Quantifying in situ adaptive immune cell cognate interactions in humans.

Two-photon excitation microscopy (TPEM) has revolutionized the understanding of adaptive immunity. However, TPEM usually requires animal models and is not amenable to the study of human disease. The recognition of antigen by T cells requires cell contact and is associated with changes in T cell shape. We postulated that by capturing these features in fixed tissue samples, we could quantify in situ adaptive immunity. Therefore, we used a deep convolutional neural network to identify fundamental distance and cell-shape features associated with cognate help (cell-distance mapping (CDM)). In mice, CDM was comparable to TPEM in discriminating cognate T cell-dendritic cell (DC) interactions from non-cognate T cell-DC interactions. In human lupus nephritis, CDM confirmed that myeloid DCs present antigen to CD4+ T cells and identified plasmacytoid DCs as an important antigen-presenting cell. These data reveal a new approach with which to study human in situ adaptive immunity broadly applicable to autoimmunity, infection, and cancer.

Artificial intelligence in cancer imaging: Clinical challenges and applications.

Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care.

Differences in Molecular Subtype Reference Standards Impact AI-based Breast Cancer Classification with Dynamic Contrast-enhanced MRI.

Background Breast cancer tumors can be identified as different luminal molecular subtypes depending on either immunohistochemical (IHC) staining or St Gallen criteria that includes Ki-67. Purpose To characterize molecular subtypes and understand the impact of disagreement among IHC and St Gallen molecular subtype reference standards on artificial intelligence classification of luminal A and luminal B tumors with use of radiomic features extracted from dynamic contrast-enhanced (DCE) MRI scans. Materials and Methods In this retrospective study, 28 radiomic features previously extracted from DCE-MRI scans of breast tumors imaged between February 2015 and October 2017 were examined in the following groups: (a) tumors classified as luminal A by both reference standards ("agreement"), (b) tumors classified as luminal A by IHC and luminal B by St Gallen ("disagreement"), and (c) tumors classified as luminal B by both ("agreement"). Luminal A or luminal B tumor classification with use of radiomic features was conducted with use of three sets: (a) IHC molecular subtyping, (b) St Gallen molecular subtyping, and (c) agreement tumors. The Kruskal-Wallis test was followed by the Mann-Whitney U test to determine pair-wise differences of radiomic features among agreement and disagreement tumors. Fivefold cross-validation with use of stepwise feature selection and linear discriminant analysis classified tumors in each set, with performance measured with use of area under the receiver operating characteristic curve (AUC). Results A total of 877 breast cancer tumors from 872 women (mean age, 48 years [range, 19-75 years]) were analyzed. Six features (sphericity, irregularity, surface area to volume ratio, variance of radial gradient histogram, sum average, volume of most enhancing voxels) were different (P ≤ .001) among agreement and disagreement tumors. AUC (median, 0.74 [95% CI: 0.68, 0.80]) was higher than when using tumors subtyped by either reference standard (IHC, 0.66 [0.60, 0.71], P = .003; St Gallen, 0.62 [0.58, 0.67], P = .001). Conclusion Differences in reference standards can hinder artificial intelligence classification performance of luminal molecular subtypes with dynamic contrast-enhanced MRI. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bae in this issue.

Artificial Intelligence and Cellular Segmentation in Tissue Microscopy Images.

With applications in object detection, image feature extraction, image classification, and image segmentation, artificial intelligence is facilitating high-throughput analysis of image data in a variety of biomedical imaging disciplines, ranging from radiology and pathology to cancer biology and immunology. Specifically, a growth in research on deep learning has led to the widespread application of computer-visualization techniques for analyzing and mining data from biomedical images. The availability of open-source software packages and the development of novel, trainable deep neural network architectures has led to increased accuracy in cell detection and segmentation algorithms. By automating cell segmentation, it is now possible to mine quantifiable cellular and spatio-cellular features from microscopy images, providing insight into the organization of cells in various pathologies. This mini-review provides an overview of the current state of the art in deep learning- and artificial intelligence-based methods of segmentation and data mining of cells in microscopy images of tissue.

