Research

Our group focuses on developing complex biomarkers for neuropsychiatric disorders, particularly schizophrenia and Alzheimer's disease, using the tools of computational anatomy developed in conjunction with our collaborators. To achieve this goal, we develop and implement precise measures of neuroanatomical structure and then relate these measures to cognition, brain activation and specific elements of clinical psychopathology. One of our primary focuses is to describe changes in any of these measures that may occur during disease progression or treatment. As an adjunct to such studies, we also conduct clinical trials with special emphasis on interventions that aim to improve cognition.

In addition to neuropathology, our interests also lie in the neuroanatomical and functional consequences of normal genetic variation. Therefore, some of our studies employ juvenile subjects so that developmental aspects of brain structure and function may be studied.

Students in our laboratory have the opportunity to learn a wide variety of experimental techniques, working with structural and functional magnetic resonance imaging, diffusion tensor imaging and quantitative image analysis. They become familiar with scientific software such as MATLAB, in addition to learning specific software packages used for brain mapping and computational anatomy.

Volunteers

NIACAL welcomes research volunteers. Please visit the Psychiatry Department volunteer page to find out how to participate.

Projects

Because of the diverse interests of the NIACAL team, we are constantly exploring novel means of studying neuological disorders. Below are some of the projects with which we're currently involved.

Mapping of Brain Structures using MRI

Complex Neuroimaging Biomarkers

  • Hippocampal subfield measurements for the early diagnosis AD and prediction of cognitive decline (PI: Lei Wang): Dr. Wang is working with Drs. Michael Weiner/Susanne Mueller (co-PIs, UCSF lead site), Dr. Paul Yushkevich (U Penn), and Dr. Koen van Leemput (Harvard) on a project entitled "ADNI 2 add-on project: Superior power of hippocampal subfield measurements compared to conventional hippocampal volumetry for the early diagnosis AD and prediction of AD related cognitive decline." This project is funded by the Alzheimer Association, aiming to use multiple approach to measure hippocampal subfields using a new high-resolution T2-weighted sequence to detect the earliest hippocampal manifestations of AD. This cross-sectional study will test if subfield volumetry is indeed superior to standard hippocampal volumetry to identify the earliest manifestation of Alzheimer’s disease.
  • Predicting FTLD & AD neuropathology in PPA using hippocampal shape (PI: Wang): By using information about specific features of neuromorphological deformity from prior studies and data from preliminary studies of cortical gray matter thinning in PPA subjects, this study proposes to assess the agreement between group classification attained by neuromorphometry and by clinical categorization and to correlate these MRI measures with a nonverbal memory assessment in the same subjects.
  • Early detection of mild cognitive impairment and dementia using multidimensional analysis of structural MRI by computational methods (PI: Wei Wen, PhD (UNSW), Wang (Subcontract)): To develop novel multidimensional imaging biomarkers for early detection of brain anatomical changes due to MCI/dementia. We aim at identifying early signatures of MCI/dementia, thus making early treatment possible.
  • Improving Sensitivity of Early Detection of AD via Multidimensional Analysis of Longitudinal MR Scans (PI: M Faisal Beg, PhD (SFU), Wang (Subcontract)): To develop multidimensional biomarkers involving metrics in cortical thickness and volume, white matter hyper-intensity, and subcortical volume and shape over multiple time-points and evaluate their ability for early detection of AD on the MCI database obtained from the University of New South Wales.

