The development of a framework of deformable image registration and segmentation for the purpose of temporal subtraction contrast-enhanced breast CT is described. An iterative histogram-based two-means clustering method was used for the segmentation. Dedicated breast CT images were segmented into background (air), adipose, fibroglandular and skin components. Fibroglandular tissue was classified as either normal or contrast-enhanced then divided into tiers for the purpose of categorizing degrees of contrast enhancement. A variant of the Demons deformable registration algorithm, intensity difference adaptive Demons (IDAD), was developed to correct for the large deformation forces that stemmed from contrast enhancement. In this application, the accuracy of the proposed method was evaluated in both mathematically-simulated and physically-acquired phantom images. Clinical usage and accuracy of the temporal subtraction framework was demonstrated using contrast-enhanced breast CT datasets from five patients. Registration performance was quantified using normalized cross correlation (NCC), symmetric uncertainty coefficient, normalized mutual information (NMI), mean square error (MSE) and target registration error (TRE). The proposed method outperformed conventional affine and other Demons variations in contrast enhanced breast CT image registration. In simulation studies, IDAD exhibited improvement in MSE (0-16%), NCC (0-6%), NMI (0-13%) and TRE (0-34%) compared to the conventional Demons approaches, depending on the size and intensity of the enhancing lesion. As lesion size and contrast enhancement levels increased, so did the improvement. The drop in the correlation between the pre- and post-contrast images for the largest enhancement levels in phantom studies is less than 1.2% (150 Hounsfield units). Registration error, measured by TRE, shows only submillimeter mismatches between the concordant anatomical target points in all patient studies. The algorithm was implemented using a parallel processing architecture resulting in rapid execution time for the iterative segmentation and intensity-adaptive registration techniques. Characterization of contrast-enhanced lesions is improved using temporal subtraction contrast-enhanced dedicated breast CT. Adaptation of Demons registration forces as a function of contrast-enhancement levels provided a means to accurately align breast tissue in pre- and post-contrast image acquisitions, improving subtraction results. Spatial subtraction of the aligned images yields useful diagnostic information with respect to enhanced lesion morphology and uptake.

Objective

Compare conspicuity of suspicious breast lesions on contrast-enhanced dedicated breast CT (CEbCT), tomosynthesis (DBT) and digital mammography (DM).

Methods

100 females with BI-RADS 4/5 lesions underwent CEbCT and/or DBT prior to biopsy in this IRB approved, HIPAA compliant study. Two breast radiologists adjudicated lesion conspicuity scores (CS) for each modality independently. Data are shown as mean CS ±standard deviation. Two-sided t-test was used to determine significance between two modalities within each subgroup. Multiple comparisons were controlled by the false-discovery rate set to 5%.

Results

50% of studied lesions were biopsy-confirmed malignancies. Malignant masses were more conspicuous on CEbCT than on DBT or DM (9.7 ±0.5, n = 25; 6.8 ± 3.1, n = 15; 6.7 ± 3.0, n = 27; p < 0.05). Malignant calcifications were equally conspicuous on all three modalities (CEbCT 8.7 ± 0.8, n = 18; DBT 8.5 ± 0.6, n = 15; DM 8.8 ± 0.7, n = 23; p = NS). Benign masses were equally conspicuous on CEbCT (6.6 ± 4.1, n = 22); DBT (6.4 ± 3.8, n = 17); DM (5.9 ± 3.6, n = 24; p = NS). Benign calcifications CS were similar between DBT (8.5 ± 1.0, n = 17) and DM (8.8 ± 0.8, n = 26; p = NS) but less conspicuous on CEbCT (4.0 ± 2.9, n = 25, p < 0.001). 55 females were imaged with all modalities. Results paralleled the entire cohort. 69%(n = 62) of females imaged by CEbCT had dense breasts. Benign/malignant lesion CSs in dense/non-dense categories were 4.8 ± 3.7, n = 33, vs 6.0 ± 3.9, n = 14, p = 0.35; 9.2 ± 0.9, n = 29 vs. 9.4 ± 0.7, n = 14; p = 0.29, respectively.