Machine Learning for Early Detection of Hypoxic-Ischemic Brain Injury After Cardiac Arrest.

BACKGROUND: Establishing whether a patient who survived a cardiac arrest has suffered hypoxic-ischemic brain injury (HIBI) shortly after return of spontaneous circulation (ROSC) can be of paramount importance for informing families and identifying patients who may benefit the most from neuroprotective therapies. We hypothesize that using deep transfer learning on normal-appearing findings on head computed tomography (HCT) scans performed after ROSC would allow us to identify early evidence of HIBI. METHODS: We analyzed 54 adult comatose survivors of cardiac arrest for whom both an initial HCT scan, done early after ROSC, and a follow-up HCT scan were available. The initial HCT scan of each included patient was read as normal by a board-certified neuroradiologist. Deep transfer learning was used to evaluate the initial HCT scan and predict progression of HIBI on the follow-up HCT scan. A naive set of 16 additional patients were used for external validation of the model. RESULTS: The median age (interquartile range) of our cohort was 61 (16) years, and 25 (46%) patients were female. Although findings of all initial HCT scans appeared normal, follow-up HCT scans showed signs of HIBI in 29 (54%) patients (computed tomography progression). Evaluating the first HCT scan with deep transfer learning accurately predicted progression to HIBI. The deep learning score was the most significant predictor of progression (area under the receiver operating characteristic curve = 0.96 [95% confidence interval 0.91-1.00]), with a deep learning score of 0.494 having a sensitivity of 1.00, specificity of 0.88, accuracy of 0.94, and positive predictive value of 0.91. An additional assessment of an independent test set confirmed high performance (area under the receiver operating characteristic curve = 0.90 [95% confidence interval 0.74-1.00]). CONCLUSIONS: Deep transfer learning used to evaluate normal-appearing findings on HCT scans obtained early after ROSC in comatose survivors of cardiac arrest accurately identifies patients who progress to show radiographic evidence of HIBI on follow-up HCT scans.

AAPM Task Group 298: Recommendations on certificate program/alternative pathway candidate education and training.

Entry into the field of clinical medical physics is most commonly accomplished through the completion of a Commission on Accreditation of Medical Physics Educational Programs (CAMPEP)-accredited graduate and residency program. To allow a mechanism to bring valuable expertise from other disciplines into clinical practice in medical physics, an "alternative pathway" approach was also established. To ensure those trainees who have completed a doctoral degree in physics or a related discipline have the appropriate background and didactic training in medical physics, certificate programs and a CAMPEP-accreditation process for these programs were initiated. However, medical physics-specific didactic, research, and clinical exposure of those entering medical physics residencies from these certificate programs is often comparatively modest when evaluated against individuals holding Master's and/or Doctoral degrees in CAMPEP-accredited graduate programs. In 2016, the AAPM approved the formation of Task Group (TG) 298, "Alternative Pathway Candidate Education and Training." The TG was charged with reviewing previous published recommendations for alternative pathway candidates and developing recommendations on the appropriate education and training of these candidates. This manuscript is a summary of the AAPM TG 298 report.

Anatomic Point-Based Lung Region with Zone Identification for Radiologist Annotation and Machine Learning for Chest Radiographs.

Our objective is to investigate the reliability and usefulness of anatomic point-based lung zone segmentation on chest radiographs (CXRs) as a reference standard framework and to evaluate the accuracy of automated point placement. Two hundred frontal CXRs were presented to two radiologists who identified five anatomic points: two at the lung apices, one at the top of the aortic arch, and two at the costophrenic angles. Of these 1000 anatomic points, 161 (16.1%) were obscured (mostly by pleural effusions). Observer variations were investigated. Eight anatomic zones then were automatically generated from the manually placed anatomic points, and a prototype algorithm was developed using the point-based lung zone segmentation to detect cardiomegaly and levels of diaphragm and pleural effusions. A trained U-Net neural network was used to automatically place these five points within 379 CXRs of an independent database. Intra- and inter-observer variation in mean distance between corresponding anatomic points was larger for obscured points (8.7 mm and 20 mm, respectively) than for visible points (4.3 mm and 7.6 mm, respectively). The computer algorithm using the point-based lung zone segmentation could diagnostically measure the cardiothoracic ratio and diaphragm position or pleural effusion. The mean distance between corresponding points placed by the radiologist and by the neural network was 6.2 mm. The network identified 95% of the radiologist-indicated points with only 3% of network-identified points being false-positives. In conclusion, a reliable anatomic point-based lung segmentation method for CXRs has been developed with expected utility for establishing reference standards for machine learning applications.

