Burciu RG, Ofori E, Archer DB, Wu SS, Pasternak O, McFarland NR, Okun MS, Vaillancourt DE. Progression Marker of Parkinson's Disease: A 4-year Multi-site Imaging Study. Brain. 2017;140 (8) :2183-92.Abstract
Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson's disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson's disease ( The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson's disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson's disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson's disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson's disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson's disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year decrease in striatal binding ratio in the putamen. Importantly, all longitudinal results were consistent across sites. In summary, this study demonstrates an increase over 1 year in free water in the posterior substantia nigra in a large cohort of de novo patients with Parkinson's disease from a multi-site cohort study and no change in healthy controls, and further demonstrates an increase of free water in Parkinson's disease over the course of 4 years. A key finding was that results are consistent across sites and the 1-year and 2-year increase in free water in the posterior substantia nigra predicts subsequent long-term progression on the Hoehn and Yahr staging system. Collectively, these findings demonstrate that free water in the posterior substantia nigra is a valid, progression imaging marker of Parkinson's disease, which may be used in clinical trials of disease-modifying therapies.
Pouch AM, Aly AH, Lasso A, Nguyen AV, Scanlan AB, McGowan FX, Fichtinger G, Gorman RC, Gorman JH, Yushkevich PA, et al. Image Segmentation and Modeling of the Pediatric Tricuspid Valve in Hypoplastic Left Heart Syndrome. Funct Imaging Model Heart. 2017;10263 :95-105.Abstract
Hypoplastic left heart syndrome (HLHS) is a single-ventricle congenital heart disease that is fatal if left unpalliated. In HLHS patients, the tricuspid valve is the only functioning atrioventricular valve, and its competence is therefore critical. This work demonstrates the first automated strategy for segmentation, modeling, and morphometry of the tricuspid valve in transthoracic 3D echocardiographic (3DE) images of pediatric patients with HLHS. After initial landmark placement, the automated segmentation step uses multi-atlas label fusion and the modeling approach uses deformable modeling with medial axis representation to produce patient-specific models of the tricuspid valve that can be comprehensively and quantitatively assessed. In a group of 16 pediatric patients, valve segmentation and modeling attains an accuracy (mean boundary displacement) of 0.8 ± 0.2 mm relative to manual tracing and shows consistency in annular and leaflet measurements. In the future, such image-based tools have the potential to improve understanding and evaluation of tricuspid valve morphology in HLHS and guide strategies for patient care.
Maier-Hein L, Vedula S, Speidel S, Navab N, Kikinis R, Eisenman M, Feussner H, Forestier G. Surgical Data Science for Next-generation Interventions. Nature Biomedical Engineering. 2017;1 :691-6.
Maier-Hein L, Vedula S, Speidel S, Navab N, Kikinis R, Park A, Eisenman M, Feussner H, Forestier G. Surgical Data Science: Enabling Next-generation Surgery. Nature Biomedical Engineering. 2017. Maier-Hein-NBE2017.pdf
Schabdach J, Wells WM, Cho M, Batmanghelich KN. A Likelihood-Free Approach for Characterizing Heterogeneous Diseases in Large-Scale Studies. Inf Process Med Imaging. 2017;10265 :170-183.Abstract
We propose a non-parametric approach for characterizing heterogeneous diseases in large-scale studies. We target diseases where multiple types of pathology present simultaneously in each subject and a more severe disease manifests as a higher level of tissue destruction. For each subject, we model theof local image descriptors as samples generated by an unknown subject-specific probability density. Instead of approximating the probability density via a parametric family, we propose to side step the parametric inference by directly estimating the divergence between subject densities. Our method maps the collection of local image descriptors to a signaturethat is used to predict a clinical measurement. We are able to interpret the prediction of the clinical variable in the population and individual levels by carefully studying the divergences. We illustrate an application this method on simulated data as well as on a large-scale lung CT study of Chronic Obstructive Pulmonary Disease (COPD). Our approach outperforms classical methods on both simulated and COPD data and demonstrates the state-of-the-art prediction on an important physiologic measure of airflow (the forced respiratory volume in one second, FEV1).
