Diffusion MRI Tractography for Improved MRI-guided Focused Ultrasound Thalamotomy Targeting for Essential Tremor
Qiyuan Tian1,2, Max Wintermark2, Kim Butts Pauly2, Diane Huss3, W. Jeffrey Elias4, and Jennifer A. McNab2

1Electrical Engineering, Stanford University, Stanford, CA, United States, 2Radiology, Stanford University, Stanford, CA, United States, 3Physical Therapy, University of Virginia, Charlottesville, VA, United States, 4Neurosurgery, University of Virginia, Charlottesville, VA, United States

Synopsis

We retrospectively studied 13 essential tremor patients treated with MRI-guided focused ultrasound. The purpose was to demonstrate the value of using diffusion MRI tractography to help localize the ventral intermediate (Vim) nucleus of the thalamus (the treatment target). Tractography between the thalamus and hand-knob region of the motor cortex was consistent from subject-to-subject and followed the expected anatomy. The thalamic voxels with high tractography streamline counts qualitatively matched the location of Vim as depicted on the Schaltenbrand-Wahren Atlas. A trend was found towards better treatment outcome scores with higher pre-treatment probabilistic tractography streamline counts within the visualized MRgFUS treatment-induced lesion.

Target Audience

Physicists, neuroscientists and clinicians who are interested in using diffusion tractography.

Introduction

MRI-guided focused ultrasound (MRgFUS) provides a less invasive way to lesion the ventral intermediate (Vim) nucleus of the thalamus as a treatment for essential tremor (ET) (1-3). Delineation of Vim is challenging because of its small size and the low intrinsic contrast between thalamic nuclei on structural MRI. Current methods to target Vim use a standard atlas overlaid on the patient’s MRI or stereotactic coordinates relative to the anterior commissure-posterior commissure line (4). We conducted a retrospective study to evaluate the value of diffusion tractography for targeting Vim in the MRgFUS treatment of ET patients (5-10). Specifically, we performed diffusion tractography on pre-treatment data to map structural connections between the thalamus and the hand-knob region of the motor cortex on the treated hemisphere. The tractography streamline counts within the MRgFUS treatment-induced lesion (as visualized on post-treatment T1-weighted images) were compared with treatment outcomes.

Methods

Data Acquisition. With IRB approval and prospective informed consent, 13 patients with medication-refractory ET were treated with transcranial MRgFUS targeting Vim contralateral to their dominant hand in an FDA-approved pilot clinical trial (1-3). Data acquisition included whole-brain diffusion tractography pre-treatment (baseline) and T1-weighted images 1 week post-treatment (parameters in Fig.1a). ROIs were drawn by a neuroradiologist (M.W.) for the thalamus and hand-knob on the baseline diffusion data, and for the lesion on the week-1 T1-weighted images (Fig.1b-d).

Data Analysis. Baseline diffusion images were corrected for eddy current distortions and bulk motion using “eddy_correct” from the FMRIB Software Library (FSL, http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/). Voxel-wise crossing fiber orientation distributions were estimated using FSL’s “bedpostx”. Probabilistic tractography was performed using FSL’s “probtrackx2” using the entire thalamus as the “seed” and the hand-knob region as the “target”. FSL’s classification option was used to determine the number of streamlines from each thalamic voxel that reach the hand-knob region and then these streamline counts were normalized by the total streamline count (for all thalamic voxels) for each subject (5). Week-1 post-treatment T1-weighted images were registered to baseline diffusion images using FSL’s “flirt”. The streamline counts within the lesion were summed and correlated with clinical outcomes.

Clinical Outcome. The efficacy of tremor suppression was measured using the Clinical Rating Scale for Tremor (CRST) (11). The three components of CRST consist of Part A (tremor localization/severity), Part B (specific motor task/function) and Part C (functional disabilities resulting from tremor). We correlated the tractography results with first: a combined A&B score for the treated hand (0 to 32), and second: the total score (reflecting tremor in all parts of the body including both sides, 0 to 160). These scores were acquired at baseline, 3 months and 1 year post-treatment, with higher scores indicating worse tremor.

Results and Discussion

Figure 2 displays the thresholded (10% of total for each subject) and volume rendered tractography results for all subjects. The tractography between the thalamus and the hand-knob region is consistent from subject-to-subject and follows the expected anatomy.

Figure 3 displays the streamline counts overlaid on an axial slice for all subjects. Streamline counts were thresholded (0.3% of the total for each subject) for improved visualization. The thalamic voxels with high streamline counts qualitatively match the expected location of Vim as depicted on the Schaltenbrand-Wahren Atlas (12) (Fig.2 lower right). The resolution of the tractography-delineated Vim was limited by the diffusion image resolution (5.2×1.8×1.8mm3 for the current study).

Figure 4 displays the CRST A&B scores for the treated hand and the CRST total scores for individual subjects and the group mean at baseline, 3 months and 1 year post-treatment. Both CRST A&B and CRST total scores decreased significantly at 3 months and recovered slightly at 1 year.

Figure 5 shows scatter plots with fitted lines for the streamline counts within the lesions versus the CRST scores. These plots indicate a trend that patients with higher streamline counts within the MRgFUS treatment-induced lesion had a better treatment outcome (i.e. lower CRST scores).

In summary, we have demonstrated the value of using a clinically feasible diffusion tractography acquisition (7 minutes) to localize Vim. An acquisition with smaller, isotropic voxels is expected to improve the accuracy of the tractography. In practice, thalamic voxels with high streamline counts to the hand-knob area could be used as an adjunct surrogate marker of Vim. The diffusion data could be acquired alongside, and used in combination with, the existing pre-treatment imaging that is used to estimate the location of Vim and then co-registered to the MR images acquired in real-time during MRgFUS treatment.

Acknowledgements

We thank Gwenaëlle Douaud and Saad Jbabdi for helpful discussion. Funding was provided by GE Healthcare, NIH: P41-EB015891, S10-RR026351.

References

1. Elias WJ, et al. A pilot study of focused ultrasound thalamotomy for essential tremor. New England Journal of Medicine. 2013;369(7):640-8.

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12. Schaltenbrand G, et al. Introdution to stereotaxis with an atlas of the human brain: Georg Thieme; 1959.

Figures

Figure 1. Data acquisition parameters (a) and example axial slices from baseline diffusion data (b=0 s/mm2) (b and c) and week-1 post-MRgFUS treatment T1-weighted data (d). Blue region in (b), green region in (c) and red region in (d) inset display the hand-drawn thalamus, hand-knob and lesion ROIs.

Figure 2. Volume rendered probabilistic tractography results (red, thresholded at 10% of total number of streamlines) with thalamus (blue) and hand-knob ROIs (green) for all 13 subjects. The zoomed region for S13 displays the intersection of thalamus and tractography.

Figure 3. Normalized and thresholded (0.3% of total) streamline counts (red-yellow) of thalamic voxels (blue) overlaid on an axial baseline b0 image for all 13 subjects. Lower right image shows the location of Vim (red arrow) on an axial section of thalamus from the Schaltenbrand-Wahren Atlas (12).

Figure 4. CRST A&B score for the treated hand (a) and CRST total score (b) for all 13 subjects at three time points: prior to the MRgFUS treatment (baseline), 3 months and 1 year post-MRgFUS treatment.

Figure 5. Scatter plots showing streamline counts within the MRgFUS treatment-induced lesion versus CRST A&B score for the treated hand measured 3 months (a) and 1 year (b) post-MRgFUS treatment, and CRST total score measured 3 months (c) and 1 year (d) post-MRgFUS treatment for all 13 subjects.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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