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 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 $\left(MT{R}_{\mathrm{asymmetry}}^{\text{'}}\right)$ , 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.