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Prostate cancer (PCa) is a common, serious form of cancer in men that is still prevalent despite ongoing developments in diagnostic oncology. Current detection methods lead to high rates of inaccurate diagnosis. We present a method to directly model and exploit temporal aspects of temporal enhanced ultrasound (TeUS) for tissue characterization, which improves malignancy prediction. We employ a probabilistic-temporal framework, namely, hidden Markov models (HMMs), for modeling TeUS data obtained from PCa patients. We distinguish malignant from benign tissue by comparing the respective log-likelihood estimates generated by the HMMs. We analyze 1100 TeUS signals acquired from 12 patients. Our results show improved malignancy identification compared to previous results, demonstrating over 85% accuracy and AUC of 0.95. Incorporating temporal information directly into the models leads to improved tissue differentiation in PCa. We expect our method to generalize and be applied to other types of cancer in which temporal-ultrasound can be recorded.

PURPOSE: To present a method that automatically detects, subtypes, and locates acute or subacute intracranial hemorrhage (ICH) on noncontrast CT (NCCT) head scans; generates detection confidence scores to identify high-confidence data subsets with higher accuracy; and improves radiology worklist prioritization. Such scores may enable clinicians to better use artificial intelligence (AI) tools. MATERIALS AND METHODS: This retrospective study included 46 057 studies from seven “internal” centers for development (training, architecture selection, hyperparameter tuning, and operating-point calibration; n = 25 946) and evaluation (n = 2947) and three "external" centers for calibration (n = 400) and evaluation (n = 16( )764). Internal centers contributed developmental data, whereas external centers did not. Deep neural networks predicted the presence of ICH and subtypes (intraparenchymal, intraventricular, subarachnoid, subdural, and/or epidural hemorrhage) and segmentations per case. Two ICH confidence scores are discussed: a calibrated classifier entropy score and a Dempster-Shafer score. Evaluation was completed by using receiver operating characteristic curve analysis and report turnaround time (RTAT) modeling on the evaluation set and on confidence score–defined subsets using bootstrapping. RESULTS: The areas under the receiver operating characteristic curve for ICH were 0.97 (0.97, 0.98) and 0.95 (0.94, 0.95) on internal and external center data, respectively. On 80% of the data stratified by calibrated classifier and Dempster-Shafer scores, the system improved the Youden indexes, increasing them from 0.84 to 0.93 (calibrated classifier) and from 0.84 to 0.92 (Dempster-Shafer) for internal centers and increasing them from 0.78 to 0.88 (calibrated classifier) and from 0.78 to 0.89 (Dempster-Shafer) for external centers (P < .001). Models estimated shorter RTAT for AI-prioritized worklists with confidence measures than for AI-prioritized worklists without confidence measures, shortening RTAT by 27% (calibrated classifier) and 27% (Dempster-Shafer) for internal centers and shortening RTAT by 25% (calibrated classifier) and 27% (Dempster-Shafer) for external centers (P < .001). CONCLUSION: AI that provided statistical confidence measures for ICH detection on NCCT scans reliably detected and subtyped hemorrhages, identified high-confidence predictions, and improved worklist prioritization in simulation. Keywords: CT, Head/Neck, Hemorrhage, Convolutional Neural Network (CNN) Supplemental material is available for this article. © RSNA, 2022

Purpose: We investigate the impact of various deep-learning-based methods for detecting and segmenting metastases with different lesion volume sizes on 3D brain MR images. Approach: A 2.5D U-Net and a 3D U-Net were selected. We also evaluated weak learner fusion of the prediction features generated by the 2.5D and the 3D networks. A 3D fully convolutional one-stage (FCOS) detector was selected as a representative of bounding-box regression-based detection methods. A total of 422 3D post-contrast T1-weighted scans from patients with brain metastases were used. Performances were analyzed based on lesion volume, total metastatic volume per patient, and number of lesions per patient. Results: The performance of detection of the 2.5D and 3D U-Net methods had recall of [Formula: see text] and precision of [Formula: see text] for lesion volume [Formula: see text] but deteriorated as metastasis size decreased below [Formula: see text] to 0.58 to 0.74 in recall and 0.16 to 0.25 in precision. Compared the two U-Nets for detection capability, high precision was achieved by the 2.5D network, but high recall was achieved by the 3D network for all lesion sizes. The weak learner fusion achieved a balanced performance between the 2.5D and 3D U-Nets; particularly, it increased precision to 0.83 for lesion volumes of 0.1 to [Formula: see text] but decreased recall to 0.59. The 3D FCOS detector did not outperform the U-Net methods in detecting either the small or large metastases presumably because of the limited data size. Conclusions: Our study provides the performances of four deep learning methods in relationship to lesion size, total metastasis volume, and number of lesions per patient, providing insight into further development of the deep learning networks.

