Proceedings of the 7th United Kingdom & Republic of ...

Proceedings of the 7th United Kingdom & Republic of Ireland Postgraduate Conference in Biomedical Engineering and Medical Physics

PGBiomed 2013

July 9th-11th, 2013 Austin Pearce Building, University of Surrey Guildford, Surrey, UK

EDITORS: Samantha Simons & Xuefei Bai © 2013 University of Surrey ISBN 978-1-84469-028-2

Department of Mechanical Engineering Sciences Department of Physics

7th UK and RI Postgraduate Conference in Biomedical Engineering and Medical Physics Guildford, Surrey, UK, 9th-11th July

Organising Committee Alex Humphries Conference Chair-Biomedical Engineering Email: [email protected] Faith Green Conference Chair-Medical Physics & Social Chair Email: [email protected] Erin Henslee Publicity Chair & Finance Chair Email: [email protected] Samantha Simons Technical Chair & Exhibition Chair-Oral Email: [email protected] Xuefei Bai Technical Chair & Exhibition Chair-Poster Email: [email protected] Dr. Daniel Abásolo Faculty Advisor-Biomedical Engineering Email: [email protected] Dr. Silvia Pani Faculty Advisor-Medical Physics Email: [email protected]

© 2013 University of Surrey

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Foreword Welcome to PGBiomed 2013, the 7th Postgraduate Biomedical Engineering and Medical Physics event in the UK and Republic of Ireland. The organising committee are delighted to bring what has proven to be a highly successful event in the past to Guildford, Surrey in 2013. This year, the conference focuses on some of the rapid developments made in the field, covering Medical Imaging, Radiotherapy, Movement Analysis, Tissue Engineering, Biomedical Signal Processing and Dielectrophoresis. The idea behind PGBiomed is to give postgraduate students the opportunity to share their work with fellow students in similar fields of study and at similar stages of research. We encourage you to share your ideas and learn from those around you, the links you forge here may benefit you in years to come and grant you an opportunity to interact with tomorrows leading specialists. We aim to provide a friendly and relaxed environment for early stage researchers to present their work, held at the University of Surrey, situated in the historic market town of Guildford. We hope you will find your surroundings comfortable and feel at ease during the event. We are very pleased to welcome four guest speakers to the conference: Ron Pethig, a professor from the University of Edinburgh who specialises in bio-electronics; Jenny Kent, a state registered Clinical Scientist working at the Defence Medical Rehabilitation Centre (DMRC), Headley Court; Ken Young, a professor and Consultant Physicist, specialising in mammography at the Royal Surrey County Hospital; and Tom Jordan, Head of Radiotherapy Physics at St. Luke’s Cancer Centre. Our speakers all have a wealth of experience in Biomedical Engineering and Medical Physics and will bring practical insights into the work they have undertaken. We are also delighted to present a careers panel session, held at the end of the conference. The panel consists of experts in industry and research across the Biomedical Engineering and Medical Physics sector who will be available to answer any questions you have on early career development, Postgraduate courses, research careers and training opportunities. The aim of this session is to help you make the most of the training and opportunities available to you after graduating, giving you ideas and inspiration for the future.


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We are very grateful to all our sponsors for their generosity: IEEE EMBS UK and RI chapter, the IET, IoP, IPEM, IMechE and the University of Surrey’s department of Mechanical Engineering Sciences and department of Physics. The help and support given by the reviewers was also essential and is also acknowledged. I am grateful to the committee who has worked tirelessly to make this event enjoyable for all concerned. I hope that you will enjoy your time in Guildford and, more importantly, gain something from your experience, be that information or inspiration.

Prof Christopher J. James Chair, IEEE UKRI EMBS Chapter


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Contents Organising Committee...................................................................................................................... i Foreword ...........................................................................................................................................ii Contents ....................................................................................................................................................... iv Guest Speakers ................................................................................................................................ ix Panel Session.................................................................................................................................... xi Oral Presentations Oral Session 1, Wednesday, 10th July 2013, 10:15-11:15 am O01.

A Quantitative Study on the Performance of PICASSO Detector in Phase Contrast Imaging with Synchrotron Radiation............................................................................................................ 1 M. Longo, L. Rigon, F. Arfelli, F.C. M. Lopez, P.R.T. Munro, R. Longo

O02.

Energy Resolution and Efficiency Comparisons of Two ASICs of Cadmium Telluride Suitable for Room Temperature Diffraction Medical Imaging ................................................... 2 C. Christodoulou, M. Wilson, M. Veale, D. O’Flynn, P. Seller, R. Speller

O03.

X-ray Phase Contrast Imaging Using the Edge Illumination Method ........................................ 3 T.P. Millard, M. Endrizzi, P.C. Diemoz, C.K. Hagen, C.Zapata, F. Vittoria, R.D. Speller, A. Olivo

O04.

Dual Image K-Edge Subtraction Using a Conventional X-ray Source ....................................... 4 N. Henthorn, S. Pani, S.C. Saifuddin

Oral Session 2, Wednesday, 10th July 2013, 3:30-5:00 pm O05.

Automated Laser Registration and Quantitative Assessment of Articular Cartilage for Lower Limb Arthroplasty ............................................................................................................... 5 S.V. Joshi, P. Rowe, G. Pierce, K.E. Ahmed, C. MacLeod

O06.

Joint Response to Translational Perturbation in Subjects with a History of Back Pain........... 6 M.M. Sperry, A.T.M. Phillips, A.H. McGregor

O07.

Translating 2D MRI Scans of the Human Forearm into 3D Dielectric Phantoms .................... 7 E. Dijemeni, C. Nzekwu

O08.

Movement Patterns and Variability of Upper Limb Motion in Real and Simulated Activities of Daily Living ................................................................................................................................... 8 S. Taylor, A. Kedgley, A. Shaheen


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O09.

Methods of Analysis for Establishing the Axial Range of Motion of the Glenohumeral Joint ... ........................................................................................................................................................... 9 A. Humphries, A.F. Shaheen, S. Cirovic

O10.

Wearable EOG Sensors for Assistive Technologies and HMI Applications............................. 10 N. Steinhausen, R. Prance, H. Prance

Oral Session 3, Thursday, 11th July 2013, 9:00-9:45 am O11.

Study of the mfVEP Signals of MS Patients Based on Frequency Domain .............................. 11 L. de Santiago, L. Boquete, A. Fernández, D. Pérez, R. Barea, R. Blanco

O12.

Electroencephalogram Lempel-Ziv Complexity Analysis in Alzheimer’s Disease with Different Coarse Graining Techniques ........................................................................................ 12 R. Morgado da Silva, D. Abásolo

O13.

Distance Measure Based on Lempel-Ziv Complexity for Analysis of Electroencephalograms in Alzheimer’s Disease ................................................................................................................... 13 S. Simons, D. Abásolo, M.Hughes

Oral Session 4, Thursday, 11th July 2013, 11:00-11:45 am O14.

Development of a New Near inFrared Multi-wavelength, Multi-channel Time Resolved Spectrometer Using a Supercontinuum Laser for Measuring Brain Tissue Haemodynamics and Metabolism .............................................................................................................................. 14 L. Dunne, J. Hebden, I. Tachtsidis

O15.

Characterisation of Glass Beads for Radiotherapy Dosimetry.................................................. 15 S. Jafari, C. Gouldstone, P.H.G. Sharpe, D.A. Bradley, C.H. Clark, A. Nisbet, N.M. Spyrou

O16.

Development of a Novel Methodology for Using a Commercial Detector Array in Dosimetry Audit of Rotational Radiotherapy ................................................................................................ 16 M. Hussein, Y. Tsang, R.A.S. Thomas, C. Gouldstone, D. Maughan, J.A.D. Snaith, S.C. Bolton, A. Nisbet, C.H. Clark

Oral Session 5, Thursday, 11th July 2013, 1:15-2:15 pm O17.

A Microfluidic Device for Neuronal Network Communication Studies ................................... 17 G. Robertson, T. Bushell, M. Zagnoni

O18.

Production of a Scaffold Using Polymer Based Substrates Mixed with Calcium Phosphate and in Contact with Cultured Osteoblast and Chondrocyte Cells ............................................ 18 E. Michailidou, M. Youseffi, P. Twigg


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O19.

A Compact Optoelectronic Tweezers System to Manipulate and Analyse Live Immune Cells . ......................................................................................................................................................... 19 A. Jeorrett, O. Millington, K. Mathieson

O20.

Development of a biomimetic micro liver through dielectrophoretic patterning in agarose .. 20 N.P. Macdonald, A. Menachery, J. Reboud, J.M. Cooper

Poster Presentations Poster Session 1, Wednesday, 10th July 2013, 1:30-2:15 pm P01.

Multi-Channel Empirical Mode Decomposition in Brain-Computer Interfaces ..................... 21 S.R.H. Davies, C.J. James

P02.

Using Partial Directed Coherence to Investigate EEG Connectivity in Motor Preparation .. 22 G. Vieira, P. Dean, L. A. Baccala, J. R. Sato, E. Amaro, A. Sterr

P03.

