Understanding individual cortical development is essential for identifying deviations linked to neurodevelopmental disorders. However, current normative modelling frameworks struggle to capture fine-scale anatomical details due to their reliance on modelling data within a population-average reference space. Here, we present a novel framework for learning individual growth trajectories from biomechanically constrained, longitudinal, diffeomorphic image registration, implemented via a hierarchical network architecture. Trained on neonatal MRI data from the Developing Human Connectome Project, the method improves the biological plausibility of warps, generating growth trajectories that better follow population-level trends while generating smoother warps, with fewer negative Jacobians, relative to state-of-the-art baselines. The resulting subject-specific deformations provide interpretable, biologically grounded mappings of development. This framework opens new possibilities for predictive modeling of brain maturation and early identification of malformations of cortical development.

We developed a generative patch based 3D image registration model that can register very high resolution images obtained from a biochemical process name tissue clearing. Tissue clearing process removes lipids and fats from the tissue and make the tissue transparent. When cleared tissues are imaged with Light-sheet fluorescent microscopy, the resulting images give a clear window to the cellular activities and dynamics inside the tissue.Thus the images obtained are very rich with cellular information and hence their resolution is extremely high (eg .2560x2160x676). Analyzing images with such high resolution is a difficult task for any image analysis pipeline.Image registration is a common step in image analysis pipeline when comparison between images are required. Traditional image registration methods fail to register images with such extant. In this paper we addressed this very high resolution image registration issue by proposing a patch-based generative network named InvGAN. Our proposed network can register very high resolution tissue cleared images. The tissue cleared dataset used in this paper are obtained from a tissue clearing protocol named CUBIC. We compared our method both with traditional and deep-learning based registration methods.Two different versions of CUBIC dataset are used, representing two different resolutions 25% and 100% respectively. Experiments on two different resolutions clearly show the impact of resolution on the registration quality. At 25% resolution, our method achieves comparable registration accuracy with very short time (7 minutes approximately). At 100% resolution, most of the traditional registration methods fail except Elastix registration tool.Elastix takes 28 hours to register where proposed InvGAN takes only 10 minutes.

The segmentation and tracking of living cells play a vital role within the biomedical domain, particularly in cancer research, drug development, and developmental biology. These are usually tedious and time-consuming tasks that are traditionally done by biomedical experts. Recently, to automatize these processes, deep learning based segmentation and tracking methods have been proposed. These methods require large-scale datasets and their full potential is constrained by the scarcity of annotated data in the biomedical imaging domain. To address this limitation, we propose Biomedical Video Diffusion Model (BVDM), capable of generating realistic-looking synthetic microscopy videos. Trained only on a single real video, BVDM can generate videos of arbitrary length with pixel-level annotations that can be used for training data-hungry models. It is composed of a denoising diffusion probabilistic model (DDPM) generating high-fidelity synthetic cell microscopy images and a flow prediction model (FPM) predicting the non-rigid transformation between consecutive video frames. During inference, initially, the DDPM imposes realistic cell textures on synthetic cell masks which are generated based on real data statistics. The flow prediction model predicts the flow field between consecutive masks and applies that to the DDPM output from the previous time frame to create the next one while keeping temporal consistency. BVDM outperforms state-of-the-art synthetic live cell microscopy video generation models. Furthermore, we demonstrate that a sufficiently large synthetic dataset enhances the performance of cell segmentation and tracking models compared to using a limited amount of available real data.

Cochlear implants (CIs) are neural prosthetics used to treat patients with severe-to-profound hearing loss. Patient-specific modeling of CI stimulation of the auditory nerve fiber (ANFs) can help audiologists improve the CI programming. These models require localization of the ANFs relative to surrounding anatomy and the CI. Localization is challenging because the ANFs are so small they are not directly visible in clinical imaging. In this work, we hypothesize the position of the ANFs can be accurately inferred from the location of the internal auditory canal (IAC), which has high contrast in CT, since the ANFs pass through this canal between the cochlea and the brain. Inspired by VoxelMorph, in this paper we propose a deep atlas-based IAC segmentation network. We create a single atlas in which the IAC and ANFs are pre-localized. Our network is trained to produce deformation fields (DFs) mapping coordinates from the atlas to new target volumes and that accurately segment the IAC. We hypothesize that DFs that accurately segment the IAC in target images will also facilitate accurate atlas-based localization of the ANFs. As opposed to VoxelMorph, which aims to produce DFs that accurately register the entire volume, our novel contribution is an entirely self-supervised training scheme that aims to produce DFs that accurately segment the target structure. This self-supervision is facilitated using a regional level set (LS) inspired loss function. We call our method Deep Atlas Based Segmentation using Level Sets (DABS-LS). Results show that DABS-LS outperforms VoxelMorph for IAC segmentation. Tests with publicly available datasets for trachea and kidney segmentation also show significant improvement in segmentation accuracy, demonstrating the generalizability of the method.

