scholarly journals Three-dimensional morphometric analysis of human kidney nephron structures in health and disease

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Suneil Bhaskara ◽  
Michael Ferkowicz ◽  
Daria Barwinska ◽  
Tarek M. Ashkar (El-Achkar)
Keyword(s):  
Kidney Disease ◽  
3D Imaging ◽  
Morphological Changes ◽  
Three Dimensional ◽  
Kidney Tissue ◽  
Human Kidney ◽  
The United States ◽  
Therapeutic Interventions ◽  
Tubular Atrophy ◽  
Tissue Clearing

Background and Hypothesis: Chronic kidney disease (CKD) is very common and affects as many as 37 million people in the United States. Diabetes and hypertension are the most common causes of CKD.  The pathogenesis of CKD is not fully elucidated. Morphological changes such as glomerulosclerosis and tubular atrophy are commonly observed with advanced disease. However, it is unclear if such changes occur at earlier stages of disease, a time when therapeutic interventions are likely to have the most benefit. Measurements of glomerular, vascular and tubular dimensions have been typically derived from thin section, but a pipeline for acquiring these morphometric measurements in 3-dimentions have not been performed. Using enhanced tissue clearing, confocal 3D imaging and volumetric segmentation and analysis, we aimed at developing an approach to measure the dimensions of various structures within the human kidney. Our overarching hypothesis is that such approach could allow the detection of morphometric changes in early disease. Experimental Design or Project Methods: Kidney tissue were used either from donor nephrectomies or stored frozen biopsies from Biobank Biopsy Cohort of Indiana (BBCI). Enhanced tissue clearing and staining for nuclei, endothelium and  proximal tubules were performed. Optical sectioning and 3D Imaging was done using confocal microscopy. Volume rendering, segmentation and analysis were done using the Imaris Software (Bitplane). Various built in and customized segmentation approaches were used. Results: Volumes spanning 200 µm in thickness encompassing entire glomeruli and tubules were obtained. 3D Rendering of these volumes allowed visualization and enabled 3D segmentation. Dimensions of entire human glomeruli (maximum and minimum diameters, glomerular volumes and cellular densities), tubules and vessels were defined in control and samples with diabetic kidney disease. Conclusion and Potential Impact: Our studies established an approach for accurate measurements of the dimensions of nephronal structures preserved in their 3D environment within tissue. We also established the feasibility of this approach in comparing changes with disease vs. control.  Such methodology will open up a new line of investigations to better understand the pathogenesis of CKD, particularly at its early stages.  

scholarly journals 4557 Defining the relationship between kidney structure and function in patients with and without diabetes and hypertension

2020 ◽  
Vol 4 (s1) ◽  
pp. 47-47
Author(s):  
Ghazal Zekavat Quinn ◽  
Matthew Palmer ◽  
Jordana Cohen ◽  
Xin Sheng ◽  
Katalin Susztak
Keyword(s):  
Regression Analysis ◽  
Kidney Disease ◽  
Structural Changes ◽  
Polynomial Regression ◽  
Interstitial Fibrosis ◽  
Kidney Tissue ◽  
The United States ◽  
Hypertensive Patients ◽  
Patients With Diabetes ◽  
The Relationship

OBJECTIVES/GOALS: Histopathological descriptions of kidney tissue provide more information about kidney disease severity and prognosis than serum measures, yet most patients with chronic kidney disease do not undergo kidney biopsy. We aim to develop a method to determine the degree of renal injury in patients with diabetes and hypertension without the need for biopsy. METHODS/STUDY POPULATION: Clinical data and renal tissue samples were collected from 864 patients undergoing tumor-associated nephrectomy in seven medical centers in the United States. Exclusion criteria included age < 18, presence of pyelonephritis or non-diabetic or hypertensive renal disease or incomplete clinical or histopathologic data. 19 histologic parameters were scored in a blinded manner by one renal pathologist. We examined the relationship between and functional variables (such as estimated glomerular filtration rate (eGFR)). Polynomial regression analysis was performed to model histopathologic variables and important clinical parameters such as eGFR RESULTS/ANTICIPATED RESULTS: 607 samples met inclusion criteria and were stratified as: control (no history of diabetes or hypertension, n = 160), hypertension alone (n = 224) and both diabetes and hypertension (n = 223). Interstitial fibrosis (IF) and glomerulosclerosis (GS) had the strongest correlations with eGFR. Regression analysis was used to model histopathologic score for a given eGFR. We found that diabetes and hypertension modified the relationship between tubulointerstitial fibrosis and eGFR. For example, while hypertensive patients without diabetes had 33% IF at an eGFR of 30 ml/min/1.73m2 (r2 = 0.64, p<0.01), hypertensive patients with diabetes had 32% IF at an eGFR of 30 ml/min/1.73m2 (r2 = .43, p<0.01) and control patients had approximately 23% IF at an eGFR of 30 ml/min/1.73m2 (r2 = 0.22, p<0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Here, we describe the relationship between renal structural changes and renal function and show that hypertension significantly modifies the relationship at a given eGFR. These data can be used to reasonably predict renal structural changes given clinical information without the need for renal biopsy and may provide prognostic value.

scholarly journals Pathogenic and protective role of macrophages in kidney disease

2013 ◽  
Vol 305 (1) ◽  
pp. F3-F11 ◽  
Author(s):  
Qi Cao ◽  
Yiping Wang ◽  
David C. H. Harris
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Protective Role ◽  
Therapeutic Use ◽  
Disease Type ◽  
Dual Role ◽  
Murine Models

Macrophages (MΦ) are located throughout kidney tissue, where they play important roles in homeostasis, surveillance, tolerance, and cytoprotection. MΦ are highly heterogeneous cells and exhibit distinct phenotypic and functional characteristics depending on their microenvironment and the disease type and stage. Recent studies have identified a dual role for MΦ in several murine models of kidney disease. In this review, we discuss the pathogenic and protective roles of the various MΦ subsets in experimental and human kidney diseases and summarize current progress toward the therapeutic use of MΦ in kidney diseases.

