0446

Quantitative assessment of cerebral oxygen extraction fraction (OEF) in the medial temporal lobe
Dengrong Jiang1, Peiying Liu1,2, Zixuan Lin1, Abhay Moghekar3, Jay J. Pillai1,4, and Hanzhang Lu1,5,6
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States, 3Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 4Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 5Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 6F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States

Synopsis

The medial temporal lobe (MTL), including the hippocampus, is a key area implicated in many brain diseases, such as Alzheimer’s disease. Since neural activity is tightly coupled to the brain’s oxygen consumption, oxygen-extraction-fraction (OEF) in the MTL (MTL-OEF) may serve as a functional biomarker for this critical region. In this work, we developed a novel non-invasive MRI technique, AS-aTRUPC, to specifically measure the MTL-OEF in the human brain. We found that in healthy volunteers, the MTL-OEF is lower than the cortical OEF. The sensitivity of our technique in detecting changes in MTL-OEF was demonstrated in caffeine challenge experiments.

INTRODUCTION

The medial temporal lobe (MTL), including the hippocampus, is a key area implicated in many brain diseases, such as Alzheimer’s disease (AD)1-3, schizophrenia4 and epilepsy5. For example, MTL atrophy has been a hallmark of AD1-3. However, structural atrophy represents a late stage of MTL impairment and is generally considered irreversible. At early stages of brain diseases, functional biomarkers may be more sensitive to tissue impairment6. Since neural activity is tightly coupled to the brain’s oxygen consumption7, oxygen-extraction-fraction (OEF) in the MTL (MTL-OEF) may serve as a functional biomarker for this critical region8. Therefore, the goal of this work is to develop a novel MRI technique to quantitatively measure MTL-OEF in the human brain.

METHODS

Principle: OEF can be estimated from the arterio-venous difference in oxygenation. MTL is mainly drained by basal-veins-of-Rosenthal (BVs) (Figure 1A), which have relatively little variations across individuals9 and provide a foundation for MTL-OEF measurement. The key step is then to measure venous oxygenation (Yv) in the BVs.
Pulse sequence: Figure 1B illustrates the proposed arterial-suppressed accelerated T2-relaxation-under-phase-contrast (AS-aTRUPC) MRI pulse sequence. Briefly, this sequence utilizes phase-contrast (PC, green boxes in Figure 1B) complex subtraction to isolate pure blood signal in the BVs, and applies T2-preparation (Figure 1B, red box) with varying effective TEs (eTEs) to quantify the blood T2, which can be converted to Yv through a calibration model10. OEF can then be calculated as OEF=(Ya−Yv)/Ya×100%, where arterial oxygenation Ya is assumed to be 98%. To minimize arterial contamination from the posterior cerebral arteries that are anatomically adjacent to BVs, arterial-suppression (AS) pulses (Figure 1B, black boxes) are used to suppress the incoming arterial blood throughout the acquisition train. To reduce the scan time, the turbo-field-echo (TFE) scheme is used to acquire multiple k-lines per TR11.
Scan Procedures: Figure 2A shows the general scan procedures to measure MTL-OEF. First, to visualize the BVs to position AS-aTRUPC, a time-of-flight (TOF) venogram was acquired. This venogram was placed coronally and covered the middle part of the brain. Second, a 3D susceptibility-weighted-imaging (SWI) scan was performed to cover the courses of bilateral BVs. Minimal-intensity-projection (mIP) images were then generated. Finally, we positioned the imaging slice of AS-aTRUPC at the same location as the SWI mIP image that showed the best coverage of bilateral BVs, and placed the AS slab below the imaging slice (Figure 2B).
Study 1: Feasibility Study: Twenty healthy subjects (10M/10F, age 33±11) were scanned to determine the normative values of MTL-OEF. TOF venogram used: 2D field-of-view (FoV)=200×200mm2, slice thickness=2mm, in-plane resolution=0.8×0.8mm2 and scan time=2.7min. SWI used: 3D FoV=180×220×50mm3, voxel-size=0.9×0.9×1.3mm3, TR/TE=30/24ms, scan time=2.2min. AS-aTRUPC used: 2D single slice, FoV=200×200mm2, slice thickness=10mm, reconstructed in-plane resolution=0.8×0.8mm2, 3 eTEs: 0, 40 and 80ms, 4 averages, velocity-encoding (VENC)=7cm/s, TFE factor=15, arterial-suppression slab thickness=40mm with a gap of 10mm below the imaging slice, scan time=4.8min.
Study 2: Caffeine challenge: To evaluate the sensitivity of AS-aTRUPC to OEF changes, on ten of the subjects (4M/6F, age 26±4), we conducted a caffeine challenge that is known to increase OEF12. The experimental procedure is listed in Figure 2C. TOF, SWI and AS-aTRUPC used the same protocols as described in Study 1. For comparison with AS-aTRUPC, we also measured the OEF in the superior-sagittal-sinus (SSS) using a global OEF technique, T2-relaxation-under-spin-tagging (TRUST) MRI, which has been validated against gold-standard 15O-PET13. The TRUST scan protocol followed the literature13. Each subject first underwent one TRUST and one AS-aTRUPC scan to measure baseline OEF values, then took one 200mg caffeine tablet and underwent another 8 TRUST and AS-aTRUPC scans.
Data analysis: The processing of AS-aTRUPC data followed similar procedures in the literature11. OEF was quantified from four region-of-interests: two on bilateral BVs, one on vein-of-Galen (GV) and one on SSS. TRUST data was processed following the literature13.

