Assessing neuronal density in peri‐infarct cortex with PET: Effects of cortical topology and partial volume correction

Abstract

The peri-infarct cortex (PIC) is the site of long-term physiologic changes after ischemic stroke. Traditional methods for delineating the peri-infarct gray matter (GM) have used a volumetric Euclidean distance metric to define its extent around the infarct. This metric has limitations in the case of cortical stroke, i.e., those where ischemia leads to infarction in the cortical GM, because the vascularization of the cerebral cortex follows the complex, folded topology of the cortical surface. Instead, we used a geodesic distance metric along the cortical surface to subdivide the PIC into equidistant rings emanating from the infarct border and compared this new approach to a Euclidean distance metric definition. This was done in 11 patients with [F-18]-Flumazenil ([18-F]-FMZ) positron emission tomography (PET) scans at 2 weeks post-stroke and at 6 month follow-up. FMZ is a PET radiotracer with specific binding to the alpha subunits of the type A γ-aminobutyric acid (GABAA) receptor. Additionally, we used partial-volume correction (PVC) of the PET images to compensate for potential cortical thinning and long-term neuronal loss in follow-up images. The difference in non-displaceable binding potential (BP ) between the stroke unaffected and affected hemispheres was 35% larger in the geodesic versus the Euclidean peri-infarct models in initial PET images and 48% larger in follow-up PET images. The inter-hemispheric BP difference was approximately 17-20% larger after PVC when compared to uncorrected PET images. PET studies of peri-infarct GM in cortical strokes should use a geodesic model and include PVC as a preprocessing step. Hum Brain Mapp 38:326-338, 2017. © 2016 Wiley Periodicals, Inc.

Mapping neuronal density in peri‐infarct cortex with PET

“…A further, compounding effect might occur after stroke, namely geometric distortion due to brain collapse following infarct cavitation and shrinkage. Importantly, both secondary degeneration and brain collapse would be expected to largely depend on infarct size, and in this line we note that we studied almost exclusively small infarcts [Carrera et al, ; Guadagno et al, ], whereas several patients in the Funck et al's [] study had large infarcts (their fig. 1), and accordingly their assessment of SNL might have been affected by both effects.…”

“…In their recently published article, Funck et al [) for the first time mapped neuronal density in the immediate (3–15 mm) peri‐infarct cortex (PIC) in 11 stroke patients by means of flumazenil (FMZ) PET, according to a longitudinal design involving scanning both 10–31 days poststroke and again ∼6 months later. To address this challenging issue, they used a sophisticated image postprocessing methodology implementing both geodesic distance metric and local partial volume effects (PVE) correction (PVC) [Funck et al, ].…”

“…Using the above sophisticated techniques, Funck et al [] found reduced GABA A ‐receptor density and normal cortical thickness in the PIC in the early subacute phase, consistent with SNL, and reduced GABA A ‐receptor density together with reduced cortical thickness—i.e., cortical atrophy—in the PIC in the chronic phase. PVC had a significant effect on estimates of GABA A ‐receptor density in the PIC in the chronic stage only, indicating that thanks to PVC, SNL was not overestimated at that stage.…”

“…Prior to the recent report by Funck et al [], two clinical FMZ PET studies had suggested the presence of patchy areas of SNL throughout the surviving ischemic penumbra [Carrera et al, ; Guadagno et al, ]. To test whether SNL affects the ultimately noninfarcted penumbra, these authors prospectively studied patients with penumbra documented on hyperacute perfusion imaging but who enjoyed major neurological recovery reflecting early reperfusion.…”

“…In sum, previous work has consistently documented the presence of SNL throughout the salvaged penumbral cortex in both rodents and man. Funck et al [] now document that SNL also as expected affects the immediate PIC, and they should be commended for taking up the major technical challenge involved. Together, the available literature establishes the presence of widespread cortical SNL after ischemic stroke in man, which has important implications for interventions aiming to improve functional outcome over and above the established benefits from early recanalization.…”