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Research Day 2017 School of Biomedical Engineering
Scientific Program
1
May 4th, 2017
Dear Colleagues:
It is my pleasure to welcome you to the 15th Annual Research Day of the School of Biomedical Engineering at Dalhousie University!
This is the premier day of the year for our School, an exciting time for our students to present their research to the public and their peers, and a great opportunity for us all to share in their discoveries. I encourage each of you, and especially the students, to participate and engage with each other through helpful comments and questions. During the breaks, lunch and the reception there will be plenty of time to continue with spirited discussion.
Original science is what we do. Albert Einstein once said, “The important thing is not to stop questioning.” This works for both the presenter and the audience on this day.
This year I have the great pleasure to welcome our two Keynote Distinguished Speakers, Dr. Andrew Pelling, PhD, University of Ottawa, who will present “Disruptive Biomaterials Found in the Grocery Store”, and Cameron Piron, President of Synaptive Medical, Toronto, who will present "Opportunities for the Fusion of Medicine, Engineering and Business”.
Dr. Pelling is Canada Research Chair in Experimental Cell Mechanics at the University of Ottawa. He is widely published including in Science and Nature journals, serves on several editorial boards, and is a Ted Talk Fellow. His research uses leading edge techniques to drive to the very heart of basic biomechanical processes in living systems, from mitosis to apoptosis, nucleus deformation, and tissue regeneration. Notable also are his award-winning art-science exhibitions.
Cameron Piron was co-founder of Sentinelle Medical, which developed MRI-based breast imaging technologies and was later acquired by Hologic Inc in 2010, at which point annual revenues had achieved $20M. More recently, he cofounded Synaptive Medical in Toronto, a rapidly growing company which develops imaging platforms that enable advanced surgical planning, navigation and visualization, making information from images more useful to surgeons.
I want to sincerely thank all those who help make this day run smoothly. Thank you very much to John Frampton and Brendan Leung who worked closely together to develop today’s program. Thank you in advance to our judges of today’s presentations, and a very heartfelt thank you to our shining young students, who both moderate and present their work in the sessions detailed in the following pages. Without them there would be no celebration today. Finally, thank you to Sandra Pereira who always works tirelessly in support of our fine School. This day is a highlight for me, and I hope for all of you.
Welcome to all and please enjoy the day!
Geoffrey Maksym, Ph.D. Professor and Director
FACULTIES OF MEDICINE and ENGINEERING | School of Biomedical Engineering
5981 University Avenue | PO Box 15000 | Halifax NS B3H 4R2 Canada
902.494.3427 | FAX: 902.494.6621 | bme@dal.ca | dal.ca/bme
DAL.CA
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School of Biomedical Engineering
Research Day 2017
DISTINGUISHED
ACADEMIC LECTURE
Andrew Pelling, PhD Professor, Dept. of Physics University of Ottawa
Disruptive Biomaterials Found in the Grocery Store
3
Biography: Award winning Scientist, Professor, Entrepreneur, TED Fellow and TED speaker,
Andrew Pelling has built a career on unapologetic curiosity, creativity and serendipity. Andrew
is a Professor and Canada Research Chair at the University of Ottawa, where he founded and
directs a curiosity-driven research lab that brings together Artists, Scientists, Social Scientists
and Engineers. The lab uses low-cost, open source materials and methods to explore speculative
living technologies of the future. He has, for instance, created human body parts made from
plants and grown living skins on LEGOs – innovations with the potential to replace prohibitively
expensive commercial biomaterials. Andrew is also the co-founder and CTO of Spiderwort Inc, a
mission driven company developing open source platforms to enable the widespread and global
adoption of biological research in all environments and economic contexts. Most recently,
Andrew co-founded and directs pHacktory, a distributed street-level research lab that amplifies
community ideas through a potent mixture of craft, serendipity and curiosity. Andrew’s work has
been in the international media spotlight for many years, with recognition in outlets such as
Wired, The Atlantic, Discovery Channel, Motherboard, Scientific American, Popular Science,
BBC, Der Spiegel, Deutsche Welle and many others, as well as numerous highlights in the
Canadian media and Scientific media.
Abstract: In this talk, I will describe how my lab draws inspiration from science fiction to
develop living technologies of the future. Although we employ a highly unconventional
approach, our research has resulted in novel, low-cost, open source materials – such as LEGOs
and apples – that are now being applied in next generation medical innovations. The Pelling Lab
is an openly curious and exploratory space where scientists, engineers and artists work in close
quarters to create living, functional, biological objects that do not exist in nature. By physically
manipulating and re-purposing living systems, the Lab has discovered an astonishing ability of
cells to deliberately adapt and respond to highly artificial and unusual stimuli. I will also discuss
how we are now moving our fundamental research in tissue engineering and regenerative
medicine through the process of commercialization and clinical trials.
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School of Biomedical Engineering
Research Day 2017
DISTINGUISHED
IDUSTRY LECTURE
Cameron Piron President and Cofounder Synaptive Medical
Opportunities for the
Fusion of Medicine,
Engineering and Business
5
Biography: Cameron Piron is an industry-recognized leader and innovator in image-guided
surgery. Prior to co-founding Synaptive Medical, Cameron was president and co-founder of
Sentinelle Medical, a medical device company that developed and manufactured advanced MRI-
based breast imaging technologies. Sentinelle grew to over 200 employees and over $20 million
in revenues before being acquired by Hologic, Inc. in 2010. Cameron studied systems design
engineering at the University of Waterloo, followed by a graduate degree at the University of
Toronto in medical biophysics. His awards include the Ontario Premier’s Catalyst Award for
Best Young Innovator in 2008; the University of Waterloo’s Alumni Achievement medal in
2009 for leading Sentinelle Medical in researching and manufacturing leading-edge MRI
technologies that allow physicians to diagnose breast cancer and other medical conditions faster
and more accurately; being named to Canada’s Top 40 Under 40™ list in 2009, which was
established by Caldwell Partners and celebrates the achievements of young Canadians in the
private, public and non-profit sectors; and being the first Canadian ever to win R&D Magazine’s
Innovator of the Year award in 2008. In 2015, Cameron was named one of Fast Company’s Most
Creative People. He is a member of Synaptive’s Board of Directors and heads the company’s
executive committee.