Clinical Applications

  • Neural Capacity as Predictors of Cognition in Extreme Survivors of Glioblastoma Multiforme (PI: Lei Wang, PhD and Kristin Swanson, PhD): This project is a collaboration between the laboratories of Professor Lei Wang (Neuroimaging and Applied Computational Anatomy Lab) and Professor Kristin Swanson (Mathematical Neuro-Oncology Lab). We plan to assess neural capacity and functional recovery in the setting of injury; specifically, the ability of the brain to recover/remodel in long-term glioblastoma multiforme patients.
  • HippoPCI: Hippocampal Predictors of Cognitive Impairment in Breast Cancer Patients (PI: Wang): This is a longitudinal magnetic resonance imaging (MRI) study where we identify predictors and mechanisms of cognitive impairment in breast cancer patients receiving hormonal treatment by using structural and functional assessments that are sensitive to the integrity of the hippocampal-cortical circuitry.
  • Corticolimbic Degeneration and Treatment of Dementia (PI: Csernansky): To determine whether drugs currently used to treat Alzheimer disease alter the underlying disease process, as assessed using markers of brain structure and cognition in dementia patients and markers of amyloid deposition and neurodegeneration in APP-transgenic mice.
  • Mapping Abnormal Neurodevelopment in Schizophrenia (PI: Csernansky): We develop neuroimaging endophenotypes in subjects with schizophrenia and their younger, non-psychotic siblings.
  • Neuromorphometry in Schizophrenia by Computer Algorithm (PI: Csernansky): To utilize high resolution MR scans and computerized methods for neuromorphometry to detect and characterize progression of brain structure abnormalities in schizophrenia subjects.
  • Antecedent Biomarkers for AD: The Adult Children Study (PI: Csernansky): To identify neuroanatomical markers that differentiate individuals who are at higher versus lower genetic risk for the development of Alzheimer disease, and to correlate these markers with cognitive and neurochemical markers of genetic risk for Alzheimer disease.

Neuroinformatics

  • SchizConnect: Large-Scale Schizophrenia Neuroimaging Data Mediation & Federation (PI: Lei Wang (Contact, NU), Jose Luis Ambite (USC), Steven Potkin (UCI), Jessica Turner (MRN), David Keator (UCI)): Large-scale data sharing and integration is needed to further the state-of-the-art schizophrenia research, but is presently not possible due to practical limitations in the way in which data are being shared. SchizConnect is a data mediation and integration resource to overcome these limitations in a low-cost manner and deliver a web portal to interact with the federated databases. Access SchizConnect at http://schizconnect.org.
  • Northwestern University Schizophrenia Data and Software Tool (NUSDAST) (PI: Wang): To make structural magnetic resonance (MR) imaging data, genotyping data, and neurocognitive data as well as analysis tools available to the schizophrenic research community. Please note that this dataset is also accessible through the SchizConnect project at: http://schizconnect.org. Here, you will be able to get additional schizophrenia neuroimaging data from FBIRN and COINS.
  • Northwestern University Neuroimaging Data Archive (NUNDA) (PI: Wang): To establish a data archive for the neuroimaging community at Northwestern University, which has the capacity to efficiently and securely store collected MR scans, and to later retrieve them in time-sensitive datasets.

Preclinical Applications

  • MDD Marker using Rat Imaging (PI: Eva Redei, PhD, Wang): Using translational approach, we develop blood and brain imaging markers for major depression in a genetic rat model, and validate their integration in patients with recurrent early onset major depression.
  • Development of a Calcium-Sensitive MRI Probe for Neural Activity (PI: Wang): Collaborating with Meade, Csernansky, Thulborn (UIC), we demonstrate the feasibility of using MRI and contrast agents to quantify neural activity as reflected by changes in tissue Ca2+ concentration. The experimental methods and data collected from this project will be applied to future studies of intracellular Ca2+ contrast agents.
  • MRI of TDP-43 Mice Model of Primary Progressive Aphasia (PI: Csernansky, Wang): Using in vivo high-field MRI, we will characterize the changes in brain architecture in a TDP-43 overexpression mouse model of PPA.

Grants

At NIACAL, we are incredibly grateful for grant support.

