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

We aimed to investigate whether combined phosphorous (31P) magnetic resonance spectroscopic imaging (MRSI) and quantitative T2' 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-dimensional 31P MRSI and oxygenation-sensitive quantitative T2' mapping (1/ T2' = 1/T2* - 1/T2) at 3 Tesla (T). PHi was measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative T2' values were averaged across the entire white matter (WM). Furthermore, T2' values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls.Quantitative T2' values were significantly increased across the entire WM and in the NAWM in patients compared to control subjects (149.51 ± 16.94 vs. 138.19 ± 12.66 ms and 147.45 ± 18.14 vs. 137.99 ± 12.19 ms, p < 0.05). WM T2' values correlated significantly with the WMH load (ρ=0.441, p = 0.006). Increased T2' was significantly associated with more alkaline pHi (ρ=0.299, p < 0.05). Both T2' 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.