Nonlinear inter-modality registration is often challenging due to the lack of objective functions that are good proxies for alignment. Here we propose a synthesis-by-registration method to convert this problem into an easier intra-modality task. We i
ntroduce a registration loss for weakly supervised image translation between domains that does not require perfectly aligned training data. This loss capitalises on a registration U-Net with frozen weights, to drive a synthesis CNN towards the desired translation. We complement this loss with a structure preserving constraint based on contrastive learning, which prevents blurring and content shifts due to overfitting. We apply this method to the registration of histological sections to MRI slices, a key step in 3D histology reconstruction. Results on two different public datasets show improvements over registration based on mutual information (13% reduction in landmark error) and synthesis-based algorithms such as CycleGAN (11% reduction), and are comparable to a registration CNN with label supervision.
Purpose: To develop a semi-automated, AI-assisted workflow for segmentation of inflammatory lesions on STIR MRI of sacroiliac joints (SIJs) in adult patients with axial spondyloarthritis. Methods: Baseline human performance in manual segmentation o
f inflammatory lesions was first established in eight patients with axial spondyloarthritis recruited within a prospective study conducted between April 2018 and July 2019. To improve readers consistency a semi-automated procedure was developed, comprising (1) manual segmentation of normal bone and disease regions (2) automatic segmentation of lesions, i.e., voxels in the disease region with outlying intensity with respect to the normal bone, and (3) human intervention to remove erroneously segmented areas. Segmentation of disease region (subchondral bone) was automated via supervised deep learning; 200 image slices (eight subjects) were used for algorithm training with cross validation, 48 (two subjects) - for testing and 500 (20 subjects) - for evaluation based on visual assessment. The data, code, and model are available at https://github.com/c-hepburn/Bone_MRI. Human and model performance were assessed in terms of Dice coefficient. Results: Intra-reader median Dice coefficients, evaluated from comparison of manual segmentation trials of inflammatory lesions, were 0.63 and 0.69 for the two readers, respectively. Inter-reader median Dice was in the range of 0.53 to 0.56 and increased to 0.84 using the semi-automated approach. Deep learning model ensemble showed average Dice of 0.94 in subchondral bone segmentation. Conclusions: We describe a semi-automated, AI-assisted workflow which improves the objectivity and consistency of radiological segmentation of inflammatory load in SIJs.
Most existing algorithms for automatic 3D morphometry of human brain MRI scans are designed for data with near-isotropic voxels at approximately 1 mm resolution, and frequently have contrast constraints as well - typically requiring T1 scans (e.g., M
P-RAGE). This limitation prevents the analysis of millions of MRI scans acquired with large inter-slice spacing (thick slice) in clinical settings every year. The inability to quantitatively analyze these scans hinders the adoption of quantitative neuroimaging in healthcare, and precludes research studies that could attain huge sample sizes and hence greatly improve our understanding of the human brain. Recent advances in CNNs are producing outstanding results in super-resolution and contrast synthesis of MRI. However, these approaches are very sensitive to the contrast, resolution and orientation of the input images, and thus do not generalize to diverse clinical acquisition protocols - even within sites. Here we present SynthSR, a method to train a CNN that receives one or more thick-slice scans with different contrast, resolution and orientation, and produces an isotropic scan of canonical contrast (typically a 1 mm MP-RAGE). The presented method does not require any preprocessing, e.g., skull stripping or bias field correction. Crucially, SynthSR trains on synthetic input images generated from 3D segmentations, and can thus be used to train CNNs for any combination of contrasts, resolutions and orientations without high-resolution training data. We test the images generated with SynthSR in an array of common downstream analyses, and show that they can be reliably used for subcortical segmentation and volumetry, image registration (e.g., for tensor-based morphometry), and, if some image quality requirements are met, even cortical thickness morphometry. The source code is publicly available at github.com/BBillot/SynthSR.
We introduce a learning strategy for contrast-invariant image registration without requiring imaging data. While classical registration methods accurately estimate the spatial correspondence between images, they solve a costly optimization problem fo
r every image pair. Learning-based techniques are fast at test time, but can only register images with image contrast and geometric content that are similar to those available during training. We focus on removing this image-data dependency of learning methods. Our approach leverages a generative model for diverse label maps and images that exposes networks to a wide range of variability during training, forcing them to learn features invariant to image type (contrast). This strategy results in powerful networks trained to generalize to a broad array of real input images. We present extensive experiments, with a focus on 3D neuroimaging, showing that this strategy enables robust registration of arbitrary image contrasts without the need to retrain for new modalities. We demonstrate registration accuracy that most often surpasses the state of the art both within and across modalities, using a single model. Critically, we show that input labels from which we synthesize images need not be of actual anatomy: training on randomly generated geometric shapes also results in competitive registration performance, albeit slightly less accurate, while alleviating the dependency on real data of any kind. Our code is available at: http://voxelmorph.csail.mit.edu
Segmentation of structural and diffusion MRI (sMRI/dMRI) is usually performed independently in neuroimaging pipelines. However, some brain structures (e.g., globus pallidus, thalamus and its nuclei) can be extracted more accurately by fusing the two
modalities. Following the framework of Bayesian segmentation with probabilistic atlases and unsupervised appearance modeling, we present here a novel algorithm to jointly segment multi-modal sMRI/dMRI data. We propose a hierarchical likelihood term for the dMRI defined on the unit ball, which combines the Beta and Dimroth-Scheidegger-Watson distributions to model the data at each voxel. This term is integrated with a mixture of Gaussians for the sMRI data, such that the resulting joint unsupervised likelihood enables the analysis of multi-modal scans acquired with any type of MRI contrast, b-values, or number of directions, which enables wide applicability. We also propose an inference algorithm to estimate the maximum-a-posteriori model parameters from input images, and to compute the most likely segmentation. Using a recently published atlas derived from histology, we apply our method to thalamic nuclei segmentation on two datasets: HCP (state of the art) and ADNI (legacy) - producing lower sample sizes than Bayesian segmentation with sMRI alone.