Abstract: As a serial entrepreneur and the president of Synaptive Medical, a company dedicated
to developing technologies with an impact to change the standard of care in neurosurgery,
Cameron has solid knowledge and expertise in understanding rules of the road for medtech-
based entrepreneurship. In this lecture, Cameron shares insights on key strategic trends and
changing dynamics in the medical devices industry. The lecture gives an overview on the basic
skills and knowledge needed to build new medical ventures and develop novel medical device
ideas from idea, to clinic to global business.
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Previous Winners of the Community Builder
Prize in Biomedical Engineering
2008
Marianne Ariganello
2011
Adrian West
2013
J. Michael Lee
2015
Eleanor Seaman-Bolton
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Previous Winners of the Annual Teaching
Prize in Biomedical Engineering
2008
Geoff Maksym
2009
J. Michael Lee
2010
Jeremy Brown
2011
Paul Gratzer
2012
Rob Adamson
2013
Janie Astephen-Wilson
2015
Daniel Boyd
2016
Sarah Wells
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Previous Winners of the George W.
Holbrook Prize in Biomedical Engineering
2010
Richard Roda
2011
Graeme Harding
2013
Matthew Walker
2014
Pouya Amiri
2015
Lauren Kiri
2016
Brandon Scott
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Previous Winners of the Allan E. Marble
Prizes in Biomedical Engineering
2002
Sean Margueratt
2010
Derek Rutherford
2003
Anna Dion 2012
Del Leary
2005
Doctoral: Mark Glazebrook
Pre-doctoral: Carolyn Lall
2013
Andre Bezanson
2006
Doctoral: Scott Landry
Pre-doctoral: Scott MacLean
2014
Caitlin Pierlot
2007
Doctoral: Janie Astephen
Pre-doctoral: Andrew Moeller
2015
Arash Momeni Boroujeni
2008
Doctoral: Marianne Ariganello
Pre-doctoral: Vargha Talebi
2016
Dan MacDougal
2009
Doctoral: Jack Fairbank
Pre-doctoral: Jennifer Krausher
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School of Biomedical Engineering
Research Day 2017 Scientific Program
Thursday, May 4, 2017
Kenneth C. Rowe Management Building, Room 1020
Morning Reception
8:00 am to 8:30 am Student & Faculty Check-In
8:30 am to 8:40 am Welcome: Dr. Geoff Maksym, Director, School of Biomedical Engineering
8:40 am to 8:45 am Opening Remarks: Dr. Richard Florizone, President, Dalhousie University
Scientific Session 1 (Chairs: Kerry Costello and Hayden Nix)
8:45 am to 9:00 am “Localization of ventricular activation using patient-specific geometry”
Shije Zhou (PhD Student), J.L. Sapp, L.J. Leon and B.M. Horacek
9:00 am to 9:15 am
“Biopatterning of keratinocytes in aqueous two-phase systems as a
potential tool for skin tissue engineering” Rishima Agarwal (MASc
Student), K.R. Ko, P.F. Gratzer and J.P. Frampton
9:15 am to 9:30 am “A small ultrasound device for imaging and ablation of cerebral tissue”
Jeffrey Woodacre (PhD Student), T. Landry and J. Brown
9:30 am to 9:45 am “Borate glass-filled hydrophilic bone cements for the therapeutic release
of strontium” Kathleen MacDonald (PhD Student) and D. Boyd
Coffee Break (9:45 am – 10:00 am)
Scientific Session 2 (Chairs: Taylor Landry and Jeremy Norman)
10:00 am to 10:15 am
“Transmission electron microscopy of the nanoscale structure and
damage in tendon collagen” Jasmin Astle (PhD Student), J.M. Lee, B.D.
Quan and E.D. Sone
10:15 am to 10:30 am
“High-throughput 3D neural cell culture analysis facilitated by aqueous
two-phase systems” Kristin Robin Ko (MASc Student), R. Agarwal and J.P.
Frampton
10:30 am to 10:45 am “Performance characterization of a real-time 64-channel high-frequency
phased array beamformer” Chris Samson (PhD Student) and J. Brown
10:45 am to 11:00 am
“Longitudinal analysis of patient satisfaction after total knee arthroplasty”
Kathryn Young (PhD Student), E.K. Laende, J.M. Flemming, M.J. Dunbar
and J.L. Wilson
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Distinguished Academic Lecture
11:00 am to 12:00 pm
Dr. Andrew Pelling, Professor, Dept. of Physics, University of Ottawa
“DISRUPTIVE BIOMATERIALS FOUND IN THE GROCERY STORE”
Introduction: Dr. Brendan Leung
Catered Lunch (12:00 pm – 1:00 pm)
Distinguished Industry Lecture
1:00 pm to 2:00 pm
Cameron Piron, President and Cofounder of Synaptive Medical
“OPPORTUNITIES FOR THE FUSION OF MEDICINE, ENGINEERING AND
BUSINESS”
Introduction: Dr. Jeremy Brown
Scientific Session 3 (Chairs: Alyne Teixeira and Emile Feniyanos)
2:00 pm to 2:15 pm “Using reliability to provide patient-specific processing of neuroimaging
data” Sarah McLeod (MASc Student), S. Beyea and T. Bardouille
2:15 pm to 2:30 pm
“Trunk neuromuscular patterns interact with clinical measures of trunk
stability to influence the risk of future low back re-injuries” Adam Quirk
(PhD Student), R.D Trudel and C.L. Hubley-Kozey
2:30 pm to 2:45 pm
“Limited dynamic range artefact removal from Fourier domain optical
coherence tomography images” Joshua Farrell (PhD Student), D.