Comments on DCM as an Effective Connectivity Measurement Tool in EEG Analysis......... 23 P. Tayaranian Hosseini, D.M. Simpson, S.L. Bell, J. Brinton, S. Wang

P04.

Analysis of Electrocardiogram Recordings with Advanced Non-linear Methods for the Evaluation of Atrial Fibrillation Organisation ........................................................................... 24 J-M. Best, D. Abásolo, R. Morgado da Silva, R. Alcaraz, J. J. Rieta

P05.

Measurement of Event Related Potential using Electric Potential Sensor ............................... 25 M. Fatoorechi, H. Prance, R. J. Prance

P06.

Simulation and Analysis of Transmembrane Voltage on the Membrane of the Internal Oganelles During Nanosecond Electroporation .......................................................................... 26 G. Jiang, Y. Alfadhl, X. Chen

P07.

Design of an Automated Fluid Handling Device for Enhanced Volumetric Flow Separation of Bioparticles Using Dielectrophoretic Forces ............................................................................... 27 C. Grant, M. P. Hughes, H.O. Fatoyinbo

P08.

A Study on the Applicability of Non-Linear Analysis of P-wave Duration Over Time to Predict Atrial Fibrillation Onset .................................................................................................. 28 A. Martínez, D. Abásolo, R. Alcaraz, J.J. Rieta

P09.

Analysis of Repolarization Dispersion to Predict Sudden Cardiac Death Survival ................ 29 J. Ramírez, A. Mincholé, P. Laguna, E. Pueyo

P10.

Development of an Evidence-based Vital-sign Data Fusion System to Detect Patient Deterioration in the Emergency Department .............................................................................. 30 M. Santos, D. Clifton, L. Tarassenko


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P11.

Optimisation

of

the

Dielectrophoretic

Well-based

System

for

Real

Time

Cell

Characterisation............................................................................................................................. 31 R. Torcal-Serrano, K. Hoettges, H. Fatoyinbo, M. Hughes P12.

A Computational Simulation of the Action Potential and Sensitivity Analysis of the Hodgkin Huxley Model ................................................................................................................................. 32 C.T. Gondwe, C.B. Beggs

P13.

The Use of Adsorbent Technology in the Treatment of SIRS/Sepsis: A Rodent Model .......... 33 E. Coutts, T. Gourlay

P14.

Intra-limb Segmental Coordination During Treadmill Ambulation: the Effects of Walking Speed Increases .............................................................................................................................. 34 M. Bisele, J. Buckley

Poster Session 2, Thursday, 11th July 2013, 10:15-11:00 am P15.

Quantifying the Knee Soft Tissue Envelope in Healthy Subject(s) – Validation of Developed System ............................................................................................................................................. 35 A. Adewumi, P. Rowe

P16.

Does Treatment For Osteoporosis Really Work? A Statistical Analysis Of Bone Mineral Density For Lumbar Spine And Femur Post-Medication .......................................................... 36 Q. Tammer, M. Youseffi, A. Rashid

P17.

The Effect of Synthetic Cannabinoid HU308 on Fibronectin and Collagen Type I Expressions in MG-63 Osteoblast Cells ....................................................................................... 37 M. Genedy, M. Youseffi, A. Abdeldayem, M.C.T. Denyer

P18.

The Effect of TGF-β3, HCl, HCl/BSA and pH on Wound Healing of Cultured Osteoblast Monolayers ..................................................................................................................................... 38 M. Genedy, M. Ahmed1 F. Sefat, M.C.T. Denyer, M. Youseffi

P19.

Fabrication of a Microfluidics Device for Studying Neural Cell Behaviour at Single Cell Level Using Proton Beam Writing ............................................................................................... 39 S. Al-Shehri, G.W. Grime, V. Palitsin, R.P. Webb, M.P. Hughes

P20.

Evaluation of Cell Detachment Methods through Determination of Biophysical Properties of Cell Membrane and Cytoplasm by Using Dielectrophoresis ..................................................... 40 S. Mahabadi, F.H. Labeed, H.M. Coley, M.P. Hughes

P21.

The Potential Effects of Low-doses of Ionising Radiation and Malignancy ............................. 41 A.A.A. Almahwasi, J.C.G. Jeynes, K.J. Kirkby, and M.J. Merchant


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P22.

Dosimetric Properties of Varian TrueBeam with and without Flattening Filter: A Monte Carlo Simulation ............................................................................................................................ 42 M.A. Najem, A. Alrushoud, S. Jafari, Z. Podolyak, N. M. Spyrou

P23.

Mammography with Synchrotron Radiation: Dosimetric Result ............................................. 43 C.Fedon, E.Quai, F.Arfelli, D.Dreossi, G.Tromba, R.Longo

P24.

Graph Node Hub and Authority Analysis of Neural Systems using Resting-state fMRI........ 44 G. Vieira, J. R. Sato, P. Dean, E. Amaro, A. Sterr, L. A. Baccala

P25.

Characterisation of a Pixellated Spectroscopic Detector for Hyperspectral Breast Imaging ..... ......................................................................................................................................................... 45 F.H. Green, S. Pani, M.C. Veale, M. D. Wilson, P. Seller

P26.

K-edge Subtraction Imaging Using a Pixellated Spectroscopic Cadmium Telluride Detector .. ......................................................................................................................................................... 46 S.C. Saifuddin, M.D. Wilson, C.M. Veale, D.A. Bradley, S. Pani

P27.

Energy Dispersive X-Ray Diffraction (EDXRD) in the Investigation of Biological Tissues, with Special Interest on the Detectability of Fat Nodules in the Liver Tissue .......................... 47 C.S. Abuchi, T. Fearn, G. Royle, R. Speller

P28.

The Synthetic Cannabinoid WIN55, 212-2 Encourages Chondrocytes Dedifferentiation ...... 48 A. Abdeldayem, M. Yousseffi, M. Genedy, M.C.T. Denyer


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Guest Speakers Prof. Kenneth Young Ken Young has been the Consultant Physicist in charge of the National Coordinating Centre for the Physics of Mammography since 1990, and Visiting Professor of Medical Physics at the University of Surrey since 2006. Since 2007 he has also been Director of Research at the Royal Surrey County Hospital. He has played a leading role in developing the technical standards for mammography in the UK and the rest of Europe and has published widely on the physics of breast cancer imaging with X-rays. Wednesday, 10th July 2013, 11:45-12:30 am Optimisation of Breast Cancer Detection Using Digital Mammography

Ms. Jenny Kent Jenny graduated in 2002 from the University of Nottingham with a BEng Mechanical Engineering. She undertook the NHS Clinical Scientist training scheme in Medical Physics and Clinical Engineering from 2003-2006, for which she was based at the Douglas Bader Rehabilitation Centre, Queen Mary's Hospital, Roehampton, also completing her MSc in Biomedical Engineering at the University of Surrey during this period. She was recruited onto her current post as a Higher Scientific Officer at the Defence Medical Rehabilitation Centre (DMRC), Headley Court in 2006. Her role principally involves conducting and facilitating research, and providing research support for projects and initiatives relevant to an injured military population. Her primary research area is in prosthetics and complex trauma rehabilitation, with a particular focus on measuring performance and predicting outcome in individuals with trans-femoral lower limb amputation(s). Following the installation of a movement laboratory at DMRC in 2011, intended for both research and clinical use, her work over the last 18 months has included the development of the laboratory physical set up and protocols, and a clinical service for patients with complex traumatic injuries. Jenny became a state registered Clinical Scientist in December 2012. Wednesday, 10th July 2013, 2:15-3:00 pm Movement Analysis with Amputees


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Mr. Tom Jordan Tom graduated from the University of Glasgow Natural Philosophy department in 1975, and went on to study for a PhD at Strathclyde University, Bioengineering Unit. In 1979 he started in radiotherapy physics at the Christie Hospital, Manchester, where he spent 19 Years becoming nationally recognized in the field of radiotherapy dosimetry. In 1999, as Head of Radiotherapy Physics, Tom successfully developed a new Cancer Centre. In 2007 he became Head of Radiotherapy Physics at St. Luke’s Cancer Centre near Guildford with the role of leading the team to implement new and better technology and treatment methods in radiotherapy, combined with links to the National Physical laboratory and the University of Surrey. This has led to co-author publications in fields related to intensity modulated radiotherapy.Having served on a number of national committees with IPEM, Tom has also contributed to training and education, regularly lecturing on the Royal Marsden Radiotherapy Physics course, NPL dosimetry course, and Coventry based QC in Radiotherapy. Thursday, 11th July 2013, 11:45-12:30 am Lessons from Radiotherapy Accidents

Prof. Ronald Pethig Professor of Bio-electronics at the University of Edinburgh will be speaking on "The applications of DEP". His research into dielectrophoresis and electrokinetic effects aims to develop generic tools for applications in cell therapy and drug discovery. Holding a PhD in Electrical Engineering and another in Chemistry, Ron was appointed to a Research Chair at the School of Electronic Engineering, Bangor University. More recently, he worked as the VP of technology at Aura BioSystems, California before being appointed at the School of Engineering and Electronics at the University of Edinburgh. His talk is aimed at an interdisciplinary audience. Thursday, 11th July 2013, 2:15-3:00 pm Dielectrophoresis: Cells Dancing to Maxwell’s Equations


