High-resolution renal perfusion mapping using contrast-enhanced ultrasonography in ischemia-reperfusion injury monitors changes in renal microperfusion

Abstract

Alterations in renal microperfusion play an important role in the development of acute kidney injury with long-term consequences. Here we used contrast-enhanced ultrasonography as a novel method for depicting intra-renal distribution of blood flow. After infusion of microbubble contrast agent, bubbles were collapsed in the kidney and post-bubble destruction refilling was measured in various regions of the kidney. Local perfusion was monitored in vivo at 15, 30, 45, 60 minutes and 24 hours after 28 min of bilateral ischemia in 12 mice. High-resolution, pixel-by-pixel, analysis was performed on each imaging clip using customized software, yielding parametric perfusion maps of the kidney, representing relative blood volume in each pixel. These perfusion maps revealed that outer medullary perfusion decreased disproportionately to the reduction in the cortical and inner medullary perfusion after ischemia. Outer medullary perfusion was significantly decreased by 69% at 60 minutes post-ischemia and remained significantly less (40%) than pre-ischemic levels at 24 hours post-ischemia. Thus, contrast-enhanced ultrasonography with high-resolution parametric perfusion maps can monitor changes in renal microvascular perfusion in space and time in mice. This novel technique can be translated to clinical use in man.

Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation

“…Audio Video Interleave (AVI) files were acquired at each pixel’s intensity as described previously (24). A Levenberg-Marquardt algorithm, which is suitable for non-linear data fitting problems, was used to solve for the perfusion parameters.…”

“…The transducer position was fixed using a mechanical positioning system. Nonlinear contrast imaging was performed with a smallanimal ultrasound scanner (Vevo 2100; VisualSonics, Toronto, ON, Canada) using a broadband linear transducer array (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) MHz, MS250, VisualSonics). B-mode images were used to initially locate the graft and to optimally position the transducer over the imaging plane.…”

“…In addition, applying a high-intensity ultrasound pulse to burst the microbubbles in a selected field, and subsequently monitoring the time and intensity by which microbubbles are resumed in the microvasculature can yield further information regarding the microvasculature patency. One of the emerging applications of CEUS is to assess the MP of tissues (18)(19)(20)(21)(22)(23)(24). Nonetheless, the application of CEUS in the diagnosis of transplant rejection remains to be fully explored.…”

The sympathetic nervous system in acute kidney injury

“…45 Studies on regional renal perfusion in mice and rats revealed that blood flow to the outer and inner renal medulla is disproportionately compromised during acute reperfusion of ischaemic kidneys, 53,54 which likely contributes to the specific localization of morphological renal alterations in response to IR. Data from a study comparing renal damage in animals with central sympathetic inhibition prior to renal artery clamping vs sympathetic inhibition after clamp release support this notion (see below).…”

Contrast-enhanced ultrasound: A promising method for renal microvascular perfusion evaluation

“…When compared to normal controls, dogs with iatrogenic hypercortisolism had significantly increased CEUS PI and AUC values in their kidneys compared to controls [25] . CEUS has also been successfully used for monitoring renal microvascular perfusion in ischemia/reperfusion injury in mice [26] , chronic renal ischemic injury in animal models [27] , porcine intra-abdominal hypertension [28] , as well as global hypoxia in piglets [29] . Examination of norepinephrinetreated dogs showed that CEUS parameters were predictive of effective renal plasma flow, suggesting that CEUS could also be used in assessing renal perfusion following pharmacologic intervention [30] .…”