Pitt Shield

Open-source, small-animal magnetic resonance-guided focused ultrasound system.

Authors: Poorman ME, Chaplin VL, Wilkens K, Dockery MD, Giorgio TD, Grissom WA, Caskey CF

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. 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. 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. 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.

Introduction

Purpose Thermal ablation
Study Objective To develop and validate an open-source, low-cost preclinical MR-guided focused ultrasound (MRgFUS) system capable of delivering quantifiable, repeatable thermal and mechanical sonications under real-time MRI guidance.
Animal model / Human subject Mus musculus (mouse); strain: not specified; age: not specified; sex: not specified
Disease model Tumor (murine tumor / cancer)
MRI or image guidance method MR-guided: anatomical MRI (T1/T2) for treatment planning, real-time PRF-shift MR thermometry for targeting/closed-loop PID control, and MR acoustic radiation force imaging (MR-ARFI) to localize/confirm the ultrasound focus
Targeted brain region(s) Subcutaneous Tumor

Outcomes and Safety

Summary of Outcomes The open-source MRgFUS system maintained stable tumor hyperthermia using closed-loop PID control.
Duration of biological effect 20 min
Safety-related matter Target temperatures were maintained with minimal overshoot and no observed tissue disruption.

Brain Region

Ultrasound Parameters

Ultrasound instrument ingle-element focused ultrasound transducer
FUS Frequency 1.1 MHz
FUS Intensity not reported
FUS Pressure not reported
FUS Mode pulsed
Pulse duration 4 ms
Duration of a single FUS session 20 min
Focal Characteristics 51.74 mm
Treatment frequency Multiple sessions

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