/FLAIR-, T2-diffusion and perfusion-weighted images and MR angiography which are performed in <30mins (Leiva-Salinas & Wintermark, 2010). However, MR provides limited accuracy to measure critical hypoperfusion.

MRI and PET hybrid modality benefits for stroke imaging

  1. [15O]H2O PET/MRI hybrids, a non-invasive method for CBF measurement, could potentially replace arterial cannulation used for [15O]H2O PET studies where continuous blood sampling is required for kinetic modelling of blood flow using an arterial input function. Arterial cannulation is invasive, increases clotting risks, is time consuming and excludes children and patients on anticoagulants (Vestergaard et al., 2021).
  2. In stroke, “Time is brain” is a common phrase used for emphasizing the time-sensitive nature of stroke damage. Every minute, 1.9 million neurons die post-stroke (Saver, 2006). With simultaneous PET-MRI imaging, single exam within a short length of time would reduce the risk of physiologic and metabolic changes that would occur between two separate exams (Miller-Thomas & Benzinger, 2017). Also, these changes would be rapid in acute stroke.   
  3. PET/MR will also enable better motion correction (Gillman et al., 2017), increasing the amount of usable data from a scan and reducing the need for a re-scan.
  4. Early identification of stroke through expression of key biomarkers, and insights into drug kinetics (thrombolytics), are emerging compelling clinical applications (Panebianco et al., 2013).


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Gillman, A., Smith, J., Thomas, P., Rose, S., & Dowson, N. (2017). PET motion correction in context of integrated PET/MR: Current techniques, limitations, and future projections. Medical Physics, 44(12), e430-e445.

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Heiss, W. D. (2016). Hybrid PET/MR Imaging in Neurology: Present Applications and Prospects for the Future. J Nucl Med, 57(7), 993-995.

Katan, M., & Luft, A. (2018). Global Burden of Stroke. Seminars in Neurology, 38(02), 208-211.

Kuriakose, D., & Xiao, Z. (2020). Pathophysiology and Treatment of Stroke: Present Status and Future Perspectives. International Journal of Molecular Sciences, 21(20), 7609.

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Miller-Thomas, M. M., & Benzinger, T. L. S. (2017). Neurologic Applications of PET/MR Imaging. Magnetic Resonance Imaging Clinics of North America, 25(2), 297-313.

Panebianco, V., Giove, F., Barchetti, F., Podo, F., & Passariello, R. (2013). High-field PET/MRI and MRS: potential clinical and research applications. Clinical and Translational Imaging, 1(1), 17-29.

Saver, J. L. (2006). Time Is Brain—Quantified. Stroke, 37(1), 263-266.

Vestergaard, M. B., Calvo, O. P., Hansen, A. E., Rosenbaum, S., Larsson, H. B. W., Henriksen, O. M., & Law, I. (2021). Validation of kinetic modeling of [15O]H2O PET using an image derived input function on hybrid PET/MRI. NeuroImage, 233, 117950.

Prepared by: Vedashree Meher, M.Sc.