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Medical Biophysics

COURSE MODULES

2017-2018

Course Modules 2017-2018

• Scientific Exposition & Ethics (mandatory) (Fri. Sept 15 – Oct 27) • Introductory Biostatistics (mandatory) (Mon. Nov 6 – Dec 18) • Biostatistics II: Data Science (Mon. Jan 8 – Feb 19)

Biology Physics

• Tumour Microenvironment (Thur. Sept 14 – Oct 26) • Radiation Biology and DNA Repair (Mon. Oct 30 –

Dec 11) • Epigenetics (Thur. Nov 2 – Dec 14) • Development, Stem Cells and Cancer (Mon. Jan 8

– Feb 19) • Cancer Immunotherapy (Thur. Mar 1 – Apr 19) • Clinical & Experimental Radiobiology I & II (Mon.

Apr. 9 – Apr. 13, inclusive full day. Equivalent to 2 modules)

• Medical Device Innovation and Entrepreneurship (Thur. Sept 7 – Dec 14)

• Overview of Medical Imaging (Wed. Sept 13 – Oct. 25)

• Biophysics of Focused Ultrasound (Tue. Nov 7 – Dec 19)

• Advanced Magnetic Resonance imaging (Wed. Nov 8 – Dec 20)

• Introduction to Bio-Microscopies (Tue. Jan 9 – Feb 20)

• Ultrasound Overview (Wed. Jan 10 – Feb 21) • Biological Imaging (Thur. Jan 11 – Feb 22) • Advanced Ultrasound (Wed. Feb 28 – Apr. 18) • Cell Biology for Physical Scientists (Spring 2018) • Clinical Imaging for Physical Scientists (Mon. Mar.

5 – Apr. 23) • Magnetic Resonance Imaging – Overview (Tues.

Mar 6 - Apr 24) • Biophotonics (Fri. Mar. 9 – Apr 27)

The following modules are planned for 2018-2019.

• Scientific Exposition & Ethics • Introductory Biostatistics • Biostatistics II: Data Science

Biology Physics

• Cell Signaling & Metabolism • Cell Biology & Cancer Models • Quantitative Cancer Genomics • Predictive Oncology & Therapeutics • Structural Biology & Proteomics • Clinical & Experimental Radiobiology I & II

• Medical Device Innovation and Entrepreneurship (Fall 2018) • Overview of Medical Imaging • Cell & Molecular Biology for Physicists -

Introduction • Introduction to Biophotonics • Biophysics of Focused Ultrasound & Thermal

Therapy • Advanced Magnetic Resonance Imaging • Introduction to Bio-Microscopies • Clinical Imaging for Physical Scientists • Nanotechnology for Medicine • Biological Imaging • Magnetic Resonance Imaging – Overview • Ultrasound – Overview

Fall 2017

TOPIC Scientific Exposition and Ethics - MANDATORY

Coordinators Drs. David Malkin and Jim Woodgett

Day & Time Fridays, 2:00 pm – 4:00 pm

Location Princess Margaret Cancer Research Tower, 101 College St., Room 4-204

Module Goals

Scientific exposition, discourse and ethics are fundamental principles to the conduct of responsible basic, translational and clinical research. This course will use a combination of didactic lectures and interactive group discussion to explore key elements of these principles under the broad headings of: 1) Principles of Ethical Conduct and Protection of Research Subjects; 2) Scientific Fraud, Plagiarism and Data Misrepresentation – Flagrant and Unintended; 3) Privacy and Confidentiality in the Genome Era (Data Sharing/Validation/Clinical Translation); and 4) Authorship Responsibility in the Spirit of Collaboration and Intellectual Property Protection. The format of each lecture will be both didactic, with the lecturer discussing fundamental issues and principles relevant to the topic, and interactive with opportunity for open discussion of a foundational aspect of the subject being addressed in the lecture.

Evaluation Method

End of course exam with a combination of short- and long- answer questions based on information discussed in the lectures, and supplemented with materials provided by the lecturers, and an end-of-course assignment which will be an essay discussing one aspect of the course – topics provided by the course co-directors. The ‘exam’ will count for 50% of the final mark and the in-class problem/discussion session will count for 50%.

Schedule Date Instructor Lecture

Sept. 15 Jim Woodgett Introduction to research ethics: responsibilities and best practices

Sept. 22 David Malkin Authorship Responsibility in the Spirit of Collaboration and Intellectual Property Protection

Sept. 29 Ivan Topisirovic Biomedical Research: Ethos, Logos... and Pathos (on research misconduct)

Oct. 6 Beth Stephenson Principles of Ethical Conduct and Protection of Research Subjects

Oct. 13 Steve Scherer Privacy and Confidentiality in the Genome Era (Data Sharing/Validation/Clinical Translation)

Oct. 20 Jim Woodgett and David Malkin Problem-Based Discussion – class participation

Oct. 27 Exam

Fall 2017

TOPIC Introductory Biostatistics - (Mandatory— 1st year students must take a biostatistics module –either Introductory or Advanced in Winter 2018)

Coordinators Dr. Jason Lerch

Day & Time Mondays, 2:00 pm – 4:00 pm*

Location Princess Margaret Cancer Centre 610 University Ave. 6th floor auditorium*

Module Goals This course will serve as a rapid introduction to probability and statistical thinking. Students will gain a thorough understanding of how statistical inference is conducted and will, by the end of the course, be able to critically assess our use of statistics in the search for scientific truths.

Evaluation Method End of module exam and a significant component of in class participation. Schedule Date Instructor Lecture

Nov. 6 J. Lerch Introduction. Distributions, histograms, plots and descriptive statistics

*Nov. 13 1:30-3:30 room 6-702/703/704

J. Lerch Least squares regression, correlations, and linear models.

Nov. 20 J. Lerch Sampling, experiment design, and concepts in statistical inference.