MacDougall and R. Adamson
2:45 pm to 3:00 pm
“Changes in gait kinetics precede structural joint changes in individuals
with knee osteoarthritis” Elysia Davis (PhD Student), S.C. Landry, D.
Ikeda, W.D. Stanish, C.L. Hubley-Kozey and J.L. Wilson
Coffee Break (3:00 pm – 3:15 pm)
Scientific Session 4 (Chairs: Tyler Herod and Jensen Doucet)
3:15 pm to 3:30 pm
“Fabrication and performance of a 128-element crossed-electrode array
for a novel 3D imaging approach” Kate Latham (PhD Student), C. Ceroici,
C. Samson, R.J. Zemp and J. Brown
3:30 pm to 3:45 pm
“Fracture mechanics of human sartorius tendons differ from that of
bovine tail tendons” Sara Sparavalo (MASc Student), S.P. Veres, S.M.
Wells and J.M. Lee
4:00 pm to 4:15 pm “Towards a miniature imaging probe for functional middle ear imaging”
Daniel MacDougall (PhD Student), M. Jahns, M. Bance and R. Adamson
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Awards and Closing
4:15 pm to 4:30 pm Presentation Judging (Atrium)
Dalhousie Biomedical Engineering Society Elections (Room 1009)
4:30 pm to 4:40 pm
George W. Holbrook, Allan Marble, & Teaching Prize in Biomedical
Engineering Award Presentations
Chairs: Dr. Geoff Maksym and Dr. Janie Wilson
4:40 pm to 4:50 pm Presentation Prizes for Research Day 2016
Chairs: Dr. Andrew Pelling and Cameron Piron
4:50 pm to 5:00 pm Closing Remarks: Dr. Geoff Maksym
Closing Reception (5:00 pm – 7:00 pm)
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School of Biomedical Engineering
Research Day 2017 Abstracts
SCIENTIFIC SESSION 1
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LOCALIZATION OF VENTRICULAR ACTIVATION USING PATIENT-
SPECIFIC GEOMETRY
Shije Zhou1, J.L. Sapp3, L.J. Leon2,1 and B.M. Horacek2,1
1School of Biomedical Engineering, 2Department of Electrical & Computer
Engineering and 3Department of Medicine, Dalhousie University
Introduction: One method for catheter ablation of scar-related ventricular tachycardia (VT)
includes induction and specific targeting of the culprit portions of the scar associated with the
exit area. This requires rapid interpretation of the 12-lead ECG and could be facilitated with a
computerized method to automatically locate the site of origin of ventricular activation. The aim
of this study was to examine a method for rapid identification of sites of early ventricular
activation using the 12-lead ECG, and to compare it to inverse solution calculation from body
surface potential mapping (BSPM).
Methods: 7 patients undergoing ablation of VT (4 epicardial; 3 endocardial) had 120-lead
BSPM done during the procedure. 1. Automated Localization: Pacing sites were identified in 3D
space using an electroanatomic mapping system and the time integral of the first 120 ms of the
QRS complex of leads I, II, V1-V6, was used in three 8-variable regression equations for
estimating x, y, and z coordinates of activation origin. 2. Inverse Mapping: The L1-norm
regularization that minimizes the sum of the absolute differences between the target value and
the estimated values method was used to reconstruct epicardial/endocardial potentials based on
patient-specific geometry obtained from computed tomography (CT). Localization error was
quantified over all pacing sites in millimeters by comparing the calculated location and the
known reference location.
Results and Discussion: By pacing ≥10 sites with known locations, patient-specific regression
coefficients can be calculated to localize ventricular activation from unknown sites with very
good accuracy for each subject; this accuracy further increases with each added pacing site. For
epicardial patients, the mean localization error in the proposed method is lower than that in the
inverse solution (11.2 vs. 28.4 mm, P=0.017). Endocardial pacing sites were also localized with
better accuracy compared to inverse solution (7.2 vs. 17.9 mm, P=0.002). The pooled site
localization accuracy of the proposed method was superior to that achieved by the inverse
solution mapping (P=0.001). Using standard 12-lead ECG recordings and incorporating pacing
information to generate patient-specific coefficients, spatial localization of the site of ventricular
activation can be achieved without significant loss of accuracy in comparison with 20-lead
BSPM technique.
Conclusions: Localization using the 12-lead ECG and pacing from at least 10 training sites can
achieve localization accuracy within 8.8 mm as compared to inverse solution, which achieved
accuracy of 23.9 mm. This compares very favourably with inverse-solution mapping and is
substantially less cumbersome. The proposed method of localizing the origin of ventricular
activation offers an easily implemented alternative to the inverse solution; its simplicity makes it
suitable for real-time applications during clinical catheter ablation.
