Acute MR-Guided High-Intensity Focused Ultrasound Lesion Assessment Using Diffusion-Weighted Imaging and Histological Analysis.
Authors: Walker MR, Zhong J, Waspe AC, Looi T, Piorkowska K, Hawkins C, Drake JM, Hodaie M
<b>Objectives:</b> The application of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of neurological conditions has been of increasing interest. Conventional MR imaging can provide structural information about the effect of MRgFUS, where differences in ablated tissue can be seen, but it lacks information about the status of the cellular environment or neural microstructure. We investigate <i>in vivo</i> acute changes in water diffusion and white matter tracts in the brain of a piglet model after MRgFUS treatment using diffusion-weighted imaging (DWI) with histological verification of treatment-related changes. <b>Methods:</b> MRgFUS was used to treat the anterior body of the fornix in four piglets. T1 and diffusion-weighted images were collected before and after treatment. Mean diffusion-weighted imaging (MDWI) images were generated to measure lesion volumes via signal intensity thresholds. Histological data were collected for volume comparison and assessment of treatment effect. DWI metric maps of fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were generated for quantitative assessment. Fornix-related fiber tracts were generated before and after treatment for qualitative assessment. <b>Results:</b> The volume of treated tissue measured via MDWI did not differ significantly from histological measurements, and both were significantly larger than the treatment cell volume. Diffusion metrics in the treatment region were significantly decreased following MRgFUS treatment, with the peak change seen at the lesion core and decreasing radially. Histological analysis confirmed an area of coagulative necrosis in the targeted region with sharp demarcation zone with surrounding brain. Tractography from the lesion core and the fornix revealed fiber disruptions following treatment. <b>Conclusions:</b> Diffusion maps and fiber tractography are an effective method for assessing lesion volumes and microstructural changes <i>in vivo</i> following MRgFUS treatment. This study demonstrates that DWI has the potential to advance MRgFUS by providing convenient <i>in vivo</i> microstructural lesion and fiber tractography assessment after treatment.
Introduction
Purpose
Thermal ablation
Study Objective
To assess acute in vivo changes in diffusion metrics and white matter tractography in a piglet brain following MRgFUS treatment, with histological verification.
Animal model / Human subject
Piglet (Sus scrofa domesticus), strain not specified, age not specified, sex not specified
MRI or image guidance method
Magnetic resonance imaging (MRI) guidance (MRgFUS)
Targeted brain region(s)
Anterior Body Of The Fornix
Outcomes and Safety
Summary of Outcomes
MRgFUS targeting the piglet fornix produced acute coagulative necrosis with significant decreases in diffusion metrics (ADC, AD, RD, MD, FA), disruption of fornix/fimbria fiber tracts, and lesion volumes larger than the nominal sonication cell, with successful ablation achieved when peak temperatures reached ≥60°C (exceeding the ~55°C necrosis threshold).
Safety-related matter
All treatments produced unintended off-target heating at the skull base and the observed ablated volumes were ~4x larger than the planned sonication cell, indicating risk of off-target tissue damage; the paper cites prior links between lesion overlap with functional tracts and adverse MRgFUS effects and recommends using lower power to limit off-target thermal dose and disruption.
Brain Region
Ultrasound Parameters
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
Single session
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