John Sled, PhD
Mouse Imaging Centre
University of Toronto
Professor and Vice-Chair, Medical Biophysics
Institute of Biomaterials & Biomedical Engineering
Department of Obstetrics and Gynaecology
Phone: 416-813-7654 ext. 309557
Alternate Contact: Katie Polanic
Alternate Phone: 416-813-7654 ext. 9536
Alternate Fax: 647-837-5832
Alternate e-mail: firstname.lastname@example.org
John G. Sled, PhD is an assistant professor in the department of medical biophysics at the University of Toronto and a scientist at the Mouse Imaging Centre (MICe) at The Hospital for Sick Children (SickKids). His current research interests include the genetic determinants of vascular patterning the use of MRI for anatomical screening of mice, the development of quantitative techniques for MRI and the imaging of pathology in multiple sclerosis.
Sled received an MEng in 1997 from the Department of Biomedical Engineering at McGill University for his work on the causes and remedies of intensity non-uniformity artifacts in MRI. He received his PhD from the department of electrical engineering at McGill University in 2001. For his PhD, he developed an MRI technique for imaging the human brain called quantitative magnetization transfer imaging. This technique, of particular interest in the study of white matter diseases such as multiple sclerosis, shows the concentration and rigidity of the semisolid components of tissue that are normally invisible to MRI. From 2001-2003, he was a postdoctoral fellow in Imaging Research at Sunnybrook and Women’s College Health Sciences Centre with Dr. R. Mark Henkelman. During that period, he investigated the use of micro-computed tomography for characterizing the microvasculature of whole organs.
- the development of new medical imaging methodologies
- the use of imaging to study mouse models of disease
- the relationship between genes and patterning of an organisms
Future Research Interests
The combination of 3D imaging, computer analysis and the fine control of mouse genetics provides an excellent window on the function of genes and the complex interactions that lead to the meso and macroscopic scale structure of an organism. Characterizing the genetic determinants of form will continue to be a theme in my research.
My research program has two aspects: the use of medical imaging technologies to study mouse models of disease and the use of magnetic resonance imaging (MRI) techniques to study paediatric neurological disorders. Research on the former is carried out at the Mouse Imaging Centre located at SickKids and (as of 2006) at The Centre for Phenogenomics. Details of some of the projects my lab is working on are as follows:
Micro-CT vascular imaging
This is a project to understand the genetic factors affecting patterning of the microvasculature. Micro-computed tomography is used to obtain high resolution 3D images of the microvasculature from intact organs. In addition to characterizing normal microvasculature, we are examining the structure of the placenta in models of interuterine growth restriction, the structure of the neurovasculature in models of neurodegeneration, as well as a number of specific mutations affecting the lung, liver, and kidney.
Screening mice for abnormal brain anatomy
This is a project to develop new methods for detecting and characterizing abnormal brain anatomy in the mouse using high resolution MRI. Whole brain 3D imaging has been demonstrated to detect subtle alterations and diffuse changes that occur in connection with genetic manipulations and that typically are overlooked by other methods. Identifying these changes guides subsequent examination of the mice and can provide insight into the function of novel genes.
Quantitative structural magnetic resonance imaging (MRI)
This is a project to develop new MRI methods yielding information about the structure of brain tissue in vivo. The current focus is on magnetization transfer, an MRI contrast mechanism that has been used extensively to study white matter disorders such as multiple sclerosis.
Sled JG, Marxen M, Henkelman RM. Analysis of micro-vasculature in whole kidney specimens using micro-CT.40th Annual Meeting of the SPIE, International Symposium on Optical Science and Technology, In Proceedings of the SPIE, vol. 5535, pp. 53-64, 2004.
Kovacevic N, Chen J, Sled JG, Henderson J, Henkelman M. Deformation based representation of groupwise average and variability. Medical Image Computer & Computer Assisted Intervention, In Lecture Notes in Computer Science, vol. 3217, pp. 615-622, 2004.
Levesque I, Sled JG, Narayanan S, Santos AC, Brass SD, Francis SJ, Arnold DL, Pike GB. The role of edema and demyelination in chronic T1 black holes: a quantitative magnetization transfer study. Journal of Magnetic Resonance Imaging vol. 21, no. 2, pp. 103-110, 2004.
Ward NL, Haninec AL, Van Slyke P, Sled JG, Struk C, Henkelman RM, Wanless IR, Dumont DJ. Angiopoietin-1 causes reversible degradation of the portal microcirculation in mice: implications for treatment of liver disease. America J. Pathology 165, vol. 3, pp. 889-899, 2004.
Marxen M, Thornton MM, Chiarot CB, Klemen G, Koprivnikar J, Sled JG, Henkelman RM. Micro CT for vascular structure analysis. Medical Physics, vol. 31, no. 2, pp. 305-313, 2004.
Also in Virtual Journal of Biological Physics Research, vol. 7, no. 3, 2004.
Sled JG, Levesque I, Santos C, Francis SJ, Narayanan S, Brass SD, Arnold DL, Pike GB. Regional variations in normal brain shown by quantitative magnetization transfer imaging. Magnetic Resonance in Medicine, vol. 51, no. 2, pp. 299-303, 2004.
Stefanovic B, Sled JG, Pike GB. Quantitative T2 contrast in the occipital lobe: does CPMG refocusing rate matter. Journal of Magnetic Resonance Imaging, vol. 18, no. 3, pp. 302-309, 2003.
Bock NA, Zadeh G, Davidson LM, Qian B, Sled JG, Henkelman RM. A. Guha. “High-resolution longitudinal screening with magnetic resonance imaging in a murine brain cancer model. Neoplasia, vol. 5, no. 6, pp. 546-554, 2003.
Kabani N, Sled JG, Shuper A, Chertkow H. Regional magnetization transfer ratio changes in mild cognitive impairment.Magnetic Resonance in Medicine, vol. 47, no. 1, pp. 143-148, 2002.
Kabani N, Sled JG, Chertkow H. Magnetization transfer ratio in mild cognitive impairment and dementia of Alzheimer’s type. NeuroImage, vol. 15, no. 3, pp.604–610, 2002.