Saito Y, Kubicki M, Koerte IK, Otsuka T, Rathi Y, Pasternak O, Bouix S, Eckbo R, Kikinis Z, von Hohenberg C, et al. Impaired White Matter Connectivity between Regions Containing Mirror Neurons, and Relationship to Negative Symptoms and Social Cognition, in Patients with First-Episode Schizophrenia. Brain Imaging Behav. 2017.Abstract
In schizophrenia, abnormalities in structural connectivity between brain regions known to contain mirror neurons and their relationship to negative symptoms related to a domain of social cognition are not well understood. Diffusion tensor imaging (DTI) scans were acquired in 16 patients with first episode schizophrenia and 16 matched healthy controls. FA and Trace of the tracts interconnecting regions known to be rich in mirror neurons, i.e., anterior cingulate cortex (ACC), inferior parietal lobe (IPL) and premotor cortex (PMC) were evaluated. A significant group effect for Trace was observed in IPL-PMC white matter fiber tract (F (1, 28) = 7.13, p = .012), as well as in the PMC-ACC white matter fiber tract (F (1, 28) = 4.64, p = .040). There were no group differences in FA. In addition, patients with schizophrenia showed a significant positive correlation between the Trace of the left IPL-PMC white matter fiber tract, and the Ability to Feel Intimacy and Closeness score (rho = .57, p = 0.034), and a negative correlation between the Trace of the left PMC-ACC and the Relationships with Friends and Peers score (rho = remove -.54, p = 0.049). We have demonstrated disrupted white mater microstructure within the white matter tracts subserving brain regions containing mirror neurons. We further showed that such structural disruptions might impact negative symptoms and, more specifically, contribute to the inability to feel intimacy (a measure conceptually related to theory of mind) in first episode schizophrenia. Further studies are needed to understand the potential of our results for diagnosis, prognosis and therapeutic interventions.
Zhang M, Liao R, Dalca AV, Turk EA, Luo J, Grant EP, Golland P. Frequency Diffeomorphisms for Efficient Image Registration. Inf Process Med Imaging. 2017;10265 :559-570.Abstract
This paper presents an efficient algorithm for large deformation diffeomorphic metric mapping (LDDMM) with geodesic shooting for image registration. We introduce a novel finite dimensional Fourier representation of diffeomorphic deformations based on the key fact that the high frequency components of a diffeomorphism remain stationary throughout the integration process when computing the deformation associated with smooth velocity fields. We show that manipulating high dimensional diffeomorphisms can be carried out entirely in the bandlimited space by integrating the nonstationary low frequency components of the displacement field. This insight substantially reduces the computational cost of the registration problem. Experimental results show that our method is significantly faster than the state-of-the-art diffeomorphic image registration methods while producing equally accurate alignment. We demonstrate our algorithm in two different applications of image registration: neuroimaging and in-utero imaging.
Dalca AV, Bouman KL, Freeman WT, Rost NS, Sabuncu MR, Golland P. Population Based Image Imputation. Inf Process Med Imaging. 2017;10265 :659-671.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 databases of clinical images contain a wealth of information, medical acquisition constraints result in sparse scans that miss much of the anatomy. These characteristics often render computational analysis impractical as standard processing algorithms tend to fail when applied to such images. Highly specialized or application-specific algorithms that explicitly handle sparse slice spacing do not generalize well across problem domains. In contrast, our goal is to enable application of existing algorithms that were originally developed for high resolution research scans to significantly undersampled scans. We introduce a model that captures fine-scale anatomical similarity across subjects in clinical image collections and use it to fill in the missing data in scans with large slice spacing. Our experimental results demonstrate that the proposed method outperforms current upsampling methods and promises to facilitate subsequent analysis not previously possible with scans of this quality.