15
BIOPATTERNING OF KERATINOCYTES IN AQUEOUS TWO-PHASE
SYSTEMS AS A POTENTIAL TOOL FOR SKIN TISSUE ENGINEERING
Rishima Agarwal1, K.R. Ko1, P.F. Gratzer1 and J.P. Frampton1
1School of Biomedical Engineering, Dalhousie University
Introduction: Extrusion-based bioprinting (EBP) is limited by loss of pattern fidelity when
printing on wet substrates. This can be overcome using aqueous two phase systems (ATPSs) as
novel ink formulations for EBP. ATPS-based inks are comprised of FDA-approved polymeric
solutions such as poly(ethylene) glycol (PEG) and dextran (DEX) that separate from each other
at low concentrations. In this study, we identified an optimal formulation that produced stable
droplets on standard tissue culture plates coated with PEG. We also demonstrate the application
of ATPS EBP by patterning an array of HEK001 cells in discrete colonies on a decellularized
dermal skin substitute (DermGEN™) to evaluate biopattern fidelity on a tissue matrix.
Methods: Four equilibrated and non-equilibrated ATPS combinations (5.0% PEG 35kDa: 5.5%
DEX 500kDa, 5.0% PEG 35kDa: 5.0 % DEX 500kDa, 5.0% PEG 35kDa: 4.5% DEX 500kDa,
and 5.0% PEG 35kDa: 4.0% DEX 500kDa) were tested for cell viability, stable ATPS formation,
and uniform cell patterning. A 1.0 μl droplet of DEX (containing ~5000 cells each) were printed
onto standard tissue culture plates coated in PEG. This process was also tested on a DermGENTM
by patterning HEK001 cells into discrete colonies with a 3 μm spacing between the colonies. A
Calcein-AM/Propidium Iodide (C-AM/PI) assay was performed to examine cell viability. Cell
proliferation and formation of adherens junctions were analyzed by immunocytochemistry.
Results and Discussion: 5.0% PEG 35kDa: 5.0% DEX 500kDa formed stable ATPSs and were
selected for biopatterning. Cells patterned in colonies displayed higher rates of cell viability and
E-cadherin junction formation compared to non-patterned cells. Moreover, when cells were
patterned on DermGENTM, stable ATPS formation and discrete cell colonies were also observed.
Conclusion: ATPS EBP is a promising technique for biopatterning of epidermal cells that may
be used for rapid re-epithelialization of wounds and other skin tissue engineering applications.
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A SMALL ULTRASOUND DEVICE FOR IMAGING AND ABLATION OF
CEREBRAL TISSUE
Jeffrey Woodacre1, T. Landry1 and J. Brown1
1 Department of Biomedical Engineering, Dalhousie University
Introduction: Combined imaging and therapeutic tools for minimally invasive procedures may
lead to increased efficacy and reduced patient risk. We are investigating the use of histotripsy
tissue ablation during ultrasound guided neurosurgery. Here, we will present our progress in
developing an endoscopic transducer for simultaneous, imaging and ablation.
Methods: A 10 mm diameter histotripsy transducer was created. The device used a quarter-
wavelength matching layer to improve bandwidth, allowing the transducer to reach cavitation
pressure in as little as one cycle. Peak pressure developed at the transducer focus was measured
for driving voltages between 15 V and 70 V using a needle hydrophone and extrapolated to
estimate a cavitation causing driving voltage. Measurements of the size of the cavitation region
were performed in de-gassed water under a microscope for a range of driving voltages, pulse
cycles, and pulse repetition rates, as-well-as in ex-vivo cerebral tissue using ultrasound guidance.
Results and Discussion: Extrapolation of hydrophone measurements estimate water cavitation
to initiate at a voltage of 150 V. Microscope measurements showed initial cavitation at a driving
voltage of 170 V. In water, the bubble cloud diameter was tunable between 0.16 mm and 0.50
mm diameter. Cloud axial length was tunable between 0.27 mm and 2.0 mm. Ablation region
size in chinchilla cerebral tissue was found to be 0.1-0.3 mm diameter when initiated inside
tissue and could be easily targeted to specific sites. Ablation rate was observed to increase once a
~0.5 mm diameter region of liquefied tissue was carved.
Conclusion: The tunability of bubble cloud size shows the ablation area and time are adjustable,
which is especially important in surgical applications where precision may be important.
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BORATE GLASS-FILLED HYDROPHILIC BONE CEMENTS FOR THE
THERAPEUTIC RELEASE OF STRONTIUM
Kathleen MacDonald1 and D. Boyd1,2
1School of Biomedical Engineering Dalhousie University and 2 Department of
Applied Oral Sciences, Dalhousie University
Introduction Composite resins are frequently considered for the release of therapeutic inorganic
ions (e.g. strontium) due to; (i) their mechanical and handling properties, and (ii) our ability to
augment their hydrophilicity. New fillers based on degradable borate glasses have been proposed
in the literature, based on their sustained release of therapeutic levels of Sr. This study now
examines the performance of contiguous composites, as Sr releasing cements for vertebroplasty.
Methods: A series of 15 hydrophilic cements were formulated, and fabricated by varying
HEMA content (15 to 45% resin weight) and glass filler loading (55 to 65% cement weight).
Cement working and setting times were evaluated and correlated with ATR-FTIR to assess
degree of conversion. Flexural strength was assessed up to 60 days (incubated using PBS, 37℃)
and ICP-OES analysis was performed to assess ion release. SEM and EDS were utilized to
examine cement surfaces after incubation.
Results and Discussion: The handling characteristics of the cements examined was
substantially equivalent to clinically utilized composite resins for orthopaedics (i.e. working
times 150-255 s, setting time 209-263 s). Flexural strength decreased from 43 to 19 MPa with
increasing HEMA content. Increasing HEMA content resulted, as expected, in greater mass gain
(up to 17%), and boron release (up to 13%). Interestingly, very low levels of Sr release were
observed (~2%), despite evidence of borate filler degradation.
