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Background: Lipedema is a distinct adipose disorder from obesity necessitating awareness as well as different management approaches to address pain and optimize quality of life (QoL). The purpose of this proof-of-principle study is to evaluate the therapeutic potential of physical therapy interventions in women with lipedema. Methods and Results: Participants with Stage 1-2 lipedema and early Stage 0-1 lymphedema (n = 5, age = 38.4 ± 13.4 years, body mass index = 27.2 ± 4.3 kg/m2) underwent nine visits of physical therapy in 6 weeks for management of symptoms impacting functional mobility and QoL. Pre- and post-therapy, participants were scanned with 3 Tesla sodium and water magnetic resonance imaging (MRI), underwent biophysical measurements, and completed questionnaires measuring function and QoL (patient-specific functional scale, PSFS, and RAND-36). Pain was measured at each visit using the 0-10 visual analog scale (VAS). Treatment effect was calculated for all study variables. The primary symptomatology measures of pain and function revealed clinically significant post-treatment improvements and large treatment effects (Cohen's d for pain VAS = -2.5 and PSFS = 4.4). The primary sodium MRI measures, leg skin sodium, and subcutaneous adipose tissue (SAT) sodium, reduced following treatment and revealed large treatment effects (Cohen's d for skin sodium = -1.2 and SAT sodium = -0.9). Conclusions: This proof-of-principle study provides support that persons with lipedema can benefit from physical therapy to manage characteristic symptoms of leg pain and improve QoL. Objective MRI measurement of reduced tissue sodium in the skin and SAT regions indicates reduced inflammation in the treated limbs. Further research is warranted to optimize the conservative therapy approach in lipedema, a condition for which curative and disease-modifying treatments are unavailable.

Background Tissue sodium (Na+) content in patients on maintenance hemodialysis (MHD) and peritoneal dialysis (PD) was previously explored using 23Na+ magnetic resonance imaging (23NaMRI). Larger studies would provide a better understanding of Na+ stores in patients on dialysis as well as the factors influencing this Na+ accumulation. Methods In this cross-sectional study, we quantified the calf muscle and skin Na+ content in 162 subjects (10 PD, 33 MHD patients and 119 controls) using 23NaMRI. Plasma levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were measured to assess systemic inflammation. Sixty-four subjects had repeat 23NaMRI scans that were analyzed to assess the repeatability of the 23NaMRI measurements. Results Patients on MHD and PD exhibited significantly higher muscle and skin Na+ accumulation compared with controls. African American patients on dialysis exhibited greater muscle and skin Na+ content compared with non–African Americans. Multivariable analysis showed that older age was associated with both higher muscle and skin Na+ and male sex was associated with increased skin Na+ deposition. Greater ultrafiltration was associated with lower skin Na+ in patients on PD (Spearman’s ρ = −0.68, P = 0.035). Higher plasma IL-6 and hsCRP levels correlated with increased muscle and skin Na+ content in the overall study population. Patients with higher baseline tissue Na+ content exhibited greater variability in tissue Na+ stores on repeat measurements. Conclusions Our findings highlight greater muscle and skin Na+ content in dialysis patients compared with controls without kidney disease. Tissue Na+ deposition and systemic inflammation seen in dialysis patients might influence one another bidirectionally.

OBJECTIVE Lipedema is characterized by pain, fatigue, and excessive adipose tissue and sodium accumulation of the lower extremities. This case-control study aims to determine whether sodium or vascular dysfunction is present in the central nervous system. METHODS Brain magnetic resonance imaging was performed at 3 T in patients with lipedema (n = 15) and control (n = 18) participants matched for sex, age, race, and BMI. Standard anatomical imaging and intracranial angiography were applied to evaluate brain volume and vasculopathy, respectively; arterial spin labeling and sodium magnetic resonance imaging were applied to quantify cerebral blood flow (CBF) (milliliters per 100 grams of tissue/minute) and brain tissue sodium content (millimoles per liter), respectively. A Mann-Whitney U test (significance criteria P