  • NIH: T32 NS047987 Training Program in the Neuroscience of Human Cognition (PI: Lei Wang and Kristin Swanson) - (09/01/2014 - 08/31/2015). Associated project: Neural Capacity as Predictors of Cognition in Extreme Survivors of Glioblastoma Multiforme
  • James S. McDonnell Foundation: “The ENDURES Study: Environmental Dynamics Underlying Responsive Extreme Survivors of Glioblastoma” (PI: Kristin Swanson, PhD; Collaborating-PI: Lei Wang) - (09/01/2014 - 08/31/2017). Associated project: Neural Capacity as Predictors of Cognition in Extreme Survivors of Glioblastoma Multiforme
  • 1U01 MH097435: SchizConnect: Large-Scale Schizophrenia Neuroimaging Data Mediation & Federation (PI: Lei Wang (Contact, NU), Jose Luis Ambite (USC), Steven Potkin (UCI), Jessica Turner (MRN)) - We propose a data mediation and integration resource to overcome limitations in large-scale data sharing and integration in state-of-the-art schizophrenia research in a low-cost manner and deliver a web portal to interact with the federated databases. (03/19/2013 - 01/31/2017). Associated project: SchizConnect: Large-Scale Schizophrenia Neuroimaging Data Mediation & Federation
  • 1R01 NR014182: HippoPCI Hippocampal Predictors of Cognitive Impairment in Breast Cancer Patients (PI: Wang) - Post-surgery adjuvant therapy produces changes in cognitive function in up 10-70% of women with breast cancer. To date, no investigation has assessed the neural correlates of adjuvant hormonal therapy, nor have any studies determined how to identify individuals at risk for treatment-related cognitive impairment. We propose to use longitudinal magnetic resonance imaging (MRI) to identify predictors and mechanisms of cognitive impairment in breast cancer patients receiving hormonal treatment. (09/26/2012 - 06/30/2017). Associated project: HippoPCI: Hippocampal Predictors of Cognitive Impairment in Breast Cancer Patients
  • Ken and Ruth Davee Award for Innovative Investigations in Affective Disorders: Neuroimaging Pilot Study Using an Animal Model of Major Depression (PI: Lei Wang, Eva Redei) - We analyze structural and resting-state functional magnetic resonance (MR) scans and behaviors of a rat model of depression that Dr. Redei has developed (i.e.,Wistar Kyoto More Immobile, or WMI) and controls. The overall goal is to provide additional, critical preliminary data to demonstrate our ability to provide neuroimaging measures that can be used to associate with transcripts of the same abundance differences in brain regions and the blood of WMI rats (to be obtained from other, ongoing studies). (09/01/2012 - 08/31/2013). Associated project: MDD Marker using Rat Imaging
  • Alzheimer Association: ADNI 2 add on project: Hippocampal Subfield Volumetry (PI: NU Subaward - Lei Wang (co-PIs Michael Weiner/Susanne Mueller, UCSF)) - ADNI 2 add-on project: Superior power of hippocampal subfield measurements compared to conventional hippocampal volumetry for the early diagnosis AD and prediction of AD related cognitive decline - Northwestern Subaward. The project is a three year cross-sectional multi-site collaborative study between Penn Image Computing and Science Lab (PICSL, University of Pennsylvania), Athinoula A Martinos Center for Biomedical Imaging (AAMCBI, Harvard), Neuroimaging and Applied Computational Anatomy Lab (NIACAL, Northwestern University) and the Center for Imaging of Neurodegenerative Diseases (CIND, University of California, San Francisco)). Dr Weiner at CIND will be responsible for the administrative oversight of the project. Dr S. Mueller at CIND will be responsible for the scientific oversight of the entire project. PICSL, AAMBI and NIACAL will be affiliated research sites with one co-investigator each. The overall goal of the project is to test a. if subfield volumetry is superior to conventional hippocampal volumetry to detect the earliest manifestation of beginning AD and b. to identify which of the currently available subfield volumetry approaches has the highest sensibility and sensitivity to differentiate between healthy controls and MCI and between amyloid positive and negative subjects. (07/01/2012 - 06/30/2015). Associated project: Hippocampal subfield measurements for the early diagnosis AD and prediction of cognitive decline
