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Certain trace elements are vital to the body and elemental imbalances can be indicators of certain diseases including cancer and liver diseases. Neutron Stimulated Emission Computed Tomography (NSECT) is being developed as spectroscopic imaging technique to non-invasively and non-destructively measure and image elemental concentrations within the body. A region of interest is illuminated via a high-energy beam of neutrons that scatter inelastically with elemental nuclei within the body. The excited nuclei then relax by emitting characteristic gamma rays. Acquiring the gamma spectrum in a tomographic manner allows not only the identification of elements, but also the formation of images representing spatial distributions of specific elements. We are developing a high-energy position-sensitive gamma camera that allows full illumination of the entire region of interest. Because current scintillation crystal based position-sensitive gamma cameras operate in too low of an energy range, we are adapting high-energy gamma imaging techniques used in space-based imaging. A High Purity Germanium (HPGe) detector provides high-resolution energy spectra while a rotating modulation collimator (RMC) placed in front of the detector modulates the incoming signal to provide spatial information. The purpose of this manuscript is to describe the near-field RMC geometry, which varies greatly from the infinite-focus space-based applications, and how it modulates the incident gamma flux. A simple geometric model is presented and then used to reconstruct two-dimensional planar images of both simulated point sources and extended sources.

This paper describes the implementation of neutron-stimulated emission computed tomography (NSECT) for non-invasive imaging and reconstruction of a multi-element phantom. The experimental apparatus and process for acquisition of multi-spectral projection data are described along with the reconstruction algorithm and images of the two elements in the phantom. Independent tomographic reconstruction of each element of the multi-element phantom was performed successfully. This reconstruction result is the first of its kind and provides encouraging proof of concept for proposed subsequent spectroscopic tomography of biological samples using NSECT.

Dedicated breast computed tomography (CT) imaging possesses the potential for improved lesion detection over conventional mammograms, especially for women with dense breasts. The breast CT images are acquired with a glandular dose comparable to that of standard two-view mammography for a single breast. Due to dose constraints, the reconstructed volume has a non-negligible quantum noise when thin section CT slices are visualized. It is thus desirable to reduce noise in the reconstructed breast volume without loss of spatial resolution. In this study, partial diffusion equation (PDE) based denoising techniques specifically for breast CT were applied at different steps along the reconstruction process and it was found that denoising performed better when applied to the projection data rather than reconstructed data. Simulation results from the contrast detail phantom show that the PDE technique outperforms Wiener denoising as well as adaptive trimmed mean filter. The PDE technique increases its performance advantage relative to Wiener techniques when the photon fluence is reduced. With the PDE technique, the sensitivity for lesion detection using the contrast detail phantom drops by less than 7% when the dose is cut down to 40% of the two-view mammography. For subjective evaluation, the PDE technique was applied to two human subject breast data sets acquired on a prototype breast CT system. The denoised images had appealing visual characteristics with much lower noise levels and improved tissue textures while maintaining sharpness of the original reconstructed volume.

Neutron stimulated emission computed tomography (NSECT) is being developed to noninvasively determine concentrations of trace elements in biological tissue. Studies have shown prominent differences in the trace element concentration of normal and malignant breast tissue. NSECT has the potential to detect these differences and diagnose malignancy with high accuracy with dose comparable to that of a single mammogram. In this study, NSECT imaging was simulated for normal and malignant human breast tissue samples to determine the significance of individual elements in determining malignancy. The normal and malignant models were designed with different elemental compositions, and each was scanned spectroscopically using a simulated 2.5 MeV neutron beam. The number of incident neutrons was varied from 0.5 million to 10 million neutrons. The resulting gamma spectra were evaluated through receiver operating characteristic (ROC) analysis to determine which trace elements were prominent enough to be considered markers for breast cancer detection. Four elemental isotopes (133Cs, 81Br, 79Br, and 87Rb) at five energy levels were shown to be promising features for breast cancer detection with an area under the ROC curve (A(Z)) above 0.85. One of these elements--87Rb at 1338 keV--achieved perfect classification at 10 million incident neutrons and could be detected with as low as 3 million incident neutrons. Patient dose was calculated for each gamma spectrum obtained and was found to range from between 0.05 and 0.112 mSv depending on the number of neutrons. This simulation demonstrates that NSECT has the potential to noninvasively detect breast cancer through five prominent trace element energy levels, at dose levels comparable to other breast cancer screening techniques.