Nov. 27 J. Lerch Probability in all its glory.

Dec. 4 J. Lerch Hypothesis testing, searching for truth, and the crisis of replicability.

Dec. 11 J. Lerch Intro to Bayesian statistics. *Dec. 18 room 6-702/703/704

Exam

Winter 2018

TOPIC Biostatistics II: Data Science (Mandatory — 1st year students must take a biostatistics module –either Introductory in Fall 2017 or Advanced)

Coordinators Dr. Paul Boutros

Day & Time Mondays at 10:00 am – 12:00 pm

Location Princess Margaret Cancer Centre 610 University Ave. 6th floor auditorium*

Module Goals

This module is a graduate level course in advanced biostatistics. It covers both theory and application in four discrete areas: statistical communication, machine-learning, time-to-event models and Bayesian statistics. Students will have an in-depth course-project applying these techniques to real-world datasets from their own research.

Evaluation Method One Assignment, Course Project.

Schedule

Date Instructor Lecture Jan. 8 (10-noon) P. Boutros Statistical Thought

*Jan. 12 (10-noon) room 6-702/703/704

P. Boutros Machine-Learning I: Theories & Architecture

*Jan. 12 (1-3pm) room 6-702/703/704

P. Boutros Machine-Learning II: Lpearners & Hyper-Parameters

Jan. 15 (10-noon) P. Boutros Time-To-Event Modeling

Jan 29 (10-noon) P. Boutros Bayesian Thinking

Feb. 19 (10-noon) P. Boutros Course Project Presentations

Medical Biophysics

BIOLOGY COURSE MODULES

2017-2018

Fall 2017

TOPIC Tumour Microenvironment

Coordinators Drs. Rama Khokha & Bradly Wouters

Day & Time Thursdays, 9:00 am – 11:00 am

Location Princess Margaret Cancer Centre, 610 University Ave, Room 7-605

Module Goals

The tumor microenvironment (TME) is a complex entity in human cancers. It is constituted by multiple structural and cellular aberrations that arise during tumorigenesis. How cellular and molecular features of TME underlie tumor development and progression, as well as how these characteristics form the basis for new biomarkers and cancer therapies will be covered in this topic.

Evaluation Method Attendance/Participation/ Presentation (60%) Exam (40%)


Sept 14 Trevor McKee Imaging TME

Sept 21 Brad Wouters Understanding and Targeting Hypoxia in TME

Sept 28 Aaron Schimmer Mitochondrial Contributions to TME

Oct 5 Rama Khokha Contribution of Proteolysis to Shaping TME

Oct 12 Tracy McGaha Immune Microenvironment of Tumors

Oct 19 Thomas Kislinger Extracellular Vesicles and TME

Oct 26 Exam

Fall 2017

TOPIC Radiation Biology & DNA Repair

Coordinators Dr. Marianne Koritzinsky & Dr. Razq Hakem

Day & Time Mondays,10:00 am – 12:00 pm

Location Princess Margaret Cancer Research Tower, 101 College Street, Room 4-204*

Module Goals

DNA repair is critical for maintaining genomic integrity and its defects increase cancer risk. In addition, mutations in genes involved in DNA damage signaling or repair have also been associated with other human diseases and syndromes. DNA damage can also be induced to treat cancer patients as is the case for radiotherapy and a number of genotoxic anti-cancer drugs widely used in the clinics. This module will focus on DNA damage repair mechanisms and the physiological response to DNA insults, including radio- and chemo- therapies.

Evaluation Method Presentation/discussion of scientific papers and participation in weekly lectures


Oct. 30 Marianne Koritzinsky Introduction to Radiation Biology

Nov. 6 Razq Hakem Preclinical models to study mechanisms of DNA double strand breaks repair and their role in cancer

Nov. 13 Karim Mekhail R-loops, DNA repair and genomic instability

*Nov. 20 Princess Margaret, 610 University Ave. room 7-605

Dick Hill Stem cells and tumor growth in response to radiation

Nov. 27 Benjamin Lok Clinical Radiotherapy Overview and Predictive Biomarkers in the Clinic

Dec. 4 Stan Liu Tumor microenvironment and radiation response

Dec. 11 David Malkin The role of p53 in cancer development

Fall 2017

TOPIC Cancer Epigenetics

Coordinators Dr. Daniel De Carvalho & Dr. Hansen He



Module Goals

Epigenetic regulation is critical in cancer development and progression. Moreover, epigenetic modifications can be used as therapeutic targets as well as biomarkers in cancer. This course will introduce basic concept in epigenetics and the frontiers in cancer epigenetics. Each class will consist of a one-hour student lecture reviewing the day’s topic, followed by a one-hour student-led interactive discussion around the specific papers.

Evaluation Method

Presentation and participation in discussion. Each student will be responsible for a lecture topic review to be held in the first hour (35% of their grade) and for a scientific manuscript presentation in the second hour (35% of their grade) of each lecture. All other students are expected to contribute to the scientific manuscript discussion in each lecture (30% of their grade). Lecturers will provide the lecture topic and suggest manuscripts to be discussed at least two weeks prior to the lecture date. The selected scientific manuscripts will need to be shared with all students at least one week before the lecture. Lecturers will be available in person or by email to provide an optional review of the students’ proposed presentation and discussion plan. The lecturers are responsible for assigning the student’s grade using an evaluation form common across all of the lectures.


