First-in-human prospective trial of sonobiopsy in high-grade glioma patients using neuronavigation-guided focused ultrasound

Jinyun Yuan; Lu Xu; Chih-Yen Chien; Yaoheng Yang; Yimei Yue; Siaka Fadera; Andrew H Stark; Katherine E Schwetye; Arash Nazeri; Rupen Desai; Umeshkumar Athiraman; Aadel A Chaudhuri; Hong Chen; Eric C Leuthardt

doi:10.1038/s41698-023-00448-y

First-in-human prospective trial of sonobiopsy in high-grade glioma patients using neuronavigation-guided focused ultrasound

NPJ Precis Oncol. 2023 Sep 16;7(1):92. doi: 10.1038/s41698-023-00448-y.

Authors

Jinyun Yuan^#¹, Lu Xu^#¹, Chih-Yen Chien^#¹, Yaoheng Yang¹, Yimei Yue¹, Siaka Fadera¹, Andrew H Stark¹, Katherine E Schwetye², Arash Nazeri³, Rupen Desai⁴, Umeshkumar Athiraman⁵, Aadel A Chaudhuri^{1

6

7

8

9}, Hong Chen^{10

11

12}, Eric C Leuthardt^{13

14

15

16

17

18}

Affiliations

¹ Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA.
² Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
³ Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
⁴ Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, 63110, USA.
⁵ Department of Anesthesia, Washington University School of Medicine, St. Louis, MO, 63110, USA.
⁶ Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO, 63108, USA.
⁷ Department of Genetics, Washington University School of Medicine, St. Louis, MO, 63110, USA.
⁸ Department of Computer Science and Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA.
⁹ Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, 63110, USA.
¹⁰ Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA. hongchen@wustl.edu.
¹¹ Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, 63110, USA. hongchen@wustl.edu.
¹² Division of Neurotechnology, Department of Neurosurgery, Washington University School of Medicine, Saint Louis, MO, 63110, USA. hongchen@wustl.edu.
¹³ Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA. leuthardte@wustl.edu.
¹⁴ Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, 63110, USA. leuthardte@wustl.edu.
¹⁵ Division of Neurotechnology, Department of Neurosurgery, Washington University School of Medicine, Saint Louis, MO, 63110, USA. leuthardte@wustl.edu.
¹⁶ Department of Neuroscience, Washington University School of Medicine, Saint Louis, MO, 63110, USA. leuthardte@wustl.edu.
¹⁷ Center for Innovation in Neuroscience and Technology, Washington University School of Medicine, Saint Louis, MO, 63110, USA. leuthardte@wustl.edu.
¹⁸ Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, Saint Louis, MO, 63130, USA. leuthardte@wustl.edu.

^# Contributed equally.

Abstract

Sonobiopsy is an emerging technology that combines focused ultrasound (FUS) with microbubbles to enrich circulating brain disease-specific biomarkers for noninvasive molecular diagnosis of brain diseases. Here, we report the first-in-human prospective trial of sonobiopsy in high-grade glioma patients to evaluate its feasibility and safety in enriching plasma circulating tumor biomarkers. A nimble FUS device integrated with a clinical neuronavigation system was used to perform sonobiopsy following an established clinical workflow for neuronavigation. Analysis of blood samples collected before and after FUS sonication showed that sonobiopsy enriched plasma circulating tumor DNA (ctDNA), including a maximum increase of 1.6-fold for the mononucleosome cell-free DNA (cfDNA) fragments (120-280 bp), 1.9-fold for the patient-specific tumor variant ctDNA level, and 5.6-fold for the TERT mutation ctDNA level. Histological analysis of surgically resected tumors confirmed the safety of the procedure. Transcriptome analysis of sonicated and nonsonicated tumor tissues found that FUS sonication modulated cell physical structure-related genes. Only 2 out of 17,982 total detected genes related to the immune pathways were upregulated. These feasibility and safety data support the continued investigation of sonobiopsy for noninvasive molecular diagnosis of brain diseases.

Abstract

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