Linxi Shi

Dedicated breast CT: Fibroglandular volume measurements in a diagnostic population

PURPOSE To determine the mean and range of volumetric glandular fraction (VGF) of the breast in a diagnostic population using a high-resolution flat-panel cone-beam dedicated breast CT system. This information is important for Monte Carlo-based estimation of normalized glandular dose coefficients and for investigating the dependence of VGF on breast dimensions, race, and pathology. METHODS Image data from a clinical trial investigating the role of dedicated breast CT that enrolled 150 women were retrospectively analyzed to determine the VGF. The study was conducted in adherence to a protocol approved by the institutional human subjects review boards and written informed consent was obtained from all study participants. All participants in the study were assigned BI-RADS(®) 4 or 5 as per the American College of Radiology assessment categories after standard diagnostic work-up and underwent dedicated breast CT exam prior to biopsy. A Gaussian-kernel based fuzzy c-means algorithm was used to partition the breast CT images into adipose and fibroglandular tissue after segmenting the skin. Upon determination of the accuracy of the algorithm with a phantom, it was applied to 137 breast CT volumes from 136 women. VGF was determined for each breast and the mean and range were determined. Pathology results with classification as benign, malignant, and hyperplasia were available for 132 women, and were used to investigate if the distributions of VGF varied with pathology. RESULTS The algorithm was accurate to within ±1.9% in determining the volume of an irregular shaped phantom. The study mean (± inter-breast SD) for the VGF was 0.172 ± 0.142 (range: 0.012-0.719). VGF was found to be negatively correlated with age, breast dimensions (chest-wall to nipple length, pectoralis to nipple length, and effective diameter at chest-wall), and total breast volume, and positively correlated with fibroglandular volume. Based on pathology, pairwise statistical analysis (Mann-Whitney test) indicated that at the 0.05 significance level, there was no significant difference in distributions of VGF without adjustment for age between malignant and nonmalignant breasts (p = 0.41). Pairwise comparisons of the distributions of VGF in increasing order of mammographic breast density indicated all comparisons were statistically significant (p < 0.002). CONCLUSIONS This study used a different clinical prototype breast CT system than that in previous studies to image subjects from a different geographical region, and used a different algorithm for analysis of image data. The mean VGF estimated from this study is within the range reported in previous studies, indicating that the choice of 50% glandular weight fraction to represent an average breast for Monte Carlo-based estimation of normalized glandular dose coefficients in mammography needs revising. In the study, the distributions of VGF did not differ significantly with pathology.

Dedicated breast CT: radiation dose for circle-plus-line trajectory

PURPOSE Dedicated breast CT prototypes used in clinical investigations utilize single circular source trajectory and cone-beam geometry with flat-panel detectors that do not satisfy data-sufficiency conditions and could lead to cone beam artifacts. Hence, this work investigated the glandular dose characteristics of a circle-plus-line trajectory that fulfills data-sufficiency conditions for image reconstruction in dedicated breast CT. METHODS Monte Carlo-based computer simulations were performed using the GEANT4 toolkit and was validated with previously reported normalized glandular dose coefficients for one prototype breast CT system. Upon validation, Monte Carlo simulations were performed to determine the normalized glandular dose coefficients as a function of x-ray source position along the line scan. The source-to-axis of rotation distance and the source-to-detector distance were maintained constant at 65 and 100 cm, respectively, in all simulations. The ratio of the normalized glandular dose coefficient at each source position along the line scan to that for the circular scan, defined as relative normalized glandular dose coefficient (RD(g)N), was studied by varying the diameter of the breast at the chest wall, chest-wall to nipple distance, skin thickness, x-ray beam energy, and glandular fraction of the breast. RESULTS The RD(g)N metric when stated as a function of source position along the line scan, relative to the maximum length of line scan needed for data sufficiency, was found to be minimally dependent on breast diameter, chest-wall to nipple distance, skin thickness, glandular fraction, and x-ray photon energy. This observation facilitates easy estimation of the average glandular dose of the line scan. Polynomial fit equations for computing the RD(g)N and hence the average glandular dose are provided. CONCLUSIONS For a breast CT system that acquires 300-500 projections over 2π for the circular scan, the addition of a line trajectory with equal source spacing and constant x-ray beam quality (kVp and HVL) and mAs matched to the circular scan, will result in less than 0.18% increase in average glandular dose to the breast per projection along the line scan.

