BreastRegNet: A Deep Learning Framework for Registration of Breast Faxitron and Histopathology Images

A standard treatment protocol for breast cancer entails administering neoadjuvant therapy followed by surgical removal of the tumor and surrounding tissue. Pathologists typically rely on cabinet X-ray radiographs, known as Faxitron, to examine the excised breast tissue and diagnose the extent of residual disease. However, accurately determining the location, size, and focality of residual cancer can be challenging, and incorrect assessments can lead to clinical consequences. The utilization of automated methods can improve the histopathology process, allowing pathologists to choose regions for sampling more effectively and precisely. Despite the recognized necessity, there are currently no such methods available. Training such automated detection models require accurate ground truth labels on ex-vivo radiology images, which can be acquired through registering Faxitron and histopathology images and mapping the extent of cancer from histopathology to x-ray images. This study introduces a deep learning-based image registration approach trained on mono-modal synthetic image pairs. The models were trained using data from 50 women who received neoadjuvant chemotherapy and underwent surgery. The results demonstrate that our method is faster and yields significantly lower average landmark error ($2.1\pm1.96$ mm) over the state-of-the-art iterative ($4.43\pm4.1$ mm) and deep learning ($4.02\pm3.15$ mm) approaches. Improved performance of our approach in integrating radiology and pathology information facilitates generating large datasets, which allows training models for more accurate breast cancer detection.

ProsDectNet: Bridging the Gap in Prostate Cancer Detection via Transrectal B-mode Ultrasound Imaging

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.

Correlated Feature Aggregation by Region Helps Distinguish Aggressive from Indolent Clear Cell Renal Cell Carcinoma Subtypes on CT

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.

Domain Generalization for Prostate Segmentation in Transrectal Ultrasound Images: A Multi-center Study

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 $mm$).

Collaborative Quantization Embeddings for Intra-Subject Prostate MR Image Registration

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.

ConFUDA: Contrastive Fewshot Unsupervised Domain Adaptation for Medical Image Segmentation

Unsupervised domain adaptation (UDA) aims to transfer knowledge learned from a labeled source domain to an unlabeled target domain. Contrastive learning (CL) in the context of UDA can help to better separate classes in feature space. However, in image segmentation, the large memory footprint due to the computation of the pixel-wise contrastive loss makes it prohibitive to use. Furthermore, labeled target data is not easily available in medical imaging, and obtaining new samples is not economical. As a result, in this work, we tackle a more challenging UDA task when there are only a few (fewshot) or a single (oneshot) image available from the target domain. We apply a style transfer module to mitigate the scarcity of target samples. Then, to align the source and target features and tackle the memory issue of the traditional contrastive loss, we propose the centroid-based contrastive learning (CCL) and a centroid norm regularizer (CNR) to optimize the contrastive pairs in both direction and magnitude. In addition, we propose multi-partition centroid contrastive learning (MPCCL) to further reduce the variance in the target features. Fewshot evaluation on MS-CMRSeg dataset demonstrates that ConFUDA improves the segmentation performance by 0.34 of the Dice score on the target domain compared with the baseline, and 0.31 Dice score improvement in a more rigorous oneshot setting.

Image quality assessment for machine learning tasks using meta-reinforcement learning

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.

Image quality assessment by overlapping task-specific and task-agnostic measures: application to prostate multiparametric MR images for cancer segmentation

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.

Learn2Reg: comprehensive multi-task medical image registration challenge, dataset and evaluation in the era of deep learning

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, in part because of the lack of availability of such diverse data. 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 benchmark 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, and the results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias.

Bridging the gap between prostate radiology and pathology through machine learning

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.