Previously, we developed a simple Laguerre-Gauss (LG) channelized Hotelling observer (CHO) for incorporation into our mass computer-aided detection (CAD) system. This LG-CHO was trained using initial detection suspicious region data and was empirically optimized for free parameters. For the study presented in this paper, we wish to create a more optimal mass detection observer based on a novel combination of LG channels. A large set of LG channels with differing free parameters was created. Each of these channels was applied to the suspicious regions, and an output test statistic was determined. A stepwise feature selection algorithm was used to determine which LG channels would combine best to detect masses. These channels were combined using a HO to create a single template for the mass CAD system. Results from free-response receiver operating characteristic curves demonstrated that the incorporation of the novel LG-CHO into the CAD system slightly improved performance in high-sensitivity regions.

The purpose of this study was to evaluate image similarity measures employed in an information-theoretic computer-assisted detection (IT-CAD) scheme. The scheme was developed for content-based retrieval and detection of masses in screening mammograms. The study is aimed toward an interactive clinical paradigm where physicians query the proposed IT-CAD scheme on mammographic locations that are either visually suspicious or indicated as suspicious by other cuing CAD systems. The IT-CAD scheme provides an evidence-based, second opinion for query mammographic locations using a knowledge database of mass and normal cases. In this study, eight entropy-based similarity measures were compared with respect to retrieval precision and detection accuracy using a database of 1820 mammographic regions of interest. The IT-CAD scheme was then validated on a separate database for false positive reduction of progressively more challenging visual cues generated by an existing, in-house mass detection system. The study showed that the image similarity measures fall into one of two categories; one category is better suited to the retrieval of semantically similar cases while the second is more effective with knowledge-based decisions regarding the presence of a true mass in the query location. In addition, the IT-CAD scheme yielded a substantial reduction in false-positive detections while maintaining high detection rate for malignant masses.

In this article, we present a characterization of the effect of difference of Gaussians (DoG) filters in the detection of mammographic regions. DoG filters have been used previously in mammographic mass computer-aided detection (CAD) systems. As DoG filters are constructed from the subtraction of two bivariate Gaussian distributions, they require the specification of three parameters: the size of the filter template and the standard deviations of the constituent Gaussians. The influence of these three parameters in the detection of mammographic masses has not been characterized. In this work, we aim to determine how the parameters affect (1) the physical descriptors of the detected regions, (2) the true and false positive rates, and (3) the classification performance of the individual descriptors. To this end, 30 DoG filters are created from the combination of three template sizes and four values for each of the Gaussians' standard deviations. The filters are used to detect regions in a study database of 181 craniocaudal-view mammograms extracted from the Digital Database for Screening Mammography. To describe the physical characteristics of the identified regions, morphological and textural features are extracted from each of the detected regions. Differences in the mean values of the features caused by altering the DoG parameters are examined through statistical and empirical comparisons. The parameters' effects on the true and false positive rate are determined by examining the mean malignant sensitivities and false positives per image (FPpI). Finally, the effect on the classification performance is described by examining the variation in FPpI at the point where 81% of the malignant masses in the study database are detected. Overall, the findings of the study indicate that increasing the standard deviations of the Gaussians used to construct a DoG filter results in a dramatic decrease in the number of regions identified at the expense of missing a small number of malignancies. The sharp reduction in the number of identified regions allowed the identification of textural differences between large and small mammographic regions. We find that the classification performances of the features that achieve the lowest average FPpI are influenced by all three of the parameters.

As more diagnostic testing options become available to physicians, it becomes more difficult to combine various types of medical information together in order to optimize the overall diagnosis. To improve diagnostic performance, here we introduce an approach to optimize a decision-fusion technique to combine heterogeneous information, such as from different modalities, feature categories, or institutions. For classifier comparison we used two performance metrics: The receiving operator characteristic (ROC) area under the curve [area under the ROC curve (AUC)] and the normalized partial area under the curve (pAUC). This study used four classifiers: Linear discriminant analysis (LDA), artificial neural network (ANN), and two variants of our decision-fusion technique, AUC-optimized (DF-A) and pAUC-optimized (DF-P) decision fusion. We applied each of these classifiers with 100-fold cross-validation to two heterogeneous breast cancer data sets: One of mass lesion features and a much more challenging one of microcalcification lesion features. For the calcification data set, DF-A outperformed the other classifiers in terms of AUC (p < 0.02) and achieved AUC=0.85 +/- 0.01. The DF-P surpassed the other classifiers in terms of pAUC (p < 0.01) and reached pAUC=0.38 +/- 0.02. For the mass data set, DF-A outperformed both the ANN and the LDA (p < 0.04) and achieved AUC=0.94 +/- 0.01. Although for this data set there were no statistically significant differences among the classifiers' pAUC values (pAUC=0.57 +/- 0.07 to 0.67 +/- 0.05, p > 0.10), the DF-P did significantly improve specificity versus the LDA at both 98% and 100% sensitivity (p < 0.04). In conclusion, decision fusion directly optimized clinically significant performance measures, such as AUC and pAUC, and sometimes outperformed two well-known machine-learning techniques when applied to two different breast cancer data sets.

