A multiresolution approach with method-informed statistical analysis for quantifying lymphatic pumping dynamics

Abstract 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 spatia...

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Main Authors: Mohammad S. Razavi, Katarina J. Ruscic, Elizabeth G. Korn, Marla Marquez, Timothy T. Houle, Dhruv Singhal, Lance L. Munn, Timothy P. Padera
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:npj Imaging
Online Access:https://doi.org/10.1038/s44303-024-00061-z
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author Mohammad S. Razavi
Katarina J. Ruscic
Elizabeth G. Korn
Marla Marquez
Timothy T. Houle
Dhruv Singhal
Lance L. Munn
Timothy P. Padera
author_facet Mohammad S. Razavi
Katarina J. Ruscic
Elizabeth G. Korn
Marla Marquez
Timothy T. Houle
Dhruv Singhal
Lance L. Munn
Timothy P. Padera
author_sort Mohammad S. Razavi
collection DOAJ
description Abstract 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.
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spelling doaj-art-23a1f7fe9e394c91a787972ee129d3812025-01-19T12:35:11ZengNature Portfolionpj Imaging2948-197X2025-01-013111110.1038/s44303-024-00061-zA multiresolution approach with method-informed statistical analysis for quantifying lymphatic pumping dynamicsMohammad S. Razavi0Katarina J. Ruscic1Elizabeth G. Korn2Marla Marquez3Timothy T. Houle4Dhruv Singhal5Lance L. Munn6Timothy P. Padera7Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical SchoolEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical SchoolMassachusetts General Hospital Department of Anesthesia, Critical Care and Pain Medicine and Harvard Medical SchoolEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical SchoolMassachusetts General Hospital Department of Anesthesia, Critical Care and Pain Medicine and Harvard Medical SchoolBeth Israel Deaconess Medical Center, Division of Plastic and Reconstructive Surgery, Department of SurgeryEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical SchoolEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical SchoolAbstract 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.https://doi.org/10.1038/s44303-024-00061-z
spellingShingle Mohammad S. Razavi
Katarina J. Ruscic
Elizabeth G. Korn
Marla Marquez
Timothy T. Houle
Dhruv Singhal
Lance L. Munn
Timothy P. Padera
A multiresolution approach with method-informed statistical analysis for quantifying lymphatic pumping dynamics
npj Imaging
title A multiresolution approach with method-informed statistical analysis for quantifying lymphatic pumping dynamics
title_full A multiresolution approach with method-informed statistical analysis for quantifying lymphatic pumping dynamics
title_fullStr A multiresolution approach with method-informed statistical analysis for quantifying lymphatic pumping dynamics
title_full_unstemmed A multiresolution approach with method-informed statistical analysis for quantifying lymphatic pumping dynamics
title_short A multiresolution approach with method-informed statistical analysis for quantifying lymphatic pumping dynamics
title_sort multiresolution approach with method informed statistical analysis for quantifying lymphatic pumping dynamics
url https://doi.org/10.1038/s44303-024-00061-z
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