Stroke Prevention Research
Dr. J. David Spence
&
Dr. Daniel Hackam

CLINICAL RESEARCH WITH NEW TREATMENTS FOR ATHEROSCLEROSIS

In collaboration with the Imaging Research Group at the Robarts Research Institute, we have developed 3-D ultrasound methods for measuring the rate of progression of atherosclerosis in the carotid arteries. This method is ideal for testing new treatments, since the rate of growth of plaque in 3 dimensions is more than 2.5 times faster than the growth in thickness, and the measurements are non-invasive. Sample sizes required to demonstrate efficacy of treatments are much smaller (approximately 150 patients per group, followed for 2-3 years) than with alternative methods.

Plaque volume is measured by Disc Segmentation, shown in the figure below:

Measurements are made in the axial plane (c); the perimeter of the plaque in each slice is traced (d and e); slices are made at 1-mm intervals, and the slices are stacked up to form a volume, and the surface contour is mapped for measurement of plaque surface roughness (f). 19-22

In the figure below, the top plaque has been measured by disc segmentation; the lower plaque has had contours applied for measurement of a new therapeutic target, "plaque surface roughness", that we believe is related to plaque instability.

 

This view shows two plaques in the left carotid, in a patient with unstable carotid plaque manifested by microemboli on transcranial Doppler. The plane shown at left (in black) is a slice in the common carotid; the plaques shown extend into the internal carotid. The upper plaque (326.75mm 3 ) has had each slice traced in cross-section (plaque envelopes in yellow); the next step is mapping of the contours, shown in the lower plaque (407.25mm3). Longitudinal and cross-sectional views of this patient's ulcerated left carotid artery are shown below.

(From Spence JD, Blake C, Landry A, Fenster A. Measurement of carotid plaque and effect of vitamin therapy for total homocysteine. Clin Chem Lab Med. 2003; 41: 1498-504. )

Ulceration in a patient with microemboli on TCD (23)

Longitudinal view of the left internal carotid in a man with 70% stenosis and microemboli on TCD. Ulcers and fissures (below) likely explain the occurrence of microemboli

 

(From Spence JD, Tamayo A, DiCicco M. Unstable carotid plaque. CMAJ. 2002;166(9):1189.)

 

The figure below shows that it is now possible to measure effects of therapy on progression of plaque volume in 3 months, in 20 patients per group. The figure shows a significant difference in rate of progression on placebo vs regression on atorvastatin 80mg daily. This approach will make it possible to test new therapies much more efficiently than in the past.