Statistical Inference for Imaging and Disease Core Publications

Dalca AV, Yu E, Golland P, Fischl B, Sabuncu MR, Iglesias JE. Unsupervised Deep Learning for Bayesian Brain MRI Segmentation. Med Image Comput Comput Assist Interv. 2019;11766 :356-65.Abstract
Probabilistic atlas priors have been commonly used to derive adaptive and robust brain MRI segmentation algorithms. Widely-used neuroimage analysis pipelines rely heavily on these techniques, which are often computationally expensive. In contrast, there has been a recent surge of approaches that leverage deep learning to implement segmentation tools that are computationally efficient at test time. However, most of these strategies rely on learning from manually annotated images. These supervised deep learning methods are therefore sensitive to the intensity profiles in the training dataset. To develop a deep learning-based segmentation model for a new image dataset (e.g., of different contrast), one usually needs to create a new labeled training dataset, which can be prohibitively expensive, or rely on suboptimal adaptation or augmentation approaches. In this paper, we propose an alternative strategy that combines a conventional probabilistic atlas-based segmentation with deep learning, enabling one to train a segmentation model for new MRI scans without the need for any manually segmented images. Our experiments include thousands of brain MRI scans and demonstrate that the proposed method achieves good accuracy for a brain MRI segmentation task for different MRI contrasts, requiring only approximately 15 seconds at test time on a GPU.
Xu J, Zhang M, Abaci Turk E, Zhang L, Grant E, Ying K, Golland P, Adalsteinsson E. Fetal Pose Estimation in Volumetric MRI using a 3D Convolution Neural Network. Med Image Comput Comput Assist Interv. 2019;11767 :403-10.Abstract
The performance and diagnostic utility of magnetic resonance imaging (MRI) in pregnancy is fundamentally constrained by fetal motion. Motion of the fetus, which is unpredictable and rapid on the scale of conventional imaging times, limits the set of viable acquisition techniques to single-shot imaging with severe compromises in signal-to-noise ratio and diagnostic contrast, and frequently results in unacceptable image quality. Surprisingly little is known about the characteristics of fetal motion during MRI and here we propose and demonstrate methods that exploit a growing repository of MRI observations of the gravid abdomen that are acquired at low spatial resolution but relatively high temporal resolution and over long durations (10-30 minutes). We estimate fetal pose per frame in MRI volumes of the pregnant abdomen via deep learning algorithms that detect key fetal landmarks. Evaluation of the proposed method shows that our framework achieves quantitatively an average error of 4.47 mm and 96.4% accuracy (with error less than 10 mm). Fetal pose estimation in MRI time series yields novel means of quantifying fetal movements in health and disease, and enables the learning of kinematic models that may enhance prospective mitigation of fetal motion artifacts during MRI acquisition.
Wang J, Wells WM, Golland P, Zhang M. Registration Uncertainty Quantification via Low-dimensional Characterization of Geometric Deformations. Magn Reson Imaging. 2019;64 :122-31.Abstract
This paper presents an efficient approach to quantifying image registration uncertainty based on a low-dimensional representation of geometric deformations. In contrast to previous methods, we develop a Bayesian diffeomorphic registration framework in a bandlimited space, rather than a high-dimensional image space. We show that a dense posterior distribution on deformation fields can be fully characterized by much fewer parameters, which dramatically reduces the computational complexity of model inferences. To further avoid heavy computation loads introduced by random sampling algorithms, we approximate a marginal posterior by using Laplace's method at the optimal solution of log-posterior distribution. Experimental results on both 2D synthetic data and real 3D brain magnetic resonance imaging (MRI) scans demonstrate that our method is significantly faster than the state-of-the-art diffeomorphic registration uncertainty quantification algorithms, while producing comparable results.
