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Last Updated: 11/19/19
Quantitative Imaging Network (QIN)

Princess Margaret Cancer Centre
Toronto, Canada

Image-based quantitative assessment of tumor hypoxia

David Jaffray, Ph.D

Cancer is a major cause of death and reduced quality of life, with roughly 1.6 million new cases in Canada and the US per year and a mortality rate of over 37%. Individual tumour diversity, which is sensitive to the local tumour microenvironment, poses significant challenges to selecting personalized treatment. The overall hypothesis of this research is that the tumor micro-environment is a significant factor in patient outcomes and response to therapy. One of the indicators of poor outcome is hypoxia that develops in solid malignant tumours when the metabolic demand for oxygen exceeds availability and strongly influences gene expression and cell phenotype, resulting in the creation of sub-populations with aggressive characteristics including genetic instability, increased metastasis, and resistance to all current forms of treatment.

Hypoxia is in particular a factor that has potential therapeutics in clinical trials, while positron-emission tomography (PET) agents can aid in non-invasively imaging of tumor hypoxia.

We seek to develop quantitative, multi-parametric approaches to hypoxia imaging to increase the predictive capacity of the hypoxia markers and improve the stratification of patients for hypoxia-targeted treatment strategies.

This work includes several aims, including the development of standardized acquisition methodology, integrating perfusion imaging methods to create a more robust tracer kinetic model for hypoxia imaging, and developing a software application to solve these models and produce quantitative metrics of hypoxia.

Thereafter, these developments will be validated in on-going clinical trials, some of which include oral pimonidazole to produce a histology gold standard against which to compare the imaging results.

Our aim to standardize hypoxia imaging protocols will provide a guideline for the imaging community to design clinical studies in hypoxia imaging with PET tracers. The development of advanced hypoxia tracer models coupled with perfusion will provide an understanding of the interplay between hypoxia and perfusion in tumors. These models can be readily adapted by other researchers in the imaging community. In addition, analysis of clinical studies of different anatomical sites will provide baseline data which can also be used for the design of future clinical trials.

QIPCM website:


  1. Foltz W, Driscoll B, Lee S, Nayak K, Nallapareddy N, Fatemi A, Ménard C, Coolens C, Chung C. Phantom Validation of DCE-MRI Magnitude and Phase-Based Vascular Input Function Measurements. 2019. Tomography - QIN Special Issue. Accepted. Coauthor or Collaborator. [IF: 2.1]

  2. Svistoun I, Driscoll B, Coolens C. Accuracy and Performance of Functional parameter estimation using a Novel Numerical Optimization Approach for GPU-Based Kinetic Compartmental Modeling. QIN Special Issue of Tomography. 2018 Dec 11. Accepted. Senior Responsible Author. [IF: 2.1]

  3. Shukla-Dave A, Obuchowski NA, Chenevert TL, Jambawalikar S, Schwartz LH, Malyarenko D, Huang W, Noworolski SM, Young RJ, Shiroishi MS, Kim H, Coolens C, Laue H, Chung C, Rosen M, Boss M, Jackson EF. Quantitative imaging biomarkers alliance (QIBA) recommendations for improved precision of DWI and DCE-MRI derived biomarkers in multicenter oncology trials. J Magn Reson Imaging. 2018 Nov 19. doi: 10.1002/jmri.26518. [Epub ahead of print] Review. Coauthor or Collaborator. [IF: 3.083]

  4. Coolens C, Driscoll B, Foltz W, Svistoun I, Sinno N, Chung C. Unified platform for multimodal voxel-based analysis to evaluate tumour perfusion and diffusion characteristics before and after radiation treatment evaluated in metastatic brain cancer. Br J Radiol. 2018 Sep 20:20170461. doi: 10.1259/bjr.20170461. [Epub ahead of print] [IF: 1.814] Principal Author.