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Panel Session Prof. Ronald Pethig Professor of Bioelectronics, School of Engineering, University of Edinburgh Dr. Jamie Harle Lecturer in Medical Physics, UCL Dr. Julie Horrocks Head of Radiation Safety, Barts and the London NHS Trust Ms. Ann Henderson Careers Adviser for Postgraduate Researchers (PGRs) and Early Career Researchers (ERCs), University of Surrey Mrs. Jeanette Holt Careers Adviser for Postgraduate Taught (PGT) programmes, University of Surrey Dr. Peter Bannister Head of Operations at Asalus Medical Instruments and from September 2013 will be taking up the role of Chairman of the IET's Healthcare Technologies Network Dr. Mike Short Vice President of Public Affairs, at Telefónica Europe and an IET Trustee since 2008 (elected IET President 2011/2012) Dr. Dimitra Darambara Chair of the Medical Physics Group at IoP Dr. Slavik Tabakov Director of King's MSc programme


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A Quantitative Study on the Performance of PICASSO Detector in Phase Contrast Imaging with Synchrotron Radiation M. Longo1, L. Rigon2,3, F. Arfelli2,3, F. C. M. Lopez2,3, P. R. T. Munro4,5, R. Longo2,3 1

Sapienza University of Rome, Roma, Italy Department of Physics, University of Trieste, Trieste, Italy 3 INFN, Sezione di Trieste, Trieste, Italy 4 Optical and Biomedical Engineering Laboratory, School of Electrical, Electronic and Computer Engineering, The University of Western Australia, Crawley, Australia 5 Centre for Microscopy, Characterization and Analysis, The University of Western Australia, Crawley, Australia 2

Abstract – The imaging capabilities of a singlephoton counting detector designed for mammography with synchrotron radiation are investigated with the aim to utilize it in the Phase Contrast imaging modality. It is demonstrated that this technique can be applied to the mammographic examinations, ensuring low doses thanks to the high efficiency of the detector, high spatial resolution and low image noise with respect to the conventional mammographic images. I. INTRODUCTION The Italian National Institute of Nuclear Physics (INFN), has developed a detector prototype, called PICASSO (Phase Imaging for Clinical Application with Silicon detector and Synchrotron radiation), based on silicon microstrip sensor [1]. The prototype meets the requirements for clinical mammography with Synchrotron Radiation (SR) as far as spatial resolution, contrast resolution, efficiency and acquisition speed are concerned. Phase Contrast (PhC) imaging techniques are developed in order to exploit the phase shift experienced by X-rays passing through matter. The Coded Apertures X-ray Phase Contrast imaging (CAXPCi) method may be implemented using the PICASSO detector and synchrotron radiation. Using this imaging method, the small and low contrast details that are usually invisible on absorption images will become detectable as a result of the edge illumination principle: the phase sensitivity of an imaging system can be strongly enhanced by illuminating only the edge of the detector pixel [2]. II. MATERIALS AND METHODS The PICASSO detector operates in the edge-on configuration, i.e. with the photons reaching the sensor on the thin side, parallel to the strips and works in single-photon counting mode. It consists of two couples of two detector layers separated along the beam propagation. The sensor has a depth of 15-20 mm and the detector’s pixel size is defined by its 50-µm pitch and 300-µm height. It is equipped with MYTHEN II frontend ASICs of 128 channels. The synchronization of the two detector’s couples, concurrent with the reconstruction of images of all layers, and the spatial resolution are evaluated in order to test the imaging capabilities of this system. All measurements were done at SYRMEP beamline of ELETTRA synchrotron radiation facility in Trieste (Italy). Objective criteria such as modulation transfer function (MTF), noise power spectrum (NPS), detective quantum efficiency (DQE), and noise equivalent quanta (NEQ) were evaluated. The CAXPCi technique was experimentally © 2013 University of Surrey

tested using the PICASSO detector. A sample consisting of five differently absorbing and phase shifting wires was studied both in absorption and CAXPCi modalities. Moreover, the first experimental study on mastectomy specimens was carried out with a simplified coded aperture system and the SR beam, under dose conditions very close to those delivered during a SR mammography on a sample of comparable thickness [3]. III. RESULTS A vertical MTF of 50% is observed at the frequency of about 13 cycles/mm. Furthermore, the experimental results show that DQE, which combines the effects of MTF and NPS, is highly influenced by MTF. As the system was exposed to a high fluence, the NPS curves are fairly constant across the spatial frequency spectrum. Moreover, a direct comparison between absorption and CAXPCi images is pursued in order to reveal the main differences between the two techniques. The results show an improved image contrast and reveal that a more accurate visibility of detail can be reached using CAXPCi modality. IV. CONCLUSION The new PICASSO data acquisition system was tested at SYRMEP beamline of ELETTRA, demonstrating good imaging capabilities and spatial resolution, which are highly relevant to mammography. The measurements performed using CAXPCi technique and PICASSO detector are promising and will be optimised in terms of clinical feasibility in order to transfer the method into clinical practice. Moreover, a new algorithm was developed and can be applied to separate and quantify absorption and phase component from CAXPCi images allowing accurate material identification [4]. REFERENCES [1] F.C.M. Lopez, L. Rigon, R. Longo, F. Arfelli, A. Bergamaschi, R.C. Chen, D. Dreossi, B. Schmitt, E. Vallazza, E. Castelli, Development of a fast read-out system of a single photon counting detector for mammography with synchrotron radiation. Jour. of Instr., 6 C12031 (2011). [2] A. Olivo and R. Speller, Modelling of a novel x-ray phase contrast imaging technique based on coded apertures. Phys. Med. Biol., Vol. 52, 6555-6573 (2007). [3] E. Castelli, M. Tonutti, F. Arfelli, R. Longo, E. Quaia, L. Rigon, D. Sanabor, F. Zanconati, D. Dreossi, A. Abrami, E. Quai, P. Bregant, K. Casarin, V. Chenda, R.H. Menk, T. Rokvic, A. Vascotto, G. Tromba, M.A. Cova, Mammography with Synchrotron Radiation: First Clinical Experience with PhaseDetection Technique. Radiology, Vol. 259: 3 (2011). [4] P.R.T. Munro, L. Rigon, K. Ignatyev, F.C.M. Lopez, D. Dreossi, R.D. Speller, A. Olivo, A quantitative, non-interferometric X-ray phase contrast imaging technique. Optics Express, Vol. 21, Issue 1, pp. 647-661 (2013).

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Energy Resolution and Efficiency Comparisons of Two ASICs of Cadmium Telluride Suitable for Room Temperature Diffraction Medical Imaging C.Christodoulou1, M. Wilson2, M. Veale2 , D. O’Flynn1, P. Seller2 and R. Speller1 1

Department of Medical Physics and Bioengineering, UCL, London, U.K. Detector Development Group, Rutherford Appleton Laboratory, Didcot, U.K. [email protected]

2

Abstract - The energy resolution and energy efficiency at 60 keV of two pixellated 80 ×80 ASICs with 250 μm pitch are considered. In recent years, improvements in the growth of Cadmium Telluride (CdTe) has improved its resolution to be comparable to that of High Purity Germanium (0.6 keV at 60 keV), often used for diffraction imaging. The benefits of the detector are discussed and the energy comparisons of two ASICs are made, demonstrating energy efficiency of 50 % and energy resolutions of 1.9 keV and 2.3 keV at 60 keV. I. INTRODUCTION A novel pixellated ASIC with an 80×80 array of pixels on a 250 µm pitch has been designed with 1 mm thick Cadmium Telluride (CdTe) as the sensor material [1]. It is of interest for diffraction medical imaging due to its operation at room temperature, small pixel size and relatively large detectors (4 cm2) that can be tiled to cover larger areas. The 2-D array of energy resolving pixels allows for the collection of an Energy Dispersive X-Ray Diffraction (EDXRD) signal per pixel, while simultaneously acquiring diffracted signal at multiple angles across the detector array. The application of the detector in a dual EDXRD and Angular Dispersive XRay Diffraction system has been demonstrated in work applied to illicit material detection and explosives [2]. It has the ability and potential to provide spatial information, and fast acquisition times, thus being more suitable to clinical environments. The energy resolution is now comparable to that of High Purity Germanium (0.6 keV at 60 keV), commonly used for lab based diffraction imaging. It is also possible to operate the detector at room temperature and it does not require cryogenic cooling. The work here considers the energy characteristics of two ASICs bonded with 1mm CdTe (Acrorad, Japan). II. METHOD An Americium-241 (Am-241) source of 359 kBq activity was placed at a distance of 19 cm from the detector to ensure a flat field image which was acquired in 14 hours. All data were processed such that any charge sharing events and corrupted data were removed from the analysis, so that only single pixel events are included in the energy spectra. The energy spectrum per pixel was analysed in MATLAB (Release 2012b, The MathWorks, Inc. Massachusetts, USA), using the inbuilt curve fitting functions and with developed code to find the FWHM of the Am-241 peak at 60 keV. The energy resolution of each pixel was measured from each Gaussian fit for the 60 keV photopeak. The energy efficiency is calculated by the ratio of the total number © 2013 University of Surrey

of events in the spectrum after corrections, and the number of 60 keV photons incident at the detector. III. RESULTS

Figure 1 Energy resolution histograms for ASIC A (left) and ASIC B (right). This distribution can be approximated as a Gaussian due to the random distribution of incident photons and noise in the detector. Material defects leads to the deviation from the Gaussian distribution.

