Background

For in vivo validation of the technique, animal experiments are of crucial importance since it allows correlating elastograms with histology. In contrary to in vitro experiments, a pulsatile pressure acts as the deformation force. Since data is acquired in the a iliac and femoral artery of a Yucatan the out of plane motion is minimal. In human coronary arteries, out of plane motion is present and therefor a special acquisition scheme was applied. A likelihood function is determined and this function represents the motion of the catheter. In these animal experiments, high likelihood values are present in the diastolic phase.

Atherosclerotic Yucatan model

External iliac and femoral arteries were made atherosclerotic by endothelial Fogarty denudation and subsequent atherosclerotic diet for the duration of 7 months. Balloon dilation was performed in the femoral arteries and the diet was discontinued. Before termination, 6 weeks after balloon dilation and discontinuation of the diet, data were acquired in the external iliac and femoral artery in 6 Yucatan pigs. In total, 24 cross-sections were investigated with a 20 MHz Visions® catheter (JOMED, Rancho Cordova, CA). The tissue was strained by the pulsatile blood pressure. Two frames acquired at end diastole with a pressure differential of approx. 4 mmHg were taken to determine the elastograms.

After the ultrasound experiments and before dissection, X-ray was used to identify the arterial segments that had been investigated by ultrasound. The specimens were frozen in liquid nitrogen. The cross-sections (7mm) were stained for collagen (picro Sirius red and polarized light) and macrophages (alcalic phosphatase). Plaques were classified as absent, as early fibrous lesion, as early fatty lesion or as advanced fibrous plaque. The mean strain in these plaques and normal cross- sections was determined.

Strains were similar in the plaque free arterial wall (0.21%) and the early (0.24%) and advanced fibrous plaques (0.22%) [1]. Higher average strain values were observed in fatty lesions (0.46%). Univariate Analysis of Variance revealed that this difference was highly significant (p=0.007). After correction for confounding by lipid content, no additional differences in average strain were found between plaques with and without macrophages (p=0.966). ROC analysis revealed a sensitivity and specificity of 100% and 80% respectively to identify fatty plaques. The presence of a high strain spot (an area with strain values higher than 1%) has 92% sensitivity and 92% specificity to identify macrophages.

Figure 1: IVUS echogram (A) and elastogram (B) of cross-section with an advanced fibrous lesion. Low strain values were found in this plaque. The plaque is mainly composed of collagen and no macrophages were found. Histology (elastin-von Gieson (C), picro-Sirius red (D), picro-Sirius red imaged with polarized light microscopy (E) and acid phosphatase (F)) reveals that the plaque was imaged from a false lumen that was created during the intervention. The region in the elastogram with no strain values corresponds to the original lumen.

References

[1] C. L. de Korte, M. Sierevogel, F. Mastik, C. Strijder, J. A. Schaar, E. Velema, G. Pasterkamp, P. W. Serruys and A. F. W. van der Steen. “Identification of Atherosclerotic Plaque Components with Intravascular Ultrasound Elastography in vivo: a Yucatan pig study.” Circulation 2002; 105(14): 1627-1630