Nov. 2 Hansen He & Daniel De Carvalho Course overview and setting expectations

Nov. 9 Cheryl Arrowsmith Chemical biology approaches to cancer epigenetics

Nov. 16 Mathieu Lupien Functional epigenetics

Nov. 23 Daniel De Carvalho Epigenetics in immunotherapy

Nov. 30 TBD Epigenetics in Molecular Pathology

Dec. 7 Michael Hoffman Machine Learning in Epigenomics

Dec. 14 Hansen He Frontier in Epitranscriptomics

Winter 2018

TOPIC Development, Stem Cells and Cancer

Coordinators Dr. Norman Iscove

Day & Time Mondays, 2:30 pm – 4:30 pm

Location Princess Margaret Cancer Research Tower, 101 College Street, TMDT, Room 4-204

Module Goals

This module will cover the nature, biology, medical applicability and cancer relevance of stem cells. It is tailored for students from physics/engineering backgrounds with minimal prior exposure to biology. The topics will be developed in a 6-session lecture series. Each topic, listed below, will be covered in 2 hr. Conceptual mastery within each topic will be tested in a written exam at the end of the series.

Evaluation Method Written examination Schedule Date Instructor Lecture

Jan 8 G. Keller Principles of embryonic development applied to derivation of adult cells and tissues from embryonic stem cells

Jan 15 J. Dick Concepts of "stemness" in human normal and leukemic hemopoiesis

Jan 22 N. Iscove Stem cells, self-renewal and the origin of leukemia

Jan 29 R. Khokha Architecture, regulation and microenvironment in the mammary epithelial stem cell system

Feb 5 C. O’Brien Architecture, regulation and microenvironment in normal and malignant gastrointestinal stem cell systems

Feb 12 L. Ailles Detection and quantitation of cancer stem cells and microenvironmental impact in epithelial and mesenchymal cancers

Feb 19 Written examination

Winter 2018

TOPIC Cancer Immunotherapy

Coordinator Dr. Tracy McGaha

Day & Time Thursdays, 2:00 pm – 4:00 pm


Module Goals

Immunotherapy has generated great excitement in the oncology community and has revolutionized clinical approaches to cancer therapy. While direct targeting of immune bottle-necks has shown promise in a range of cancer types, it is now becoming clear that many other therapeutic approaches owe their efficacy partially through induction of anti-tumour immunity. The course will cover general approaches to cellular and biologics mediated targeting of cancer, the impact of chemotherapy on anti-tumour immunity and clinical management of cancer from an immune-oncology perspective including discussion of adverse reactions to immunotherapy including the autoimmune pathology.

Evaluation Method

Schedule

Date Instructor Lecture

March 1 Tracy McGaha Targeting the TME (macrophages and beyond)

Mar 8 Daniel de Carvalho Intersection of chemotherapy and immunotherapy

Mar 15 Pamela Ohashi Tumour infiltrating lymphocyte infusion therapy: Concept and practical challenges

Mar 22 Marcus Butler Clinical considerations for immunotherapy (adverse responses and clinical management)

Mar 29 Jayne Danska Checkpoint inhibition therapy

Apr 5 Naoto Hirano Cellular engineering for immunotherapy

Apr 12 No Class

Apr 19 Evaluation

Winter 2018

MONDAY APRIL 9, 2018 Time Lecture Faculty speakers 8:45-‐9:00 Coffee served 9:00-‐9:30 Introduction to course Marianne Koritzinsky 9:30-‐10:15 1 Importance of radiobiology in the clinic Scott Bratman 10:15-‐10:30 Break 10:30-‐11:15 2 Hallmarks of cancer Marianne Koritzinsky 11:15-‐12:00 3 Radiation induced damage and the DNA damage response Brad Wouters 12:00-‐1:00 Lunch 1:00-‐1:30 T1 Tutorial and Question period (L2,3) Marianne, Brad 1:30-‐2:15 4 Molecular basis of cell death Brad Wouters 2:15-‐3:00 5 Cell survival -‐ in vitro and in vivo Bert van der Kogel 3:00-‐3:15 Break 3:15-‐4:00 6 Quantifying cell kill and cell survival Mike Joiner 4:00-‐5:00 T2 Tutorial and Question period (L4,5,6) Brad, Bert, Mike

TUESDAY APRIL 10, 2018 Time Lecture Faculty speakers 8:45-‐9:00 Coffee served 9:00-‐9:45 7 LET and RBE Dick Hill 9:45-‐10:30 8 Particles in radiotherapy Mike Joiner 10:30-‐10:45 Break

TOPIC Clinical & Experimental Radiobiology I & II

Coordinator Dr. Marianne Koritzinsky

Day & Time April 9 to 13, 8:45 am – 5:00 pm (Apr 13 8:45 am – 12:30pm)

Location WW126 – Woodsworth College, 117-119 St. George Street

Module Goals

This program provides a comprehensive overview of radiation biology with a particular emphasis on aspects of direct relevance to the practice of radiation oncology. It addresses the molecular and cellular responses to radiation-induced damage that influence cell death in both tumors and normal tissues. Quantitation of radiation effects and the underlying biological basis for fractionation of radiotherapy and dose-response relationships in the clinic are covered in depth. The biological basis for current approaches to improve radiotherapy will be described including novel fractionation schemes, retreatment issues, targeting hypoxia, biological modifiers and combined radiotherapy/chemotherapy. Suggested textbook for this topic is: https://www.amazon.ca/Clinical-Radiobiology-Fourth-Michael-Joiner/dp/0340929669/ref=sr_1_5?ie=UTF8&qid=1465580914&sr=8-5&keywords=clinical+and+radiobiology This topic is also offered through the Department of Radiation Oncology to residents in radiation oncology and physics, as well as other radiobiology researchers.

