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Deep Learning Enables Reduced Gadolinium Dose for Contrast-Enhanced Blood-Brain Barrier Opening.

Authors: Lee PY, Wei HJ, Pouliopoulos AN, Forsyth BT, Yang Y, Zhang C, Laine AF, Konofagou EE, Wu CC, Guo J

Focused ultrasound (FUS) can be used to open the blood-brain barrier (BBB), and MRI with contrast agents can detect that opening. However, repeated use of gadolinium-based contrast agents (GBCAs) presents safety concerns to patients. This study is the first to propose the idea of modeling a volume transfer constant (Ktrans) through deep learning to reduce the dosage of contrast agents. The goal of the study is not only to reconstruct artificial intelligence (AI) derived Ktrans images but to also enhance the intensity with low dosage contrast agent T1 weighted MRI scans. We successfully validated this idea through a previous state-of-the-art temporal network algorithm, which focused on extracting time domain features at the voxel level. Then we used a Spatiotemporal Network (ST-Net), composed of a spatiotemporal convolutional neural network (CNN)-based deep learning architecture with the addition of a three-dimensional CNN encoder, to improve the model performance. We tested the ST-Net model on ten datasets of FUS-induced BBB-openings aquired from different sides of the mouse brain. ST-Net successfully detected and enhanced BBB-opening signals without sacrificing spatial domain information. ST-Net was shown to be a promising method of reducing the need of contrast agents for modeling BBB-opening K-trans maps from time-series Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) scans.

Introduction

Purpose Drug delivery with BBB opening
Study Objective To develop and validate a spatiotemporal deep learning model that predicts Ktrans maps and enhances low-dose T1-weighted MRI to detect focused ultrasound–induced blood–brain barrier openings, thereby reducing gadolinium contrast agent dosage.
Animal model / Human subject Mouse (C576J/BL), 3–6 months old, sex not stated
Disease model Blood-brain barrier opening (FUS-induced)
MRI or image guidance method MRI
Targeted brain region(s) Striatum

Outcomes and Safety

Summary of Outcomes FUS produced targeted, transient BBB opening in mice, ST-net precisely detected BBB opening and reconstructed full-dose Ktrans maps from low-dose DCE-MRI, outperforming low-dose GKM and T-net
Safety-related matter No tissue damage or adverse effect

Brain Region

Ultrasound Parameters

Ultrasound instrument Single-element, spherical-segment FUS transducer
FUS Frequency 0.5 MHz
FUS Pressure 0.3 MPa
FUS Mode pulsed
Pulse duration 10 ms
Duration of a single FUS session 120 s (2 minutes)
Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency single

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