Highlights • The attention mechanism can rank MR measures by relative importance. • Proposed guideline for use of the attention mechanism with MR measures. • Attention weights and quantitative MR measures can potentially form new patterns., Introduction During the last decade, a multitude of novel quantitative and semiquantitative MRI techniques have provided new information about the pathophysiology of neurological diseases. Yet, selection of the most relevant contrasts for a given pathology remains challenging. In this work, we developed and validated a method, Gated-Attention MEchanism Ranking of multi-contrast MRI in brain pathology (GAMER MRI), to rank the relative importance of MR measures in the classification of well understood ischemic stroke lesions. Subsequently, we applied this method to the classification of multiple sclerosis (MS) lesions, where the relative importance of MR measures is less understood. Methods GAMER MRI was developed based on the gated attention mechanism, which computes attention weights (AWs) as proxies of importance of hidden features in the classification. In the first two experiments, we used Trace-weighted (Trace), apparent diffusion coefficient (ADC), Fluid-Attenuated Inversion Recovery (FLAIR), and T1-weighted (T1w) images acquired in 904 acute/subacute ischemic stroke patients and in 6,230 healthy controls and patients with other brain pathologies to assess if GAMER MRI could produce clinically meaningful importance orders in two different classification scenarios. In the first experiment, GAMER MRI with a pretrained convolutional neural network (CNN) was used in conjunction with Trace, ADC, and FLAIR to distinguish patients with ischemic stroke from those with other pathologies and healthy controls. In the second experiment, GAMER MRI with a patch-based CNN used Trace, ADC and T1w to differentiate acute ischemic stroke lesions from healthy tissue. The last experiment explored the performance of patch-based CNN with GAMER MRI in ranking the importance of quantitative MRI measures to distinguish two groups of lesions with different pathological characteristics and unknown quantitative MR features. Specifically, GAMER MRI was applied to assess the relative importance of the myelin water fraction (MWF), quantitative susceptibility mapping (QSM), T1 relaxometry map (qT1), and neurite density index (NDI) in distinguishing 750 juxtacortical lesions from 242 periventricular lesions in 47 MS patients. Pair-wise permutation t-tests were used to evaluate the differences between the AWs obtained for each quantitative measure. Results In the first experiment, we achieved a mean test AUC of 0.881 and the obtained AWs of FLAIR and the sum of AWs of Trace and ADC were 0.11 and 0.89, respectively, as expected based on previous knowledge. In the second experiment, we achieved a mean test F1 score of 0.895 and a mean AW of Trace = 0.49, of ADC = 0.28, and of T1w = 0.23, thereby confirming the findings of the first experiment. In the third experiment, MS lesion classification achieved test balanced accuracy = 0.777, sensitivity = 0.739, and specificity = 0.814. The mean AWs of T1map, MWF, NDI, and QSM were 0.29, 0.26, 0.24, and 0.22 (p

LUX-ZEPLIN (LZ) is a second-generation direct dark matter experiment with spin-independent WIMP-nucleon scattering sensitivity above $1.4 \times 10^{-48}$ cm$^{2}$ for a WIMP mass of 40 GeV/c$^{2}$ and a 1000 d exposure. LZ achieves this sensitivity through a combination of a large 5.6 t fiducial volume, active inner and outer veto systems, and radio-pure construction using materials with inherently low radioactivity content. The LZ collaboration performed an extensive radioassay campaign over a period of six years to inform material selection for construction and provide an input to the experimental background model against which any possible signal excess may be evaluated. The campaign and its results are described in this paper. We present assays of dust and radon daughters depositing on the surface of components as well as cleanliness controls necessary to maintain background expectations through detector construction and assembly. Finally, examples from the campaign to highlight fixed contaminant radioassays for the LZ photomultiplier tubes, quality control and quality assurance procedures through fabrication, radon emanation measurements of major sub-systems, and bespoke detector systems to assay scintillator are presented., Comment: 45 pages (79 inc. tables), 7 figures, 9 tables

The interpretation of medical images is a challenging task, often complicated by the presence of artifacts, occlusions, limited contrast and more. Most notable is the case of chest radiography, where there is a high inter-rater variability in the detection and classification of abnormalities. This is largely due to inconclusive evidence in the data or subjective definitions of disease appearance. An additional example is the classification of anatomical views based on 2D Ultrasound images. Often, the anatomical context captured in a frame is not sufficient to recognize the underlying anatomy. Current machine learning solutions for these problems are typically limited to providing probabilistic predictions, relying on the capacity of underlying models to adapt to limited information and the high degree of label noise. In practice, however, this leads to overconfident systems with poor generalization on unseen data. To account for this, we propose a system that learns not only the probabilistic estimate for classification, but also an explicit uncertainty measure which captures the confidence of the system in the predicted output. We argue that this approach is essential to account for the inherent ambiguity characteristic of medical images from different radiologic exams including computed radiography, ultrasonography and magnetic resonance imaging. In our experiments we demonstrate that sample rejection based on the predicted uncertainty can significantly improve the ROC-AUC for various tasks, e.g., by 8% to 0.91 with an expected rejection rate of under 25% for the classification of different abnormalities in chest radiographs. In addition, we show that using uncertainty-driven bootstrapping to filter the training data, one can achieve a significant increase in robustness and accuracy., Under review at Medical Image Analysis

