Nicolas D. Prionas

Contrast-enhanced Dedicated Breast CT: Initial Clinical Experience

PURPOSE To quantify contrast material enhancement of breast lesions scanned with dedicated breast computed tomography (CT) and to compare their conspicuity with that at unenhanced breast CT and mammography. MATERIALS AND METHODS Approval of the institutional review board and the Radiation Use Committee and written informed consent were obtained for this HIPAA-compliant study. Between September 2006 and April 2009, 46 women (mean age, 53.2 years; age range, 35-72 years) with Breast Imaging Reporting and Data System category 4 or 5 lesions underwent unenhanced breast CT and contrast material-enhanced breast CT before biopsy. Two radiologists independently scored lesion conspicuity for contrast-enhanced breast CT versus mammography and for contrast-enhanced breast CT versus unenhanced breast CT. Mean lesion voxel intensity was measured in Hounsfield units and normalized to adipose tissue intensity on manually segmented images obtained before and after administration of contrast material. Regression models focused on conspicuity and quantified enhancement were used to estimate the effect of pathologic diagnosis (benign vs malignant), lesion type (mass vs calcifications), breast density, and interradiologist variability. RESULTS Fifty-four lesions (25 benign, 29 malignant) in 46 subjects were analyzed. Malignant lesions were seen significantly better at contrast-enhanced breast CT than at unenhanced breast CT (P < .001) or mammography (P < .001). Malignant calcifications (malignant lesions manifested mammographically as microcalcifications only, n = 7) were seen better at contrast-enhanced breast CT than at unenhanced breast CT (P < .001) and were seen similarly at contrast-enhanced breast CT and mammography. Malignant lesions enhanced 55.9 HU +/- 4.0 (standard error), whereas benign lesions enhanced 17.6 HU +/- 6.1 (P < .001). Ductal carcinoma in situ (n = 5) enhanced a mean of 59.6 HU +/- 2.8. Receiver operating characteristic curve analysis of lesion enhancement yielded an area under the receiver operating characteristic curve of 0.876. CONCLUSION Conspicuity of malignant breast lesions, including ductal carcinoma in situ, is significantly improved at contrast-enhanced breast CT. Quantifying lesion enhancement may aid in the detection and diagnosis of breast cancer.

The characterization of breast anatomical metrics using dedicated breast CT

PURPOSE Accurate anatomical characterization of the breast is useful in breast phantom development and computer modeling of breast imaging technologies. Capitalizing on the three-dimensional capabilities of dedicated breast CT (bCT), a number of parameters which describe breast shape and fibroglandular distribution are defined. METHODS Among 219 bCT data sets, the effective diameter and length of the pendant breast as well as the breast volume were measured and characterized for each bra cup size. The volume glandular fraction (VGF) was determined as a function of patient age, BIRADS density, bra cup size, and breast diameter. The glandular fraction was examined in coronal and sagittal planes of the breast, and the radial distribution of breast glandular fraction within a coronal bCT image was examined for three breast regions. The areal glandular fraction (AGF) was estimated from two-dimensional projections of the breast (simulated by projecting bCT data sets) and was compared to the corresponding VGF. RESULTS The effective breast diameter and length increase with increasing bra cup size. The mean breast diameters (+/- standard error) of bra cup sizes A/AA, B, C, and D/DD were 11.1 +/- 0.5, 11.4 +/- 0.3, 13.0 +/- 0.2, and 13.7 +/- 0.2 cm, respectively. VGF was lower among older women and those with larger breast diameter and larger bra cup size. VGF increased as a function of the reported BIRADS density. AGF increased with VGF. Fibroglandular tissue was distributed primarily in the central portion of the breast. CONCLUSIONS Breast metrics were examined and a number of parameters were defined which may be useful for breast modeling. The reported data may provide researchers with useful information for characterizing the breast for various imaging or dosimetry tasks.

Volume assessment accuracy in computed tomography: a phantom study.

