Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.
Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, USA.
Magn Reson Med. 2020 Nov;84(5):2671-2683. doi: 10.1002/mrm.28299. Epub 2020 Apr 25.
The goal of this study is to implement a noninvasive method for in vivo mapping of hepatocyte size. This method will have a broad range of clinical and preclinical applications, as pathological changes in hepatocyte sizes are relevant for the accurate diagnosis and assessments of treatment response of liver diseases.
Building on the concepts of temporal diffusion spectroscopy in MRI, a clinically feasible imaging protocol named IMPULSED (Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion) has been developed, which is able to report measurements of cell sizes noninvasively. This protocol acquires a selected set of diffusion imaging data and fits them to a model of water compartments in tissues to derive robust estimates of the cellular structures that restrict free diffusion. Here, we adapt and further develop this approach to measure hepatocyte sizes in vivo. We validated IMPULSED in livers of mice and rats and implemented it to image healthy human subjects using a clinical 3T MRI scanner.
The IMPULSED-derived mean hepatocyte sizes for rats and mice are about 15-20 µm and agree well with histological findings. Maps of mean hepatocyte size for humans can be achieved in less than 15 minutes, a clinically feasible scan time.
Our results suggest that this method has potential to overcome major limitations of liver biopsy and provide noninvasive mapping of hepatocyte sizes in clinical applications.
本研究旨在实现一种用于活体肝细胞大小无创成像的方法。该方法具有广泛的临床前和临床应用，因为肝细胞大小的病理变化与肝脏疾病的准确诊断和治疗反应评估相关。
基于 MRI 中的时扩散光谱学概念，开发了一种名为 IMPULSED（使用有限光谱编辑扩散进行微观结构参数成像）的临床可行的成像方案，该方案能够无创地报告细胞大小的测量结果。该方案采集一组选定的扩散成像数据，并将其拟合到组织中水隔室的模型中，以得出对限制自由扩散的细胞结构的稳健估计。在这里，我们对其进行了调整和进一步开发，以在活体中测量肝细胞大小。我们在大鼠和小鼠的肝脏中验证了 IMPULSED，并在使用临床 3T MRI 扫描仪的情况下将其用于对健康人类受试者进行成像。
大鼠和小鼠的 IMPULSED 衍生平均肝细胞大小约为 15-20 µm，与组织学发现吻合良好。人类的平均肝细胞大小图可以在不到 15 分钟的时间内获得，这是一个可行的临床扫描时间。
我们的结果表明，该方法有可能克服肝活检的主要限制，并在临床应用中提供对肝细胞大小的无创成像。
