Oxygen Mapping within Healthy and Acutely Infarcted Brain Tissue in Humans Using the NMR Relaxation of Lipids: A Proof-Of-Concept Translational Study

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.

Assessing Tumor Oxygenation for Predicting Outcome in Radiation Oncology: A Review of Studies Correlating Tumor Hypoxic Status and Outcome in the Preclinical and Clinical Settings

“…However, a quantitative aspect could not be demonstrated in rhabdomyosarcomas and glioma models, and lipids T 1 and global T 1 turned out to be less predictive of the outcome of radiation therapy than $R_2^{*}$ (101). Considering the clinical application of MOBILE, the method has demonstrated its ability to identify hypoxia in stroke areas (124). The method is currently being investigated in human gliomas, with a pilot study showing that global R 1 and lipid R 1 values are significantly lower in tumors than in the “normal appearing white matter” of patients or the healthy brains of volunteers and that lipid R 1 measurements enable discrimination between tumor areas and peritumoral edema (125).…”

The Role of Imaging Biomarkers to Guide Pharmacological Interventions Targeting Tumor Hypoxia

“…The method provided highly sensitive and quantitative measurements of oxygenation in lipid-rich mammary cancer models (Colliez et al, 2014). However, while sensitive to changes in tissue oxygen content, the lipid R 1 turned out to be no more sensitive than water R 1 in tissues with lower lipid content, an observation that was done in preclinical models and in patients (Colliez et al, 2015;Cao-Pham et al, 2016b;Safronova et al, 2016).…”

In vivo electron paramagnetic resonance oximetry and applications in the brain

“… 46 The authors demonstrated, in a proof-of-concept study, that the method is sensitive to changes in tissue pO 2 in animal tumor, stroke and liver models in addition to studies on a clinical MR with healthy volunteers and brain infarcted patients. 47 48 The studies suggested that MOBILE has the potential to provide noninvasive and qualitative measurements of tissue pO 2 limited to the amount of lipids in the tissue of interest.…”