  • T32 NS047987-05 NINDS: Training Program in the Neuroscience of Human Cognition (PI: Paller. Predoctoral student: Matthew Schroeder) - The project for this program focuses on identifying the neural regions responsible to acquisition and consolidation of a conditioned task in rabbits using manganese-enhanced MRI. (09/20/2011 - 09/19/2013). Associated project: Acquisition and consolidation of trace eyeblink conditioning in rabbits using prestimulus theta activity and manganese-enhanced MRI
  • CNADC Pilot Grant: Predicting FTLD & AD neuropathology in PPA using hippocampal shape: A pilot study (PI: Wang) - By using information about specific features of neuromorphological deformity from prior studies and data from preliminary studies of cortical gray matter thinning in PPA subjects, this study proposes to assess the agreement between group classification attained by neuromorphometry and by clinical categorization and to correlate these MRI measures with a nonverbal memory assessment in the same subjects. (07/01/2011 - 06/12/2012). Associated project: Predicting FTLD & AD neuropathology in PPA using hippocampal shape
  • T32 NS047987-05 NINDS: Training Program in the Neuroscience of Human Cognition (PI: Paller. Postdoctoral Fellow: Derin Cobia) - The project for this program focuses on identification and analysis of working memory circuits in neuropsychologically defined schizophrenia subtypes. (01/01/2011 - 12/31/2011).
  • Brain Research Foundation: Development of a Calcium-Sensitive MRI Probe for Neural Activity (PI: Wang) - We demonstrate the feasibility of using MRI and contrast agents to quantify neural activity as reflected by changes in tissue Ca2+ concentration. The experimental methods and data collected from this project will be applied to future studies of intracellular Ca2+ contrast agents. (05/03/2010 - 05/02/2011). Associated project: Development of a Calcium-Sensitive MRI Probe for Neural Activity
  • The Michael J. Fox Foundation for Parkinson’s Disease: DTI MRI imaging as a biomarker for Parkinson’s Disease diagnosis and disease progression (PI: Simuni/Gitelman) - Establish validity of DTI high resolution MRI imaging in the diagnosis and measure of progression on PD. (12/01/2009 - 11/30/2011).
  • 1 R01 MH084803 NIMH: Schizophrenia Data and Software Tool Federation using BIRN Infrastructure (PI: Wang) - To make structural magnetic resonance (MR) imaging data, genotyping data, and neurocognitive data as well as analysis tools available to the schizophrenic research community. (07/01/2009 - 12/31/2012). Associated project: Northwestern University Schizophrenia Data and Software Tool (NUSDAST)
  • Northwestern Memorial Hospital: Northwestern University Neuroimaging Data Archive (NUNDA) (PI: Csernansky/Wang) - To establish a data archive for the neuroimaging community at Northwestern University. (10/01/2008 - 10/01/2011). Associated project: Northwestern University Neuroimaging Data Archive (NUNDA)
  • Australian National Health and Medical Research Council: Early detection of mild cognitive impairment and dementia using multidimensional analysis (PI: Wen (Wang, Subcontract)) - To develop novel multidimensional imaging biomarkers for early detection of brain anatomical changes due to MCI. We aim at identifying early signatures of MCI, thus making early treatment possible. (11/01/2007 - 10/31/2011).
  • P50 MH71616 NIMH : Mapping Abnormal Neurodevelopment in Schizophrenia (PI: Csernansky) - The Conte Center for Neuroscience of Mental Disorders is a multi-institutional collaboration between scientists with special expertise in psychiatry, neurobiology, neuroimaging and biomedical engineering. (09/20/2007 - 07/20/2009). Associated project: Mapping Abnormal Neurodevelopment in Schizophrenia
  • 2 R01 MH56584-09 NIMH: Neuromorphometry in Schizophrenia by Computer Algorithm (PI: Csernansky) - To utilize high resolution MR scans and computerized methods for neuromorphometry to detect and characterize progression of brain structure abnormalities in schizophrenia subjects. (03/01/2007 - 02/28/2012). Associated project: Neuromorphometry in Schizophrenia by Computer Algorithm