Intravital imaging of adriamycin-induced renal pathology using two-photon microscopy and optical coherence tomography

Hengchang Guo,Moshe Levi,Qinggong Tang,Tikina Smith,Erik Anderson,Hsing-Wen Wang,Yu Chen,Yi Liu,Peter M Andrews,Reuben Falola

doi:10.1142/s179354581850030x

Abstract

Adriamycin (doxorubicin), a common cancer chemotherapeutic drug, can be used to induce a model of chronic progressive glomerular disease in rodents. In our studies, we evaluated renal changes in a rat model after Adriamycin injection using two-photon microscopy (TPM), optical coherence tomography (OCT) and Doppler OCT (DOCT). Taking advantage of deep penetration and fast scanning speed for three-dimensional (3D) label-free imaging, OCT/DOCT system was able to reveal glomerular and tubular pathology noninvasively and in real time. By imaging renal pathology following the infusion of fluorophore-labeled dextrans of different molecular weights, TPM can provide direct views of glomerular and tubular flow dynamics with the onset and progression of renal disease. Specifically, glomerular permeability and filtration, proximal and distal tubular flow dynamics can be revealed. 6–8 weeks after injection of Adriamycin, TPM and OCT/DOCT imaging revealed glomerular sclerosis, compromised flow across the glomerular wall, tubular atrophy, tubular dilation, and variable intra-tubular flow dynamics. Our results indicate that TPM and OCT/DOCT provide real-time imaging of renal pathology in vivo that has not been previously available using conventional microscopic procedures.

Highlights

Kidney disease has been monitored using a number of di®erent imaging modalities, including ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI).[5,9]. These techniques allow for noninvasive, deep penetration and wideeld-of-view imaging, they do not have su±cient resolution to detect changes in renal microcirculation and pathology associated with microanatomy
Our objective is to demonstrate the feasibility of using noninvasive intravital imaging techniques Two-photon microscopy (TPM)/optical coherence tomography (OCT) to observe renal function within living kidneys in real time and evaluate the onset and progression of Chronic kidney disease (CKD),[46,47,48,49,50,51] and compare the characteristics of each modality
Our studies indicate that combining TPM and OCT/Doppler OCT (DOCT) can be a valuable procedure for evaluating renal histopathology

Summary

Introduction

Chronic kidney disease (CKD) is a growing health problem among the aging population.[1,2,3,4,5] It associates with a decline in renal function characterized pathologically by reduced glomerularltration rate (GFR), glomerulosclerosis, interstitialbrosis and tubular atrophy/dilation.[1,2,4,6] Adriamycin (doxorubicin) has been used to induce a model of CKD in rodents producing results similar to human CKD.[7,8]. Kidney disease has been monitored using a number of di®erent imaging modalities, including ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI).[5,9] these techniques allow for noninvasive, deep penetration and wideeld-of-view imaging, they do not have su±cient resolution to detect changes in renal microcirculation and pathology associated with microanatomy. Two-photon microscopy (TPM) is a rapidly emerging technology for high-resolution °uorescence molecular imaging and intravital studies.[14,19,20,21,22,23,24,25,26,27,28,29,30] TPM has been used for kidney function studies to image blood °ow, glomerularltration and permeability, tubular °ow dynamics and tubular re-absorption.[14,15,16,31,32,33]

Objectives

Methods

Results

Conclusion