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

BACKGROUND: We aimed to investigate whether combined phosphorous ((31)P) magnetic resonance spectroscopic imaging (MRSI) and quantitative [Formula: see text] mapping are able to detect alterations of the cerebral oxygen extraction fraction (OEF) and intracellular pH (pH(i)) as markers the of cellular energy metabolism in cerebral small vessel disease (SVD). MATERIALS AND METHODS: 32 patients with SVD and 17 age-matched healthy control subjects were examined with 3-dimensional (31)P MRSI and oxygenation-sensitive quantitative [Formula: see text] mapping (1/ [Formula: see text] = 1/T(2)* - 1/T(2)) at 3 Tesla (T). PH(i) was measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative [Formula: see text] values were averaged across the entire white matter (WM). Furthermore, [Formula: see text] values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls. RESULTS: Quantitative [Formula: see text] 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 [Formula: see text] values correlated significantly with the WMH load (ρ=0.441, p = 0.006). Increased [Formula: see text] was significantly associated with more alkaline pH(i) (ρ=0.299, p < 0.05). Both [Formula: see text] and pH(i) 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). CONCLUSIONS: 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.