Neutron stimulated emission computed tomography (NSECT) is presented as a new technique for in vivo tomographic spectroscopic imaging. A full implementation of NSECT is intended to provide an elemental spectrum of the body or part of the body being interrogated at each voxel of a three-dimensional computed tomographic image. An external neutron beam illuminates the sample and some of these neutrons scatter inelastically, producing characteristic gamma emission from the scattering nuclei. These characteristic gamma rays are acquired by a gamma spectrometer and the emitting nucleus is identified by the emitted gamma energy. The neutron beam is scanned over the body in a geometry that allows for tomographic reconstruction. Tomographic images of each element in the spectrum can be reconstructed to represent the spatial distribution of elements within the sample. Here we offer proof of concept for the NSECT method, present the first single projection spectra acquired from multi-element phantoms, and discuss potential biomedical applications.

Architectural distortion (AD) is a sign of malignancy often missed during mammographic interpretation. The purpose of this study was to explore the application of fractal analysis to the investigation of AD in screening mammograms. The study was performed using mammograms from the Digital Database for Screening Mammography (DDSM). The fractal dimension (FD) of mammographic regions of interest (ROIs) was calculated using the circular average power spectrum technique. Initially, the variability of the FD estimates depending on ROI location, mammographic view and breast side was studied on normal mammograms. Then, the estimated FD was evaluated using receiver operating characteristics (ROC) analysis to determine if it can discriminate ROIs depicting AD from those depicting normal breast parenchyma. The effect of several factors such as ROI size, image subsampling and breast density was studied in detail. Overall, the average FD of the normal ROIs was statistically significantly higher than that of the ROIs with AD. This result was consistent across all factors studied. For the studied set of implementation parameters, the best ROC performance achieved was 0.89 +/- 0.02. The generalizability of these conclusions across different digitizers was also demonstrated.

Purpose: To evaluate the scatter, dose, and effective detective quantum efficiency (DQE) performance of a slot-scan digital chest radiography system compared with that of a full-field digital radiography system., Materials and Methods: Scatter fraction of a slot-scan system was measured for an anthropomorphic and a geometric phantom by using a posterior beam-stop technique at 117 and 140 kVp. Measurements were repeated with a full-field digital radiography system with and without a 13:1 antiscatter grid at 120 and 140 kVp. For both systems, the effective dose was measured on posteroanterior and lateral views for standard clinical techniques by using dosimeters embedded in a female phantom. The effective DQEs of the two systems were assessed by taking into account the scatter performance and the DQE of each system. The statistical significance of all the comparative differences was ascertained by means of t test analysis., Results: The slot-scan system and the full-field system with grid yielded scatter fractions of 0.13-0.14 and 0.42-0.48 in the lungs and 0.30-0.43 and 0.69-0.78 in the mediastinum, respectively. The sum of the effective doses for posteroanterior and lateral views for the slot-scan system (0.057 mSv +/- 0.003 [+/- standard deviation]) was 34% lower than that for the full-field system (0.086 mSv +/- 0.001, P < .05) at their respective clinical peak voltages (140 and 120 kVp, respectively). The effective DQE of the slot-scan system was equivalent to that of the full-field system in the lung region but was 37% higher in the dense regions (P < .05)., Conclusion: The slot-scan design leads to marked scatter reduction compared with the more conventional full-field geometries with a grid. The improved scatter performance of a slot-scan geometry can effectively compensate for low DQE and lead to improved image quality., (Copyright RSNA, 2005.)