OBJECTIVE The aim of this study is to compare tissue sodium and fat content in the upper and lower extremities of participants with lipedema versus controls using magnetic resonance imaging (MRI). METHODS MRI was performed at 3.0 T in females with lipedema (n = 15, age = 43.2 ± 10.0 years, BMI = 30.3 ± 4.4 kg/m2 ) and controls without lipedema (n = 14, age = 42.8 ± 13.2 years, BMI = 28.8 ± 4.4 kg/m2 ). Participants were assessed for pain and disease stage. Sodium MRI was performed in the forearm and calf to quantify regional tissue sodium content (TSC, mmol/L). Chemical-shift-encoded water-fat MRI was performed in identical regions for measurement of fat/water (ratio). RESULTS In the calf, skin TSC (16.3 ± 2.6 vs. 14.4 ± 2.2 mmol/L, P = 0.04), muscle TSC (20.3 ± 3.0 vs. 18.3 ± 1.7 mmol/L, P = 0.03), and fat/water (1.03 ± 0.37 vs. 0.56 ± 0.21 ratio, P

Background: Lipedema and Dercum's disease (DD) are incompletely characterized adipose tissue diseases, and objective measures of disease profiles are needed to aid in differential diagnosis. We hypothesized that fluid properties, quantified as tissue water bioimpedance in the upper and lower extremities, differ regionally between these conditions. Methods and Results: Women (cumulative n = 156) with lipedema (n = 110), DD (n = 25), or without an adipose disease matched for age and body mass index to early stage lipedema patients (i.e., controls n = 21) were enrolled. Bioimpedance spectroscopy (BIS) was applied to measure impedance values in the arms and legs, indicative of extracellular water levels. Impedance values were recorded for each limb, as well as the leg-to-arm impedance ratio. Regression models were applied to evaluate hypothesized relationships between impedance and clinical indicators of disease (significance criteria: two-sided p

PURPOSE: Breast cancer treatment-related lymphedema (BCRL) is a common co-morbidity of breast cancer therapies, yet factors that contribute to BCRL progression remain incompletely characterized. We investigated whether magnetic resonance imaging (MRI) measures of subcutaneous adipose tissue were uniquely elevated in women with BCRL. METHODS: MRI at 3.0 T of upper extremity and torso anatomy, fat and muscle tissue composition, and T2 relaxometry were applied in left and right axillae of healthy control (n = 24) and symptomatic BCRL (n = 22) participants to test the primary hypothesis that fat-to-muscle volume fraction is elevated in symptomatic BCRL relative to healthy participants, and the secondary hypothesis that fat-to-muscle volume fraction is correlated with MR relaxometry of affected tissues and BCRL stage (significance criterion: two-sided p < 0.05). RESULTS: Fat-to-muscle volume fraction in healthy participants was symmetric in the right and left sides (p = 0.51); in BCRL participants matched for age, sex, and BMI, fat-to-muscle volume fraction was elevated on the affected side (fraction = 0.732 ± 0.184) versus right and left side in controls (fraction = 0.545 ± 0.221, p < 0.001). Fat-to-muscle volume fraction directly correlated with muscle T2 (p = 0.046) and increased with increasing level of BCRL stage (p = 0.041). CONCLUSION: Adiposity quantified by MRI is elevated in the affected upper extremity of women with BCRL and may provide a surrogate marker of condition onset or severity. CLINICAL TRIAL: NCT02611557.

PURPOSE: Breast cancer treatment-related lymphedema (BCRL) evaluation is frequently performed using portable measures of limb volume and bioimpedance asymmetry. Here quantitative magnetic resonance imaging (MRI) is applied to evaluate deep and superficial tissue impairment, in both surgical and contralateral quadrants, to test the hypothesis that BCRL impairment is frequently bilateral and extends beyond regions commonly evaluated with portable external devices. METHODS: 3-Tesla MRI was applied to investigate BCRL topographical impairment. Female BCRL (n=33; age=54.1±11.2; stage=1.5±0.8) and healthy (n=33; age=49.4±11.0) participants underwent quantitative upper-limb MRI relaxometry (T(2)), bioimpedance asymmetry, arm volume asymmetry, and physical evaluation. Parametric tests were applied to evaluate study measurements (i) between BCRL and healthy participants, (ii) between surgical and contralateral limbs, and (iii) in relation to clinical indicators of disease severity. Two-sided p-value

