Search

Interpreting traditional B-mode ultrasound images can be challenging due to image artifacts (e.g., shadowing, speckle), leading to low sensitivity and limited diagnostic accuracy. While Magnetic Resonance Imaging (MRI) has been proposed as a solution, it is expensive and not widely available. Furthermore, most biopsies are guided by Transrectal Ultrasound (TRUS) alone and can miss up to 52% cancers, highlighting the need for improved targeting. To address this issue, we propose ProsDectNet, a multi-task deep learning approach that localizes prostate cancer on B-mode ultrasound. Our model is pre-trained using radiologist-labeled data and fine-tuned using biopsy-confirmed labels. ProsDectNet includes a lesion detection and patch classification head, with uncertainty minimization using entropy to improve model performance and reduce false positive predictions. We trained and validated ProsDectNet using a cohort of 289 patients who underwent MRI-TRUS fusion targeted biopsy. We then tested our approach on a group of 41 patients and found that ProsDectNet outperformed the average expert clinician in detecting prostate cancer on B-mode ultrasound images, achieving a patient-level ROC-AUC of 82%, a sensitivity of 74%, and a specificity of 67%. Our results demonstrate that ProsDectNet has the potential to be used as a computer-aided diagnosis system to improve targeted biopsy and treatment planning., Comment: Accepted in NeurIPS 2023 (Medical Imaging meets NeurIPS Workshop)

Renal cell carcinoma (RCC) is a common cancer that varies in clinical behavior. Indolent RCC is often low-grade without necrosis and can be monitored without treatment. Aggressive RCC is often high-grade and can cause metastasis and death if not promptly detected and treated. While most kidney cancers are detected on CT scans, grading is based on histology from invasive biopsy or surgery. Determining aggressiveness on CT images is clinically important as it facilitates risk stratification and treatment planning. This study aims to use machine learning methods to identify radiology features that correlate with features on pathology to facilitate assessment of cancer aggressiveness on CT images instead of histology. This paper presents a novel automated method, Correlated Feature Aggregation By Region (CorrFABR), for classifying aggressiveness of clear cell RCC by leveraging correlations between radiology and corresponding unaligned pathology images. CorrFABR consists of three main steps: (1) Feature Aggregation where region-level features are extracted from radiology and pathology images, (2) Fusion where radiology features correlated with pathology features are learned on a region level, and (3) Prediction where the learned correlated features are used to distinguish aggressive from indolent clear cell RCC using CT alone as input. Thus, during training, CorrFABR learns from both radiology and pathology images, but during inference, CorrFABR will distinguish aggressive from indolent clear cell RCC using CT alone, in the absence of pathology images. CorrFABR improved classification performance over radiology features alone, with an increase in binary classification F1-score from 0.68 (0.04) to 0.73 (0.03). This demonstrates the potential of incorporating pathology disease characteristics for improved classification of aggressiveness of clear cell RCC on CT images., Comment: Submitted to Medical Image Analysis

Prostate biopsy and image-guided treatment procedures are often performed under the guidance of ultrasound fused with magnetic resonance images (MRI). Accurate image fusion relies on accurate segmentation of the prostate on ultrasound images. Yet, the reduced signal-to-noise ratio and artifacts (e.g., speckle and shadowing) in ultrasound images limit the performance of automated prostate segmentation techniques and generalizing these methods to new image domains is inherently difficult. In this study, we address these challenges by introducing a novel 2.5D deep neural network for prostate segmentation on ultrasound images. Our approach addresses the limitations of transfer learning and finetuning methods (i.e., drop in performance on the original training data when the model weights are updated) by combining a supervised domain adaptation technique and a knowledge distillation loss. The knowledge distillation loss allows the preservation of previously learned knowledge and reduces the performance drop after model finetuning on new datasets. Furthermore, our approach relies on an attention module that considers model feature positioning information to improve the segmentation accuracy. We trained our model on 764 subjects from one institution and finetuned our model using only ten subjects from subsequent institutions. We analyzed the performance of our method on three large datasets encompassing 2067 subjects from three different institutions. Our method achieved an average Dice Similarity Coefficient (Dice) of $94.0\pm0.03$ and Hausdorff Distance (HD95) of 2.28 $mm$ in an independent set of subjects from the first institution. Moreover, our model generalized well in the studies from the other two institutions (Dice: $91.0\pm0.03$; HD95: 3.7$mm$ and Dice: $82.0\pm0.03$; HD95: 7.1 $mm$)., Comment: Accepted to the journal of Medical Image Analysis (MedIA)