Rationale and Objectives: The purpose of this study was to validate the performance of a previously developed computer aid for breast mass classification for mammography on a new, independent database of cases not used for algorithm development., Materials and Methods: A computer aid (classifier) based on the likelihood ratio (LRb) was previously developed on a database of 670 mass cases. The 670 cases (245 malignant) from one medical institution were described using 16 features from the American College of Radiology Breast Imaging-Reporting and Data System lexicon and patient history findings. A separate database of 151 (43 malignant) validation cases were collected that were previously unseen by the classifier. These new validation cases were evaluated by the classifier without retraining. Performance evaluation methods included Receiver Operating Characteristic (ROC), round-robin, and leave-one-out bootstrap sampling., Results: The performance of the classifier on the training data yielded an average ROC area of 0.90 +/- 0.02 and partial ROC area (0.90AUC) of 0.60 +/- 0.06. The exact nonparametric performance on the validation set of 151 cases yielded a ROC area of 0.88 and 0.90AUC of 0.57. Using a 100% sensitivity cutoff threshold established on the training data (100% negative predictive value), the classifier correctly identified 100% of the malignant masses in the validation test set, while potentially obviating 26% of the biopsies performed on benign masses., Conclusion: The LRb classifier performed consistently on new data that was not used for classifier development. The LRb classifier shows promise as a potential aid in reducing the number of biopsies performed on benign masses.

Purpose: To evaluate the variability of true-positive and false-positive cues by using a commercially available computer-aided detection (CAD) system for analysis of 50 malignancies in a screening population., Materials and Methods: Fifty breast cancers detected at screening were analyzed by using a commercially available CAD system. Mean patient age was 62.2 years. Each set of mammograms (craniocaudal and mediolateral oblique views) was digitized and analyzed by the CAD system 10 times. One radiologist compared CAD output with the location of the malignancy at mammography and determined whether each lesion was marked accurately in one mammographic view, both views, or neither. Sensitivity and reproducibility of the CAD system were determined for both case- and image-based analysis., Results: Overall sensitivity of the CAD system when at least one of the two mammographic views was marked correctly (case-base sensitivity) was 82.4%. Sensitivity when each mammographic view was considered separately (image-based sensitivity) was 61.1%. For case-based analysis, variability in true-positive CAD cues was demonstrated for 14 of 50 (28%) cases. For image-based analysis, inconsistency in CAD output was observed in 33 of 100 (33%) mammographic views that contained malignancies detected at screening. However, the CAD system consistently detected 40-43 of the 50 breast cancers in each of the 10 CAD runs. Variability for false-positive marks was significantly greater than that for true-positive marks., Conclusion: Inconsistency was demonstrated for CAD analysis of breast cancers detected at screening. However, the CAD system was reasonably consistent in the overall number of cancers identified from run to run. Greater variability of the CAD system was also demonstrated for false-positive marks, as compared with true-positive marks.

While mammography is a highly sensitive method for detecting breast tumours, its ability to differentiate between malignant and benign lesions is low, which may result in as many as 70% of unnecessary biopsies. The purpose of this study was to develop a highly specific computer-aided diagnosis algorithm to improve classification of mammographic masses. A classifier based on the likelihood ratio was developed to accommodate cases with missing data. Data for development included 671 biopsy cases (245 malignant), with biopsy-proved outcome. Sixteen features based on the BI-RADS lexicon and patient history had been recorded for the cases, with 1.3 +/- 1.1 missing feature values per case. Classifier evaluation methods included receiver operating characteristic and leave-one-out bootstrap sampling. The classifier achieved 32% specificity at 100% sensitivity on the 671 cases with 16 features that had missing values. Utilizing just the seven features present for all cases resulted in decreased performance at 100% sensitivity with average 19% specificity. No cases and no feature data were omitted during classifier development, showing that it is more beneficial to utilize cases with missing values than to discard incomplete cases that cannot be handled by many algorithms. Classification of mammographic masses was commendable at high sensitivity levels, indicating that benign cases could be potentially spared from biopsy.