Evaluation Method Exam

10:45-‐11:15 T3 Tutorial and Question period (L7,8) Dick, Mike

11:15-‐12:00 9 Dose response relationships in radiotherapy -‐ TCP, NTCP, therapeutic ratio Soren Bentzen

12:00-‐1:00 Lunch 1:00-‐1:45 10 The linear-‐quadratic approach to fractionation Mike Joiner 1:45-‐2:15 T4 Tutorial and Question period (L9,10) Soren, Mike 2:15-‐2:30 Break 2:30-‐3:30 11 Modified fractionation schedules (and limits) Soren Bentzen 3:30-‐3:45 T5 Tutorial and Question period (L11) Soren 3:45-‐5:00 W The LQ-‐model workshop Mike Joiner and Soren Bentzen

WEDNESDAY APRIL 11, 2018 Time Lecture Faculty speakers 8:45-‐9:00 Coffee served 9:00-‐9:30 12 Dose rate effect -‐ intro to RB concepts Bert van der Kogel 9:30-‐10:15 13 Clinical radiobiology of brachytherapy Gerard Morton 10:15-‐10:45 T6 Tutorial and Question period (L12,13) Bert, Gerard 10:45-‐11:00 Break 11:00-‐11:45 14 Pathogenesis of normal tissue side effecets Shun Wong 11:45-‐12:30 15 The volume effect in radiotherapy Bert van der Kogel 12:30-‐1:30 Lunch 1:30-‐2:15 16 Retreatment tolerance of normal tissues Shun Wong 2:15-‐3:00 T7 Tutorial and Question period (L14-‐16) Shun, Bert 3:00-‐3:15 Break 3:15-‐4:00 17 Stromal effects Stan Liu 4:00-‐4:15 T8 Tutorial and Question period (L17) Dick, Stan 4:15-‐5:00 18 Oxygen effect Marianne Koritzinsky

THURSDAY APRIL 12, 2018 Time Lecture Faculty speakers 8:45-‐9:00 Coffee served 9:00-‐9:45 19 Hypoxia and tumor microenvironment Marianne Koritzinsky 9:45-‐10:30 20 Clinical approaches to target hypoxia Mike Milosevic 10:30-‐11:15 T9 Tutorial and Question period (L18-‐20) Marianne, Mike 11:15-‐11:30 Break 11:30-‐12:15 21 Stereotactic and high dose radiotherapy Arjun Saghal 12:15-‐12:30 T10 Tutorial and Question period (L21) Arjun 12:30-‐1:30 Lunch 1:30-‐2:15 22 Predictive biomarkers and patient individualization Scott Bratman 2:15-‐3:00 23 Tumor growth, stem cells, and response to irradiation Dick Hill 3:00-‐3:30 T11 Tutorial and Question period (L22,23) Scott, Dick 3:30-‐3:45 Break 3:45-‐4:30 24 Radiation-‐induced malignancies David Hodgson 4:30-‐5:00 T12 Tutorial and Question period (L24)

FRIDAY APRIL 13, 2018 Time Lecture Faculty speakers 8:45-‐9:00 Coffee served 9:00-‐9:45 25 Combined radiotherapy and chemotherapy Anthony Brade 9:45-‐10:30 26 Biological response modifiers in tumors – concepts Marianne Koritzinsky 10:30-‐10:45 Break

10:45-‐11:30 27 Biological response modifiers in tumors – clinical implementation Athony Brade

11:30-‐12:00 T13 Tutorial and Question period (25-‐27) Anthony, Marianne 12:00-‐12:30 Concluding remarks Marianne

Medical Biophysics

PHYSICS COURSE MODULES

2017-2018

Fall 2017

Schedule next page…

TOPIC Medical Device Innovation and Entrepreneurship

Coordinators Dr. Graham Wright, Dr. Brian Courtney, Dr. Ahmed Nasef

Lecture Day & Time Thursdays at 5:00 PM – 6:00 PM, 14 weeks starting September 7 to December 14, inclusive Lectures will also be webcast and available for review

Location Sunnybrook, 2075 Bayview Ave, M-Wing, M6-502 Organizational meeting is scheduled for Thursday Sept. 14, 4:00-5:00pm

Module Goals

Innovations in Medical technology have led to revolutionary advancements in health care. As new devices and technologies are developed, patients are benefiting from more targeted, less invasive treatments. However, new standard of care technologies won’t reach the bedside unless inventors have the skills to bring them to market. The Medical Device Innovation and Entrepreneurship course is an opportunity to explore and navigate the principles underlying the challenges of medical device development. The course is designed to engrain the key mindsets and skill sets that help make successful medtech entrepreneurs. The course addresses the fundamental aspects from developing an idea to commercial success, enabling students to gain knowledge of the role of intellectual property management, regulatory pathways, reimbursement mechanisms, funding models, and business strategy in the successful commercialization of new medical device technologies. The course is delivered using a mix of lectures, guest speakers, workshops, team projects, recommended readings and online learning materials. In addition, students get the opportunity to network with local experts and thought leaders in the medtech field. The module is recommended for students who would like to: (1) catalyze innovation in major medtech companies; (2) build their own medtech start-ups; (3) draw on world-class innovative research conducted in Canadian universities, research institutes and hospitals; and (4) lead translational research projects.

