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  • Crescenzi, R., Donahue, P. M. C., Mahany, H., Lants, S. K., & Donahue, M. J. (2020). CEST MRI quantification procedures for breast cancer treatment-related lymphedema therapy evaluation. Magnetic Resonance in Medicine, 83(5), 1760–1773. https://doi.org/10.1002/mrm.28031

    Purpose To 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. Methods Females 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). Results B1 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. Conclusion Chemical 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.

    View for free on onlinelibrary.wiley.com
  • Crescenzi, R., Donahue, P. M., Braxton, V. G., Scott, A. O., Mahany, H. B., Lants, S. K., & Donahue, M. J. (2018). 3.0 T relaxation time measurements of human lymph nodes in adults with and without  lymphatic insufficiency: Implications for magnetic resonance lymphatic imaging. NMR in Biomedicine, 31(12), e4009. https://doi.org/10.1002/nbm.4009

    The purpose of this work was to quantify 3.0 T (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). MR relaxometry was performed over bilateral axillary regions at 3.0 T 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°) method with B(1) correction (dual-T(R) method, T(R1) /T(R2)  = 30/130 ms), and T(2) maps using a multi-echo (T(E)  = 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 < 0.05). Linear regression was applied to evaluate how LN relaxometry varied with age, BMI, and clinical indicators of disease. LN substructure relaxation times (mean ± standard deviation) in healthy controls were T(1) cortex, 1435 ± 391 ms; T(1) hilum, 714 ± 123 ms; T(2) cortex, 102 ± 12 ms, and T(2) hilum, 119 ± 21 ms. T(1) of the LN cortex was significantly reduced in the contralateral axilla of BCRL patients compared with the axilla on the surgical side (p < 0.001) and compared with bilateral control values (p < 0.01). The LN cortex T(1) asymmetry discriminated cases from controls (p = 0.004) in a multiple linear regression, accounting for age and BMI. Human 3.0 T T(1) and T(2) 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.

    View for free on www.ncbi.nlm.nih.gov
  • Crescenzi, R., Marton, A., Donahue, P. M. C., Mahany, H. B., Lants, S. K., Wang, P., Beckman, J. A., Donahue, M. J., & Titze, J. (2018). Tissue Sodium Content is Elevated in the Skin and Subcutaneous Adipose Tissue in  Women with Lipedema. Obesity (Silver Spring, Md.), 26(2), 310–317. https://doi.org/10.1002/oby.22090

    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 < 0.001). Skin sodium content was directly correlated with fat-to-water volume (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.

    View for free on www.ncbi.nlm.nih.gov
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