Our purpose in this study was to evaluate the fundamental image quality characteristics of a new slot-scan digital chest radiography system (ThoraScan, Delft Imaging Systems/Nucletron, Veenendaal, The Netherlands). The linearity of the system was measured over a wide exposure range at 90, 117, and 140 kVp with added Al filtration. System uniformity and reproducibility were established with an analysis of images from repeated exposures. The modulation transfer function (MTF) was evaluated using an established edge method. The noise power spectrum (NPS) and the detective quantum efficiency (DQE) of the system were evaluated at the three kilo-voltages over a range of exposures. Scatter fraction (SF) measurements were made using a posterior beam stop method and a geometrical chest phantom. The system demonstrated excellent linearity, but some structured nonuniformities. The 0.1 MTF values occurred between 3.3-3.5 mm(-1). The DQE(0.15) and DQE(2.5) were 0.21 and 0.07 at 90 kVp, 0.18 and 0.05 at 117 kVp, and 0.16 and 0.03 at 140 kVp, respectively. The system exhibited remarkably lower SFs compared to conventional full-field systems with anti-scatter grid, measuring 0.13 in the lungs and 0.43 in the mediastinum. The findings indicated that the slot-scan design provides marked scatter reduction leading to high effective DQE (DQEeff) of the system and reduced patient dose required to achieve high image quality.

In previous research, we have developed a computer-aided detection (CAD) system designed to detect masses in mammograms. The previous version of our system employed a simple but imprecise method to localize the masses. In this research, we present a more robust segmentation routine for use with mammographic masses. Our hypothesis is that by more accurately describing the morphology of the masses, we can improve the CAD system's ability to distinguish masses from other mammographic structures. To test this hypothesis, we incorporated the new segmentation routine into our CAD system and examined the change in performance. The developed iterative, linear segmentation routine is a gray level-based procedure. Using the identified regions from the previous CAD system as the initial seeds, the new segmentation algorithm refines the suspicious mass borders by making estimates of the interior and exterior pixels. These estimates are then passed to a linear discriminant, which determines the optimal threshold between the interior and exterior pixels. After applying the threshold and identifying the object's outline, two constraints on the border are applied to reduce the influence of background noise. After the border is constrained, the process repeats until a stopping criterion is reached. The segmentation routine was tested on a study database of 183 mammographic images extracted from the Digital Database for Screening Mammography. Eighty-three of the images contained 50 malignant and 50 benign masses; 100 images contained no masses. The previously developed CAD system was used to locate a set of suspicious regions of interest (ROIs) within the images. To assess the performance of the segmentation algorithm, a set of 20 features was measured from the suspicious regions before and after the application of the developed segmentation routine. Receiver operating characteristic (ROC) analysis was employed on the ROIs to examine the discriminatory capabilities of each individual feature before and after the segmentation routine. A statistically significant performance increase was found in many of the individual features, particularly those describing the mass borders. To examine how the incorporation of the segmentation routine affected the performance of the overall CAD system, free-response ROC (FROC) analysis was employed. When considering only malignant masses, the FROC performance of the system with the segmentation routine appeared better than the previous system. When detecting 90% of the malignant masses, the previous system achieved 4.9 false positives per image (FPpI) compared to the post-segmentation system's 4.2 FPpI. At 80% sensitivity, the respective FPpI were 3.5 and 1.6.

A classification and regression tree (CART) model was trained to classify 41 clinical specimens as disease/nondisease based on 26 variables computed from the mass-to-charge ratio (m/z) and peak heights of proteins identified by mass spectroscopy. The CART model built on all of the specimens (no cross-validation) had an error rate of 4/41 = 10%. The CART model suggests that mass spectra peaks in the 8000-10,000, 20,000-30,000, 45,000-60, 000, and >125,000 m/z ranges may be valuable in distinguishing between the disease/nondisease specimens. The area under the receiver operating characteristics curve was 0.80 +/- 0.07 for leave-one-out cross-validation.

The purpose of this study was to develop a knowledge-based scheme for the detection of masses on digitized screening mammograms. The computer-assisted detection (CAD) scheme utilizes a knowledge databank of mammographic regions of interest (ROIs) with known ground truth. Each ROI in the databank serves as a template. The CAD system follows a template matching approach with mutual information as the similarity metric to determine if a query mammographic ROI depicts a true mass. Based on their information content, all similar ROIs in the databank are retrieved and rank-ordered. Then, a decision index is calculated based on the query's best matches. The decision index effectively combines the similarity indices and ground truth of the best-matched templates into a prediction regarding the presence of a mass in the query mammographic ROI. The system was developed and evaluated using a database of 1465 ROIs extracted from the Digital Database for Screening Mammography. There were 809 ROIs with confirmed masses (455 malignant and 354 benign) and 656 normal ROIs. CAD performance was assessed using a leave-one-out sampling scheme and Receiver Operating Characteristics analysis. Depending on the formulation of the decision index, CAD performance as high as A(zeta) = 0.87 +/- 0.01 was achieved. The CAD detection rate was consistent for both malignant and benign masses. In addition, the impact of certain implementation parameters on the detection accuracy and speed of the proposed CAD scheme was studied in more detail.

