CEST MRI quantification procedures for breast cancer treatment-related lymphedema therapy evaluation

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 B-0 and B-1 heterogeneity, and T-1 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. B-1 efficiency and T-1 were calculated in series with chemical exchange saturation transfer in bilateral axilla (B-1 amplitude = 2 mu T, Delta omega = +/- 5.5 ppm, slices = 9, spatial resolution = 1.8 x 1.47 x 5.5 mm(3)). B-1 dispersion measurements (B-1 = 1-3 mu T; increment = 0.5 mu T) 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 B-1 efficiency were calculated, including proton transfer ratio (PTR'), magnetization transfer ratio asymmetry (MTRasymmetry '), 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 B-1 dispersion experiments showed nonlinear dependence of Z-values on B-1 efficiency in the upper extremities; PTR' showed < 1% mean fractional difference between subject-specific and group-level correction procedures. PTR'(APT) significantly correlated with T-1 (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.