Objective and Hypothesis Introduction • Most brain surgeries involving deep tumor / cyst resections are done using invasive craniotomies. (See Fig. 1) • Invasive craniotomies entail substantial amount of blood loss, potential infections, long recovery periods, and an additional cranioplasty surgery later on. • Magnetic Resonance Imaging (MRI)-guided minimally invasive laser ablation systems, such as Visualase (Medtronic), have recently been adopted. [1] • Due to fundamental limitation in the penetration depth of optical waves, the probe has to be inserted into the brain tissue, placing vital structures at potential risk. (Fig. 2) • HIFU (High Intensity Focused Ultrasound): Transcranial HIFU has been developed to non- invasively ablate brain tumors. An example include Exablate Neuro, InsighTec. (Fig. 3) • Despite the promises for treatment of movement disorders (e.g. Essential Tremors or Parkinson disease [2]), this approach faces a significant challenge for neuro-oncology ablative purposes: • Ultrasound is highly attenuated when passing through the skull, and excessive power (650-800W) is required to penetrate the brain [3]. • Consequently, there is a demand for HIFU tools that accommodate patient safety and are FDA-friendly. • This study reports the design and fabrication of a miniaturized therapeutic probe with the following specifications: 1.5 MHz, 45 mm radius of curvature rectangular aperture of 9x32 mm. • While this study demonstrates successful proof-of-principle ablation of lesions on a BSA based gel phantom, future directions of this study involved cadaveric validation, as well as further miniaturization of probe allowing it to fit within the human ventricles. Conclusions Acknowledgments References [1] Patel P, Patel NV, DannishSF. J Neurosurg. 2016 Oct;125(4):853- 860. [2] O’Reilly MA, Hynynen K. North American Hyperthermia Group. 2015;31(3):310-318. [3] McDannold N, Clement GT, Black P, Jolesz F, Hynynen K (2010). Neurosurgery, 66(2): 323-332. [4] Manbachi A, et al. WO2018160657A1 [5] Imani F et al., IEEE Transactions on Biomedical Engineering, vol. 60, no. 6, pp. 1608-1618, June 2013. [6] N'Djin WA, Burtnyk M, Lipsman N, Bronskill M, Kucharczyk W, Schwartz ML, Chopra R. Med Phys 2014 Sep 41 9 093301 [7] MacDonell J, Patel N, Rubino S, et al. Neurosurgical focus. 2018;44(2):E11. [8] Zhang X, Ellens N, Belzberg M, Miller P, Cohen AR, Brem H, Siewerdsen JH, A Manbachi (2017, July 30-August 3). 59 th AAPM Annual Meeting & Exhibition (Denver, CO), Abstract #37878 [9] Lafon C, Zderic V, Noble ML, Yuen JC, Kaczkowski PJ, Sapozhnikov OA, Chavrier F, Crum LA, Vaezy S (2005). Ultrasound Med Biol. 31(10):1383-1389 This study was funded by TEDCO (Maryland Technology Development Corporation)’s MII (Maryland Innovation Initiative) funding, as well as Coulter Foundation and Johns Hopkins University, Whiting School of Engineering’s Cohen Translational Funding opportunities. The authors would also like to thank Sonic Concepts, Inc (Bothell, Washington) for manufacturing of the custom probe, as well as Maryland Development Center for support in the software development. Results and Discussion • Building on these data, a custom HIFU transducer with a hybrid imaging/therapeutic tip was designed and manufactured (Fig. 6b). • the transducer was verified to be functional in a phantom model. This was performed to demonstrate proof-of-concept in ablating a region of interest, according to the criteria listed in Fig. 6c. Minimally Invasive Theranostic Device for Ablative Neuro-Oncology Nao Gamo 1 , Rajiv Iyer 2 , Stephen Restaino 3 , Kyle Morrison 4 , Alan Cohen 2 , Henry Brem 1,2 , Mari Groves 2 , and Amir Manbachi 1 1 Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 2 Department of Neurosurgery, Johns Hopkins University, Baltimore, MD 3 Maryland Development Center, Baltimore, MD, 4 Sonic Concepts Inc., Seattle, WA Numerical Modeling Simulations Equipment to drive the probe Software development Fabricated custom prototype imaging probe modified from off- the-shelf Initial version of the customized therapeutic probe (larger size) Cavitation at Focus (Test 1) (Test 2) • Objective: Here, we report the design, development, and cadaveric testing of a novel HIFU device for brain tumor ablation. This device is designed to access the ventricular space via a minimally invasive burr hole in the skull (Fig. 4), allowing ultrasound to reach targets deep in the brain, while eliminating the need for high power to penetrate the skull. [4] • In this study, our aimed to study the following question for an Intraventricular Ultrasound approach: Can we Design a Minimally Invasive Image-Guided Therapeutic Probe (with enhanced or comparable level of safety and efficacy when compared to larger apertures) to fit within the Cerebral Ventricular Space for Ablative Neuro-Oncology purposes? Fig. 4 – Solution Concept Study Design and Methods • Simulations: were performed (in MATLAB) to validate the efficacy of the proposed design in providing sufficient heating and precise lesioning and to determine the required acoustic power level. [8] • Prototyping: a number of fabrication iterations was performed in collaboration with Sonic Concepts, Inc (Bothell, Washington) to arrive at an alpha prototype of a custom-probe providing both imaging and therapeutic ablation. • Software Development: was conducted using MATLAB installed on a Vantage 64 system by Verasonics, Inc (Kirkland, WA), a platform that allowed to store, study and modify the signal as per needed. • Testing: Verification was done through assessing the precision of the system to create a cavity inside a BSA (Bovine Serum Albumin) based gel phantom, as previously reported by [9]. (See Fig. 5) Results and Discussions • Our simulation modeling in [2] determined the appropriate parameters for an initial prototype with power (12-35W) and heat (peak temperature at 65C, 10s sonication) to precisely focus ultrasound 3cm away (1-5cm), creating a lesion with a depth of field of 1x0.15c. [8]. • These data show that our system can provide the same efficacy of treatment with 2 orders of magnitude less power. Fig. 5 – Methods : (a) Numerical Modeling Simulations; (b) Prototyping of the Custom Probe; (c) Software Development and Functionalizing of the system; (d) Verification testing of the probe on BSA gel phantoms (a) (b) (c) (d) Fig. 1 – Craniotomy Fig. 2 – Visualase laser ablation system Fig. 3 – InsighTec’s Exablate Neuro Fig. 6 – (a) A burr hole (red) is placed on the skull for device (white) access into the lateral ventricle (green); (b) Isometric 3D view of the custom-designed manufactured transducer; (c) Testing was conducted to evaluate whether the probe can ablate with the specified criteria.