1. DIET – An emerging non- invasive, portable and low- cost approach to breast cancer screening Prof J. Geoffrey Chase Univ of Canterbury Dept of Mechanical Engineering, Centre for Bio-Engineering Christchurch, New Zealand

2. Overview 1.Background 2.DIET Technology 3.Clinical results 4.Summary

3. The Problem  Breast cancer was the most common cause of female cancer death in 1999  Over the period 1972 to 1997, the annual number of breast cancer deaths increased from 427 to 643 [1]  Breast cancer is over represented among Maori (in NZ) and other ethnic groups worldwide [1] NZ Ministry of Health, 2002

4. Breast Cancer Screening Reduces Mortality (Tabar et al, 2003) No real difference Results due to improving care Screening = More early detection +20%

5. Why? Low Compliance & Access Source: NZ Ministry of Health, Trends and Projections 2002. What you don’t see can kill you! [Breast Screen Aotearoa] Goal is 70% every 2 years, but we get ~60% -- 40% missing! Predominant compliance rates in the US and EU range from 50-80% based on many factors Eligible populations (over 50 years) are growing demographically for next 10-20 years Certain sub-groups have very low screening rates and thus much higher mortality Occurrence rates don’t seem to particularly favor any group

6. Screening  Screening has resulted is fewer deaths and earlier treatment  Concerns of screening  Patient dose  When should women start screening  Costs  Resources  Impacts of false positives (in a gold-standard test that can only be done infrequently at older ages)  However, fundamentally, mammography is a scarce and increasingly costly resource …  One thus cannot simply go get a repeat test to confirm, especially if you are younger

7. Current Diagnostic Techniques  Palpation/Clinical Breast Examination (CBE)  Very subjective  Primary form of diagnosis  Most mammograms occur after being found this way first  Mammography  only modality recommended for screening  X-rays, breast compression (painful)  Lower compliance due to pain, cost and access  Ultrasound  High level of operator skills  Significant (sensor) noise  MRI  Very accurate, but expensive  Very few can be served  No screening programs in most developing nations!  Cost and X-Ray dose are major factors Mammography MRI

8. Problems with Existing Techniques  Currently, predominant breast cancer screening methods are:  Uncomfortable  Subject the patient to doses of radiation  Require expensive, location specific equipment and clinical staff.  They thus have relatively limited throughput (not enough capacity)  They are also low contrast as cancerous tissue density varies only ~5-10% from healthy tissue  Coupled with resulting low compliance rates the average tumour size detected is ~1cm = 10x larger than possible

9. What’s Needed?  An all new approach  Must be clinically and commercially feasible  Must address compliance (w/ screening ) issues  Must offer high throughput in terms of speed to test and access  An ideal design list would include:  Low cost equipment with no need for specialist technician  Portable  No X-Ray dose  Equal efficacy (1cm detection) compared to mammography  Greater comfort (no compression)  Succinctly: less invasive, low cost screening system with more objective diagnosis (less ‘human error’)

10. The DIET Concept  DIET = Digital Imaging-based Elasto-Tomography  Can we meet all these needs? Governors Bay, ChristchurchSunset over Southern Alps, Christchurch

11. The DIET System Concept

12. Advantages of the DIET Concept  Screening from a younger age (no radiation dose)  Possible to build a history (every year!)  Less painful alternative (equals higher compliance)  Accuracy (initial target 1cm)  Portability and ease of use (no specialised technician and no loss of compliance due to travel)  Scalability (will improve as silicon technology used improves)  Should be low cost (low-cost technologies used)

13. Prototype Development Laboratory Hardware 1 st Clinical prototype

14. DIET device at Canterbury BC

15. So, does it work??  If we could measure surface motions could we detect cancerous lesions, from surface data only? Lake Mathieson, Mirror Lakes West Coast of S. Island Lindis Pass and into Wanaka Cental Otago, S. Island

16. So, how does it work? And does it?  3 main steps:  Vibration and image capture  Surface motion: (a) tracking and (b) characterisation  Diagnose based on surface motion  Proof of concept clinical trials as part of ergonomic and comfort trials shown  Multiple volunteers, multiple frequencies of actuation  Test of technology and proof of clinical concept

17. Step 1: Vibration & Image Capture  Vibrate breast from underneath and capture digital image sequences from 5 cameras Silicone gel with fiducial markers Simulation of human breast

18. Step 2a: Surface Motion Tracking  Markers tracked in 2D, then 3D correspondences  Optical flow skin tracking (better resolution) Camera 1Camera 2Full 3D reconstruction Fiducial trackingSkin tracking

19. Step 2b: Motion characterisation  Motion data is parameterised to allow diagnostic processing  Elliptical path characterises motion in 3D (at each frequency)  Motion flows around a hard tumor like water around a rock changing amplitude and phase asymmetrically Z-amplitude Z-phase

20. Step 3: Diagnosis from tumour effect on motion  Silicone phantom with 20mm tumour at 6 o’clock  Motion images alone can potentially give yes/no answer about tumour inclusion  Readily automated... Entirely objective Re Amplitudez-phase

21. In vivo results (preliminary)  Breast from ongoing trial  30mm tumour between 1-2 o’clock, left outer upper quadrant  Same effects as in phantoms are observed TOP BOTTOM LEFTRIGHT Z-phaseRe z -amplitude

22. Some more visual outcomes  Both breasts of each subject shown at one frequency  120mm not shown, as it is almost entire breast 30mm @ 1:30 o’clock20 + 8mm @ 2:30 o’clock 11mm @ 10:30 o’clock

23. DIET human trial summary  Ergonomics/Calibration trial  18 Subjects, age 49.3 (SD 8.5)  36 breasts imaged (both on each subject)  4 breasts with malignant tumors (11, 30, 20+8, 120mm)  2 breasts with benign cysts (clusters of 10-21mm, )  30 healthy breasts  Range of sizes and shapes see below.

24. First Uses: A 3 word case  Under-age  Under-served  Under-equipped Plenty of “room” for a new modality like this

25. A Brief Summary  DIET is an all new approach to breast cancer screening that offers several potential advantages over current methods  Initial simulation and experimental proof of concept studies showed that it might be possible to achieve realistic screening (~1cm inclusion size detection)  The main imaging and reconstruction steps are technologically challenging  Initial proof of concept experiments on silicone phantoms have been successful in identifying inclusions both via reconstruction and from disturbances in surface motion

26. Acknowledgements Prof Geoff ChaseDr Geoff Shaw Dr Thomas Desaive Christina Starfinger Dr. Chris Hann Richard Brown Rodney Elliot Crispen Berg Dr. Richard Wien & Dr. Larry Ray DIET Project Team 2004 Jerome Rouze Arnaud Milsant Ashton Peters DIET Project Team 2005 Wili Berger Ben Petit Michael Wiertlewski Fabrice Jandet Edouard Ravni Anthony Hii Stefan Wortmann Shig Kinoshita

27. Questions?