A reference-based approach using whole-brain segmentation for estimating blood activity concentration in CBV...

Quantitative imaging of cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO₂), and cerebral blood volume (CBV) using ¹⁵O-labeled compounds is useful for evaluating cerebral ischemia. However, quantitative PET requires measurement of blood activity concentration, which is typically obtained by arterial blood sampling. Although image-derived and reference-based input function methods have been developed for CBF, OEF, and CMRO₂ quantification, a non-invasive method for obtaining blood activity concentration for CBV measurement has not been established. This study aimed to develop and validate a reference-based method for estimating blood activity concentration from C¹⁵O PET images.

Among 186 subjects, mean CBV and the coefficient of variation (CV) were calculated for each brain segment in 64 subjects (Group A; moyamoya disease (MMD) present/absent, 20/44). In an independent cohort of 122 subjects (Group B; MMD present/absent, 35/87), blood activity concentration was estimated for each brain segment by reproducing the reference mean CBV obtained from Group A. The segment-based estimates were combined using CV-weighted averaging. The estimated blood activity concentrations were compared with those obtained by arterial blood sampling.

The mean ± SD of CBV across all segments in Group A was 0.039 ± 0.011 ml/g overall, 0.037 ± 0.009 ml/g in subjects without MMD, and 0.043 ± 0.012 ml/g in subjects with MMD. In Group B, the percentage differences between reference-based and measured blood activity concentrations were 0.35 ± 9.8%, -1.4 ± 8.8%, and 4.8 ± 10.6% in the overall, MMD-absent, and MMD-present groups, respectively, using the all-segment approach. When the CBV-matched segment approach was applied, the corresponding differences were -0.60 ± 8.8%, -1.4 ± 8.4%, and 1.5 ± 9.4%, respectively.

The reference-based blood activity concentrations showed good agreement with those obtained by arterial blood sampling, and the CBV-matched segment approach reduced the difference in the MMD-present group. The proposed method may enable non-invasive and automated estimation of blood activity concentration for quantitative CBV measurement without arterial blood sampling.