Abaci Turk E, Stout JN, Ha C, Luo J, Gagoski B, Yetisir F, Golland P, Wald LL, Adalsteinsson E, Robinson JN, et al. Placental MRI: Developing Accurate Quantitative Measures of Oxygenation. Top Magn Reson Imaging. 2019;28 (5) :285-97.Abstract
The Human Placenta Project has focused attention on the need for noninvasive magnetic resonance imaging (MRI)-based techniques to diagnose and monitor placental function throughout pregnancy. The hope is that the management of placenta-related pathologies would be improved if physicians had more direct, real-time measures of placental health to guide clinical decision making. As oxygen alters signal intensity on MRI and oxygen transport is a key function of the placenta, many of the MRI methods under development are focused on quantifying oxygen transport or oxygen content of the placenta. For example, measurements from blood oxygen level-dependent imaging of the placenta during maternal hyperoxia correspond to outcomes in twin pregnancies, suggesting that some aspects of placental oxygen transport can be monitored by MRI. Additional methods are being developed to accurately quantify baseline placental oxygenation by MRI relaxometry. However, direct validation of placental MRI methods is challenging and therefore animal studies and ex vivo studies of human placentas are needed. Here we provide an overview of the current state of the art of oxygen transport and quantification with MRI. We suggest that as these techniques are being developed, increased focus be placed on ensuring they are robust and reliable across individuals and standardized to enable predictive diagnostic models to be generated from the data. The field is still several years away from establishing the clinical benefit of monitoring placental function in real time with MRI, but the promise of individual personalized diagnosis and monitoring of placental disease in real time continues to motivate this effort.
Schirmer MD, Dalca AV, Sridharan R, Giese A-K, Donahue KL, Nardin MJ, Mocking SJT, McIntosh EC, Frid P, Wasselius J, et al. White Matter Hyperintensity Quantification in Large-scale Clinical Acute Ischemic Stroke Cohorts - The MRI-GENIE Study. Neuroimage Clin. 2019;23 :101884.Abstract
White matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype linked to prediction of diagnosis and prognosis of diseases, such as acute ischemic stroke (AIS). However, current approaches to its quantification on clinical MRI often rely on time intensive manual delineation of the disease on T2 fluid attenuated inverse recovery (FLAIR), which hinders high-throughput analyses such as genetic discovery. In this work, we present a fully automated pipeline for quantification of WMH in clinical large-scale studies of AIS. The pipeline incorporates automated brain extraction, intensity normalization and WMH segmentation using spatial priors. We first propose a brain extraction algorithm based on a fully convolutional deep learning architecture, specifically designed for clinical FLAIR images. We demonstrate that our method for brain extraction outperforms two commonly used and publicly available methods on clinical quality images in a set of 144 subject scans across 12 acquisition centers, based on dice coefficient (median 0.95; inter-quartile range 0.94-0.95; p < 0.01) and Pearson correlation of total brain volume (r = 0.90). Subsequently, we apply it to the large-scale clinical multi-site MRI-GENIE study (N = 2783) and identify a decrease in total brain volume of -2.4 cc/year. Additionally, we show that the resulting total brain volumes can successfully be used for quality control of image preprocessing. Finally, we obtain WMH volumes by building on an existing automatic WMH segmentation algorithm that delineates and distinguishes between different cerebrovascular pathologies. The learning method mimics expert knowledge of the spatial distribution of the WMH burden using a convolutional auto-encoder. This enables successful computation of WMH volumes of 2533 clinical AIS patients. We utilize these results to demonstrate the increase of WMH burden with age (0.950 cc/year) and show that single site estimates can be biased by the number of subjects recruited.
Luo J, Toews M, Machado I, Frisken S, Zhang M, Preiswerk F, Sedghi A, Ding H, Pieper S, Golland P, et al. A Feature-Driven Active Framework for Ultrasound-Based Brain Shift Compensation, in MICCAI 2018. Vol LNCS 11073. Granada, Spain: Springer ; 2018 :30-38.Abstract
A reliable Ultrasound (US)-to-US registration method to compensate for brain shift would substantially improve Image-Guided Neurological Surgery. Developing such a registration method is very challenging, due to factors such as the tumor resection, the complexity of brain pathology and the demand for fast computation. We propose a novel feature-driven active registration framework. Here, landmarks and their displacement are first estimated from a pair of US images using corresponding local image features. Subsequently, a Gaussian Process (GP) model is used to interpolate a dense deformation field from the sparse landmarks. Kernels of the GP are estimated by using variograms and a discrete grid search method. If necessary, the user can actively add new landmarks based on the image context and visualization of the uncertainty measure provided by the GP to further improve the result. We retrospectively demonstrate our registration framework as a robust and accurate brain shift compensation solution on clinical data.