Artificial intelligence in the interpretation of breast cancer on MRI.

Advances in both imaging and computers have led to the rise in the potential use of artificial intelligence (AI) in various tasks in breast imaging, going beyond the current use in computer-aided detection to include diagnosis, prognosis, response to therapy, and risk assessment. The automated capabilities of AI offer the potential to enhance the diagnostic expertise of clinicians, including accurate demarcation of tumor volume, extraction of characteristic cancer phenotypes, translation of tumoral phenotype features to clinical genotype implications, and risk prediction. The combination of image-specific findings with the underlying genomic, pathologic, and clinical features is becoming of increasing value in breast cancer. The concurrent emergence of newer imaging techniques has provided radiologists with greater diagnostic tools and image datasets to analyze and interpret. Integrating an AI-based workflow within breast imaging enables the integration of multiple data streams into powerful multidisciplinary applications that may lead the path to personalized patient-specific medicine. In this article we describe the goals of AI in breast cancer imaging, in particular MRI, and review the literature as it relates to the current application, potential, and limitations in breast cancer. Level of Evidence: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:1310-1324.

Comparison of Breast MRI Tumor Classification Using Human-Engineered Radiomics, Transfer Learning From Deep Convolutional Neural Networks, and Fusion Methods.

Digital image-based signatures of breast tumors may ultimately contribute to the design of patient-specific breast cancer diagnostics and treatments. Beyond traditional human-engineered computer vision methods, tumor classification methods using transfer learning from deep convolutional neural networks (CNNs) are actively under development. This article will first discuss our progress in using CNN-based transfer learning to characterize breast tumors for various diagnostic, prognostic, or predictive image-based tasks across multiple imaging modalities, including mammography, digital breast tomosynthesis, ultrasound (US), and magnetic resonance imaging (MRI), compared to both human-engineered feature-based radiomics and fusion classifiers created through combination of such features. Second, a new study is presented that reports on a comprehensive comparison of the classification performances of features derived from human-engineered radiomic features, CNN transfer learning, and fusion classifiers for breast lesions imaged with MRI. These studies demonstrate the utility of transfer learning for computer-aided diagnosis and highlight the synergistic improvement in classification performance using fusion classifiers.

Tailoring steroids in the treatment of COVID-19 pneumonia assisted by CT scans: three case reports.

In this article, we analyze and report cases of three patients who were admitted to Renmin Hospital, Wuhan University, China, for treating COVID-19 pneumonia in February 2020 and were unresponsive to initial treatment of steroids. They were then received titrated steroids treatment based on the assessment of computed tomography (CT) images augmented and analyzed with the artificial intelligence (AI) tool and output. Three patients were finally recovered and discharged. The result indicated that sufficient steroids may be effective in treating the COVID-19 patients after frequent evaluation and timely adjustment according to the disease severity assessed based on the quantitative analysis of the images of serial CT scans.

Digital Mammography in Breast Cancer: Additive Value of Radiomics of Breast Parenchyma.