Author(s): Akerib, DS; Akerlof, CW; Alqahtani, A; Alsum, SK; Anderson, TJ; Angelides, N; Araujo, HM; Armstrong, JE; Arthurs, M; Bai, X; Balajthy, J; Balashov, S; Bang, J; Baxter, A; Bensinger, J; Bernard, EP; Bernstein, A; Bhatti, A; Biekert, A; Biesiadzinski, TP; Birch, HJ; Boast, KE; Boxer, B; Bras, P; Buckley, JH; Bugaev, VV; Burdin, S; Busenitz, JK; Cabrita, R; Carels, C; Carlsmith, DL; Carmona-Benitez, MC; Cascella, M; Chan, C; Chott, NI; Cole, A; Cottle, A; Cutter, JE; Dahl, CE; De Viveiros, L; Dobson, JEY; Druszkiewicz, E; Edberg, TK; Eriksen, SR; Fan, A; Fiorucci, S; Flaecher, H; Fraser, ED; Fruth, T; Gaitskell, RJ; Genovesi, J; Ghag, C; Gibson, E; Gilchriese, MGD; Gokhale, S; Van Der Grinten, MGD; Hall, CR; Harrison, A; Haselschwardt, SJ; Hertel, SA; Hor, JYK; Horn, M; Huang, DQ; Ignarra, CM; Jahangir, O; Ji, W; Johnson, J; Kaboth, AC; Kamaha, AC; Kamdin, K; Kazkaz, K; Khaitan, D; Khazov, A; Khurana, I; Kocher, CD; Korley, L; Korolkova, EV; Kras, J; Kraus, H; Kravitz, S; Kreczko, L; Krikler, B; Kudryavtsev, VA; Leason, EA; Lee, J | Abstract: The LUX-ZEPLIN (LZ) experiment will enable a neutrinoless double β decay search in parallel to the main science goal of discovering dark matter particle interactions. We report the expected LZ sensitivity to Xe136 neutrinoless double β decay, taking advantage of the significant (g600 kg) Xe136 mass contained within the active volume of LZ without isotopic enrichment. After 1000 live-days, the median exclusion sensitivity to the half-life of Xe136 is projected to be 1.06×1026 years (90% confidence level), similar to existing constraints. We also report the expected sensitivity of a possible subsequent dedicated exposure using 90% enrichment with Xe136 at 1.06×1027 years.

PURPOSE Multiparametric MRI (mpMRI) has shown promise in the detection and localization of prostate cancer foci. Although techniques have been previously introduced to delineate lesions from mpMRI, these techniques were evaluated in datasets with T2 maps available. The generation of T2 map is not included in the clinical prostate mpMRI consensus guidelines; the acquisition of which requires repeated T2-weighted (T2W) scans and would significantly lengthen the scan time currently required for the clinically recommended acquisition protocol, which includes T2W, diffusion-weighted (DW), and dynamic contrast-enhanced (DCE) imaging. The goal of this study is to develop and evaluate an algorithm that provides pixel-accurate lesion delineation from images acquired based on the clinical protocol. METHODS Twenty-five pixel-based features were extracted from the T2-weighted (T2W), apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) images. The pixel-wise classification was performed on the reduced space generated by locality alignment discriminant analysis (LADA), a version of linear discriminant analysis (LDA) localized to patches in the feature space. Postprocessing procedures, including the removal of isolated points identified and filling of holes inside detected regions, were performed to improve delineation accuracy. The segmentation result was evaluated against the lesions manually delineated by four expert observers according to the Prostate Imaging-Reporting and Data System (PI-RADS) detection guideline. RESULTS The LADA-based classifier (60 ± 11%) achieved a higher sensitivity than the LDA-based classifier (51 ± 10%), thereby demonstrating, for the first time, that higher classification performance was attained on the reduced space generated by LADA than by LDA. Further sensitivity improvement (75 ± 14%) was obtained after postprocessing, approaching the sensitivities attained by previous mpMRI lesion delineation studies in which nonclinical T2 maps were available. CONCLUSION The proposed algorithm delineated lesions accurately and efficiently from images acquired following the clinical protocol. The development of this framework may potentially accelerate the clinical uses of mpMRI in prostate cancer diagnosis and treatment planning.