Evaluation Method Group presentations on market and stakeholder analysis, prior art, and preliminary concept with associated regulatory and reimbursement plans for identified clinical need (+ Participation in weekly lectures)

Schedule


Thurs., Sept. 7 5:00-6:00pm

Anne Snowdopn

Global Trends in Health Systems Innovation

Thurs., Sept. 14 4:00-6:00pm

Graham Wright & Brian Courtney

Organizational Meeting (4:00-5:00pm) Medtech Innovation Basics: Clinical Needs Finding & Market Analysis (5:00-6:00pm)

Thurs., Sept. 21 5:00-6:00pm Robert Harrison Introduction to Medtech Entrepreneurship

Thurs., Sept. 28 5:00-6:00pm Harold Wodlinger Business Models Fundamentals in Medtech

Thurs., Oct. 5 5:00-8:00pm Gabriella Chan Navigating the Patent World: An Introduction

Thurs., Oct. 12 5:00-6:00pm TBC Reimbursement of Medical Devices in Canada

Thurs., Oct. 19 5:00-8:00pm Joseph Ferenbok Ideation & Brainstorming

Thurs., Oct. 26 5:00-8:00pm Jayson Parker Medical Device Regulation Primer: Focus on Digital

Health Thurs., Nov. 2 5:00-6:00pm Gilad Shoham Medical Device Design

Thurs., Nov. 9 5:00-6:00pm Brian Bloom Raising Capital – Talking to Investors

Thurs., Nov. 16 5:00-6:00pm Stefano Picone Medtech Start-ups: Valuations, Cap Tables, Cash Flow

Budgeting, and Financial Models Thurs., Nov. 23 5:00-6:00pm TBC Marketing & Sales Strategy in Medtech

Thurs., Nov. 30 5:00-6:00pm TBC Medtech Innovation Basics: Quality & Process

Management Thurs., Dec. 14 5:00-6:00pm Team Presentations

Fall 2017

TOPIC Overview of Medical Imaging

Coordinators John G. Sled

Day & Time Wednesdays, 9:30 – 11:30 am

Location Sunnybrook, 2075 Bayview Ave., S-wing, room SG22

Module Goals

This module provides the mathematical preliminaries of medical imaging and introduces concepts of image formation, inverse problems, stochastic processes and instrument performance that are common to many medical imaging modalities. An introduction and historical perspective on the major medical imaging technologies is also presented. This course is a recommended prerequisite for the imaging modules offered in the physics stream.

Evaluation Method Exam (70%) and lab report (30%) Schedule Date Instructor Lecture

Sept. 13 Mark Henkelman Introduction to Medical Imaging: a brief history Sept. 20

John G. Sled Linear Systems and Fourier Transform Theory I

Sept. 27 John G. Sled Linear Systems and Fourier Transform Theory II

Oct. 4 John G. Sled X-rays, Projection and Tomography

Oct. 11 James Mainprize X-ray CT lab (may need to be scheduled on multiple days to accommodate the number of lab groups)

Oct. 18 John G. Sled Image formation and Inverse problems

Oct. 25 Exam

Fall 2017

TOPIC Biophysics of focused ultrasound, thermal biophysics

Coordinator Dr. David Goertz

Day & Time Tuesdays, 12:30 – 2:30 pm

Location Sunnybrook, 2075 Bayview Ave, S-Wing, Room S615

Module Goals

Focused ultrasound can induce both thermal and non-thermal effects in biological tissues. These biophysical interactions form the basis of a range of therapeutic applications in current medical practice and in leading-edge research. The first half of this course will focus on thermal biophysics, drawing examples from focused ultrasound therapy as well as from other thermal modalities, such as radiofrequency and microwave. The physical and biophysical interaction mechanisms between the energy sources and tissue will be emphasized. Fundamentals of thermal dosimetry will be covered, with reference to the relevant tissue properties, the models of energy propagation within tissues, experimental techniques for dosimetry measurements, and the resulting biological effects. In the second half of this course non-thermal bioeffects of focused ultrasound will be examined. The physical mechanisms behind these mechanical effect will be covered, with an emphasis on cavitation and cavitation-mediated effects. Treatment monitoring considerations for non-thermal therapies will be discussed. The current status of thermal medicine and of focused ultrasound therapies will be reviewed using select clinical and pre-clinical examples.

Evaluation Method Exam Schedule Date Instructor Subject

Nov 7 David Goertz Biology/Rationale/Nomenclature

Nov 14 David Goertz Blood Flow/Modelling/Energy Delivery

Nov 21 David Goertz Energy Delivery(Cont’d)/Thermometry/Treatment Monitoring

Nov 28 David Goertz Non-Thermal Mechanisms of Ultrasound/Bioeffects

Dec 5 David Goertz Cavitation/Cavitation Nucleating Agents

Dec 12 David Goertz Treatment Monitoring for Non-Thermal Therapies

Dec 19 Exam

Fall 2017

TOPIC Advanced Magnetic Resonance Imaging

Coordinator Charles Cunningham

Day & Time Wednesdays, 12:30 – 2:30 pm

Location Sunnybrook, 2075 Bayview Ave, M-Wing. Room M6-620

Module Goals To gain an advanced understanding of how MRI works

Evaluation Method Assignments only Schedule Date Instructor Subject

Nov 8 Cunningham Phase encoding, frequency encoding, hybrids, RF pulses

Nov 15 Macgowan Effects of motion, ghosting, motion compensation methods (e.g., gradient moment nulling, navigators, fast imaging).

Nov 22 Macgowan Phase contrast and flow (2D & 4D), non-contrast angio, myocardial tagging, clinical implementation

Nov 29 Santyr MRI Contrast Mechanisms, endogenous and exogenous

Dec 6 Santyr paramagnetic, susceptibility-based, CEST contrast, magnetization transfer, hyperpolarized agents

Dec 13 Beatty Image reconstruction - non-cartesian sampling and gridding

Dec 20 Beatty Multi-channel signal acquisition and image reconstruction

Winter 2018

TOPIC Introduction to Bio-Microscopies

Coordinator Dr. Brian Wilson

Day & Time Tuesdays at 9:00 am – 11:00 am


Module Goals

Various forms of microscopy are widely used in biomedical research as well as in clinical medicine. Major classes of microscopy include: A) optical microscopy (wide-field, fluorescence, laser-scanning confocal, Raman, bioluminescence, near-field, super-resolution, non-linear, light-sheet, intravital), together with a variety of fluorescent and other probes (dyes, fluorescent proteins, small-molecules); B) electron microscopy, in both transmission and surface-scanning modes and: C) scanning-probe microscopy (atomic force, scanning tunneling, near-field). The goal of this Module is to introduce the basic physical principles of the different forms of microscopy and survey the different techniques, instruments and probes used in studying bio-specimens (cells, tissues, biomaterials), illustrating these with examples of biomedical applications. The role of digital techniques and image processing/analysis will be considered.