Image registration is useful for quantifying morphological changes in longitudinal MR images from prostate cancer patients. This paper describes a development in improving the learning-based registration algorithms, for this challenging clinical application often with highly variable yet limited training data. First, we report that the latent space can be clustered into a much lower dimensional space than that commonly found as bottleneck features at the deep layer of a trained registration network. Based on this observation, we propose a hierarchical quantization method, discretizing the learned feature vectors using a jointly-trained dictionary with a constrained size, in order to improve the generalisation of the registration networks. Furthermore, a novel collaborative dictionary is independently optimised to incorporate additional prior information, such as the segmentation of the gland or other regions of interest, in the latent quantized space. Based on 216 real clinical images from 86 prostate cancer patients, we show the efficacy of both the designed components. Improved registration accuracy was obtained with statistical significance, in terms of both Dice on gland and target registration error on corresponding landmarks, the latter of which achieved 5.46 mm, an improvement of 28.7\% from the baseline without quantization. Experimental results also show that the difference in performance was indeed minimised between training and testing data., Comment: preprint version, accepted for MICCAI 2022 (25th International Conference on Medical Image Computing and Computer Assisted Intervention)

In this paper, we consider image quality assessment (IQA) as a measure of how images are amenable with respect to a given downstream task, or task amenability. When the task is performed using machine learning algorithms, such as a neural-network-based task predictor for image classification or segmentation, the performance of the task predictor provides an objective estimate of task amenability. In this work, we use an IQA controller to predict the task amenability which, itself being parameterised by neural networks, can be trained simultaneously with the task predictor. We further develop a meta-reinforcement learning framework to improve the adaptability for both IQA controllers and task predictors, such that they can be fine-tuned efficiently on new datasets or meta-tasks. We demonstrate the efficacy of the proposed task-specific, adaptable IQA approach, using two clinical applications for ultrasound-guided prostate intervention and pneumonia detection on X-ray images., Comment: Accepted to Medical Image Analysis; Final published version available at: https://doi.org/10.1016/j.media.2022.102427

Image quality assessment (IQA) in medical imaging can be used to ensure that downstream clinical tasks can be reliably performed. Quantifying the impact of an image on the specific target tasks, also named as task amenability, is needed. A task-specific IQA has recently been proposed to learn an image-amenability-predicting controller simultaneously with a target task predictor. This allows for the trained IQA controller to measure the impact an image has on the target task performance, when this task is performed using the predictor, e.g. segmentation and classification neural networks in modern clinical applications. In this work, we propose an extension to this task-specific IQA approach, by adding a task-agnostic IQA based on auto-encoding as the target task. Analysing the intersection between low-quality images, deemed by both the task-specific and task-agnostic IQA, may help to differentiate the underpinning factors that caused the poor target task performance. For example, common imaging artefacts may not adversely affect the target task, which would lead to a low task-agnostic quality and a high task-specific quality, whilst individual cases considered clinically challenging, which can not be improved by better imaging equipment or protocols, is likely to result in a high task-agnostic quality but a low task-specific quality. We first describe a flexible reward shaping strategy which allows for the adjustment of weighting between task-agnostic and task-specific quality scoring. Furthermore, we evaluate the proposed algorithm using a clinically challenging target task of prostate tumour segmentation on multiparametric magnetic resonance (mpMR) images, from 850 patients. The proposed reward shaping strategy, with appropriately weighted task-specific and task-agnostic qualities, successfully identified samples that need re-acquisition due to defected imaging process., Comment: Accepted for publication at the Journal of Machine Learning for Biomedical Imaging (MELBA) https://www.melba-journal.org

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi-task medical image registration data set for comprehensive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https://learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, accuracy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image registration. This paper describes datasets, tasks, evaluation methods and results of the challenge, as well as results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias. While no single approach worked best across all tasks, many methodological aspects could be identified that push the performance of medical image registration to new state-of-the-art performance. Furthermore, we demystified the common belief that conventional registration methods have to be much slower than deep-learning-based methods.

