School of Biomedical Engineering

Research Day 2018

Scientific Program

May 10th, 2018

Dear Colleagues:

It is my pleasure to welcome you to the 16th 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.

This year I have the great pleasure to welcome our two Keynote Distinguished Speakers, Leyla Soleymani, PhD, from McMaster University, who will present work from her lab on “Materials Innovations for Next Generation Biosensing”, and James Schellenberg, PhD, Founder and CEO of Cubresa, Inc., who will present "Interfaces: The Evolving Roles of Medical Technology and Artificial Intelligence in Our Society”.

Dr. Soleymani is the Canada Research Chair in Miniaturized Biomedical Devices at McMaster University. She is widely published with many papers in highly-regarded journals such as Lab-on-a-Chip, Advanced Functional Materials, Angewandte Chemie, and Nature Nanotechnology. In addition to her Canada Research Chair, she is also a past recipient of the Douglas R. Colton Medal for Research Excellence. This award is given for research leading to new understanding and novel developments in microsystems and related technologies.

Dr. James Schellenberg has had management experience in numerous start-up technology companies from 1989 to the present. He has also participated both as an investor and contributor in various other technology companies, including Texar Corporation, Edge Networks Inc., Esion Networks Inc., Photonami Inc. and iMagicTV, and he is currently the Founder and CEO of Cubresa, Inc., a Canadian-based company commercializing nuclear imaging products.

I want to sincerely thank all those who help make this day run smoothly. 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 1

School of Biomedical Engineering Research Day 2018

DISTINGUISHED ACADEMIC LECTURE

Biography: Leyla Soleymani obtained her PhD degree in Electrical Engineering from University

of Toronto in 2010, and she is currently Associate Professor at the Department of Engineering

Physics and the School of Biomedical Engineering at McMaster University. She is currently the

Canada Research Chair in Miniaturized Biomedical Devices, and she is working towards making

new materials and methods for creating point-of-care and continuous monitoring biosensors.

Abstract: Since its commercialization in the 1980’s, the glucose biosensor has played a vital role

in patient-centered management of diabetes. Motivated by this success, there is a major research

effort towards developing a wide range of handheld biosensors for health monitoring and disease

management. In this talk, I will provide an overview of the scientific and technological challenges

behind biosensor development. I will then discuss the progress made in our lab in creating

nanoscale and multi lengthscale materials systems towards addressing the challenges related to

biosensor sensitivity and specificity, as well as technical challenges related to the fabrication and

miniaturization of biosensors. Finally, I will demonstrate the development of biosensing assays for

detection or proteins, small molecules, and nucleic acids for point-of-care diagnostics.

Leyla Soleymani, PhD Associate Professor, School of Biomedical Engineering and Dept. of Engineering Physics, McMaster University

Materials Innovations for Next Generation Biosensing

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School of Biomedical Engineering Research Day 2018

DISTINGUISHED INDUSTRY LECTURE

Biography: James Schellenberg has participated in start-up technology companies from 1989 to

the present. He has executive management experience with Broadband Networks Inc., Nortel Inc.,

Centara Corporation, James Schellenberg Inc. and most recently with IMRIS Inc. He has

participated both as an investor and contributor for numerous technology based companies,

including Texar Corporation, Edge Networks Inc., Esion Networks Inc., Photonami Inc. and

iMagicTV. James graduated with a Ph.D. in Electrical Engineering from the University of

Manitoba in 1990 and has filed over 10 patents.

Abstract: I will propose that the primary type of problem that newly graduated engineers will be

faced with over the next 30 years will be related to interfaces: the interface between human and

artificial systems, the interface between engineering and ethics, and perhaps the interface between

science and religious belief. In the talk I will briefly mention Cubresa’s work on medical imaging

equipment for the mind-brain interface, and then discuss these three types of interfaces in the light

of modern findings and events. One event that has happened recently is the statement from Roger

McNamee of Elevation Partners (early investor in Facebook): “We used to believe technology was

goodness – we don’t believe that anymore”. Much like the atom bomb scientists of the 40’s, it is

time for Pugwash 2.0. This is especially true in light of artificial intelligence, robotic systems, and

the statements of Bill Joy in the late 90’s.

James Schellenberg, PhD Founder and CEO Cubresa, Inc.

Interfaces: The Evolving Roles of Medical Technology and Artificial Intelligence in Our Society

3

Previous Winners of the Community Builder Prize in Biomedical Engineering

2008 Marianne Ariganello

2011

Adrian West

2013 J. Michael Lee

2015

Eleanor Seaman-Bolton

2017 Rishima Agarwal

4

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

2017

Jeremy Brown

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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

2017

Kristin Robin Ko

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Previous Winners of the Allan E. Marble Prizes in Biomedical Engineering

2002 Sean Margueratt

2003

Anna Dion

2005 Doctoral: Mark Glazebrook Pre-doctoral: Carolyn Lall

2006

Doctoral: Scott Landry Pre-doctoral: Scott MacLean

2007

Doctoral: Janie Astephen Pre-doctoral: Andrew Moeller

2008

Doctoral: Marianne Ariganello Pre-doctoral: Vargha Talebi

2009 Doctoral: Jack Fairbank

Pre-doctoral: Jennifer Krausher

2010 Derek Rutherford

2012

Del Leary

2013 Andre Bezanson

2014

Caitlin Pierlot

2015 Arash Momeni Boroujeni

2016

Dan MacDougal

2017 Brett Dickey

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School of Biomedical Engineering Research Day 2018 Scientific Program Thursday, May 10, 2018 Kenneth C. Rowe Management Building, Room 1009

