Feasibility of diffusion and probabilistic white matter analysis in patients implanted with a deep brain stimulator.

Deep brain stimulation (DBS) for Parkinson\u27s disease (PD) is an established advanced therapy that produces therapeutic effects through high frequency stimulation. Although this therapeutic option leads to improved clinical outcomes, the mechanisms of the underlying efficacy of this treatment are not well understood. Therefore, investigation of DBS and its postoperative effects on brain architecture is of great interest. Diffusion weighted imaging (DWI) is an advanced imaging technique, which has the ability to estimate the structure of white matter fibers; however, clinical application of DWI after DBS implantation is challenging due to the strong susceptibility artifacts caused by implanted devices. This study aims to evaluate the feasibility of generating meaningful white matter reconstructions after DBS implantation; and to subsequently quantify the degree to which these tracts are affected by post-operative device-related artifacts. DWI was safely performed before and after implanting electrodes for DBS in 9 PD patients. Differences within each subject between pre- and post-implantation FA, MD, and RD values for 123 regions of interest (ROIs) were calculated. While differences were noted globally, they were larger in regions directly affected by the artifact. White matter tracts were generated from each ROI with probabilistic tractography, revealing significant differences in the reconstruction of several white matter structures after DBS. Tracts pertinent to PD, such as regions of the substantia nigra and nigrostriatal tracts, were largely unaffected. The aim of this study was to demonstrate the feasibility and clinical applicability of acquiring and processing DWI post-operatively in PD patients after DBS implantation. The presence of global differences provides an impetus for acquiring DWI shortly after implantation to establish a new baseline against which longitudinal changes in brain connectivity in DBS patients can be compared. Understanding that post-operative fiber tracking in patients is feasible on a clinically-relevant scale has significant implications for increasing our current understanding of the pathophysiology of movement disorders, and may provide insights into better defining the pathophysiology and therapeutic effects of DBS

Methodological considerations for neuroimaging in deep brain stimulation of the subthalamic nucleus in Parkinson’s disease patients

Deep brain stimulation (DBS) of the subthalamic nucleus is a neurosurgical intervention for Parkinson’s disease patients who no longer appropriately respond to drug treatments. A small fraction of patients will fail to respond to DBS, develop psychiatric and cognitive side-effects, or incur surgery-related complications such as infections and hemorrhagic events. In these cases, DBS may require recalibration, reimplantation, or removal. These negative responses to treatment can partly be attributed to suboptimal pre-operative planning procedures via direct targeting through low-field and low-resolution magnetic resonance imaging (MRI). One solution for increasing the success and efficacy of DBS is to optimize preoperative planning procedures via sophisticated neuroimaging techniques such as high-resolution MRI and higher field strengths to improve visualization of DBS targets and vasculature. We discuss targeting approaches, MRI acquisition, parameters, and post-acquisition analyses. Additionally, we highlight a number of approaches including the use of ultra-high field (UHF) MRI to overcome limitations of standard settings. There is a trade-off between spatial resolution, motion artifacts, and acquisition time, which could potentially be dissolved through the use of UHF-MRI. Image registration, correction, and post-processing techniques may require combined expertise of traditional radiologists, clinicians, and fundamental researchers. The optimization of pre-operative planning with MRI can therefore be best achieved through direct collaboration between researchers and clinicians

Use of functional neuroimaging and optogenetics to explore deep brain stimulation targets for the treatment of Parkinson's disease and epilepsy

Deep brain stimulation (DBS) is a neurosurgical therapy for Parkinson’s disease and epilepsy. In DBS, an electrode is stereotactically implanted in a specific region of the brain and electrical pulses are delivered using a subcutaneous pacemaker-like stimulator. DBS-therapy has proven to effectively suppress tremor or seizures in pharmaco-resistant Parkinson’s disease and epilepsy patients respectively. It is most commonly applied in the subthalamic nucleus for Parkinson’s disease, or in the anterior thalamic nucleus for epilepsy. Despite the rapidly growing use of DBS at these classic brain structures, there are still non-responders to the treatment. This creates a need to explore other brain structures as potential DBS-targets. However, research in patients is restricted mainly because of ethical reasons. Therefore, in order to search for potential new DBS targets, animal research is indispensable. Previous animal studies of DBS-relevant circuitry largely relied on electrophysiological recordings at predefined brain areas with assumed relevance to DBS therapy. Due to their inherent regional biases, such experimental techniques prevent the identification of less recognized brain structures that might be suitable DBS targets. Therefore, functional neuroimaging techniques, such as functional Magnetic Resonance Imaging and Positron Emission Tomography, were used in this thesis because they allow to visualize and to analyze the whole brain during DBS. Additionally, optogenetics, a new technique that uses light instead of electricity, was employed to manipulate brain cells with unprecedented selectivity