There is a broad push in the cancer imaging community to eventually replace linear tumor measurements with three‐dimensional evaluation of tumor volume. To evaluate the potential accuracy of volume measurement in tumors by CT, a gelatin phantom consisting of 55 polymethylmethacrylate (PMMA) spheres spanning diameters from 1.6 mm to 25.4 mm was fabricated and scanned using thin slice (0.625 mm) CT (GE LightSpeed 16). Nine different reconstruction combinations of field of view dimension (FOV=20,30,40 cm) and CT kernel (standard, lung, bone) were analyzed. Contiguous thin‐slice images were averaged to produce CT images with greater thicknesses (1.25, 2.50, 5.0 mm). Simple grayscale thresholding techniques were used to segment the PMMA spheres from the gelatin background, where a total of 1800 spherical volumes were evaluated across the permutations studied. The geometric simplicity of the phantom established upper limits on measurement accuracy. In general, smaller slice thickness and larger sphere diameters produced more accurate volume assessment than larger slice thickness and smaller sphere diameter. The measured volumes were smaller than the actual volumes by a common factor depending on slice thickness; overall, 0.625 mm slices produced on average 18%, 1.25 mm slices produced 22%, 2.5 mm CT slices produced 29%, and 5.0 mm slices produced 39% underestimates of volume (mm3). Field of view did not have a significant effect on volume accuracy. Reconstruction algorithm significantly affected volume accuracy (p<0.0001), with the lung kernel having the smallest error, followed by the bone and standard kernels. The results of this investigation provide guidance for CT protocol development and may guide the development of more advanced techniques to promote quantitatively accurate CT volumetric analysis of tumors. PACS number: 87.57.Q‐

Experimentally determined spectral optimization for dedicated breast computed tomography

PURPOSE The current study aimed to experimentally identify the optimal technique factors (x-ray tube potential and added filtration material/thickness) to maximize soft-tissue contrast, microcalcification contrast, and iodine contrast enhancement using cadaveric breast specimens imaged with dedicated breast computed tomography (bCT). Secondarily, the study aimed to evaluate the accuracy of phantom materials as tissue surrogates and to characterize the change in accuracy with varying bCT technique factors. METHODS A cadaveric breast specimen was acquired under appropriate approval and scanned using a prototype bCT scanner. Inserted into the specimen were cylindrical inserts of polyethylene, water, iodine contrast medium (iodixanol, 2.5 mg/ml), and calcium hydroxyapatite (100 mg/ml). Six x-ray tube potentials (50, 60, 70, 80, 90, and 100 kVp) and three different filters (0.2 mm Cu, 1.5 mm Al, and 0.2 mm Sn) were tested. For each set of technique factors, the intensity (linear attenuation coefficient) and noise were measured within six regions of interest (ROIs): Glandular tissue, adipose tissue, polyethylene, water, iodine contrast medium, and calcium hydroxyapatite. Dose-normalized contrast to noise ratio (CNRD) was measured for pairwise comparisons among the six ROIs. Regression models were used to estimate the effect of tube potential and added filtration on intensity, noise, and CNRD. RESULTS Iodine contrast enhancement was maximized using 60 kVp and 0.2 mm Cu. Microcalcification contrast and soft-tissue contrast were maximized at 60 kVp. The 0.2 mm Cu filter achieved significantly higher CNRD for iodine contrast enhancement than the other two filters (p = 0.01), but microcalcification contrast and soft-tissue contrast were similar using the copper and aluminum filters. The average percent difference in linear attenuation coefficient, across all tube potentials, for polyethylene versus adipose tissue was 1.8%, 1.7%, and 1.3% for 0.2 mm Cu, 1.5 mm Al, and 0.2 mm Sn, respectively. For water versus glandular tissue, the average percent difference was 2.7%, 3.9%, and 4.2% for the three filter types. CONCLUSIONS Contrast-enhanced bCT, using injected iodine contrast medium, may be optimized for maximum contrast of enhancing lesions at 60 kVp with 0.2 mm Cu filtration. Soft-tissue contrast and microcalcification contrast may also benefit from lower tube potentials (60 kVp). The linear attenuation coefficients of water and polyethylene slightly overestimate the values of their corresponding tissues, but the reported differences may serve as guidance for dosimetry and quality assurance using tissue equivalent phantoms.

Kilovoltage Rotational External Beam Radiotherapy on a Breast Computed Tomography Platform: A Feasibility Study

