Deep brain stimulation (DBS) is a Food and Drug Administration (FDA) approved neurosurgical procedure that has emerged as the gold-standard treatment for drug-resistant Parkinson's disease (PD), the second most common neurodegenerative disorder, which affects more patients than the combined number of people diagnosed with multiple sclerosis, muscular dystrophy, and Lou Gehrig's disease. DBS is also used to treat refractory chronic pain, a debilitating condition that affects more than 100 million Americans. Despite the general effectiveness of DBS, its underlying mechanisms of action are still unclear. Uncertainties remain about which circuits are affected, which exact fiber bundles need to be targeted, and the most efficacious stimulation protocol. The meticulous use of neuroimaging, both for target verification and for monitoring treatment-induced changes in the functional connectivity of affected brain networks is an essential step in interpreting clinical outcomes, testing new hypotheses and, consequently, designing enhanced therapeutic protocols. In this regard, magnetic resonance imaging (MRI) appears excellently poised as a high-resolution, non-invasive imaging tool, which could help address these open questions. However, the interaction of the radiofrequency (RF) fields of MRI scanners and the implanted electrodes imposes serious safety hazards that restrict the applicability of MRI for DBS patients. As a result, available MRI methodologies for DBS patients are limited in resolution and suffer from severe image artifacts that confound studies of the functional connectivity of affected brain networks. This program develops and validates novel MRI methodologies tailored and validated for patient-specific geometries, which will bring MRI to bear on the clinical questions regarding the mechanism and targeting of DBS treatment.
The specific aims of this project are, therefore: (1) to develop and validate a patient-adjustable, reconfigurable MRI transmit coil, integrated with a 32-channel close-fit brain array, which enables the reduction of the unwanted interaction of RF fields and implanted electrodes up to 100-fold below levels produced by currently available systems, while increasing the signal-to-noise ratio (SNR) up to four times at the level of cortical structures; (2) the validation of developed methodologies with comprehensive electromagnetic simulations and phantom experiments to determine the safe range of imaging parameters and optimize clinical imaging protocols; and (3) devising methodologies which use the developed technology to enhance prediction of altered patterns of functional connectivity of the cortico-striatal loops in advanced Parkinson's patients. The immediate goal of this project is to develop and optimize MRI methodologies to enhance structural and functional imaging of PD-affected brain networks at field intensities that are FDA approved for DBS imaging and to apply these methodologies for enhanced functional mapping of cortico-striatal loops in advanced PD patients. The outcome serves as the launching point for the long-term goal of enabling the study of dynamic DBS-induced changes in the functional architecture of the brain.

Public Health Relevance

Parkinson's disease is the second most common neurodegenerative disease affecting more than one million people in America. Deep brain stimulation (DBS) is a surgical procedure which uses implanted electrodes to send electrical pulses to regions deep within the brain to treat symptoms of Parkinson's disease. High resolution magnetic resonance imaging (MRI) of the brain after the surgery is very useful for verifying the location of the electrodes and for monitoring changes in the brain due to treatment. Today however, MRI is not fully accessible to these patients because of safety concerns. In this work, we develop novel MRI technologies that for the first time enable clinicians to safely acquire high-resolution images of patients' brains with DBS implants to obtain information about the function and structure of affected brain networks.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Career Transition Award (K99)
Project #
5K99EB021320-02
Application #
9336924
Study Section
Special Emphasis Panel (ZEB1)
Program Officer
Wang, Shumin
Project Start
2016-09-01
Project End
2018-06-30
Budget Start
2017-09-01
Budget End
2018-06-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
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Golestanirad, Laleh; Angelone, Leonardo M; Iacono, Maria Ida et al. (2017) Local SAR near deep brain stimulation (DBS) electrodes at 64 and 127 MHz: A simulation study of the effect of extracranial loops. Magn Reson Med 78:1558-1565
Golestanirad, Laleh; Iacono, Maria Ida; Keil, Boris et al. (2017) Construction and modeling of a reconfigurable MRI coil for lowering SAR in patients with deep brain stimulation implants. Neuroimage 147:577-588
Bonmassar, Giorgio; Golestanirad, Laleh (2017) EM fields comparison between planar vs. solenoidal ?MS coil designs for nerve stimulation. Conf Proc IEEE Eng Med Biol Soc 2017:3576-3579
Golestanirad, Laleh; Keil, Boris; Angelone, Leonardo M et al. (2017) Feasibility of using linearly polarized rotating birdcage transmitters and close-fitting receive arrays in MRI to reduce SAR in the vicinity of deep brain simulation implants. Magn Reson Med 77:1701-1712