Sodium, Adipose, and Lymphatic Translational Sciences (SALT)
SALT Lab (Rachelle Crescenzi, PhD)
The SALT Lab studies Sodium, Adipose, and Lymphatic Translational (SALT) Sciences and is directed by Rachelle Crescenzi, PhD. Their research seeks to visualize the lymphatic system in health and disease using noninvasive magnetic resonance imaging (MRI). SALT MRI strategies use noninvasive sodium 23Na-MRI to measure where sodium is stored in the body, and how it gets out through the lymphatic system. They also are developing non-tracer MR lymphangiography and related vascular imaging techniques to support the study of circulatory diseases.
Dr. Crescenzi’s lab is supported by the National Heart, Lung and Blood Institute of the NIH. They are currently conducting 2 observational imaging clinical trials (1R01HL155523, 1R01HL157378) to define the complex relationship between sodium storage and lymphatic clearance in patients with lower-extremity lymphedema or lipedema who suffer from poorly understood vascular disease pathways. We welcome student trainees, researchers, and patient volunteers to message us with interest in participating in these studies by contacting our group email: saltlab@uvahealth.org.
Contributions to Science
Dr. Crescenzi and the SALT Lab have contributed several research discoveries related to the non-invasive MRI methods for measuring physiology of the lymphatic system and related metabolism of sodium and adipose tissue. Click the below topics to read more.
Overview
Dr. Crescenzi collaborated with scientists and clinicians conducting a clinical trial (NCT02611557) to image women with unilateral breast cancer treatment-related lymphedema (BCRL) before and after manual lymphatic drainage (MLD) therapy, and over two years of progression. She developed a clinically-feasible imaging protocol that incorporates (a.) non-tracer magnetic resonance (MR) lymphangiography, (b-c.) quantitative MR relaxometry, and (d.) Chemical Exchange Saturation Transfer (CEST) MRI of protein accumulation sensitive to lymphatic physiology (related publications listed respectively). This work began by measuring the fundamental parameters for generating MRI contrast, MR relaxation time parameters, in lymphatic tissue for the first time in vivo. MR relaxometry further demonstrated indicators of lymphatic fluid relocation to deeper and contralateral tissues following MLD therapy in patients with BCRL. This mechanism is complementary to reduced lymph stasis and lymphatic vessel cross-sectional area, and changes in proteinaceous fluid in deep tissues following therapy.
Impact
These research discoveries have relevance for informing personalized lymphedema risk assessment, and for guiding prophylactic therapies for lymphedema which otherwise lacks objective measures of disease. More recently, Dr. Crescenzi translated lymphatic imaging methods to lower-extremities and began a trial in 2020 (NCT05242900) to image patients with leg lymphedema using quantitative MR lymphangiography, Dixon-fat-and-water MRI, and 23Na sodium MRI.
Related Publications
- Crescenzi R*, Donahue PM*, Harley K, Desai AA, Scott AO, et al. Lymphedema Evaluation Using Noninvasive 3T MR Lymphangiography. Journal of Magnetic Resonance Imaging. 2017 Feb 28; doi: 10.1002/jmri.25670. PMID: 28245075.
- Crescenzi R, Donahue PM, Braxton VG, Scott AO, Mahany HB, Lants SK, Donahue MJ. “3.0 T relaxation time measurements of human lymph nodes in adults with and without lymphatic insufficiency: Implications for magnetic resonance lymphatic imaging.” NMR Biomed. 2018; e4009. NIHMSID: NIHMS986504. doi: 10.1002/nbm.4009.
- Donahue PM, Crescenzi R, Scott AO, Braxton V, Desai A, et al. Bilateral Changes in Deep Tissue Environment After Manual Lymphatic Drainage in Patients with Breast Cancer Treatment-Related Lymphedema. Lymphatic Research and Biology. 2017 Mar;15(1):45-56. doi: 10.1089/lrb.2016.0020. PMID: 28323572.
- Crescenzi R, Donahue PMC, Mahany H, Lants SK, Donahue MJ. CEST MRI quantification procedures for breast cancer treatment-related lymphedema therapy evaluation. Magn Reson Med. May 2020;83(5):1760-1773. doi:10.1002/mrm.28031.
Overview
Lipedema is an understudied disease for which there are no objective diagnostic or screening protocols, and it is often misdiagnosed as common obesity. Not only are objective diagnostics needed for lipedema, therapies to address the primary symptoms of lower-extremity excessive adipose tissue deposition and pain remain underdeveloped. To this end, Dr. Crescenzi demonstrated the relevance of quantitative multinuclear magnetic resonance imaging (MRI) of sodium and adipose tissue deposition to differentiating patients with lipedema from obesity. (a.) Sodium MRI quantified high endogenous tissue sodium content in legs of patients with lipedema compared to females without lipedema with similar body-mass-index (BMI). (b.) High tissue sodium was observed in an independent cohort of patients with lipedema, and is specific to the legs and not the arms, and (c.) leg tissue sodium and pain reduce following conservative physical therapy in patients with early stage lipedema. (d.) Neuroimaging of cerebrovascular perfusion revealed potential vascular mechanisms of lipedema, and current ongoing research in the lab focuses on a mechanistic understanding of tissue sodium and adipose pathology in lipedema.