Background Previous studies have suggested that breast parenchymal texture features may reflect the biologic risk factors associated with breast cancer development. Therefore, combining the characteristics of normal parenchyma from the contralateral breast with radiomic features of breast tumors may improve the accuracy of digital mammography in the diagnosis of breast cancer. Purpose To determine whether the addition of radiomic analysis of contralateral breast parenchyma to the characterization of breast lesions with digital mammography improves lesion classification over that with radiomic tumor features alone. Materials and Methods This HIPAA-compliant, retrospective study included 182 patients (age range, 25-90 years; mean age, 55.9 years ± 14.9) who underwent mammography between June 2002 and July 2009. There were 106 malignant and 76 benign lesions. Automatic lesion segmentation and radiomic analysis were performed for each breast lesion. Radiomic texture analysis was applied in the normal regions of interest in the contralateral breast parenchyma to assess the mammographic parenchymal patterns. The classification performance of both individual features and the output from a Bayesian artificial neural network classifier was evaluated with the leave-one-patient-out method by using the area under the receiver operating characteristic curve (AUC) as the figure of merit in the task of differentiating between malignant and benign lesions. Results The performance of the combined lesion and parenchyma classifier in the differentiation between malignant and benign mammographic lesions was better than that with the lesion features alone (AUC = 0.84 ± 0.03 vs 0.79 ± 0.03, respectively; P = .047). Overall, six radiomic features-spiculation, margin sharpness, size, circularity from the tumor feature set, and skewness and power law beta from the parenchymal feature set-were selected more than 50% of the time during the feature selection process on the combined feature set. Conclusion Combining quantitative radiomic data from tumors with contralateral parenchyma characterizations may improve diagnostic accuracy for breast cancer. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Shaffer in this issue.

Combined Benefit of Quantitative Three-Compartment Breast Image Analysis and Mammography Radiomics in the Classification of Breast Masses in a Clinical Data Set.

Purpose To investigate the combination of mammography radiomics and quantitative three-compartment breast (3CB) image analysis of dual-energy mammography to limit unnecessary benign breast biopsies. Materials and Methods For this prospective study, dual-energy craniocaudal and mediolateral oblique mammograms were obtained immediately before biopsy in 109 women (mean age, 51 years; range, 31-85 years) with Breast Imaging Reporting and Data System category 4 or 5 breast masses (35 invasive cancers, 74 benign) from 2013 through 2017. The three quantitative compartments of water, lipid, and protein thickness at each pixel were calculated from the attenuation at high and low energy by using a within-image phantom. Masses were automatically segmented and features were extracted from the low-energy mammograms and the quantitative compartment images. Tenfold cross-validations using a linear discriminant classifier with predefined feature signatures helped differentiate between malignant and benign masses by means of (a) water-lipid-protein composition images alone, (b) mammography radiomics alone, and (c) a combined image analysis of both. Positive predictive value of biopsy performed (PPV3) at maximum sensitivity was the primary performance metric, and results were compared with those for conventional diagnostic digital mammography. Results The PPV3 for conventional diagnostic digital mammography in our data set was 32.1% (35 of 109; 95% confidence interval [CI]: 23.9%, 41.3%), with a sensitivity of 100%. In comparison, combined mammography radiomics plus quantitative 3CB image analysis had PPV3 of 49% (34 of 70; 95% CI: 36.5%, 58.9%; P < .001), with a sensitivity of 97% (34 of 35; 95% CI: 90.3%, 100%; P < .001) and 35.8% (39 of 109) fewer total biopsies (P < .001). Conclusion Quantitative three-compartment breast image analysis of breast masses combined with mammography radiomics has the potential to reduce unnecessary breast biopsies. © RSNA, 2018 Online supplemental material is available for this article.

Fast bilateral breast coverage with high spectral and spatial resolution (HiSS) MRI at 3T.