Evaluation Method Multiple-choice examination

Schedule

Date Instructor Subject

Jan 9 Brian Wilson Introduction and Optical Microscopies-I

Jan 16 Brian Wilson Optical Microscopies-II

Jan 23 Brian Wilson Optical Microscopies-III

Jan 30 Chris Yip/TBC Scanning-Probe Microscopy

Feb 6 John Rubinstein/TBC Electromagnetic Microscopy

Feb 13 Sergio Grinstein/TBC Biomedical Applications

Feb 20 Exam

Winter 2018

TOPIC Ultrasound Overview

Coordinators Dr. Christine Demore

Day & Time Wednesdays,12:30 pm – 2:30 pm

Location Sunnybrook, 2075 Bayview Avenue, S-Wing, Room S615

Module Goals

Ultrasound is a high-resolution and rapid imaging modality that applies high- frequency acoustic waves to create images based on echoes that are generated by acoustic impedance heterogeneity between different materials in a sample. Ultrasound imaging has many clinical applications from monitoring fetus in pregnancy, to diagnostic imaging of breast, abdomen and vasculature, and guiding interventional tools in minimally-invasive procedures. This course will introduce the principles of ultrasound imaging starting with a general overview of this imaging modality and its applications. It will cover basic physics of ultrasound, transducers and beam forming, interaction of ultrasound waves with tissue, signal processing and image formation, flow detection, contrast imaging, and ultrasound elastography. The Overview of Medical Imaging or equivalent preparation is a prerequisite for this module.

Evaluation Method Lab report (35%) and exam (65%)


Jan 10 Christine Demore General overview, basic physics of ultrasound

Jan 17 Christine Demore Array transducers, Interaction of ultrasound waves with tissue

Jan 24 Christine Demore Ultrasound signal processing, beam forming, image formation

Jan 31 Christine Demore Ultrasound flow detection and imaging

Feb 7 Christine Demore Contrast imaging and assorted topics

Feb 14 Lab with TAs

Feb 21 Exam

Winter 2018

TOPIC Biological Imaging

Coordinators Dr. Jason Lerch & Dr. Brian Nieman

Day & Time Thursdays, 10:00 am -12:00 pm


Module Goals

Imaging has been used to probe important questions in biology. This module will focus on how imaging can be, and has been, used to address such questions. A series of topics will address (1) the knowledge gaps at the beginning of the project; (2) the methodological developments and advances required to address those gaps; and (3) how imaging advanced our knowledge of the field.

Evaluation Method Students will be asked to write a short grant proposal on a novel project to answer a question in biology using state of the art imaging. In addition, there will be marks for course participation.

Schedule

Date Instructor Lecture (order likely to change)

Jan 11 J. Lerch, B. Nieman Course intro and the study of brain plasticity

Jan 18 C. Macgowan Cardiac development

Jan 25 B. Stefanovic Vascular coupling

Feb 1 J. Sled Foetal development

Feb 8 B. Nieman Late effects of brain irradiation

Feb 15 B. Nieman, J. Lerch Internal grant reviews: peer reviews of grant proposals

Feb 22 Final grant proposal due.

Winter 2017

TOPIC Advanced Ultrasound

Coordinator Dr. David Goertz

Day & Time Wednesdays, 12:30 – 2:30 pm

Location Sunnybrook, 2075 Bayview Ave. S-Wing, Room S615

Module Goals

This module builds upon the introductory material covered in the Ultrasound Overview course and is intended to provide a more substantial foundation for students pursuing thesis research involving biomedical ultrasound. Linear and nonlinear wave interactions with tissue will be covered, along with their implications for imaging and therapeutic applications. Selected topics will then be presented, including transducer principles of design and fabrication, advanced beamforming methods, cavitation and contrast agents. The module will be offered in alternate years. Pre-requisite: Ultrasound Overview module or its equivalent.

Evaluation Method Exam

Schedule Date Instructor Subject

Feb 28 David Goertz Wave interactions with tissue

Mar 7 David Goertz Wave interactions with tissue

Mar 14 Christine Demore Transducers

Mar 21 Meaghan O’Reilly Beamforming

Mar 28 Peter Burns Cavitation and contrast agents

Apr 4 David Goertz Selected Topics

Apr 11 No Class

Apr 18 Exam

SPRING 2018

TOPIC Cell and Molecular Biology for Physicists - Introduction

Coordinator TBA

Day & Time SRING 2018

Location TBA

Module Goals

This course introduces physical scientists to the basic concepts of cell and molecular biology including structure and function of nucleic acids (DNA and RNA) and proteins, DNA replication, transcription, translation, genetics, regulation of gene expression, cell growth and differentiation, basic developmental biology and immunology. The course will stress breadth rather than depth and is designed to introduce physical scientists whose research impinges on biology to the concepts and methodologies of molecular biology.

Evaluation Method TBA

Schedule Spring TBA

Winter 2018

NB this is a provisional timetable and the order of the lectures may vary.

