Razavi Mohammad S, Ruscic Katarina J, Korn Elizabeth G, Marquez Marla, Houle Timothy T, Singhal Dhruv, Munn Lance L, Padera Timothy P
Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
College of Engineering, University of Nebraska-Lincoln, Nebraska, Lincoln, 68588, USA.
Npj Imaging. 2025 Jan 17;3(1):2. doi: 10.1038/s44303-024-00061-z.
Despite significant strides in lymphatic system imaging, the timely diagnosis of lymphatic disorders remains elusive. This is driven by the absence of standardized, non-invasive, reliable, quantitative methods for real-time functional analysis of lymphatic contractility with adequate spatial and temporal resolution. Here, we address this unmet need by integrating near-infrared fluorescence lymphangiography imaging with an innovative analytical workflow that combines data acquisition, signal processing, and statistical analysis to integrate traditional peak-and-valley analysis with advanced wavelet time-frequency analyses. Variance component analysis was used to evaluate the drivers of variance attributable to each experimental variable for each lymphangiography measurement type. Generalizability studies were used to assess the reliability of measured parameters and how reliability improves as the number of repeat measurements per subject increases. This allowed us to determine the minimum number of repeat measurements needed per subject for acceptable measurement reliability. This approach not only offers detailed insights into lymphatic pumping behaviors across species, sex and age, but also significantly boosts the reliability of these measurements by incorporating multiple regions of interest and evaluating the lymphatic system under various gravitational loads. For example, the reliability of the peak-and-valley analysis of human lymphatic vessels was increased 3-fold using the described approach. By addressing the critical need for improved imaging and quantification methods, our study offers a new standard approach for the imaging and analysis of lymphatic function that can improve our understanding, diagnosis, and treatment of lymphatic diseases. The results highlight the importance of comprehensive data acquisition strategies to fully capture the dynamic behavior of the lymphatic system.
尽管在淋巴系统成像方面取得了重大进展，但淋巴疾病的及时诊断仍然难以实现。这是由于缺乏标准化、非侵入性、可靠的定量方法，无法以足够的空间和时间分辨率对淋巴收缩性进行实时功能分析。在这里，我们通过将近红外荧光淋巴管造影成像与创新的分析工作流程相结合来满足这一未满足的需求，该工作流程将数据采集、信号处理和统计分析相结合，将传统的峰谷分析与先进的小波时频分析相结合。方差成分分析用于评估每种淋巴管造影测量类型中每个实验变量的方差驱动因素。泛化研究用于评估测量参数的可靠性，以及随着每个受试者重复测量次数的增加，可靠性如何提高。这使我们能够确定每个受试者为获得可接受的测量可靠性所需的最小重复测量次数。这种方法不仅能深入了解不同物种、性别和年龄的淋巴泵血行为，还通过纳入多个感兴趣区域并在各种重力负荷下评估淋巴系统，显著提高了这些测量的可靠性。例如，使用所述方法，人类淋巴管峰谷分析的可靠性提高了3倍。通过满足对改进成像和量化方法的迫切需求，我们的研究为淋巴功能成像和分析提供了一种新的标准方法，可增进我们对淋巴疾病的理解、诊断和治疗。结果突出了全面数据采集策略对于充分捕捉淋巴系统动态行为的重要性。
