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

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.

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.

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.

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.