Scaling‐law for the energy dependence of anatomic power spectrum in dedicated breast CT

PURPOSE To determine the x-ray photon energy dependence of the anatomic power spectrum of the breast when imaged with dedicated breast computed tomography (CT). METHODS A theoretical framework for scaling the empirically determined anatomic power spectrum at one x-ray photon energy to that at any given x-ray photon energy when imaged with dedicated breast CT was developed. Theory predicted that when the anatomic power spectrum is fitted with a power curve of the form k f(-β), where k and β are fit coefficients and f is spatial frequency, the exponent β would be independent of x-ray photon energy (E), and the amplitude k scales with the square of the difference in energy-dependent linear attenuation coefficients of fibroglandular and adipose tissues. Twenty mastectomy specimens based numerical phantoms that were previously imaged with a benchtop flat-panel cone-beam CT system were converted to 3D distribution of glandular weight fraction (f(g)) and were used to verify the theoretical findings. The 3D power spectrum was computed in terms of f(g) and after converting to linear attenuation coefficients at monoenergetic x-ray photon energies of 20-80 keV in 5 keV intervals. The 1D power spectra along the axes were extracted and fitted with a power curve of the form k f(-β). The energy dependence of k and β were analyzed. RESULTS For the 20 mastectomy specimen based numerical phantoms used in the study, the exponent β was found to be in the range of 2.34-2.42, depending on the axis of measurement. Numerical simulations agreed with the theoretical predictions that for a power-law anatomic spectrum of the form k f(-β), β was independent of E and k(E) = k(1)[μ(g)(E) - μ(a)(E)](2), where k(1) is a constant, and μ(g)(E) and μ(a)(E) represent the energy-dependent linear attenuation coefficients of fibroglandular and adipose tissues, respectively. CONCLUSIONS Numerical simulations confirmed the theoretical predictions that in dedicated breast CT, the spatial frequency dependence of the anatomic power spectrum will be independent of x-ray photon energy, and the amplitude of the anatomic power spectrum scales by the square of difference in linear attenuation coefficients of fibroglandular and adipose tissues.

Dedicated Breast CT: Feasibility for Monitoring Neoadjuvant Chemotherapy Treatment.

Objectives: In this prospective pilot study, the feasibility of non-contrast dedicated breast computed tomography (bCT) to determine primary tumor volume and monitor its changes during neoadjuvant chemotherapy (NAC) treatment was investigated. Materials and Methods: Eleven women who underwent NAC were imaged with a clinical prototype dedicated bCT system at three time points – pre-, mid-, and post-treatment. The study radiologist marked the boundary of the primary tumor from which the tumor volume was quantified. An automated algorithm was developed to quantify the primary tumor volume for comparison with radiologists segmentation. The correlation between pre-treatment tumor volumes from bCT and MRI, and the correlation and concordance in tumor size between post-treatment bCT and pathology were determined. Results: Tumor volumes from automated and radiologists segmentations were correlated (Pearsons r = 0.935, P < 0.001) and were not different over all time points [P = 0.808, repeated measures analysis of variance (ANOVA)]. Pre-treatment tumor volumes from MRI and bCT were correlated (r = 0.905, P < 0.001). Tumor size from post-treatment bCT was correlated with pathology (r = 0.987, P = 0.002) for invasive ductal carcinoma larger than 5 mm and the maximum difference in tumor size was 0.57 cm. The presence of biopsy clip (3 mm) limited the ability to accurately measure tumors smaller than 5 mm. All study participants were pathologically assessed to be responders, with three subjects experiencing complete pathologic response for invasive cancer and the reminder experiencing partial response. Compared to pre-treatment tumor volume, there was a statistically significant (P = 0.0003, paired t-test) reduction in tumor volume at mid-treatment observed with bCT, with an average tumor volume reduction of 47%. Conclusions: This pilot study suggests that dedicated non-contrast bCT has the potential to serve as an expedient imaging tool for monitoring tumor volume changes during NAC. Larger studies are needed in future.

Semi-automated segmentation and classification of digital breast tomosynthesis reconstructed images

Digital breast tomosynthesis (DBT) is a limited-angle tomographic x-ray imaging technique that reduces the effect of tissue superposition observed in planar mammography. An integrated imaging platform that combines DBT with near infrared spectroscopy (NIRS) to provide co-registered anatomical and functional imaging is under development. Incorporation of anatomic priors can benefit NIRS reconstruction. In this work, we provide a segmentation and classification method to extract potential lesions, as well as adipose, fibroglandular, muscle and skin tissue in reconstructed DBT images that serve as anatomic priors during NIRS reconstruction. The method may also be adaptable for estimating tumor volume, breast glandular content, and for extracting lesion features for potential application to computer aided detection and diagnosis.

