Computer-assisted imaging algorithms facilitate histomorphometric quantification of kidney damage in rodent renal failure models

Klapczynski, Marcin; Gagné, Geneviève; Morgan, Sherry J.; Larson, Kelly J.; LeRoy, Bruce E.; Blomme, Eric A.G.; Cox, Bryan F.; Shek, Eugene W.

doi:10.4103/2153-3539.95456

Cited by 34 publications

(29 citation statements)

References 21 publications

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“…Like fibrosis quantification, DIA was used in another study to quantify inflammation areas but with poor discriminant capacity because of the inability to distinguish the noninflamed from mildly inflamed group. 46 More recently, Klapczynski et al 47 developed a computer-assisted imaging algorithm, which notably performed neutrophil quantification after identification of these cells by a nuclear algorithm used to identify immunohistochemically stained neutrophils as positive nuclei and using immunohistochemical Nuclear Classifier. To the best of our knowledge, we are the first to develop a reproducible automated label-free technique to quantify active inflammation on renal graft biopsies.…”

Section: Discussionmentioning

confidence: 99%

Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier–Transform Infrared Imaging Technique

Vuiblet

Fere

Gobinet

et al. 2015

JASN

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Renal interstitial fibrosis and interstitial active inflammation are the main histologic features of renal allograft biopsy specimens. Fibrosis is currently assessed by semiquantitative subjective analysis, and color image analysis has been developed to improve the reliability and repeatability of this evaluation. However, these techniques fail to distinguish fibrosis from constitutive collagen or active inflammation. We developed an automatic, reproducible Fourier-transform infrared (FTIR) imaging-based technique for simultaneous quantification of fibrosis and inflammation in renal allograft biopsy specimens. We generated and validated a classification model using 49 renal biopsy specimens and subsequently tested the robustness of this classification algorithm on 166 renal grafts. Finally, we explored the clinical relevance of fibrosis quantification using FTIR imaging by comparing results with renal function at 3 months after transplantation (M3) and the variation of renal function between M3 and M12. We showed excellent robustness for fibrosis and inflammation classification, with .90% of renal biopsy specimens adequately classified by FTIR imaging. Finally, fibrosis quantification by FTIR imaging correlated with renal function at M3, and the variation in fibrosis between M3 and M12 correlated well with the variation in renal function over the same period. This study shows that FTIRbased analysis of renal graft biopsy specimens is a reproducible and reliable label-free technique for quantifying fibrosis and active inflammation. This technique seems to be more relevant than digital image analysis and promising for both research studies and routine clinical practice.

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Section: Discussionmentioning

confidence: 99%

Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier–Transform Infrared Imaging Technique

Vuiblet

Fere

Gobinet

et al. 2015

JASN

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“…Once this “teaching” is complete, the software has the ability to identify NFTs and NPs on any PHF-1-stained section in a very reproducible manner. This pattern recognition software has been successfully used in a variety of pathologic conditions, ranging from kidney failure to breast carcinoma (38, 39). …”

Section: Introductionmentioning

confidence: 99%

Digital Pathology and Image Analysis for Robust High-Throughput Quantitative Assessment of Alzheimer Disease Neuropathologic Changes

Neltner

Abner

Schmitt

et al. 2012

J Neuropathol Exp Neurol

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Quantitative neuropathologic methods provide information that is important for both research and clinical applications. The technological advancement of digital pathology and image analysis offers new solutions to enable valid quantification of pathological severity that is reproducible between raters regardless of experience. Using an Aperio ScanScope XT and its accompanying image analysis software, we designed algorithms for quantitation of amyloid and tau pathologies on 65 β-amyloid (6F/3D antibody) and 48 phospho-tau (PHF-1)-immunostained sections of human temporal neocortex. Quantitative digital pathologic data were compared with manual pathology counts. There were excellent correlations between manually counted and digitally analyzed neuropathologic parameters (R2 values 0.56-0.72). Data were highly reproducible among 3 participants with varying degrees of expertise in neuropathology (Intra-class correlation coefficient values >0.910). Digital quantification also provided additional parameters, including average plaque area, which show statistically significant differences when samples are stratified according to APOE allele status (average plaque area 380.9 μm2 in ApoE ε4 carriers vs. 274.4 μm2 for non-carriers, p < 0.001). Thus, digital pathology offers a rigorous and reproducible method for quantifying AD neuropathologic changes and may provide additional insight into morphologic characteristics that were previously more challenging to assess due to technical limitations.