Prostate cancer is the second deadliest cancer for American men. While Magnetic Resonance Imaging (MRI) is increasingly used to guide targeted biopsies for prostate cancer diagnosis, its utility remains limited due to high rates of false positives and false negatives as well as low inter-reader agreements. Machine learning methods to detect and localize cancer on prostate MRI can help standardize radiologist interpretations. However, existing machine learning methods vary not only in model architecture, but also in the ground truth labeling strategies used for model training. In this study, we compare different labeling strategies, namely, pathology-confirmed radiologist labels, pathologist labels on whole-mount histopathology images, and lesion-level and pixel-level digital pathologist labels (previously validated deep learning algorithm on histopathology images to predict pixel-level Gleason patterns) on whole-mount histopathology images. We analyse the effects these labels have on the performance of the trained machine learning models. Our experiments show that (1) radiologist labels and models trained with them can miss cancers, or underestimate cancer extent, (2) digital pathologist labels and models trained with them have high concordance with pathologist labels, and (3) models trained with digital pathologist labels achieve the best performance in prostate cancer detection in two different cohorts with different disease distributions, irrespective of the model architecture used. Digital pathologist labels can reduce challenges associated with human annotations, including labor, time, inter- and intra-reader variability, and can help bridge the gap between prostate radiology and pathology by enabling the training of reliable machine learning models to detect and localize prostate cancer on MRI., Comment: Indrani Bhattacharya and David S. Lim contributed equally as first authors. Geoffrey A. Sonn and Mirabela Rusu contributed equally as senior authors

The interpretation of prostate MRI suffers from low agreement across radiologists due to the subtle differences between cancer and normal tissue. Image registration addresses this issue by accurately mapping the ground-truth cancer labels from surgical histopathology images onto MRI. Cancer labels achieved by image registration can be used to improve radiologists' interpretation of MRI by training deep learning models for early detection of prostate cancer. A major limitation of current automated registration approaches is that they require manual prostate segmentations, which is a time-consuming task, prone to errors. This paper presents a weakly supervised approach for affine and deformable registration of MRI and histopathology images without requiring prostate segmentations. We used manual prostate segmentations and mono-modal synthetic image pairs to train our registration networks to align prostate boundaries and local prostate features. Although prostate segmentations were used during the training of the network, such segmentations were not needed when registering unseen images at inference time. We trained and validated our registration network with 135 and 10 patients from an internal cohort, respectively. We tested the performance of our method using 16 patients from the internal cohort and 22 patients from an external cohort. The results show that our weakly supervised method has achieved significantly higher registration accuracy than a state-of-the-art method run without prostate segmentations. Our deep learning framework will ease the registration of MRI and histopathology images by obviating the need for prostate segmentations., Comment: Accepted to MICCAI 2021

Magnetic resonance imaging (MRI) is an increasingly important tool for the diagnosis and treatment of prostate cancer. However, interpretation of MRI suffers from high inter-observer variability across radiologists, thereby contributing to missed clinically significant cancers, overdiagnosed low-risk cancers, and frequent false positives. Interpretation of MRI could be greatly improved by providing radiologists with an answer key that clearly shows cancer locations on MRI. Registration of histopathology images from patients who had radical prostatectomy to pre-operative MRI allows such mapping of ground truth cancer labels onto MRI. However, traditional MRI-histopathology registration approaches are computationally expensive and require careful choices of the cost function and registration hyperparameters. This paper presents ProsRegNet, a deep learning-based pipeline to accelerate and simplify MRI-histopathology image registration in prostate cancer. Our pipeline consists of image preprocessing, estimation of affine and deformable transformations by deep neural networks, and mapping cancer labels from histopathology images onto MRI using estimated transformations. We trained our neural network using MR and histopathology images of 99 patients from our internal cohort (Cohort 1) and evaluated its performance using 53 patients from three different cohorts (an additional 12 from Cohort 1 and 41 from two public cohorts). Results show that our deep learning pipeline has achieved more accurate registration results and is at least 20 times faster than a state-of-the-art registration algorithm. This important advance will provide radiologists with highly accurate prostate MRI answer keys, thereby facilitating improvements in the detection of prostate cancer on MRI. Our code is freely available at https://github.com/pimed//ProsRegNet., Comment: Accepted to Medical Image Analysis (MedIA)