We propose to investigate the use of the subregion Hotelling observer for the basis of a computer aided detection scheme for masses in mammography. A database of 1320 regions of interest (ROIs) was selected from the DDSM database collected by the University of South Florida using the Lumisys scanner cases. The breakdown of the cases was as follows: 656 normal ROIs, 307 benign ROIs, and 357 cancer ROIs. Each ROI was extracted at a size of 1024 x 1024 pixels and sub-sampled to 128 x 128 pixels. For the detection task, cancer and benign cases were considered positive and normal was considered negative. All positive cases had the lesion centered in the ROI. We chose to investigate the subregion Hotelling observer as a classifier to detect masses. The Hotelling observer incorporates information about the signal, the background, and the noise correlation for prediction of positive and negative and is the optimal detector when these are known. For our study, 225 subregion Hotelling observers were set up in a 15 x 15 grid across the center of the ROIs. Each separate observer was designed to "observe," or discriminate, an 8 x 8 pixel area of the image. A leave one out training and testing methodology was used to generate 225 "features," where each feature is the output of the individual observers. The 225 features derived from separate Hotelling observers were then narrowed down by using forward searching linear discriminants (LDs). The reduced set of features was then analyzed using an additional LD with receiver operating characteristic (ROC) analysis. The 225 Hotelling observer features were searched by the forward searching LD, which selected a subset of 37 features. This subset of 37 features was then analyzed using an additional LD, which gave a ROC area under the curve of 0.9412 +/- 0.006 and a partial area of 0.6728. Additionally, at 98% sensitivity the overall classifier had a specificity of 55.9% and a positive predictive value of 69.3%. Preliminary results suggest that using subregion Hotelling observers in combination with LDs can provide a strong backbone for a CAD scheme to help radiologists with detection. Such a system could be used in conjunction with CAD systems for false positive reduction.

The likelihood ratio (LR) is an optimal approach for deciding which of two alternate hypotheses best describes a given situation. We adopted this formalism for predicting whether biopsy results of mammographic masses will be benign or malignant, aiming to reduce the number of biopsies performed on benign lesions. We compared the performance of this LR-based algorithm (LRb) to a case-based reasoning (CBR) classifier, which provides a solution to a new problem using past similiar cases. Each classifier used mammographers' BI-RADS descriptions of mammographic masses as input. The database consisted of 646 biopsy-proven mammography cases. Performance was evaluated using Receiver Operating Characteristic (ROC) analysis, Round Robin sampling, and bootstrap. The ROC areas (AUC) for the LRb and CBR were 0.91+/- 0.01 and 0.92 +/- 0.01, respectively. The partial ROC area index (0.90AUC) was the same for both classifiers, 0.59 +/- 0.05. At a sensitivity of 98%, the CBR would spare 204 (49%) of benign lesions from biopsy; the LRb would spare 209 (51%) benign lesions. The performance of the two classifiers was very similar, with no statistical differences in AUC or 0.90AUC. Although the CBR and LRb originate from different fields of study, their implementations differ only in the estimation of the probability density functions (PDFs) of the feature distributions. The CBR performs this estimation implicitly, while using various similarity metrics. On the other hand, the estimation of the PDFs is specified explicitly in the LRb implementation. This difference in the estimation of the PDFs results in the very small difference in performance, and at 98% sensitivity, both classifiers would spare about half of the benign mammographic masses from biopsy. The CBR and LRb are equivalent methods in implementation and performance.