Impact
These research discoveries have relevance for development of a clinically-feasible radiologic screening protocol to distinguish lipedema from obesity, employing physical therapy earlier in patients with lipedema for reducing tissue sodium and pain, as well as understanding the extent of blood and/or lymphatic microvascular involvement in lipedema.
Related Publications
- Crescenzi R, Marton A, Donahue PM, Mahany HB, Lants SK, Wang P, Beckman JA, Donahue MJ, Titze J. Tissue Sodium Content is Elevated in the Skin and Subcutaneous Adipose Tissue in Women with Lipedema. Obesity. 2018 Feb;26(2):310-317. doi: 10.1002/oby.22090. PMID: 29280322.
- Crescenzi R, Donahue PMC, Petersen KJ, et al. Upper and Lower Extremity Measurement of Tissue Sodium and Fat Content in Patients with Lipedema. Obesity (Silver Spring). May 2020;28(5):907-915. doi:10.1002/oby.22778.
- Donahue PMC, Crescenzi R, Petersen KJ, Garza M, Patel N, Lee C, Chen SC, Donahue MJ. Physical Therapy in Women with Early Stage Lipedema: Potential Impact of Multimodal Manual Therapy, Compression, Exercise, and Education Interventions. Lymphat Res Biol. 2021 Nov 8;. doi: 10.1089/lrb.2021.0039. [Epub ahead of print] PubMed PMID: 34748408.
- Petersen KJ, Garza M, Donahue PMC, Harkins KD, Marton A, Titze J, Donahue MJ, Crescenzi R. Neuroimaging of cerebral blood flow and sodium in women with lipedema. Obesity (Silver Spring). 2020;28(7):1292-1300. doi:10.1002/oby.22837
Overview
Sodium and lymphatic physiology are implicated in a growing number of cardiovascular, renal, peripheral vascular, and cerebrovascular diseases. To develop biomarkers of disease and potential treatment mechanisms, Dr. Crescenzi develops multi-nuclear MRI technologies in the UVA Radiology Imaging Core. Multi-nuclear MRI technologies support investigator-initiated studies across the University of Virginia.
Impact
Developing MRI tools to explore lymphatic clearance of tissue sodium enable future studies to develop (in preclinical models) and test (in clinical populations) novel diagnostic and treatment strategies for mitigating poor salt handling in disease.
Related Publications
- Ertuglu L, Sahinoz M, Alsouqi A, Deger SM, Guide A, Stewart TG, Pike M, Robinson-Cohen C, Akwo E, Pridmore M, Crescenzi R, Madhur MS, Harrison DG, Luft FC, Titze J, Ikizler TA. High tissue-sodium associates with systemic inflammation and insulin resistance in obese individuals. Nutrition, Metabolism and Cardiovascular Diseases. https://doi.org/10.1016/j.numecd.2023.03.024.
- Alsouqi A, Deger SM, Sahinoz M, Mambungu C, Clagett AR, Bian A, Guide A, Stewart TG, Pike M, Robinson‐Cohen C, Crescenzi R, Madhur MS, Harrison DG, Ikizler TA. Tissue Sodium in Patients with Early Stage Hypertension: A randomized controlled trial. Amer. Heart Association. 2022, 11(8), e022723, https://doi.org/10.1161/JAHA.121.022723
- Liu J, Shelton EL, Crescenzi R, Colvin DC, Kirabo A, Zhong J, Delpire EJ, Yang HC, Kon V. Kidney Injury Causes Accumulation of Renal Sodium That Modulates Renal Lymphatic Dynamics. Int J Mol Sci. 2022 Jan 27;23(3). doi: 10.3390/ijms23031428. PubMed PMID: 35163352; PubMed Central PMCID: PMC8836121.
- Sahinoz M, Tintara S, Deger SM, Alsouqi A, Crescenzi R, Mambungu C, Vincz A, Mason O, Prigmore HL, Guide A, Stewart TG, Harrison D, Luft FC, Titze J, Ikizler T. A. Tissue sodium stores in peritoneal dialysis and hemodialysis patients determined by 23-sodium magnetic resonance imaging. Nephrol Dial Transplant, 2021 Jul;36(7):1307-17. doi:10.1093/ndt/gfaa350.
Contact
We welcome student trainees, researchers, and patient volunteers to message us with interest in participating in these studies by contacting our group email: saltlab@uvahealth.org.