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Quantitative analysis of positron emission tomography (PET) brain imaging data requires a metabolite-corrected arterial input function (AIF) for estimation of distribution volume and related outcome measures. Collecting arterial blood samples adds risk, cost, measurement error, and patient discomfort to PET studies. Minimally invasive AIF estimation is possible with simultaneous estimation (SIME), but at least one arterial blood sample is necessary. In this study, we describe a noninvasive SIME (nSIME) approach that utilizes a pharmacokinetic input function model and constraints derived from machine learning applied to an electronic health record database consisting of &#x201C;long tail&#x201D; data (digital records, paper charts, and handwritten notes) that were collected ancillary to the PET studies. We evaluated the performance of nSIME on 95 &#x005B;<sup>11</sup>C&#x005D;DASB PET scans that had measured AIFs. The results indicate that nSIME is a promising alternative to invasive AIF measurement. The general framework presented here may be expanded to other metabolized radioligands, potentially enabling quantitative analysis of PET studies without blood sampling. A glossary of technical abbreviations is provided at the end of this paper.

Toward Noninvasive Quantification of Brain Radioligand Binding by Combining Electronic Health Records and Dynamic PET Imaging Data