TOPIC Clinical Imaging for Physical Scientists

Coordinators Anne Martel, Korosh Khalili and Sarah Johnson

Day & Time Mondays, 9:15-11:15

Location Sunnybrook, 2075 Bayview Ave., S-Wing, room SG22

Module Goals

This course seeks to provide an introduction to human anatomy and physiology for physical scientists with an interest in clinical imaging. Basic normal anatomy and physiology will be presented from a radiological perspective in lectures structured according to the major organ systems. A practical anatomy lab is included, through which students will have an opportunity to experience the three dimensional relationships of the structures they seek to image. In the lectures, examples of specific disease processes will be considered together with findings from X-ray, computed tomography, ultrasound, radionuclide and nuclear magnetic resonance imaging. Course evaluation will be based on participation in weekly sessions, and a written assignment.

Evaluation Method Written assignment Schedule Date Instructor Lecture

Mar 5 Dr. Korosh Khalili Gastro-Intestinal Imaging

Mar 12 Dr. Michael McInnis Chest Imaging

Mar 19 Dr. Eugene Yu Neuroimaging

Mar 26 Dr. Howard Leong-Poi Cardiac Imaging

Apr 2 Dr. David Salonen Musculoskeletal Imaging

Apr 9 No Class

Apr 16 Dr. Anne Agur Anatomy lab (9-11am MSB, St George campus)

Apr 23 Dr. Jose Sarazzin Genito-Urinary Imaging

Winter 2018

TOPIC Magnetic resonance imaging - Overview

Coordinator Simon Graham

Day & Time Tuesdays, 12:30 – 2:30 pm

Location Sunnybrook, 2075 Bayview Ave. S-Wing, Room S615

Module Goals

Since development of the first hospital-grade systems in the 1980s, magnetic resonance imaging (MRI) continues to make a profound impact on how physicians evaluate soft tissues within the human body. This course provides students with an overview of MRI technology covering the underlying physical principles of signal generation, signal contrast mechanisms, process of image formation, and basic instrumentation. The course is a prerequisite for students who subsequently wish to take Advanced Topics in MRI.

Evaluation Method Lab and Exam Schedule Date Instructor Subject

March 6 J. Chen Basic physics 1

March 13 J. Chen Basic physics 2

March 20 B. Nieman Imaging physics 1

March 27 B. Nieman Imaging physics 2

April 3 M. Pop Laboratory

April 10 No class

April 17 M. Pop Instrumentation

April 24 S. Graham Exam

Winter 2018

TOPIC Introduction to Biophotonics

Coordinators Alex Vitkin and Lothar Lilge

Day & Time Fridays, 10:00 am – 12:00 noon


Module Goals

The use of light in medical diagnostics, therapeutics and biomedical research is increasing, driven by the advent of new light sources, inexpensive imaging detectors, advanced fiber-optic delivery systems, better understanding of light-tissue interactions, and proven clinical and research applications. The course will focus mostly on in vivo photonics and initially cover (1) the relevant issues of light propagation in / interaction with turbid media such as tissue. The bulk of the course will focus on (2) particular technical implementations and research / pre-clinical / clinical results in photo-diagnostics (effects of tissue on light) and photo-therapeutics (effects of light on tissue). Advanced topics such as (3) molecular imaging, nanophotonics, optical clearing and theragnostics will also be briefly covered. As such, the course goals include basic competencies in these there [(1)-(3)] areas.

Evaluation Method Class participation and short oral exit exam

Schedule


March 9 Alex Vitkin Basic biophotonics – light propagation in tissue (Maxwell’s equations, transport / diffusion theory and statistical Monte Carlo methods), light-tissue interactions, tissue optical properties, fundamentals of photodiagnostics and phototherapeutics.

March 16 Alex Vitkin

Diagnostic imaging, discussions of resolution, contrast, turbidity, imaging depth issues. High resolution diagnostics including optical coherence imaging, photoacoustics, optical projection tomography, confocal and multi-photon techniques; low(er) resolution approaches including diffuse optical imaging

March 23 Lothar Lilge Diagnostic spectroscopy techniques including hyperspectral imaging, fluorescence and Raman spectroscopy

March 30 Lothar Lilge Photo-therapeutics based on non-thermal interactions (photo bio-modulation therapy)

April 6 Lothar Lilge Photo-therapeutics based on temporally-controlled (rapidly pulsed) laser delivery, including photo-ablation and selective photothermolysis

April 20 Alex Vitkin Selected advanced topics such as nanophotonics, molecular imaging, optical clearing and theragnostics

April 27 Oral exit exam

Medical Biophysics

Modules 2018-2019

(These are not offered in 2017-2018)

Fall 2018

TOPIC Cell Signaling & Metabolism

Coordinators Drs. Jane McGlade & Vuk Stambolic


Location TBA

Module Goals

This module will cover a spectrum of topics in cell biology and biochemistry, including cell-to-cell communication, sensing of extracellular signals, surface receptors as signaling modalities, second messengers, modular architecture of proteins, post-translational modifications as instructive signals, intracellular signal transduction and signaling pathways, effectors of signaling pathways, protein stability and turnover. The module will also encompass a series of themes in cellular metabolism, including cellular energetics, nutrient transport and utilization, plasticity in metabolic networks, cellular metabolism in disease and the interface between cell signaling and cell metabolism. The use of model systems in the study of signaling and metabolism, as well as methodologies for cell signaling research will be discussed. The students should expect to get an advanced understanding of signaling networks and metabolic pathways and knowledge of means for their interrogation.

