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.

Recent studies have provided evidence that cortical brain ischemia may influence choroid plexus function, and such communication may be mediated by either traditional CSF circulation pathways and/or a possible glymphatic pathway. Here we investigated the hypothesis that improvements in arterial health following neoangiogenesis alter (i) intracranial CSF volume and (ii) choroid plexus perfusion in humans. CSF and tissue volume measurements were obtained from T1-weighted MRI, and cortical and choroid plexus perfusion were obtained from perfusion-weighted arterial spin labeling MRI, in patients with non-atherosclerotic intracranial stenosis (e.g. Moyamoya). Measurements were repeated after indirect surgical revascularization, which elicits cortical neoangiogenesis near the revascularization site ( n = 23; age = 41.8 ± 13.4 years), or in a cohort of participants at two time points without interval surgeries ( n = 10; age = 41.7 ± 10.7 years). Regression analyses were used to evaluate dependence of perfusion and volume on state (time 1 vs. 2). Post-surgery, neither CSF nor tissue volumes changed significantly. In surgical patients, cortical perfusion increased and choroid plexus perfusion decreased after surgery; in participants without surgeries, cortical perfusion reduced and choroid plexus perfusion increased between time points. Findings are discussed in the context of a homeostatic mechanism, whereby arterial health, paravascular flow, and/or ischemia can affect choroid plexus perfusion.

2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;48:1120-1128.

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.