Chronic kidney disease (CKD) is characterized by a progressive loss of renal function over time. Histopathological analysis of the condition of glomeruli and the proximal convolutional tubules over time can provide valuable insights into the progression of CKD. Optical coherence tomography (OCT) is a technology that can analyze the microscopic structures of a kidney in a nondestructive manner. Recently, we have shown that OCT can provide real-time imaging of kidney microstructures in vivo without administering exogenous contrast agents. A murine model of CKD induced by intravenous Adriamycin (ADR) injection is evaluated by OCT. OCT images of the rat kidneys have been captured every week up to eight weeks. Tubular diameter and hypertrophic tubule population of the kidneys at multiple time points after ADR injection have been evaluated through a fully automated computer-vision system. Results revealed that mean tubular diameter and hypertrophic tubule population increase with time in post-ADR injection period. The results suggest that OCT images of the kidney contain abundant information about kidney histopathology. Fully automated computer-aided diagnosis based on OCT has the potential for clinical evaluation of CKD conditions.
The main cause of delayed renal function following the transplant of donor kidneys is ischemic induced acute tubular necrosis (ATN). The ability to determine the degree of ATN suffered by donor kidneys prior to their transplant would enable transplant surgeons to use kidneys that might otherwise be discarded and better predict post-transplant renal function. Currently, there are no reliable tests to determine the extent of ATN of donor kidneys prior to their transplant. In ongoing clinical trials, we have been using optical coherence tomography (OCT) to non-invasively image the superficial proximal tubules of human donor kidneys prior to and following transplant, and correlate these observations with post-transplant renal function. Thus far we have studied over 40 living donor kidneys and 10 cadaver donor kidneys, and demonstrated that this imaging can be performed in a sterile and expeditious fashion in the operating room (OR). Because of many variables associated with a diverse population of donors/recipients and transplant operation parameters, more transplant data must be collected prior to drawing definite conclusions. Nevertheless, our observations have thus far mirrored our previously published laboratory results indicating that damage to the kidney proximal tubules as indicated by tubule swelling is a good measure of post-transplant ATN and delayed graft function. We conclude that OCT is a useful procedure for analyzing human donor kidneys.
Chronic Kidney Disease (CKD) is characterized by a progressive loss in renal function over time. Pathology can provide valuable insights into the progression of CKD by analyzing the status of glomeruli and the uriniferous tubules over time. Optical coherence tomography (OCT) is a new procedure that can analyze the microscopic structure of the kidney in a non-invasive manner. This is especially important because there are significant artifacts associated with excision biopsies and immersion fixation procedures. Recently, we have shown that OCT can provide real time images of kidney microstructure and Doppler OCT (DOCT) can image glomerular renal blood flow in vivo without administrating exogenous contrast agents. In this study, we used OCT to evaluate CKD in a model induced by intravenous Adriamycin injection into Munich-Wistar rats. We evaluated tubular density and tubular diameter from OCT images at several post- Adriamycin induction time points and compared them with conventional light microscopic histological imaging. Proteinurea and serum creatinine were used as physiological markers of the extent of CKD. Preliminary OCT results revealed changes in tubular density due to tubular necrosis and interstitial fibrosis within the first 4 weeks following Adriamycin injection. From week 4 to 8 after Adriamycin induction, changes in tubular density and diameter occurred due to both tubular loss and tubular dilation. The results suggest OCT can provide additional information about kidney histopathology in CKD. DOCT revealed reduced blood flow in some glomeruli probably as a consequence of focal glomerularsclerosis.
Peter Andrews, Yu Chen, Jeremiah Wierwille, Daniel Joh, Peter Alexandrov, Derek Rogalsky, Patrick Moody, Allen Chen, Matthew Cooper, Jennifer Verbesey, Wei Gong, Hsing-Wen Wang
The treatment of choice for patients with end-stage renal disease is kidney transplantation. However, acute tubular necrosis (ATN) induced by an ischemic insult (e.g., from prolonged ex vivo storage times, or non-heart beating cadavers) is a major factor limiting the availability of donor kidneys. In addition, ischemic induced ATN is a significant risk factor for eventual graft survival and can be difficult to discern from rejection. Currently, there are no rapid and reliable tests to determine ATN suffered by donor kidneys and whether or not donor kidneys might exhibit delayed graft function. OCT (optical coherence tomography) is a rapidly emerging imaging modality that can function as a type of “optical biopsy”, providing cross-sectional images of tissue morphology in situ and in real-time. In a series of recent clinical trials, we evaluated the ability of OCT to image those features of the renal microstructure that are predictive of ATN. Specifically, we found that OCT could effectively image through the intact human renal capsule and determine the extent of acute tubular necrosis. We also found that Doppler based OCT (i.e., DOCT) revealed renal blood flow dynamics that is also reported to be a determiner of post-transplant renal function. This kind of information will allow transplant surgeons to make the most efficient use of available donor kidneys, eliminate the possible use of bad donor kidneys, provide a measure of expected post-transplant renal function, and allow better distinction between post-transplant immunological rejection and ischemic-induced acute renal failure.
Optical coherence tomography (OCT) is an emerging medical imaging technology that enables high-resolution, noninvasive, cross-sectional imaging of microstructure in biological tissues in situ and in real time. When combined with small-diameter catheters or needle probes, OCT offers a practical tool for the minimally invasive imaging of living tissue morphology. We evaluate the ability of OCT to image normal kidneys and discriminate pathological changes in kidney structure. Both control and experimental preserved rat kidneys were examined ex vivo by using a high-resolution OCT imaging system equipped with a laser light source at 1.3-µm wavelength. This system has a resolution of 3.3 µm (depth) by 6 µm (transverse). OCT imaging produced cross-sectional and en face images that revealed the sizes and shapes of the uriniferous tubules and renal corpuscles. OCT data revealed significant changes in the uriniferous tubules of kidneys preserved following an ischemic or toxic (i.e., mercuric chloride) insult. OCT data was also rendered to produce informative three-dimensional (3-D) images of uriniferous tubules and renal corpuscles. The foregoing observations suggest that OCT can be a useful non-excisional, real-time modality for imaging pathological changes in donor kidney morphology prior to transplantation.
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