Collaborations

Major Biomedical Research Collaborations

The current portfolio of collaborations includes four driving biomedical research projects (DBPs) with independent government funding: (1) an investigation of the impact of traumatic brain injury on the health of retired NFL football players; (2) a clinical study of the crippling neurologic and psychiatric effects of HIV, methamphetamine use, and schizophrenia; (3) methods for automated modeling of white matter fascicles from diffusion MRI in schizophrenia; and (4) computational tool development for precision neurosurgical interventions that spare "eloquent" tissues related to motor control, sensory function, and speech.

Chronic Traumatic Encephalopathy

Collaborating Investigators: Martha Shenton PhD, Robert Stern, PhD, and Alexander Lin, PhD 
Collaborating Institutions: Boston University, Boston, MA; Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.
Grant Number: NIH NINDS R01NS078337
Grant PI: Robert Stern, PhD; Subcontract PI: Martha Shenton, PhD, BWH 
Grant Period: 12/01/2016-11/30/2022 
NAC Personnel and Cores: Carl-Fredrik Westin, Lauren O’Donnell, Ofer Pasternak, Yogesh Rathi, Microstructure Imaging Core; William M. Wells, Spatio-Temporal Modeling of Disease Core; Steve Pieper, Slicer Core.
Joint Publications

This study is investigating the long-term effects of mild repetitive brain injury in at risk populations with a technical focus on microstructure imaging (TRD1 - Microstructure Imaging Core). The goal of the collaboration is twofold: to develop new measures for quantifying tissue alterations using image analysis at a microstructure scale and to use these measures to identify potential biomarkers of chronic traumatic encephalopathy (CTE), also known as “repetitive head injury.” The NINDS-funded project centered at Boston University is studying the clinical effects of CTE in a cohort of retired football players. CTE may develop in individuals with no history of symptomatic concussion and may result from repetitive subconcussive trauma. Recent studies have demonstrated that these sub concussive injuries are very common in athletes (over 1000 per player per football season (Crisco, 2010) and can result in both cognitive and neurophysiological changes, even in high school athletes (Talavage, 2010). Given the millions of youth, high school, and collegiate athletes participating in contact sports involving mild traumatic brain injury (mTBI), as well as the growing concern over repeated mTBI in military personnel (Cozarelli, 2010), CTE may represent an important and previously under-recognized public health issue. Specifically, the microstructure imaging core (TRD1) is developing new technology to study microstructural tissue alterations in mild repetitive brain injury (mTBI).
The outcome of this collaboration is expected to provide technical, clinical, and scientific impact. Open-source NAC tools for measuring potential biomarkers will help the technical imaging analysis field, in general, and may aid the clinical diagnosis of CTE. Furthermore, the identification of new biomarkers is expected to improve scientific understanding of CTE. Both groups share the common goal of furthering understanding of traumatic brain injury through imaging. A significant synergy exists between the clinical study and the technical capabilities and imaging research of NAC.
 

Translational Methamphetamine AIDS Research Center (TMARC)

Collaborating Investigators: Gregory G. Brown, PhD, Amanda Bischoff Grethe, PhD
Collaborating Institution: University of California, San Diego, CA
Grant Number: NIH NIDA P50DA026306
Grant PI: Igor Grant, MD
Grant Period: 06/01/2008-05/31/2019
NAC Personnel and Cores: William M. Wells, Spatio-Temporal Modeling of Disease Core.
Joint Publications