PURPOSE To demonstrate the feasibility of a dedicated breast computed tomography (bCT) platform to deliver rotational kilovoltage (kV) external beam radiotherapy (RT) for partial breast irradiation, whole breast irradiation, and dose painting. METHODS AND MATERIALS Rotational kV-external beam RT using the geometry of a prototype bCT platform was evaluated using a Monte Carlo simulator. A point source emitting 178 keV photons (approximating a 320-kVp spectrum with 4-mm copper filtration) was rotated around a 14-cm voxelized polyethylene disk (0.1 cm tall) or cylinder (9 cm tall) to simulate primary and primary plus scattered photon interactions, respectively. Simulations were also performed using voxelized bCT patient images. Beam collimation was varied in the x-y plane (1-14 cm) and in the z-direction (0.1-10 cm). Dose painting for multiple foci, line, and ring distributions was demonstrated using multiple rotations with varying beam collimation. Simulations using the scanners native hardware (120 kVp filtered by 0.2-mm copper) were validated experimentally. RESULTS As the x-y collimator was narrowed, the two-dimensional dose profiles shifted from a cupped profile with a high edge dose to an increasingly peaked central dose distribution with a sharp dose falloff. Using a 1-cm beam, the cylinder edge dose was <7% of the dose deposition at the cylinder center. Simulations using 120-kVp X-rays showed distributions similar to the experimental measurements. A homogeneous dose distribution (<2.5% dose fluctuation) with a 20% decrease in dose deposition at the cylinder edge (i.e., skin sparing) was demonstrated by weighted summation of four dose profiles using different collimation widths. Simulations using patient bCT images demonstrated the potential for treatment planning and image-guided RT. CONCLUSIONS Rotational kV-external beam RT for partial breast irradiation, dose painting, and whole breast irradiation with skin sparing is feasible on a bCT platform with the potential for high-resolution image-guided RT.

SBRT and HDR brachytherapy produce lower PSA nadirs and different PSA decay patterns than conventionally fractionated IMRT in patients with low- or intermediate-risk prostate cancer

PURPOSE To compare patterns of prostate-specific antigen (PSA) response following stereotactic body radiation therapy (SBRT), high-dose-rate (HDR) brachytherapy, and conventionally fractionated intensity modulated radiation therapy (IMRT) in patients with low- or intermediate-risk prostate cancer (CaP). METHODS AND MATERIALS Eligible study patients included 439 patients with low- or intermediate-risk prostate cancer who were treated with radiation therapy (RT) alone between 2003 and 2013, remained free of biochemical recurrence, and had at least 2 PSA values within the first year following RT. Of these, 130 were treated with SBRT, 220 with HDR brachytherapy, and 89 with IMRT. Multivariate regression analysis was used to compare PSA nadirs (nPSA), time to nPSA, and PSA bounce parameters among the 3 modalities. Indicator variable analysis was used to develop empirical models of PSA decay using the treatment modalities as indicator variables. RESULTS Significantly more patients treated with SBRT or HDR brachytherapy achieved raw nPSAs of <0.5 ng/mL compared with patients treated with IMRT (76.2% and 75.9% vs 44.9%, respectively; P < .0001 for SBRT or HDR brachytherapy vs IMRT). On multivariate analysis, nPSA was significantly lower with SBRT and HDR compared with IMRT (P < .0001). Time to nPSA and bounce parameters was not significantly different among IMRT, SBRT, and HDR. Overall, SBRT and HDR brachytherapy caused significantly larger PSA decay rates (P < .001). When truncating follow-up at 1000 days, the corresponding decay rates were larger for all 3 modalities, with no significant differences between them. CONCLUSIONS Stereotactic body radiation therapy and HDR brachytherapy produce lower nPSAs than IMRT. Within 1000 days of follow-up, the modalities produce similar rates of PSA decay; subsequently, decay continues (albeit at a slower pace) after SBRT and HDR brachytherapy but plateaus with IMRT. Because nPSA is a validated predictor of long-term outcome, these data not only suggest a distinct radiobiological effect with SBRT and HDR brachytherapy, but also predict for clinical outcomes that might equal or surpass those of IMRT.

Analysis of breast CT lesions using computer-aided diagnosis: an application of neural networks on extracted morphologic and texture features

Dedicated cone-beam breast CT (bCT) scanners have been developed as a potential alternative imaging modality to conventional X-ray mammography in breast cancer diagnosis. As with other modalities, quantitative imaging (QI) analysis can potentially be utilized as a tool to extract useful numeric information concerning diagnosed lesions from high quality 3D tomographic data sets. In this work, preliminary QI analysis was done by designing and implementing a computer-aided diagnosis (CADx) system consisting of image preprocessing, object(s) of interest (i.e. masses, microcalcifications) segmentation, structural analysis of the segmented object(s), and finally classification into benign or malignant disease. Image sets were acquired from bCT patient scans with diagnosed lesions. Iterative watershed segmentation (IWS), a hybridization of the watershed method using observer-set markers and a gradient vector flow (GVF) approach, was used as the lesion segmentation method in 3D. Eight morphologic parameters and six texture features based on gray level co-occurrence matrix (GLCM) calculations were obtained per segmented lesion and combined into multi-dimensional feature input data vectors. Artificial neural network (ANN) classifiers were used by performing cross validation and network parameter optimization to maximize area under the curve (AUC) values of the resulting receiver-operating characteristic (ROC) curves. Within these ANNs, biopsy-proven diagnoses of malignant and benign lesions were recorded as target data while the feature vectors were saved as raw input data. With the image data separated into post-contrast (n = 55) and pre-contrast sets (n = 39), a maximum AUC of 0.70 ± 0.02 and 0.80 ± 0.02 were achieved, respectively, for each data set after ANN application.