Background: Bioimpedance spectroscopy (BIS) demonstrates proficiency in early identification of breast cancer treatment-related lymphedema (BCRL) development. Dual-tab electrodes were designed for consistent and easy electrode placement, however, single-tab electrodes positioned to mimic dual-tab placement on the body may make BIS technology more accessible in community hospitals and outpatient settings. The purpose of this study is to evaluate use of single-tab electrodes for BIS measurements and assess whether single-tab electrodes provide consistent BIS measurements in controls and patients with BCRL. Methods and Results: Upper limb BIS ratios were obtained using ImpediMed L-Dex(®) U400 in controls (n = 13; age = 23–75 years; 9 repeated measurements) using dual-tab and single-tab electrodes. BCRL patients (n = 17; Stage = 1.65 ± 0.49; number nodes removed = 16.3 ± 7.7; age = 50.9 ± 10.6 years; age range = 33–77 years) and healthy controls (n = 19) were evaluated to determine if single-tab electrodes provided discriminatory capacity for detecting BCRL. Intraclass correlation coefficients (ICC), linear mixed-effects models, Wilcoxon rank-sum tests, and linear regression with two-sided p-values

OBJECTIVE To test the hypothesis that tissue sodium and adipose content are elevated in patients with lipedema; if confirmed, this could establish precedence for tissue sodium and adipose content representing a discriminatory biomarker for lipedema. METHODS Participants with lipedema (n = 10) and control (n = 11) volunteers matched for biological sex, age, BMI, and calf circumference were scanned with 3.0-T sodium and conventional proton magnetic resonance imaging (MRI). Standardized tissue sodium content was quantified in the calf skin, subcutaneous adipose tissue (SAT), and muscle. Dixon MRI was employed to quantify tissue fat and water volumes of the calf. Nonparametric statistical tests were applied to compare regional sodium content and fat-to-water volume between groups (significance: two-sided P ≤ 0.05). RESULTS Skin (P = 0.01) and SAT (P = 0.04) sodium content were elevated in lipedema (skin: 14.9 ± 2.9 mmol/L; SAT: 11.9 ± 3.1 mmol/L) relative to control participants (skin: 11.9 ± 2.0 mmol/L; SAT: 9.4 ± 1.6 mmol/L). Relative fat-to-water volume in the calf was elevated in lipedema (1.2 ± 0.48 ratio) relative to control participants (0.63 ± 0.26 ratio; P

Purpose To exploit the long 3.0T relaxation times and low flow velocity of lymphatic fluid to develop a noninvasive 3.0T lymphangiography sequence and evaluate its relevance in patients with lymphedema. Materials and Methods A 3.0T turbo-spin-echo (TSE) pulse train with long echo time (TEeffective = 600 msec; shot-duration = 13.2 msec) and TSE-factor (TSE-factor = 90) was developed and signal evolution simulated. The method was evaluated in healthy adults (n = 11) and patients with unilateral breast cancer treatment-related lymphedema (BCRL; n = 25), with a subgroup (n = 5) of BCRL participants scanned before and after manual lymphatic drainage (MLD) therapy. Maximal lymphatic vessel cross-sectional area, signal-to-noise-ratio (SNR), and results from a five-point categorical scoring system were recorded. Nonparametric tests were applied to evaluate study parameter differences between controls and patients, as well as between affected and contralateral sides in patients (significance criteria: two-sided P < 0.05). Results Patient volunteers demonstrated larger lymphatic cross-sectional areas in the affected (arm = 12.9 ± 6.3 mm2; torso = 17.2 ± 15.6 mm2) vs. contralateral (arm = 9.4 ± 3.9 mm2; torso = 9.1 ± 4.6 mm2) side; this difference was significant both for the arm (P = 0.014) and torso (P = 0.025). Affected (arm: P = 0.010; torso: P = 0.016) but not contralateral (arm: P = 0.42; torso: P = 0.71) vessel areas were significantly elevated compared with control values. Lymphatic cross-sectional areas reduced following MLD on the affected side (pre-MLD: arm = 8.8 ± 1.8 mm2; torso = 31.4 ± 26.0 mm2; post-MLD: arm = 6.6 ± 1.8 mm2; torso = 23.1 ± 24.3 mm2). This change was significant in the torso (P = 0.036). The categorical scoring was found to be less specific for detecting lateralizing disease compared to lymphatic-vessel areas. Conclusion A 3.0T lymphangiography sequence is proposed, which allows for upper extremity lymph stasis to be detected in ∼10 minutes without exogenous contrast agents. Level of Evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1349–1360.