Image registration is the process of bringing different images into a common coordinate system - a technique widely used in various applications of computer vision, such as remote sensing, image retrieval, and, most commonly, medical imaging. Deep learning based techniques have been applied successfully to tackle various complex medical image processing problems, including medical image registration. Over the years, several image registration techniques have been proposed using deep learning. Deformable image registration techniques such as Voxelmorph have been successful in capturing finer changes and providing smoother deformations. However, Voxelmorph, as well as ICNet and FIRE, do not explicitly encode global dependencies (i.e. the overall anatomical view of the supplied image) and, therefore, cannot track large deformations. In order to tackle the aforementioned problems, this paper extends the Voxelmorph approach in three different ways. To improve the performance in case of small as well as large deformations, supervision of the model at different resolutions has been integrated using a multi-scale UNet. To support the network to learn and encode the minute structural co-relations of the given image-pairs, a self-constructing graph network (SCGNet) has been used as the latent of the multi-scale UNet - which can improve the learning process of the model and help the model to generalise better. And finally, to make the deformations inverse-consistent, cycle consistency loss has been employed. On the task of registration of brain MRIs, the proposed method achieved significant improvements over ANTs and VoxelMorph, obtaining a Dice score of 0.8013 \pm 0.0243 for intramodal and 0.6211 \pm 0.0309 for intermodal, while VoxelMorph achieved 0.7747 \pm 0.0260 and 0.6071 \pm 0.0510, respectively

Longitudinal assessment of brain atrophy, particularly in the hippocampus, is a well-studied biomarker for neurodegenerative diseases, such as Alzheimer's disease (AD). In clinical trials, estimation of brain progressive rates can be applied to track therapeutic efficacy of disease modifying treatments. However, most state-of-the-art measurements calculate changes directly by segmentation and/or deformable registration of MRI images, and may misreport head motion or MRI artifacts as neurodegeneration, impacting their accuracy. In our previous study, we developed a deep learning method DeepAtrophy that uses a convolutional neural network to quantify differences between longitudinal MRI scan pairs that are associated with time. DeepAtrophy has high accuracy in inferring temporal information from longitudinal MRI scans, such as temporal order or relative inter-scan interval. DeepAtrophy also provides an overall atrophy score that was shown to perform well as a potential biomarker of disease progression and treatment efficacy. However, DeepAtrophy is not interpretable, and it is unclear what changes in the MRI contribute to progression measurements. In this paper, we propose Regional Deep Atrophy (RDA), which combines the temporal inference approach from DeepAtrophy with a deformable registration neural network and attention mechanism that highlights regions in the MRI image where longitudinal changes are contributing to temporal inference. RDA has similar prediction accuracy as DeepAtrophy, but its additional interpretability makes it more acceptable for use in clinical settings, and may lead to more sensitive biomarkers for disease monitoring in clinical trials of early AD.

Unsupervised learning-based medical image registration approaches have witnessed rapid development in recent years. We propose to revisit a commonly ignored while simple and well-established principle: recursive refinement of deformation vector fields across scales. We introduce a recursive refinement network (RRN) for unsupervised medical image registration, to extract multi-scale features, construct normalized local cost correlation volume and recursively refine volumetric deformation vector fields. RRN achieves state of the art performance for 3D registration of expiratory-inspiratory pairs of CT lung scans. On DirLab COPDGene dataset, RRN returns an average Target Registration Error (TRE) of 0.83 mm, which corresponds to a 13% error reduction from the best result presented in the leaderboard. In addition to comparison with conventional methods, RRN leads to 89% error reduction compared to deep-learning-based peer approaches.

The recent application of Deep Learning in various areas of medical image analysis has brought excellent performance gain. The application of deep learning technologies in medical image registration successfully outperformed traditional optimization based registration algorithms both in registration time and accuracy. In this paper, we present a densely connected convolutional architecture for deformable image registration. The training of the network is unsupervised and does not require ground-truth deformation or any synthetic deformation as a label. The proposed architecture is trained and tested on two different version of tissue cleared data, 10\% and 25\% resolution of high resolution dataset respectively and demonstrated comparable registration performance with the state-of-the-art ANTS registration method. The proposed method is also compared with the deep-learning based Voxelmorph registration method. Due to the memory limitation, original voxelmorph can work at most 15\% resolution of Tissue cleared data. For rigorous experimental comparison we developed a patch-based version of Voxelmorph network, and trained it on 10\% and 25\% resolution. In both resolution, proposed DenseDeformation network outperformed Voxelmorph in registration accuracy.

Deformable registration of clinical scans is a fundamental task for many applications, such as population studies or the monitoring of long-term disease progression in individual patients. This task is challenging because, in contrast to high-resolution research-quality scans, clinical images are often sparse, missing up to 85% of the slices in comparison. Furthermore, the anatomy in the acquired slices is not consistent across scans because of variations in patient orientation with respect to the scanner. In this work, we introduce Sparse VoxelMorph (SparseVM), which adapts a state-of-the-art learning-based registration method to improve the registration of sparse clinical images. SparseVM is a fast, unsupervised method that weights voxel contributions to registration in proportion to confidence in the voxels. This leads to improved registration performance on volumes with voxels of varying reliability, such as interpolated clinical scans. SparseVM registers 3D scans in under a second on the GPU, which is orders of magnitudes faster than the best performing clinical registration methods, while still achieving comparable accuracy. Because of its short runtimes and accurate behavior, SparseVM can enable clinical analyses not previously possible. The code is publicly available at voxelmorph.mit.edu.

MIT has published details of "VoxelMorph", a new machine-learning algorithm, which is over 1,000 times faster at registering brain scans and other 3-D images. Medical image registration is a common technique that involves overlaying two images – such as magnetic resonance imaging (MRI) scans – to compare and analyse anatomical differences in great detail. If a patient has a brain tumour, for instance, doctors can overlap a brain scan from several months ago onto a more recent scan to analyse small changes in the tumour's progress. Unfortunately, this process can often take hours, as traditional systems meticulously align each of potentially a million pixels in the combined scans. In a pair of upcoming conference papers, however, researchers from the Massachusetts Institute of Technology (MIT) describe how to overcome this problem.