Conclusions: While highly hydrophilic modification of the composites resulted in increased
glass degradation, increased strontium release was not observed via ICP-OES. SEM and EDS of
cement surfaces revealed strontium rich precipitates, likely the cause of this observation.
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School of Biomedical Engineering
Research Day 2017 Abstracts
SCIENTIFIC SESSION 2
19
TRANSMISSION ELECTRON MICROSCOPY OF THE NANOSCALE
STRUCTURE AND DAMAGE IN TENDON COLLAGEN
Jasmin Astle1, J.M. Lee1,2, B.D. Quan3 and E.D. Sone3
1Biomedical Engineering, Dalhousie University; 2Department of Applied Oral
Sciences, Dalhousie University; 3Institute of Biomaterials and Biomedical
Engineering, University of Toronto
Introduction: Damage to tendon is actually damage to the collagen of its extracellular matrix.
At the nanoscale, overloaded collagen undergoes plastic deformation at discrete locations along
the length of the collagen fibrils; these form kink-like structures, called discrete plasticity
damage, when unloaded. Discrete plasticity damage has been visualized in previous work using
scanning electron microscopy (SEM) and atomic force microscopy (AFM). This work will use
transmission electron microscopy (TEM) to observe discrete plasticity damage and identify the
morphologies of other mechanisms of damage at the nanoscale.
Methods: Bovine tail tendons were put through 5 sub-rupture tensile overload cycles to induce
damage. After 2 hours in fixative, individual fibres were isolated from the tendons, under a
dissecting microscope, and placed in fresh fixative overnight. Samples were en-bloc stained
using osmium tetroxide and uranyl acetate, dehydrated in ethanol and embedded in Embed 812
resin. Ultra-thin sections were taken using a Leica EM UC6-NT ultra-microtome and transferred
onto 600 mesh nickel TEM grids and post-stained using 2% uranyl acetate. Images were
captured using a FEI Technai 20 TEM.
Results and Discussion: The embedding and post-staining protocols were optimized for tendon
collagen, resulting in remarkably improved quality and consistency of TEM images, with highly
detailed banding. Discrete plasticity kinks have been identified in TEM images, along with other
structural motifs, that are unique to damaged samples and not visible in AFM/SEM images.
Conclusions: There may be multiple mechanisms of damage in tendon collagen, some of which
may only be identifiable using a non-topographical, nanoscale imaging technique, like TEM.
20
HIGH-THROUGHPUT 3D NEURAL CELL CULTURE ANALYSIS
FACILITATED BY AQUEOUS TWO-PHASE SYSTEMS
Kristin Robin Ko1, R. Agarwal1 and J.P. Frampton1
1School of Biomedical Engineering, Dalhousie University
Introduction: The three-dimensional (3D) culture of neural cells in extracellular matrix (ECM)
gels holds promise for modeling neurodegenerative diseases. However, air-liquid interfacial
tension and evaporation can result in inconsistent 3D cultures at low volumes. Thick-layer
hydrogels can counter these factors, but large diffusion distances, high cost, and incompatibility
with standard imaging tools, plate readers and assays limit their use. To address these
limitations, we have developed a thin-layer, 3D culture technique using a commonly used self-
assembling ECM hydrogel (Matrigel) combined with an aqueous two-phase system (ATPS).
Methods: A dextran T10 (D10) and hydroxypropyl methylcellulose 4000 cPs (HPMC) ATPS
was used to confine small volumes of Matrigel containing the model neural cell line, SH-SY5Y,
into thin layers in a 96-well plate format. SH-SY5Y cells were differentiated and cell viability
and morphology were observed under epifluorescence microscopy. The ATPS-Matrigel 3D
culture method was characterized by monitoring the distribution of 3.0 µm microbeads within
gel constructs without cells.
Results: Matrigel evaporation was eliminated in the ATPS-Matrigel 3D culture method, and
small volumes (20 µl and lower) formed evenly thin gels. SH-SY5Y cells were observed to
extend neurite-like processes in three-dimensions when differentiated, and cell viability
remained high, suggesting minimal negative impact of the protocol on cell growth.
Conclusion: We demonstrate a low cost, simple, high-throughput, 3D neuronal cell culture
system that is compatible with well-established equipment and commercially available
materials.
21
PERFORMANCE CHARACTERIZATION OF A REAL-TIME 64-
CHANNEL HIGH-FREQUENCY PHASED ARRAY BEAMFORMER
Chris Samson1 and J. Brown1
1School of Biomedical Engineering, Dalhousie University
Background: In comparison to conventional low-frequency beamformers, high-frequency
phased array beamforming has an added level of complexity with respect to both analog and
digital electronics. The result is prohibitively high sampling and data capture rates which impose
stringent processing requirements. We have developed a high-frequency beamformer capable of
transmitting and capturing 64 channels in parallel, that uses a new sub-Nyquist approach to
reduce sampling and data rates.
Methods: The beamformer uses 10 synchronized FPGAs and the system architecture includes: 1
transmit motherboard, 1 receive motherboard, 8 transmit daughter cards, and 8 receive daughter
cards. Each daughter card manages 8 channels. Each transmit daughter card has 8 channels of
high voltage transmit electronics and low noise preamplifiers. The receive daughter cards
perform filtering, time-gain amplification, digitization, and data capture via an on-board FPGA.
Variable sampling is performed by capturing and demodulating the receive data at ¾ λ. System
performance was tested on a 64-element 45 MHz linear phased array.