Oestreich LKL, Lyall AE, Pasternak O, Kikinis Z, Newell DT, Savadjiev P, Bouix S, Shenton ME, Kubicki M, Kubicki M, Whitford TJ, et al. Characterizing White Matter Changes in Chronic Schizophrenia: A Free-water Imaging Multi-site Study. Schizophr Res. 2017;189 :153-61.Abstract
Diffusion tensor imaging (DTI) studies in chronic schizophrenia have found widespread but often inconsistent patterns of white matter abnormalities. These studies have typically used the conventional measure of fractional anisotropy, which can be contaminated by extracellular free-water. A recent free-water imaging study reported reduced free-water corrected fractional anisotropy (FAT) in chronic schizophrenia across several brain regions, but limited changes in the extracellular volume. The present study set out to validate these findings in a substantially larger sample. Tract-based spatial statistics (TBSS) was performed in 188 healthy controls and 281 chronic schizophrenia patients. Forty-two regions of interest (ROIs), as well as average whole-brain FAT and FW were extracted from free-water corrected diffusion tensor maps. Compared to healthy controls, reduced FAT was found in the chronic schizophrenia group in the anterior limb of the internal capsule bilaterally, the posterior thalamic radiation bilaterally, as well as the genu and body of the corpus callosum. While a significant main effect of group was observed for FW, none of the follow-up contrasts survived correction for multiple comparisons. The observed FAT reductions in the absence of extracellular FW changes, in a large, multi-site sample of chronic schizophrenia patients, validate the pattern of findings reported by a previous, smaller free-water imaging study of a similar sample. The limited number of regions in which FAT was reduced in the schizophrenia group suggests that actual white matter tissue degeneration in chronic schizophrenia, independent of extracellular FW, might be more localized than suggested previously.
Ofori E, Krismer F, Burciu RG, Pasternak O, McCracken JL, Lewis MM, Du G, McFarland NR, Okun MS, Poewe W, et al. Free Water Improves Detection of Changes in the Substantia Nigra in Parkinsonism: A Multisite Study. Mov Disord. 2017;32 (10) :1457-64.Abstract
BACKGROUND: Imaging markers that are sensitive to parkinsonism across multiple sites are critically needed for clinical trials. The objective of this study was to evaluate changes in the substantia nigra using single- and bi-tensor models of diffusion magnetic resonance imaging in PD, MSA, and PSP. METHODS: The study cohort (n = 425) included 107 healthy controls and 184 PD, 63 MSA, and 71 PSP patients from 3 movement disorder centers. Bi-tensor free water, free-water-corrected fractional anisotropy, free-water-corrected mean diffusivity, single-tensor fractional anisotropy, and single-tensor mean diffusivity were computed for the anterior and posterior substantia nigra. Correlations were computed between diffusion MRI measures and clinical measures. RESULTS: In the posterior substantia nigra, free water was greater for PSP than MSA and PD patients and controls. PD and MSA both had greater free water than controls. Free-water-corrected fractional anisotropy values were greater for PSP patents than for controls and PD patients. PSP and MSA patient single-tensor mean diffusivity values were greater than controls, and single-tensor fractional anisotropy values were lower for PSP patients than for healthy controls. The parkinsonism effect size for free water was 0.145 in the posterior substantia nigra and 0.072 for single-tensor mean diffusivity. The direction of correlations between single-tensor mean diffusivity and free-water values and clinical scores was similar at each site. CONCLUSIONS: Free-water values in the posterior substantia nigra provide a consistent pattern of findings across patients with PD, MSA, and PSP in a large cohort across 3 sites. Free water in the posterior substantia nigra relates to clinical measures of motor and cognitive symptoms in a large cohort of parkinsonism. © 2017 International Parkinson and Movement Disorder Society.
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.
