A pre-clinical MRI-guided all-in-one focused ultrasound system for murine brain studies

Abstract This paper describes the design and initial proof-of-concept of a single pre-clinical transcranial focused ultrasound (FUS) system capable of performing histotripsy (mechanical ablation), hyperthermia, blood-brain barrier opening (BBBO), sonodynamic therapy, or neuromodulation in a murine b...

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Main Authors: Tarana Parvez Kaovasia, Sarah Duclos, Dinank Gupta, Kourosh Kalayeh, Mario Fabiilli, Douglas C. Noll, Jonathan Sukovich, Aditya Pandey, Zhen Xu, Timothy L. Hall
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-84078-9
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author Tarana Parvez Kaovasia
Sarah Duclos
Dinank Gupta
Kourosh Kalayeh
Mario Fabiilli
Douglas C. Noll
Jonathan Sukovich
Aditya Pandey
Zhen Xu
Timothy L. Hall
author_facet Tarana Parvez Kaovasia
Sarah Duclos
Dinank Gupta
Kourosh Kalayeh
Mario Fabiilli
Douglas C. Noll
Jonathan Sukovich
Aditya Pandey
Zhen Xu
Timothy L. Hall
author_sort Tarana Parvez Kaovasia
collection DOAJ
description Abstract This paper describes the design and initial proof-of-concept of a single pre-clinical transcranial focused ultrasound (FUS) system capable of performing histotripsy (mechanical ablation), hyperthermia, blood-brain barrier opening (BBBO), sonodynamic therapy, or neuromodulation in a murine brain. We have termed it the All-in-One FUS system for murine brain studies, which is the first FUS system of its kind. The 1.5 MHz ultrasound transducer was fabricated and driven using a custom electronic driver to produce 3-cycle pulses with a focal peak-negative pressure (P-) of up to 87 MPa at a low duty cycle (< 0.1%) for histotripsy as well as 50% duty cycle pulsed-ultrasound with a spatial-peak temporal-average intensity (Ispta) of up to 251 W/cm2 for the other FUS modalities. This All-in-One system can be guided by MRI or stereotactically to maximize its flexibility. To validate the design of the system, histotripsy, BBBO, and hyperthermia were performed in naïve brains of two mice for each modality. Histotripsy and BBBO were performed using MRI-based stereotactic co-registration. The therapeutic effect was confirmed using T2-weighted MR-images for histotripsy, and T1-weighted Gadolinium contrast-enhanced MR-images for BBBO. For hyperthermia, an MRI-compatible insert was designed to fit inside the 80 mm imaging coil of a 7-Tesla small-animal MRI-system, with T2-weighted MR-images used to confirm targeting, and MR-thermometry used to monitor the thermal dose delivered.
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spelling doaj-art-9010f4d936e14d9e894816704a2aa5d62025-01-05T12:15:12ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-024-84078-9A pre-clinical MRI-guided all-in-one focused ultrasound system for murine brain studiesTarana Parvez Kaovasia0Sarah Duclos1Dinank Gupta2Kourosh Kalayeh3Mario Fabiilli4Douglas C. Noll5Jonathan Sukovich6Aditya Pandey7Zhen Xu8Timothy L. Hall9Department of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Radiology, University of MichiganDepartment of Radiology, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Neurosurgery, University of MichiganDepartment of Biomedical Engineering, University of MichiganDepartment of Biomedical Engineering, University of MichiganAbstract This paper describes the design and initial proof-of-concept of a single pre-clinical transcranial focused ultrasound (FUS) system capable of performing histotripsy (mechanical ablation), hyperthermia, blood-brain barrier opening (BBBO), sonodynamic therapy, or neuromodulation in a murine brain. We have termed it the All-in-One FUS system for murine brain studies, which is the first FUS system of its kind. The 1.5 MHz ultrasound transducer was fabricated and driven using a custom electronic driver to produce 3-cycle pulses with a focal peak-negative pressure (P-) of up to 87 MPa at a low duty cycle (< 0.1%) for histotripsy as well as 50% duty cycle pulsed-ultrasound with a spatial-peak temporal-average intensity (Ispta) of up to 251 W/cm2 for the other FUS modalities. This All-in-One system can be guided by MRI or stereotactically to maximize its flexibility. To validate the design of the system, histotripsy, BBBO, and hyperthermia were performed in naïve brains of two mice for each modality. Histotripsy and BBBO were performed using MRI-based stereotactic co-registration. The therapeutic effect was confirmed using T2-weighted MR-images for histotripsy, and T1-weighted Gadolinium contrast-enhanced MR-images for BBBO. For hyperthermia, an MRI-compatible insert was designed to fit inside the 80 mm imaging coil of a 7-Tesla small-animal MRI-system, with T2-weighted MR-images used to confirm targeting, and MR-thermometry used to monitor the thermal dose delivered.https://doi.org/10.1038/s41598-024-84078-9Therapeutic ultrasoundBrainHistotripsyBlood-brain barrier openingHyperthermiaMagnetic resonance imaging (MRI)
spellingShingle Tarana Parvez Kaovasia
Sarah Duclos
Dinank Gupta
Kourosh Kalayeh
Mario Fabiilli
Douglas C. Noll
Jonathan Sukovich
Aditya Pandey
Zhen Xu
Timothy L. Hall
A pre-clinical MRI-guided all-in-one focused ultrasound system for murine brain studies
Scientific Reports
Therapeutic ultrasound
Brain
Histotripsy
Blood-brain barrier opening
Hyperthermia
Magnetic resonance imaging (MRI)
title A pre-clinical MRI-guided all-in-one focused ultrasound system for murine brain studies
title_full A pre-clinical MRI-guided all-in-one focused ultrasound system for murine brain studies
title_fullStr A pre-clinical MRI-guided all-in-one focused ultrasound system for murine brain studies
title_full_unstemmed A pre-clinical MRI-guided all-in-one focused ultrasound system for murine brain studies
title_short A pre-clinical MRI-guided all-in-one focused ultrasound system for murine brain studies
title_sort pre clinical mri guided all in one focused ultrasound system for murine brain studies
topic Therapeutic ultrasound
Brain
Histotripsy
Blood-brain barrier opening
Hyperthermia
Magnetic resonance imaging (MRI)
url https://doi.org/10.1038/s41598-024-84078-9
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