PURPOSE: To develop and assess a full-coverage, sensitivity encoding (SENSE)-accelerated breast high spatial and spectral resolution (HiSS) magnetic resonance imaging (MRI) within clinically reasonable times as a potential nonenhanced MRI protocol for breast density measurement or breast cancer screening. MATERIALS AND METHODS: Sixteen women with biopsy-proven cancer or suspicious lesions, and 13 women who were healthy volunteers or were screened for breast cancer, received 3T breast MRI exams, including SENSE-accelerated HiSS MRI, which was implemented as a submillimeter spatial resolution echo-planar spectroscopic imaging (EPSI) sequence. In postprocessing, fat and water resonance peak height and integral images were generated from EPSI data. The postprocessing software was custom-designed, and new algorithms were developed to enable processing of whole-coverage axial HiSS datasets. Water peak height HiSS images were compared to pre- and postcontrast T1 -weighted images. Fat suppression was quantified as parenchymal-to-suppressed-fat signal ratio in HiSS water peak height and nonenhanced T1 -weighted images, and artifact levels were scored. RESULTS: Approximately a 4-fold decrease in acquisition speed, with a concurrent 2.5-fold decrease in voxel size, was achieved, with low artifact levels, and with spectral signal-to-noise ratio (SNR) of 45:1. Fat suppression was 1.9 times more effective (P < 0.001) in HiSS images than in T1 -weighted images (SPAIR), and HiSS images showed higher SNR in the axilla. HiSS MRI visualized 10 of 13 malignant lesions identified on dynamic contrast-enhanced (DCE)-MRI, and did not require skin removal in postprocessing to generate maximum intensity projection images. CONCLUSION: We demonstrate full-coverage, SENSE-accelerated breast HiSS MRI within clinically reasonable times, as a potential protocol for breast density measurement or breast cancer screening. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1341-1348.

Using computer-extracted image phenotypes from tumors on breast magnetic resonance imaging to predict breast cancer pathologic stage.

BACKGROUND: The objective of this study was to demonstrate that computer-extracted image phenotypes (CEIPs) of biopsy-proven breast cancer on magnetic resonance imaging (MRI) can accurately predict pathologic stage. METHODS: The authors used a data set of deidentified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. In total, 91 biopsy-proven breast cancers were analyzed from patients who had information available on pathologic stage (stage I, n = 22; stage II, n = 58; stage III, n = 11) and surgically verified lymph node status (negative lymph nodes, n = 46; ≥ 1 positive lymph node, n = 44; no lymph nodes examined, n = 1). Tumors were characterized according to 1) radiologist-measured size and 2) CEIP. Then, models were built that combined 2 CEIPs to predict tumor pathologic stage and lymph node involvement, and the models were evaluated in a leave-1-out, cross-validation analysis with the area under the receiver operating characteristic curve (AUC) as the value of interest. RESULTS: Tumor size was the most powerful predictor of pathologic stage, but CEIPs that captured biologic behavior also emerged as predictive (eg, stage I and II vs stage III demonstrated an AUC of 0.83). No size measure was successful in the prediction of positive lymph nodes, but adding a CEIP that described tumor "homogeneity" significantly improved discrimination (AUC = 0.62; P = .003) compared with chance. CONCLUSIONS: The current results indicate that MRI phenotypes have promise for predicting breast cancer pathologic stage and lymph node status. Cancer 2016;122:748-757. © 2015 American Cancer Society.

Clinical significance of noncalcified lung nodules in patients with breast cancer.

Patients with breast cancer are increasingly likely to have chest computed tomography (CT) performed. In many cases, small lung nodules will be detected, raising concern for metastases and causing considerable patient anxiety. The majority of these nodules, however, are benign, though the specific probability of malignancy is uncertain in any given case. Therefore, we analyzed the results of chest CT scans of a large number of patients with breast cancer, to determine characteristics and clinical significance of noncalcified lung nodules. 3313 patients were investigated, and 4889 CT scans from 1325 patients were retrospectively reviewed. Among the 1325 patients, 812 (59 %) had at least one noncalcified lung nodule, of which 330 (41 %) had malignant nodules, 197 (24 %) had large (≥10 mm) nodules, and 586 (72 %) had multiple nodules. Large nodules were more often malignant than benign (P < 0.001). In patients with multiple large nodules, the rate of malignancy rate was 83 %, and most of these were metastases. In the case of very small (2-4 mm) nodules, the malignancy rates for solitary and multiple nodules were 8 and 20 %, respectively. Lung metastases were more likely with breast cancer cell grade 3 (22 %) than grade 1-2 (10 %) (P < 0.001) and when patients were clinical stage 2-3 (14 %) than stage 0-1 (7.9 %) (P = 0.03). Lung metastases are highly likely in patients with multiple nodules greater than 10 mm. Higher cancer cell grades and clinical stage are also related to an increased likelihood of lung metastases. The great majority of small lung nodules in breast cancer patients are benign.