Figure 1 shows two histograms of the measured FWHM distribution for the two ASICs. Pixels with noisy or no spectral response were not considered in the analysis. These pixels equated to 3.8% of detector A, and 18.5% of detector B. The mean value of energy resolution was found to be 1.9 ± 0.3 keV at 60 keV for detector A and 2.3 ± 0.4 keV for detector B. The energy resolution is material, bonding and electronic component dependent (e.g. noise of the readout electronics.). Another ASIC of 1 mm CdTe has been shown to have a mean resolution of 0.8 keV at 60 keV [1]. The detection efficiency of 60 keV photons was found to be approximately 50.6 ± 0.2% for detector A and 49.8 ± 0.2%. The efficiency was calculated by the ratio of the total number of events in the 60keV peak after corrections and the number of 60keV photon incident on the detector. The efficiency also accounts for losses due to dead pixels, excluding the pixel areas equal to the percentage areas previously given. III. CONCLUSION The energy resolution of the two ASICs, as well as that used in [1] are more comparable to High Purity Germanium of 0.6 keV at 60 keV, with the two ASICs here having energy resolution values of 1.9 ± 0.3 keV and 2.3 ± 0.4 keV. Previously HPGe has been the detector of choice for lab based diffraction studies, but the 2-D detector array enables the prospect of a room temperature based system, with fast acquisition times, better suited to clinical environments in the future. REFERENCES [1] P. Seller at al., Pixellated Cd(Zn)Te high-energy instrument, Journal of Instrumentation 9th International Conference on Position Sensitive Detectors (PSD9), 2011. [2] D. O'Flynn et al., Explosive detection using pixellated X-ray diffraction (PixD), Journal of Instrumentation, 8, 2013. 2


X-ray Phase Contrast Imaging Using the Edge Illumination Method T. P. Millard1, M. Endrizzi1, P. C. Diemoz1, C. K. Hagen1, C. Zapata1, F. Vittoria1, R. D. Speller1 and A. Olivo1 1

Department of Medical Physics and Bioengineering, University College London, London, UK [email protected], [email protected]

X-ray phase contrast imaging (XPCi) is an emerging alternative to conventional x-ray radiography with the potential to give greatly increased image contrast in all applications of x-ray imaging. The Edge Illumination method developed at UCL allows for XPCi to be carried out with commercially available x-ray sources and detectors. Here we introduce the UCL prototype systems, and show why this system design has the potential for translation to a wide range of medical, industrial and security applications. I. INTRODUCTION XPCi has previously been implemented using highly coherent synchrotron radiation, and microfocal x-ray sources [1-3]. Other methods have shown that XPCi can be performed with conventional x-ray sources [4]. The Edge Illumination method, as discussed here, was first developed at synchrotrons in the late 1990s, with a recent adaptation to conventional sources and the construction of two prototype systems [5,6]. This method has the added benefits of low dose, sensible exposure times and ability to withstand vibrations that can be expected in a practical environment.

and to validate quantitative phase and absorption retrieval. It has also been used to demonstrate biological applications. One of these being mammography, for which approximately 100 in vitro breast tissue samples containing various types of tumours were imaged with the aim of showing enhanced detail visibility with equivalent dose to conventional mammography.

Figure 2. Diagram showing the layout of the UCL prototype Edge Illumination XPCi systems.

III. RESULTS Figure 3 shows planar images of a highlighter pen, taken using a UCL prototype Edge Illumination system, clearly showing higher contrast in the phase based image. It is this increased contrast which makes XPCi such an exciting development, with Edge Illumination making this increase in contrast easily accessible. Other results demonstrating the range of applications of the Edge Illumination method will be shown.

II. TECHNICAL INFORMATION An Edge Illumination system uses two gratings, with one placed before (sample mask) and the other after (detector mask) the sample. The first mask splits the xray beam into independent mini-beams. If these minibeams undergo refraction as they pass through a sample they will be deviated either on to or off of the second mask apertures. In this way phase effects generate contrast in an Edge Illumination system. Figure 1 illustrates this principle.

Figure 3. Image on the left is an x-ray absorption image, and the image on the right is an x-ray phase based image. Both were acquired with a UCL prototype system under the same conditions.

IV. CONCLUSION An Edge Illumination XPCi method has the potential to transform all forms of x-ray imaging. As Edge Illumination can be implemented using current technology, and is easily scaled to large fields of view, translation of the method to clinical and other environments is already feasible. This would allow for the increased contrast of XPCi to be widely available away from synchrotrons. Figure 1. Diagram showing the Edge Illumination principle.

Two prototype systems have been built at UCL. One of these has been used to demonstrate the methods effectiveness at high energy; which would give the benefit of lower dose in radiography [7]. It has also been used to demonstrate potential security applications. The second system has been used to develop 3D methods, © 2013 University of Surrey

REFERENCES [1] [2] [3] [4] [5] [6] [7]

A. Snigirev et al Rev. Sci. Instrum. 66 (1995) 5486 A. Momose et al Nat. Med. 2 (1996) 473 S. W. Wilkins et al Nature 384 (1995) 335 F. Pfeiffer et al Nat. Phys. 2 (2006) 258 A. Olivo et al Med. Phys. 28 (2001) 1610 A. Olivo and R. Speller Appl. Phys. Lett. 91 (2007) 174106 K. Ignatyev et al J Appl Phys. 110 (2011) 014906 3


Dual Image K-Edge Subtraction Using A Conventional X-ray Source 1

N. Henthorn1, S. Pani1 and S.C. Saifuddin1

Department of Physics, University of Surrey, Guildford, UK [email protected], [email protected], [email protected] Abstract – This study proposes, and demonstrates, the use of K-edge subtraction (KES) with a polychromatic X-ray source. A dual-energy algorithm is compared to traditional logarithmic subtraction, with the dual-energy algorithm giving a contrast of 0.45 ± 0.01 and the traditional logarithmic subtraction giving a contrast of 0.38 ± 0.04. Contrastto-noise ratio (CNR) was investigated at varying doses; with a CNR of 24.1 ± 0.9 measured at the lowest dose of 256μGy.

Figure 1. Two pseudo monochromatic X-ray spectra used, with average energies 26.2keV and 43.5keV.

I. INTRODUCTION

III. RESULTS AND DISCUSSION

KES is an X-ray imaging method for removing image backgrounds and leaving the distribution of a contrast medium, making it useful for imaging the blood system. Locations of tumors can be identified due to their preferential blood supply. So KES can be used for assessment of tumors. KES requires two image acquisitions below and above the K-edge of a given contrast agent respectively. This is usually done with monochromatic X-rays from a synchrotron source. Use of a synchrotron source has obvious drawbacks for most clinical settings, due to size, cost and availability. This study proposes the use of KES with a conventional polychromatic X-ray source.

Figure 2 shows the images obtained through traditional logarithmic subtraction and through the method suggested by Lehmann et al. Images following the Lehmann method show much better removal of background objects. The pair of images were logarithmically subtracted to produce an image heavily made up from the contrast agent, but with visible background detail. The traditional subtraction algorithm assumes that the mass attenuation coefficient of the background object is invariant across the high and low energy spectra. This is a fair assumption when using monochromatic X-rays but breaks down with a polychromatic source due to the broad nature of the spectra. This gives rise to a nonnegligible change in the mass attenuation coefficient of the background material leading to poor removal. Dose investigations were carried out; these showed that all tubes were visible even to the lowest measured entrance dose of 256μGy, where typical entrance dose in mammography is several mGy [3].

II. METHODS A custom made non-uniform PMMA phantom, simulating breast structures, was imaged. The phantom had tubes of different diameters attached to it, filled with an iodine based contrast agent. A „Comet MXR225‟ W-anode X-ray source was used, operating at 5mA. IPEM report 78 software [1] was used to simulate two X-ray spectra with average energies above and below the iodine K-edge of 33keV (figure 1) through modification of kVp and filtration. The optimum pair of spectra was chosen as the one giving maximum CNR on images; by having average energies as close as possible to the K-edge, thus maximising contrast. Images of the phantom were taken with energies above and below the iodine K-edge. They were combined by a simple logarithmic subtraction algorithm as well as by a more generic dual-energy algorithm proposed by Lehmann et al [2]. The latter method uses the mass attenuation coefficients of the iodine and background materials to form a coordinate system where each point represents a linear combination of the two materials. The method produces two images from the original raw images. One image shows the distribution of the contrast agent and one image contains all background materials, which gives useful anatomical information.


a)

b)

Figure 2. a) Traditional logarithmic subtraction. b) Lehmann dualenergy method.