This project is investigating the effects (and interactions) of methamphetamine abuse and HIV infection on brain function with a technical focus on spatio-temporal modeling (TRD2 - Spatio-Temporal Modeling Core). The overall goal of the collaboration is to advance computational methods to analyze the temporal and spatial information available in functional magnetic resonance imaging (fMRI) datasets. These new computational methods will be used to investigate the biological problem of identifying dysfunctional brain systems that underlie the impaired use of feedback in shaping adaptive behavior among patients with HIV infection and/or a history of methamphetamine use. The project is a collaboration with Dr. Greg Brown, currently with the Translational Methamphetamine and AIDS Research Center (TMARC), an NIH-funded center focused on fMRI analysis.
HIV and methamphetamine (METH) use commonly co-occur and represent a major burden on the healthcare system, due in part to their individual and combined toxic effects on neural systems that underlie higher-level neurocognitive functions, such as risky decision-making. The UCSD TMARC supports ongoing fMRI studies of the brain mechanisms that underlie basic feedback mechanisms in HIV+ and/or METH+ patients. The Cued Reward Task used in these studies assesses reward cuing and reward processing, but not the use of rewarding feedback to solve problems. The NAC-TMARC collaboration will be aimed at analyzing the data from the Cued Reward Task using an advanced image analysis method developed by members of NAC. Currently, the fMRI analysis plan calls for a voxel-wise analysis of the group effects. However, single-voxel analyses will miss important findings related to the functional connectivity of brain areas. Moreover, the current analyses assume that the neural response generated by the feedback task is mediated by the same hemodynamic response in all study groups. Given that both HIV infection and methamphetamine use have been associated with cerebrovascular disease, the assumption of a single hemodynamic model for all analyses cannot be justified. The one study that investigated the homogeneity assumption found differences in the response function between HIV infected individuals and healthy controls (Juengst, 2007). An alternative method capable of identifying distributed patterns of brain activation that avoids the strong assumption of a single hemodynamic model is required. NAC has a computational method that uses a state-space model (SSM) to analyze fMRI data that not only yields only spatial maps of distributed brain activity but also identifies the temporal structure of the activity. The brain state-space method will provide maps of the spatial distribution of brain activity related to reward expectancy and reward feedback while avoiding the strong assumption that a single hemodynamic response is common to fMRI data in all groups.
 

Statins Augment Small Vessel Function and Improve Stroke Outcomes--A Stroke Genetics Network Consortium Project

Collaborating Investigator: Steven J. Kittner, MD
Collaborating Institution: Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Grant Number: NINDS R01NS082285
Grant PI: Natalia Rost
Grant Period: 09/25/2013-08/31/2018
NAC Personnel and Cores: Polina Golland, Christian Wachinger, Ramesh Sridharan, Anatomical Variability Core.
Joint Publications
 
This project is investigating the vascular protective effects of statins in acute ischemic stroke (AIS), where cerebral tissue damage and clinical outcomes have been linked to microvascular dysfunction manifested by white matter hyper-intensity on MRI. The NAC team is working closely with the MGH SiGN site (N.S. Rost, PI) to develop algorithms for automatic quantification of cerebrovascular disease burden and stroke in the MRI scans of the SiGN consortium (Sridharan et al., 2013; Dalca et al., 2014, submitted). Processing and analysis of such datasets is challenging due to low resolution, poor contrast, misaligned images, and restricted field of view. The NAC researchers have adapted existing registration and segmentation methods and have built a computational pipeline for spatial normalization and feature extraction. The resulting aligned dataset enables clinically meaningful analysis of spatial distributions of relevant anatomical features and of their evolution with age and disease progression. The group has demonstrated this approach in a study of more than 800 patients. By combining data from several modalities the method automatically segments important biomarkers, such as white matter hyper-intensity, and characterizes the evolution of pathology in this heterogeneous cohort. The current methodological development includes improved classification of leukoaraiosis vs. chronic stroke and statistical modeling of disease burden with age.
 

National Center for Image Guided Therapy

Collaborating Investigators: Alexandra Golby, MD, Tina Kapur, PhD
Collaborating Institution: Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.
Funding Status: Active
Grant Number: NIH NIBIB BTRR EB015898
Grant PI: Clare M. Tempany, MD
Grant Period: 07/01/2016-06/30/2020
NAC Personnel and Cores: Steve Pieper, James Miller, Allen Tannenbaum, Slicer Core; Polina Golland, Anatomic Variability Core; Michael Halle, Atlas Infrastructure Project.
Co-located with NAC in the Department of Radiology at Brigham and Women’s Hospital, the National Center for Image Guided Therapy (NCIGT) is a vital pathway for the clinical application of NAC technologies and provides NAC investigators with critical exposure to the specific challenges of medical practice. As an NIH-funded Biomedical Technology Research Resource, NCIGT serves as a national center for all aspects of research into medical procedures that are enhanced by imaging. NCIGT provides a unique, centralized infrastructure for translational research in the area of image-guided therapy. The Slicer core (TRD4 - Slicer Core) is currently developing computational tools for precision neurosurgical intervention that spare "eloquent" tissues related to motor control, sensory function, and speech during image guided therapy.
 
