Reconstruction of input functions from a dynamic PET image with sequential administration of ¹⁵O₂ and H215O for noninvasive and ultra-rapid measurement of CBF, OEF, and CMRO₂

Abstract

CBF, OEF, and CMRO images can be quantitatively assessed using PET. Their image calculation requires arterial input functions, which require invasive procedure. The aim of the present study was to develop a non-invasive approach with image-derived input functions (IDIFs) using an image from an ultra-rapid O and CO protocol. Our technique consists of using a formula to express the input using tissue curve with rate constants. For multiple tissue curves, the rate constants were estimated so as to minimize the differences of the inputs using the multiple tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects ( n = 24). The estimated IDIFs were well-reproduced against the measured ones. The difference in the calculated CBF, OEF, and CMRO values by the two methods was small (<10%) against the invasive method, and the values showed tight correlations ( r = 0.97). The simulation showed errors associated with the assumed parameters were less than ∼10%. Our results demonstrate that IDIFs can be reconstructed from tissue curves, suggesting the possibility of using a non-invasive technique to assess CBF, OEF, and CMRO.

Quantification of brain oxygen extraction and metabolism with [15O]-gas PET: A technical review in the era of PET/MRI

“…For in vivo datasets, the IDIF rate constants were jointly estimated from multiple observed tissue curves, and mean values of the rate parameters were used to generate the final IDIF for OEF and CMRO 2 analysis. During sequential inhalation of [ 15 O]-water and [ 15 O]-CO 2 , the estimated IDIFs showed great fidelity ( R 2 correlation = 0.97) to measured input functions from blood in cerebrovascular patients ( Kudomi et al, 2018 ).…”

“…Kudomi et al developed an IDIF approach for [ 15 O]-oxygen that parameterizes the IDIF formula based on the underlying [ 15 O]-oxygen exponential kinetic model ( Kudomi et al, 2018 ). This IDIF expression assumed a constant generation rate of recirculating water ( k ) and analytical relationships with the brain tissue activity curves measured by PET.…”

A Noninvasive Method for Quantifying Cerebral Metabolic Rate of Oxygen by Hybrid PET/MRI: Validation in a Porcine Model

“…Alternately, the effects of RW can be minimized by short scan times following a single inhalation of 15 O-O2 (6). More recently, approaches incorporating image-derived input functions have been proposed to avoid measuring the arterial input function (AIF), which is an invasive and inherently noisy procedure (7,8). However, the accuracy of these approaches depends on either an empirical factor relating the total AIF and its RW component, or careful measurement of a coefficient to scale the arterial time-activity curve (TAC).…”

Imaging Acute Stroke: From One-Size-Fit-All to Biomarkers

“…However, due to the technical complexity, 15 O PET is not widely performed in clinical settings, with issues involving requirement of on-site cyclotron and radiochemistry facility because of the short half-life of 15 O (2 min), real-time artery blood sampling and analyzing to obtain the regional CBF (rCBF), as well as complex post processing (87). Efforts have been made to streamline the 15 O-PET examination for routine clinical practice, including: (i) quantitative voxel-byvoxel maps of rCBF without a direct arterial input function ( 88 (90). Attempts were also made in animal stroke studies.…”