Digital breast tomosynthesis guided near infrared spectroscopy: volumetric estimates of fibroglandular fraction and breast density from tomosynthesis reconstructions

A multimodality system combining a clinical prototype digital breast tomosynthesis with its imaging geometry modified to facilitate near-infrared spectroscopic imaging has been developed. The accuracy of parameters recovered from near-infrared spectroscopy is dependent on fibroglandular tissue content. Hence, in this study, volumetric estimates of fibroglandular tissue from tomosynthesis reconstructions were determined. A kernel-based fuzzy c-means algorithm was implemented to segment tomosynthesis reconstructed slices in order to estimate fibroglandular content and to provide anatomic priors for near-infrared spectroscopy. This algorithm was used to determine volumetric breast density (VBD), defined as the ratio of fibroglandular tissue volume to the total breast volume, expressed as percentage, from 62 tomosynthesis reconstructions of 34 study participants. For a subset of study participants who subsequently underwent mammography, VBD from mammography matched for subject, breast laterality and mammographic view was quantified using commercial software and statistically analyzed to determine if it differed from tomosynthesis. Summary statistics of the VBD from all study participants were compared with prior independent studies. The fibroglandular volume from tomosynthesis and mammography were not statistically different (p=0.211, paired t-test). After accounting for the compressed breast thickness, which were different between tomosynthesis and mammography, the VBD from tomosynthesis was correlated with (r =0.809, p<0.001), did not statistically differ from (p>0.99, paired t-test), and was linearly related to, the VBD from mammography. Summary statistics of the VBD from tomosynthesis were not statistically different from prior studies using high-resolution dedicated breast computed tomography. The observation of correlation and linear association in VBD between mammography and tomosynthesis suggests that breast density associated risk measures determined for mammography are translatable to tomosynthesis. Accounting for compressed breast thickness is important when it differs between the two modalities. The fibroglandular volume from tomosynthesis reconstructions is similar to mammography indicating suitability for use during near-infrared spectroscopy.

Calibration and optimization of 3D digital breast tomosynthesis guided near infrared spectral tomography

Calibration of a three-dimensional multimodal digital breast tomosynthesis (DBT) x-ray and non-fiber based near infrared spectral tomography (NIRST) system is challenging but essential for clinical studies. Phantom imaging results yielded linear contrast recovery of total hemoglobin (HbT) concentration for cylindrical inclusions of 15 mm, 10 mm and 7 mm with a 3.5% decrease in the HbT estimate for each 1 cm increase in inclusion depth. A clinical exam of a patients breast containing both benign and malignant lesions was successfully imaged, with greater HbT was found in the malignancy relative to the benign abnormality and fibroglandular regions (11 μM vs. 9.5 μM). Tools developed improved imaging system characterization and optimization of signal quality, which will ultimately improve patient selection and subsequent clinical trial results.

X-ray scatter correction for dedicated cone beam breast CT using a forward-projection model

Purpose The quality of dedicated cone‐beam breast CT (CBBCT) imaging is fundamentally limited by x‐ray scatter contamination due to the large irradiation volume. In this paper, we propose a scatter correction method for CBBCT using a novel forward‐projection model with high correction efficacy and reliability. Method We first coarsely segment the uncorrected, first‐pass, reconstructed CBBCT images into binary‐object maps and assign the segmented fibroglandular and adipose tissue with the correct attenuation coefficients based on the mean x‐ray energy. The modified CBBCT are treated as the prior images toward scatter correction. Primary signals are first estimated via forward projection on the modified CBBCT. To avoid errors caused by inaccurate segmentation, only sparse samples of estimated primary are selected for scatter estimation. A Fourier‐Transform based algorithm, herein referred to as local filtration hereafter, is developed to efficiently estimate the global scatter distribution on the detector. The scatter‐corrected images are obtained by removing the estimated scatter distribution from measured projection data. Results We evaluate the method performance on six patients with different breast sizes and shapes representing the general population. The results show that the proposed method effectively reduces the image spatial non‐uniformity from 8.27 to 1.91% for coronal views and from 6.50 to 3.00% for sagittal views. The contrast‐to‐deviation ratio is improved by an average factor of 1.41. Comparisons on the image details reveal that the proposed scatter correction successfully preserves fine structures of fibroglandular tissues that are lost in the segmentation process. Conclusion We propose a highly practical and efficient scatter correction algorithm for CBBCT via a forward‐projection model. The method is attractive in clinical CBBCT imaging as it is readily implementable on a clinical system without modifications in current imaging protocols or system hardware.

