Abstract

The clinical applicability of brain oxygenation mapping using the MOBILE (Mapping of Oxygen By Imaging Lipids relaxation Enhancement) magnetic resonance (MR) technique was assessed in the clinical setting of normal brain and of acute cerebral ischemia as a founding proof-of-concept translational study. Changes in the oxygenation level within healthy brain tissue can be detected by analyzing the spin-lattice proton relaxation (‘Global T 1 ’ combining water and lipid protons) because of the paramagnetic properties of molecular oxygen. It was hypothesized that selective measurement of the relaxation of the lipid protons (‘Lipids T 1 ’) would result in enhanced sensitivity of pO2 mapping because of higher solubility of oxygen in lipids than in water, and this was demonstrated in pre-clinical models using the MOBILE technique. In the present study, 12 healthy volunteers and eight patients with acute (48–72 hours) brain infarction were examined with the same clinical 3T MR system. Both Lipids R1 (R1 = 1/T1) and Global R1 were significantly different in the infarcted area and the contralateral unaffected brain tissue, with a higher statistical significance for Lipids R1 (median difference: 0.408 s-1; p<0.0001) than for Global R1 (median difference: 0.154 s-1; p = 0.027). Both Lipids R1 and Global R1 values in the unaffected contralateral brain tissue of stroke patients were not significantly different from the R1 values calculated in the brain tissue of healthy volunteers. The main limitations of the present prototypic version of the MOBILE sequence are the long acquisition time (4 min), hampering robustness of data in uncooperative patients, and a 2 mm slice thickness precluding accurate measurements in small infarcts because of partial volume averaging effects.

Highlights

  • Mapping brain oxygenation is a key challenge in the clinical workup of many cerebral disorders, including acute/chronic ischemia, neoplastic processes, and a wide range of neurodegenerative disorders [1,2]

  • A significant correlation has been established between Lipids R1 values and pO2 values recorded with Electron Paramagnetic Resonance [15], suggesting the quantitative value of MOBILE in this pre-clinical setting

  • In the second cohort we investigated whether it is capable of detecting brain oxygen deprivation in the paradigmatic pathological condition of acute decrease in oxygen supply within a lipid-rich biological tissue

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Summary

Introduction

Mapping brain oxygenation is a key challenge in the clinical workup of many cerebral disorders, including acute/chronic ischemia, neoplastic processes, and a wide range of neurodegenerative disorders [1,2]. The technique referred to as ‘Oxygen-enhanced MRI’ measures the proton T1 relaxation time, which is mainly influenced by the water protons We called this measurement ‘Global T1’ in the present study. The MOBILE (Mapping of Oxygen by Imaging Lipids relaxation Enhancement) sequence was developed to increase the sensitivity of T1 measurements by selectively recording the T1 of the lipids, a specific measurement we called ‘Lipids T1‘. This method is conceptually based on the higher solubility of oxygen in lipids than in water and the demonstrated ability to monitor changes in tissue oxygenation in brain, muscles, liver and tumors in a preclinical setting [14]. In the second cohort we investigated whether it is capable of detecting brain oxygen deprivation in the paradigmatic pathological condition of acute decrease in oxygen supply within a lipid-rich biological tissue

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