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Reliability of connectivity-based thalamic segmentation for targeting in

noninvasive neuromodulation using MR-guided Focused Ultrasound

Angela E. Downes M.D.1, Jeffrey Elias M.D.2, Nader Pouratian M.D., Ph.D.3

1 Department of Neurosurgery, Morsani, College of Medicine, University of South Florida, Tampa, Florida

2 Department of Neurosurgery, University of Virginia Health Sciences Center, University of Virginia, Charlottesville, VA

3Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA

MR-guided Focused Ultrasound

MR-guided Focused Ultrasound

Martin E, Jeanmonod D: High-intensity focused ultrasound for noninvasive functional neurosurgery. Ann Neurol.2009.

Essential Tremor

• Excellent study model • Most common movement disorder

• Surgical therapies

• Deep brain stimulation • RF thalamotomy • SRS

• VIM

Surgical treatments

• Lesioning is not extinct…

• DBS has complications

How can we make it better?

• Traditional Targeting Methods – Indirect targeting

– Direct targeting

– Intraoperative microelectrode recordings

Indirect Targeting

Limited due to intersubject anatomic variability

STN (relative to midcommisural point): X: 10-12 mm lateral Y: 2-4 mm posterior Z: 4-6 mm inferior

GPi (relative to midcommisural point): X: 19-22 mm lateral Y: 2-4 mm anterior Z: 4-5 mm inferior

VIM (relative to midcommisural point): X: Upper extremity: 12-14 mm lateral of midline Lower extremity: 14-16 mm lateral of midline Y: 5-6 mm anterior to PC OR 25% of the length of AC-PC behind MCP Z: 0 mm inferior

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Improved Structural Imaging: Direct Targeting

Limited because (1) not all targets are visible (e.g., within the thalamus) (2) Even if visualized, connectivity and function of visualized

structure not known for the individual patient VIM Thalamus

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Intraoperative Microelectrode Recordings

Identify electrophysiological activity consistent with target

2013… What tools do we have now? Brain mapping

Advances in neuroimaging

Structural

Diffusion weighted

Probabilistic diffusion

tractography

Fractional anisotropy

7T MRI

Functional

fMRI, PET

Connectivity-based thalamic segmentation

Pouratian et al. Journal of N

eurosurgery. 2011.

Validation of connectivity-based thalamic segmentation for DBS targeting for tremor

DBS Electrode

Region of Maximal Thalamic Connectivity With Premotor Cortex

Validation of connectivity-based thalamic targeting for FUS

• Hypothesis: Optimal location for FUS lesion colocalizes with thalamic voxels with the highest probability of connectivity with primary motor cortex

• Retrospective image analysis • 15 patients 12 connectivity maps

Primary motor connectivity

Primary somatosensory connectivity

FUS Lesion

Probabilistic connectivity based thalamic targeting

Excellent outcome High concordance

Poorer outcome Low concordance

Concordance of Automated M1-Thalamus with Final DBS FUS Lesion Position

A

B

C

Poorer outcome High concordance

Concordance of Automated M1-Thalamus with Final DBS FUS Lesion Position

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0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

ROC Curve 2 mm Sphere

Future directions

• Try different cortical connectivity – Premotor cortex, supplementary motor cortex

• Unknowns with FUS – Where is efficacious point in lesion? – Variaiblity across patients with size, shape,

intensity of lesion

• Incorporate side effects into analysis

Conclusions

• Tailored therapies

• Probabilistic tractography correlates both structure and function

• FUS has a real future as a noninvasive neurosurgical tool