Modulating Brain Perfusion, Functional Connectivity, and Metabolite Patterns through tb-TUS
Poster No:
60
Submission Type:
Late-Breaking Abstract Submission
Authors:
Daniel Keeser1, Lukas Roell2, Veronica Meedt1, Maximilian Haßlberger3, Maxim Korman1, Maximilian Lueckel4, Theresa Faeßler1, Kai-Yen Chang1, Lucia Bulubas1, Frank Padberg1, Florian Raabe5, Peter Falkai1, Til Bergmann6, Boris-Stephan Rauchmann7
Institutions:
1University Hospital LMU, Munich, Germany, 2University Hospital LMU / University of Melbourne, Munich /Melbourne, Bavaria, 3Technical University Munich (TUM), Munich, Germany, 4Leibniz-Institut für Resilienzforschung (LIR) gGmbH, Mainz, Germany, 5Max Planck Institute of Psychiatry, Munich, Germany, 6Johannes Gutenberg University Medical Center, Mainz, Germany, 7Department of Neuroradiology, University Hospital LMU, Munich, Germany
First Author:
Co-Author(s):
Introduction:
Among currently available non-invasive brain stimulation techniques, transcranial focused ultrasound stimulation (TUS) has gained growing interest in recent years. In this study, the effects of theta-burst TUS (tb-TUS) on cerebral blood flow, functional connectivity and metabolite concentrations in the human motor cortex were investigated.
Methods:
Seventeen healthy subjects participated in a double-blind, sham-controlled crossover study. Participants were randomly assigned to receive either active or sham theta-burst tFUS targeting the left motor cortex M1. Multimodal magnetic resonance imaging (MRI) was conducted at baseline, immediately before stimulation, and immediately after stimulation (Fig. 1). The MRI protocol included pseudo-continuous arterial spin labeling (pcASL) to measure CBF, resting-state functional MRI (rs-fMRI) to assess functional connectivity, and magnetic resonance spectroscopy (MRS) to quantify metabolite levels. Before tFUS stimulation, spatial targeting was guided by T1-weighted MRI-based acoustic simulations to ensure sufficient energy delivery while maintaining safety standards. This precise targeting is crucial because the skull's varying thickness and density significantly affect how ultrasound waves travel through it. Simulations were performed individually using k-Wave (Treeby & Cox, 2010) in MATLAB, with pseudo-CT scans generated via the MR-to-pCT for FUS acoustic simulations code (Yaakub et al., 2023) to account for skull thickness. Theta-burst stimulation was delivered using the four-element NeuroFUS PRO - CTX500 Transducer (500 kHz; Brainbox Ltd., Cardiff, UK). To ensure precise positioning, the transducer was guided by a neuronavigation system (LOCALITE, Bonn, Germany) based on each participant's T1-weighted MRI.
Figure 1. Experimental Design. Seventeen healthy volunteers (mean age=26.31, SD=3.34; 8 women). Repeated measurement design over three days, including baseline and randomized active/sham theta burst TUS (tbTUS) stimulation conditions in a cross-over design. Multimodal MRI imaging including 1. pcASL, 2. rs-fMRI, 3.MRS, 4.FT-fMRI and structural 5.T1w/T2w scans. Simulations were perfomed using k-wave toolbox.
Figure 1. Experimental Design. Seventeen healthy volunteers (mean age=26.31, SD=3.34; 8 women). Repeated measurement design over three days, including baseline and randomized active/sham theta burst TUS (tbTUS) stimulation conditions in a cross-over design. Multimodal MRI imaging including 1. pcASL, 2. rs-fMRI, 3.MRS, 4.FT-fMRI and structural 5.T1w/T2w scans. Simulations were perfomed using k-wave toolbox.
·Fig. 1. Experimental Design
Results:
A significant interaction between session and condition was observed for both CBF (F = 5.96, p = 0.015) and rs-fMRI (F = 3.88, p = 0.049). Post-hoc analyses indicated that active tFUS stimulation significantly reduced CBF (d = -0.25, p < 0.001) and functional connectivity (d = -0.30, p < 0.001) within the motor cortex, whereas sham stimulation had no effect. No significant changes in the concentrations of GABA, glutamate, or Glx were detected.
Figure 2. A) Regions of interest (precentral, paracentral and postcentral). B) Post-Pre pcASL effects of active and sham tb-TUS. C) Post-Pre within-region rs-fMRI effects of active and sham tb-TUS. D) Example MRS ROI placement at the left M1 region. E) Baseline (BL), Pre-Post active and sham tb-TUS effects on GABA, Glu and Glx.
Figure 2. A) Regions of interest (precentral, paracentral and postcentral). B) Post-Pre pcASL effects of active and sham tb-TUS. C) Post-Pre within-region rs-fMRI effects of active and sham tb-TUS. D) Example MRS ROI placement at the left M1 region. E) Baseline (BL), Pre-Post active and sham tb-TUS effects on GABA, Glu and Glx.
·Fig. 3. Results
Conclusions:
These results demonstrate that theta-burst tFUS applied to the motor cortex can modulate local CBF and functional connectivity in healthy individuals. The motor cortex was selected as the initial target due to its well-defined physiology and relatively simple organization compared to other cortical regions, making it suitable for this proof-of-concept investigation. This study provides mechanistic insights into the effects of tFUS on the human brain, informing future research aimed at applying this technique to more complex brain regions and, potentially, treating challenging neuropsychiatric disorders.
Brain Stimulation:
Sonic/Ultrasound 1
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
Multivariate Approaches 2
Novel Imaging Acquisition Methods:
BOLD fMRI
MR Spectroscopy
Imaging Methods Other
Perception, Attention and Motor Behavior:
Motor Behavior Other
Keywords:
FUNCTIONAL MRI
GABA
Glutamate
Magnetic Resonance Spectroscopy (MRS)
ULTRASOUND
1|2Indicates the priority used for review
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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
Yaakub SN, White TA, Kerfoot E, Verhagen L, Hammers A, Fouragnan EF. Pseudo-CTs from T1-weighted MRI for planning of low-intensity transcranial focused ultrasound neuromodulation: An open-source tool. Brain Stimul. 2023 Jan-Feb;16(1):75-78. doi: 10.1016/j.brs.2023.01.838.