Monitoring Of Renal Ischemia-Reperfusion Injury Using Optical Coherence Tomography

The kidney is an important organ of the human body.Its function is to filter plasma,reabsorb useful substances and excrete metabolic product in the form of urine.When the kidney subjected to acute or chronic injuries,the histological structure would change,as well as the renal function.Renal ischemia-reperfusion(IR)is an inevitable process in renal surgery,such as partial nephrectomy and renal transplantation.The surgery is prone to cause renal microstructural injury,resulting in a delayed renal function.The proximal tubule is the most sensitive to ischemia,and acute tubule necrosis(ATN)are a major cause of renal failure.There are some shortcomings in renal clinical diagnosis,non-real-time,invasive,expensive,and low resolution.To seek a new method for noninvasive and rapid real-time imaging the kidney,will be beneficial to the clinical IR injury assessment,as well on the renal source screening before transplantation and the monitoring of renal activity after transplantation.Optical coherence tomography(OCT)has a feature of noninvasive,high sensitivity,high resolution,deep penetration depth in biological tissue and fast imaging speed.OCT provides real-time imaging of living biological tissues in two and three dimensions in the micron order.And further get tissue microstructure and in vivo blood flow information.OCT has been used in various fields of biomedicine,such as ophthalmology,skin,gastrointestinal tract,urinary system and so on.The spatial resolution of the OCT can meet the need of ‘optical biopsy’ for renal microstructure and the imaging speed can meet the need of real-time monitoring.In view of this,OCT is expected to be a promising diagnostic tool.This dissertation investigates OCT as a diagnostic technology in imaging and evaluating renal IR injury.The work includes establishing renal IR model of living animals,monitoring the kidney using OCT,assessing IR injury by the changes of microstructure,optical properties,and texture features,and then extracting feature parameters for evaluating the renal status.A multi-dimensional quantitative evaluation of the IR injury was performed through the pathological changes revealed by two-photon microscopy and OCT.The specific research contents are summarized as follows.Firstly,since the lateral and axial resolution of OCT is independent,an automatic detection algorithm for the spatial resolution is developed,based on the imaging of a point spread function(PSF)model composed of Fe O nanoparticles.The spatial resolution in the light field of three OCT systems,one swept-source OCT(SS-OCT)of 1300 nm,one spectral domain OCT(SD-OCT)of 1300 nm and another of 900 nm,were derived from the PSF distribution along three mutually orthogonal axes.On this basis,the deconvolution algorithm for improving lateral resolution was further studied.Lucy-Richardson algorithm with known PSF was applied to OCT images,the optimum PSF was determined using an evaluation function based on image information entropy.The results showed that the proposed method can improve the resolution,reduce the noise,and improve the local signal-to-noise ratio and dynamic range.Secondly,a Wistar rat renal ischemia-reperfusion model was built for the study of in vivo kidney OCT imaging.The imaging performance of three OCT systems mentioned above was compared,in terms of spatial resolution,image signal-to-noise ratio,penetration depth in the kidney,and imaging depth of the visual microstructure.The SD-OCT system with a central wavelength of 1300 nm and 900 nm was eventually determined to perform the imaging study of renal IR injury.Time series OCT images during the IR process showed that the renal tubule was highly sensitive to ischemia,confirming the feasibility of applying OCT for the detection of IR injury.To quantitatively evaluate renal IR injury,algorithms of image adaptive threshold segmentation,tissue microstructure quantification,optical attenuation coefficient extraction and renal tubule distribution uniformity evaluation algorithm using fractal dimension were studied.Through the statistical analysis of IR injury caused by different ischemia time,the key parameters to distinguish kidney injury were determined,and the OCT optical characterization of normal and damaged kidneys was obtained.The results indicated that OCT imaging of the living kidney can be a promising method for rapid,realtime clinical diagnosis.A renal ischemia-reperfusion model with mannitol intervention was constructed to investigate the renal protective effect of mannitol through OCT monitoring.Under the same ischemia time,the IR injury of the ischemia group and the mannitol intervention group was compared.The results showed that the renal tubular density and optical attenuation coefficient of the two groups were significantly different,and mannitol had a certain protective effect on the microstructure of the kidney during the IR process.Finally,to confirm the objectivity of quantitative evaluation of microstructure injury from OCT images,and to investigate the microscopic mechanisms of renal tubular changes during ischemia-reperfusion process,two-photon microscopy(TPM)observation of fresh kidney tissues were conducted based on a rat kidney ischemia-reperfusion model.The morphological features of renal IR injury were extracted from TPM image,and the quantitative parameters of injury were determined.IR injuries were quantified by functional tubular density and tubular diameter.The results showed that imaging combined with OCT and TPM has a promising prospect in renal activity monitoring.