  5. Coolens C, Mohseni H, Dhody S, Ma S, Keller H, Jaffray DA. Quantification accuracy for dynamic contrast enhanced (DCE) CT imaging: phantom and quality assurance framework. Eur J Radiol. 2018 Sep;106(2018):192-198. Principal Author. [IF: 2.462]

  6. Low L, Ramadan S, Coolens C, Naguib HE. 3D Printing Complex Lattice Structures for Permeable Liver Phantom Fabrication. Bioprinting. 2018 Jun 18;11(2018):e00025. In press. Coauthor or Collaborator. [IF: N/A]

  7. Elhalawani E, Ger RB, Mohamed ASR, Awan MJ, Ding Y, Li K, Fave XJ, Beers AL, Driscoll B, Hormuth DA II, van Houdt PJ, He R, Zhou S, Mathieu KB, Li H, Coolens C, Chung C, Bankson JA, Huang W, Wang J, Sandulache VC, Lai SY, Howell RM, Stafford RJ, Yankeelov TE, van der Heide UA, Frank SJ, Barboriak DP, Hazle JD, Court LE, Kalpathy-Cramer J, Fuller CD l. Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Head and Neck Cancers. Sci Data. 2018 Feb 13;5:18008 doi: 10.1038/sdata.2018.8. Coauthor. [IF: 4.836]

  8. Fedorov A, Hall L, McNitt-Gray M, Balagurunathan Y, Goldgof D, Gillies R, Tarbox L, Napel S, Kinahan P, LaViolette PS, Sharma A, Jones EF, Casavant TL, Rubin D, Coolens C, Hylton N, Aerts H, Prior F, Taouli B. Response to NCI Request for Information (RFI): Input on Development of the NCI Imaging Data Commons. National Cancer Institute (NCI). 2018 Apr 3;NOT-CA-18-060. Coauthor or Collaborator.

  9. Bringing cutting-edge imaging tecniques to clinical trials. Ontario Institute of Cancer Research News. 2018. Interview

  10. Validation of 18-F-FAZA PET-CT image-derived blood SUV values. World Federation of Nuclear Medicine and Biology 2018 Meeting, Melbourne, Australia.

  11. Vines DC, Scollard DA, Driscoll BD, Keller H, Shek T, Han K, Jaffray DA. Validation of 18-F-FAZA PET-CT image-derived blood SUV values. World J Nucl Med. 2018;17(Suppl 1):82.

  12. Kathy Han, Tina Shek, Douglass Vines, Brandon Driscoll, Anthony Fyles, David Jaffray, Harald Keller, Ur Metser, Melania Pintilie, Jason Xie, Ivan Yeung, Michael Milosevic. Measurement of Tumor Hypoxia in Patients with Locally Advanced Cervical Cancer using Positron Emission Tomography (PET) with 18FFluoroazomyin Arabinoside (18F-FAZA). International Journal of Radiation Oncology*Biology*Physics (2018). 102(4):1202-1209.

  13. J Haynes, TD McKee , AC Haller , Y Wang , C Leung , DMA Gendoo , E Lima-Fernandes , A Kreso , R Wolman , Eva Szentgyorgyi , DC Vines , B Haibe-Kains , BG Wouters , U Metser, DA Jaffray , M Smith, CA O'Brien. (2018) Administration of Hypoxia-Activated Prodrug Evofosfamide after Adjuvant Therapy Enhances Therapeutic Outcome and Targets Cancer-Initiating Cells in Colorectal Cancer. Clinical Cancer Research (2018). 24(9):2116-2127.

  14. M Ding, T van der Kwast, R Vellanki, W Foltz, TD McKee, N Sonenberg, PP Pandolfi, M Koritzinsky, BG Wouters. The mTOR Targets 4E-BP1/2 Restrain Tumor Growth and Promote Hypoxia Tolerance in PTEN-driven Prostate Cancer. Molecular Cancer Research (2018). 16(4):682-695.

  15. Mitsuteru Yoshida, Hisashi Oishi, Tereza Martinu, David M. Hwang, Trevor D. McKee, Xiaohui Bai, Zehong Guan, Hae-Ra Cho, Stephen Juvet, Marcelo Cypel, Shaf Keshavjee, Mingyao Liu. (2018) Pentraxin 3 Deficiency Enhances Features of Chronic Lung Allograft Dysfunction in a Mouse Orthotopic Lung Transplantation Model. Oncotarget (2018). 9(9): 8489-8501.

  16. D Xia, R Casanova, D Machiraju, TD McKee, W Weder, AH Beck, A Soltermann. (2018) Computationally-Guided Development of a Stromal Inflammation Histologic Biomarker in Lung Squamous Cell Carcinoma. Scientific Reports (2018). 8:3941.

  17. H Rezaeeyan, R Shirzad, TD McKee, N Saki. (2018) Role of Chemokines in Metastatic Niche: New insights along with a Diagnostic and Prognostic Approach. APMIS (2018). 126(5):359-370.

Princess Margaret Hospital.
Princess Margaret Hospital.