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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

  • Rafael Rodriguez-Rojas
  • Jose A. Pineda-Pardo
  • Raul Martinez-Fernandez
  • Rosalie V. Kogan
  • Carlos A. Sanchez-Catasus
  • Marta del Alamo
  • Frida Hernández
  • Lina García-Cañamaque
  • Klaus L. Leenders
  • Jose A. ObesoEmail author
Original Article
Part of the following topical collections:
  1. Neurology

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.

Keywords

Parkinson’s disease MR-guided focused ultrasound Subthalamotomy Positron emission tomography Metabolic brain network 

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

Notes

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 information

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

Compliance with ethical standards

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.

Informed consent

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

Supplementary material

259_2019_4497_MOESM1_ESM.docx (917 kb)
ESM 1 (DOCX 916 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Rafael Rodriguez-Rojas
    • 1
    • 2
  • Jose A. Pineda-Pardo
    • 1
    • 2
  • Raul Martinez-Fernandez
    • 1
    • 2
  • Rosalie V. Kogan
    • 3
  • Carlos A. Sanchez-Catasus
    • 3
  • Marta del Alamo
    • 1
  • Frida Hernández
    • 1
  • Lina García-Cañamaque
    • 4
  • Klaus L. Leenders
    • 3
  • Jose A. Obeso
    • 1
    • 2
    Email author
  1. 1.Centro Integral de Neurociencias (CINAC)University Hospital HM Puerta del SurMadridSpain
  2. 2.CIBERNEDInstitute Carlos IIIMadridSpain
  3. 3.Department of Nuclear Medicine and Molecular ImagingUniversity Medical Center Groningen (UMCG)GroningenThe Netherlands
  4. 4.Department of Nuclear MedicineUniversity Hospital HM Puerta del SurMadridSpain

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