MRI assessment of cerebral oxygen extraction fraction in the medial temporal lobe

The medial temporal lobe (MTL) is a key area implicated in many brain diseases, such as Alzheimer’s disease. As a functional biomarker, the oxygen extraction fraction (OEF) of MTL may be more sensitive than structural atrophy of MTL, especially at the early stages of diseases. However, there is a lack of non-invasive techniques to measure MTL-OEF in humans. The goal of this work is to develop an MRI technique to assess MTL-OEF in a clinically practical time without using contrast agents. The proposed method measures venous oxygenation (Y(v)) in the basal veins of Rosenthal (BVs), which are the major draining veins of the MTL. MTL-OEF can then be estimated as the arterio-venous difference in oxygenation. We developed an MRI sequence, dubbed arterial-suppressed accelerated T(2)-relaxation-under-phase-contrast (AS-aTRUPC), to quantify the blood T(2) of the BVs, which was then converted to Y(v) through a well-established calibration model. MTL-OEF was calculated as (Y(a) − Y(v))/Y(a) × 100%, where Y(a) was the arterial oxygenation. The feasibility of AS-aTRUPC to quantify MTL-OEF was evaluated in 16 healthy adults. The sensitivity of AS-aTRUPC in detecting OEF changes was assessed by a caffeine ingestion (200 mg) challenge. For comparison, T(2)-relaxation-under-spin-tagging (TRUST) MRI, which is a widely used global OEF technique, was also acquired. The dependence of MTL-OEF on age was examined by including another seven healthy elderly subjects. The results showed that in healthy adults, MTL-OEF of the left and right hemispheres were correlated (P = 0.005). MTL-OEF was measured to be 23.9 ± 3.6% (mean ± standard deviation) and was significantly lower (P < 0.0001) than the OEF of 33.3 ± 2.9% measured in superior sagittal sinus (SSS). After caffeine ingestion, there was an absolute percentage increase of 9.1 ± 4.0% in MTL-OEF. Additionally, OEF in SSS measured with AS-aTRUPC showed a strong correlation with TRUST OEF (intra-class correlation coefficient = 0.94 with 95% confidence interval [0.91, 0.96]), with no significant bias (P = 0.12). MTL-OEF was found to increase with age (MTL-OEF = 20.997 + 0.100 × age; P = 0.02). In conclusion, AS-aTRUPC MRI provides non-invasive assessments of MTL-OEF and may facilitate future clinical applications of MTL-OEF as a disease biomarker.