Purpose: Recent small-cohort studies have investigated using Molecular Breast Imaging (MBI) with 99mTc-sestamibi to assess tumor response following neoadjuvant chemotherapy (NAC). We present a robust automated methodology to estimate true functional uptake diameters in MBI capable of accurate size-based response assessment.
Methods: Over 1,000 unique simulated images, sampling clinically-relevant tumor diameters (d=5-25mm), tumor depths (z=1-11cm), tumor/background volumetric-concentration ratios (TBR=10,20,40), breast thicknesses (b=1-12cm), were generated using our validated Geant4-based simulation of GE Discovery NM750b MBI to design and test a diameter estimation methodology. The methodology’s accuracy/precision was additionally tested on simulated images of 78 ellipsoid tumors and phantom images of 3 spheres (d=9.89,15.43,24.82mm, TBR=10,20, z=2,3cm) within a b=9cm container.
Results: Our methodology calculates uptake diameter as 1.17*FWHM+1.64, where FWHM is automatically interpolated from a background-corrected profile through the tumor centroid (orientation user-specified) in a 3x3 median filtered single-detector image. The resulting absolute error [mean=accuracy,1σ=precision] for d≥15mm spherical tumors was [0.1mm, 0.9mm], with accuracy differing <0.6mm across tumor depths, TBRs, and breast thicknesses. Thus, we are able to accurately measure tumor uptake diameters ≥15mm and identify differences ≥3mm (corresponding to ≥20% change after intervention) with >99% confidence, independently of most common biologic (e.g., uptake distribution) and imaging (e.g., view and compression) conditions during acquisition. These values are clinically relevant, as ultrasound size analysis in 28 patients revealed that 1) pre-NAC all tumors had diameters ≥15mm and 2) mid-NAC 100% of partial responders (per RECIST1.1) and 89% of patients had changes ≥3mm. Methodology performance remained constant at [0.1mm, 0.7mm] with d≥15mm ellipsoid tumors but decreased to [1.9mm, 2.3mm] with all d=10mm simulated tumors. Performance in the phantom images was [0.0mm, 1.1mm], [2.2mm, 1.7mm], and [5.5mm, 5.0mm] for 24.82mm, 15.43mm, and 9.89mm spheres, respectively.
Conclusion: Our automated methodology accurately estimates functional uptake diameters ≥15mm. MBI-based response assessment in 70+ patients undergoing NAC is underway.
Funding Support, Disclosures, and Conflict of Interest: Research supported in part by GE Healthcare