Automatic segmentation of abdominal anatomy on computed tomography (CT) images can support diagnosis, treatment planning, and treatment delivery workflows. Segmentation methods using statistical models and multi-atlas label fusion (MALF) require inter-subject image registrations, which are challenging for abdominal images, but alternative methods without registration have not yet achieved higher accuracy for most abdominal organs. We present a registration-free deep-learning-based segmentation algorithm for eight organs that are relevant for navigation in endoscopic pancreatic and biliary procedures, including the pancreas, the gastrointestinal tract (esophagus, stomach, and duodenum) and surrounding organs (liver, spleen, left kidney, and gallbladder). We directly compared the segmentation accuracy of the proposed method to the existing deep learning and MALF methods in a cross-validation on a multi-centre data set with 90 subjects. The proposed method yielded significantly higher Dice scores for all organs and lower mean absolute distances for most organs, including Dice scores of 0.78 versus 0.71, 0.74, and 0.74 for the pancreas, 0.90 versus 0.85, 0.87, and 0.83 for the stomach, and 0.76 versus 0.68, 0.69, and 0.66 for the esophagus. We conclude that the deep-learning-based segmentation represents a registration-free method for multi-organ abdominal CT segmentation whose accuracy can surpass current methods, potentially supporting image-guided navigation in gastrointestinal endoscopy procedures.

Detecting malignant pulmonary nodules at an early stage can allow medical interventions which may increase the survival rate of lung cancer patients. Using computer vision techniques to detect nodules can improve the sensitivity and the speed of interpreting chest CT for lung cancer screening. Many studies have used CNNs to detect nodule candidates. Though such approaches have been shown to outperform the conventional image processing based methods regarding the detection accuracy, CNNs are also known to be limited to generalize on under-represented samples in the training set and prone to imperceptible noise perturbations. Such limitations can not be easily addressed by scaling up the dataset or the models. In this work, we propose to add adversarial synthetic nodules and adversarial attack samples to the training data to improve the generalization and the robustness of the lung nodule detection systems. To generate hard examples of nodules from a differentiable nodule synthesizer, we use projected gradient descent (PGD) to search the latent code within a bounded neighbourhood that would generate nodules to decrease the detector response. To make the network more robust to unanticipated noise perturbations, we use PGD to search for noise patterns that can trigger the network to give over-confident mistakes. By evaluating on two different benchmark datasets containing consensus annotations from three radiologists, we show that the proposed techniques can improve the detection performance on real CT data. To understand the limitations of both the conventional networks and the proposed augmented networks, we also perform stress-tests on the false positive reduction networks by feeding different types of artificially produced patches. We show that the augmented networks are more robust to both under-represented nodules as well as resistant to noise perturbations., Comment: Published on IEEE Trans. on Medical Imaging

The LUX-ZEPLIN dark matter search aims to achieve a sensitivity to the WIMP-nucleon spin-independent cross-section down to (1--2)$\times10^{-12}$\,pb at a WIMP mass of 40 GeV/$c^2$. This paper describes the simulations framework that, along with radioactivity measurements, was used to support this projection, and also to provide mock data for validating reconstruction and analysis software. Of particular note are the event generators, which allow us to model the background radiation, and the detector response physics used in the production of raw signals, which can be converted into digitized waveforms similar to data from the operational detector. Inclusion of the detector response allows us to process simulated data using the same analysis routines as developed to process the experimental data., Comment: 24 pages, 19 figures; Corresponding Authors: A. Cottle, V. Kudryavtsev, D. Woodward

The increasing incidence of pancreatic cancer will make it the second deadliest cancer in 2030. Imaging based early diagnosis and image guided treatment are emerging potential solutions. Artificial intelligence (AI) can help provide and improve widespread diagnostic expertise and accurate interventional image interpretation. Accurate segmentation of the pancreas is essential to create annotated data sets to train AI, and for computer assisted interventional guidance. Automated deep learning segmentation performance in pancreas computed tomography (CT) imaging is low due to poor grey value contrast and complex anatomy. A good solution seemed a recent interactive deep learning segmentation framework for brain CT that helped strongly improve initial automated segmentation with minimal user input. This method yielded no satisfactory results for pancreas CT, possibly due to a sub-optimal neural network architecture. We hypothesize that a state-of-the-art U-net neural network architecture is better because it can produce a better initial segmentation and is likely to be extended to work in a similar interactive approach. We implemented the existing interactive method, iFCN, and developed an interactive version of U-net method we call iUnet. The iUnet is fully trained to produce the best possible initial segmentation. In interactive mode it is additionally trained on a partial set of layers on user generated scribbles. We compare initial segmentation performance of iFCN and iUnet on a 100CT dataset using dice similarity coefficient analysis. Secondly, we assessed the performance gain in interactive use with three observers on segmentation quality and time. Average automated baseline performance was 78% (iUnet) versus 72% (FCN). Manual and semi-automatic segmentation performance was: 87% in 15 min. for manual, and 86% in 8 min. for iUNet. We conclude that iUnet provides a better baseline than iFCN and can reach expert manual performance significantly faster than manual segmentation in case of pancreas CT. Our novel iUnet architecture is modality and organ agnostic and can be a potential novel solution for semi-automatic medical imaging segmentation in general.

