Optical imaging is a non-invasive imaging modality that can visualize functional dynamics of blood volume and oxygen consumption associated with brain physiology and pathology. The Culver group has developed a novel high-density diffuse optical tomography (HD-DOT) system that achieves fMRI-comparable image quality and sensitivity and can detect cortical resting state networks (RSN) using functional connectivity and cortical blood flow responses to tasks. This technological innovation now opens up new avenues of research into patient populations that cannot be imaged with fMRI. A prime example of this new opportunity is individuals with implanted deep brain stimulators (DBS). The systems-level impact of DBS responsible for clinical benefit and potential side-effects is still not fully understood and could be useful in optimizing DBS, potentially providing short-cuts to the current trial-and-error approach to programming and electrode selection. Currently, investigations into the brain networks involved in DBS are difficult due to the significant limitations of conventional neuroimaging techniques. Due to contraindications from implanted hardware, these patients cannot be safely imaged with MRI for research purposes. Although blood flow can be measured by PET in these patients, studies are limited due to radiation exposure limits and poor temporal resolution (e.g. minutes). In contrast, HD-DOT allows us to measure cortical hemodynamics in response to task or DBS conditions and measure resting state networks with comparable temporal and spatial resolution to fMRI and with greater comfort (patients sit in a comfortable chair during scanning) and no radiation exposure. We have previously shown the feasibility of assessing cortical RSNs and task-induced responses in a small number of patients with subthalamic nucleus (STN) DBS. The work proposed here will establish the utility and sensitivity of HD-DOT to answer important clinical and theoretical questions in two different DBS populations.

Public Health Relevance

We have developed a novel high-density diffuse optical tomography (HD-DOT) system that can measure functional connectivity and cortical blood flow responses to tasks. This technique can now be applied to patient populations that cannot be imaged with fMRI. A prime example of this new opportunity is individuals with implanted deep brain stimulators (DBS). The impact of DBS responsible for clinical benefit and potential side- effects is still not fully understood and could be useful clinically. We have previously shown the feasibility of using HD-DOT in a small number of patients with subthalamic nucleus (STN) DBS. The work proposed here will establish the utility and sensitivity of HD-DOT to answer important clinical and theoretical questions in two different DBS populations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS098020-01A1
Application #
9242769
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Chen, Daofen
Project Start
2016-09-01
Project End
2018-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
1
Fiscal Year
2016
Total Cost
$228,750
Indirect Cost
$78,750
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Jinnah, H A; Comella, Cynthia L; Perlmutter, Joel et al. (2018) Longitudinal studies of botulinum toxin in cervical dystonia: Why do patients discontinue therapy? Toxicon 147:89-95