PDF(Pubmed)
Abstract：
UNASSIGNED: Recent evidence suggests the blood-to-brain influx rate (K1 ) in TSPO PET imaging as a promising biomarker of blood-brain barrier (BBB) permeability alterations commonly associated with peripheral inflammation and heightened immune activity in the brain. However, standard compartmental modeling quantification is limited by the requirement of invasive and laborious procedures for extracting an arterial blood input function. In this study, we validate a simplified blood-free methodologic framework for K1 estimation by fitting the early phase tracer dynamics using a single irreversible compartment model and an image-derived input function (1T1K-IDIF).
UNASSIGNED: The method is tested on a multi-site dataset containing 177 PET studies from two TSPO tracers ([11C]PBR28 and [18F]DPA714). Firstly, 1T1K-IDIF K1 estimates were compared in terms of both bias and correlation with standard kinetic methodology. Then, the method was tested on an independent sample of [11C]PBR28 scans before and after inflammatory interferon-α challenge, and on test-retest dataset of [18F]DPA714 scans.
UNASSIGNED: Comparison with standard kinetic methodology showed good-to-excellent intra-subject correlation for regional 1T1K-IDIF-K1 (ρintra = 0.93 ± 0.08), although the bias was variable depending on IDIF ability to approximate blood input functions (0.03-0.39 mL/cm3/min). 1T1K-IDIF-K1 unveiled a significant reduction of BBB permeability after inflammatory interferon-α challenge, replicating results from standard quantification. High intra-subject correlation (ρ = 0.97 ± 0.01) was reported between K1 estimates of test and retest scans.
UNASSIGNED: This evidence supports 1T1K-IDIF as blood-free alternative to assess TSPO tracers\' unidirectional blood brain clearance. K1 investigation could complement more traditional measures in TSPO studies, and even allow further mechanistic insight in the interpretation of TSPO signal.
UNASSIGNED: The method is tested on a multi-site dataset containing 177 PET studies from two TSPO tracers ([11C]PBR28 and [18F]DPA714). Firstly, 1T1K-IDIF K1 estimates were compared in terms of both bias and correlation with standard kinetic methodology. Then, the method was tested on an independent sample of [11C]PBR28 scans before and after inflammatory interferon-α challenge, and on test-retest dataset of [18F]DPA714 scans.
UNASSIGNED: Comparison with standard kinetic methodology showed good-to-excellent intra-subject correlation for regional 1T1K-IDIF-K1 (ρintra = 0.93 ± 0.08), although the bias was variable depending on IDIF ability to approximate blood input functions (0.03-0.39 mL/cm3/min). 1T1K-IDIF-K1 unveiled a significant reduction of BBB permeability after inflammatory interferon-α challenge, replicating results from standard quantification. High intra-subject correlation (ρ = 0.97 ± 0.01) was reported between K1 estimates of test and retest scans.
UNASSIGNED: This evidence supports 1T1K-IDIF as blood-free alternative to assess TSPO tracers\' unidirectional blood brain clearance. K1 investigation could complement more traditional measures in TSPO studies, and even allow further mechanistic insight in the interpretation of TSPO signal.
摘要：
■最近的证据表明，TSPOPET成像中的血-脑流入率（K1）是血脑屏障（BBB）通透性改变的有希望的生物标志物，通常与外周炎症和免疫活动增强有关。然而,标准的室建模量化受到用于提取动脉血输入功能的侵入性和费力程序的要求的限制。在这项研究中,我们通过使用单个不可逆区室模型和图像衍生输入函数(1T1K-IDIF)拟合早期时相示踪剂动力学,验证了K1估计的简化无血方法学框架.
■在包含来自两种TSPO示踪剂（[11C]PBR28和[18F]DPA714）的177项PET研究的多位点数据集上测试了该方法。首先,1T1K-IDIFK1估计值在偏倚和相关性方面与标准动力学方法进行了比较。然后，该方法在炎性干扰素-α攻击前后的[11C]PBR28扫描的独立样本上进行了测试，以及[18F]DPA714扫描的测试-重测数据集。
■与标准动力学方法的比较显示，区域1T1K-IDIF-K1（ρintra=0.93±0.08）的受试者内相关性良好，尽管偏倚取决于IDIF对血液输入功能的近似能力（0.03-0.39mL/cm3/min）。1T1K-IDIF-K1揭示了炎症干扰素-α攻击后BBB通透性的显著降低，从标准定量复制结果。在测试和重新测试扫描的K1估计之间报告了高的受试者内相关性（ρ=0.97±0.01）。
■该证据支持1T1K-IDIF作为无血替代品来评估TSPO示踪剂\'单向血脑清除。K1调查可以补充TSPO研究中更传统的措施，甚至允许在TSPO信号的解释中进一步的机械洞察。
■在包含来自两种TSPO示踪剂（[11C]PBR28和[18F]DPA714）的177项PET研究的多位点数据集上测试了该方法。首先,1T1K-IDIFK1估计值在偏倚和相关性方面与标准动力学方法进行了比较。然后，该方法在炎性干扰素-α攻击前后的[11C]PBR28扫描的独立样本上进行了测试，以及[18F]DPA714扫描的测试-重测数据集。
■与标准动力学方法的比较显示，区域1T1K-IDIF-K1（ρintra=0.93±0.08）的受试者内相关性良好，尽管偏倚取决于IDIF对血液输入功能的近似能力（0.03-0.39mL/cm3/min）。1T1K-IDIF-K1揭示了炎症干扰素-α攻击后BBB通透性的显著降低，从标准定量复制结果。在测试和重新测试扫描的K1估计之间报告了高的受试者内相关性（ρ=0.97±0.01）。
■该证据支持1T1K-IDIF作为无血替代品来评估TSPO示踪剂\'单向血脑清除。K1调查可以补充TSPO研究中更传统的措施，甚至允许在TSPO信号的解释中进一步的机械洞察。