IV. CONCLUSION The study shows the success of the Lehmann dualenergy method and demonstrated the practicality of KES with a polychromatic source. It was shown that KES gives a higher contrast than a single planar X-ray image. A more complex phantom, closely resembling the human blood system, is required to fully test the subtraction algorithm. REFERENCES

[1] A.J. Reilly, D. Sutton, “Report 78 Spectrum Processor”, IPEM, 1997 [2] L.A. Lehmann, A. Macovski, W.R. Brody, N.J. Pelc, S.J. Rieder, A.L. Hall, “Generalized Image Combinations in Dual kVp Digital Radiography”, Med. Phys., vol 8, 1981, pp. 659-667 [3] D.R. Dance, C.L. Skinner, G. Alm Carlsson, “Breast Dosimetry”, Applied Radiation and Isotopes, vol. 50, 1999, pp. 185-203

4


Automated Laser Registration and Quantitative Assessment of Articular Cartilage for Lower Limb Arthroplasty S. V. Joshi1, P. Rowe1, G. Pierce2, K. E. Ahmed3, C. MacLeod2 1

2

Department of Biomedical Engineering, University of Strathclyde, Glasgow, UK Centre for Ultrasonic Engineering (CUE), Department of Electronic & Electrical Engineering, University of Strathclyde, Glasgow, UK 3 University of Glasgow, Dental School, Glasgow, UK [email protected], [email protected]

Abstract - Currently one of the most important aspects of CAOS (Computer Assisted Orthopaedic Surgeries), ‘image registration’ is associated with various problems being invasive, time consuming and therefore costly. Thus the rationale for this study was to develop a novel automated 3D Laser image registration technique for CAOS. I. INTRODUCTION Image registration is a process of developing a spatial relationship between pre-operative data, such as Computerised Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans and the physical patient in the operation theatre. [1] Current image registration for most CAOS applications is achieved by probing along the articulating surface of the femur and tibial plateau and using these digitised points a rigid body is formed which is then fitted to the pre-operative scan data using a best fit type minimisation. [2] However this approach is invasive, often takes 10-15 minutes thus it is costly. The goal of this study was to develop a novel automated, contactless, and cost-effective registration method by acquiring 3D Laser scans of the patient’s knee intra-operatively. II. METHODS A number of techniques based on triangulation principle using hand held and automated 3D Laser scanners for acquiring geometry of non-reflective objects have been developed which was used to scan the surface geometry of a porcine femur with four screws drilled in it. [3] The distances between the screws and the geometry of the bone were measured using digital vernier callipers as well as measurements acquired from the 3D scans. Additionally, a pre-calibrated dental model was scanned using a 650 nm FARO™ Laser arm and our 3D Laser scanner and scans were registered using the global surface registration approach in Geomagic Qualify package. Laser module of class II, 670 nm wavelength with the power output NO (p 0.05) for the spine and 0.0225g/cm2 (p < 0.05) for the total femur where n=44 patients.


• 3 DEXA scans was -0.0349g/cm2 (p < 0.05) for the spine and 0.00912g/cm2 (p > 0.05) for the total femur where n=17 patients. • 4 DEXA scans was -0.0229g/cm2 (p > 0.05) for the spine and 0.0162g/cm2 (p > 0.05) for the total femur where n=9 patients. • 5 DEXA scans was 0.0097g/cm2 (p > 0.05) for the spine and -0.0133g/cm2 (p > 0.05) for the total femur where n=3 patients. No. of DEXA scans patients had

No. of years between initial & final scan 2 6 7 8

2 (n = 44) 3 (n = 17) 4 (n = 9) 5 (n = 3)

Difference in BMD (g/cm2) at spine 0.0098 -0.0349 -0.0229 0.0097

Pvalue

>0.05 0.05 >0.05

Difference in BMD (g/cm2) at femur 0.0225 0.00912 0.0162 -0.0133

Pvalue

0.05 >0.05 >0.05

Table 1. Mean difference between initial and final BMD. Change in BMD, T and Z scores at the Spine and Femur 2 Spine BMD

4

6

Spine T -2.50

0.900 0.885

-1.0

-2.75

0.870

Spine Z -0.8

-1.2

0.855 -3.00

0.840

-1.4 Femur BMD

0.77

-1.90

Femur T

-1.95

0.76

Femur Z

-0.7 -0.8

-2.00 0.75

-0.9

-2.05 -2.10

0.74 2

4

6

-1.0

DEXA Scan

2

4

6

Figure 1. Individual change in BMD, T and Z scores over 6 DEXA scans for one of the patients

IV. CONCLUSIONS It has been statistically proven using data from the 73 patients who had 2, 3, 4 or 5 scans that there is no significant difference between the initial and final BMD. The medications prescribed were only able to stabilise the BMD preventing further bone loss. This is further supported by individual patient data where in post baseline DEXA scans, the BMD at both sites dropped significantly before increasing to slightly above baseline BMD after 9 years. Therefore an alternative approach must be considered where this disease could be prevented earlier on in life especially for postmenopausal women. REFERENCES [1] Tucker, K., (2009) Osteoporosis prevention and nutrition. Current Osteoporosis Reports, Vol. 7 (4), page 111-117. [2] Ema.europa (2012) European Medicines Agency - Calcitonin. [online] Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicin es/human/referrals/Calcitonin/human_referral_000319.jsp&mi d=WC0b01ac0580024e99 [Accessed: 19 April 2013].

36


The Effect of Synthetic Cannabinoid HU308 on Fibronectin and Collagen Type I Expressions in MG-63 Osteoblast Cells 1

M. Genedy1, 2, M. Youseffi1, A. Abdeldayem1,2 and M.C.T. Denyer2

School of engineering design & technology-Medical Engineering, University of Bradford, Bradford, UK 2 Institute of pharmaceutical innovation, school of life science, University of Bradford, Bradford, UK [email protected], [email protected], [email protected]

Abstract - Endocannabinoids (ligands) and their receptors have been identified in the skeleton system. It has also been indicated that their functions in bone are physiologically regulated by CB2 receptors [1]. The current paper investigates the effect of CB2 selective agonist HU308 with different concentrations on collagen type I and fibronectin expressions in MG63 osteoblast cells. Immunofluorescence images indicated that both Collagen type I and fibronectin were induced using higher concentrations of HU308 with decreased cell proliferation compared to lower concentrations. This finding further justified the role of high concentrations of CB2 agonists in the inhibition of cell migration and tumour invasion. I. INTRODUCTION MG-63 osteoblast cell line used in the present study was treated with two different concentrations of CB2 selective receptor agonist HU308 (500nM and 2µM) and immunofluorescence images of collagen type I and fibronectin expression were obtained. As known, collagen type I was found to be directly associated with cell proliferation [2]. Also, presence or absence of fibronectin deposited around a given cell can determine whether that cell participates in migratory movements during development [3]. II. MATERIALS AND METHODS MG-63 osteoblasts cells were incubated for 30 hours in the presence of HU308 with two concentrations. immunofluorescence was then carried out with addition of 4% formaldehyde for 7 minutes followed by 0.1% triton-X 100 for 5 minutes, then separated by washes with HBSS. Cells were incubated at room temperature with collagen type I and fibronectin primary anti-bodies diluted in 1% BSA/HBSS for 1 hour, followed by a secondary antibody Ab- Alexor fluor 488nM. Before imaging, cell nucleuses were stained with Dapi blue staining in order to identify live cells. III. RESULTS Results indicated that MG-63 osteoblast cells treated with CB2-selective agonist HU308 with concentration of 2µM induced collagen type I and fibronectin expression significantly compared with lower concentrations of HU308 and control groups with no treatments. It was also visible from the dapi staining of live nucleus in higher concentration groups that cell stained for either collagen type I or fibronectin represented higher ratio of green fluorescence (protein staining) compared with


lower concentrations of 500nM and control groups, Figure 1. In addition, an underlying network of fibronectin expressions in MG-63 osteoblast cells was visible in treatments of 2µM HU308. A

C

B

D

C

E

Figure 1. Immunofluorescence Images (A, B, C) Collagen type I (control, 500nM and 2µM HU308), (D, E, F) fibronectin (control, 500nM and 2µM HU308), respectively.

