Quantitative measurement of mammographic density in breast-tissue explants using portable NMR: Precision and accuracy.

PURPOSE: Single-sided portable NMR (pNMR) has previously been demonstrated to be suitable for quantification of mammographic density (MD) in excised breast tissue samples. Here we investigate the precision and accuracy of pNMR measurements of MD ex vivo as compared with the gold standards. METHODS: Forty-five breast-tissue explants from 9 prophylactic mastectomy patients were measured. The relative tissue water content was taken as the MD-equivalent quantity. In each sample, the water content was measured using some combination of three pNMR techniques (apparent T2, diffusion, and T1 measurements) and two gold-standard techniques (computed microtomography [µCT] and hematoxylin and eosin [H&E] histology). Pairwise correlation plots and Bland-Altman analysis were used to quantify the degree of agreement between pNMR techniques and the gold standards. RESULTS: Relative water content measured from both apparent T2 relaxation spectra, and diffusion decays exhibited strong correlation with the H&E and µCT results. Bland-Altman analysis yielded average bias values of -0.4, -2.6, 2.6, and 2.8 water percentage points (pp) and 95% confidence intervals of 13.1, 7.5, 11.2, and 11.8 pp for the H&E - T2, µCT - T2, H&E - diffusion, and µCT - diffusion comparison pairs, respectively. T1-based measurements were found to be less reliable, with the Bland-Altman confidence intervals of 27.7 and 33.0 pp when compared with H&E and µCT, respectively. CONCLUSION: Apparent T2-based and diffusion-based pNMR measurements enable quantification of MD in breast-tissue explants with the precision of approximately 10 pp and accuracy of approximately 3 pp or better, making pNMR a promising measurement modality for radiation-free quantification of MD.

Portable NMR for quantification of breast density in vivo: Proof-of-concept measurements and comparison with quantitative MRI.

Mammographic Density (MD) is the degree of radio-opacity of the breast in an X-ray mammogram. It is determined by the Fibroglandular: Adipose tissue ratio. MD has major implications in breast cancer risk and breast cancer chemoprevention. This study aimed to investigate the feasibility of accurate, low-cost quantification of MD in vivo without ionising radiation. We used single-sided portable nuclear magnetic resonance ("Portable NMR") due to its low cost and the absence of radiation-related safety concerns. Fifteen (N = 15) healthy female volunteers were selected for the study and underwent an imaging routine consisting of 2D X-ray mammography, quantitative breast 3T MRI (Dixon and T1-based 3D compositional breast imaging), and 1D compositional depth profiling of the right breast using Portable NMR. For each participant, all the measurements were made within 3-4 h of each other. MRI-determined tissue water content was used as the MD-equivalent quantity. Portable NMR depth profiles of tissue water were compared with the equivalent depth profiles reconstructed from Dixon and T1-based MR images, which were used as the MD-equivalent reference standard. The agreement between the depth profiles acquired using Portable NMR and the reconstructed reference-standard profiles was variable but overall encouraging. The agreement was somewhat inferior to that seen in breast tissue explant measurements conducted in vitro, where quantitative micro-CT was used as the reference standard. The lower agreement in vivo can be attributed to an uncertainty in the positioning of the Portable NMR sensor on the breast surface and breast compression in Portable NMR measurements. The degree of agreement between Portable NMR and quantitative MRI is encouraging. While the results call for further development of quantitative Portable NMR, they demonstrate the in-principle feasibility of Portable NMR-based quantitative compositional imaging in vivo and show promise for the development of safe and low-cost protocols for quantification of MD suitable for clinical applications.