The purpose of this study was to identify and characterize clusters in a heterogeneous breast cancer computer-aided diagnosis database. Identification of subgroups within the database could help elucidate clinical trends and facilitate future model building. A self-organizing map (SOM) was used to identify clusters in a large (2258 cases), heterogeneous computer-aided diagnosis database based on mammographic findings (BI-RADS) and patient age. The resulting clusters were then characterized by their prototypes determined using a constraint satisfaction neural network (CSNN). The clusters showed logical separation of clinical subtypes such as architectural distortions, masses, and calcifications. Moreover, the broad categories of masses and calcifications were stratified into several clusters (seven for masses and three for calcifications). The percent of the cases that were malignant was notably different among the clusters (ranging from 6 to 83%). A feed-forward back-propagation artificial neural network (BP-ANN) was used to identify likely benign lesions that may be candidates for follow up rather than biopsy. The performance of the BP-ANN varied considerably across the clusters identified by the SOM. In particular, a cluster (#6) of mass cases (6% malignant) was identified that accounted for 79% of the recommendations for follow up that would have been made by the BP-ANN. A classification rule based on the profile of cluster #6 performed comparably to the BP-ANN, providing approximately 25% specificity at 98% sensitivity. This performance was demonstrated to generalize to a large (2177) set of cases held-out for model validation.

Purpose: To ascertain the optimum x-ray spectrum for chest radiography with a cesium iodide-amorphous silicon flat-panel detector., Materials and Methods: End points for optimization included the ratio of tissue contrast to bone contrast and a figure of merit (FOM) equal to the square of the signal-to-noise ratio of tissue divided by incident exposure to the patient. Studies were conducted with both computer spectrum modeling and experimental measurement in narrow-beam and full-field exposure conditions for four tissue thicknesses (8-32 cm). Three parameters that affect spectra were considered: the atomic number (Z) of filter material (Z = 13, 26, 29, 42, 50, 56, 64, 74, and 82), kilovoltage (from 50 to 150 kVp), and filter thickness (from 0.25 to 2.00 half-value layer [HVL])., Results: Computer modeling and narrow-beam experimental data showed similar trends for the full range of parameters evaluated. Spectrum model results showed that copper filtration at 120 kVp or more was optimum for FOM. The ratio of contrasts showed a trend to be higher with higher kilovoltage and only a minor variation with filter material. Full-field experimental results, which reflect the added contribution of x-ray scatter, differed in magnitude but not trends from the narrow-beam data in all cases except the ratio of contrasts in the mediastinum., Conclusion: The best performance overall, including both FOM and ratio of contrasts, was at 120 kVp with 1-HVL copper filtration (0.2 mm). With this beam spectrum and an increase in tube output (ie, milliampere seconds) of about 50%, a chest radiograph can be obtained with image quality approximately equal to that with a conventional spectrum but with about 25% less patient exposure., (Copyright RSNA, 2002)

Approximately 70-85% of breast biopsies are performed on benign lesions. To reduce this high number of biopsies performed on benign lesions, a case-based reasoning (CBR) classifier was developed to predict biopsy results from BI-RADS findings. We used 1433 (931 benign) biopsy-proven mammographic cases. CBR similarity was defined using either the Hamming or Euclidean distance measure over case features. Ten features represented each case: calcification distribution, calcification morphology, calcification number, mass margin, mass shape, mass density, mass size, associated findings, special cases, and age. Performance was evaluated using Round Robin sampling, Receiver Operating Characteristic (ROC) analysis, and bootstrap. To determine the most influential features for the CBR, an exhaustive feature search was performed over all possible feature combinations (1022) and similarity thresholds. Influential features were defined as the most frequently occurring features in the feature subsets with the highest partial ROC areas (0.90AUC). For CBR with Hamming distance, the most influential features were found to be mass margin, calcification morphology, age, calcification distribution, calcification number, and mass shape, resulting in an 0.90AUC of 0.33. At 95% sensitivity, the Hamming CBR would spare from biopsy 34% of the benign lesions. At 98% sensitivity, the Hamming CBR would spare 27% benign lesions. For the CBR with Euclidean distance, the most influential feature subset consisted of mass margin, calcification morphology, age, mass density, and associated findings, resulting in 0.90AUC of 0.37. At 95% sensitivity, the Euclidean CBR would spare from biopsy 41% benign lesions. At 98% sensitivity, the Euclidean CBR would spare 27% benign lesions. The profile of cases spared by both distance measures at 98% sensitivity indicates that the CBR is a potentially useful diagnostic tool for the classification of mammographic lesions, by recommending short-term follow-up for likely benign lesions that is in agreement with final biopsy results and mammographer's intuition.

