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Principal Investigator: Rachelle L Crescenzi
Organization: VANDERBILT UNIVERSITY MEDICAL CENTER
Fiscal Year: 2024
Award: $498,183
Funding agency: National Heart Lung and Blood Institute
The overall goal of this work is to address clinical unmet needs for patients with lipedema using advanced
magnetic resonance imaging (MRI) methods of vascular and molecular dysfunction, in sequence with portable
clinical measures of adiposity and edema. Specifically, lipedema is a disease marked by subcutaneous adipose
tissue (SAT) accumulation in the lower extremities accompanied by somatic pain and edema, poor quality of life
and significant psychological distress. Importantly, lipedema is commonly misdiagnosed as obesity, yet
symptoms are refractory to interventions for obesity leading to delayed diagnosis typically 22 years after
symptom onset. A recent call to action for lipedema highlights the need for additional lipedema research, as
fundamental gaps persist in our knowledge regarding both disease mechanisms and potential treatments. Over
the past five years and with support from the Lipedema Foundation, we have developed a whole-body imaging
strategy for patients with lipedema to provide a more complete, quantitative perspective on condition features,
as well as to refine appropriate imaging tools. We have demonstrated that lipedema is distinct from obesity using
multi-modal fat-water MRI and limb bioimpedance. We optimized sodium and fat-fraction MRI to demonstrate
significantly elevated tissue sodium and SAT volume in the lower extremities, but not upper extremities, of
females with lipedema compared to matched controls. In preliminary data we demonstrate that skin sodium can
be mobilized by a standard lymphatic therapy, complete decongestive therapy (CDT). Recent findings of
elevated arterial perfusion and inflammatory profiles in lipedema raise significant questions about how blood and
lymphatic circulation are involved in disease pathogenesis. Here we propose for the first time to apply molecular
and vascular (blood and lymphatic) imaging together with common clinical tools to test the following hypotheses:
Hypothesis (1): ultrasound can be used as a more accessible alternative to MRI for measuring subcutaneous fat
deposition and distinguishing lipedema from obesity; Hypothesis (2): tissue sodium reduces following CDT in the
lower extremities, but not in the untreated upper extremities, of patients with lipedema consistent with
improvements in symptomatology; Hypothesis (3): lower-extremity blood flow velocity is elevated, while
lymphatic flow velocity reduced, in patients with lipedema compared to matched controls. Impact: Successful
completion of this study will (1) determine modalities appropriate for lipedema screening, (2) demonstrate effects
of lymphatic stimulation on tissue sodium in lipedema, and (3) advance our understanding of the circulatory
mechanisms involved in lipedema.
Terms: <Address><Adipose tissue><Affect><Analgesia Tests><Angiogram><Angiography><Awareness><BMI><BMI percentile><BMI z-score><Blood><Blood Circulation><Blood Flow Velocity><Blood Reticuloendothelial System><Blood Vessels><Blood flow><Bloodstream><Body Tissues><Body fat><Body mass index><Characteristics><Clinical><Clinical Trials><Data><Deposit><Deposition><Diagnosis><Diet><Disease><Disorder><Dropsy><Dysfunction><Edema><Exercise><Extremities><Fats><Fatty Tissue><Fatty acid glycerol esters><Female><Foundations><Functional disorder><Future><General Radiology><Goals><Hydrogen Oxide><Hydrops><Image><Imaging Device><Imaging Instrument><Imaging Tool><Inflammatory><Investigation><Investigators><Knowledge><Leg><Limb structure><Limbs><Lipedema><Lower Extremity><Lower Limb><Lymphangiogram><Lymphangiography><Lymphatic><Lymphedema><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Manuals><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Medicine><Membrum inferius><Membrum superius><Modality><Molecular><Morbidity><Morbidity - disease rate><NMR Imaging><NMR Tomography><Na element><Nociception Tests><Non-Trunk><Nuclear Magnetic Resonance Imaging><Obesity><Pain><Pain Assessment><Pain Measurement><Pain measure><Painful><Pathogenesis><Pathologic><Patients><Perfusion><Pharmaceutical Agent><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Phenotype><Physiatric Procedure><Physical Medicine Procedure><Physical Therapeutics><Physical therapy><Physiology><Physiopathology><Physiotherapy><QOL><Quality of life><Quetelet index><Radiology><Radiology Specialty><Refractory><Reporting><Research><Research Personnel><Researchers><Sensitivity and Specificity><Skin><Sodium><Symptoms><System><Techniques><Technology><Testing><Time><Tissues><Upper Extremity><Upper Limb><Vascular Diseases><Vascular Disorder><Visualization><Water><Woman><Work><Zeugmatography><adipose><adiposity><angiographic imaging><arm><blood vessel disorder><case control><case-controlled><compare to control><comparison control><corpulence><design><designing><diagnostic screening><diets><evidence base><image-based method><imaging><imaging biomarker><imaging marker><imaging method><imaging modality><imaging-based biological marker><imaging-based biomarker><imaging-based marker><improved><inflammation marker><inflammatory marker><lymph channel><lymph edema><lymph flow><lymph vessel><lymphatic channel><lymphatic circulation><lymphatic edema><lymphatic flow><lymphatic imaging><lymphatic insufficiency><lymphatic transport><lymphatic vessel><multi-modality><multimodality><novel><obesity intervention><obesity therapy><obesity treatment><pain assay><pathophysiology><pharmaceutical><portability><psychological distress><screening><screenings><secondary lymphedema><subcutaneous><subdermal><symptomatology><tool><ultrasound><vascular><vascular dysfunction><vasculopathy><volunteer><white adipose tissue><whole body imaging><whole body scanning><yellow adipose tissue>