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, body-mass-index, and calf circumference were scanned noninvasively with 3.0T sodium and conventional proton MRI. Standardized tissue sodium content was quantified in skin, subcutaneous adipose tissue (SAT), and calf 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 ratio 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 (skin: 11.9±2.0 mmol/L; SAT: 9.4±1.6 mmol/L) participants. Relative fat volume in the calf was elevated in lipedema (1.2±0.48 ratio) relative to control (0.63±0.26 ratio, p<0.001) participants. Skin sodium content was directly correlated with fat-to-water volume ratio (Spearman’s-rho=0.54, p=0.01). Conclusions Internal metrics of tissue sodium and adipose content are elevated in patients with lipedema potentially providing objective imaging-based biomarkers for differentially diagnosing the under-recognized condition of lipedema from obesity.

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. Methods A 3.0T turbo-spin-echo (TSE) pulse train with long echo time (TEeffective=600ms; shot-duration=13.2ms) 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±6.3mm2; torso=17.2±15.6mm2) vs. contralateral (arm=9.4±3.9mm2; torso=9.1±4.6mm2) 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±1.8mm2; torso=31.4±26.0mm2; post-MLD: arm=6.6±1.8mm2; torso=23.1±24.3mm2). 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 approximately 10 minutes without exogenous contrast agents.

PurposeTo quantify chemical exchange saturation transfer contrast in upper extremities of participants with lymphedema before and after standardized lymphatic mobilization therapy using correction procedures for B0 and B1 heterogeneity, and T1 relaxation.MethodsFemales with (n = 12) and without (n = 17) breast cancer treatment‐related lymphedema (BCRL) matched for age and body mass index were scanned at 3.0T MRI. B1 efficiency and T1 were calculated in series with chemical exchange saturation transfer in bilateral axilla (B1 amplitude = 2µT, Δω = ±5.5 ppm, slices = 9, spatial resolution = 1.8 × 1.47 × 5.5 mm3). B1 dispersion measurements (B1 = 1‐3 µT; increment = 0.5 µT) were performed in controls (n = 6 arms in 3 subjects). BCRL participants were scanned pre‐ and post‐manual lymphatic drainage (MLD) therapy. Chemical exchange saturation transfer amide proton transfer (APT) and nuclear Overhauser effect (NOE) metrics corrected for B1 efficiency were calculated, including proton transfer ratio (PTR'), magnetization transfer ratio asymmetry , and apparent exchange‐dependent relaxation (AREX'). Nonparametric tests were used to evaluate relationships between metrics in BCRL participants pre‐ versus post‐MLD (two‐sided P < 0.05 required for significance).ResultsB1 dispersion experiments showed nonlinear dependence of Z‐values on B1 efficiency in the upper extremities; PTR' showed < 1% mean fractional difference between subject‐specific and group‐level correction procedures. PTR'APT significantly correlated with T1 (Spearman's rho = 0.57, P < 0.001) and body mass index (Spearman's rho = −0.37, P = 0.029) in controls and with lymphedema stage (Spearman's rho = 0.48, P = 0.017) in BCRL participants. Following MLD therapy, PTR'APT significantly increased in the affected arm of BCRL participants (pre‐ vs. post‐MLD: 0.41 ± 0.05 vs. 0.43 ± 0.03, P = 0.02), consistent with treatment effects from mobilized lymphatic fluid.ConclusionChemical exchange saturation transfer metrics, following appropriate correction procedures, respond to lymphatic mobilization therapies and may have potential for evaluating treatments in participants with secondary lymphedema.

Purpose: To quantify 3.0T (i) T1 and T2 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 T1 maps were calculated using a multi-flip-angle (20, 40, 60 degrees) method with B1-correction (dual-TR method, TR1/TR2=30/130 ms), and T2 maps using a multi-echo (TE=9–189 ms; 12 ms intervals) method. T1 and T2 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<0.05). Linear regression was applied to evaluate how LN relaxometry varied with age, BMI, and clinical indicators of disease. Results: LN substructure relaxation times (mean ± standard deviation) in healthy controls were: T1 cortex=1435±391 ms, T1 hilum=714±123 ms; T2 cortex=102±12 ms, and T2 hilum=119±21 ms. T1 of the LN cortex was significantly reduced in the contralateral axilla of BCRL patients compared to the axilla on the surgical side (p<0.001) and compared to bilateral control values (p<0.01). The LN cortex T1 asymmetry discriminated cases vs. controls (p=0.004) in a multiple linear regression, accounting for age and BMI. Conclusion: Human 3.0T T1 and T2 relaxation times in axillary LNs were quantified for the first time in vivo. Measured values are relevant for optimizing acquisition parameters in anatomical lymphatic imaging sequences, and can serve as a reference for novel functional and molecular LN imaging methods that require quantitative knowledge of LN relaxation times.