Lars Couture

Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition

Amyloid-β (Aβ) plaque deposition can precede the clinical manifestations of dementia of the Alzheimer type (DAT) by many years and can be associated with changes in brain metabolism. Both the Aβ plaque deposition and the changes in metabolism appear to be concentrated in the brains default-mode network. In contrast to prior studies of brain metabolism which viewed brain metabolism from a unitary perspective that equated glucose utilization with oxygen consumption, we here report on regional glucose use apart from that entering oxidative phosphorylation (so-called “aerobic glycolysis”). Using PET, we found that the spatial distribution of aerobic glycolysis in normal young adults correlates spatially with Aβ deposition in individuals with DAT and cognitively normal participants with elevated Aβ, suggesting a possible link between regional aerobic glycolysis in young adulthood and later development of Alzheimer pathology.

Regional White Matter Hyperintensity Burden in Automated Segmentation Distinguishes Late-Life Depressed Subjects From Comparison Subjects Matched for Vascular Risk Factors

OBJECTIVE Segmented brain white matter hyperintensities were compared between subjects with late-life depression and age-matched subjects with similar vascular risk factor scores. Correlations between neuropsychological performance and whole brain-segmented white matter hyperintensities and white and gray matter volumes were also examined. METHOD Eighty-three subjects with late-life depression and 32 comparison subjects underwent physical examination, psychiatric evaluation, neuropsychological testing, vascular risk factor assessment, and brain magnetic resonance imaging (MRI). Automated segmentation methods were used to compare the total brain and regional white matter hyperintensity burden between depressed patients and comparison subjects. RESULTS Depressed patients and comparison subjects did not differ in demographic variables, including vascular risk factor, or whole brain-segmented volumes. However, depressed subjects had seven regions of greater white matter hyperintensities located in the following white matter tracts: the superior longitudinal fasciculus, fronto-occipital fasciculus, uncinate fasciculus, extreme capsule, and inferior longitudinal fasciculus. These white matter tracts underlie brain regions associated with cognitive and emotional function. In depressed patients but not comparison subjects, volumes of three of these regions correlated with executive function; whole brain white matter hyperintensities correlated with executive function; whole brain white matter correlated with episodic memory, processing speed, and executive function; and whole brain gray matter correlated with processing speed. CONCLUSIONS These findings support the hypothesis that the strategic location of white matter hyperintensities may be critical in late-life depression. Further, the correlation of neuropsychological deficits with the volumes of whole brain white matter hyperintensities and gray and white matter in depressed subjects but not comparison subjects supports the hypothesis of an interaction between these structural brain components and depressed status.

Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG), is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF), oxygen (CMRO2) and glucose (CMRGlu) metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

Quantitative hemodynamic PET imaging using image-derived arterial input function and a PET/MR hybrid scanner.

Positron emission tomography (PET) with 15O-tracers is commonly used to measure brain hemodynamic parameters such as cerebral blood flow, cerebral blood volume, and cerebral metabolic rate of oxygen. Conventionally, the absolute quantification of these parameters requires an arterial input function that is obtained invasively by sampling blood from an artery. In this work, we developed and validated an image-derived arterial input function technique that avoids the unreliable and burdensome arterial sampling procedure for full quantitative 15O-PET imaging. We then compared hemodynamic PET imaging performed on a PET/MR hybrid scanner against a conventional PET only scanner. We demonstrated the proposed imaging-based technique was able to generate brain hemodynamic parameter measurements in strong agreement with the traditional arterial sampling based approach. We also demonstrated that quantitative 15O-PET imaging can be successfully implemented on a PET/MR hybrid scanner.

REGIONAL BRAIN AEROBIC GLYCOLYSIS ACROSS THE COGNITIVELY NORMAL ADULT LIFE SPAN

thicknesses. Siemens Healthcare MRIs had very similar fitted curves for surface, thickness, and volume, while Philips Medical Systems MRIs had thickness curves with a wider discrepancy, albeit surfaces and volumes were similar. Conclusions: OEMs andMFS produce small, but non-negligible effects on cortical surfaces, thicknesses, and volumes. These effects need to be taken into account when designing multi-centric studies and/or making between-scanner comparisons.

Correlation between ASL and o-15 water PET in the adult children study

and insula) and in temporal lobe. Volume of WMHs was distinctive of dementia status in YO but not in OO. Conclusions:The emphasis on decline in medial temporal and posterior brain regions in the non-demented OO is different from the documented “fronto-temporal” pattern in young elders and the temporo-parietal pattern in typical Alzheimer’s disease. Absence of dementia in the OO correlates with relatively preserved anterior cortex and the temporal lobe, which could inform mechanisms of cognitive maintenance in late life.

Comparison of cerebral glucose metabolism 18F-FDG, early frames of 11C-PiB, and cerebral blood flow 15O-H2O in autosomal dominant Alzheimer’s disease

Values Nelly Joseph-Mathurin, Yi Su, Andrei Vlassenko, Lars Couture, Tyler Blazey, Karl A. Friedrichsen, Christopher J. Owen, Russ C. Hornbeck, Lisa Cash, Trish A. Stevenson, Beau Ances, Chengjie Xiong, Virginia Buckles, Krista L. Moulder, John C. Morris, Randall Bateman, Marcus E. Raichle, Tammie L. S. Benzinger,Washington University School ofMedicine, St Louis, MO, USA. Contact e-mail: mathurinn@npg.wustl.edu