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“…In separate studies, lungs sections were stained for active caspase 3 with anticleaved caspase-3 antibody (1:200) (Cell Signaling, Danvers, MA). Quantification was performed using Genie and the Nuclear Algorithm (Aperio) software to score nuclear density in the alveolar compartment as described previously, and data were expressed as number of caspase 3-active positive cells/mm 2 (18,19).…”

Section: Lung Histology and Immunochemistrymentioning

confidence: 99%

Nicotinamide Phosphoribosyltransferase Inhibitor Is a Novel Therapeutic Candidate in Murine Models of Inflammatory Lung Injury

Moreno‐Vinasco¹,

Quijada

Sammani³

et al. 2014

Am J Respir Cell Mol Biol

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We previously identified the intracellular nicotinamide phosphoribosyltransferase (iNAMPT, aka pre-B-cell colony enhancing factor) as a candidate gene promoting acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI) with circulating nicotinamide phosphoribosyltransferase potently inducing NF-kB signaling in lung endothelium. iNAMPT also synthesizes intracellular nicotinamide adenine dinucleotide (iNAD) in response to extracellular oxidative stress, contributing to the inhibition of apoptosis via ill-defined mechanisms. We now further define the role of iNAMPT activity in the pathogenesis of ARDS/VILI using the selective iNAMPT inhibitor FK-866. C57/B6 mice were exposed to VILI (40 ml/kg, 4 h) or LPS (1.5 mg/kg, 18 h) after osmotic pump delivery of FK-866 (100 mg/kg/d, intraperitoneally). Assessment of total bronchoalveolar lavage (BAL) protein, polymorphonuclear neutrophil (PMN) levels, cytokine levels (TNFa, IL-6, IL-1a), lung iNAD levels, and injury scores revealed that FK-866-mediated iNAMPT inhibition successfully reduced lung tissue iNAD levels, BAL injury indices, inflammatory cell infiltration, and lung injury scores in LPS-and VILI-exposed mice. FK-866 further increased lung PMN apoptosis, as reflected by caspase-3 activation in BAL PMNs. These findings support iNAMPT inhibition via FK-866 as a novel therapeutic agent for ARDS via enhanced apoptosis in inflammatory PMNs. Keywords: apoptosis; FK-866; nicotinamide phosphoribosyltransferase; polymorphonuclear neutrophil; vascular endothelium Clinical RelevanceWe previously identified NAMPT as a candidate gene promoting both acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). We now further define the role of intracellular nicotinamide phosphoribosyltransferase (NAMPT) activity in the pathogenesis of ARDS/VILI using the selective intracellular NAMPT inhibitor FK-866. These findings support intracellular NAMPT inhibition via FK-866 as a novel therapeutic agent for ARDS via enhanced apoptosis in inflammatory polymorphonuclear neutrophils.Acute respiratory distress syndrome (ARDS) is a devastating inflammatory lung syndrome characterized by diffuse alveolar infiltration, hypoxemia, and respiratory failure that develops in response to a variety of local and systemic insults (e.g., sepsis, pneumonia, and trauma). Hallmarks of ARDS include profound inflammation, deranged alveolar capillary permeability, leukocyte extravasation, spatial heterogeneity, and lung edema, which contribute to multiorgan dysfunction and increased mortality. The exposure to mechanical stress via mechanical ventilation, a supportive intervention strategy for severe respiratory failure, also contributes to multiorgan dysfunction and ARDS mortality.We and others have previously demonstrated that the circulating cytozyme pre-B-cell colony enhancing factor (NAMPT) is a biomarker in sepsis and sepsis-induced ARDS with genetic variants conferring ARDS susceptibility (1-3).

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Computer-assisted imaging algorithms facilitate histomorphometric quantification of kidney damage in rodent renal failure models

Cited by 34 publications

References 21 publications

Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier–Transform Infrared Imaging Technique

Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier–Transform Infrared Imaging Technique

Digital Pathology and Image Analysis for Robust High-Throughput Quantitative Assessment of Alzheimer Disease Neuropathologic Changes

Nicotinamide Phosphoribosyltransferase Inhibitor Is a Novel Therapeutic Candidate in Murine Models of Inflammatory Lung Injury

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