Results and Discussion: The transmit timing accuracy has been measured to be ±650ps and the
timing accuracy for the dynamically varied A/D clocks on the receive beamformer was measured
to be ±1.0ns. The pulse width can be controlled with 800ps step sizes and the transmit
amplitudes can reach ±48V. The maximum data capture rate for the system is 115 Gb/s. Under
optimal imaging conditions choosing 128 lines, 4 focal zones, and averaging 2 frames, the
system generates images at 37 fps. The beamforming performance on the 45 MHz phased array
yielded 55 dB of dynamic range and the 6dB lateral and axial resolutions were measured to be 90
and 40 μm respectively.
Conclusion: This system is the world’s first high-frequency phased array beamformer capable of
capturing and processing 64 channels in parallel. This project forms the basis of a strong research
platform in the field of high-frequency ultrasonics.
22
LONGITUDINAL ANALYSIS OF PATIENT SATISFACTION AFTER
TOTAL KNEE ARTHROPLASTY
Kathryn Young1, E.K. Laende1, J.M. Flemming1,2, M.J. Dunbar1,3 and J.L. Wilson1
1School of Biomedical Engineering, Dalhousie University; 2Mathematics and
Statistics, Dalhousie University; and 3Department of Surgery, Dalhousie
University
Introduction: Total knee arthroplasty (TKA) has high patient outcome variability, yet the
identification of high-risk surgical candidates remains inconclusive. The objective of this study
was to characterize changes in patient-reported satisfaction up to two years following TKA, and
identify patient factors that are meaningful in early identification of poor satisfaction over time.
Methods: On a prospective cohort of primary TKA patients, demographic data was collected
one week pre-TKA, and patient-reported outcomes were captured pre-TKA and six weeks,
twelve weeks, six months, one and two years post-TKA. Satisfaction on a Visual Analog Scale
(VAS) at one-year was used to define a binary response; “fully satisfied” for scores ≥ 90, and
“not fully satisfied” for scores ≤ 89. A binomial generalized linear mixed effects model was
used to examine demographic and questionnaire factors associated with satisfaction
longitudinally.
Results and Discussion: Stepwise improvements in satisfaction occurred within the first six
months post-TKA (p≤0.01; n=86). At baseline, fully satisfied patients had lower Pain
Catastrophizing Scores (p=0.02), and better EQ-5D scores (p=0.001). At six weeks post-TKA,
fully satisfied patients had better Oxford Knee Scores (OKS) (p=0.01), EQ-VAS (p<0.01) and
Pain-VAS scores (p=0.03). Key factors that improved the odds ratio (OR) of a satisfaction
response included better OKS (OR=2.1, p<0.001) and EQ-VAS scores (OR=1.3, p=0.03), and
less pain (OR=1.7, p<0.001).
Conclusions: This study captured longitudinal changes in patient satisfaction, supporting the
ability to predict high-risk patients preoperatively or closely following surgery. Findings can
inform patient-specific treatment, post-TKA care, and expectation management strategies.
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School of Biomedical Engineering
Research Day 2017 Abstracts
SCIENTIFIC SESSION 3
24
USING RELIABILITY TO PROVIDE PATIENT-SPECIFIC PROCESSING
OF NEUROIMAGING DATA
Sarah McLeod1, S. Beyea1,2 and T. Bardouille2
1School of Biomedical Engineering, Dalhousie University, 2IWK Health Centre
Introduction: Functional neuroimaging plays a key role in pre-surgical planning and improving
surgical outcomes. My team has developed ROCr (Receiver Operating Characteristic reliability)
- a tool to assess intra-session reliability of functional neuroimaging data. Different settings
(“pipelines”) can be used to process the data and will give slightly different brain maps.
However, it is unclear which pipeline is best for each patient. ROCr can score the reliability of
the map generated by each pipeline. We hypothesize that pipelines with higher reliability scores
will have more focal localization results compared to the standard analysis pipeline.
Methods: Ten participants underwent three MEG (magnetoencephalography) imaging sessions
of right MNS (median nerve stimulation) to localize the primary somatosensory cortex (S1).
Twelve pipelines were used to analyze each dataset, producing 12 brain maps per session per
subject. From each brain map, an estimate of the S1 location was obtained. The ROCr
framework was used to determine a measure of intra-session reliability (Fr) for each brain map.
Finally, the reliability measures were compared to the intra-subject focality of S1 location.
Results and Discussion: Using the pipelines with higher intra-session reliability scores resulted
in more focal results for 6/10 subjects (p < 0.001). The remaining four subjects had equivalent
focality between the standard pipelines and the ROCr-selected pipelines. These results indicate
that using the pipeline with highest intra-session reliability will give results that are just as good
as, and in many cases better than, the standard analysis pipeline.
Conclusions: Based on the analyzed data, ROCr performs expected, giving it credibility as a
future tool for automated pipeline selection for analysis of neuroimaging data.
25
TRUNK NEUROMUSCULAR PATTERNS INTERACT WITH CLINICAL
MEASURES OF TRUNK STABILITY TO INFLUENCE THE RISK OF
FUTURE LOW BACK RE-INJURIES
Adam Quirk1, R.D Trudel2, and C.L. Hubley-Kozey1
1School of Biomedical Engineering, Dalhousie University; 2Department of
National Defence
Introduction: Theoretical models suggest impaired osteoligamentous stiffness could be
compensated for by changing the recruitment patterns of trunk musculature to prevent the risk of
future low back injury (LBI). The purpose of this study was to determine if a clinical measure of
osteoligamentous stiffness would interact with measures of trunk muscle activation patterns
during dynamic tasks to predict who would and would not develop LBI in one-year.
