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

Annemarie Reiländer; Ulrich Pilatus; Jan-Rüdiger Schüre; Manoj Shrestha; Ralf Deichmann; Ulrike Nöth; Elke Hattingen; René-Maxime Gracien; Marlies Wagner; Alexander Seiler

doi:10.1016/j.cccb.2023.100162

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

Cereb Circ Cogn Behav. 2023 Feb 10:4:100162. doi: 10.1016/j.cccb.2023.100162. eCollection 2023.

Authors

Annemarie Reiländer^{1

2}, Ulrich Pilatus³, Jan-Rüdiger Schüre³, Manoj Shrestha², Ralf Deichmann², Ulrike Nöth², Elke Hattingen³, René-Maxime Gracien^{1

2}, Marlies Wagner^{2

3}, Alexander Seiler^{1

2}

Affiliations

¹ Department of Neurology, Goethe University Hospital Frankfurt, Schleusenweg 2-16, Frankfurt 60528, Germany.
² Brain Imaging Center, Goethe University Hospital Frankfurt, Frankfurt Germany.
³ Institute of Neuroradiology, Goethe University Hospital Frankfurt, Frankfurt Germany.

Abstract

Background: We aimed to investigate whether combined phosphorous (³¹P) magnetic resonance spectroscopic imaging (MRSI) and quantitative $T_{2}^{'}$ 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 ³¹P MRSI and oxygenation-sensitive quantitative $T_{2}^{'}$ mapping (1/ $T_{2}^{'}$ = 1/T₂* - 1/T₂) at 3 Tesla (T). PH_i was measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative $T_{2}^{'}$ values were averaged across the entire white matter (WM). Furthermore, $T_{2}^{'}$ values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls.

Results: Quantitative $T_{2}^{'}$ 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 $T_{2}^{'}$ values correlated significantly with the WMH load (ρ=0.441, p = 0.006). Increased $T_{2}^{'}$ was significantly associated with more alkaline pH_i (ρ=0.299, p < 0.05). Both $T_{2}^{'}$ 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.

Keywords: BBB, blood-brain barrier; CBF, cerebral blood flow; CBV, cerebral blood volume; CMRO2, Cerebral metabolic rate of oxygen; Cellular energy metabolism; DTI, diffusion tensor imaging; GE, gradient echo; Hb, hemoglobin; ICA, internal carotid artery; MR spectroscopy; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; MRSI, magnetic resonance spectroscopic imaging; Microstructural impairment; NAWM, normal-appearing white matter; OEF, oxygen extraction fraction; Oxygen extraction fraction; PI, Pulsatility index; RF, radio frequency; SVD, cerebral small vessel disease; Small vessel disease; TR, repetition time; WM, white matter; WMH, white matter hyperintensities; pHi, intracellular pH; quantitative MRI.