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. Joshua Leon, Dean, Faculty of Engineering

Scientific Session 1 (Chairs: Andre Bezanson and Nicky Tam)

8:45 am to 9:00 am “Overload damage to female human sartorius tendon collagen over four decades of age” Emile Feniyanos (MASc Student), S.P. Veres, S.M. Wells and J.M. Lee

9:00 am to 9:15 am “Screening immunotherapy agents in polymer solution microreactors: preliminary evaluation of cytotoxicity and cell phenotype” Alyne Teixeira (PhD Student), J. Wang and J.P. Frampton

9:15 am to 9:30 am “A rendering pipeline and software architecture for processing and visualization of optical coherence tomography data in a clinical setting” Joshua Farrell (PhD Student), D. MacDougall, F. Morin and R. Adamson

9:30 am to 9:45 am “Patients not reporting improvements in pain and function post-total knee arthroplasty demonstrate poor improvement during gait” Kathryn Young (PhD Student), M.J. Dunbar and J.L. Wilson

Coffee Break (9:45 am – 10:00 am)

Scientific Session 2 (Chair: Kristin Robin Ko)

10:00 am to 10:15 am “Toward the development of an endoscopic histotripsy device” Jeffrey Woodacre (PhD Student) and J. Brown

10:15 am to 10:30 am “Transmission electron microscopy reveals new details of the initiation of collagen fibril damage during tendon overload” Jasmin Astle (PhD Student), E.D. Sone, B.D. Quan, S.P. Veres and J.M. Lee

10:30 am to 10:45 am “Chemotherapeutic-loaded polyphosphate glass microspheres for transarterial chemoembolization” Hayden Nix (MASc Student), A. Momeni, D. Chevrier and M.J. Filiaggi

10:45 am to 11:00 am “Respiratory impedance modelling predictions using graded 3He inhaled gas magnetic resonance imaging” Cody Church (MSc Student), H. Young, D. Capaldi, G. Parraga and G.N. Maksym

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Distinguished Academic Lecture

11:00 am to 12:00 pm

Dr. Leyla Soleymani, Associate Professor, School of Biomedical Engineering and Dept. of Engineering Physics, McMaster University “Materials Innovations for Next Generation Biosensing” Introduction: Dr. John P. Frampton

Catered Lunch (12:00 pm – 1:00 pm)

Distinguished Industry Lecture

1:00 pm to 2:00 pm

Dr. James Schellenberg, Founder and CEO of Cubresa, Inc. “Interfaces: The Evolving Roles of Medical Technology and Artificial Intelligence in Our Society” Introduction: Dr. Steven Beyea

Scientific Session 3 (Chair: Rishima Agarwal)

2:00 pm to 2:15 pm “Trunk repositioning sense is related to changes in trunk muscle activation patterns during controlled lifting” Adam Quirk (PhD Student), R.D Trudel and C.L. Hubley-Kozey

2:15 pm to 2:30 pm “The effects of optical clearing agents on tympanoplasty graft materials for use in middle ear optical coherence tomography” Francis Morin (MASc Student), M. Khalid-Raja, C. Morrisson, D. McDougall, R. Adamson and D.P. Morris

2:30 pm to 2:45 pm “Three-dimensional ultrasound imaging results and development of an endoscopic crossed electrode array” Kate Latham (PhD Student), C. Samson, A. Bezanson and J. Brown

Coffee Break (2:45 pm – 3:00 pm)

Scientific Session 4 (Chairs: Nicky Tam and Kathleen MacDonald)

3:00 pm to 3:15 pm "Sparse orthogonal diverging wave imaging on a high-frequency phased array” Chris Samson (PhD Student), R. Adamson and J. Brown

3:15 pm to 3:30 pm “Synthesis, characterization, and risk assessment of a novel degradable, imageable uterine artery embolic agent” Jensen Doucet (MASc Student) and D. Boyd

3:30 pm to 3:45 pm “Thermomechanical analysis of collagen crosslinking in the lumbar intervertebral disc annulus” Tyler Herod (MASc Student), J.M. Lee and S.P. Veres

3:45 pm to 4:00 pm “Photoacoustic tomography for use in endoscopic brain surgery” Taylor Landry (MASc Student) and R. Adamson

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Awards and Closing

4:00 pm to 4:15 pm Presentation Judging (Atrium) Dalhousie Biomedical Engineering Society Elections (Room 1009)

4:15 pm to 4:25 pm School of Biomedical Engineering Awards Chair: Dr. Geoff Maksym

4:25 pm to 4:35 pm Presentation Prizes for Research Day 2018 Chairs: Dr. Leyla Soleymani and Dr. James Schellenberg

4:35 pm to 4:45 pm Closing Remarks: Dr. Geoff Maksym

Closing Reception (4:45 pm – 7:00 pm)

