Changes in CT angiographic opacification of porcine coronary artery wall with patchy altered flow in vasa vasorum

Abstract

To evaluate the potential of whole-body CT to detect localized areas of decreased or increased vascularity in coronary arterial walls. We used both microsphere embolization of coronary artery vasa vasorum to generate small areas of hypoperfusion and surrounding hyperperfusion of the arterial wall and diet-induced hypercholesterolemia. As a stimulus for localized angiogenesis, such as occurs in early plaque formation in the coronary arterial wall, microspheres were injected selectively into the LAD coronary artery lumens of anesthetized pigs. Fourteen pigs (acute) then had a segment of their LAD harvested during injection of contrast medium and snap-frozen for subsequent cryo-static micro-CT. An additional thirteen pigs (chronic) were allowed to recover, fed a high cholesterol diet and 3 months later were again anesthetized and a segment of the LAD artery harvested and scanned. The spatial distribution of the contrast agent within the arterial wall was measured in contiguous micro-CT images at right angles to the lumen axis with the area of wall in each cross-sectional image being approximately (0.1 mm)³ in size. In the acute animals there were no localized areas of increased contrast around the hypoperfused embolized perfusion territories in the arterial wall, but in the chronic animals the hypoperfused areas were surrounded by increased contrast. These results suggest that CT might be able to detect localized regions of increased vascularity in the arterial wall as an indicator of early atherosclerotic stimulation of vasa vasorum proliferation.

Appendix

The model used to analyze the increased perfusion around an embolized area of the arterial wall assumed that the hypoperfused area was elliptical in shape and is surrounded by a ring of hyper-vascularized tissue. These areas were determined using the directly measured width (along artery lumen axis) of the hypoperfused area (D_x) and the width of the hyper-vascularized ring (th). D_x, the diameter of the perfusion defect in the axial direction, was measured as the distance between the two hyper-vascularization peaks on the perfusion profile along the axial length of the vessel wall, CT (x) is the average CT gray scale value of the vessel wall in the ROI over the arterial wall in one CT slice. Dx and th was measured as the thickness of the hyper-vascularized ring on the profile. The hypoperfused area’s diameter in the arterial circumferential direction, D_y, could not be directly observed, and was calculated using the following measurements: CT(x) is the average CT gray scale value of the vessel wall in the ROI over the arterial wall in one CT slice. D_x and th as defined above, CT₁ is CT value of ‘normal’ myocardium, and CT₃ is CT value within the hypoperfused area. The hypoperfused and hyperemic tissues and the normal tissue were each assumed to be of uniform CT values. The CT value of the hypoperfused area was assumed to be 0.533/cm, which is the CT value of myocardium when no contrast agent is in the blood stream. The intensity of normal perfused tissue could be observed anywhere outside the boundaries of the hyper-vascularized region. The two remaining unknowns were CT₂ (the CT value in the hyperperfused region) and D_y (the circumference diameter of the perfused defect). These were calculated from the perfusion distribution using two specific points of interest—the maximum of the hyperperfused area, and the minimum value in the hypoperfused region as illustrated in Fig. 7.

Fig. 7

Upper panel is a schematic of an enface view of an unrolled coronary artery wall. The darker gray elliptical anulus is the hyperemic zone around the hypoperfused zone. The lower panel plots the average circumferential CT gray scale of the total wall CT gray scale value within each contiguous transverse slice along the axis of the arterial lumen

At position x the average CT value along the entire circumference (L) of the arterial wall within a single transluminal section is $\overline{CT}$(x).

The equation for the average CT value’s minimum in the hypoperfused region is:

$$ \overline{CT}_{\hbox{min} } = (CT_{1} (L - 2th - D_{y} ) + CT_{2} *2th + CT_{3} *D_{y} )/L $$

The equation for the maximum value in the hyper-perfused region is:

$$ \begin{gathered} \overline{CT}_{\hbox{max} } = (CT_{1} *(L - 2\Updelta Y_{o} (x)) + CT_{2} *2\Updelta Y_{o} (x))/L \end{gathered} $$

where

$$ \begin{gathered} {\Updelta Y_{0} (x)} \sqrt {\left( {1 - \frac{{D_{x}^{2} }}{{(D_{x} + 2th)^{2} }}} \right)\left( {\frac{{(D_{y} + 2th)^{2} }}{4}} \right)} \hfill \\ \end{gathered} $$

and ΔY₀ is the (outer) chord of the hypoperfused area in a cross-section at position x.

At x the vertical chord of the outer edge of the hyperemic rim is ΔY₀(x) is the chord at the inner edge of the hyperemic ring. D_x is the measured axial diameter of the hypoperfused area and D_y is the calculated diameter in the circumferential diameter. The hyperemic zone width is th:

• (a) Between x locations −(D _x /2) − th and −(D _x /2) and between (D _x /2) and (D _x /2) + th: $\overline{CT} (x) = \left[ {CT_{1} (L(x) - \Updelta Y_{0} (x)) + \,\Updelta Y_{0} (x)(CT_{2} )} \right]/L(x)$

• (b) Between −(D _x /2) and (D _x /2):

  $$ \overline{CT} (x) = \left[ {CT_{1} (L(x) - \Updelta Y_{0} (x)) + (\Updelta Y_{0} (x) - \Updelta Y_{i} (x))(CT_{2} ) + \Updelta Y_{i} (x)*CT_{3} } \right]/L(x) $$

• (c) As the area of the elliptical hypoperfused region = ΣΔ_y(x)

  then D_y = ΣΔ_y(x)/(π·D_x)

  $$ \begin{aligned} \, \Updelta Y_{0} (x) & = \sqrt {\left[ {1 - \frac{{x^{2} }}{{\left( {\left( {D_{x} + 2th} \right)/2} \right)^{2} }}} \right]\left[ {\left( {D_{y} + 2th} \right)/2} \right]} \\ \, \Updelta Y_{i} (x) & = \sqrt {\left[ {1 - \frac{{x^{2} }}{{\left( {D_{x} /2} \right)^{2} }}} \right]\left[ {\left( {D_{y} /2} \right)} \right]} \\ \end{aligned} $$

Noise in the perfusion profile as well as deviations of the hypoperfused area’s shape from elliptical made it difficult to use an analytical solution to calculate the CT₂ and D_y variables. Hence, we adjusted an estimate of the values of D_y and CT₂ empirically by overlaying a plot of the model onto the perfusion profile and then adjusting the variables until the model best fit to the perfusion profile such that the modeled profile in the regions around $\overline{\text{CT}}_{\hbox{min} }$ and $\overline{\text{CT}}_{ \hbox{max} }$.

Once the best fit values of D_y was established:

The area of the hypoperfused region, A_hypo = (π/4)D_y * D_x and

The area of the hyperperfused region, A_hyper = (π/4)[(D_x + 2th)(D_y + 2th) − A_hypo)].