Longitudinal volume analysis from computed tomography: Reproducibility using adrenal glands as surrogate tumors

This study aims to determine the precision (reproducibility) of volume assessment in routine clinical computed tomography (CT) using adrenal glands as surrogate tumors. Seven patients at our institution were identified retrospectively as having received numerous abdominal CT scans (average 13.1, range 5 to 20). The adrenal glands were used as surrogate tumors, assuming no actual volume change. Left and right adrenal gland volumes were assessed by hand segmentation for each patient scan. Over 1240 regions of interest were outlined in total. The reproducibility, expressed as the coefficient of variation (COV), was used to characterize measurement precision. The average volumes were 5.9 and 4.5 cm3 for the left and right adrenal gland, respectively, with COVs of 17.8% and 18.9%, respectively. Using one patient’s data (20 scans) as an example surrogate for a spherical tumor, it was calculated that a 13% change in volume (4.2% change in diameter) could be determined with statistical significance at P=0.05. For this case, cursor positioning error in linear measurement of object size, by even 1 pixel on the CT image, corresponded to a significant change in volume (P=0.05). The precision of volume determination was dependent on total volume. Precision improved with increasing object size (r2 =0.367). Given the small dimensions of the adrenal glands, the ~18% COV is likely to be a high estimate compared to larger tumors. Modern CT scanners working with thinner sections (i.e. <1 mm) are likely to produce better measurement precision. The use of volume measurement to quantify changing tumor size is supported as a more precise metric than linear measurement.

TU‐E‐303A‐03: Breast CT as a Platform for Image Guided Therapies of Breast Cancer

Dedicated breast computed tomography(CT)systems were designed and fabricated in our laboratory using off‐the‐shelf components (x‐ray system,detector, and bearing) integrated into a custom designed system. For imaging, a 360 degree acquisition using cone beam geometry is used to acquire 500 projection images which are reconstructed to produce a high resolution ∼512 × 512 × 512 CT volume data set. In addition to the diagnostic imaging capabilities of the bCT scanner, the system appears to be an excellent platform for image guidance of interventional procedures such as robotic biopsy, radiofrequency ablation, and cryoablation. In addition to percutaneous procedures, the bCT system may also be an excellent platform for rotational beam radiation therapy. Computer simulations and physical phantom‐based experiments were used to define the dose distributions possible using the bCT system for radiation therapy. A number of beam energies from 120 kVp to 480 kVp were simulated. Initial results suggest that in addition to homogeneous dose distributions for treating the whole breast, that focused therapeutic approaches using collimators may be possible. The pendent position of the breast with the women prone is also thought to be a more reproducible approach to fractionated radiotherapy of the breast. Educational goals are to inform the attendee of the possible benefits of breast cancer therapies delivered from a breast CT platform Research support for this project has been provide in part by Varian Medical Systems, Fuji Medical Systems, and Hologic Corporation, in addition to the NIH

Short-Course Vs Long-Course Radiotherapy: Pros and Cons

Neoadjuvant radiotherapy is the standard of care for locally advanced rectal cancer, which can be delivered with short-course (SC) fractionation, 25 Gy in 5 fractions, or in a conventionally fractionated, long-course (LC) schedule over 25–30 fractions with concurrent chemotherapy. The merits of each approach are discussed and appropriate patient selection is recommended. Head-to-head randomized trials have shown little or no significant difference between SC and LC regimens in terms of local control or overall survival; LC results in more pathologic downstaging, but without improvement in sphincter preservation. Both treatment schedules remain viable options depending on the clinical scenario, with SC recommended for expedited treatment and LC when downstaging is needed. Future efforts aim to identify the optimal combination and timing of neoadjuvant radiotherapy and chemotherapy as well as the optimal delay until surgery to maximize response and disease outcomes. Given its shorter course, similar outcomes, and acceptable toxicity profile, SC radiation is likely to become increasingly prevalent as new neoadjuvant regimens are identified.