Maier-Hein KH, Neher PF, Houde J-C, Côté M-A, Garyfallidis E, Zhong J, Chamberland M, Yeh F-C, Lin Y-C, Ji Q, et al. The Challenge of Mapping the Human Connectome Based on Diffusion Tractography. Nat Commun. 2017;8 (1) :1349.Abstract
Tractography based on non-invasive diffusion imaging is central to the study of human brain connectivity. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain data set with ground truth tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. Here, we report the encouraging finding that most state-of-the-art algorithms produce tractograms containing 90% of the ground truth bundles (to at least some extent). However, the same tractograms contain many more invalid than valid bundles, and half of these invalid bundles occur systematically across research groups. Taken together, our results demonstrate and confirm fundamental ambiguities inherent in tract reconstruction based on orientation information alone, which need to be considered when interpreting tractography and connectivity results. Our approach provides a novel framework for estimating reliability of tractography and encourages innovation to address its current limitations.
Norton I, Essayed WI, Zhang F, Pujol S, Yarmarkovich A, Golby AJ, Kindlmann G, Wasserman D, Estepar RSJ, Rathi Y, et al. SlicerDMRI: Open Source Diffusion MRI Software for Brain Cancer Research. Cancer Res. 2017;77 (21) :e101-e103.Abstract
Diffusion MRI (dMRI) is the only noninvasive method for mapping white matter connections in the brain. We describe SlicerDMRI, a software suite that enables visualization and analysis of dMRI for neuroscientific studies and patient-specific anatomic assessment. SlicerDMRI has been successfully applied in multiple studies of the human brain in health and disease, and here, we especially focus on its cancer research applications. As an extension module of the 3D Slicer medical image computing platform, the SlicerDMRI suite enables dMRI analysis in a clinically relevant multimodal imaging workflow. Core SlicerDMRI functionality includes diffusion tensor estimation, white matter tractography with single and multi-fiber models, and dMRI quantification. SlicerDMRI supports clinical DICOM and research file formats, is open-source and cross-platform, and can be installed as an extension to 3D Slicer ( More information, videos, tutorials, and sample data are available at Cancer Res; 77(21); e101-3. ©2017 AACR.
Dalca AV, Bouman K L, Freeman WT, Rost NS, Sabuncu MR, Golland P. Population Based Image Imputation. Inf Process Med Imaging. 2017;10265 (659-71).
Zhang M, Liao R, Dalca AV, Turk E, Luo J, Grant E, Golland P. Frequency Diffeomorphisms for Efficient Image Registration. Inf Process Med Imaging. 2017;10265 :559-70.
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.
Herz C, Fillion-Robin J-C, Onken M, Riesmeier J, Lasso A, Pinter C, Fichtinger G, Pieper S, Clunie D, Kikinis R, et al. DCMQI: An Open Source Library for Standardized Communication of Quantitative Image Analysis Results using DICOM. Cancer Research. 2017;77 (21) :e87-e90.Abstract
Quantitative analysis of clinical image data is an active area of research that holds promise for precision medicine, early assessment of treatment response, and objective characterization of the disease. Interoperability, data sharing, and the ability to mine the resulting data are of increasing importance, given the explosive growth in the number of quantitative analysis methods being proposed. The Digital Imaging and Communications in Medicine (DICOM) standard is widely adopted for image and metadata in radiology. dcmqi (DICOM for Quantitative Imaging) is a free, open source library that implements conversion of the data stored in commonly used research formats into the standard DICOM representation. dcmqi source code is distributed under BSD-style license. It is freely available as a precompiled binary package for every major operating system, as a Docker image, and as an extension to 3D Slicer. Installation and usage instructions are provided on Harvard DASH.
