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Calibrated fMRI for dynamic mapping of CMRO2 responses using MR-based measurements of whole-brain venous oxygen saturation - PubMed

Calibrated fMRI for dynamic mapping of CMRO2 responses using MR-based measurements of whole-brain venous oxygen saturation

Erin K Englund et al. J Cereb Blood Flow Metab. 2020 Jul.

Abstract

Functional MRI (fMRI) can identify active foci in response to stimuli through BOLD signal fluctuations, which represent a complex interplay between blood flow and cerebral metabolic rate of oxygen (CMRO2) changes. Calibrated fMRI can disentangle the underlying contributions, allowing quantification of the CMRO2 response. Here, whole-brain venous oxygen saturation (Yv) was computed alongside ASL-measured CBF and BOLD-weighted data to derive the calibration constant, M, using the proposed Yv-based calibration. Data were collected from 10 subjects at 3T with a three-part interleaved sequence comprising background-suppressed 3D-pCASL, 2D BOLD-weighted, and single-slice dual-echo GRE (to measure Yv via susceptometry-based oximetry) acquisitions while subjects breathed normocapnic/normoxic, hyperoxic, and hypercapnic gases, and during a motor task. M was computed via Yv-based calibration from both hypercapnia and hyperoxia stimulus data, and results were compared to conventional hypercapnia or hyperoxia calibration methods. Mean M in gray matter did not significantly differ between calibration methods, ranging from 8.5 ± 2.8% (conventional hyperoxia calibration) to 11.7 ± 4.5% (Yv-based calibration in response to hyperoxia), with hypercapnia-based M values between (p = 0.56). Relative CMRO2 changes from finger tapping were computed from each M map. CMRO2 increased by ∼20% in the motor cortex, and good agreement was observed between the conventional and proposed calibration methods.

Keywords: Arterial spin labeling; BOLD; calibrated fMRI; cerebral metabolic rate of oxygen; magnetic resonance imaging.

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Figures

Figure 1.
Figure 1.

OxBOLD pulse sequence showing interleaved approach for ASL, BOLD, and susceptometry-based oximetry (SBO) data. Relative slice/slab locations are shown on the right, where the dark red block corresponds to the 3D ASL FOV with labeling plane is shown in green, the light red boxes show the BOLD-weighted slices, and the blue shows the single-slice SBO acquisition location. The relative longitudinal magnetization (Mz/M0) over the course of one TR is shown on bottom for gray matter (GM, T1 = 1300 ms), white matter (WM, T1 = 800 ms), local blood (e.g. not accounting for blood flowing in from the labeling plane, T1 = 1660 ms), and cerebrospinal fluid (CSF, T1 = 4000 ms). The background-suppression pulses during the ASL labeling and post labeling delay periods reduce the static tissue signal to ∼1% of its initial value. A delay is allotted between the ASL and BOLD acquisitions and again between BOLD and SBO acquisitions to allow for signal recovery.

Figure 2.
Figure 2.

Targeted (line) and measured (dots) end-tidal oxygen (top) and carbon dioxide (bottom) data in a representative subject. OxBOLD data were acquired during baseline (normoxic/normocapnic air), hyperoxia (+230 mmHg from baseline), and hypercapnia (+8 mmHg from baseline) periods. The finger tapping task was performed while breathing normocapnic/normoxic air between the hyperoxia and hypercapnia periods to make efficient use of scan time. The finger tapping task was 70 s off, then 70 s on, repeated twice. In most subjects, the nominal targeted baseline PETO2 was lower than the measured PETO2, as is shown here.

Figure 3.
Figure 3.

Baseline and gas stimulus images for ASL (signal intensity, SI, difference from control and label acquisitions), ΔBOLD, and susceptometry-based oximetry (SBO). Left panel shows anatomic images for reference. Perfusion-weighted signal was relatively unchanged in response to hyperoxia but increased substantially during hypercapnia. The BOLD response was similarly more prominent in response to hypercapnia, though both hyperoxia and hypercapnia stimuli elicited a positive BOLD response. The phase data were converted to venous oxygen saturation through the SBO model. The phase contrast between the superior sagittal sinus (indicated by the arrow) decreases during hyperoxia and hypercapnia, corresponding to an increase in venous oxygen saturation.

Figure 4.
Figure 4.

M maps showing axial acquisition, and sagittal and coronal reformats in a representative subject. M maps were obtained from hyperoxia (HO) and hypercapnia (HC) gas stimulus data using the proposed Yv-based model and conventional models. Maps demonstrate relative mutual agreement in this representative subject.

Figure 5.
Figure 5.

Bland–Altman analysis plots assessing the agreement of M (top series) and rCMRO2 (bottom series) between the various calibration models. Overall the mean bias was near zero, and the calculated limits of agreement (±1.96×standard deviation) encompassed zero.

Figure 6.
Figure 6.

Relative CMRO2 change in response to a finger tapping task in a representative subject. Focal CMRO2 increases are observed in the motor cortex. While these data are derived from the same task-based BOLD and ASL data, the M maps used to convert the relative BOLD and CBF changes differ.

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