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Title: Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

Abstract

Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction as determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.

Authors:
 [1];  [2];  [3];  [2];  [1]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Univ. of California, Davis, CA (United States). Center for Biophotonics Science and Technology
  2. Univ. of California, Davis, CA (United States). Davis Medical Center
  3. California Northstate Univ. College of Medicine, Elk Grove, CA (United States)
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE; National Science Foundation (NSF)
OSTI Identifier:
1361609
Report Number(s):
LLNL-JRNL-694546
Journal ID: ISSN 1083-3668
Grant/Contract Number:
AC52-07NA27344
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Biomedical Optics
Additional Journal Information:
Journal Volume: 22; Journal Issue: 5; Journal ID: ISSN 1083-3668
Publisher:
SPIE
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Raman, Rajesh N., Pivetti, Christopher D., Ramsamooj, Rajendra, Troppmann, Christoph, and Demos, Stavros G. Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy. United States: N. p., 2017. Web. doi:10.1117/1.JBO.22.5.056001.
Raman, Rajesh N., Pivetti, Christopher D., Ramsamooj, Rajendra, Troppmann, Christoph, & Demos, Stavros G. Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy. United States. doi:10.1117/1.JBO.22.5.056001.
Raman, Rajesh N., Pivetti, Christopher D., Ramsamooj, Rajendra, Troppmann, Christoph, and Demos, Stavros G. Wed . "Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy". United States. doi:10.1117/1.JBO.22.5.056001. https://www.osti.gov/servlets/purl/1361609.
@article{osti_1361609,
title = {Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy},
author = {Raman, Rajesh N. and Pivetti, Christopher D. and Ramsamooj, Rajendra and Troppmann, Christoph and Demos, Stavros G.},
abstractNote = {Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction as determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.},
doi = {10.1117/1.JBO.22.5.056001},
journal = {Journal of Biomedical Optics},
number = 5,
volume = 22,
place = {United States},
year = {Wed May 03 00:00:00 EDT 2017},
month = {Wed May 03 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
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  • Tissue that has undergone significant yet unknown amount of ischemic injury is frequently encountered in organ transplantation and trauma clinics. With no reliable real-time method of assessing the degree of injury incurred in tissue, surgeons generally rely on visual observation which is subjective. In this work, we investigate the use of optical spectroscopy methods as a potentially more reliable approach. Previous work by various groups was strongly suggestive that tissue autofluorescence from NADH obtained under UV excitation is sensitive to metabolic response changes. To test and expand upon this concept, we monitored autofluorescence and light scattering intensities of injured vs.more » uninjured rat kidneys via multimodal imaging under 355 nm, 325 nm, and 266 nm excitation as well as scattering under 500 nm illumination. 355 nm excitation was used to probe mainly NADH, a metabolite, while 266 nm excitation was used to probe mainly tryptophan to correct for non-metabolic signal artifacts. The ratio of autofluorescence intensities derived under these two excitation wavelengths was calculated and its temporal profile was fit to a relaxation model. Time constants were extracted, and longer time constants were associated with kidney dysfunction. Analysis of both the autofluorescence and light scattering images suggests that changes in microstructure tissue morphology, blood absorption spectral characteristics, and pH contribute to the behavior of the observed signal which may be used to obtain tissue functional information and offer predictive capability.« less
  • DNA damage activates specific cell signaling cascades for DNA repair, cell cycle arrest, senescence, and/or cell death. Recent studies have demonstrated DNA damage response (DDR) in experimental models of acute kidney injury (AKI). In cisplatin-induced AKI or nephrotoxicity, the DDR pathway of ATR/Chk2/p53 is activated and contributes to renal tubular cell apoptosis. In ischemic AKI, DDR seems more complex and involves at least the ataxia telangiectasia mutated (ATM), a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, and p53; however, while ATM may promote DNA repair, p53 may trigger cell death. Targeting DDR for kidney protection in AKI therefore reliesmore » on a thorough elucidation of the DDR pathways in various forms of AKI.« less
  • Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15 mg/kg). Glomerular filtrationmore » rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72 h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24 h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6 h post-dose, which preceded significant declines of GFR and ERPF (24 h), increased plasma Cr and BUN (72 h), and associated with renal acute tubular necrosis at 72 h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident. - Highlights: ► CDDP causes direct damage to kidneys without affecting EEG or CVS function. ► α-GST and albumin detect DIKI earlier when compared with traditional indices. ► Integrated “cardiovascular-EEG-renal” model to better understand DIKI mechanisms ► Promotes 3R's principles in drug discovery and development.« less