We describe the design and assembly of the LUX-ZEPLIN experiment, a direct detection search for cosmic WIMP dark matter particles. The centerpiece of the experiment is a large liquid xenon time projection chamber sensitive to low energy nuclear recoils. Rejection of backgrounds is enhanced by a Xe skin veto detector and by a liquid scintillator Outer Detector loaded with gadolinium for efficient neutron capture and tagging. LZ is located in the Davis Cavern at the 4850' level of the Sanford Underground Research Facility in Lead, South Dakota, USA. We describe the major subsystems of the experiment and its key design features and requirements. info:eu-repo/semantics/publishedVersion

Purpose To evaluate the performance of an artificial intelligence (AI) based software solution tested on liver volumetric analyses and to compare the results to the manual contour segmentation. Materials and methods We retrospectively obtained 462 multiphasic CT datasets with six series for each patient: three different contrast phases and two slice thickness reconstructions (1.5/5 mm), totaling 2772 series. AI-based liver volumes were determined using multi-scale deep-reinforcement learning for 3D body markers detection and 3D structure segmentation. The algorithm was trained for liver volumetry on approximately 5000 datasets. We computed the absolute error of each automatically- and manually-derived volume relative to the mean manual volume. The mean processing time/dataset and method was recorded. Variations of liver volumes were compared using univariate generalized linear model analyses. A subgroup of 60 datasets was manually segmented by three radiologists, with a further subgroup of 20 segmented three times by each, to compare the automatically-derived results with the ground-truth. Results The mean absolute error of the automatically-derived measurement was 44.3 mL (representing 2.37 % of the averaged liver volumes). The liver volume was neither dependent on the contrast phase (p = 0.697), nor on the slice thickness (p = 0.446). The mean processing time/dataset with the algorithm was 9.94 s (sec) compared to manual segmentation with 219.34 s. We found an excellent agreement between both approaches with an ICC value of 0.996. Conclusion The results of our study demonstrate that AI-powered fully automated liver volumetric analyses can be done with excellent accuracy, reproducibility, robustness, speed and agreement with the manual segmentation.

The study aimed to determine the relationship between T2-weighted magnetic resonance imaging (MRI) signal and histologic sub-patterns in prostate cancer areas with different Gleason grades.MR images of prostates (n = 25) were obtained prior to radical prostatectomy. These were processed as whole-mount specimens with tumors and the peripheral zone was annotated digitally by two pathologists. Gleason grade 3 was the most prevalent grade and was subdivided into packed, intermediate, and sparse based on gland-to-stroma ratio. Large cribriform, intraductal carcinoma, and small cribriform glands (grade 4 group) were separately annotated but grouped together for statistical analysis. The log MRI signal intensity for each contoured region (n = 809) was measured, and pairwise comparisons were performed using the open-source software R version 3.0.1.Packed grade 3 sub-pattern has a significantly lower MRI intensity than the grade 4 group (P 0.00001). Sparse grade 3 has a significantly higher MRI intensity than the packed grade 3 sub-pattern (P 0.0001). No significant difference in MRI intensity was observed between the Gleason grade 4 group and the sparse sub-pattern grade 3 group (P = 0.54). In multivariable analysis adjusting for peripheral zone, the P values maintained significance (packed grade 3 group vs grade 4 group, P 0.001; and sparse grade 3 sub-pattern vs packed grade 3 sub-pattern, P 0.001).This study demonstrated that T2-weighted MRI signal is dependent on histologic sub-patterns within Gleason grades 3 and 4 cancers, which may have implications for directed biopsy sampling and patient management.

Prostate cancer (PCa) is a common, serious form of cancer in men that is still prevalent despite ongoing developments in diagnostic oncology. Current detection methods lead to high rates of inaccurate diagnosis. We present a method to directly model and exploit temporal aspects of temporal enhanced ultrasound (TeUS) for tissue characterization, which improves malignancy prediction. We employ a probabilistic-temporal framework, namely, hidden Markov models (HMMs), for modeling TeUS data obtained from PCa patients. We distinguish malignant from benign tissue by comparing the respective log-likelihood estimates generated by the HMMs. We analyze 1100 TeUS signals acquired from 12 patients. Our results show improved malignancy identification compared to previous results, demonstrating over 85% accuracy and AUC of 0.95. Incorporating temporal information directly into the models leads to improved tissue differentiation in PCa. We expect our method to generalize and be applied to other types of cancer in which temporal-ultrasound can be recorded.