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School of Biomedical Engineering Research Day 2018 Abstracts

SCIENTIFIC SESSION 1

11

OVERLOAD DAMAGE TO FEMALE HUMAN SARTORIUS TENDON

COLLAGEN OVER FOUR DECADES OF AGE

Emile Feniyanos1, S.P. Veres1,2, S.M. Wells1 and J.M. Lee1

1School of Biomedical Engineering, Dalhousie University, Halifax, Canada; 2Division of Engineering,

Saint Mary’s University, Halifax, Canada

Introduction: As men and women remain physically active into the geriatric years, changes in soft

tissue injuries and healing with age are becoming more important to clinical care. The sex-linked

differences in structure and function of tendons in humans are not well understood, although some

differences have been studied in the context of sports injuries. It is similarly unclear whether such

differences are modulated with ageing. The present study is the first segment of a rare comparative study

of tendons over four decades of adult life from both sexes.

Methods: Human sartorius tendons were collected from the CHDA Regional Tissue Bank, harvested

from female non-diabetic individuals spanning four decades of age: 20-60. For each paired set of

tendons, one was subject to uniaxial mechanical overload that simulates damage during injury. The

induced structural damage was observed at the nanometer scale using scanning electron microscopy. The

second tendon underwent thermomechanical testing to evaluate the thermal stability of the tendon

collagen, the primary protein in tendon.

Results and Discussion: Interestingly, we found that tendon stiffness and strength were strongly

correlated with body mass index (BMI) (p < 0.0050 and p < 0.0196 respectively). As with male tendons,

most mechanical parameters were age-independent. SEM imaging showed that tissue plasticity was not

associated with the 'discrete plasticity' mechanism. Curiously, thermal stability of tendon collagen, as

observed with collagen denaturation temperature (Td), declined significantly with age, from 67.8℃

65.1℃ (p < 0.0001).

Conclusions: Over four decades of adulthood, female tendons showed biomechanical and structural

evidence of high energy elastic fracture of collagen without significant plasticity.

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SCREENING IMMUNOTHERAPY AGENTS IN POLYMER SOLUTION

MICROREACTORS: PRELIMINARY EVALUATION OF CYTOTOXICITY

AND CELL PHENOTYPE

Alyne G. Teixeira1, J. Wang2 and J.P. Frampton1

1School of Biomedical Engineering, Dalhousie University; 2Department of Microbiology &

Immunology, Dalhousie University

Introduction: Immunotherapy agents such as vaccines are designed to modulate the immune system for

prevention and treatment of many diseases. However, conventional assays for evaluating

immunotherapies require considerable amounts of biomolecules, cells and reagents, do not retain cell

viability for further manipulation, and demand complex and expensive procedures. To address these

obstacles to the efficient evaluation of immunotherapy agent safety and efficacy, a bioassay designed to

identify and evaluate novel immunotherapy agents has been developed, in which polymer solutions are

used to confine immune cells and reagents together in microdroplet reactors.

Methods: A small library of polymer solutions including albumin, alginate, dextran, Ficoll, gum arabic,

hydroxypropyl cellulose, hydroxypropyl methylcellulose, methyl cellulose, poly(2-ethyl-2-oxazoline)

and poly(ethylene glycol) were screened for appropriate handling characteristics (i.e., viscosity, phase-

separation, compatibility with salts used in culture medium, and acute cytotoxicity). Following

identification of appropriate candidate systems for confinement of cells, cell viability

(calceinAM/propidium iodide staining) and phenotype (aggregation and cell morphology) were assessed.

Polymer solutions above the critical concentrations required for phase-separation were incubated with

various types of immune cells for up to 7 days. The immune cell types used for evaluation included K-

562 (human lymphoblast), RPMI 8226 (human B lymphocyte), Jurkat (human T lymphocyte) and murine

splenocytes (lymphocytes). Proof-of-concept analysis of cytokine secretion from microdroplet cultured

cells was also conducted using TNF-α and IL-6 ELISAs.

Results and Discussion: Based on preliminary screening of handling characteristics, several systems

were selected for cytotoxicity screening over multiples days of cell culture. Overall, the polyethylene

glycol-dextran system performed best with cells, but cell viability was slightly lower compared to control

medium. Nevertheless, the number of live cells in the polymer solutions remained high over the course

of 7 days. Subtle changes in cell phenotype were also observed in cells cultured in polymer solutions.

From day 3, cell morphology began to change in cells cultured in polymer solutions, with some cells

attaching to the culture plate and becoming elongated. Additional morphological changes were observed

by day 7, which suggest that the polymer solutions may have some effects on cell stimulation. However,

cytokine ELISAs demonstrated that the assay systems performed as expected for vaccine adjuvant

screening.

Conclusions: Cells cultured in polymer solutions used for microreactor design display minor alteration

in cell viability and phenotype compared to control cells cultured without polymer solutions. Overall, the

data show that phase-separating polymers are promising candidates for development of new bioassays

for screening immunotherapy agents.

