research day 2017 - dalhousie university...it is my pleasure to welcome you to the 15th annual...

Research Day 2017 School of Biomedical Engineering

Scientific Program

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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 | [email protected] | dal.ca/bme

DAL.CA

mailto:[email protected]

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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

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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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Research Day 2017

DISTINGUISHED

IDUSTRY LECTURE

Cameron Piron President and Cofounder Synaptive Medical

Opportunities for the

Fusion of Medicine,

Engineering and Business

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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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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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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.

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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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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.

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HIGH-THROUGHPUT 3D NEURAL CELL CULTURE ANALYSIS

FACILITATED BY AQUEOUS TWO-PHASE SYSTEMS

Kristin Robin Ko1, R. Agarwal1 and J.P. Frampton1


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.

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PERFORMANCE CHARACTERIZATION OF A REAL-TIME 64-

CHANNEL HIGH-FREQUENCY PHASED ARRAY BEAMFORMER

Chris Samson1 and J. Brown1


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.

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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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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


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




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


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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