MR Imaging Radiomics Signatures for Predicting the Risk of Breast Cancer Recurrence as Given by Research Versions of MammaPrint, Oncotype DX, and PAM50 Gene Assays.

Purpose To investigate relationships between computer-extracted breast magnetic resonance (MR) imaging phenotypes with multigene assays of MammaPrint, Oncotype DX, and PAM50 to assess the role of radiomics in evaluating the risk of breast cancer recurrence. Materials and Methods Analysis was conducted on an institutional review board-approved retrospective data set of 84 deidentified, multi-institutional breast MR examinations from the National Cancer Institute Cancer Imaging Archive, along with clinical, histopathologic, and genomic data from The Cancer Genome Atlas. The data set of biopsy-proven invasive breast cancers included 74 (88%) ductal, eight (10%) lobular, and two (2%) mixed cancers. Of these, 73 (87%) were estrogen receptor positive, 67 (80%) were progesterone receptor positive, and 19 (23%) were human epidermal growth factor receptor 2 positive. For each case, computerized radiomics of the MR images yielded computer-extracted tumor phenotypes of size, shape, margin morphology, enhancement texture, and kinetic assessment. Regression and receiver operating characteristic analysis were conducted to assess the predictive ability of the MR radiomics features relative to the multigene assay classifications. Results Multiple linear regression analyses demonstrated significant associations (R2 = 0.25-0.32, r = 0.5-0.56, P < .0001) between radiomics signatures and multigene assay recurrence scores. Important radiomics features included tumor size and enhancement texture, which indicated tumor heterogeneity. Use of radiomics in the task of distinguishing between good and poor prognosis yielded area under the receiver operating characteristic curve values of 0.88 (standard error, 0.05), 0.76 (standard error, 0.06), 0.68 (standard error, 0.08), and 0.55 (standard error, 0.09) for MammaPrint, Oncotype DX, PAM50 risk of relapse based on subtype, and PAM50 risk of relapse based on subtype and proliferation, respectively, with all but the latter showing statistical difference from chance. Conclusion Quantitative breast MR imaging radiomics shows promise for image-based phenotyping in assessing the risk of breast cancer recurrence. © RSNA, 2016 Online supplemental material is available for this article.

Automated Breast Ultrasound in Breast Cancer Screening of Women With Dense Breasts: Reader Study of Mammography-Negative and Mammography-Positive Cancers.

OBJECTIVE: The objective of our study was to assess and compare, in a reader study, radiologists' performance in the detection of breast cancer using full-field digital mammography (FFDM) alone and using FFDM with 3D automated breast ultrasound (ABUS). MATERIALS AND METHODS: In this multireader, multicase, sequential-design reader study, 17 Mammography Quality Standards Act-qualified radiologists interpreted a cancer-enriched set of FFDM and ABUS examinations. All imaging studies were of asymptomatic women with BI-RADS C or D breast density. Readers first interpreted FFDM alone and subsequently interpreted FFDM combined with ABUS. The analysis included 185 cases: 133 noncancers and 52 biopsy-proven cancers. Of the 52 cancer cases, the screening FFDM images were interpreted as showing BI-RADS 1 or 2 findings in 31 cases and BI-RADS 0 findings in 21 cases. For the cases interpreted as BI-RADS 0, a forced BI-RADS score was also given. Reader performance was compared in terms of AUC under the ROC curve, sensitivity, and specificity. RESULTS: The AUC was 0.72 for FFDM alone and 0.82 for FFDM combined with ABUS, yielding a statistically significant 14% relative improvement in AUC (i.e., change in AUC = 0.10 [95% CI, 0.07-0.14]; p < 0.001). When a cutpoint of BI-RADS 3 was used, the sensitivity across all readers was 57.5% for FFDM alone and 74.1% for FFDM with ABUS, yielding a statistically significant increase in sensitivity (p < 0.001) (relative increase = 29%). Overall specificity was 78.1% for FFDM alone and 76.1% for FFDM with ABUS (p = 0.496). For only the mammography-negative cancers, the average AUC was 0.60 for FFDM alone and 0.75 for FFDM with ABUS, yielding a statistically significant 25% relative improvement in AUC with the addition of ABUS (p < 0.001). CONCLUSION: Combining mammography with ABUS, compared with mammography alone, significantly improved readers' detection of breast cancers in women with dense breast tissue without substantially affecting specificity.