Halle M, Talos I-F, Jakab M, Makris N, Meier D, Wald LL, Fischl B, Kikinis R. Multi-modality MRI-based Atlas of the Brain. Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; 2017. Publisher's VersionAbstract
The Neuroimage Analysis Center's Computational Clinical Anatomy Core and the Surgical Planning Laboratory at Brigham and Women's Hospital is pleased to make available a multi-modality MRI-based atlas of the brain. Data was acquired at the Martinos Center for Biomedical Imaging (courtesy Dr. Lawrence Wald) on a Siemens 3T scanner, using a multi-array head coil, in a healthy, 42 year old male. The data set consists of : 1. a volumetric whole head MPRAGE series (voxel size 0.75 mm isotropic). 2. a volumetric whole head T2-weighted series (voxel size 0.75 mm isotropic). 3. a downsampled version of both acquisitions at 1mm isotropic resolution. 4. a per voxel labeling of the structures based on the 1mm volumes. 5. a color file mapping label values to RadLex-ontology derived names and colors suitable for display. 6. MRML files for displaying the volumes in 3D Slicer version 3.6 or greater, available for download. The atlas data is made available under terms of the 3D Slicer License section B.
The Slicer4 version also consists of 1. hypotalamic parcellation (courtesy Nikos Makris [Neuroimage. 2013]) 2. cerebellar parcellation (courtesy Nikos Makris [J Cogn Neurosci. 2003], [Neuroimage. 2005]) 3.head and neck muscles segmentation 4. anatomical model hierarchy 5. several pre-defined Scene Views (“anatomy teaching files”). All in a mrb (Medical Reality Bundle) archive file that contains the mrml scene file and all data for loading into Slicer 4 for displaying the volumes in 3D Slicer version 4.0 or greater, available for download.
This work is funded as part of the Neuroimaging Analysis Center, grant number P41 RR013218, by the NIH's National Center for Research Resources (NCRR) and grant number P41 EB015902, by the NIH's National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the Google Faculty Research Award.
Contributors: Ilwoo Lyu and Martin Styner: Sulcal Curves, Samira Farough: Ventricular System, Ibraheem Naeem and Maria Naeem: Head and Neck Muscles, George Papadimitriou: Cerebellar Parcellation, Madiha Tahir: White Matter.
This atlas maybe viewed with our Open Anatomy Browser.
Kapur T, Tempany CM. Proceedings of the 9th Image Guided Therapy Workshop. 2017;9 :1-54. 2017 IGT Workshop Proceedings
Niethammer M, Pohl KM, Janoos F, Wells WM. Active Mean Fields for Probabilistic Image Segmentation: Connections with Chan-Vese and Rudin-Osher-Fatemi Models. SIAM J. Imaging Sci. 2017;10 (3) :1069-1103.Abstract
Segmentation is a fundamental task for extracting semantically meaningful regions from an image. The goal of segmentation algorithms is to accurately assign object labels to each image location. However, image noise, shortcomings of algorithms, and image ambiguities cause uncertainty in label assignment. Estimating this uncertainty is important in multiple application domains, such as segmenting tumors from medical images for radiation treatment planning. One way to estimate these uncertainties is through the computation of posteriors of Bayesian models, which is computationally prohibitive for many practical applications. However, most computationally efficient methods fail to estimate label uncertainty. We therefore propose in this paper the active mean fields (AMF) approach, a technique based on Bayesian modeling that uses a mean-field approximation to efficiently compute a segmentation and its corresponding uncertainty. Based on a variational formulation, the resulting convex model combines any label-likelihood measure with a prior on the length of the segmentation boundary. A specific implementation of that model is the Chan-Vese segmentation model, in which the binary segmentation task is defined by a Gaussian likelihood and a prior regularizing the length of the segmentation boundary. Furthermore, the Euler-Lagrange equations derived from the AMF model are equivalent to those of the popular Rudin-Osher-Fatemi (ROF) model for image denoising. Solutions to the AMF model can thus be implemented by directly utilizing highly efficient ROF solvers on log-likelihood ratio fields. We qualitatively assess the approach on synthetic data as well as on real natural and medical images. For a quantitative evaluation, we apply our approach to the tt icgbench dataset.