III. DISCUSSION AND CONCLUSIONS It was indicated in the current finding that higher concentrations have significantly induced both collagen type I and fibronectin expression. It is suggested that suppression of collagen synthesis resulted in down regulation of genes associated with osteoblast mineralization and that the increase in collagen type I is associated with decrease in cell proliferation and increased osteoblast mineralization. This was further confirmed in our results published elsewhere [1] which indicated a higher proliferation factor amongst lower HU308 concentrations. On the other hand expression of fibronectin has also been associated with cell migration in vitro. It has been established by various studies that the presence or absence of fibronectin deposited around a given cell can determine whether that cell participates in migratory movements during development, and it was indicated that the phenotype of the migrating cell appears to be that of lacking cell surface fibronectin in vitro [2]. Therefore, if cell migration is restricted, tumour invasion in carcinogenic cells is inhibited further establishing the role of synthetic cannabinoids in cancer research studies. REFERENCES

[1]M. GENEDY, M. YOUSEFFI and M.C.T. DENYER. 2012. 22nd Annual symposium of the international cannabinoid society. [2] OWEN, T. A., ARONOW, M., S. 1990. J Cell Physiol, 143, 42030 [3] RUOSLAHTI, E. 1984. Cancer Metastasis Rev, 3, 43-51

37


The Effect of TGF-β3, HCl, HCl/BSA and pH on Wound Healing of Cultured Osteoblast Monolayers M. Genedy1, 2, M. Ahmed1, F. Sefat1,2, M.C.T. Denyer2 and M. Youseffi1 1

2

School of engineering, design & technology-Medical engineering department Institute of pharmaceutical innovation-school of life science, University of Bradford, Bradford, UK [email protected], [email protected]

Abstract - Using confluent monolayers of human osteoblasts an in vitro study was carried out in order to investigate the wound healing properties with TGF-β3, HCl and HCl/BSA additions over a period of 30 hours with imaging at every five hours. Control flasks allowed comparison between the rates of wound healing along with pH measurements over a period of 24 hours with each measurement being recorded every two hours. Results showed that there was little or no correlation between pH in the range 6.4-7.4 and wound healing rates. I. INTRODUCTION There are various stimulants for cultured osteoblasts with in vivo and in vitro applications. TGF-β isoforms modulate osteoblast differentiation and formation of bone as they activate smad-dependant pathways which are responsible for skeleton formation. TGF-β3 has also been shown to reduce scarring and promote better collagen organization in vivo. During culture, factors such as pH have to be regulated to keep the cells alive and active. As the body’s pH is between 7.0 and 7.5 cells work best around this pH, therefore, it’s important to investigate and compare the wound closure response of cultured osteoblast monolayers to TGF-β3, HCl and BSA/HCl additions in correlation with other factors such as pH. II. MATERIALS AND METHODS EXPERIMENT 1 – WOUND HEALING MG63 bone cells were cultured in standard 25cm2 culture flasks with 1:5 ratio cell suspension (50,000 cells/ml) in DMEM, incubated at 37°C and were split upon reaching confluency, usually every 3-4 days. Once cells became confluent, a wound was inflicted using a 1mm disposable sterilised pipette with average scratch width of 300μm10-30μm SD, 1.7-5μm SEM. After wounding cultures were then treated with 50ng/ml TGF3. The same method was applied for culturing the cells with HCl and BSA/HCl as solvent (HCl) and carrier (BSA) with working concentrations of 50ng/ml. The wounds were imaged every 5 hours for a period of 30 hours. Image J software was used in order to measure the distance between the wound edges. Six vertical lines at semi-random horizontal distances were drawn and the distances between the intersections of the lines with the wound edges were measured. EXPERIMENT 2 – pH Cells were cultured in eight, six well petri dishes and left to become fully confluent. Once confluent a wound was created using a 1mm disposable sterilised pipette. The pH of each solution was measured every 2 hours for a period of 24 hours. © 2013 University of Surrey

III. RESULTS AND DISCUSSION Our results suggest that wound healing occurred very slowly in control culture flasks and 61% of wound remained open after 30 hours (see Figure 1) whereas TGF3 addition caused model wounds to heal fully after ~25 hours followed by HCl and BSA/HCl culture flasks which showed very similar healing results with high percentage of wound closure and only 10% of the wound remained open after 25 hours (see Figure 1). pH results are given in Figure 2 and it can be seen that pH increased with time in all solutions with TGF-β3 being the most alkaline having an average pH of 7.42 and HCl being the most acidic with average pH of 6.47. Control had average pH of 7.27 and HCl/BSA resulted in an acidic pH of 6.49. Judging by the results the acidic wounds (HCl and HCl/BSA culture flasks) healed as fast as the alkaline wound with addition of TGF-β3 suggesting little correlation between pH in the range 6.47.4 and wound healing rate. However, it is believed [1] that the acidic environment causes osteoclastic reabsorption allowing osteoblasts to form new bone at a faster pace. Acidic environments are also known to increase the amount of Cathepsin B which is an inflammatory and angiogenic marker indicating wound healing at a faster rate [1]. HCl is a known antimicrobial agent and it supresses bacteria in the wound area making the wound more readily available to heal. IV. CONCLUSIONS

Graphs of % wound closure Figure 1 (left) and pH measurements Figure 2 (right), for different treatments.

HCl, HCl/BSA and TGF-β3 treatments showed increase in the rate of healing compared to the control with very slow healing rate. pH values in the range 6.4-7.4 showed little or no correlation with wound healing rates. REFERENCES

[1] HAN, S.H., CHAE, S.W., CHOI, J.Y., KIM, E.C., CHAE, H.J., AND KIM, H.R. 2009.

38


Fabrication of a Microfluidics Device for Studying Neural Cell Behaviour at Single Cell Level using Proton Beam Writing 1

S. Al-Shehri1, G. W.Grime1 , V. Palitsin1, R.P.Webb1, M. P. Hughes2 Ion Beam Centre, Advanced Technology Institute, 2 Centre for Biomedical Engineering, University of Surrey, Guildford, Surrey, UK [email protected]

Abstract: The proton beam writing (PBW) technique has extra ability over other lithography techniques in the fabrication of three-dimensional structures with a high aspect ratio, straight and smooth sidewalls. These features potentially facilitate the fabrication rapid prototyping of microfluidic systems. This paper reports the use of multiple energy exposures (2.50.75 MeV) in order to fabricate buried channels in SU-8 resist (55 µm thickness), as part of a project to develop functional microfluidic networks. I.

INTRODUCTION

This paper highlights the main advantages of using PBW over UV lithography (UVL) as a microfabrication technique, Figure 1. PBW utilises a highly focused beam of high-energy (MeV) protons to create micro/nanostructures on a wide range of materials such as polymers [1].

Figure 1: Schematic diagram shows the comparison between PBW and other lithography techniques into resist material [1].

II.

MATERIALS AND METHODS

A polymer (so called SU-8) microfluidics device has been fabricated for neuron cell applications using PBW at Ion Beam Centre, Surrey University. The neuron cell arrays (NCA) device is composed of buried channels networks Fig.2(a) and the fabrication concept is illustrated in Fig.2(b).

(a)

(b)

Figure 3: Optical image of Neuron cell arrays structure fabricated by PBW (a) and UVL (b). For comparison purposes, image (b) taken from [2].

It is obvious that the channels produced by PBW Fig.3(a) have straight walls, contrasting with that pattered by UVL Fig.3(b). Another issue associated with using UVL is that the surface roughness is relatively high comparing to that machining by proton beam. These geometrical imperfections have a profound impact on the NCA function. For example, the cell can be trapped in the narrow channels which lead to uncontrolled consequential effects on the functionality of this device.

(a)

(b)

Figure 4: SEM images of the channels fabricated by PBW (a) UVlithography (b) [2].

Furthermore, manufacturing enclosed channel Fig.2 (a) is considered one of the most attractive attribute of PBW techniques in terms of easy fabrication in one layer. As a result, this helps to overcome the media evaporation issues. Additionally, buried channels assist in guiding the cells in the right track whereas it is difficult to be controlled in case of micro-trenches. IV.

(a)

(b)

Figure 2: (a) strategy of fabrication buried channel and (b) is the actual enclosed channel (8µm width) in SU-8.

III.

RESULTS AND DISCUSSION

Neuron cell device Fig.3(a) is dedicated to study the cells behaviour at a single level.


CONCLUSION

A prototype of a microfluidics device (NCA) with straight and smooth sidewalls has been successfully produced using PBW technique. It was also shown that patterning a buried channel as a three dimensional structure can be done easily and effectively in one layer of the material comparing to UVL. REFERENCES

[1] F. Watt, et al., "Proton beam writing," Materials Today, vol. 10, pp. 20-29, Jun 2007. [2] F. T. Jaber, et al., "Action potential recording from dielectrophoretically positioned neurons inside micro-wells of a planar microelectrode array," Journal of Neuroscience Methods, vol. 182, pp. 225-235, Sep 15 2009.

39


Evaluation of Cell Detachment Methods through Determination of Biophysical Properties of Cell Membrane and Cytoplasm by Using Dielectrophoresis S. Mahabadi, F. H. Labeed, H. M. Coley, M. P. Hughes The Centre for Biomedical Engineering, University of Surrey, Guildford, UK [email protected], [email protected] and [email protected] Abstract – Adherent cells grown in the lab need to be detached from the surfaces on which they are grown, but the damage caused to the cells is the subject of debate. In this study, the effects of the seven different cell detachment methods have been examined. The investigation has been carried out through determination of the cell dielectric properties including conductivity and permittivity of membrane and cytoplasm by employing dielectrophoresis (DEP) technique. Scraping appeared to be the most harmful detachment method, as it causes a substantial reduction in the membrane conductivity of the cells when compared to other methods. I. INTRODUCTION Dielectrophoresis (DEP) has become more significant in recent years due its potential for the investigation of the dielectric properties of cells, including the conductivity and permittivity of the membrane and cytoplasm by employing non-uniform AC electric fields. It has been shown to be effective, for example, for discrimination between healthy and affected cells through their alteration of their dielectric properties [1,2]. A recent topic of interest regards the effect of cell detachment on the well-being of adherent cell lines [3]. These cells grow in attachment to a plastic culture flask, and must be detached from this flask in order for experimentation to occur; however, it is not wellestablished that the detachment affects the properties of the cells. In this study, seven different cell detachments methods have been evaluated through determination of the dielectric properties of adherent cell lines by employing DEP. II. METHODS Six different cell detachment reagents were examined (Trypsin-EDTA 0.25x, Trypsin-EDTA 1x, Dissociation Fluid, Dissociation Buffer and Accutase), as well as a reagent-free scraping method. HN5 cells were cultured in RPMI medium supplemented with 1640 with 10% heat-inactivated foetal calf serum (FCS), 2mM L-glutamine in a standard cell culture incubator at 5% CO2 and 37 °C. Cells were detached by six different fluids in different times of incubation. After detaching the adherent cells, they were examined through placing them in 3-D electrode microwell kit. The DEP experiments have carried out by 3-D electrode microwell system developed in University of Surrey [4].