Pace DF, Dalca AV, Brosch T, Geva T, Powell AJ, Weese J, Moghari MH, Golland P. Iterative Segmentation from Limited Training Data: Applications to Congenital Heart Disease. Deep Learn Med Image Anal Multimodal Learn Clin Decis Support (2018). 2018;11045 :334-42.Abstract
We propose a new iterative segmentation model which can be accurately learned from a small dataset. A common approach is to train a model to directly segment an image, requiring a large collection of manually annotated images to capture the anatomical variability in a cohort. In contrast, we develop a segmentation model that recursively evolves a segmentation in several steps, and implement it as a recurrent neural network. We learn model parameters by optimizing the intermediate steps of the evolution in addition to the final segmentation. To this end, we train our segmentation propagation model by presenting incomplete and/or inaccurate input segmentations paired with a recommended next step. Our work aims to alleviate challenges in segmenting heart structures from cardiac MRI for patients with congenital heart disease (CHD), which encompasses a range of morphological deformations and topological changes. We demonstrate the advantages of this approach on a dataset of 20 images from CHD patients, learning a model that accurately segments individual heart chambers and great vessels. Compared to direct segmentation, the iterative method yields more accurate segmentation for patients with the most severe CHD malformations.
Wang J, Wells WM, Golland P, Zhang M. Efficient Laplace Approximation for Bayesian Registration Uncertainty Quantification. Med Image Comput Comput Assist Interv. 2018;11070 :880-8.Abstract
This paper presents a novel approach to modeling the pos terior distribution in image registration that is computationally efficient for large deformation diffeomorphic metric mapping (LDDMM). We develop a Laplace approximation of Bayesian registration models entirely in a bandlimited space that fully describes the properties of diffeomorphic transformations. In contrast to current methods, we compute the inverse Hessian at the mode of the posterior distribution of diffeomorphisms directly in the low dimensional frequency domain. This dramatically reduces the computational complexity of approximating posterior marginals in the high dimensional imaging space. Experimental results show that our method is significantly faster than the state-of-the-art diffeomorphic image registration uncertainty quantification algorithms, while producing comparable results. The efficiency of our method strengthens the feasibility in prospective clinical applications, e.g., real- time image-guided navigation for brain surgery.
Dalca AV, Bouman KL, Freeman WT, Rost NS, Sabuncu MR, Golland P. Medical Image Imputation from Image Collections. IEEE Trans Med Imaging. 2018.Abstract
We present an algorithm for creating high resolution anatomically plausible images consistent with acquired clinical brain MRI scans with large inter-slice spacing. Although large data sets of clinical images contain a wealth of information, time constraints during acquisition result in sparse scans that fail to capture much of the anatomy. These characteristics often render computational analysis impractical as many image analysis algorithms tend to fail when applied to such images. Highly specialized algorithms that explicitly handle sparse slice spacing do not generalize well across problem domains. In contrast, we aim to enable application of existing algorithms that were originally developed for high resolution research scans to significantly undersampled scans. We introduce a generative model that captures fine-scale anatomical structure across subjects in clinical image collections and derive an algorithm for filling in the missing data in scans with large inter-slice spacing. Our experimental results demonstrate that the resulting method outperforms state-of-the-art upsampling super-resolution techniques, and promises to facilitate subsequent analysis not previously possible with scans of this quality. Our implementation is freely available at https://github.com/adalca/papago.
