Pharmacokinetic modelling and adaptive design for regional tissue flow and extraction for preclinical PET/CT

临床前正电子发射断层扫描/计算机断层扫描（PET/CT）是一种成熟的非侵入性成像工具，用于研究疾病的发生和进展以及支持新药的开发。本项目旨在开发和验证一种新的PET/CT生物标志物，用于评估区域组织灌注变化，即基于18F-NaF PET图像的流动和提取。灌注可以通过血液被输送到组织的速率来测量。相对灌注评估常用于诊断和评价一些心脑血管疾病的治疗效果。不幸的是，体内和无创灌注的绝对定量仍然具有挑战性，因为示踪剂灌注不一定反映血液灌注。最近的试点实验表明，通过使用不同的放射性示踪剂递送策略，可以更好地估计灌注。您将通过数据分析和药代动力学建模来跟踪这些实验，以确定示踪剂流动是否可以从混淆效应中分离出来，您还将使用自适应设计来建立理想的成像、重建和分析方案，以实现这种分离。

Preclinical Positron Emission Tomography/Computed Tomography (PET/CT) is a well-established non-invasive imaging tool for studying disease development and progression as well as for supporting the development of novel drugs. This project aims to develop and validate a new PET/CT biomarker for assessment of regional tissue perfusion changes, namely flow and extraction, based on 18F-NaF PET images. Perfusion can be measured as the rate at which the blood is delivered to the tissue. Relative perfusion assessments are often used for diagnosis and evaluation of treatment response of a number of cardiovascular and brain diseases. Unfortunately absolute quantification of perfusion in vivo and non-invasively remains challenging because tracer perfusion doesn't necessarily reflect blood perfusion. Recent pilot experiments have shown that better estimates of perfusion can be achieved via the use of different radiotracer delivery strategies. You will follow-up these experiments with data analysis and pharmacokinetic modelling to establish whether tracer flow can be separated from confounding effects and you will also use adaptive design to establish what is the ideal imaging, reconstruction and analysis protocol for achieving this separation.