The human thalamus is a brain structure that comprises numerous, highly specific nuclei. Since these nuclei are known to have different functions and to be connected to different areas of the cerebral cortex, it is of great interest for the neuroimag
ing community to study their volume, shape and connectivity in vivo with MRI. In this study, we present a probabilistic atlas of the thalamic nuclei built using ex vivo brain MRI scans and histological data, as well as the application of the atlas to in vivo MRI segmentation. The atlas was built using manual delineation of 26 thalamic nuclei on the serial histology of 12 whole thalami from six autopsy samples, combined with manual segmentations of the whole thalamus and surrounding structures (caudate, putamen, hippocampus, etc.) made on in vivo brain MR data from 39 subjects. The 3D structure of the histological data and corresponding manual segmentations was recovered using the ex vivo MRI as reference frame, and stacks of blockface photographs acquired during the sectioning as intermediate target. The atlas, which was encoded as an adaptive tetrahedral mesh, shows a good agreement with with previous histological studies of the thalamus in terms of volumes of representative nuclei. When applied to segmentation of in vivo scans using Bayesian inference, the atlas shows excellent test-retest reliability, robustness to changes in input MRI contrast, and ability to detect differential thalamic effects in subjects with Alzheimers disease. The probabilistic atlas and companion segmentation tool are publicly available as part of the neuroimaging package FreeSurfer.
Nonlinear registration of 2D histological sections with corresponding slices of MRI data is a critical step of 3D histology reconstruction. This task is difficult due to the large differences in image contrast and resolution, as well as the complex n
onrigid distortions produced when sectioning the sample and mounting it on the glass slide. It has been shown in brain MRI registration that better spatial alignment across modalities can be obtained by synthesizing one modality from the other and then using intra-modality registration metrics, rather than by using mutual information (MI) as metric. However, such an approach typically requires a database of aligned images from the two modalities, which is very difficult to obtain for histology/MRI. Here, we overcome this limitation with a probabilistic method that simultaneously solves for registration and synthesis directly on the target images, without any training data. In our model, the MRI slice is assumed to be a contrast-warped, spatially deformed version of the histological section. We use approximate Bayesian inference to iteratively refine the probabilistic estimate of the synthesis and the registration, while accounting for each others uncertainty. Moreover, manually placed landmarks can be seamlessly integrated in the framework for increased performance. Experiments on a synthetic dataset show that, compared with MI, the proposed method makes it possible to use a much more flexible deformation model in the registration to improve its accuracy, without compromising robustness. Moreover, our framework also exploits information in manually placed landmarks more efficiently than MI, since landmarks inform both synthesis and registration - as opposed to registration alone. Finally, we show qualitative results on the public Allen atlas, in which the proposed method provides a clear improvement over MI based registration.
Multi-atlas segmentation (MAS), first introduced and popularized by the pioneering work of Rohlfing, Brandt, Menzel and Maurer Jr (2004), Klein, Mensh, Ghosh, Tourville and Hirsch (2005), and Heckemann, Hajnal, Aljabar, Rueckert and Hammers (2006), i
s becoming one of the most widely-used and successful image segmentation techniques in biomedical applications. By manipulating and utilizing the entire dataset of atlases (training images that have been previously labeled, e.g., manually by an expert), rather than some model-based average representation, MAS has the flexibility to better capture anatomical variation, thus offering superior segmentation accuracy. This benefit, however, typically comes at a high computational cost. Recent advancements in computer hardware and image processing software have been instrumental in addressing this challenge and facilitated the wide adoption of MAS. Today, MAS has come a long way and the approach includes a wide array of sophisticated algorithms that employ ideas from machine learning, probabilistic modeling, optimization, and computer vision, among other fields. This paper presents a survey of published MAS algorithms and studies that have applied these methods to various biomedical problems. In writing this survey, we have three distinct aims. Our primary goal is to document how MAS was originally conceived, later evolved, and now relates to alternative methods. Second, this paper is intended to be a detailed reference of past research activity in MAS, which now spans over a decade (2003 - 2014) and entails novel methodological developments and application-specific solutions. Finally, our goal is to also present a perspective on the future of MAS, which, we believe, will be one of the dominant approaches in biomedical image segmentation.
