Background

Identification of different plaque components is of crucial importance to detect the rupture prone plaque. Typical parameters of these plaques are an eccentric plaque with a large atheroma covered by a thin fibrous cap [1]. The presence of macrophages in the cap further increases the vulnerability of these plaques [2]. It is known that the mechanical properties of fibrous and fatty plaque components are different [3]. Furthermore, fibrous caps with inflammation by macrophages are locally weakened [4]. All the stress that is applied on the plaque by the blood is concentrated in the cap since the lipid pool is unable to withstand forces on it [5]. The cap will rupture if it is unable to withstand the stress applied on it. This increased circumferential stress will result in an increased radial strain of the tissue. Therefore, a method that is capable of measuring the strain provides information that may influence clinical decision-making.

Plaque characterization

A validation study on excised human coronary (n=4) and femoral (n=9) arteries was performed (figure 2). Data were acquired at room temperature at intraluminal pressures of 80 and 100mmHg. Coronary arteries were measured using a solid state 20 MHz array catheter (EndoSonics, Rancho Cordova, CA, USA). Femoral arteries were investigated using a single element 30 MHz catheter (DuMed/ EndoSonics, Rijswijk, The Netherlands) that was connected to a modified motor unit (containing the pulser and receiver and a stepper-motor to rotate the catheter). The rf-data was stored and processed off-line. The visualized segments were stained on the presence of collagen, smooth muscle cells and macrophages. Matching of elastographic data and histology was performed using the IVUS echogram. The cross-sections were segmented in regions (n=125) based on the strain value on the elastogram. The dominant plaque types in these regions (fibrous, fibro-fatty or fatty) were obtained from histology and correlated with the average strain and echo-intensity.

Figure 2: Intravascular echogram (a) and elastogram (b) of a diseased human femoral artery with the corresponding histology: (c) picro-Sirius red with polarized light microscopy, (d) anti alfa-actin and (e) anti CD-68 antibody. The echogram reveals an eccentric plaque from 2 to 11 o’clock. The elastogram reveals high strain in the plaque in the plaque between 2 and 4 o’clock whereas low strain values were found in the remaining plaque area (both compared to the non diseased part of the vessel.) The histology reveals a fatty plaque region between 2 and 4 (absence of collagen (c) and smooth muscle cells (d) and rich on macrophages (e)) and a fibrous composition in the remaining part (rich on collagen (c) and smooth muscle cells (d) and absence of macrophages (e)).

Mean strain values of 0.27%, 0.45% and 0.60% were found for fibrous, fibro/fatty and fatty plaque components [6]. The strain for the three plaque types as determined by histology differed significantly (p=0.0002). This difference was independent on the type of artery (coronary or femoral) and was mainly evident between fibrous and fatty tissue (p=0.0004). The plaque types did not reveal echo-intensity differences in the IVUS echogram (p=0.992). Conversion of the strain into Young's modulus values was performed. Because the pressure differential and thus the stress are only known at the boundary between lumen and vessel-wall and due to non-linearity of this parameter this gives only a first order approximation of the modulus. Conversion of strain in modulus resulted in values of 493kPa, 296 kPa and 222 kPa for fibrous, fibro/fatty and fatty plaques. Although these values are higher than values measured by Lee et al [3], the ratio between fibrous and fatty material is similar. Since fibrous and fatty tissue demonstrated a different strain value and high strain values were often co-localised with increased concentrations of macrophages, these results reveal the potential of identification of the vulnerable plaque.

Vulnerable Plaque detection

Although plaque vulnerability is associated with the plaque composition, detection of a lipid or fibrous composition does not directly warrant identification of the vulnerable plaque. Therefore, a study to evaluate the predictive power of elastography to identify the vulnerable plaque was performed.
Diseased coronary arteries (n=24) were measured in vitro. Elastographic data was acquired at intracoronary pressures of 80 and 100 mmHg using a standard IVUS catheter (JOMED). After the ultrasound experiments, the cross-sections were stained for collagen and fat, smooth muscle cells (SMC), and macrophages. In histology, a vulnerable plaque was defined as a lesion with a large atheroma (>40%), a thin fibrous cap with moderate to heavy infiltration of macrophages. A plaque was considered vulnerable in elastography when a high strain region was present at the lumen-plaque boundary that was surrounded by low strain values. Using this definition, the instability of the region is assessed.
Vulnerable plaques (n=23) were correctly identified by elastography in 20 cases. Non-vulnerable plaques (n=31) were detected 27 times but false positive diagnosed as vulnerable in 4 cases [7,8]. This corresponds to a sensitivity and a specificity are both 87% and an 83% positive predictive value and a 90% negative predictive value.

References

[1] E. Falk, P. Shah and V. Fuster. "Coronary plaque disruption." Circulation, 92(3) (1995) 657-671.
[2] P.R. Moreno, E. Falk, I.F. Palacios, J.B. Newell, V. Fuster and J.T. Fallon. "Macrophage infiltration in acute coronary syndromes: implcations for plaque rupture." Circulation, 90(2) (1994) 775-778.
[3] R.T. Lee, G. Richardson, H.M. Loree, A.J. Gordzinsky, S.A. Gharib, F.J. Schoen and N. "Pandian, Prediction of mechanical properties of human atherosclerotic tissue by high-frequency intravascular ultrasound imaging." Arteriscler Thromb, 12 (1992) 1-5.
[4] C.L. Lendon, M.J. Davies, G.V.R. Born and P.D. Richardson. "Atherosclerotic plaque caps are locally weakened when macrophage density is increased." Atherosclerosis, 87 (1991) 87-90.
[5] P.D. Richardson, M.J. Davies and G.V.R. Born. "Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques." Lancet, 21 (1989) 941-944.
[6] C. L. de Korte, G. Pasterkamp, A. F. W. van der Steen, H. A. Woutman, N. Bom. “Characterization of plaque components with intravascular elastography in human femoral and coronary arteries in vitro” Circulation 2000; 102(6): 617-623
[7] J. A. Schaar, C. L. de Korte, F. Mastik, C. Strijder, G. Pasterkamp, A. F. W. van der Steen. “Vulnerable plaque detection with intravascular elastography: a sensitivity and specificity study” Circulation 2001; 104(6): II-459
[8] J. A. Schaar, C. L. de Korte, F. Mastik, C. Strijder, G. Pasterkamp, P. W. Serruys A. F. W. van der Steen. “Vulnerable plaque characterisation with intravascular elastography” J Am Coll Cardiol 2002; 39(5 suppl A): 19A