Mov Disord

Background:Deep brain stimulation of the subthalamic nucleus is a widely-used adjunctive therapy for motor symptoms of Parkinson disease, but with variable motor response. Predicting motor response remains difficult and novel approaches may improve surgical outcomes as well as understanding regarding pathophysiological mechanisms.Objective:To determine whether pre-operative resting state functional connectivity MRI predicts motor response from deep brain stimulation of the subthalamic nucleus.Methods:We collected preoperative resting-state functional MRI from 70 participants undergoing subthalamic nucleus deep brain stimulation. For this cohort, we analyzed strength of STN functional connectivity with seeds determined by stimulation-induced (ON/OFF) 15O H2O PET regional cerebral blood flow differences in a partially overlapping group (n = 42). We correlated STN-seed functional connectivity strength with postoperative motor outcomes and applied linear regression to predict motor outcomes.Results:Preoperative functional connectivity between left subthalamic nucleus and ipsilateral internal globus pallidus correlated with postsurgical motor outcomes (r = 120.39, p = 0.0007), with stronger preoperative functional connectivity relating to greater improvement. Left pallidal-subthalamic nucleus connectivity also predicted motor response to DBS after controlling for covariates.Interpretation:Preoperative pallidal-subthalamic nucleus resting-state functional connectivity predicts motor benefit from deep brain stimulation, though this should be validated prospectively before clinical application. These observations suggest that integrity of pallidal-subthalamic nucleus circuits may be critical to motor benefits from deep brain stimulation.U19 NS110456/NS/NINDS NIH HHSUnited States/UH3 TR002065/TR/NCATS NIH HHSUnited States/R01 DK064832/DK/NIDDK NIH HHSUnited States/U54 NS116025/NS/NINDS NIH HHSUnited States/RF1 AG064937/AG/NIA NIH HHSUnited States/R01 NS075321/NS/NINDS NIH HHSUnited States/R01 NS075527/NS/NINDS NIH HHSUnited States/K23 NS041248/NS/NINDS NIH HHSUnited States/R01 NS097799/NS/NINDS NIH HHSUnited States/P01 NS080675/NS/NINDS NIH HHSUnited States/R01 HD085930/HD/NICHD NIH HHSUnited States/R01 NS109487/NS/NINDS NIH HHSUnited States/R01 NS107281/NS/NINDS NIH HHSUnited States/R01 ES025991/ES/NIEHS NIH HHSUnited States/R01 AG050263/AG/NIA NIH HHSUnited States/F31 NS071639/NS/NINDS NIH HHSUnited States/R01 NS058797/NS/NINDS NIH HHSUnited States/C06 RR020092/RR/NCRR NIH HHSUnited States/R01 EB009352/EB/NIBIB NIH HHSUnited States/R01 NS103957/NS/NINDS NIH HHSUnited States/P30 NS098577/NS/NINDS NIH HHSUnited States/R01 NS041509/NS/NINDS NIH HHSUnited States/U54 TR001456/TR/NCATS NIH HHSUnited States/R01 HD070855/HD/NICHD NIH HHSUnited States/P30 NS048056/NS/NINDS NIH HHSUnited States/R01 NS097437/NS/NINDS NIH HHSUnited States/R01 ES029524/ES/NIEHS NIH HHSUnited States/U54 NS065701/NS/NINDS NIH HHSUnited States/UL1 TR000448/TR/NCATS NIH HHSUnited States/R21 AG063974/AG/NIA NIH HHSUnited States/U24 CA204854/CA/NCI NIH HHSUnited States/R61 AT010753/AT/NCCIH NIH HHSUnited States/U10 NS077384/NS/NINDS NIH HHSUnited States/UL1 TR002345/TR/NCATS NIH HHSUnited States/UH2 TR002065/TR/NCATS NIH HHSUnited States/R01 NS092865/NS/NINDS NIH HHSUnited States/R01 OH011661/OH/NIOSH CDC HHSUnited States/T32 EB021955/EB/NIBIB NIH HHSUnited States/2022-03-01T00:00:00Z33211330PMC798781211017vault:3678

Imaging the subthalamic nucleus in Parkinson’s disease

This thesis is comprised of a set of work that aims to visualize and quantify the anatomy, structural variability, and connectivity of the subthalamic nucleus (STN) with optimized neuroimaging methods. The study populations include both healthy cohorts and individuals living with Parkinson's disease (PD). PD was chosen specifically due to the involvement of the STN in the pathophysiology of the disease. Optimized neuroimaging methods were primarily obtained using ultra-high field (UHF) magnetic resonance imaging (MRI). An additional component of this thesis was to determine to what extent UHF-MRI can be used in a clinical setting, specifically for pre-operative planning of deep brain stimulation (DBS) of the STN for patients with advanced PD. The thesis collectively demonstrates that i, MRI research, and clinical applications must account for the different anatomical and structural changes that occur in the STN with both age and PD. ii, Anatomical connections involved in preparatory motor control, response inhibition, and decision-making may be compromised in PD. iii. The accuracy of visualizing and quantifying the STN strongly depends on the type of MR contrast and voxel size. iv, MRI at a field strength of 3 Tesla (T) can under certain circumstances be optimized to produce results similar to that of 7 T at the expense of increased acquisition time

小動物におけるEEGとfMRIの同時計測法の確立

Tohoku University川島隆太課