| Gaps in the Field of Lymphatic Research | 2026–27 Update | 2 CLINICAL GAPS 1. Early Diagnosis One of the most frustrating aspects of caring for patients living with lymphatic disease is the relative lack of highly sensitive and specific non-invasive tests and blood biomarkers. Without these essential diagnostic tools, a delay in diagnosis is inevitable and often results in increased morbidity and mortality. Imaging: • An urgent need in novel non-invasive imaging techniques and devices. • A need for further investigation of proposed techniques: ■ Fat-weighted whole-body MRI (e.g., Lipedema–fat to water ratio is greater than obesity) ■ Water-weighted MRI of soft tissue ■ Standardized sodium 23NA-MRI ■ MR Lymphangiogram techniques ■ Non-tracer MRL sensitive to edema and vascular morphology ■ Procedure for comparative analysis of ICG imaging of lymphatic vessels ■ Other—PET? Functional MRI? There is a clinical need for development of non- invasive imaging of lymphatic physiology to aid diagnosis and understanding of all lymphatic diseases, including lymphedema and lipedema (e.g., non-invasive MRL, anatomical and sodium MRI, spectrometry MRI). Biomarkers: • Development of non-invasive assessment for genotyping of somatic mutations that are safer than biopsy (i.e., circulating free DNA). • Novel biomarkers utilizing bodily fluids (urine, cyst fluid, pleural effusions, edematous fluid, saliva, and blood). Omics: Transcriptomics, proteomics and metabolomics, and microbiome studies: • Define transcriptional machinery of lymphangiogenic pathways. • Characterizing the role of the lymphatic vasculature in immune activation (outside lymphoid organs). • Developing therapeutic lymphangiogenesis concepts. • In solid organ transplants, would competent lymphatics enhance graft health? • In breast cancer patients, can preemptive and targeted therapy safely accelerate lymphatic repair? • Single Cell RNA techniques and atlas mapping • How does the microbiome affect lymphatic health? Lymphatic research has experienced a near explosion of activity in recent years, as awareness of the importance of lymphatic mechanisms to the continuum of human biology and disease has grown. This ‘lymphatic continuum’ now easily encompasses cardiovascular disease, respiratory inflammation, obesity, autoimmune disease, and chronic transplant rejection, among many other pathologic conditions. An exponential growth in technological tools for research has made possible a similar growth in our comprehension of the molecular regulatory processes that govern the normal development and function of the lymphatic system. —Stanley Rockson, M.D., LE&RN Co-Founder, Allan and Tina Neill Professor of Lymphatic Research and Medicine at Stanford University School of Medicine ‘‘ ‘‘
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