Simultaneous PET/MRI in stroke: a case series

Abstract

Prospective studies on magnetic resonance imaging (MRI)-guided systemic thrombolysis >4.5 hours after stroke onset did not reach their primary end points. It was discussed and observed in post hoc data re-assessment that this was partly because of limited MRI accuracy to measure critical hypoperfusion. We report the first cases of simultaneous [(15)O]H2O-positron emission tomography (PET)/MRI in stroke patients and an ovine model. Discrepancies between simultaneously obtained PET and MRI readouts were observed that might explain the above current limitations of stroke MRI. By offering highly complementary information, [(15)O]H2O-PET/MRI might help to identify critically hypoperfused tissue resulting in an improved patient stratification in thrombolysis trials.

Figure 1

[¹⁵O]H₂O PET/MRI in a typical human MCA infarction. A 78-year-old, right-handed woman with left hemiparesis and dysarthria upon waking up. Diffusion-weighted MRI showed a disturbance in the right MCA territory (red-bordered area, 22 mL). Perfusion_[MRI] flow delays in the right PCA territory did not result in a perfusion restriction according to PET and may thus indicate sufficient collateral flow secondary to the MCA occlusion. Perfusion_[MRI] indicated a penumbral volume (white-bordered areas) of 42 mL for T_max >6 seconds. According to perfusion_[PET] (17 mL, white-bordered area) a smaller penumbral volume was predicted that corresponded better with the follow-up infarct size according to T2 FLAIR (infarct growth of 7.5 mL) on day 5. Note: a slight change to time-based variables (TTP_delay >4.2 seconds, T_max >4 seconds; see Supplementary Methods) leads to misclassification and overestimation of the penumbra (79 mL and 121 mL, respectively). MCA, middle cerebral artery; MRI, magnetic resonance imaging; PCA, posterior cerebral artery; PET, positron emission tomography.

Figure 2

(A) [¹⁵O]H₂O PET/MRI 4.5 hours after middle cerebral artery occlusion in sheep. ADC imaging indicated a respective disturbance (blue-bordered area). Applying several thresholds for perfusion_[MRI] could not reveal the same extent of the critically hypoperfused brain tissue as defined by perfusion_[PET]. MR hypoperfusion either extended to the contralateral hemisphere or did not account for the penumbral part below the infarction core. According to perfusion_[PET], penumbral volume was 9.8 mL (white-bordered area in upper row). Perfusion_[MRI] yielded penumbral volumes of 27.2/6.3/5.4 mL (T_max=2/4/6 seconds) or 14.2/5.0/4.5 mL (TTP_delay=2/4.2/6 seconds; white-bordered areas in lower rows). Note: susceptibility artefacts in perfusion_[MRI], leading to slight spatial distortions especially close to the surface of the upper part of the sheep brain, were not corrected and may have affected correct ROI overlap and the resulting penumbral volumes. (B and C) Pooled regression analysis of regional values of perfusion_[MRI] (TTP_delay (top) T_max (second row) and CBF (third row)) and the reference method perfusion_[PET]. The data were obtained in four human stroke patients (B) on the basis of 83 brain volumes of interest defined by an anatomic standard atlas, and in stroke sheep (C) on the basis of 15 manually defined brain volumes of interest. The dotted lines in the top and middle rows of B represent respective MR penumbra thresholds applied in this study. In humans and sheep, a moderate-to-strong linear relation between pooled TTP_delay/T_max/CBF and the PET-derived gold standard CBF values was observed. Individual regression was performed for CBF in humans (bottom row) and yielded stronger linear relations between both measures. ADC, apparent diffusion coefficient; MRI, magnetic resonance imaging; PET, positron emission tomography; ROI, region of interest.