Stereotactic Transcranial Focused Ultrasound Targeting System for Murine Brain Models.

An inexpensive, accurate focused ultrasound stereotactic targeting method guided by pretreatment magnetic resonance imaging (MRI) images for murine brain models is presented. An uncertainty of each sub-component of the stereotactic system was analyzed. The entire system was calibrated using clot phantoms. The targeting accuracy of the system was demonstrated with an in vivo mouse glioblastoma (GBM) model. The accuracy was quantified by the absolute distance difference between the prescribed and ablated points visible on the pre treatment and posttreatment MR images, respectively. A precalibration phantom study ( N = 6 ) resulted in an error of 0.32 ± 0.31, 0.72 ± 0.16, and 1.06 ± 0.38 mm in axial, lateral, and elevational axes, respectively. A postcalibration phantom study ( N = 8 ) demonstrated a residual error of 0.09 ± 0.01, 0.15 ± 0.09, and 0.47 ± 0.18 mm in axial, lateral, and elevational axes, respectively. The calibrated system showed significantly reduced ( ) error of 0.20 ± 0.21, 0.34 ± 0.24, and 0.28 ± 0.21 mm in axial, lateral, and elevational axes, respectively, in the in vivo GBM tumor-bearing mice ( N = 10 ).

Introduction

Purpose other

Study Objective Develop and evaluate an inexpensive, accurate stereotactic transcranial focused ultrasound system for murine brain models using pre-treatment MRI guidance, and quantify targeting accuracy in phantoms and in vivo glioblastoma mice

Animal model / Human subject mouse (C57BL/6 Albino female, GL261 glioblastoma model)

Disease model glioblastoma (GBM)

MRI or image guidance method none pre-treatment 7T MRI (T2-weighted FSE) for planning; no real-time MRI guidance during FUS (stereotactic registration with fiducials)

Targeted brain region(s) lateral ventricle

Target coordinates not fixed (tumor centroid based on MRI, typical injection coordinates: 1 mm posterior to coronal suture, 2.5-3 mm right of sagittal suture, 2 mm deep)

Outcomes and Safety

Summary of Outcomes Stereotactic FUS system (1 MHz, 32 MPa, 1.5 µs pulses, 1 Hz PRF, 100 s) achieved sub-millimeter targeting accuracy in clot phantoms (total error 0.50 mm post-calibration) and in vivo GBM mice (total error 0.48 mm). Pre-calibration phantom error was 1.4 mm. System calibration using MRI field distortion correction (multiplicative factor) significantly improved accuracy. No in vivo safety or efficacy outcomes reported.

Brain Region

Ultrasound Parameters

Ultrasound instrument in-house 8-element histotripsy transducer, 1 MHz, custom-built, 3D-printed fixture frame with fiducials, 3-axis motor positioner

FUS Frequency 1MHz

FUS Pressure 32 MPa (peak negative pressure, free-field estimate)

FUS Mode pulsed

Pulse duration 1.5 µs (1.5 cycles at 1 MHz)

Duration of a single FUS session 100s

Treatment frequency single session (single point ablation per animal)

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