Purpose: To compare the performance of a computer-aided diagnosis (CAD) system for diagnosis of previously detected lesions, based on radiologist-extracted findings on masses and calcifications., Materials and Methods: A feed-forward, back-propagation artificial neural network (BP-ANN) was trained in a round-robin (leave-one-out) manner to predict biopsy outcome from mammographic findings (according to the Breast Imaging Reporting and Data System) and patient age. The BP-ANN was trained by using a large (>1,000 cases) heterogeneous data set containing masses and microcalcifications. The performances of the BP-ANN on masses and microcalcifications were compared with use of receiver operating characteristic analysis and a z test for uncorrelated samples., Results: The BP-ANN performed significantly better on masses than microcalcifications in terms of both the area under the receiver operating characteristic curve and the partial receiver operating characteristic area index. A similar difference in performance was observed with a second model (linear discriminant analysis) and also with a second data set from a similar institution., Conclusion: Masses and calcifications should be considered separately when evaluating CAD systems for breast cancer diagnosis., (Copyright RSNA, 2002)

Our purpose in this study is to develop a parameter optimization technique for the segmentation of suspicious microcalcification clusters in digitized mammograms. In previous work, a computer-aided diagnosis (CAD) scheme was developed that used local histogram analysis of overlapping subimages and a fuzzy rule-based classifier to segment individual microcalcifications, and clustering analysis for reducing the number of false positive clusters. The performance of this previous CAD scheme depended on a large number of parameters such as the intervals used to calculate fuzzy membership values and on the combination of membership values used by each decision rule. These parameters were optimized empirically based on the performance of the algorithm on the training set. In order to overcome the limitations of manual training and rule generation, the segmentation algorithm was modified in order to incorporate automatic parameter optimization. For the segmentation of individual microcalcifications, the new algorithm used a neural network with fuzzy-scaled inputs. The fuzzy-scaled inputs were created by processing the histogram features with a family of membership functions, the parameters of which were automatically extracted from the distribution of the feature values. The neural network was trained to classify feature vectors as either positive or negative. Individual microcalcifications were segmented from positive subimages. After clustering, another neural network was trained to eliminate false positive clusters. A database of 98 images provided training and testing sets to optimize the parameters and evaluate the CAD scheme, respectively. The performance of the algorithm was evaluated with a FROC analysis. At a sensitivity rate of 93.2%, there was an average of 0.8 false positive clusters per image. The results are very comparable with those taken using our previously published rule-based method. However, the new algorithm is more suited to generalize its performance on a larger population, depends on two monotonic outputs making its evaluation much easier and can be trained in an automatic way making practical its application on a large database.

Perceptrons are typically trained to minimize mean square error (MSE). In computer-aided diagnosis (CAD), model performance is usually evaluated according to other more clinically relevant measures. The purpose of this study was to investigate the relationship between MSE and the area (A(z)) under the receiver operating characteristic (ROC) curve and the high-sensitivity partial ROC area ((0.90)A'(z)). A perceptron was used to predict lesion malignancy based on two mammographic findings and patient age. For each performance measure, the error surface in weight space was visualized. Comparison of the surfaces indicated that minimizing MSE tended to maximize A(z), but not (0.90)A'(z).

Objective: Given a predictive model for identifying very likely benign breast lesions on the basis of Breast Imaging Reporting and Data System (BI-RADS) mammographic findings, this study evaluated the model's ability to generalize to a patient data set from a different institution., Materials and Methods: The artificial neural network model underwent three trials: it was optimized over 500 biopsy-proven lesions from Duke University Medical Center or "Duke," evaluated on 1,000 similar cases from the University of Pennsylvania Health System or "Penn," and reoptimized for Penn., Results: Trial A's Duke-only model yielded 98% sensitivity, 36% specificity, area index (A(z)) of 0.86, and partial A(z) of 0.51. The cross-institutional trial B yielded 96% sensitivity, 28% specificity, A(z) of 0.79, and partial A(z) of 0.28. The decreases were significant for both A(z) (p = 0.017) and partial A(z) (p < 0.001). In trial C, the model reoptimized for the Penn data yielded 96% sensitivity, 35% specificity, A(z) of 0.83, and partial A(z) of 0.32. There were no significant differences compared with trial B for specificity (p = 0.44) or partial A(z) (p = 0.46), suggesting that the Penn data were inherently more difficult to characterize., Conclusion: The BI-RADS lexicon facilitated the cross-institutional test of a breast cancer prediction model. The model generalized reasonably well, but there were significant performance decreases. The cross-institutional performance was encouraging because it was not significantly different from that of a reoptimized model using the second data set at high sensitivities. This study indicates the need for further work to collect more data and to improve the robustness of the model.