Objectives : Temporal enhanced ultrasound (TeUS) is a new ultrasound-based imaging technique that provides tissue-specific information. Recent studies have shown the potential of TeUS for improving tissue characterization in prostate cancer diagnosis. We study the temporal properties of TeUS—temporal order and length—and present a new framework to assess their impact on tissue information. Methods : We utilize a probabilistic modeling approach using hidden Markov models (HMMs) to capture the temporal signatures of malignant and benign tissues from TeUS signals of nine patients. We model signals of benign and malignant tissues (284 and 286 signals, respectively) in their original temporal order as well as under order permutations. We then compare the resulting models using the Kullback–Liebler divergence and assess their performance differences in characterization. Moreover, we train HMMs using TeUS signals of different durations and compare their model performance when differentiating tissue types. Results : Our findings demonstrate that models of order-preserved signals perform statistically significantly better (85% accuracy) in tissue characterization compared to models of order-altered signals (62% accuracy). The performance degrades as more changes in signal order are introduced. Additionally, models trained on shorter sequences perform as accurately as models of longer sequences. Conclusion : The work presented here strongly indicates that temporal order has substantial impact on TeUS performance; thus, it plays a significant role in conveying tissue-specific information. Furthermore, shorter TeUS signals can relay sufficient information to accurately distinguish between tissue types. Significance : Understanding the impact of TeUS properties facilitates the process of its adopting in diagnostic procedures and provides insights on improving its acquisition.

Image guidance systems that register scans of the prostate obtained using transrectal ultrasound (TRUS) and magnetic resonance imaging are becoming increasingly popular as a means of enabling tumor-targeted prostate cancer biopsy and treatment. However, intraoperative segmentation of TRUS images to define the three-dimensional (3-D) geometry of the prostate remains a necessary task in existing guidance systems, which often require significant manual interaction and are subject to interoperator variability. Therefore, automating this step would lead to more acceptable clinical workflows and greater standardization between different operators and hospitals. In this work, a convolutional neural network (CNN) for automatically segmenting the prostate in two-dimensional (2-D) TRUS slices of a 3-D TRUS volume was developed and tested. The network was designed to be able to incorporate 3-D spatial information by taking one or more TRUS slices neighboring each slice to be segmented as input, in addition to these slices. The accuracy of the CNN was evaluated on data from a cohort of 109 patients who had undergone TRUS-guided targeted biopsy, (a total of 4034 2-D slices). The segmentation accuracy was measured by calculating 2-D and 3-D Dice similarity coefficients, on the 2-D images and corresponding 3-D volumes, respectively, as well as the 2-D boundary distances, using a 10-fold patient-level cross-validation experiment. However, incorporating neighboring slices did not improve the segmentation performance in five out of six experiment results, which include varying the number of neighboring slices from 1 to 3 at either side. The up-sampling shortcuts reduced the overall training time of the network, 161 min compared with 253 min without the architectural addition.

Objective: This paper presents the results of a new approach for selection of RF time series features based on joint independent component analysis for in vivo characterization of prostate cancer. Methods: We project three sets of RF time series features extracted from the spectrum, fractal dimension, and the wavelet transform of the ultrasound RF data on a space spanned by five joint independent components. Then, we demonstrate that the obtained mixing coefficients from a group of patients can be used to train a classifier, which can be applied to characterize cancerous regions of a test patient. Results: In a leave-one-patient-out cross validation, an area under receiver operating characteristic curve of 0.93 and classification accuracy of 84% are achieved. Conclusion: Ultrasound RF time series can be used to accurately characterize prostate cancer, in vivo without the need for exhaustive search in the feature space. Significance: We use joint independent component analysis for systematic fusion of multiple sets of RF time series features, within a machine learning framework, to characterize PCa in an in vivo study.

Though large-scale datasets are essential for training deep learning systems, it is expensive to scale up the collection of medical imaging datasets. Synthesizing the objects of interests, such as lung nodules, in medical images based on the distribution of annotated datasets can be helpful for improving the supervised learning tasks, especially when the datasets are limited by size and class balance. In this paper, we propose the class-aware adversarial synthesis framework to synthesize lung nodules in CT images. The framework is built with a coarse-to-fine patch in-painter (generator) and two class-aware discriminators. By conditioning on the random latent variables and the target nodule labels, the trained networks are able to generate diverse nodules given the same context. By evaluating on the public LIDC-IDRI dataset, we demonstrate an example application of the proposed framework for improving the accuracy of the lung nodule malignancy estimation as a binary classification problem, which is important in the lung screening scenario. We show that combining the real image patches and the synthetic lung nodules in the training set can improve the mean AUC classification score across different network architectures by 2%.