PURPOSE: To quantify 3.0T (i) T(1) and T(2) relaxation times of in vivo human lymph nodes (LNs), and (ii) LN relaxometry differences between healthy LNs and LNs from patients with lymphatic insufficiency secondary to breast cancer treatment-related lymphedema (BCRL). MATERIALS AND METHODS: MR relaxometry was performed over bilateral axillary regions at 3.0T in healthy female controls (105 LNs from 20 participants) and patients with BCRL (108 LNs from 20 participants). Quantitative T(1) maps were calculated using a multi-flip-angle (20, 40, 60 degrees) method with B(1)-correction (dual-TR method, TR(1)/TR(2)=30/130 ms), and T(2) maps using a multi-echo (TE=9–189 ms; 12 ms intervals) method. T(1) and T(2) were quantified in the LN cortex and hilum. A Mann-Whitney U-test was applied to compare LN relaxometry values between patients and controls (significance: two-sided p

Background: Breast cancer treatment-related lymphedema (BCRL) arises from a mechanical insufficiency following cancer therapies. Early BCRL detection and personalized intervention require an improved understanding of the physiological processes that initiate lymphatic impairment. Here, internal magnetic resonance imaging (MRI) measures of the tissue microenvironment were paired with clinical measures of tissue structure to test fundamental hypotheses regarding structural tissue and muscle changes after the commonly used therapeutic intervention of manual lymphatic drainage (MLD). Methods and Results: Measurements to identify lymphatic dysfunction in healthy volunteers (n = 29) and patients with BCRL (n = 16) consisted of (1) limb volume, tissue dielectric constant, and bioelectrical impedance (i.e., non-MRI measures); (2) qualitative 3 Tesla diffusion-weighted, T1-weighted and T2-weighted MRI; and (3) quantitative multi-echo T2 MRI of the axilla. Measurements were repeated in patients immediately...

T-1-rho (T1ρ) magnetic resonance imaging (MRI) and disc height ratio (DHR) are potential biomarkers of degenerative disk disease (DDD) related to biochemical composition and morphology of the intervertebral disk (IVD), respectively. To objectively detect DDD at an early stage, the hypothesis was tested that the average T1ρ relaxation time of the nucleus pulposus (NP) correlates with the disk height of degenerate IVDs, measured by MRI. Studies were performed on a 3-T Siemens Tim Trio clinical MRI scanner (Siemens Healthcare, Malvern, Pennsylvania, United States) on patients being treated for low back pain whose disks were categorized into (1) painful and (2) nonpainful subgroups based on provocative diskography and (3) age-matched healthy controls. Painful disks presented both low DHR and T1ρ values, nonpainful disks measured the highest DHR and extended to a higher range of T1ρ, and control disks presented a midrange DHR with the highest T1ρ values. T1ρ MRI evaluated in the NP of IVDs may be useful to establish a threshold (120 milliseconds here) above which indicates a healthy disk, and disks measuring low NP T1ρ (50 to 120 milliseconds here) would require disk height analysis to further categorize the disk. Combining T1ρ MRI and disk height analysis may hold promise in predicting painful disks without provocative diskography, and predictive models should be developed.