Structural and functional connectivity predicts MRgFUS thalamotomy outcome in Parkinson’s disease

1539 

Abstract Submission 

Alberto Cacciola¹, Gianpaolo Basile¹, Giuseppe Acri¹, Lilla Bonanno², Augusto Ielo², Silvia Marino², Amelia Brigandì², Chiara Sorbera², Rosa Morabito², Giuseppe Di Lorenzo², Antonio Cerasa^3,4,5, Angelo Quartarone²

¹University of Messina, Messina, Italy, ²IRCCS Centro Neurolesi “Bonino Pulejo”, Messina, Italy, ³S. Anna Institute, Crotone, Italy, ⁴Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy, Messina, Italy, ⁵University of Calabria, Rende, Italy

Alberto Cacciola  
University of Messina
Messina, Italy

Gianpaolo Basile, Dr.  
University of Messina
Messina, Italy

Giuseppe Acri  
University of Messina
Messina, Italy

Lilla Bonanno  
IRCCS Centro Neurolesi “Bonino Pulejo”
Messina, Italy

Augusto Ielo  
IRCCS Centro Neurolesi “Bonino Pulejo”
Messina, Italy

Silvia Marino  
IRCCS Centro Neurolesi “Bonino Pulejo”
Messina, Italy

Amelia Brigandì  
IRCCS Centro Neurolesi “Bonino Pulejo”
Messina, Italy

Chiara Sorbera  
IRCCS Centro Neurolesi “Bonino Pulejo”
Messina, Italy

Rosa Morabito  
IRCCS Centro Neurolesi “Bonino Pulejo”
Messina, Italy

Giuseppe Di Lorenzo  
IRCCS Centro Neurolesi “Bonino Pulejo”
Messina, Italy

Antonio Cerasa  
S. Anna Institute|Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy|University of Calabria
Crotone, Italy|Messina, Italy|Rende, Italy

Angelo Quartarone  
IRCCS Centro Neurolesi “Bonino Pulejo”
Messina, Italy

Magnetic Resonance-guided Focused UltraSound (MRgFUS) thalamotomy has been demonstrated to effectively reduce tremor symptoms in Parkinson's disease (PD). Emerging evidence suggests that its efficacy may depend on the connectivity between the target and other brain areas, more than the choice of the target site itself. However, evidence demonstrating whether brain connectivity can predict clinical outcomes in tremor-dominant PD patients is still missing. Herein, we characterize the structural and functional connectivity associated with successful focused ultrasound ablation of the Ventral intermediate thalamic nucleus (Vim) and assess its potential to predict treatment outcome.

Twelve tremor-dominant PD patients were retrospectively included in this study. All patients underwent unilateral MRgFUS thalamotomy and received preoperative and 24-hour postoperative structural MRI. Treatment outcome was measured as the percentage change in motor score of the Unified Parkinson Disease Rating Scale (UPDRS-III) assessed one week after the treatment. Segmentation of the ablation core was performed on each subject postoperative images by two independent raters and the Dice coefficient was computed to assess accuracy segmentation. To identify the spatial relationship between the ablation site and the Vim, each patient's thalamus was segmented into thalamic nuclei through the THOMAS automated segmentation using White-Matter null images synthesized from preoperative T1w images. We examined how different ablation features (ablation volume, Vim-ablation overlap, Euclidean distance between ablation core and Vim centroids and, Euclidean distance between Vim-ablation overlap and Vim centroids) correlated with clinical outcome. We then combined our PD dataset with publicly available normative human connectome data (diffusion tractography and resting state functional connectivity) to identify connectivity patterns reliably associated with clinical improvement. The structural and functional connectivity profiles were then independently employed to predict clinical outcome in a leave-one-patient-out cross-validation design.

We found no significant correlations between standard ablation features (ablation volume, Vim-ablation overlap, Euclidean distance between ablation and Vim centroids and, Euclidean distance between Vim-ablation overlap and Vim centroids) and 1-week post-treatment clinical outcome (all p>0.05). In contrast, connectivity between the area of ablation and a distributed network of brain regions correlated with clinical improvement including structural connectivity to pre-supplementary, supplementary motor area, superior frontal gyrus, and cerebellum. Similar patterns of functional connectivity, and anticorrelation between the ablation area and primary somatosensory cortex and the most lateral part of primary motor cortex, were correlated with clinical outcome. Finally, leave-one-patient-out cross-validation showed that both structural (R² = 0.53; R = 0.73; p = 0.002) and functional connectivity (R² = 0.23; R = 0.48; p = 0.007) fingerprints are predictive of clinical improvement within the cohort. The prediction errors were on average 5.58±13.95  and 5.40±10.35 from actual UPDRS-III improvements, for structural and functional connectivity respectively.

While neither target volume- nor distance-based measures correlated with clinical outcome, our results suggest that both target structural and functional connectivity are independent predictors of clinical improvement in tremor-dominant MRgFUS-thalamotomized PD patients. Being based on publicly available normative connectome, this predictive approach did not require advanced diffusion and functional imaging that may be not routinely available in the clinical setting. The present pilot study suggests the future potential for patient-specific connectomics surgical targeting, while warranting future work to test and validate the present findings in independent cohorts.

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) ²

Connectivity (eg. functional, effective, structural) ¹

Cortex

Degenerative Disease

FUNCTIONAL MRI

Movement Disorder

MRI

STRUCTURAL MRI

Thalamus

Tractography

ULTRASOUND