A non-invasive hybrid PET/MR method for imaging the cerebral metabolic rate of oxygen

Introduction: Positron emission tomography (PET) is the gold standard for imaging the cerebral metabolic rate of oxygen (CMRO₂); however, the technique is invasive as it requires arterial sampling and complex due to the need to correct for recirculating [¹⁵O]H₂O and blood-borne activity [1]. We propose a non-invasive hybrid PET/ magnetic resonance imaging (MRI) method (PMROx) that uses MRI measurements of whole-brain (WB) CMRO₂ to calibrate [¹⁵O]O₂-PET. With PMROx, cerebral blood flow (CBF) images are obtained with a similar non-invasive PET/MRI approach combining [¹⁵O]H₂O PET with phase-contrast MRI [2]. Alternatively, PET imaging can be reduced to just [¹⁵O]O₂ inhalation by incorporating the MRI-based perfusion method, arterial spin labeling (PMROx_ASL) [3]. Here we present a comparison between PMROx and PMROx_ASL in animal experiments that also incorporated an established PET-alone method for validation [4]. The sensitivity of PMROx_ASL to altered metabolism was investigated by increasing the anesthetics.

Methods: [¹⁵O]H₂O and [¹⁵O]O₂ PET data were acquired in a hybrid PET/MR scanner (3 T Siemens Biograph mMR), together with simultaneous MRI oximetry (OxFlow [5]) and perfusion (ASL), from juvenile pigs (n = 8). Animals were anesthetized with 3% isoflurane and 6 mL/kg/h propofol. Arterial sampling was performed for PET-alone measurements. Cerebral metabolism was reduced by increasing the propofol infusion to 20 mL/kg/h.

Results: Significant correlations were found between regional CMRO₂ measurements from PET and each of the PMROx methods (i.e. using either [¹⁵O]water or ASL to image CBF) with no significant differences between average CMRO₂ from the three techniques: 1.89 ± 0.16 (PMROx), 1.88 ± 0.24 (PMROx_ASL) and 1.81 ± 0.10 mLO₂/100g/min (PET). Moreover, PMROx and PMROx_ASL were sensitive to propofol-induced reduction in CMRO₂ (Fig. 1).

Conclusions: This study provides an initial validation of a non-invasive PET/MRI technique that circumvents many of the complexities of PET-only CMRO₂ imaging. PMROx not only avoids arterial sampling, but can reduce the PET imaging procedure to [¹⁵O]O₂ by incorporating ASL-CBF images. Future studies in humans are required to validate this approach. References: [1] Mintun MA, Raichle ME, Martin WR, Herscovitch P. Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography. J Nucl Med. 1984;25:177-87. [2] Ssali T, Anazodo UC, Thiessen JD, Prato FS, St. Lawrence K. A noninvasive method for quantifying cerebral blood flow by hybrid PET/MRI. J Nucl Med. 2018;59:1329-1334. [3] Günther M, Oshio K, Feinberg DA. Single-shot 3D imaging techniques improve arterial spin labeling perfusion measurements. Magn Reson Med. 2005;54:491-498. [4] Kudomi N, Hirano Y, Koshino K, et al. Rapid quantitative CBF and CMRO2 measurements from a single PET scan with sequential administration of dual 15O-labeled tracers. J Cereb Blood Flow Metab. 2013;33:440-448. [5] Jain V, Langham MC, Wehrli FW. MRI estimation of global brain oxygen consumption rate. J Cereb Blood Flow Metab. 2010;30:1598-1607. Figure 1. Group-wise CBF, OEF and CMRO₂ images obtained with DBFM, PMROx and PMROx_ASL techniques for baseline (n = 8, top three rows). CBF and CMRO₂ results from PMROx and PMROx_ASL for the lower metabolic condition (n = 6) are presented on the bottom two rows. MPRAGE from one animal was included for anatomical reference.

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