Luo J, Frisken S, Machado I, Zhang M, Pieper S, Golland P, Toews M, Unadkat P, Sedghi A, Zhou H, et al. Using the Variogram for Vector Outlier Screening: Application to Feature-based Image Registration. Int J Comput Assist Radiol Surg. 2018;13 (12) :1871-80.Abstract
PURPOSE: Matching points that are derived from features or landmarks in image data is a key step in some medical imaging applications. Since most robust point matching algorithms claim to be able to deal with outliers, users may place high confidence in the matching result and use it without further examination. However, for tasks such as feature-based registration in image-guided neurosurgery, even a few mismatches, in the form of invalid displacement vectors, could cause serious consequences. As a result, having an effective tool by which operators can manually screen all matches for outliers could substantially benefit the outcome of those applications. METHODS: We introduce a novel variogram-based outlier screening method for vectors. The variogram is a powerful geostatistical tool for characterizing the spatial dependence of stochastic processes. Since the spatial correlation of invalid displacement vectors, which are considered as vector outliers, tends to behave differently than normal displacement vectors, they can be efficiently identified on the variogram. RESULTS: We validate the proposed method on 9 sets of clinically acquired ultrasound data. In the experiment, potential outliers are flagged on the variogram by one operator and further evaluated by 8 experienced medical imaging researchers. The matching quality of those potential outliers is approximately 1.5 lower, on a scale from 1 (bad) to 5 (good), than valid displacement vectors. CONCLUSION: The variogram is a simple yet informative tool. While being used extensively in geostatistical analysis, it has not received enough attention in the medical imaging field. We believe there is a good deal of potential for clinically applying the proposed outlier screening method. By way of this paper, we also expect researchers to find variogram useful in other medical applications that involve motion vectors analyses.
Chen Y, Georgiou TT, Ning L, Tannenbaum A. Matricial Wasserstein-1 Distance. IEEE Control Syst Lett. 2017;1 (1) :14-9.Abstract
We propose an extension of the Wasserstein 1-metric (W1) for density matrices, matrix-valued density measures, and an unbalanced interpretation of mass transport. We use duality theory and, in particular, a "dual of the dual" formulation of W1. This matrix analogue of the Earth Mover's Distance has several attractive features including ease of computation.
Wachinger C, Brennan M, Sharp GC, Golland P. Efficient Descriptor-Based Segmentation of Parotid Glands With Nonlocal Means. IEEE Trans Biomed Eng. 2017;64 (7) :1492-1502.Abstract
OBJECTIVE: We introduce descriptor-based segmentation that extends existing patch-based methods by combining intensities, features, and location information. Since it is unclear which image features are best suited for patch selection, we perform a broad empirical study on a multitude of different features. METHODS: We extend nonlocal means segmentation by including image features and location information. We search larger windows with an efficient nearest neighbor search based on kd-trees. We compare a large number of image features. RESULTS: The best results were obtained for entropy image features, which have not yet been used for patch-based segmentation. We further show that searching larger image regions with an approximate nearest neighbor search and location information yields a significant improvement over the bounded nearest neighbor search traditionally employed in patch-based segmentation methods. CONCLUSION: Features and location information significantly increase the segmentation accuracy. The best features highlight boundaries in the image. SIGNIFICANCE: Our detailed analysis of several aspects of nonlocal means-based segmentation yields new insights about patch and neighborhood sizes together with the inclusion of location information. The presented approach advances the state-of-the-art in the segmentation of parotid glands for radiation therapy planning.
Hong Y, Golland P, Zhang M. Fast Geodesic Regression for Population-Based Image Analysis. Int Conf Med Image Comput Comput Assist Interv. 2017;20 (Pt1) :317-25.Abstract
Geodesic regression on images enables studies of brain development and degeneration, disease progression, and tumor growth. The high-dimensional nature of image data presents significant computational challenges for the current regression approaches and prohibits large scale studies. In this paper, we present a fast geodesic regression method that dramatically decreases the computational cost of the inference procedure while maintaining prediction accuracy. We employ an efficient low dimensional representation of diffeomorphic transformations derived from the image data and characterize the regressed trajectory in the space of diffeomorphisms by its initial conditions, i.e., an initial image template and an initial velocity field computed as a weighted average of pairwise diffeomorphic image registration results. This construction is achieved by using a first-order approximation of pairwise distances between images. We demonstrate the efficiency of our model on a set of 3D brain MRI scans from the OASIS dataset and show that it is dramatically faster than the state-of-the-art regression methods while producing equally good regression results on the large subject cohort.

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