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.

Denoising diffusion probabilistic models (DDPMs) have achieved unprecedented success in computer vision. However, they remain underutilized in medical imaging, a field crucial for disease diagnosis and treatment planning. This is primarily due to the high computational cost associated with the use of large number of time steps (e.g., 1,000) in diffusion processes. Training a diffusion model on medical images typically takes days to weeks, while sampling each image volume takes minutes to hours. To address this challenge, we introduce Fast-DDPM, a simple yet effective approach capable of simultaneously improving training speed, sampling speed, and generation quality. Unlike DDPM, which trains the image denoiser across 1,000 time steps, Fast-DDPM trains and samples using only 10 time steps. The key to our method lies in aligning the training and sampling procedures to optimize time-step utilization. Specifically, we introduced two efficient noise schedulers with 10 time steps: one with uniform time step sampling and another with non-uniform sampling. We evaluated Fast-DDPM across three medical image-to-image generation tasks: multi-image super-resolution, image denoising, and image-to-image translation. Fast-DDPM outperformed DDPM and current state-of-the-art methods based on convolutional networks and generative adversarial networks in all tasks. Additionally, Fast-DDPM reduced the training time to 0.2× and the sampling time to 0.01× compared to DDPM. Our code is publicly available at: https://github.com/mirthAI/Fast-DDPM.

Micro-ultrasound (micro-US) is a novel 29-MHz ultrasound technique that provides 3-4 times higher resolution than traditional ultrasound, potentially enabling low-cost, accurate diagnosis of prostate cancer. Accurate prostate segmentation is crucial for prostate volume measurement, cancer diagnosis, prostate biopsy, and treatment planning. However, prostate segmentation on micro-US is challenging due to artifacts and indistinct borders between the prostate, bladder, and urethra in the midline. This paper presents MicroSegNet, a multi-scale annotation-guided transformer UNet model designed specifically to tackle these challenges. During the training process, MicroSegNet focuses more on regions that are hard to segment (hard regions), characterized by discrepancies between expert and non-expert annotations. We achieve this by proposing an annotation-guided binary cross entropy (AG-BCE) loss that assigns a larger weight to prediction errors in hard regions and a lower weight to prediction errors in easy regions. The AG-BCE loss was seamlessly integrated into the training process through the utilization of multi-scale deep supervision, enabling MicroSegNet to capture global contextual dependencies and local information at various scales. We trained our model using micro-US images from 55 patients, followed by evaluation on 20 patients. Our MicroSegNet model achieved a Dice coefficient of 0.939 and a Hausdorff distance of 2.02 mm, outperforming several state-of-the-art segmentation methods, as well as three human annotators with different experience levels. Our code is publicly available at https://github.com/mirthAI/MicroSegNet and our dataset is publicly available at https://zenodo.org/records/10475293.

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.

The use of MRI for prostate cancer diagnosis and treatment is increasing rapidly. However, identifying the presence and extent of cancer on MRI remains challenging, leading to high variability in detection even among expert radiologists. Improvement in cancer detection on MRI is essential to reducing this variability and maximizing the clinical utility of MRI. To date, such improvement has been limited by the lack of accurately labeled MRI datasets. Data from patients who underwent radical prostatectomy enables the spatial alignment of digitized histopathology images of the resected prostate with corresponding pre-surgical MRI. This alignment facilitates the delineation of detailed cancer labels on MRI via the projection of cancer from histopathology images onto MRI. We introduce a framework that performs 3D registration of whole-mount histopathology images to pre-surgical MRI in three steps. First, we developed a novel multi-image super-resolution generative adversarial network (miSRGAN), which learns information useful for 3D registration by producing a reconstructed 3D MRI. Second, we trained the network to learn information between histopathology slices to facilitate the application of 3D registration methods. Third, we registered the reconstructed 3D histopathology volumes to the reconstructed 3D MRI, mapping the extent of cancer from histopathology images onto MRI without the need for slice-to-slice correspondence. When compared to interpolation methods, our super-resolution reconstruction resulted in the highest PSNR relative to clinical 3D MRI (32.15 dB vs 30.16 dB for BSpline interpolation). Moreover, the registration of 3D volumes reconstructed via super-resolution for both MRI and histopathology images showed the best alignment of cancer regions when compared to (1) the state-of-the-art RAPSODI approach, (2) volumes that were not reconstructed, or (3) volumes that were reconstructed using nearest neighbor, linear, or BSpline interpolations. The improved 3D alignment of histopathology images and MRI facilitates the projection of accurate cancer labels on MRI, allowing for the development of improved MRI interpretation schemes and machine learning models to automatically detect cancer on MRI.

Deep learning has become the de facto method for medical image segmentation, with 3D segmentation models excelling in capturing complex 3D structures and 2D models offering high computational efficiency. However, segmenting 2.5D images, characterized by high in-plane resolution but lower through-plane resolution, presents significant challenges. While applying 2D models to individual slices of a 2.5D image is feasible, it fails to capture the spatial relationships between slices. On the other hand, 3D models face challenges such as resolution inconsistencies in 2.5D images, along with computational complexity and susceptibility to overfitting when trained with limited data. In this context, 2.5D models, which capture inter-slice correlations using only 2D neural networks, emerge as a promising solution due to their reduced computational demand and simplicity in implementation. In this paper, we introduce CSA-Net, a flexible 2.5D segmentation model capable of processing 2.5D images with an arbitrary number of slices. CSA-Net features an innovative Cross-Slice Attention (CSA) module that effectively captures 3D spatial information by learning long-range dependencies between the center slice (for segmentation) and its neighboring slices. Moreover, CSA-Net utilizes the self-attention mechanism to learn correlations among pixels within the center slice. We evaluated CSA-Net on three 2.5D segmentation tasks: (1) multi-class brain MR image segmentation, (2) binary prostate MR image segmentation, and (3) multi-class prostate MR image segmentation. CSA-Net outperformed leading 2D, 2.5D, and 3D segmentation methods across all three tasks, achieving average Dice coefficients and HD95 values of 0.897 and 1.40 mm for the brain dataset, 0.921 and 1.06 mm for the prostate dataset, and 0.659 and 2.70 mm for the ProstateX dataset, demonstrating its efficacy and superiority. Our code is publicly available at: https://github.com/mirthAI/CSA-Net.