Developing a novel dual-injection FDG-PET imaging methodology to study the functional neuroanatomy of gait

Gait is an excellent indicator of physical, emotional, and mental health. Previous studies have shown that gait impairments in ageing are common, but the neural basis of these impairments are unclear. Existing methodologies are suboptimal and novel paradigms capable of capturing neural activation related to real walking are needed. In this study, we used a hybrid PET/MR system and measured glucose metabolism related to both walking and standing with a dual-injection paradigm in a single study session. For this study, 15 healthy older adults (10 females, age range: 60.5-70.7 years) with normal cognition were recruited from the community. Each participant received an intravenous injection of [¹⁸F]-2-fluoro-2-deoxyglucose (FDG) before engaging in two distinct tasks, a static postural control task (standing) and a walking task. After each task, participants were imaged. To discern independent neural functions related to walking compared to standing, we applied a bespoke dose correction to remove the residual ¹⁸F signal of the first scan (PET_STAND) from the second scan (PET_WALK) and proportional scaling to the global mean, cerebellum, or white matter (WM). Whole-brain differences in walking-elicited neural activity measured with FDG-PET were assessed using a one-sample t-test. In this study, we show that a dual-injection paradigm in healthy older adults is feasible with biologically valid findings. Our results with a dose correction and scaling to the global mean showed that walking, compared to standing, increased glucose consumption in the cuneus (Z = 7.03), the temporal gyrus (Z = 6.91) and the orbital frontal cortex (Z = 6.71). Subcortically, we observed increased glucose metabolism in the supraspinal locomotor network including the thalamus (Z = 6.55), cerebellar vermis and the brainstem (pedunculopontine/mesencephalic locomotor region). Exploratory analyses using proportional scaling to the cerebellum and WM returned similar findings. Here, we have established the feasibility and tolerability of a novel method capable of capturing neural activations related to actual walking and extended previous knowledge including the recruitment of brain regions involved in sensory processing. Our paradigm could be used to explore pathological alterations in various gait disorders.