Prostate cancer is the third leading causes of death in men. However, the disease is curable if diagnosed early. During the past decades, multi-parametric magnetic resonance imaging (mpMRI) has been shown to be superior to trans-rectal ultrasound (TRUS) in detecting and localizing prostate cancer lesions to guide prostate biopsies and radiation therapies. The goal of this paper is to develop a simple and accurate graph-based regression framework for voxel-wise detection and grading of prostate cancer using mpMRIs. In the framework, groups of features were first extracted from the mpMRIs, and a graph-based multi-kernel model was proposed to learn the weights of the groups of features and the similarity matrix simultaneously. A Lapalacian regression model was then used to estimate the PI-RADS score of each voxels which characterizes how likely a voxel is cancerous. Experimental results of detection and grading of prostate lesions evaluated by six metrics show that the proposed method yielded convincing results.

Sonography synthesis has a wide range of applications, including medical procedure simulation, clinical training and multimodality image registration. In this paper, we propose a machine learning approach to simulate ultrasound images at given 3D spatial locations (relative to the patient anatomy), based on conditional generative adversarial networks (GANs). In particular, we introduce a novel neural network architecture that can sample anatomically accurate images conditionally on spatial position of the (real or mock) freehand ultrasound probe. To ensure an effective and efficient spatial information assimilation, the proposed spatially-conditioned GANs take calibrated pixel coordinates in global physical space as conditioning input, and utilise residual network units and shortcuts of conditioning data in the GANs' discriminator and generator, respectively. Using optically tracked B-mode ultrasound images, acquired by an experienced sonographer on a fetus phantom, we demonstrate the feasibility of the proposed method by two sets of quantitative results: distances were calculated between corresponding anatomical landmarks identified in the held-out ultrasound images and the simulated data at the same locations unseen to the networks; a usability study was carried out to distinguish the simulated data from the real images. In summary, we present what we believe are state-of-the-art visually realistic ultrasound images, simulated by the proposed GAN architecture that is stable to train and capable of generating plausibly diverse image samples., Comment: Accepted to MICCAI RAMBO 2017

To develop and evaluate a technique for the registration of in vivo prostate magnetic resonance (MR) images to digital histopathologic images by using image-guided specimen slicing based on strand-shaped fiducial markers relating specimen imaging to histopathologic examination.The study was approved by the institutional review board (the University of Western Ontario Health Sciences Research Ethics Board, London, Ontario, Canada), and written informed consent was obtained from all patients. This work proposed and evaluated a technique utilizing developed fiducial markers and real-time three-dimensional visualization in support of image guidance for ex vivo prostate specimen slicing parallel to the MR imaging planes prior to digitization, simplifying the registration process. Means, standard deviations, root-mean-square errors, and 95% confidence intervals are reported for all evaluated measurements.The slicing error was within the 2.2 mm thickness of the diagnostic-quality MR imaging sections, with a tissue block thickness standard deviation of 0.2 mm. Rigid registration provided negligible postregistration overlap of the smallest clinically important tumors (0.2 cm(3)) at histologic examination and MR imaging, whereas the tested nonrigid registration method yielded a mean target registration error of 1.1 mm and provided useful coregistration of such tumors.This method for the registration of prostate digital histopathologic images to in vivo MR images acquired by using an endorectal receive coil was sufficiently accurate for coregistering the smallest clinically important lesions with 95% confidence.

Diagnosing illnesses, developing and comparing treatment methods, and conducting research on the organization of the peripheral nervous system often require the analysis of peripheral nerve images to quantify the number, myelination, and size of axons in a nerve. Current methods that require manually labeling each axon can be extremely time-consuming as a single nerve can contain thousands of axons. To improve efficiency, we developed a computer-assisted axon identification and analysis method that is capable of analyzing and measuring sub-images covering the nerve cross-section, acquired using a scanning electron microscope. This algorithm performs three main procedures - it first uses cross-correlation to combine the acquired sub-images into a large image showing the entire nerve cross-section, then identifies and individually labels axons using a series of image intensity and shape criteria, and finally identifies and labels the myelin sheath of each axon using a region growing algorithm with the geometric centers of axons as seeds. To ensure accurate analysis of the image, we incorporated manual supervision to remove mislabeled axons and add missed axons. The typical user-assisted processing time for a two-megapixel image containing over 2000 axons was less than 1h. This speed was almost eight times faster than the time required to manually process the same image. Our method has proven to be well suited for identifying axons and their characteristics, and represents a significant time savings over traditional manual methods.

