Interdisciplinary Research Stimulating Health Technology Innovation in IMSaT Dr Mike MacDonald IMSaT and Physics University of Dundee 23 April 2010

Background

IMSaT Institute for Medical Science and Technology (IMSaT) launched in January 2008 by University of Dundee to promote joint activity between medicine, life sciences and the physical sciences and engineering IMSaT Medicine Life Sciences Science and Engineering

IMSaT Institute for Medical Science and Technology (IMSaT) launched in January 2008 by University of Dundee to promote joint activity between medicine, life sciences and the physical sciences and engineering IMSaT Medicine Life Sciences Science and Engineering

Realisation More than £6M investment More than £17M awards since launch Now ~50 staff and students Facilities almost completed IMSaT Ninewells Hospital

Facilities

Cell biology and nanomedicine Interventional MRI Surgical Technology Photonics Ultrasonics Local Laboratories IMSaT Infrastructure

Cell biology and nanomedicine Interventional MRI Surgical Technology Photonics Ultrasonics Local Laboratories IMSaT Infrastructure

Cell biology and nanomedicine Interventional MRI Surgical Technology Photonics Ultrasonics Local Laboratories IMSaT Infrastructure

Staff and Collaborators

IMSaT Research Leaders Prof. Andreas Melzer, Director, specialism in MRI- guided intervention and surgery Prof. Sir Alfred Cuschieri, Chief Scientific Advisor, specialism in minimal access surgery Dr Sandy Cochran, Team Leader in medical ultrasound Dr Stuart Brown, Team Leader in surgical technology Dr Mike MacDonald, Team Leader in biophotonics Dr Paul Prentice, Team Leader in photoacoustics Dr Lijun Wang, Team Leader in cell biology and nanomedicine

Andreas Melzer – pre-clinical Alfred Cuschieri – clinician/scientist Sandy Cochran – engineer / physicist Stuart Brown – mechanical engineer Mike MacDonald – applied physicist Paul Prentice – applied physicist Lijun Wang – life scientist TBC – clinician TBC – life scientist Research Leader Backgrounds

Some Local Collaborators Prof. Alistair Thomson, Surgery and Molecular Oncology, Ninewells Hospital Dr George Corner, Medical Physics/Ultrasound, Ninewells Hospital Dr Elaine Henry, Gastroenterology, Ninewells Hospital Dr Graeme Houston, Oncology, Ninewells Hospital Dr Zhihong Huang, Ultrasound, Dundee University Dr Rob Keatch, Tissue Engineering, Dundee Univ. Dr Graeme MacLeod, Anaesthesia, Ninewells Hospital

Some External Collaborators University of Birmingham, Materials University of Bristol, Mechanical Engineering Fraunhofer IKTS, Materials University of Glasgow, Electronic Engineering Institute for Cancer Research, Medical Physics Insightec (Israel), Focused ultrasound surgery Penn State University, Materials University of Southampton, Engineering Trondheim University, Surgical technology Weidlinger Associates (USA), Design software

Some Previous/Present Collaboration

Strategy and Delivery

Strategic Dimensions Key Target Area Image-guided intervention Applications Oncology, Cardiovascular, and Other (e.g. Anaesthesia, Surgical techniques) Technology MRI, ultrasound, and biophotonic imaging, with state-of-the-art intervention, including surgical technology and devices Collaboration Strong bias towards scientific, engineering and clinical collaboration Clinical application Strong bias towards clinical application of research outcomes

IMSaT’s strategic plan includes a project pipeline for commercialisation of research Commercialisation

Large Projects Nanoporation (£1.8M) – Targeted drug delivery Sonotweezers (£1.5M) – Particle / cell manipulation Lightsheet microscopy (£0.7M) – embryo imaging Biomag (£1.4M) – Surgical manipulation of magnetised tissue Laparoscopy (£2.5M) – New tools for keyhole surgery IIIOS (£3.7M) – Interventional imaging operating system DPFS (£0.6M) - Device / model development

Sample of Other Projects Ultrasonic virtual histology (3 x grad student) Devices for ultrasonic cutting (3 x grad student) Integration of Si and piezoelectrics (1 x postdoc) Ultrasound guided regional anaesthesia (2 x grad student, 1 x undergrad) Laser generated ultrasound (1 x grad student) Photoacoustic imaging (1 x grad student) Optical anastamotic perfusion assessment (1 x ungrad) MRgFUS (4 x grad student) Tissue motion tracking (2 x grad student) Microbubble processing (1 x grad student) Nerve regeneration with magnetic nanoparticles (1 x postdoc) Organ retraction in surgery (1 x postdoc) Ultrasound phantoms (1 x postdoc)

Case Study 1: Ultrasound innovation

UGRA Regional anaesthesia gaining wide acceptance Clinical aim is to introduce anaesthetic locally around nerve to block pain, typically in limb Benefits include long lasting postoperative pain relief, accelerated rehabilitation, improvements in quality of life Potential side effects include convulsions / cardiac arrest from intravascular injection and permanent nerve damage and loss of function from intraneural injection Unmet need is for a specialised ultrasound probe for ultrasound-guided regional anaesthesia (UGRA) Requirements relate to imaging performance and ergonomics

New Imaging Configuration Cable outlet Array casing Needle Position of electroacoustic transducer components Ultrasound beam Cable outlet Needle Array casing Ultrasound beam Position of electro- acoustic transducer components Needle oblique to ultrasound beam from conventional transducer, can’t penetrate spine Needle parallel to ultrasound beam when inserted through alternate transducer design 

Previous Solution Optimised for epidural injection in obese subjects only

Lumbar Spine Image AG – Acoustic gap II – Interspinous interspace SP – Spinous process SP II AG II

Clinical Trial and Future Work Previous clinical trial Transducer safety confirmed, including CE marking More than 50 obese subjects at multiple sites Primary end point: time to insert needle Trial completed; 20% time saving New MRC DPFS funding awarded £250k over 18 months to develop device for more widely used regional nerve blocks Technical issues, ergonomics and IP all important

Case Study: MRgFUS

MRgFUS: MRI-guided Focused Ultrasound Surgery Risks of surgical therapy outweigh potential benefits for many patients E.g. frail, elderly patients and patients with benign tumours Non-invasive focused ultrasound surgery is a possibility Image guidance is crucial

Simple Ultrasonic Hyperthermia Custom transducer for high intensity focused ultrasound (HIFU) Hyperthermia applied to poultry breast in vitro, max. intensity 240 W cm -2

Illustrative Results Visual Histology HFUS SEM

Illustrative Results Visual Histology HFUS SEM Necrosed tissue Viable tissue

Image Guidance MRI presently the leading image guidance technique MRgFUS - MRI- guided focused ultrasound surgery Ultrasound guidance also possible

MRgFUS Thiel cadaver with InSightec Exablate 2000 system

Matrix Array Transducer Preliminary trials of hyperthermic necrosis of cadaveric liver

Robot-mounted Matrix Array Demonstration of possible future of image-guided surgery

Summary and the Future

IMSaT and its partners now allow seamless translation of basic research into clinical progress Imaging is a key topic in Dundee Many projects now under way Case study: MR-guided focused ultrasound surgery Great potential; many major companies and universities engaged in clinical studies Summary

Next Steps Stronger theming Less opportunistic funding, stronger focus on strategy Commercialisation Recruitment of business liaison person Enhanced marketing/sales Revised website, planned exhibition and conference attendance ISO13485/GLP Certification To reduce barriers to clinical adoption Additional facilities Establishment of full preclinical resource unit