Dataset Information

Image-Guided Focused-Ultrasound CNS Molecular Delivery: An Implementation via Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

ABSTRACT: Focused ultrasound (FUS) exposure with microbubbles can transiently open the blood-brain barrier (BBB) to deliver therapeutic molecules into CNS tissues. However, delivered molecular distribution/concentration at the target need to be controlled. Dynamic Contrast-Enhanced Magnetic-Resonance Imaging (DCE-MRI) is a well-established protocol for monitoring the pharmacokinetic/pharmacodynamic behavior of FUS-BBB opening. This study investigates the feasibility of using DCE-MRI to estimate molecular CNS penetration under various exposure conditions and molecule sizes. In the 1^st stage, a relationship among the imaging index K_trans, exposure level and molecular size was calibrated and established. In the 2^nd stage, various exposure levels and distinct molecules were applied to evaluate the estimated molecular concentration discrepancy with the quantified ones. High correlation (r²?=?0.9684) between K_trans and transcranial mechanical index (MI) implies K_trans can serve as an in vivo imaging index to mirror FUS-BBB opening scale. When testing various molecules with the size ranging 1-149?kDa, an overall correlation of r²?=?0.9915 between quantified and predicted concentrations was reached, suggesting the established model can provide reasonably accurate estimation. Our work demonstrates the feasibility of estimating molecular penetration through FUS-BBB opening via DCE-MRI and may facilitate development of FUS-induced BBB opening in brain drug delivery.

SUBMITTER: Chai WY

PROVIDER: S-EPMC5841286 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

Image-Guided Focused-Ultrasound CNS Molecular Delivery: An Implementation via Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

Chai Wen-Yen WY Chu Po-Chun PC Tsai Chih-Hung CH Lin Chung-Yin CY Yang Hung-Wei HW Lai Hsin-Yi HY Liu Hao-Li HL

Scientific reports 20180307 1

Focused ultrasound (FUS) exposure with microbubbles can transiently open the blood-brain barrier (BBB) to deliver therapeutic molecules into CNS tissues. However, delivered molecular distribution/concentration at the target need to be controlled. Dynamic Contrast-Enhanced Magnetic-Resonance Imaging (DCE-MRI) is a well-established protocol for monitoring the pharmacokinetic/pharmacodynamic behavior of FUS-BBB opening. This study investigates the feasibility of using DCE-MRI to estimate molecular ...[more]

PMID: 29515222

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Project description:BACKGROUND:MR-guided focused ultrasound or high-intensity focused ultrasound (MRgFUS/MRgHIFU) is a non-invasive therapeutic modality with many potential applications in areas such as cancer therapy, drug delivery, and blood-brain barrier opening. However, the large financial costs involved in developing preclinical MRgFUS systems represent a barrier to research groups interested in developing new techniques and applications. We aim to mitigate these challenges by detailing a validated, open-source preclinical MRgFUS system capable of delivering thermal and mechanical FUS in a quantifiable and repeatable manner under real-time MRI guidance. METHODS:A hardware and software package was developed that includes closed-loop feedback controlled thermometry code and CAD drawings for a therapy table designed for a preclinical MRI scanner. For thermal treatments, the modular software uses a proportional integral derivative controller to maintain a precise focal temperature rise in the target given input from MR phase images obtained concurrently. The software computes the required voltage output and transmits it to a FUS transducer that is embedded in the delivery table within the magnet bore. The delivery table holds the FUS transducer, a small animal and its monitoring equipment, and a transmit/receive RF coil. The transducer is coupled to the animal via a water bath and is translatable in two dimensions from outside the magnet. The transducer is driven by a waveform generator and amplifier controlled by real-time software in Matlab. MR acoustic radiation force imaging is also implemented to confirm the position of the focus for mechanical and thermal treatments. RESULTS:The system was validated in tissue-mimicking phantoms and in vivo during murine tumor hyperthermia treatments. Sonications were successfully controlled over a range of temperatures and thermal doses for up to 20 min with minimal temperature overshoot. MR thermometry was validated with an optical temperature probe, and focus visualization was achieved with acoustic radiation force imaging. CONCLUSIONS:We developed an MRgFUS platform for small-animal treatments that robustly delivers accurate, precise, and controllable sonications over extended time periods. This system is an open source and could increase the availability of low-cost small-animal systems to interdisciplinary researchers seeking to develop new MRgFUS applications and technology.

Dataset Information

Image-Guided Focused-Ultrasound CNS Molecular Delivery: An Implementation via Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

Publications

Image-Guided Focused-Ultrasound CNS Molecular Delivery: An Implementation via Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

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