Purpose Defining prostate cancer (PCa) lesion clinical target volumes (CTVs) for multiparametric magnetic resonance imaging (mpMRI) could support focal boosting or treatment to improve outcomes or lower morbidity, necessitating appropriate CTV margins for mpMRI-defined gross tumor volumes (GTVs). This study aimed to identify CTV margins yielding 95% coverage of PCa tumors for prospective cases with high likelihood. Methods and Materials Twenty-five men with biopsy-confirmed clinical stage T1 or T2 PCa underwent pre-prostatectomy mpMRI, yielding T2-weighted, dynamic contrast-enhanced, and apparent diffusion coefficient images. Digitized whole-mount histology was contoured and registered to mpMRI scans (error ≤2 mm). Four observers contoured lesion GTVs on each mpMRI scan. CTVs were defined by isotropic and anisotropic expansion from these GTVs and from multiparametric (unioned) GTVs from 2 to 3 scans. Histologic coverage (proportions of tumor area on co-registered histology inside the CTV, measured for Gleason scores [GSs] ≥6 and ≥7) and prostate sparing (proportions of prostate volume outside the CTV) were measured. Nonparametric histologic-coverage prediction intervals defined minimal margins yielding 95% coverage for prospective cases with 78% to 92% likelihood. Results On analysis of 72 true-positive tumor detections, 95% coverage margins were 9 to 11 mm (GS ≥ 6) and 8 to 10 mm (GS ≥ 7) for single-sequence GTVs and were 8 mm (GS ≥ 6) and 6 mm (GS ≥ 7) for 3-sequence GTVs, yielding CTVs that spared 47% to 81% of prostate tissue for the majority of tumors. Inclusion of T2-weighted contours increased sparing for multiparametric CTVs with 95% coverage margins for GS ≥6, and inclusion of dynamic contrast-enhanced contours increased sparing for GS ≥7. Anisotropic 95% coverage margins increased the sparing proportions to 71% to 86%. Conclusions Multiparametric magnetic resonance imaging–defined GTVs expanded by appropriate margins may support focal boosting or treatment of PCa; however, these margins, accounting for interobserver and intertumoral variability, may preclude highly conformal CTVs. Multiparametric GTVs and anisotropic margins may reduce the required margins and improve prostate sparing.

Recent studies highlight temporal ultrasound data as highly promising in differentiating between malignant and benign tissues in prostate cancer patients. Since Hidden Markov Models can be used for capturing order and patterns in time varying signals, we employ them to model temporal aspects of ultrasound data that are typically not incorporated in existing models. By comparing order-preserving and orderaltering models, we demonstrate that the order encoded in the series is necessary to model the variability in ultrasound data of prostate tissues. In future studies, we will investigate the influence of order on the differentiation between malignant and benign tissues.

This paper presents the results of a computer-aided intervention solution to demonstrate the application of RF time series for characterization of prostate cancer, in vivo. Methods: We pre-process RF time series features extracted from 14 patients using hierarchical clustering to remove possible outliers. Then, we demonstrate that the mean central frequency and wavelet features extracted from a group of patients can be used to build a nonlinear classifier which can be applied successfully to differentiate between cancerous and normal tissue regions of an unseen patient. Results: In a cross-validation strategy, we show an average area under receiver operating characteristic curve (AUC) of 0.93 and classification accuracy of 80%. To validate our results, we present a detailed ultrasound to histology registration framework. Conclusion: Ultrasound RF time series results in differentiation of cancerous and normal tissue with high AUC.

Purpose: MRI-targeted, 3D transrectal ultrasound (TRUS)-guided prostate biopsy aims to reduce the 21–47% false negative rate1 of clinical 2D TRUS-guided sextant biopsy, but still has a substantial false negative rate. This could be improved via biopsy needle target optimization, accounting for uncertainties due to guidance system errors and image registration errors. As an initial step toward this broader goal, we elucidated the impact of biopsy needle delivery error on the probability of obtaining tumour samples and on core involvement. These are both important parameters to patient risk stratification and treatment decision. Methods: We investigated this for cancer of all grades, and separately for intermediate/high grade (≥Gleason 4+3) cancer. We used expert-contoured gold-standard prostatectomy histology to simulate targeted biopsies using an isotropic Gaussian needle delivery error from 1 to 6 mm, and investigated the amount of cancer obtained in each biopsy core as determined by histology. Results: Needle delivery error resulted in core involvement variability that could influence treatment decisions; the presence or absence of cancer in 1/3 or more of each needle core can be attributed to needle delivery error of 4 mm (as observed in practice2). Conclusions: Repeated biopsies of the same tumour target can yield percent core involvement measures with sufficient variability to influence the decision between active surveillance and treatment. However, this may be mitigated by making more than one biopsy attempt at selected tumour targets.