Positron emission tomography with [
18F] fluorodeoxyglucose (FDG-PET) plays a well-established role in assisting early detection of
frontotemporal lobar degeneration (
FTLD). Here, we examined the impact of intensity normalization to different reference areas on accuracy of FDG-PET to discriminate between patients with mild
FTLD and healthy elderly subjects. FDG-PET was conducted at two centers using different acquisition protocols: 41
FTLD patients and 42 controls were studied at center 1, 11
FTLD patients and 13 controls were studied at center 2. All PET images were intensity normalized to the cerebellum, primary sensorimotor cortex (SMC), cerebral global mean (CGM), and a reference cluster with most preserved FDG uptake in the aforementioned patients group of center 1. Metabolic deficits in the patient group at center 1 appeared 1.5, 3.6, and 4.6 times greater in spatial extent, when tracer uptake was normalized to the reference cluster rather than to the cerebellum, SMC, and CGM, respectively. Logistic regression analyses based on normalized values from
FTLD-typical regions showed that at center 1, cerebellar, SMC, CGM, and cluster normalizations differentiated patients from controls with accuracies of 86%, 76%, 75% and 90%, respectively. A similar order of effects was found at center 2. Cluster normalization leads to a significant increase of statistical power in detecting early
FTLD-associated metabolic deficits. The established
FTLD-specific cluster can be used to improve detection of
FTLD on a single case basis at independent centers - a decisive step towards early diagnosis and prediction of
FTLD syndromes enabling specific
therapies in the future.