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  • Grad Student Opening in Arterial Structure

    GRADUATE STUDENT RESEARCH OPENING

    PROJECT TITLE:
    Structural organization of arteries and saccular aneurysms
    of the human brain.

    GRANT FUNDING:
    Heart and Stroke Foundation of Ontario with minor funding
    from the American Heart Association.

    GRADUATE STIPEND: $16,880 per annum.

    INTRODUCTION:
    The saccular brain aneurysm is a thin walled balloon-like
    out pouching of a brain artery, forming usually at the
    branching region of the artery (Ferguson, 1989). They are
    relatively common, as learned from autopsy studies, with the
    small aneurysms of less than 2 mm in size having an incidence
    of approximately 10% in middle or later age. A few enlarge in
    size, and those greater than 5 mm in size are considered
    clinically to be at risk of rupture. Rupture can be
    catastrophic and fatal, or minor with bleeding into the base of
    the brain that causes an extremely severe headache. Treatment
    of the nonfatal ruptures is by neurosurgery. Some centres are
    experimenting with less invasive procedures to "seal up" the
    aneurysm. From a basic science perspective the enlargement and
    rupture is clearly biomechanical, with the principal structural
    fabric of layered collagen remodeling and eventually rendering
    the aneurysmal wall too weak to sustain arterial blood
    pressure, or so weak that it fails catastrophically.

    COLLABORATIONS:
    The research has a strong collaborative component,
    coupling the microscopical and stereological methods of the
    London Medical Biophysics Group (Canham and Ferguson) with the
    Mechanical Engineering Group in Baltimore, Maryland, at UMBC
    (Humphrey). The researchers in Baltimore, working with
    neurosurgeons and neuropathologists at Johns Hopkins Medical
    Center, obtain the aneurysms as intact structures, investigate
    their micromechanical behaviour using surface markers on
    pressure cycled aneurysms, after which the aneurysmal tissue
    and adjacent blood vessels are fixed at arterial pressure and
    shipped to our London group. For larger aneurysms we plan to
    collaborate as well with the advanced imaging researchers at
    the Robarts Research Institute.

    METHODS:
    The research focuses on the organizational structure of
    the collagen fabric in bifurcation regions of brain arteries
    (where aneurysms develop) and throughout the wall of the
    aneurysm itself. Two light microscopical methods, centered on
    polarized light optics, provide the basis for obtaining primary
    structural data on collagen (collagen is birefringent) which
    can be enhanced by birefringent enhancement stains such as
    picro-sirius red or toluidine blue ferricyanide. Quantitative
    directional organizational data, in three dimensions, are
    obtained using the Zeiss universal stage attachment for the
    polarizing microscope (Canham et al. 1991, 1996). The strength
    of molecular cross linking of collagen, and thus collagen's
    strength as a biopolymer, can be assessed through the
    measurement of phase retardation (Whittaker et al., 1988;
    Nollie et al., 1996).

    THE SCIENTIFIC HYPOTHESIS is that the molecular strength of
    aneurysmal collagen, measured optically, will reveal collagen
    less suited to bear tensile load, and that the directional
    organization of the stronger collagen in the outer aneurysmal
    wall will be incomplete for providing a strong spherical
    surface to resist enlargement or rupture of the larger
    aneurysm.

    SHORT REFERENCE LIST:

    Canham, PB, Finlay, HM, Dixon, JG, and Ferguson, SE (1991).
    Layered collagen fabric of cerebral aneurysms quantitatively
    assessed by the Universal stage and polarized light
    microscopy. Anat. Rec. 231: 579-592.

    Canham, PB, Finlay, HM, and Tong, SY (1996). Stereological
    analysis of the layered collagen of human intracranial
    aneurysms. J. Microsc. 183: 170-180.

    Ferguson, GG (1989). Intracranial arterial aneurysms a
    surgical perspective. In Handbook of Clinical Neurology, Vol.
    11: Vascular Disorders, Part III (ed by J.F. Toole), p.41-87.

    Nollie, GJ, Sandhu, HS, Cernovsky, ZZ, and Canham, PB. (1996).
    Regional differences in molecular cross-linking of periodontal
    ligament collagen of rat incisor, by polarizing microscopy.
    Conn. Tiss. Res. 33: 283-289.

    Whittaker, P, Schwab, ME, and Canham PB. (1988). The molecular
    organization of collagen in saccular aneurysms assessed by
    polarized light microscopy. Conn. Tiss. Res. 17:43-54.

    APPLICANTS need to be qualified for MSc or PhD research
    training in Medical Biophysics, with a background in Physics,
    Biophysics, Applied Mathematics, Engineering or Biology. For
    the biology background applicant preference will be given to
    students with a demonstrated ability in physical and
    mathematical sciences. Preference is also give to Canadian
    students, partly because of the higher tuition fee required of
    non Canadian students. Students interested should send a
    transcript of their grades and a letter, outlining their
    reasons for wishing to undertake graduate research on this
    project.

    CORRESPOND TO:
    Peter B. Canham, Ph.D.
    Professor and Chair
    Dept. of Medical Biophysics
    Medical Sciences Building
    The University of Western Ontario
    London ON CANADA N6A 5C1
    email: pcanham@julian.uwo.ca
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