 
NAC Technology in Action
 

The all-digital AMIGO Operating Suite

The Advanced Multimodality Image Guided Operating Suite (AMIGO) is an innovative surgical and interventional environment and the clinical translational testbed of NCIGT. More important, it serves as a laboratory and clinical testbed for NAC image-guidance technologies. The Slicer CaseHub framework, currently in development by NAC, will provide the context through which to apply these techniques in AMIGO. This will be accomplished by interoperating with commercial systems already present in AMIGO. As a general rule, commercial medical systems are preferred over in-house software for clinical cases because vendors provide support and testing. However, commercial surgical navigation systems and radiology workstations, by nature of their regulated environment, have only limited configurability, whereas the Slicer software is fully open and can be configured by NAC personnel to incorporate new analysis steps. Through the use of standards-based communication strategies, including DICOM and OpenIGTLink, Slicer has access to the same intraprocedural scans and tracked instrument data used in the commercial systems. This enables the clinical team to move easily back and forth between systems with minimal duplication of effort, permitting the acquisition of comprehensive information for both clinical and research-related activities relevant to each case. In addition, the Slicer CaseHub will be able to integrate a spectrum of data sources and novel devices, such as robots, in ways not yet available in any commercial system.

 

A variety of possible data sources and interactions will be available through the Slicer CaseHub framework as shown here in the context of AMIGO procedures.3D Slicer experimental tools are being used to collect data during neurosurgery. Shown here are two 3D Slicer screen captures comparing before and after manual registration to fuse MR (grayscale) and Ultrasound (green) images from an AMIGO neurosurgery case. Visual identification of corresponding structures in the two images along with manual tools to adjust the transformation permitted us to correct the registration. This analysis was performed in the weeks following the procedure, but as an experiment, it has provided valuable insight into the requirements and design options for tools to support intraprocedural steered registration. As of early 2014, we have been running 3D Slicer in parallel with the commercial navigation system (Brainlab) in AMIGO. MR data is transferred to 3D Slicer via DICOM, and ultrasound data are collected via a dedicated video capture device and reconstructed using the Public Library of Ultrasound (PLUS) system. The ultrasound probe is tracked by the Brainlab system and coordinates are sent to 3D Slicer via OpenIGTLink. This combination of technologies allows us to capture data during the procedure for subsequent analysis.

Other Active Research Collaborations

INTRUST: Injury and Traumatic Stress

Collaborating Investigators:  Ross Zafonte, Martha Shenton
Collaborating Institutions:  Brigham & Women's Hospital, Spaulding Rehabilitation Hospital
Grant Number: W81XWH-07-CC-CS-DoD
Grant Period: 12/01/2008-11/30/2014 
NAC Personnel and Cores: C-F. Westin, PI, Lauren O'Donnell, Yogesh Rathi, Microstructure Imaging Core, Steve Pieper, Slicer Core
Joint Publications

Encephalographic MRI and Epilepsy Discharge Localization

Collaborating Investigators: Darren Orbach
Collaborating Institutions:  Children's Hospital, Boston, MA
Grant Number: NIH NINDS R21NS076859
Grant Period: 09/01/2011-08/31/2014
NAC Personnel and Cores: Sandy Wells, Spatio-Temporal Modeling of Disease Core
Joint Publications

Biomarkers and Risk Factors for Disease Progression in MS

Collaborating Investigators: Dominik Meier
Collaborating Institutions:  Brigham & Women's Hospital
Grant Number: National Multiple Sclerosis Research Grant RG 4256A4/2
Grant Period: 10/01/2010-09/30/2014 
NAC Personnel and Cores: William M. Wells, Matthew Toews, Spatio-Temporal Modeling of Disease Core
Joint Publications

SPARKit Software Platform and Adaptive Radiotherapy Kit

Collaborating Investigators: Gabor Fichtinger
Collaborating Institutions: Queen's University, Kingston, Ontario, Canada
Grant Number: Cancer Care Ontario (CCO), System Prototyping in Image-Guided Intervention Unit
Grant Period: 09/22/2010-07/31/2015
NAC Personnel and Cores: Steve Pieper, Slicer Core
Joint Publications

QIN: Quantitative MRI of Prostate Cancer as a Biomarker and Guide for Treatment

Collaborating Investigators: Fiona Fennessy
Collaborating Institutions: Brigham & Women's Hospital
Grant Number: NIH NCI 1U01CA151261
Grant Period: 09/22/2010-07/31/2015 
NAC Personnel and Cores: Steve Pieper, Nicole Aucoin, Wendy Plesniak, Slicer Core
Joint Publications

Novel Computational Methods from Higher Order Diffusion MRI in Autism

Collaborating Investigators: Ragini Verma
Collaborating Institutions: University of Pennsylvania, Philadelphia, PA
Grant Number: NIH NIMH R01MH092862
Grant Period: 09/28/2010-06/31/2015
NAC Personnel and Cores: C-F. Westin, Demian Wasserman, Microstructure Imaging Core'
Joint Publications

