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M.h. Sherebrin
02-25-1997, 02:43 AM
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