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Functional impact of subthalamotomy by magnetic resonance–guided focused ultrasound in Parkinson’s disease: a hybrid PET/MR study of resting-state brain metabolism

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Subthalamotomy using magnetic resonance–guided focused ultrasound (MRgFUS) has become a potential treatment option for the cardinal features of Parkinson’s disease (PD). The purpose of this study was to evaluate the effects of MRgFUS-subthalamotomy on brain metabolism using different scale levels.

Methods

We studied resting-state glucose metabolism in eight PD patients before and after unilateral MRgFUS-subthalamotomy using hybrid [18F]FDG-PET/MR imaging. We used statistical nonparametric mapping (SnPM) to study regional metabolic changes following this treatment and also quantified whole-brain treatment-related changes in the expression of a spatial covariance-based Parkinson’s disease–related metabolic brain pattern (PDRP). Modulation of regional and network activity was correlated with clinical improvement as measured by changes in Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor scores.

Results

After subthalamotomy, there was a significant reduction in FDG uptake in the subthalamic region, globus pallidus internus, motor and premotor cortical regions, and cingulate gyrus in the treated hemisphere, and the contralateral cerebellum (p < 0.001). Diffuse metabolic increase was found in the posterior parietal and occipital areas. Treatment also resulted in a significant decline in PDRP expression (p < 0.05), which correlated with clinical improvement in UPDRS motor scores (rho = 0.760; p = 0.002).

Conclusions

MRgFUS-subthalamotomy induced metabolic alterations in distributed nodes of the motor, associative, and limbic circuits. Clinical improvement was associated with reduction in the PDRP expression. This treatment-induced modulation of the metabolic network is likely to mediate the clinical benefit achieved following MRgFUS-subthalamotomy.

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Abbreviations

BGTC:

basal ganglia-thalamocortical network

CBTC:

cerebellum-thalamocortical pathways

DARTEL:

Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra

MRgFUS:

magnetic resonance–guided focused ultrasound

rCMRglc:

regional Cerebral Metabolic Rate of glucose consumption

RN:

red nucleus

STN:

subthalamic nucleus

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Acknowledgments

This work was supported by Fundación Hospitales de Madrid and Insightec. [18F]-FDG/PET studies were partially funded by Siemens-Healthcare S.L.U. The work at the University Medical Center of Groningen (UMCG) has been supported by the Dutch organization Stichting Parkinson Fonds. The sponsors had no role in the preparation and execution of the study and/or manuscript. We wish to thank the University Hospital HM-Puerta del Sur and in particular Dr. Santiago Ruiz de Aguiar, medical director, and members of the Radiology Department Silvia Casas and Ursula Alcañas, for their support.

Funding

This study was funded by Insightec (grant number NCT02912871).

Author information

Authors and Affiliations

  1. Centro Integral de Neurociencias (CINAC), University Hospital HM Puerta del Sur, Madrid, Spain

    Rafael Rodriguez-Rojas, Jose A. Pineda-Pardo, Raul Martinez-Fernandez, Marta del Alamo, Frida Hernández & Jose A. Obeso

  2. CIBERNED, Institute Carlos III, Madrid, Spain

    Rafael Rodriguez-Rojas, Jose A. Pineda-Pardo, Raul Martinez-Fernandez & Jose A. Obeso

  3. Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen (UMCG), Groningen, The Netherlands

    Rosalie V. Kogan, Carlos A. Sanchez-Catasus & Klaus L. Leenders

  4. Department of Nuclear Medicine, University Hospital HM Puerta del Sur, Madrid, Spain

    Lina García-Cañamaque

Authors
  1. Rafael Rodriguez-Rojas
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  2. Jose A. Pineda-Pardo
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Corresponding author

Correspondence to Jose A. Obeso.

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Conflict of interest

RRR received a travel grant from the Movement Disorders Society to attend a scientific congress and reimbursement of travel expenses from the Organization for Human Brain Mapping. RMF received payment from Insightec for travel and accommodation to attend scientific meetings. RVK has received research grants from Stichting Parkinson Fonds. CKLL has received research grants from Stichting Parkinson Fonds. JAO received research support from the Spanish Science and Education Ministry and the European Union, honoraria for lecturing at meetings organized by GSK, Lundbeck, and UCB, TEVA-Neuroscience, and Boehringer Ingelheim and serves on two advisory boards (2014, 2017) on behalf of Insightec. All other authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments. The study was approved by the institutional Ethics Review Board.

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Informed consent was obtained from all individual participants included in the study.

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Rodriguez-Rojas, R., Pineda-Pardo, J.A., Martinez-Fernandez, R. et al. Functional impact of subthalamotomy by magnetic resonance–guided focused ultrasound in Parkinson’s disease: a hybrid PET/MR study of resting-state brain metabolism. Eur J Nucl Med Mol Imaging 47, 425–436 (2020). https://doi.org/10.1007/s00259-019-04497-z

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