Quantitation of tumor uptake with molecular breast imaging

Purpose: We developed scatter and attenuation-correction techniques for quantifying images obtained with Molecular Breast Imaging (MBI) systems. Methods: To investigate scatter correction, energy spectra of a ^99mTc point source were acquired with 0-7-cm-thick acrylic to simulate scatter between the detector heads. System-specific scatter correction factor, k, was calculated as a function of thickness using a dual energy window technique. To investigate attenuation correction, a 7-cm-thick rectangular phantom containing ^99mTc-water simulating breast tissue and fillable spheres simulating tumors was imaged. Six spheres 10-27 mm in diameter were imaged with sphere-to-background ratios (SBRs) of 3.5, 2.6, and 1.7 and located at depths of 0.5, 1.5, and 2.5 cm from the center of the water bath for 54 unique tumor scenarios (3 SBRs × 6 sphere sizes × 3 depths). Phantom images were also acquired in-air under scatter- and attenuation-free conditions, which provided ground truth counts. To estimate true counts, T, from each tumor, the geometric mean (GM) of the counts within a prescribed region of interest (ROI) from the two projection images was calculated as T=C1C2eμtF, where C are counts within the square ROI circumscribing each sphere on detectors 1 and 2, μ is the linear attenuation coefficient of water, t is detector separation, and the factor F accounts for background activity. Four unique F definitions - standard GM, background-subtraction GM, MIRD Primer 16 GM, and a novel "volumetric GM" - were investigated. Error in T was calculated as the percentage difference with respect to in-air. Quantitative accuracy using the different GM definitions was calculated as a function of SBR, depth, and sphere size. Sensitivity of quantitative accuracy to ROI size was investigated. We developed an MBI simulation to investigate the robustness of our corrections for various ellipsoidal tumor shapes and detector separations. Results: Scatter correction factor k varied slightly (0.80-0.95) over a compressed breast thickness range of 6-9 cm. Corrected energy spectra recovered general characteristics of scatter-free spectra. Quantitatively, photopeak counts were recovered to <10% compared to in-air conditions after scatter correction. After GM attenuation correction, mean errors (95% confidence interval, CI) for all 54 imaging scenarios were 149% (-154% to +455%), -14.0% (-38.4% to +10.4%), 16.8% (-14.7% to +48.2%), and 2.0% (-14.3 to +18.3%) for the standard GM, background-subtraction GM, MIRD 16 GM, and volumetric GM, respectively. Volumetric GM was less sensitive to SBR and sphere size, while all GM methods were insensitive to sphere depth. Simulation results showed that Volumetric GM method produced a mean error within 5% over all compressed breast thicknesses (3-14 cm), and that the use of an estimated radius for nonspherical tumors increases the 95% CI to at most ±23%, compared with ±16% for spherical tumors. Conclusion: Using DEW scatter- and our Volumetric GM attenuation-correction methodology yielded accurate estimates of tumor counts in MBI over various tumor sizes, shapes, depths, background uptake, and compressed breast thicknesses. Accurate tumor uptake can be converted to radiotracer uptake concentration, allowing three patient-specific metrics to be calculated for quantifying absolute uptake and relative uptake change for assessment of treatment response.