Diffusion and Functional MRI in Euroeconomics

Collaborating Investigators: Hans Knutsson, Camilla Josephson
Collaborating Institutions: Linkoping University, Linkoping, Sweden
Grant Number: VINOVA (Sweden) 2011-01368
Grant Period: 04/01/2011-03/31/2014
NAC Personnel and Cores: C-F. Westin, Lauren O'Donnell, Demian Wasserman, Microstructure Imaging Core
Joint Publications

Optimization of High Dose Conformal Therapy

Collaborating Investigators: |John Balter, Randall Ten Haken
Collaborating Institutions:  University of Michigan, Ann Arbor, MI
Grant Number: NIH NCI 5P01CA059827
Grant Period: 02/01/1997-06/30/2012 
NAC Personnel and Cores: William M. Wells, Petter Risholm, Spatio-Temporal Modeling of Disease Core
Joint Publications

NA-MIC: National Alliance for Medical Image Computing

Collaborating Investigators: Ron Kikinis, Ross Whitaker, Will Schroeder,
Collaborating Institutions:  Brigham & Women's Hospital, Boston, MA, University of Utah, Salt Lake City, UT, Kitware, Clifton Park, NY
Grant Number: NIH NIBIB U54EB005149
Grant Period: 09/17/2004-06/30/2014
NAC Personnel and Cores: C-F. Westin, Lauren O'Donnell, Yogesh Rathi, Microstructure Imaging Core,
Steve Pieper, Slicer Core
Joint Publications

Using Computed Tomographic Imaging as a Biomarker for Clinical COPD Research

Collaborating Investigators: George Washko,
Collaborating Institutions:  Brigham & Women's Hospital, Boston, MA
Grant Number: NIH NHLBI K23HL089353
Grant Period: 08/01/2008-06/30/2013
NAC Personnel and Cores: C-F. Westin, Microstructure Imaging Core, William M. Wells, Petter Risholm, Spatio-Temporal Modeling of Disease Core
Joint Publications 

fMRI Investigations of Visual Recognition and Attention

Collaborating Investigators: Nancy Kanwisher
Collaborating Institutions:  Masachusetts Institute of Technology, Cambridge, MA
Grant Number: NIH NEI R01EY13455
Grant Period: 08/01/1996-12/31/2014
NAC Personnel and Cores: Polina Golland,  Danial Lashkari, Ramesh Sridharan, G. Chen, Anatomic Variability Core
Joint Publications

Center for Integrative Biomedical Computing

Collaborating Investigators: Rob MacLeod, Christopher Johnson
Collaborating Institutions: University of Utah, Salt Lake City, UT
Grant Number: NIH NCRR P41RR012553
Grant Period: 09/01/2000-07/31/2015
NAC Personnel and Cores: Steve Pieper, Slicer Core
Joint Publications

Stroke Genetics Network (SiGN)

Collaborating Investigators: Steven Kittner, Natalia  Rost
Collaborating Institutions: University of Maryland, Baltimore, MD, Massachusetts General Hospital, Boston, MA
Grant Number: NIH NINSA U01NS069208
Grant Period: 07/01/2010-06/30/2015
NAC Personnel and Cores: Polina Golland, Anatomic Variability Core
Joint Publications

Computational Anatomy and Multidimensional Modeling

Collaborating Investigators: David Shattuck, Arthur Toga
Collaborating Institutions: University of California, Los Angeles, CA
Grant Number: NIH NCRR P41RR013642
Grant Period: 09/30/1998-07/31/2012
NAC Personnel and Cores: Steve Pieper, Slicer Core
Joint Publications

I2B2: Informatics for Integrating Biology and the Bedside

Collaborating Investigators: Shawn Murphy
Collaborating Institutions: Massachusetts General Hospital, Boston, MA
Grant Number: NIH NLM U54LM008748
Grant Period: 09/30/1998-07/31/2012
NAC Personnel and Cores: Steve Pieper, Slicer Core
Joint Publications

Center for Functional Imaging Technologies

Collaborating Investigators: Bruce R. Rosen, Bruce Fischl
Collaborating Institutions: Massachusetts General Hospital, Boston, MA
Grant Number: NIH NCRR P41RR014075
Grant Period: 09/01/2000-05/31/2014
NAC Personnel and Cores: Polina Golland, Christian Wachinger, Kayhan Batmanghelich, Ramesh Sridharan, Anatomic Variability Core, William M. Wells, Spatio-Temporal Modeling of Disease
Joint Publications