Photon-counting hexagonal pixel array CdTe detector: Spatial resolution characteristics for image-guided interventional applications

PURPOSE High-resolution, photon-counting, energy-resolved detector with fast-framing capability can facilitate simultaneous acquisition of precontrast and postcontrast images for subtraction angiography without pixel registration artifacts and can facilitate high-resolution real-time imaging during image-guided interventions. Hence, this study was conducted to determine the spatial resolution characteristics of a hexagonal pixel array photon-counting cadmium telluride (CdTe) detector. METHODS A 650 μm thick CdTe Schottky photon-counting detector capable of concurrently acquiring up to two energy-windowed images was operated in a single energy-window mode to include photons of 10 keV or higher. The detector had hexagonal pixels with apothem of 30 μm resulting in pixel pitch of 60 and 51.96 μm along the two orthogonal directions. The detector was characterized at IEC-RQA5 spectral conditions. Linear response of the detector was determined over the air kerma rate relevant to image-guided interventional procedures ranging from 1.3 nGy/frame to 91.4 μGy/frame. Presampled modulation transfer was determined using a tungsten edge test device. The edge-spread function and the finely sampled line spread function accounted for hexagonal sampling, from which the presampled modulation transfer function (MTF) was determined. Since detectors with hexagonal pixels require resampling to square pixels for distortion-free display, the optimal square pixel size was determined by minimizing the root-mean-squared-error of the aperture functions for the square and hexagonal pixels up to the Nyquist limit. RESULTS At Nyquist frequencies of 8.33 and 9.62 cycles/mm along the apothem and orthogonal to the apothem directions, the modulation factors were 0.397 and 0.228, respectively. For the corresponding axis, the limiting resolution defined as 10% MTF occurred at 13.3 and 12 cycles/mm, respectively. Evaluation of the aperture functions yielded an optimal square pixel size of 54 μm. After resampling to 54 μm square pixels using trilinear interpolation, the presampled MTF at Nyquist frequency of 9.26 cycles/mm was 0.29 and 0.24 along the orthogonal directions and the limiting resolution (10% MTF) occurred at approximately 12 cycles/mm. Visual analysis of a bar pattern image showed the ability to resolve close to 12 line-pairs/mm and qualitative evaluation of a neurovascular nitinol-stent showed the ability to visualize its struts at clinically relevant conditions. CONCLUSIONS Hexagonal pixel array photon-counting CdTe detector provides high spatial resolution in single-photon counting mode. After resampling to optimal square pixel size for distortion-free display, the spatial resolution is preserved. The dual-energy capabilities of the detector could allow for artifact-free subtraction angiography and basis material decomposition. The proposed high-resolution photon-counting detector with energy-resolving capability can be of importance for several image-guided interventional procedures as well as for pediatric applications.

Large-angle x-ray scatter in Talbot-Lau interferometry for breast imaging.

Monte Carlo simulations were used to investigate large-angle x-ray scatter at design energy of 25 keV during small field of view (9.6 cm × 5 cm) differential phase contrast imaging of the breast using Talbot-Lau interferometry. Homogenous, adipose and fibroglandular breasts of uniform thickness ranging from 2 to 8 cm encompassing the field of view were modeled. Theoretically determined transmission efficiencies of the gratings were used to validate the Monte Carlo simulations, followed by simulations to determine the x-ray scatter reaching the detector. The recorded x-ray scatter was classified into x-ray photons that underwent at least one Compton interaction (incoherent scatter) and Rayleigh interaction alone (coherent scatter) for further analysis. Monte Carlo based estimates of transmission efficiencies showed good correspondence [Formula: see text] with theoretical estimates. Scatter-to-primary ratio increased with increasing breast thickness, ranging from 0.11 to 0.22 for 2-8 cm thick adipose breasts and from 0.12 to 0.28 for 2-8 cm thick fibroglandular breasts. The analyzer grating reduced incoherent scatter by ~18% for 2 cm thick adipose breast and by ~35% for 8 cm thick fibroglandular breast. Coherent scatter was the dominant contributor to the total scatter. Coherent-to-incoherent scatter ratio ranged from 2.2 to 3.1 for 2-8 cm thick adipose breasts and from 2.7 to 3.4 for 2-8 cm thick fibroglandular breasts.