Impaired oxygen extraction and adaptation of intracellular energy metabolism in cerebral small vessel disease.

Abstract

We aimed to investigate whether combined phosphorous (31P) magnetic resonance spectroscopic imaging (MRSI) and quantitative mapping are able to detect alterations of the cerebral oxygen extraction fraction (OEF) and intracellular pH (pHi) as markers the of cellular energy metabolism in cerebral small vessel disease (SVD). 32 patients with SVD and 17 age-matched healthy control subjects were examined with 3-dimensional31P MRSI and oxygenation-sensitive quantitative mapping (1/ =1/T2* - 1/T2) at 3 Tesla (T). PHiwas measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative values were averaged across the entire white matter (WM).Furthermore, values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls. Quantitative values were significantly increased across the entire WM and in the NAWM in patients compared to control subjects (149.51±16.94vs. 138.19±12.66ms and 147.45±18.14vs. 137.99±12.19ms, p<0.05).WM values correlated significantly with the WMH load (ρ=0.441, p=0.006). Increased was significantly associated with more alkaline pHi(ρ=0.299, p<0.05). Both and pHi were significantly positively correlated with vascular pulsatility in the distal carotid arteries (ρ=0.596, p=0.001 and ρ=0.452, p=0.016). This exploratory study found evidence of impaired cerebral OEF in SVD, which is associated with intracellular alkalosis as an adaptive mechanism. The employed techniques provide new insights into the pathophysiology of SVD with regard to disease-related consequences on the cellular metabolic state.