Methods: Thirty-two recovered LBI participants recruited from the military performed two
highly controlled dynamic (lifting (HTT), and supine leg loading (TST)) tasks where they were
requested to minimize lumbopelvic motion. Electromyograms (EMG) were collected from 24
trunk muscle sites. Spatial-temporal analysis of EMG data were determined from principal
component (PC) analysis on time and maximum voluntary isometric contraction amplitude
normalized ensemble average waveforms. Participants were separated in four groups: those
classified with (CI+) and without (CI-) clinical instability (CI), and then sub-categorised as those
with re-injury (RE) or no re-injury (NoRE) based on one-year follow up. Mixed model ANOVA
(group, muscle) were conducted on PC scores (α=0.05).
Results and Discussion: For those with (CI+) and without (CI-) an instability, (6/12) and (9/20)
experienced a RE. Group effects were identified for 6/11 PC scores. The overall activation
amplitudes (PC1) of the antagonist muscles (back extensors and abdominals for the TST and
HTT respectively) revealed, those CI+ with No-RE had higher PC1 than RE. Conversely those
CI- with RE had higher PC1 than No-Re. These data suggest for those CI+ increasing antagonist
activation may compensate for reduced osteoligamentous stiffness to reduce the risk of future re-
injury. However, this pattern is mal-adaptive in those CI-.
Conclusions: The results of this study suggest neuromuscular patterns interact with clinical
measures of osteoligamentous stiffness in a way that modifies the risk of future re-injury.
26
LIMITED DYNAMIC RANGE ARTEFACT REMOVAL FROM FOURIER
DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGES
Joshua Farrell1, D. MacDougall1 and R. Adamson1,2
1School of Biomedical Engineering, Dalhousie University; 2Department of
Electrical and Computer Engineering, Dalhousie University
Introduction: We demonstrate a technique for removing artefacts that occur in Fourier-domain
optical coherence tomography (OCT) when the range of reflectances in an OCT image exceeds
the point-spread function dynamic range of the source. Such artefacts present a major problem in
images that contain an air-tissue interface. The technique relies on artefact detection and removal
using a sliding threshold filter in the wavelet domain and produces artefact-free images while
preserving structural information occluded by the artefacts.
Methods: The first step in our approach to removing limited PSF dynamic range artefacts consists
of performing a wavelet decomposition on a logarithmic intensity-weighted OCT image. At each
stage of the decomposition a detection operation is performed to identify one-pixel wide dynamic
range artefacts. Lines affected by the artefact that are identified in the approximation coefficients
are removed and replaced by the linear interpolation of the adjacent lines. Importantly, whenever
artefacts are more than one pixel wide at a particular wavelet decomposition level they are not
removed. However, as the wavelet decomposition proceeds to higher levels, a level will eventually
be reached where a multi-pixel wide artefact in the original image has been reduced to a single
pixel wide artefact. Thus, all artefacts are removed, but only at the level of the wavelet
decomposition at which the artefact is one pixel wide. Wavelet based image despeckling can also
be run concurrently with artefact removal as both operations operate on the detail and
approximation coefficients respectively, independently of each other.
Results and Discussion: The combination of detection, interpolation and despeckling results in
an image with no visible trace of the original artefact.
Conclusion: We introduced a post-processing algorithm for removing artefacts that occur in FD-
OCT images when the sample dynamic range exceeds the dynamic range of the PSF.
27
CHANGES IN GAIT KINETICS PRECEDE STRUCTURAL JOINT
CHANGES IN INDIVIDUALS WITH KNEE OSTEOARTHRITIS
E.M. Davis1, S.C. Landry4, D. Ikeda, MSc1, W.D. Stanish, MD2, C.L. Hubley-
Kozey, PhD1,3, J.L. Astephen Wilson, PhD1,2
1School of Biomedical Engineering, 2Faculty of Medicine, 3School of
Physiotherapy, Dalhousie University, Halifax, Nova Scotia, Canada, 5Faculty of
Kinesiology, Acadia University, Wolfville, Nova Scotia, Canada
Introduction: Longitudinal analysis of joint level biomechanics in concert with radiographic
monitoring of the knee joint may yield information regarding the factors related to mechanically
induced knee osteoarthritis (OA) progression before the augmented structure of the joint is
visible on a radiograph. The purpose of this study was to measure the 3-year change in
biomechanical features of gait, previously linked to OA severity and progression.
Methods: 28 individuals with moderate OA and 22 asymptomatic (ASYM) adults visited the
DOHM Laboratory at baseline and follow-up (3 years) for three-dimensional gait analysis.
Principal component analysis (PCA) was used to extract key features of variability in the
respective waveforms. Standardized X-rays of the knee joints enabled the grouping of
individuals based on structural OA progression. Longitudinal changes in magnitude and patterns
of 3D knee moments and electromyography waveforms (from PCA) were compared for three
groups using one way ANOVAs (P < 0.05).
Results and Discussion: There were no significant differences in any gait features of the
ASYM-Non-Progression (ASYM-NP) group between baseline and 3 years. At follow-up, the
OA-NP group and the PG both displayed a higher early stance flexion moment, less mid-stance
internal rotation moment, and a greater overall magnitude of the lateral gastrocnemius activity.
The loading environment of the knee of the OA-NP group changed without radiographic
evidence of deterioration of the joint structure. These changes were in the same direction as the
PG.
Conclusions: Certain changes to the loading environment of the knee joint occur before
structural changes are evident, suggesting that gait biomechanics are not only a reflection of the
current joint structure, but may have a preceding role in its degradation.
