Development of an Mri-guided Robotic Platform for Focused Ultrasound Induced Sonothrombolysis of Brain Intraventricular Blood Clots

Soucier, Nathan 1, 2 ; Looi, Thomas 2 ; Raisbeck, Sam 2 ; Pichardo, Samuel 2 ; Waspe, Adam 2 ; Drake, James 2

1. Institute of Biomaterials and Biomedical Engineering, University of Toronto; 2. Centre for Image Guided Innovation and Therapeutic Intervention, Hospital for Sick Children, Toronto, Ontario

Purpose and Hypothesis: Bleeding into the cerebral ventricles of premature infants known as Intraventricular hemorrhage (IVH) remains a common and major complication when very premature (< 32 weeks) with low birthweight (<1 Kg). IVH commonly obstructs the flow of cerebrospinal fluid (CSF), consequently, leading to increased accumulation of CSF under increased pressure, termed hydrocephalus, resulting in a secondary brain injury if untreated. This is currently treated via a spinal tap or an invasive brain surgery to insert a cerebral shunt which drains the excess CSF, relieving the accumulated CSF and reducing intracranial pressure. The purpose of this research is to provide a non-invasive incisionless method of treating IVH by directly dissolving the blood clot in the brain, to reduce the effects caused by hydrocephalus and increased pressure in the brain. Magnetic Resonance guided Focused Ultrasound (MRgFUS) is a non-invasive method of delivering accurately focused high energy ultrasound sufficient to produce thrombolysis.  The infant fontanelle is a natural ultrasound window for treating the premature brain.  Our hypothesis is that a blood clot in a piglet model of an IVH can be dissolved by at least 50% using a robotic MRI-guided focused ultrasound (MRgFUS) platform with a targeting accuracy of < 2 mm. 

Methods: A 1.2MHz, 256-element phased array focused ultrasound (FUS) transducer (Imasonic, Voray-sur-l'Ognon, France) is mounted on a five degree-of-freedom MRI compatible robot that operates in the bore of a clinical 3T MRI scanner (Achieva 3.0T Tx, Philips Healthcare, Best Netherlands) to achieve precise image-guided targeting. The robot’s operable workspace will be evaluated by defining the window of transmission through the fontanelle and range of maneuverability within the bore of the MRI. Clot volume reduction and targeting accuracy will then be assessed with a goal of more than 50% decrease in volume with targeting capabilities within ±2 mm. This will initially be tested using in-vitro phantom models and porcine cadaver heads, followed by in-vivo animal tests using an established piglet model of an IVH.

Preliminary Results and Conclusions: The robot, FUS and MRI have been successfully integrated into one system, including the development of software that provides a graphical user interface that allows for control of the platform. A porcine model of IVH has been developed, and thrombolysis of IVH clots demonstrated. The results from this work will provide a new method of treating premature babies with IVH that is both drug-free and non-invasive, thereby reducing the long term neurodevelopmental effects cause by hydrocephalus.