Evaluation Method Written assignment

Schedule

Date Instructor Lecture Sept – Oct 2018 TBA

Fall 2018

TOPIC Cell Biology & Cancer Models

Coordinators Laurie Ailles and Eldad Zacksenhaus



Module Goals

Neoplastic transformation and metastasis are characterized by acquisition of autonomous self-renewal and uncontrolled cell division, increased motility, epithelial-to-mesenchymal transition (EMT), invasion/dissemination, homing to distal tissues and ultimately formation of macrometastases. Cells resist such oncogenic transformation by inducing programmed cell death (apoptosis), senescence and macro-autophagy. The latter two escape routes also have pro-oncogenic effects in certain contexts. Understanding the biology of these processes is the key to many existing as well as novel/future strategies for cancer therapy. This course will introduce basic concepts in cancerous cell cycle, apoptosis, senescence, autophagy and the metastatic cascade, and review recent publications in these fields. It will then discuss Genetically Engineered Mouse Models (GEMM) and patient derived models, and how such models are used to study oncogenic transformation and dissemination, as well as identifying effective therapies.

Evaluation Method Short exam with multiple-choice questions

Schedule


Nov – Dec 2018 TBA

Winter 2019

TOPIC Nanotechnology for Medicine

Coordinators Dr. Gang Zheng

Day & Time Jan – Feb 2019

Location TBA

Module Goals

This course is not a basic survey, but a critical and timely analysis of the current state of the nanomedicine field, how it has become incorporated in to multiple disciplines, and the factors that must be considered for its future progress and successful clinical implementation. The course will begin with an introduction to nanotechnology, the unique physical properties that define nanoscale materials, and the state of art techniques to study the nanobiointerface. The course will focus on the design considerations for nanoparticles will be considered through a discussion of how they interface with biology, which make them advantageous additions to the toolkit of agents for disease diagnosis and therapy. The course will then progress to sophisticated approaches for nanomedicine applications. Finally, the course will conclude by covering challenges and opportunities in translation of nanomedicines to the clinic.

Evaluation Method

Each student will produce a written report of a topic covered in the course but unrelated to their thesis project plus an oral presentation on the March 1st class.

o Format: journal mini-review style, max. 5 pages (1.5 space, pt. 12 font) with one figure plus references.

o Evaluation criteria will be heavily weighted on quality of analysis. The grade will be a combination of attendance and participation (10%), written report (70%) and oral presentation (20%)

Schedule

Date Instructor Lecture Jan – Feb 2019 TBA

Winter 2019

TOPIC Predictive Oncology & Therapeutics

Coordinators Drs. Benjamin Haibe-Kains & Ming Tsao

Day & Time Mondays,10:00 am – 12:00 pm

Location TBA

Module Goals

One of the main challenges in precision medicine is the selection of the therapeutic strategy that will benefit the most to each individual patient. With the advent of high-throughput profiling technologies, more and more data can be generated to deeply characterize the molecular state of cancer cells and the phenotypes resulting from drug treatment both in vitro and in vivo. The “Predictive Oncology & Therapeutics” course will be composed of a series of didactic lectures on the key topics related to drug development. Each session will tackle of these topics with at least 30 minutes of questions and debates regarding the content of the lecture and its applications in biomedicine. The goal of this course is to provide students with a translational view of drug development, from basic research to clinical implementation. The students are expected to learn about the biological, computational and clinical aspects of the development of cancer therapeutics and their associated biomarkers (companion tests).

Evaluation Method Short exam with multiple-choice questions

Schedule

Date Instructor Lecture Mar – Apr 2019 TBA

Winter 2019

TOPIC Quantitative Cancer Genomics

Coordinators Drs. Mathieu Lupien & Trevor Pugh


Location TBA

Module Goals

Each class will consist of a 1-hour student lecture reviewing the day's topic in detail, followed by interactive discussion around a specific paper, case report, or mini-workshop illustrating the application of research findings in a novel way (e.g. clinical application, meta-analysis, new use for old data). The organizing Instructor will provide a list of topics that must be covered by the student in the review portion of the class and moderate discussion during the more open portion.

Evaluation Method

Each student will be responsible for a Lecture Topic Review to be held in the first hour of each class (50% of their grade). Each student is also responsible for contributing to the Interactive Manuscript Discussion to follow in the second hour of each class (50% of their grade). The class accepts a minimum of 7 and maximum of 14 students. Instructors are to provide the lecture topic and can suggest manuscripts to be discussed in the second hour at least one week prior to the start date. On the Monday prior to student’s presentation (3 days before), lecturers will be available in person or by email to provide an optional review of the student’s proposed presentation and discussion plan. The Instructors are responsible for assigning the student’s grade using an evaluation form common across all of the lectures.

Schedule


Jan – Feb 2019 TBA

Winter 2019

TOPIC Structural Biology & Proteomics

Coordinators Drs. Mitsu Ikura & John Rubinstein

Day & Time March – April 2019

Location Princess Margaret Cancer Centre, Room TBA

Module Goals

This course offers 6 lectures that are focused on the current hot topics in structural biology and proteomics. Three lectures are designated to discuss structural biology, in which you will learn (1) protein structure and dynamics, (2) structures of membrane proteins, and (3) structures of supermolecular assembly. These courses will discuss the recent development in structural elucidation of biological macromolecules. You will learn how various research tools such as X-ray crystallography, NMR spectroscopy, and electron microscopy are used to determine atomic-resolution structures of complicated biological macromolecules (i.e. proteins, nucleic acids, etc) and their complexes. In the other three lectures designated to proteomics research, you will study various applications of mass spectrometry-based proteomics. Mass spectrometry has become an indispensable tool for a variety of biomedical research. The lectures intend to cover (1) large-scale mapping protein-protein interactomes in genomes, (2) global characterization of post-translational modifications (such as protein phosphorylation and ubiquitination) in proteomes, and (3) development of biomarkers for diagnosis. These lectures are designed to help students to grasp the overview of the latest advancement in structural biology and proteomics, the very active research fields in biology.

Evaluation Method Report or essay (to be confirmed)

Schedule

Date Instructor Lecture Mar – April 2019 TBA TBA

medical biophysics - preventovariancancermedbio.utoronto.ca/sites/default/files/resources/module...

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