28
School of Biomedical Engineering
Research Day 2017 Abstracts
SCIENTIFIC SESSION 4
29
FABRICATION AND PERFORMANCE OF A 128-ELEMENT CROSSED-
ELECTRODE ARRAY FOR A NOVEL 3D IMAGING APPROACH
Kate Latham1, C. Ceroici2, C. Samson1, R.J. Zemp2 and J. Brown1
1 School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia; 2Department of Electrical and Computer Engineering, University of Alberta,
Edmonton, Canada
Introduction: We have developed a new, fast and simple 3D imaging approach referred to as
Simultaneous Azimuth and Fresnel Elevation (SAFE) compounding for a 2D crossed electrode
relaxor array. The principle behind this technique is to perform conventional plane wave imaging
compounding with the top set of electrodes, while implementing a reconfigurable Fresnel
elevation lens with the bottom electrodes. A Fresnel lens would usually result in unacceptable
secondary lobe levels, however, these lobes can be suppressed by compounding different Fresnel
patterns. The elevation Fresnel lens can be simultaneously compounded with the plane waves in
azimuth to increase the beam quality, resulting in no loss in frame rate.
Methods: If a Fresnel pattern is changed upon sequential pulsing to focus to n spatially different
focal spots that are nearby, but separate enough that the Fresnel pattern changes, the pressure
fields can be averaged to reduce side lobe energy. The compounded Fresnel lens is also capable
of steering, thus enabling collection of multiple elevation slices with no added beamforming
complexity. A 10MHz, 64x64 element crossed electrode relaxor array was fabricated on a
electrostrictive 1-3 composite substrate to reduce crosstalk and increase the element directivity.
2D images were generated using a Verasonics Vantage system with custom biasing electronics.
Results and Discussion: The electrostrictive composite array has a measured electromechanical
coupling coefficient (kt) of 0.63 with a bias voltage of 90V and a measured two-way pulse
bandwidth of 60%. The electrical impedance magnitude on resonance was measured to be 70
ohms with a phase angle of -40 degrees. 2D images were generated of a wire phantom in a water
bath using the SAFE compounding technique.
Conclusions: While data collection for elevation steering and volumetric 3D imaging is
ongoing, the SAFE compounding imaging technique is a promising approach because it allows a
volumetric image to be captured at real time frame rates without the addition of extra
beamforming channels compared to a 1D array.
30
FRACTURE MECHANICS OF HUMAN SARTORIUS TENDONS DIFFER
FROM THAT OF BOVINE TAIL TENDONS
Sara Sparavalo1, Samuel P. Veres1,2, Sarah M. Wells1,3, and J. Michael Lee1,4
1School of Biomedical Engineering, Dalhousie University; 2Division of
Engineering, Saint Mary’s University; 3Department of Physics and Atmospheric
Science, Dalhousie University; 4Department of Applied Oral Sciences, Dalhousie
University
Introduction: Soft tissue injuries are a result of damage to the structure of collagen within the
extracellular matrix. Overload-damage in bovine tail tendons has been used as an in vitro mimic of soft
tissue injury, and has been shown to exhibit a series of nanoscale kinks within the fibrils of the tendon
collagen – a mechanism termed ‘discrete plasticity’. It is thought that the formation of these kinks
toughens the collagen fibrils via strain energy absorption. The failure mechanisms present within human
tendons, and their associated fracture mechanics, are currently being investigated.
Methods: Sartorius tendons from donors of varying ages (17-60 years) were collected from the NSHA
Tissue Bank and were ruptured to induce damage and collect mechanical loading data. Both damaged and
control samples were visualized with high magnification scanning electron microscopy (SEM) to assess
damage motifs which were then compared with SEM images of ruptured bovine tail tendon samples.
Results and Discussion: SEM images of ruptured human sartorius tendons do not show the same damage
motifs as found in bovine tail tendons. The damaged fibrils show hairpin turns, twists, and disassembly of
higher order structures – mechanisms different from that of discrete plasticity. It is possible that the
sartorius tendon has a different mechanism of failure, or that the tissues are heavily glycated.
Conclusions: This research is the first to examine the nanoscale failure mechanisms present within
human tendons, and shows that the failure mechanisms of collagen can vary depending on tendon type
and source.
31
TOWARDS A MINIATURE IMAGING PROBE FOR FUNCTIONAL
MIDDLE EAR IMAGING
Daniel MacDougall1, Matthew Jahns1, M. Bance1,3, R. Adamson1,2
1School of Biomedical Engineering, Dalhousie University; 2Department of
Electrical Engineering, Dalhousie University; 3Department of Surgery, Dalhousie
University
Introduction: We have previously demonstrated our ability to produce 3D images in the human
middle ear using optical coherence tomography (OCT), but integrating the novel functionality
into a new device that meets the end user’s needs, i.e. clinical otologists and audiologists,
remains a challenge that requires iterative design to hone form and function. Our current work
surrounds the development of a miniaturized imaging probe designed specifically to meet the
needs of functional trans-tympanic OCT imaging of the human middle ear.
Methods: This work surrounds the analysis of the end user’s needs to accommodate the shape of
the human ear canal, and how the device will be handled and used in the clinic. It entails the
miniaturization of the required functional blocks to accommodate all the necessary optical,
mechanical and electronic subsystems.
Results and Discussion: Our prototype-in-development design combines several features that
address key issues to make it well suited for OCT in the ear. The design combines gradient-index
rod lenses for deep insertion into the ear canal, custom ground spherical lenses for laser beam
manipulation, a micro-electromechanical (MEMS) tilting mirror for beam steering, a mini-
microphone from a mobile phone, a mini-speaker from a hearing aid, and a CCD for
conventional en-face imaging; all enclosed within a miniature handheld package. While the
functional prototype has not yet been built, design considerations and modelling will be shown
along with 3D printed mock-ups.
Conclusions: We have demonstrated the steps we have taken towards developing a novel,
miniature and application specific imaging probe for OCT imaging in the human middle ear.
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