Maccioni Lucia, Michelle Carranza Mellana, Brusaferri Ludovica, Silvestri Erica, Bertoldo Alessandra, Schubert Julia J, Nettis Maria A, Mondelli Valeria, Howes Oliver, Turkheimer Federico E, Bottlaender Michel, Bodini Benedetta, Stankoff Bruno, Loggia Marco L, Veronese Mattia
Department of Information Engineering, University of Padova, Padova, Italy.
Paris Brain Institute, ICM, CNRS, Inserm, Sorbonne Université, Paris, France.
Front Neurosci. 2024 Jul 22;18:1395769. doi: 10.3389/fnins.2024.1395769. eCollection 2024.
Recent evidence suggests the blood-to-brain influx rate ( ) in imaging as a promising biomarker of blood-brain barrier () 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 estimation by fitting the early phase tracer dynamics using a single irreversible compartment model and an image-derived input function ().
The method is tested on a multi-site dataset containing 177 studies from two tracers ([C]PBR28 and [F]DPA714). Firstly, estimates were compared in terms of both bias and correlation with standard kinetic methodology. Then, the method was tested on an independent sample of [C]PBR28 scans before and after inflammatory interferon- challenge, and on test-retest dataset of [F]DPA714 scans.
Comparison with standard kinetic methodology showed good-to-excellent intra-subject correlation for regional ( = 0.93 ± 0.08), although the bias was variable depending on ability to approximate blood input functions (0.03-0.39 mL/cm/min). unveiled a significant reduction of permeability after inflammatory interferon- challenge, replicating results from standard quantification. High intra-subject correlation ( = 0.97 ± 0.01) was reported between estimates of test and retest scans.
This evidence supports as blood-free alternative to assess tracers' unidirectional blood brain clearance. investigation could complement more traditional measures in studies, and even allow further mechanistic insight in the interpretation of signal.
最近的证据表明，成像中的血脑流入率（）是血脑屏障（）通透性改变的一个有前景的生物标志物，这种改变通常与外周炎症和大脑中增强的免疫活动相关。然而，标准的房室模型量化受到提取动脉血输入函数所需的侵入性和费力程序的限制。在本研究中，我们通过使用单一不可逆房室模型和图像衍生输入函数（）拟合早期示踪剂动力学，验证了一种用于估计的简化无血方法框架。
该方法在一个多站点数据集上进行测试，该数据集包含来自两种示踪剂（[C]PBR28和[F]DPA714）的177项研究。首先，根据偏差和与标准动力学方法的相关性对估计值进行比较。然后，该方法在炎性干扰素-挑战前后的[C]PBR28扫描独立样本以及[F]DPA714扫描的重测数据集上进行测试。
与标准动力学方法的比较显示，区域的受试者内相关性良好至优秀（=0.93±0.08），尽管偏差因近似血输入函数的能力而异（0.03-0.39 mL/cm/min）。揭示了炎性干扰素-挑战后通透性的显著降低，重复了标准量化的结果。测试和重测扫描的估计值之间报告了高受试者内相关性（=0.97±0.01）。
这一证据支持作为评估示踪剂单向血脑清除的无血替代方法。在研究中，调查可以补充更传统的测量方法，甚至可以在信号解释中提供进一步的机制性见解。