13

A RENDERING PIPELINE AND SOFTWARE ARCHITECTURE FOR

PROCESSING AND VISUALIZATION OF OPTICAL COHERENCE

TOMOGRAPHY DATA IN A CLINICAL SETTING

Joshua Farrell1, D. MacDougall1, F. Morin1 and R. Adamson1,2

1School of Biomedical Engineering, Dalhousie University; 2Department of Electrical and Computer

Engineering, Dalhousie University

Introduction: We demonstrate techniques for the visualization and processing of optical coherence

tomography (OCT) data for presentation in a clinically relevant and intuitive manner. We also propose a

suitable software framework to support such processing and visualization while being flexible, reliable,

stable and supportable. Topics to be covered are: The 3D visualization of OCT data in real-time using

volumetric ray-casting and geometrical correction of volumetric OCT data. These processing steps are

implemented within a software architecture capable of supporting the range of functionality required in

a clinical imaging system.

Methods: We render 3D OCT middle ear images using a custom image processing pipeline centered on

a volumetric ray-casting engine. When an OCT volume stack of a middle ear is visualized using

volumetric ray-casting, a 3D array containing the image data is created. A cube is then formed within a

virtual 3D space that represents the physical bounds and geometric properties of the OCT dataset.

Geometric transformations of the cube are efficiently computed on a graphics processing unit (GPU) and

the projection of the cube faces onto a viewing surface are used to calculate voxel data from the array for

visualization. This approach allows straightforward application of custom processing steps developed for

middle ear OCT images, namely removal of the eardrum from images and remapping of OCT data

acquired along a spherical grid to an undistorted Cartesian grid. These features are implemented within

the context of a new software framework for acquiring, processing and displaying OCT image data that

provides a real-time, intuitive, and flexible development platform.

Results and Discussion: We present benchmark results comparing our ray-caster to the leading open-

source 3D rendering engine and demonstrate specific capabilities of the renderer relevant to middle ear

imaging. Design considerations in a clinical imaging system suitable for multi-site deployment are

discussed.

Conclusion: The processing pipeline and supporting architecture appear well-suited to use in clinical

real-time imaging applications.

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PATIENTS NOT REPORTING IMPROVEMENTS IN PAIN AND FUNCTION

POST-TOTAL KNEE ARTHROPLASTY DEMONSTRATE POOR

IMPROVEMENT DURING GAIT

Kathryn Young1, M.J. Dunbar1,2 and J.L. Wilson1,2

1School of Biomedical Engineering, Dalhousie University; 2Department of Surgery, Dalhousie

University

Introduction: Over 20% of osteoarthritis (OA) patients do not report clinically relevant pain and

function improvements after total knee arthroplasty (TKA). This study 1) examined if patients not

reporting meaningful improvements (non-responders) demonstrated improvements during gait, and 2)

characterized baseline features of non-responders, to aid in preoperative identification.

Methods: Forty-six patients underwent gait analysis and completed Western Ontario and McMaster

University Osteoarthritis Index (WOMAC) questionnaires pre- and one-year post-TKA. Pain and

function non-responders were defined by changes ≤23 and 19 on WOMAC sub-scores. Within group

pre/post-TKA gait differences were compared by paired t-tests. Regression models examined pre-TKA

features contributing to being a responder in pain and function.

Results and Discussion: Pre-TKA, non-responders in pain (12/46) and function (10/46) had less OA

severity(p=0.030), and pain non-responders were less symptomatic(p=0.037) and walked at slower

speeds(p=0.041). Post-TKA, both non-responder groups showed reductions in dynamic varus angle

magnitudes(p≤0.005) and pain non-responders had an increase in flexion moment range(p=0.029).

Responders showed reductions in dynamic varus magnitudes, and improved adduction moment, flexion

moment and flexion angle mechanics(p≤0.028). From regression, larger dynamic varus magnitudes

contributed to less gains in self-reported pain. Greater BMI and less severe sagittal features contributed

to less gains in self-reported function.

Conclusions: Non-responders in self-reported pain and function demonstrate poor objective function

improvements during gait. Pre-operative characterization of non-responders may aid identifying clinical

subgroups who are at greater risk of poor outcomes from standard TKA.

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School of Biomedical Engineering Research Day 2018 Abstracts

SCIENTIFIC SESSION 2

16

A SMALL ULTRASOUND DEVICE FOR IMAGING AND ABLATION OF

CEREBRAL TISSUE

Jeffrey Woodacre1 and J. Brown1

1 School of Biomedical Engineering, Dalhousie University

Introduction: Histotripsy is an ultrasonic ablation technique used to non-thermally liquify soft-tissue in

the body using cavitation, causing no damage to surrounding tissue. Previous work has shown that a

round, 10 mm diameter histotripsy device with a 7 mm focus can ablate cerebral tissue while being co-

registered with ultrasound imaging to provide feedback of the ablation site. This 10 mm co-registered

device was the first step in the development of an endoscopic histotripsy device. The next step, and what

is presented in this work, is the development of a truly endoscopic form factor: a 5 mm x 5 mm square

histotripsy transducer but without co-registration.

Methods: A KLM model for a 5 mm x 5 mm square transducer was created to determine optimal design

parameters prior to fabrication. An aluminum lens was machined using a CNC milling technique and

attached to a 5 MHz, 1-3 piezoelectric composite using Epotek 301 epoxy. An inductor was placed in

series with the composite to improve acoustic power output and the entire device was sealed in a 3D

printed casing with a parylene matching layer deposited on the lens face for optimal output at 6.8 MHz.