Manganese-enhanced MRI detection of impaired calcium regulation in a mouse model of cardiac hypertrophy.

The aim of this study was to use manganese (Mn)-enhanced MRI (MEMRI) to detect changes in calcium handling associated with cardiac hypertrophy in a mouse model, and to determine whether the impact of creatine kinase ablation is detectable using this method. Male C57BL/6 (C57, n = 11) and male creatine kinase double-knockout (CK-M/Mito(-/-) , DBKO, n = 12) mice were imaged using the saturation recovery Look-Locker T1 mapping sequence before and after the development of cardiac hypertrophy. Hypertrophy was induced via subcutaneous continuous 3-day infusion of isoproterenol, and sham mice not subjected to cardiac hypertrophy were also imaged. During each scan, the contrast agent Mn was administered and the resulting change in R1 (=1/T1) was calculated. Two anatomical regions of interest (ROIs) were considered, the left-ventricular free wall (LVFW) and the septum, and one ROI in an Mn-containing standard placed next to the mouse. We found statistically significant (p < 0.05) decreases in the uptake of Mn in both the LVFW and septum following the induction of cardiac hypertrophy. No statistically significant decreases were detected in the standard, and no statistically significant differences were found among the sham mice. Using a murine model, we successfully demonstrated that changes in Mn uptake as a result of cardiac hypertrophy are detectable using the functional contrast agent and calcium mimetic Mn. Our measurements showed a decrease in the relaxivity (R1) of the myocardium following cardiac hypertrophy compared with normal control mice.

Relationships between computer-extracted mammographic texture pattern features and BRCA1/2 mutation status: a cross-sectional study.

INTRODUCTION: Mammographic density is similar among women at risk of either sporadic or BRCA1/2-related breast cancer. It has been suggested that digitized mammographic images contain computer-extractable information within the parenchymal pattern, which may contribute to distinguishing between BRCA1/2 mutation carriers and non-carriers. METHODS: We compared mammographic texture pattern features in digitized mammograms from women with deleterious BRCA1/2 mutations (n = 137) versus non-carriers (n = 100). Subjects were stratified into training (107 carriers, 70 non-carriers) and testing (30 carriers, 30 non-carriers) datasets. Masked to mutation status, texture features were extracted from a retro-areolar region-of-interest in each subject's digitized mammogram. Stepwise linear regression analysis of the training dataset identified variables to be included in a radiographic texture analysis (RTA) classifier model aimed at distinguishing BRCA1/2 carriers from non-carriers. The selected features were combined using a Bayesian Artificial Neural Network (BANN) algorithm, which produced a probability score rating the likelihood of each subject's belonging to the mutation-positive group. These probability scores were evaluated in the independent testing dataset to determine whether their distribution differed between BRCA1/2 mutation carriers and non-carriers. A receiver operating characteristic analysis was performed to estimate the model's discriminatory capacity. RESULTS: In the testing dataset, a one standard deviation (SD) increase in the probability score from the BANN-trained classifier was associated with a two-fold increase in the odds of predicting BRCA1/2 mutation status: unadjusted odds ratio (OR) = 2.00, 95% confidence interval (CI): 1.59, 2.51, P = 0.02; age-adjusted OR = 1.93, 95% CI: 1.53, 2.42, P = 0.03. Additional adjustment for percent mammographic density did little to change the OR. The area under the curve for the BANN-trained classifier to distinguish between BRCA1/2 mutation carriers and non-carriers was 0.68 for features alone and 0.72 for the features plus percent mammographic density. CONCLUSIONS: Our findings suggest that, unlike percent mammographic density, computer-extracted mammographic texture pattern features are associated with carrying BRCA1/2 mutations. Although still at an early stage, our novel RTA classifier has potential for improving mammographic image interpretation by permitting real-time risk stratification among women undergoing screening mammography.