Conclusion

Malignant masses are more conspicuous on CEbCT than DM or DBT. Malignant microcalcifications are equally conspicuous on all three modalities. Benign calcifications remain better visualized by DM and DBT than with CEbCT. We observed no differences in benign masses on all modalities. CS of both benign and malignant lesions were independent of breast density.

Advances in knowledge

CEbCT is a promising diagnostic imaging modality for suspicious breast lesions.

Purpose

Dedicated breast computed tomography (bCT) technology for the purpose of breast cancer screening has been a focus of research at UC Davis since the late 1990s. Previous studies have shown that improvement in spatial resolution characteristics of this modality correlates with greater microcalcification detection, a factor considered a potential limitation of bCT. The aim of this study is to improve spatial resolution as characterized by the modulation transfer function (MTF) via changes in the scanner hardware components and operational schema.

Methods

Four prototypes of pendant-geometry, cone-beam breast CT scanners were designed and developed spanning three generations of design evolution. To improve the system MTF in each bCT generation, modifications were made to the imaging components (x-ray tube and flat-panel detector), system geometry (source-to-isocenter and detector distance), and image acquisition parameters (technique factors, number of projections, system synchronization scheme, and gantry rotational speed).

Results

Characterization of different generations of bCT systems shows these modifications resulted in a 188% improvement of the limiting MTF properties from the first to second generation and an additional 110% from the second to third. The intrinsic resolution degradation in the azimuthal direction observed in the first generation was corrected by changing the acquisition from continuous to pulsed x-ray acquisition. Utilizing a high resolution detector in the third generation, along with modifications made in system geometry and scan protocol, resulted in a 125% improvement in limiting resolution. An additional 39% improvement was obtained by changing the detector binning mode from 2 × 2 to 1 × 1.

Conclusions

These results underscore the advancement in spatial resolution characteristics of breast CT technology. The combined use of a pulsed x-ray system, higher resolution flat-panel detector and changing the scanner geometry and image acquisition logic resulted in a significant fourfold improvement in MTF.

Purpose

Compare conspicuity of ductal carcinoma in-situ (DCIS) to benign calcifications on unenhanced (bCT), contrast-enhanced dedicated breast CT (CEbCT) and mammography (DM).

Methods and materials

The institutional review board approved this HIPAA-compliant study. 42 women with Breast Imaging Reporting and Data System 4 or 5 category micro-calcifications had breast CT before biopsy. Three subjects with invasive disease at surgery were excluded. Two breast radiologists independently compared lesion conspicuity scores (CS) for CEbCT, to bCT and DM. Enhancement was measured in Hounsfield units (HU). Mean CS ± standard deviations are shown. Receiver operating characteristic analysis (ROC) measured radiologists' discrimination performance by comparing CS to enhancement alone. Statistical measurements were made using ANOVA F-test, Wilcoxon rank-sum test and robust linear regression analyses.

Results

39 lesions (17 DCIS, 22 benign) were analyzed. DCIS (8.5 ± 0.9, n=17) was more conspicuous than benign micro-calcifications (3.6 ± 2.9, n=22; p<0.0001) on CEbCT. DCIS was equally conspicuous on CEbCT and DM (8.5 ± 0.9, 8.7 ± 0.8, n=17; p=0.85) and more conspicuous when compared to bCT (5.3 ± 2.6, n=17; p<0.001). All DCIS enhanced; mean enhancement (90HU ± 53HU, n=17) was higher compared to benign lesions (33 ± 30HU, n=22) (p<0.0001). ROC analysis of the radiologists' CS showed high discrimination performance (AUC=0.94) compared to enhancement alone (AUC=0.85) (p<0.026).

Conclusion

DCIS is more conspicuous than benign micro-calcifications on CEbCT. DCIS visualization on CEbCT is equal to mammography but improved compared to bCT. Radiologists' discrimination performance using CEBCT is significantly higher than enhancement values alone. CEbCT may have an advantage over mammography by reducing false positive examinations when calcifications are analyzed.