Focused ultrasound simultaneous irradiation/MRI imaging, and two-stage general kinetic model

Sheng-Yao Huang; Chia-En Ko; Gin-Shin Chen; I-Fang Chung; Feng-Yi Yang

doi:10.1371/journal.pone.0100280

Focused ultrasound simultaneous irradiation/MRI imaging, and two-stage general kinetic model

PLoS One. 2014 Jun 20;9(6):e100280. doi: 10.1371/journal.pone.0100280. eCollection 2014.

Authors

Sheng-Yao Huang¹, Chia-En Ko², Gin-Shin Chen³, I-Fang Chung⁴, Feng-Yi Yang⁵

Affiliations

¹ Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
² Department of Diagnostic Radiology, Mackay Memorial Hospital of Tan-Shui, Taipei, Taiwan.
³ Division of Medical Engineering Research, National Health Research Institutes, Miaoli County, Taiwan.
⁴ Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan; Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan.
⁵ Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.

Abstract

Many studies have investigated how to use focused ultrasound (FUS) to temporarily disrupt the blood-brain barrier (BBB) in order to facilitate the delivery of medication into lesion sites in the brain. In this study, through the setup of a real-time system, FUS irradiation and injections of ultrasound contrast agent (UCA) and Gadodiamide (Gd, an MRI contrast agent) can be conducted simultaneously during MRI scanning. By using this real-time system, we were able to investigate in detail how the general kinetic model (GKM) is used to estimate Gd penetration in the FUS irradiated area in a rat's brain resulting from UCA concentration changes after single FUS irradiation. Two-stage GKM was proposed to estimate the Gd penetration in the FUS irradiated area in a rat's brain under experimental conditions with repeated FUS irradiation combined with different UCA concentrations. The results showed that the focal increase in the transfer rate constant of Ktrans caused by BBB disruption was dependent on the doses of UCA. Moreover, the amount of in vivo penetration of Evans blue in the FUS irradiated area in a rat's brain under various FUS irradiation experimental conditions was assessed to show the positive correlation with the transfer rate constants. Compared to the GKM method, the Two-stage GKM is more suitable for estimating the transfer rate constants of the brain treated with repeated FUS irradiations. This study demonstrated that the entire process of BBB disrupted by FUS could be quantitatively monitored by real-time dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood-Brain Barrier / metabolism*
Contrast Media / metabolism
Gadolinium DTPA / metabolism
Kinetics
Magnetic Resonance Imaging*
Male
Models, Biological*
Rats
Rats, Sprague-Dawley
Ultrasonics*

Substances

Contrast Media
gadodiamide
Gadolinium DTPA

Grants and funding

This study was supported by grants from the National Science Council of Taiwan (no. NSC 101-2320-B-010-036-MY3, NSC 102-2221-E-010-005-MY3, and NSC 102-2221-E-010-014), Cheng Hsin General Hospital Foundation (no. 102F218C11 and 103F003C17), Biophotonics & Molecular Imaging Research Center, and the Ministry of Education, Aim for the Top University Plan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.