RESULTS AND DISCUSSION

Study 1: Figure 3 shows representative AS-aTRUPC data. Complex subtraction between the phase reference (“Ref” in Figure 1B) and the velocity-encoded (“Enc” in Figure 1B) images yields a complex difference image, in which the tissue signals are cancelled out, leaving only the blood signal in the vessels (thereby eliminating partial volume effects). Across the subjects, OEF in BV, GV and SSS were 24.5±4.5%, 24.8±4.0% and 34.4±4.0%, respectively (Figure 4). OEF in BV (which represents the MTL-OEF) was similar to OEF in GV (paired t-test P=0.66), but both of them were considerably lower than OEF in SSS (P<0.0001). This is consistent with previous reports that veins draining the deep brain (e.g., BV, GV) have lower OEF than veins draining the cortical region (e.g., SSS)11,14.
Study 2: As illustrated in Figure 5A, after caffeine ingestion, OEF showed an expected increase in all veins. Comparing the last time point to the baseline, the caffeine-induced OEF increases were 9.3±4.1%, 10.7±3.8% and 10.6±2.9% in BV, GV and SSS, respectively (P<0.0001 for all veins), demonstrating the sensitivity of AS-aTRUPC. In addition, OEF in SSS measured by AS-aTRUPC agreed well with TRUST OEF, with a strong correlation (intraclass-correlation-coefficient=0.94, Figure 5B) and no significant bias (P=0.12), suggesting that AS-aTRUPC has similar accuracy in OEF measurement compared to TRUST.

CONCLUSION

We have developed a novel MRI technique to measure MTL-OEF, which facilitates future studies of brain diseases such as AD.

Acknowledgements

No acknowledgement found.

References

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Figures

Figure 1. Illustrations of BVs and AS-aTRUPC sequence. (A) BVs run alongside the MTL and midbrain and drain into vein-of-Galen. (B) Sequence diagram of AS-aTRUPC. Three eTEs by T2-preparation (red box) are acquired in an interleaved fashion. At each eTE, a phase reference (Ref) image and a velocity-encoded (Enc) image are acquired. Multiple k-lines (green boxes) are acquired per TR. Arterial-suppression (AS) pulses (black boxes) are played before T2-preparation and before each excitation pulse. At the end of TR, post-saturation (blue box) resets magnetization to 0.

Figure 2. Experimental design. (A) Step-by-step scan procedures to measure MTL-OEF. (B) TOF maximum-intensity-projection images showing the BVs (red arrows). The positions of the SWI scan (blue box), the imaging slice (yellow box) and the AS slab (green box) of AS-aTRUPC are shown in the sagittal TOF image. (C) Experiment procedures of the caffeine challenge study. TOF and SWI were used to position the AS-aTRUPC scans before (baseline) and after caffeine ingestion (challenge).

Figure 3. Representative AS-aTRUPC data. (A) Phase reference, velocity-encoded and complex difference images are shown for eTE=0ms, while zoom-in views are shown for all eTEs. (B) Averaged signal intensities in a region-of-interest delineated by the red contour in (A) as a function of eTEs. The fitted equation is also shown.

Figure 4. Comparison of OEF in BV, GV and SSS across the subjects. Median, interquartile range, minimum and maximum of the data points are shown in the box plots.

Figure 5. Results of caffeine challenge study. (A) OEF at baseline (Time=0) and after caffeine ingestion. Error bars represent standard errors of the OEF values across the subjects at each time point. (B) Scatter plot between OEF in SSS measured by AS-aTRUPC and TRUST OEF. Dashed line represents the fitted line.

Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)
0446
DOI: https://doi.org/10.58530/2022/0446