Positron emission tomography (PET) remains the gold standard for quantitative imaging of the cerebral metabolic rate of oxygen (CMRO₂); however, it is an invasive and complex procedure that requires accounting for recirculating [¹⁵O]H₂O (RW) and the cerebral blood volume (CBV). This study presents a non-invasive reference-based technique for imaging CMRO₂ that was developed for PET/magnetic resonance imaging (MRI) with the goal of simplifying the PET procedure while maintaining its ability to quantify metabolism. The approach is to use whole-brain (WB) measurements of oxygen extraction fraction (OEF) and cerebral blood flow (CBF) to calibrate [¹⁵O]O₂-PET data, thereby avoiding the need for invasive arterial sampling. Here we present the theoretical framework, along with error analyses, sensitivity to PET noise and inaccuracies in input parameters, and initial assessment on PET data acquired from healthy participants. Simulations showed that neglecting RW and CBV corrections caused errors in CMRO₂ of less than 10% for changes in regional OEF of 25%. These predictions were supported by applying the reference-based approach to PET data, which resulted in remarkably similar CMRO₂ images to those generated by analyzing the same data using a modeling approach that incorporated the arterial input functions and corrected for CBV contributions. Significant correlations were observed between regional CMRO₂ values from the two techniques (slope=1.000.04, R ²>0.98) with no significant differences found for integration times of 3 and 5 min. In summary, results demonstrate the feasibility of producing quantitative CMRO₂ images by PET/MRI without the need for invasive blood sampling.

正电子发射断层扫描 (PET) 仍然是脑氧代谢率定量成像的金标准 (CMRO ₂ )；然而，这是一种侵入性和复杂的过程，需要考虑再循环 [ ¹⁵ O]H ₂ O (RW) 和脑血容量 (CBV)。本研究提出了一种用于 CMRO ₂成像的非侵入性参考技术，该技术是为 PET/磁共振成像 (MRI) 开发的，其目标是简化 PET 程序，同时保持其量化代谢的能力。该方法是使用氧气提取分数 (OEF) 和脑血流量 (CBF) 的全脑 (WB) 测量值来校准 [ ¹⁵ O]O ₂-PET 数据，从而避免对侵入性动脉取样的需要。在这里，我们介绍了理论框架、误差分析、对 PET 噪声的敏感性和输入参数的不准确性，以及对从健康参与者获得的 PET 数据的初步评估。模拟表明，对于 25% 的区域 OEF 变化，忽略 RW 和 CBV 校正会导致 CMRO _{2 中}的误差小于 10%。这些预测得到了将基于参考的方法应用于 PET 数据的支持，这导致 CMRO ₂图像与使用结合动脉输入函数并校正 CBV 贡献的建模方法分析相同数据生成的图像非常相似。区域 CMRO ₂之间观察到显着相关性来自两种技术的值（斜率 = 1.000.04，R ² > 0.98），没有发现积分时间为 3 分钟和 5 分钟的显着差异。总之，结果证明了通过 PET/MRI生成定量 CMRO ₂图像而不需要侵入性采血的可行性。