Noninvasive real-time imaging of intima thickness after rat carotid artery balloon injury using ultrasound biomicroscopy.
OBJECTIVE
High frequency ultrasound imaging for small animal research (ultrasound biomicroscopy, UBM) has recently become available. Here, we evaluated the possibility to determine intima thickness in the rat carotid artery after balloon injury and to monitor intimal hyperplasia formation by UBM during pharmacological treatment.


METHODS
Balloon injury of the left carotid artery was performed on Sprague-Dawley rats. Carotid arteries of all animals were examined by Vevo 770 UBM (VisualSonics Inc.) using 55 MHz probe at day 1, 7, 14 and 21 after the injury. Whole vessel wall, intima and media thicknesses as well as lumen diameter were measured at different levels. Histomorphometric analyses were performed on day 14 and 21. A group of animals were treated with picropodophyllin, an insulin-like growth factor-1 receptor inhibitor.


RESULTS
Ex-vivo comparison of UBM and histology demonstrated an excellent correspondence of intimal tears, and the internal and external elastic membranes could be identified. We found also an agreement (Bland-Altman test) between histological measurements and UBM delineations of the rat carotid artery wall layers, with a significant correlation for intima-media thickness (r=0.97; p<0.0001) and intima measurements. We were able to follow changes in the vessel wall structure and vessel diameter as a response to balloon injury in real time. Furthermore, the therapeutic effect of picropodophyllin could be assessed using UBM.


CONCLUSIONS
UBM provides a reliable noninvasive, in-vivo visualization of rat vasculature. It allows us to perform longitudinal studies of intimal thickness progression and regression as well as lumen changes in individual animals.
Razuvaev
Anton
A
Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17176 Stockholm, Sweden. anton.razuvaev@ki.se
Lund
Kent
K
Roy
Joy
J
Hedin
Ulf
U
Caidahl
Kenneth
K
D000818:Animals; D002339:Carotid Arteries / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000473:pathology*; D002404:Catheterization / Q000009:adverse effects; D003952:Diagnostic Imaging; D018450:Disease Progression; D008297:Male; D033401:Microscopy, Acoustic / Q000379:methods*; D015588:Observer Variation; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D017539:Tunica Intima / Q000473:pathology*; D014465:Ultrasonics
C415032:picropodophyllin; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin