Longitudinal analysis of structural changes following unilateral focused ultrasound thalamotomy

Francesco Sammartino, Fang-Cheng Yeh, Vibhor Krishna, Francesco Sammartino, Fang-Cheng Yeh, Vibhor Krishna

Abstract

Objective: Focused ultrasound thalamotomy is an emerging treatment for essential tremor, and it is ideal for studying reorganization in the human brain after acute injury because it creates a controlled thalamic ablation without breaching the cortex. However, there is not yet a metric capable of detecting microstructural changes in the presence of acute phase edema with good sensitivity in the chronic phase, when the lesion boundaries become inconspicuous.

Methods: We prospectively studied microstructural changes at the lesion site using generalized q-sampling imaging with restricted diffusion imaging. We obtained diffusion-weighted MRI scans preoperatively, 1 day after (n = 18), and 1 year after (n = 9) focused ultrasound thalamotomy. The restricted diffusion imaging maps were compared at the group level, controlling for improvement in contralateral hand tremor.

Results: The restricted diffusion imaging metric significantly increased in the 1 day post images, and the area with restricted diffusivity extended beyond the lesion boundaries identified on T2-weighted imaging. Two distinct zones of microstructural changes were identified, and the lesion area was identifiable at 1 year. The anterior and medial aspects of the lesion had a significant changes in RDI at 1 year, potentially signifying reorganization. The voxels with significant changes in restricted diffusion imaging values extend beyond the VIM into the surrounding white matter.

Interpretation: Correcting for free water contamination with restricted diffusion imaging allowed us to study microstructural changes after focused ultrasound thalamotomy. We observed statistically significant changes in RDI in the anterior and medial aspect of the lesion at 1 year. Whether these changes represent tissue reorganization remains to be confirmed in future studies. These findings may support performing additional ablations antero-medially for durable efficacy.

Keywords: Focused ultrasound; Free water correction, Lesion characteristics; Thalamotomy; Tractography.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
(A) Lesion boundaries become inconspicuous after FUS-T in contrast to radiofrequency thalamotomy (B). The structural T2-weighted images are compared between a patient with left radiofrequency thalamotomy (imaging obtained 18 years after surgery) and a patient (B) who had focused ultrasound thalamotomy (imaging obtained 1 year after surgery) for the treatment of essential tremor. In contrast to the radiofrequency lesion, both fractional anisotropy (FA) and mean diffusivity (MD) maps in the corresponding location fail to reveal the FUS-T lesion.
Fig. 2
Fig. 2
Processing pipeline: flow chart that illustrates the steps of the dMRI processing pipeline from acquisition to statistical analysis.
Fig. 3
Fig. 3
Group-level comparison of diffusion metrics at the slab level: Thresholded maps resulting from the t-test (FSL randomise, 5000 permutations with TFCE), comparing baseline and 1 day post values. From the top: RDI (A), FA (B), MD (C) comparison maps (threshold p < 0.05).
Fig. 4
Fig. 4
The different zones resulting from RDI clustering. (A) Green: zone 1; Yellow: zone 2; Blue: zone 3; Red: zone 4. (B) Violin plots for the group level RDI percentage changes in each zone, between baseline and 1 day post, and between 1 day and 1 year post maps. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 5
Fig. 5
Differences in streamline counts between zone 1 and zone 2 at 1 year (B) compared to pre-surgical baseline (A). Tractography using DSISTUDIO software for the nine patients with 1-year data; group template seeding from the group-level mask of zone 1 (green) and zone 2 (yellow). (C) Boxplots showing the number of streamlines per cluster and per time point. ** = t-test p-value < 0.001.
Fig. 6
Fig. 6
Illustration of RDI changes at the single-patient level (ID 9 in Supplementary Table 1) between (A) baseline, (B) 1 day post imaging, and (C) 1 year post imaging. Right: RDI maps; Left: the corresponding T2 image. The median RDI values in zone 1, in this case, were 3.09 (SD 0.56) at 1 day post and 2.54 (SD 0.30) at 1 year post, while the values in the surrounding cluster were 2.20 (SD 0.32) and 1.36 (SD 0.28). (D) Bar graph showing the median RDI in zone 1 between baseline (left), 1 day post (middle), and 1 year post (right) at the group level. * = comparisons that are significant with p 

Fig. 7

Group-level comparison of RDI values.…

Fig. 7

Group-level comparison of RDI values. (A) Voxels with a significant increase in RDI…

Fig. 7
Group-level comparison of RDI values. (A) Voxels with a significant increase in RDI at 1 day post-FUS-T across all patients (FSL randomise t-test, 18 comparisons, 5000 permutations with TFCE). (B) Voxels with significant RDI increase when accounting for tremor improvement at 3 months. (C) Voxels with significant RDI decrease at 1 year. (D) Surviving voxels after the t-test between 1 day post and 1 year post RDI images, after adjusting for percentage of tremor improvement.

Supplementary Fig. 1

ROC curves of (A–B)…

Supplementary Fig. 1

ROC curves of (A–B) RDI to predict lesion size and percentage of…

Supplementary Fig. 1
ROC curves of (A–B) RDI to predict lesion size and percentage of tremor improvement at 3 months; (C–D) FA to predict lesion size and tremor improvement.

Supplementary Fig. 2

Zoomed insets of Fig.…

Supplementary Fig. 2

Zoomed insets of Fig. 3 (A-B-C follow the same label order).

Supplementary Fig. 2
Zoomed insets of Fig. 3 (A-B-C follow the same label order).
All figures (9)
Fig. 7
Fig. 7
Group-level comparison of RDI values. (A) Voxels with a significant increase in RDI at 1 day post-FUS-T across all patients (FSL randomise t-test, 18 comparisons, 5000 permutations with TFCE). (B) Voxels with significant RDI increase when accounting for tremor improvement at 3 months. (C) Voxels with significant RDI decrease at 1 year. (D) Surviving voxels after the t-test between 1 day post and 1 year post RDI images, after adjusting for percentage of tremor improvement.
Supplementary Fig. 1
Supplementary Fig. 1
ROC curves of (A–B) RDI to predict lesion size and percentage of tremor improvement at 3 months; (C–D) FA to predict lesion size and tremor improvement.
Supplementary Fig. 2
Supplementary Fig. 2
Zoomed insets of Fig. 3 (A-B-C follow the same label order).

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