Evaluation of non-invasive, semi-quantitative 15O PET for patients with cerebrovascular steno-occlusive disease
2019
1181 Objectives: Quantification of cerebral blood flow (CBF) and oxygen metabolism plays important roles in the understanding of brain pathophysiology for patients with cerebrovascular disease. Oxygen-15 PET (15O PET) is the gold standard method: CBF, oxygen extraction fraction (OEF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2) are determined with a use of the blood-sampled arterial input function (BSAIF). However, the invasive procedure is not always feasible and hampers the widespread use in routine clinical practice. In addition, recently-emerged PET/MRI scanners complicate the blood sampling. The present study focused on a simplified semi-quantitative 15O PET method [Iguchi 2014] and compared with the conventional AIF method in patients with cerebrovascular steno-occlusive disease. Methods: Subjects and PET acquisition: Patients with occlusion or severe stenosis of the unilateral internal carotid artery (ICA) or middle cerebral artery (MCA) were included (n=10). The 15O PET study included three emission scans: 4-min scanning with 1-min inhalation of C15O, 3-min scanning with 1.5-min inhalation of 15O2, and 1.5-min scanning with bolus injection of H215O. BSAIF measured for each patient was used for the calculation of quantitative CBF and OEF, which were the reference standards for evaluating the non-invasive method. Non-invasive AIF estimation: AIF for each patient can be non-invasively determined based on a time activity curve (TAC) measured at ICA, however, which includes activity from surrounding tissues and underestimates blood activity due to partial volume effect. In the present method, the measured ICA TACs are corrected through the reference region modeling [Iguchi 2014]: Step 1) two TACs are obtained from IC (C1) and surrounding tissue (C2) regions of interest (ROIs). Non-invasive AIF (ICAIF) is assumed to be a linear sum of scaled two TACs, i.e. ICAIF = αC1 - βC2; Step 2) scaling coefficients (α, β) are determined by matching between the PET-measured TAC in the reference region and the calculated TAC using ICAIF (one-tissue with blood volume compartmental modeling). Elliptical ROIs were bilaterally placed on the MCA cortical regions, and the normal hemisphere ROI was defined as “reference region” in where CBF, OEF, and CBV were assumed to be normal values, i.e., 50 (mL/100 mL/min), 40 (%), and 4 (mL/100 mL), respectively. Data analysis: Once ICAIF was estimated, semi-quantitative CBF and OEF were calculated with ARG method, the same manner with BSAIF. OEF was also calculated based on dynamic PET images with basis-function fitting (no need of C15O) [Kudomi 2013]. In addition, more simplified count-based method was also investigated: H215O raw image and 15O2/H215O ratio image are simply regarded as CBF and OEF maps, respectively. Ischemic-to-normal ROI ratios of CBF and OEF were compared between the methods. Results: Ischemic-to-normal CBF ratios were almost identical between BSAIF and ICAIF (correlation coefficient r = 0.996; Figure 1). Count-based method also showed strong correlation (r = 0.989) but with significant positive biases for lower CBF ratios, indicating that the count-based method underestimates the degree of CBF reduction in ischemic regions. ICAIF provided overall good results of ARG-calculated OEF ratio (r = 0.911) but failed to provide consistent results of basis function-calculated OEF ratio for some patients due to subject head motion during PET scanning and/or poor image quality for the dynamic fitting analysis (Figure 2). Count-based method showed lesser correlation (r = 0.881), probably due to not accounting for CBV. Conclusions: The present non-invasive method provides relative CBF and OEF with sufficiently high accuracy when ARG calculations are applied. References: Iguchi S, et al., Japanese journal of CBFM 2014; 26: 172 (“Noninvasive estimation of arterial input function in rapid O-15 gas PET”, in Japanese); Kudomi N, et al., JCBFM 2013; 33: 440-448;
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