Device pressure was measured using a needle hydrophone and cavitation was attempted using our in-

house pulser design.

Results and Discussion: The device was found to be capable of causing a cavitation bubble cloud when

reflecting off a high impedance surface (shock-scattering histotripsy), but will need a higher driving

voltage to cavitate at the intrinsic cavitation threshold. Pressure field is less focused than for the previous

device iteration.

Conclusion: A 5 mm x 5 mm device was successfully shown to be capable of cavitation , and is likely

the basis for the miniature endoscopic iteration of a co-registered ablation device.

17

TRANSMISSION ELECTRON MICROSCOPY REVEALS NEW DETAILS OF

THE INITIATION OF COLLAGEN FIBRIL DAMAGE DURING TENDON

OVERLOAD

Jasmin Astle1, E.D. Sone2, B.D. Quan2, S.P. Veres1,3 and J.M. Lee1

1School of Biomedical Engineering, Dalhousie University; 2Institute of Biomaterials and Biomedical

Engineering, University of Toronto; 3Division of Engineering, Saint Mary’s University

Introduction: Mechanically overloaded bovine tail tendons display “discrete plasticity”: nano-scale

damage that occurs in the form of kinks in collagen fibrils. Three techniques that can be used to visualize

nano-scaled damage include: scanning electron microscopy (SEM), atomic force microscopy (AFM),

and transmission electron microscopy (TEM). Discrete plasticity damage has been explored via SEM of

longitudinally sectioned tendon, and AFM of single collagen fibrils. We have used TEM to further

investigate overloaded bovine tail tendons. This technique offers new information about the mechanism

of damage in fibrillar collagen.

Methods: Damage was induced in bovine tail tendons via 5 sub-rupture overload cycles. Fibres were

isolated from damaged tendons, fixed and en bloc stained. Samples were then dehydrated and embedded

in EMbed 812 resin. Sections (~70 nm) were taken using an EM UC6-NT ultramicrotome, post-stained

with uranyl acetate, and imaged using an FEI Tecnai-12 TEM.

Results and Discussion: TEM has revealed what may be the initiation of discrete plasticity damage

within fibrils: dark-staining, longitudinally offset patches, located on opposite margins of a fibril. These

dark patches may indicate increased exposure of charged amino acids to staining due to a disruption in

the organization of collagen at the molecular or supramolecular level. This is consistent with denatured

collagen present at discrete plasticity kinks observed with SEM. A breakdown of some fibrils into their

more intensely staining subfibrillar components, along with slanted D-banding, have been identified in

both damaged and undamaged tendons.

Conclusions: These results may suggest that localized changes in collagen supramolecular organization

are not always translated to the formation of kinks in fibrillar collagen.

18

CHEMOTHERAPEUTIC-LOADED POLYPHOSPHATE GLASS

MICROSPHERES FOR TRANSARTERIAL CHEMOEMBOLIZATION

Hayden Nix1, A. Momeni1, D. Chevrier2 and M.J. Filiaggi2

1School of Biomedical Engineering, Dalhousie University; 2Department of Applied Oral Sciences,

Dalhousie University

Introduction: The standard of care for patients suffering from intermediate stage hepatocellular

carcinoma is transarterial chemoembolization (TACE), a procedure involving the injection of

chemotherapy (e.g., doxorubicin or DOX) and an embolic agent into the tumour’s vasculature.

Polyphosphate glass microspheres (PGM) that are resorbable, radiopaque, and hemostatic are currently

under development as an improved TACE treatment platform. This work evaluates the capacity of PGMs

to be loaded with DOX and the mechanisms of drug release.

Methods: Coacervate, a viscous colloid-rich liquid, was synthesized by dissolving sodium

polyphosphate glass in water and adding Ba2+, Ca2+, and Cu2+ to facilitate precipitation. Coacervates were

loaded with DOX by freeze-drying and rehydrating the coacervate with an aqueous DOX solution. DOX-

loaded coacervate was subsequently injected into a water-in-oil emulsion, yielding DOX-loaded PGMs.

In vitro drug release and degradation studies were conducted by submerging PGMs contained within

dialysis tubing in different elution media (pH 6.5 or 7.4) at 37C for 28-days. Eluted DOX concentration

was measured at 480nm absorbance.

Results and Discussion: Synthesis conditions were optimized to yield DOX-loaded PGMs that were

spherical, with high yields in the clinically relevant 100-300µm size fraction. In vitro DOX release was

shown to be mediated by the pH of the elution media, with a linear release profile exhibited at pH 6.5

and essentially limited or no release at pH 7.4.

Conclusion: PGMs can be loaded with DOX, and release DOX at a sustained rate via a pH-mediated

mechanism. PGMs hold promise as a novel TACE treatment platform.