III. RESULTS DEP was used to extract the values of conductivity and permittivity of both membrane and cytoplasm. It was found that the values of cytoplasmic permittivity for all detachment methods were within 5% of each other. For the other parameters, scraper cells were found to be substantially lower in membrane conductivity (by 50%), cytoplasmic conductivity (by up to 68%) and membrane permittivity (by over 83%). The other techniques were all within 5%, 3% of each other for these three parameters respectively. IV. DISCUSSION As mentioned above, all the methods except scraping have relatively the same influence on the conductivity and permittivity of the membrane which resulted to reach relative dielectric properties values. But, the time of incubation and the amount of the each fluids used for cell detachments were not the same, as these two factors could have significant impacts on the cells properties especially on the cell membrane. Trypsin_ EDTA seemed to be the best choice for cell detachment among the other fluids due to its quick performance on the cell detachment of adherent cells. V. CONCLUSION The results indicated a substantial reduction in the values of the conductivity of the both cells membrane for the cells detached by scrapers comparing to the cells detached through using the dissociation reagents. Unlike the scraping method, no significant change was observed in conductivity and permittivity of the membrane for the cells detached through detachment fluids. REFERENCES [1] F. H. Labeed, H. M. Coley and M. P. Hughes. Differences in the biophysical properties of membrane and cytoplasm of apoptotic cells revealed using dielectrophoresis. Biochimica Et Biophysica Acta (BBA) - General Subjects 1760(6), pp. 922-929. 2006. [2] E. A. Henslee, M. B. Sano, A. D. Rojas, E. M. Schmelz and R. V. Davalos. Selective concentration of human cancer cells using contactless dielectrophoresis. Electrophoresis 32(18), pp. 25232529. 2011. [3] Van Veldhoven, Paul P., and Robert M. Bell. "Effect of harvesting methods, growth conditions and growth phase on diacylglycerol levels in cultured human adherent cells." Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism 959.2 (1988): 185-196. [4] Hughes, Michael P., and Kai F. Hoettges, eds. Microengineering in biotechnology. Humana Press, 2010.

40


The Potential Effects of Low-doses of Ionising Radiation and Malignancy 1

A.A.A. Almahwasi1, J.C.G. Jeynes1, K.J. Kirkby1 and M.J. Merchant1

Ion Beam Centre, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, UK [email protected], [email protected], [email protected], [email protected] Abstract - Radiation-induced non-targeted effects, such as genomic instability have been proposed as a very early stage in radiation carcinogenesis. Many studies have identified genomic instability in a variety of cell-lines immediately post-irradiation. The novelty of this project is to investigate the potential induction of genomic instability in the progeny of irradiated normal human fibroblasts using low doses of radiations in-vitro. The data obtained show that the number of γH2A.X foci and giant cells formation is increased compared to the unirradiated control, precisely at 0.2 Gray. This indicates a probability of radiation-induced genomic instability, which relates to malignancy (cancer) induction. I. INTRODUCTION Proton therapy is a promising treatment modality for cancer that may have distinct advantages over conventional radiotherapy. This relates to its ability to deliver a very high dose of linear energy transfer (LET) radiation to deeply seated or critically located tumours and thus minimizing radiation dose to the surrounding normal tissues [1]. Many proton therapy facilities are currently operating or under construction world-wide. Moreover, treatment of cancer with ion beam is considered as a rapidly developing field of research [2]. However, concerns exist because of the rare but serious potential effects of the minimal low doses of radiation, which might be received by normal tissues adjacent a targeted tumor volume during proton therapy treatment. This research is designed to investigate the effect of lowdoses of different qualities of ionizing radiation on the normal human tissues adjacent the treated cancerous region [3]. II. MATERIALS AND METHODS A. Cell culture The normal human skin fibroblasts (AG01522D) were maintained according to the recommended protocols and prepared for irradiation in VNBL (Vertical Nanobeam Laboratory) at University of Surrey. B. Cell Irradiations X-ray irradiations performed at RSCH (Royal Surrey County Hospital) using a Gulmay kilovoltage therapeutic unit. The unit was operated at 250 kVp, 12 mA and a dose rate of 0.6 Gray/min. Irradiations delivered to the targeted cells as a single dose of 0.2, 0.4, 0.6, 1, 2, 3, 4 and 5 Gy. After irradiations, all treated cells were incubated and allowed to proliferate (2-3 weeks) until the time at which they were fixed and stained for analysis. Then, clonogenic survival, γH2A.X staining and giant cell assays were used to identify and evaluate the effect of radiation in the progeny of irradiated cells. © 2013 University of Surrey

C. Data Analysis The images of γH2A.X foci and giant cells formations were captured using time-lapse fluorescence microscope. The surviving curve was constructed by OriginLab 8.6 software using Linear Quadratic (LQ) and Induced Repair (IndRep) models. III. RESULTS AND DISCUSSION Cells irradiated with low-doses of X-ray (0.2 Gy) show high levels of giant cells and γH2A.X foci formations in their progeny compared to controls and cells irradiated with higher doses of 2-5 Gy (data not shown). This co-indicates with the hyper-radiosensitivity (HRS) region observed at 0.2 Gy in the survival curve of AG01522D cells, Figure 1. These results suggest that radiation-induced genomic instability and hyperradiosensitivity at low doses.

Figure 1. Shows the survival curve of AG01522D cells.

IV. CONCLUSION The X-ray results support the emerging link between the effect of low-doses of radiation and the potential induction of genomic instability and hyperradiosensitivity (HRS) in the progeny of irradiated cells. While they still remain to be confirmed, these effects could occur when using low-doses of heavy charge particles, such as protons and they may have a significant contribution to cancer induction or progression. REFERENCES [1] D. Schulz-Ertner and H. Tsujii, “Particle radiation therapy using proton and heavier ion beam”, Journal of Clinical Oncology, vol. 25, 2007, pp. 953-964. [2] M. B. Sowa, L. E. Kathmann, B. A. Holben, B. D. Thrall and G. A. Kimmel, “Low-LET microbeam investigation of the track-end dependence of electron-induced damage in normal human diploid fibroblasts”, Radiation Research, vol. 164, 2005, pp. 677-679. [3] M. Tubiana and A. Aurengo, “Dose-effect relationship and estimation of the carcinogenic effects of low doses of ionizing radiation”, International Journal of Radiation Oncology Biology Physics, vol.2, 2005, pp. 134-151.

41


Dosimetric Properties of Varian TrueBeam with and without Flattening Filter: A Monte Carlo Simulation 1

M. A. Najem1, A. Alrushoud1, S. Jafari1, Z. Podolyak1, N. M. Spyrou1

Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford, UK [email protected]

The modern Varian medical linacs, TrueBeam, can operate with and without a flattening filter (FF). In this study we aimed to compare the dosimetric properties of TrueBeam when operated in either mode by evaluating the percentage depth dose (PDD) and beam profile (BP) through Monte Carlo (MC) simulations to achieve these objectives. Results showed an increased beam dose rate and entrance dose with the flattening filter free (FFF) beam, whilst the out-of-field dose was decreased. It is concluded that the Varian TrueBeam system with FFF offers several advantages for cancer treatment using intensity modulated radiotherapy (IMRT). I.

INTRODUCTION

Varian has introduced a new class of medical linear accelerators called TrueBeam, which can operate with and without FF [1]. Several researchers have investigated and measured the dosimetric properties of TrueBeam linacs [2]. However, only a few number of MC simulations were performed to study this due to Varian confidentiality issues on the geometrical configuration information of the TrueBeam linac head which has been recently released [3]. The aim of the present work is to compare the dosimetric quantities, such as beam dose rate, entrance dose and out-of-field dose for both TrueBeam modes. II.

III.

