Quantitative evaluation of contrast-enhanced ultrasonography in the diagnosis of chronic ischemic renal disease in a dog model

Abstract

Objectives: The aim of this feasibility study was to prospectively explore in a dog model of chronic ischemic renal disease (CIRD) the hypothesis that real-time contrast-enhanced ultrasonography (CEUS) can quantitatively evaluate the early perfusion changes of renal cortex.

Materials and methods: In this animal care and use committee-approved study, the model of CIRD was carried out in healthy dogs (10.0~12.0 kg, n=5), by placing the Ameroid ring constrictors on the distal portion of right renal artery through operation. CEUS monitoring of right kidney perfusion was performed by intravenous bolus injection of 0.6 ml Sulfur hexafluoride filled microbubbles (SonoVue; Bracco S.P.A., Milan, Italy) every week after operation. The slope rate of ascending curve (A) and descending curve (α), area under curve (AUC), derived peak intensity (DPI), and time to peak (TTP) were measured in renal cortex using commercial quantification software (Q-LAB version 6; Philips Medical Systems, Bothell,WA,USA). The sensitivity of CEUS was compared with blood serum urea nitrogen (BUN) and serum creatinine (SCr) level.

Results: With the progression of CIRD, dogs showed delayed enhancement and perfusion in renal CEUS curve. Earliest significant changes happened 4 weeks after operation on DPI and TTP which changed from 13.04 ± 2.71 to 15.58 ± 4.75 dB and 9.03 ± 2.01 to 10.62 ± 6.04 sec, respectively (P<.05).

Conclusions: CEUS can display the perfusion changes of CIRD in the early period.

Figure 1. The gamma-variate function represents a suitable curve fit approximation of the time-intensity curve (TIC).

With the formula for the gamma-variate function, quantitative perfusion parameters such as the slope rate of ascending curve (A), the slope rate of descending curve (α), area under curve (AUC), derived peak intensity (DPI), time to peak (TTP) were measured to estimate renal blood flow.

Figure 2. CEUS renal perfusion images.

CEUS renal perfusion images were converted into a time-intensity curve (TIC) by Q-LAB quantification software, which was generated from the region of interest (ROI). (a) TIC of dog’s right kidney before operation. (b) TIC of dog’s right kidney 5 weeks after the placement of AC. (c) TIC of dog’s right kidney 7 weeks after the placement of AC. TIC showed weekly delayed enhancement and perfusion in the renal perfusion curve. The slope rate of ascending curve was lower and descending curve was higher. It took more time to reach the peak intensity.

Figure 3. Changes of quantitative indexes in dogs’ CIRD models (1∼12 weeks after operation).

With the progress of CIRD, area under curve (AUC), time to peak (TTP), derived peak intensity (DPI) and the slope rate of descending curve (α) gradually increased, however the slope rate of ascending curve (A)decreased.

Figure 4. Pathologic changes of vessel inside and outside AC.

(a) Vessel outside AC: slight hyperplasia of the vascular smooth muscle. (b) Vessel inside AC: Obvious hyperplasia of the vascular smooth muscle, narrowing of the renal artery with wall thickening. (hematoxylin and eosin, original magnification ×40).