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RESPIRATORY IMPEDANCE MODELLING PREDICTIONS USING GRADED 3He INHALED GAS MAGNETIC RESONANCE IMAGING

Cody Church1, H. Young3,4, D. Capaldi3,4, G. Parraga3,4,5 and G.N. Maksym1,2

1Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, Canada; 2School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia, Canada; 3Robarts

Research Institute, The University of Western Ontario, London, Canada; 4Department of Medical

Biophysics, The University of Western Ontario, London, Canada; 5Graduate Program in Biomedical

Engineering, The University of Western Ontario, London, Canada

Introduction: Asthma is characterized by airway narrowing and small airway closures directly observed

by accumulation of ventilation defects visible by magnetic resonance imaging (MRI), as well as increased

impedance as assessed by oscillometry. However, the changes in the impedance that can be predicted by

the images do not agree. One limitation is that binary images are used. Here we explore using k-means

clustering algorithm to more accurately model impedances in asthma.

Methods: An anatomically-derived airway tree from high-resolution computed tomography with 64,895

airways was scaled to MRI images from 8 patients by rigid-registration and scaled from total lung

capacity (TLC) to functional residual capacity (FRC), followed by a deformable registration using the

multi-modality independent neighborhood descriptor. For each patient, impedance was simulated in two

ways, 1st for a defect lung with binary closures and 2nd for a tree with a graded-closure scheme.

Results and Discussion: Registration accuracy by the percent volume overlap was 81 +/- 1%. Modelling

impedances for a lung with a graded-closure scheme exhibited little to no changes to the high frequency

dependence (> 20 Hz). Qualitatively, impedance predictions for the graded-closure scheme better typified

the typical asthmatic. Quantitatively, comparing the defect (binary) model to the graded-closure model,

the resistance at 5 Hz increased by 260 +/- 60%, and the reactance at 5 Hz decreased by 1000 +/- 600 %.

Conclusions: A graded-closure scheme dramatically affected the impedance predictions in the low

frequency regime (≤ 5Hz), with the characteristic frequency dependence seen in asthma. Utilizing the

greater information present in MRI provided better impedance predictions, associated with small-airway

mechanics important in asthma.

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School of Biomedical Engineering Research Day 2018 Abstracts

SCIENTIFIC SESSION 3

21

TRUNK REPOSITIOINING SENSE IS RELATED TO CHANGES IN TRUNK

MUSCLE ACTIVATION PATTERNS DURING CONTROLLED LIFTING

Adam Quirk1, R.D Trudel2 and C.L. Hubley-Kozey1

1School of Biomedical Engineering, Dalhousie University; 2Department of National Defence

Introduction: Control of joint stability requires accurate sensory feedback to modify muscle activation

to changing external forces. Theoertical models suggest that those with less percise feedback control

must change muscle activation to ensure joint stability. Yet there is little supporting evidence. The

purpose of this study was to determine whether trunk positioning sense is related to trunk muscle

activation patterns during a controlled dynamic lifting task.

Methods: 40 participants, recruited from a military population, performed a highly controlled dynamic

lifting (HTT) task. Electromyograms (EMG) were collected from 24 trunk muscle sites. Spatial-temporal

EMG features were determined from principal component (PC) analysis on time and amplitude

(maximum voluntary isometric) normalized ensemble average waveforms. Proprioception was assessed

using a trunk repositioning task where participants were positioned in a standard seat position. For 5 trials

participants attempted to match this position from a slumped seated position with their eyes closed.

Relative trunk angle was measured in the sagittal plane and absolute error was calculated for each trial

vs. the standard position. Participants were separated into two groups (high or low proprioception error

(PE)) based on a median split of the absolute error. Mixed model ANOVA (group, muscle) were

conducted on PC scores (α=0.05).

Results and Discussion: There were no demographic differences (sex, mass, height, age) between

groups. For the back extensors PC2 (differential response to the lateral flexion moment) captured a group

main effect showing high PE were less responsiveness using frontal plane antagonist co-activation

compared to low PE. For the abdominals PC1 (overall magnitude) had a group main effect showing high

PE had higher antagonist activation than low PE.

Conclusions: These results suggest those with less ability to sense the position of their trunk adjust

muscle activation patterns to increase and sustain general trunk stiffness, thereby reducing their reliance

on feedback control to adjust muscular activation.

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THE EFFECTS OF OPTICAL CLEARING AGENTS ON TYMPANOPLASTY GRAFT

MATERIALS FOR USE IN MIDDLE EAR OPTICAL COHERENCE TOMOGRAPHY

Francis Morin1, M. Khalid-Raja2, C. Morrisson3, D. McDougall1, R. Adamson1,4 and D.P. Morris2

1School of Biomedical Engineering, Dalhousie University; 2Department of Surgery, Dalhousie

University; 3Division of Otolaryngology, Nova Scotia Health Authority; 4Department of Electrical and

Computer Engineering, Dalhousie University

Introduction: Optical coherence tomography (OCT) is a novel non-invasive modality for imaging

structures in the middle ear. While OCT can produce excellent images through normal tympanic

membranes, ears that have tympanoplasty grafts are difficult to image due to the opacity of typical graft

materials. We assess the optical opacity of commonly used tympanoplasty materials including

perichondrium, fascia, and cartilage. We also examine the use of biocompatible optical clearing agents

(OCA) and penetration enhancers (PE) including glycerine, propylene glycol, polypropylene glycol,

polyethylene glycol and hyaluronic acid.

Methods: The optical attenuation of OCT illumination through grafts was assessed in vitro by imaging

the materials in front of a calibrated reference reflector. OCAs and PEs were tested on porcine auricular

cartilage and on human perichondrium, cartilage and fascia harvested from consenting patients during ear

surgeries. Human graft materials were placed into a cadaveric temporal bone model and treated with

OCAs. OCT images of these temporal bones obtained before and after treatment with OCA were assessed

for image quality and signal-to-noise ratio (SNR) in specific anatomic regions of interest.

Results and Discussion: Graft type, thickness and hydration determine transparency. While untreated

cartilage grafts severely limit middle ear OCT SNR, OCA treatment decreases graft optical attenuation

and dramatically improves image quality and SNR.

Conclusions: Many otology patients have a history of tympanoplasty. Our results show that OCAs offer

a viable pathway for improving the transparency of grafts and have the potential to greatly expand the

clinical utility of middle ear OCT.

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THREE-DIMENSIONAL ULTRASOUND IMAGING RESULTS AND

DEVELOPMENT OF AN ENDOSCOPIC CROSSED ELECTRODE ARRAY

Kate Latham1, C. Samson1, A. Bezanson1 and J. Brown1

1School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia

Introduction: Ultrasound systems based on 2D matrix arrays capable of 3D imaging present several

technical challenges including the number of elements/beamforming channels, the high impedance of the

small elements, and image acquisition time for a 3D volume. The fabrication challenges become

insurmountable both at high frequencies and when packaging in an endoscopic form factor. Crossed

electrode arrays have addressed some of these issues, especially the huge reduction in number of elements

(2N compared to N2). For this reason, we have adopted this type of array design for our high frequency

3D imaging system.

Methods: A 10MHz, 128 element crossed electrode relaxor array was fabricated on a electrostrictive 1-

3 composite and was tested to demonstrate the performance of the array and imaging scheme.

Development is now focused on a 30MHz version of the array packaged into an endoscopic form factor.

A crucial challenge in miniaturizing the probe design is electrically connecting to elements on the front

side and back side of the array without adding packaging bulk. A process has been developed to bring

the back side connections to the front face which allows the final size of the tip of the probe to measure

only 4.4 x 5.4 mm. The testing setup for the 30MHz array includes the in-house developed high frequency

beamformer with a new 64 channel high voltage biasing module.

Results and Discussion: 3D images were generated by imaging a two-wire phantom in a water bath

using a reconfigurable acoustic Fresnel lens to focus to 32 elevation slices to build up the volume image.

Conclusions: The previously presented 10MHz 2D array has been translated into the development of the

first high frequency endoscopic crossed electrode imaging array.

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School of Biomedical Engineering Research Day 2018 Abstracts

SCIENTIFIC SESSION 4

25

SPARSE ORTHOGONAL DIVERGING WAVE IMAGING ON A HIGH-

FREQUENCY PHASED ARRAY

Chris Samson1, R. Adamson1,2 and J. Brown1,2

1School of Biomedical Engineering, Dalhousie University; 2Department of Electrical Engineering,

Dalhousie University

Introduction: Ultrafast imaging techniques have emerged as having an advantage over conventional B-

mode imaging techniques. Ultrafast imaging opens applications where >1000 fps is required to resolve

various phenomena such as shear and mechanical wave propagation. The measurement and analysis of

these waves offer clinically significant insight into the physiology of tissue that cannot be obtained from

conventional B-mode images. This work presents a new ultrafast imaging technique whereby orthogonal

Hadamard codes are surfed onto a diverging wave and is the first implementation of ultrafast imaging on

a high-frequency phased array.

Methods: Hadamard codes allows for a synthetic aperture (SA) beamforming strategy where all elements

are pulsed simultaneously, thereby increasing the SNR by √𝑁 compared to conventional SA

beamforming, where N is the number of array elements. A complete set of orthogonal basis codes is

defined by N Hadamard codes. The number of codes can be reduced by sparsely selecting rows from the

Hadamard encode matrix so that the codes containing the lowest spatial frequency components are used.

When an incomplete set of Hadamard codes are used the directivity deteriorates. This drawback is

mitigated by surfing the encoded waves on a diverging wave. The directivity and sidelobe levels are

compared for 64, 32, 16, 8, and 4 Hadamard codes.

Results and Discussion: The sidelobe levels were simulated to be at -65, -60, -58, -53, and -48 dB for

64, 32, 16, 8, and 4 Hadamard encoded emission events. Using the above-mentioned numbers of

Hadamard codes, the FWHM directivity is 56ᶿ, 52ᶿ, 48ᶿ, 40ᶿ, and 50ᶿ, compared to 56ᶿ, 30ᶿ, 22ᶿ, 22ᶿ, and

20ᶿ when the Hadamard codes are not surfed on a diverging wave.

Conclusion: Preliminary results favor the use of sparse orthogonal diverging wave imaging as a method

for trading off frame rate and image quality for high-frequency phased arrays.