Magnetic Resonance Imaging (MRI) is widely used for screening and staging prostate cancer. However, many prostate cancers have subtle features which are not easily identifiable on MRI, resulting in missed diagnoses and alarming variability in radiologist interpretation. Machine learning models have been developed in an effort to improve cancer identification, but current models localize cancer using MRI-derived features, while failing to consider the disease pathology characteristics observed on resected tissue. In this paper, we propose CorrSigNet, an automated two-step model that localizes prostate cancer on MRI by capturing the pathology features of cancer. First, the model learns MRI signatures of cancer that are correlated with corresponding histopathology features using Common Representation Learning. Second, the model uses the learned correlated MRI features to train a Convolutional Neural Network to localize prostate cancer. The histopathology images are used only in the first step to learn the correlated features. Once learned, these correlated features can be extracted from MRI of new patients (without histopathology or surgery) to localize cancer. We trained and validated our framework on a unique dataset of 75 patients with 806 slices who underwent MRI followed by prostatectomy surgery. We tested our method on an independent test set of 20 prostatectomy patients (139 slices, 24 cancerous lesions, 1.12M pixels) and achieved a per-pixel sensitivity of 0.81, specificity of 0.71, AUC of 0.86 and a per-lesion AUC of $0.96 \pm 0.07$, outperforming the current state-of-the-art accuracy in predicting prostate cancer using MRI., Comment: Accepted to MICCAI 2020

The current study detects different morphologies related to prostate pathology using deep learning models; these models were evaluated on 2,121 hematoxylin and eosin (H&E) stain histology images captured using bright field microscopy, which spanned a variety of image qualities, origins (whole slide, tissue micro array, whole mount, Internet), scanning machines, timestamps, H&E staining protocols, and institutions. For case usage, these models were applied for the annotation tasks in clinician-oriented pathology reports for prostatectomy specimens. The true positive rate (TPR) for slides with prostate cancer was 99.7% by a false positive rate of 0.785%. The F1-scores of Gleason patterns reported in pathology reports ranged from 0.795 to 1.0 at the case level. TPR was 93.6% for the cribriform morphology and 72.6% for the ductal morphology. The correlation between the ground truth and the prediction for the relative tumor volume was 0.987 n. Our models cover the major components of prostate pathology and successfully accomplish the annotation tasks.

Magnetic resonance imaging (MRI) has great potential to improve prostate cancer diagnosis. It can spare men with a normal exam from undergoing invasive biopsy while making biopsies more accurate in men with lesions suspicious for cancer. Yet, the subtle differences between cancer and confounding conditions, render the interpretation of MRI challenging. The tissue collected from patients that undergo pre-surgical MRI and radical prostatectomy provides a unique opportunity to correlate histopathology images of the entire prostate with MRI in order to accurately map the extent of prostate cancer onto MRI. Here, we introduce the RAPSODI (framework for the registration of radiology and pathology images. RAPSODI relies on a three-step procedure that first reconstructs in 3D the resected tissue using the serial whole-mount histopathology slices, then registers corresponding histopathology and MRI slices, and finally maps the cancer outlines from the histopathology slices onto MRI. We tested RAPSODI in a phantom study where we simulated various conditions, e.g., tissue specimen rotation upon mounting on glass slides, tissue shrinkage during fixation, or imperfect slice-to-slice correspondences between histology and MRI. Our experiments showed that RAPSODI can reliably correct for rotations within $\pm15^{\circ}$ and shrinkage up to 10%. We also evaluated RAPSODI in 89 patients from two institutions that underwent radical prostatectomy, yielding 543 histopathology slices that were registered to corresponding T2 weighted MRI slices. We found a Dice coefficient of 0.98$ \pm $0.01 for the prostate, prostate boundary Hausdorff distance of 1.71$ \pm $0.48 mm, a urethra deviation of 2.91$ \pm $1.25 mm, and a landmark deviation of 2.88$ \pm $0.70 mm between registered histopathology images and MRI. Our robust framework successfully mapped the extent of disease from histopathology slices onto MRI., Comment: version 2