RESULTS AND DISCUSSION

The calculated PDDs and BPs were found to be in good agreement with the measurement results (Figure 1). Differences of < 2% were obtained between the calculated and measured results at all points. PDDs of 6 MV and 10 MV beams without FF have relatively faster fall off after Dmax compared with PDDs with FF which is due to X-ray spectra softness of unflattened beams. Table 1 shows the calculated variations between beam dose rate, entrance dose and out-of-field dose with and without FF. The increased beam dose rate reduces beamon time, suitable for treatments requiring organ motion control. The decrease in out-of-field dose for the unflattened beams was due to the reduction in head scatter. Entrance dose increased when the FF was removed and which might add extra dose to the patient surface. Table 1. The dosimetric quantities calculated with and without FF. 6 MV 10 MV Increase in the dose rate 220% 320% Increase in the entrance dose 7.9% 15.3% Decrease in the out-of-field dose 28.4% 44.6%

MATERIALS AND METHODS

MC simulations were performed using phase space files obtained from Varian as radiation sources using the BEAMnrc code in order to calculate the dosimetric quantities with and without FF for the 6 MV and 10 MV photon beams [4]. The calculations were performed for 10×10 cm2 field size at the isocentre. MC results scored as new phase space files and used for the irradiation of a 30×30×30 cm3 water phantom created using DOSXYZnrc code [4]. The water phantom was divided into 5×5×2 mm3 voxels. The number of histories in each simulation was set to produce an uncertainty < 2% at all points. Five dosimetric properties were calculated for each photon beam energy with and without FF. These included: radiation beam dose rate, PDD and the entrance dose at the central axis. BP and the out-of-field dose across the central axis at the depth of maximum dose (Dmax) were also calculated. The calculated results were then compared with measured data obtained from University College London Hospital.


Figure 1. The calculated and measured PDD and BP data.

IV.

CONCLUSION

Dosimetric properties of the TrueBeam linac with and without FF were calculated for the 6 MV and 10 MV photon beams. Beam dose rate for unflattened beams was increased and the out-of-field dose was reduced. However, the surface dose was increased. The study concludes that using the unflattened beam mode will be useful for IMRT treatment techniques. REFERENCES [1]

Chang, Z., et al., Commissioning and dosimetric characteristics of TrueBeam system: Composite data of three TrueBeam machines. Medical Physics, 2012. 39: p. 6981. Glide-Hurst, C., et al., Commissioning of the Varian TrueBeam linear accelerator: A multi-institutional study. Medical Physics, 2013. 40: p. 031719. [3] Constantin, M., et al., Modeling the TrueBeam linac using a CAD to Geant4 geometry implementation: Dose and IAEA-compliant phase space calculations. Medical Physics, 2011. 38: p. 4018. [4] Treurniet, J. R., et al., BEAMnrc, DOSXYZnrc and BEAMDP GUI User’s Manual, NRCC Report, PIRS-0623(rev C), NRCC Ottawa 2010. [2]

42


Mammography with Synchrotron Radiation: Dosimetric Result C.Fedon1, E.Quai2, F.Arfelli1, D.Dreossi2, G.Tromba2, R.Longo1

1

Dipartimento di Fisica Università di Trieste & INFN Sezione di Trieste (Italy) 2 Sincrotrone Trieste SCpA, Basovizza, Trieste (Italy) [email protected], [email protected], [email protected], [email protected], [email protected] Abstract - At ELETTRA, in Trieste, there is the only synchrotron radiation (SR) facility for performing mammographic exams using monochromatic and tunable SR beam. In the present study the Mean Glandular Dose (MGD) and Entrance Skin Exposure (ESE) delivered to 70 patients, who underwent clinical exams with both Digital Mammography and Mammography with SR (MSR) are compared. The results show that both MGD and ESE in MSR are lower than in DM. Moreover the ESE in MSR exams is approximately independent from the breast thickness.

III. RESULTS SRM improves the image quality depicting with high resolution both the normal anatomic structure of the breast and the abnormal findings [3] in addition to a decrease of MGD by a mean factor of 50%, as shown in Fig. (1, left side), where red dots represent the dose delivered at DM, while blue triangles represent the dose of MSR.

I. INTRODUCTION Nowadays the main instrument available for reducing breast cancer mortality is mammography screening of asymptomatic women. Usually screenings are based on digital mammography (DM), but these examinations are reported to have a sensitivity of 60% − 90% and a specificity of 80% − 95% [1]. Thus, further exams are requested in case of equivocal diagnosis (as ultrasonography (US), MRI etc.). Synchrotron radiation can be easily monochromatized, is tunable in energy, has a laminar shape and have sufficient spatial coherence to allow the exploitation of phase effects [2]. In order to investigate questionable or suspicious breast abnormalities identified at combined DM and US exams, a phase contrast technique based on SR has been proposed and performed at the SYRMEP beamline of the Elettra Synchrotron (Trieste, Italy) [3]. II. MATERIAL A patient is recruited for MSR if she satisfied one of the criteria reported in [3], such as palpable mass, focal asymmetry, architectural distortion, equivocal or suspicious mass at DM, still not clarified at US. In a MSR exam, the patient lies prone on a movable support with the breast hanging in a pendant geometry. The SR beam is monochromatic, stationary, laminar and selectable in energy from 17 to 22 keV according to breast thickness and glandularity. The beam energy is set as low as possible with the constrain that the MGD must be comparable to or lower than that delivered at DM according to Dance [4] . In MSR exams, the MGD is calculated by using Boone Monte Carlo calculations [5] and by measuring the ESE with high precise ionization chamber calibrated according to Italian national standard.


Figure 1. MGD delivered at DM, red dots, and MGD at MSR blue triangles (left side); ESE measured at DM, red dots, and ESE at MSR, blue triangles (right side). The error bars are related to one standard deviation.

The analysis of Fig. (1, right side) shows that, at DM, the ESE increases at the increasing of breast thickness, as thicker breast requires a longer exposure time compared to a thinner breast. When SR is used, the ESE is kept constant tuning beam energy: the monochromatic beam has not the low energy component that contributs mainly to the ESE IV. CONCLUSION These analysis show that MSR delivers a lower MGD to the patients and also a smaller ESE than DM. New Monte Carlo simulation of MSR is under development using GEANT4 to be used for better exam optimization and for the extension to breast tomography. REFERENCES [1] International Agency for Research on Cancer (IARC). Screening techniques. In: Vainio H, Bianchini F, eds. Handbook of cancer prevention. Vol 7, Breast cancer screening. 2002; 30-31. [2] Fitzgerald R. Phase-sensitive x-ray imaging. Phys Today, 2000; 53(7), pp 23-26. [3] Castelli E. , et al. Mammography with Synchrotron Radiation: First Clinical Experience with Phase-Detection Technique. Radiology, 2011; Vol 259(3), pp. 684-694. [4] Dance D.R. Monte Carlo calculation of conversion factors for the estimation of mean glandular breast dose. Phys. Med. Biol, 1990; 35:1211-1219. [5] Boone J.M. Normalized glandular dose (DgN) coefficients for arbitrary x-ray spectra in mammography: Computer-fit values of Monte Carlo derived data. Med. Phys. 29 (5), May 2002; pp 869-87.

43


Graph Node Hub and Authority Analysis of Neural Systems using Resting-state fMRI 1

G. Vieira1, J. R. Sato2, P. Dean3, E. Amaro1, A. Sterr2, L. A. Baccala1

Inter-institutional Grad Program on Bioinformatics, Universidade de São Paulo, São Paulo, Brazil Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, São Paulo, Brazil 3 School of Psychology, University of Surrey, Guildford, UK [email protected], [email protected], [email protected], [email protected], [email protected], [email protected] 2

Abstract - This paper reports a novel method for connectivity analysis using weighted and directed graphs. Results show that Hub and Authority provide biologically relevant data from fMRI connectivity analysis of the resting state. I. INTRODUCTION The resting-state network (RSN) has a complex connectivity pattern with many nodes making up different sub-networks such as the Default Mode Network (DMN)[1]. Previous RSN studies have ignored connection direction and strength, and hence neglect the role of subcortical regions, such as the thalamus and brainstem. In this study, Partial Directed Coherence (PDC) was used to build weighted and directed graphs allowing consideration of two novel indexes for brain connectivity analysis, Hub and Authority. Hubs (outgoing information) represent high-level processing and Authorities (incoming information) represent low– level summation. II. METHODS fMRI data of 198 healthy volunteers from The 1000 Functional Connectome Project were analysed. Preprocessing used the FEAT v5.98 with standard parameters. Functional connectivity between two regions was inferred by summing the squares of the pairwise generalized PDC within the 0-0.1Hz frequency band[2]. Each subject had their connectivity matrix A computed in the standard space and analysed via the topological indices Hub h and Authority a . The reciprocal relationship between these indices, such that a good Hub sends information to nodes which are good Authorities and a good Authority receives information from a good Hub, is given by[3]: Τ h = Aa and a = A h , where h = [h1 , , hK ] , a = [a 1 , , a K ] and K is the number of nodes. This equation is equivalent to: Τ Τ h = AA h and a = A Aa , which means that h and a are the eigenvectors of the largest eigenvalues of A A T and A T A respectively. Each index was statistically analysed separately. The subject's index vector was assumed independent and index values at each node within subjects were included as repeated measures. After detecting nodes lacking homogeneity by the nonparametric Friedman test, a posthoc Mann-Whitney analysis was carried out to identify those nodes whose rank values were greater than the average expected value of r = ( K  1) / 2 .


III. RESULTS Post-hoc analysis revealed two topographically distinct subnetworks (p

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