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SYNTHESIS, CHARACTERIZATION, AND RISK ASSESSMENT OF A NOVEL

DEGRADABLE, IMAGEABLE UTERINE ARTERY EMBOLIC AGENT

Jensen Doucet1 and D. Boyd1

1School of Biomedical Engineering, Dalhousie University

Introduction: Transarterial embolization (TAE) is a minimally invasive procedure proven to reduce

hospital stays, health care costs, and recovery times, all while maximizing quality of life for patients.

Next generation microspheres for TAE are required to be degradable and exhibit multi-modal

imageability. Controlled modifications to borate networks may permit the development of such materials

for TAE. Accordingly, two series of novel borate networks were investigated as candidate degradable

radiopaque embolic agents for use in uterine artery embolization.

Methods: The effect of substitutions of SrO or Ga2O3 for Rb2O on the structure and contiguous properties

of borate networks was evaluated. Glasses were characterized using density, differential scanning

calorimetry, 11B MAS-NMR. Multimodal imageability was assessed with CT and MRI. Degradation

characteristics and mass loss were assessed using simulated physiological conditions using cell culture

media supplemented with FBS at 37°C, over 6, 12, 24, 36, and 48 hours.

Results and Discussion: 11B NMR showed that increasing substitution of Sr causes a slight decrease in

tetrahedrally coordinated boron, while increasing substitutions of Ga decreased tetrahedrally coordinated

boron substantially in the networks. Degradation rates were controlled by composition and structural

chemistry and ranged from 100% degradation at 6h to 40% degradation at 48 h. All compositions were

found to exhibit significant radiopacity upon CT imaging with values of over 3200 HU at 120 kVp,

without confounding MRI scanning protocols.

Conclusions: Controlled compositional and structural modifications to borate networks provides a

platform for the development of next generation embolic microsphere therapies.

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THERMOMECHANICAL ANALYSIS OF COLLAGEN CROSSLINKING IN THE

LUMBAR INTERVERTEBRAL DISC ANNULUS

Tyler Herod1, J.M. Lee1 and S.P. Veres1, 2

1School of Biomedical Engineering, Dalhousie University; 2Division of Engineering, Saint Mary’s

University, Halifax, Canada

Introduction: Low back pain is often attributed to damage to the posterior region of the lumbar

intervertebral disc annulus, which contains fewer, thinner lamellae compared to other regions. Little is

known about the how the annulus’ structure varies at smaller levels in the collagen hierarchy. In this

study we investigated how the thermal stability and crosslinking of collagen molecules within the

annulus of lumbar discs changes with both circumferential location and disc level.

Methods: Small rectangular bone-annulus-bone samples were cut from the anterior and posterior

regions of the lumbar spines of mature ewes. Matched-pair anterior-posterior samples were split between

three groups: (i) hydrothermal isometric tension (HIT) testing, (ii) HIT testing with sodium borohydride

treatment, and (iii) differential scanning calorimetry (DSC). For HIT experiments, the denaturation

temperature and half-time of load decay were determined. For DSC experiments, the onset temperature,

peak temperature, full-width at half-maximum, and specific enthalpy were calculated.

Results: Molecular-level collagen structure of the disc annulus varied significantly with circumferential

location, but not disc level. Collagen molecules in the posterior annulus showed significantly greater

thermal stability and higher levels of thermally-stable intermolecular collagen crosslinking when

compared to the anterior annulus.

Conclusions: Significant variations in collagen structure of the lumbar disc annulus exist. Compared to

the anterior, the posterior annulus is composed of more robustly structured collagen fibrils, which may

be an important factor in compensating for its microstructural shortcomings. If so, deficiencies at this

fine level of collagen structure may put the posterior annulus at risk of mechanical failure, leading to

painful tears or herniation.

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PHOTOACOUSTIC TOMOGRAPHY FOR USE IN ENDOSCOPIC BRAIN

SURGERY

Taylor Landry1 and R. Adamson1

1Department of Biomedical Engineering, Dalhousie University

Introduction: In previous work, our group has demonstrated the use of an endoscopic 64-element phased

ultrasound array that operates with a center frequency of 45MHz. Even though this device is suitable for

brain surgery and can be used to image soft tissue, it does not provide the contrast necessary to image

vasculature. The ability to image vasculature would allow surgeons to avoid major blood vessels and to

closer resect tumors such as glioblastomas.

Methods: Building upon the previous work by modifying the 64-element phased array, we include

photoacoustic tomography (PAT): an imaging modality that uses light and sound waves to produce an

image. The resultant pressure waves produced by this modality can be recorded using the phased array

transducer and the high optical contrast combined with the higher resolution of ultrasound will allow for

the imaging of vasculature. As a preliminary experiment, a 1.2 mm diameter piston transducer and an

808 nm diode laser with 0.52 mJ of pulse energy were used to collect the ultrasound and photoacoustic

images of a 40 µm diameter hair. Measurements of the lateral resolution for both ultrasound and PAT

were recorded and compared to theory.

Results and Discussion: From scans taken in 0.02 mm increments in the cross-sectional plane of the

hair, the FWHM lateral resolution was found to be 0.32 mm and 1.36 mm for ultrasound and PAT

respectively. In comparison with theoretical calculations of the increase in resolution between ultrasound

and PAT the results were found to be as expected.

Conclusions: Using the simplified case of a single-element ultrasound transducer, a photoacoustic signal

was successfully obtained.

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