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Translational Medicine

Sled Lab

Principal Investigator

John Sled, PhD

Post-docs, Fellows
Jason P. Lerch
Jian Yang

Research Technologist
Lisa Yu

PhD Students
Brige Chugh
Monique Rennie

Students
Mojdeh Zamyadi

Research Activities

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 The Hospital for Sick Children and (as of 2006) at the 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 onmagnetization transfer, an MRI contrast mechanism that has been used extensively to study white matter disorders such as multiple sclerosis.

Publications

Narayanan S, Francis SJ, Sled JG, Santos AC, Antel S, Levesque I, Brass S, Lapierre Y, Sappey-Marinier D, Pike GB, Arnold DL. Axonal injury in the cerebral normal-appearing white matter of patients with multiple sclerosis is related to concurrent demyelination in lesions but not to concurrent demyelination in normal-appearing white matter. Neuroimage vol. 29, pp. 637-642, 2006.

Nieman BJ, Flenniken AM, Adamson SL, Henkelman RM, Sled JG. Anatomical phenotyping in the brain and skull of mutant mice by magnetic resonance imaging and computer tomography. Physiological Genomics vol. 24, pp. 154-162, 2006 (Cover illustration).

Kulandavelu S, Qu D, Sunn N, Mu J, Rennie MY, Whiteley KJ, Walls JR, Bock NA, Sun JCH, Covelli A, Sled JG, Adamson SL. Embryonic and neonatal phenotyping of genetically engineered mice. ILAR vol. 47, no. 2, pp.103-117, 2006.

Marxen M, Sled JG, Yu LX, Paget C, Henkelman RM. Comparing microsphere deposition and flow modeling in 3D vascular trees. American Journal of Physiology: Heart and Circulatory Physiology 291(5):H2136-H2141, 2006.

Henkelman RM, Baghdadi L, Sled JG. Presentation of 3D isotropic imaging data for optimal viewing. Magn. Reson. Med 56(6):1371-1374, 2006.

Books/Chapters in Books

  1. Henkelman RM, Chen XJ, Sled JG. Disease phenotyping: Structural and functional readouts. In: Imaging in Drug Discovery and Early Clinical Trials. Ed. Marcus Rubin, pp. 153-184. Berlin: Birkhäuser Verlag, 2005.

Contact Information

Admin Assistant
Lynda Cockroft
e-mail: cockroft@phenogenomics.ca

Mailing Address
Mouse Imaging Centre
The Hospital for Sick Children
The Centre for Phenogenomics
25 Orde St.
Toronto, ON M5T 3H7

Tel: (647) 837-5820
Fax: (647) 837-5832
e-mail: jgsled@phenogenomics.ca

Website: Mouse Imaging Centre