Shock Wave Lithotripters With Broad Focus Result in Greater Stress in Human Kidney Stones: Numerical Simulation

2008 ◽  
Author(s):  
Haibiao Luo ◽  
Robin O. Cleveland ◽  
James C. Williams
Keyword(s):  
Shock Wave ◽  
Shock Waves ◽  
Kidney Stones ◽  
Three Dimensional ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Micro Computed Tomography ◽  
Displacement Fields ◽  
Computed Tomography Images ◽  
Shock Wave Lithotripters

Shock wave lithotripsy (SWL) has been used to treat kidney stones for decades. However, there is growing recognition that shock waves induces trauma to kidney tissue [1, 2]. The poor understanding of stone comminution mechanisms means that the design of new lithotripters is principally a practice of empiricism [3]. A mechanistic understanding of stone comminution would provide a criterion to develop new lithotripsy systems. In this work, a three-dimensional finite-difference time-domain (FDTD) solution to the linear elastic equations was employed [4] to investigate the stress and displacement fields of kidney stones subject to lithotripsy shock waves. The kidney stone models were obtained from micro-computed tomography images (resolution of 20 μm) and have diameters from 2 mm to 5 mm.

scholarly journals Perspective: Extending the Utility of Three-Dimensional Organoids by Tissue Clearing Technologies

2021 ◽  
Vol 9 ◽  
Author(s):  
Etsuo A. Susaki ◽  
Minoru Takasato
Keyword(s):  
Large Scale ◽  
3D Imaging ◽  
Imaging Techniques ◽  
3D Structure ◽  
Disease Onset ◽  
Three Dimensional ◽  
Cell Labeling ◽  
Tissue Clearing ◽  
Cellular Components ◽  
3D Imaging Techniques

An organoid, a self-organizing organ-like tissue developed from stem cells, can exhibit a miniaturized three-dimensional (3D) structure and part of the physiological functions of the original organ. Due to the reproducibility of tissue complexity and ease of handling, organoids have replaced real organs and animals for a variety of uses, such as investigations of the mechanisms of organogenesis and disease onset, and screening of drug effects and/or toxicity. The recent advent of tissue clearing and 3D imaging techniques have great potential contributions to organoid studies by allowing the collection and analysis of 3D images of whole organoids with a reasonable throughput and thus can expand the means of examining the 3D architecture, cellular components, and variability among organoids. Genetic and histological cell-labeling methods, together with organoid clearing, also allow visualization of critical structures and cellular components within organoids. The collected 3D data may enable image analysis to quantitatively assess structures within organoids and sensitively/effectively detect abnormalities caused by perturbations. These capabilities of tissue/organoid clearing and 3D imaging techniques not only extend the utility of organoids in basic biology but can also be applied for quality control of clinical organoid production and large-scale drug screening.

scholarly journals An atlas of healthy and injured cell states and niches in the human kidney

2021 ◽  
Author(s):  
Blue B. Lake ◽  
Rajasree Menon ◽  
Seth Winfree ◽  
Qiwen Hu ◽  
Ricardo Melo Ferreira ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Immune Responses ◽  
Large Scale ◽  
3D Imaging ◽  
Kidney Injury ◽  
Human Kidney ◽  
Cell Types ◽  
Molecular Signatures ◽  
Imaging Analysis ◽  
Future Studies

Understanding kidney disease relies upon defining the complexity of cell types and states, their associated molecular profiles, and interactions within tissue neighborhoods. We have applied multiple single-cell or -nucleus assays (>400,000 nuclei/cells) and spatial imaging technologies to a broad spectrum of healthy reference (n = 42) and disease (n = 42) kidneys. This has provided a high resolution cellular atlas of 100 cell types that include rare and novel cell populations. The multi-omic approach provides detailed transcriptomic profiles, epigenomic regulatory factors, and spatial localizations for major cell types spanning the entire kidney. We further identify and define cellular states altered in kidney injury, encompassing cycling, adaptive or maladaptive repair, transitioning and degenerative states affecting several segments. Molecular signatures of these states permitted their localization within injury neighborhoods using spatial transcriptomics, and large-scale 3D imaging analysis of ~1.2 million neighborhoods provided linkages to active immune responses. These analyses further defined biological pathways relevant to injury niches, including signatures underlying the transition from reference to predicted maladaptive states that were associated with a decline in kidney function during chronic kidney disease. This human kidney cell atlas, including injury cell states and neighborhoods, will be a valuable resource for future studies.

scholarly journals Quantitative Large-Scale Three-Dimensional Imaging of Human Kidney Biopsies: A Bridge to Precision Medicine in Kidney Disease

Nephron ◽  
2018 ◽  
Vol 140 (2) ◽  
pp. 134-139 ◽  
Author(s):  
Seth Winfree ◽  
Pierre C. Dagher ◽  
Kenneth W. Dunn ◽  
Michael T. Eadon ◽  
Michael Ferkowicz ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Precision Medicine ◽  
Large Scale ◽  
Three Dimensional ◽  
Human Kidney ◽  
Three Dimensional Imaging

Design and calibration of an IVEM for general 3-dimensional imaging of non-diffracting materials

1992 ◽  
Vol 50 (2) ◽  
pp. 1040-1041
Author(s):  
Neil Rowlands ◽  
Jeff Price ◽  
Michael Kersker ◽  
Seichi Suzuki ◽  
Steve Young ◽  
...  
Keyword(s):  
3D Imaging ◽  
Tomographic Reconstruction ◽  
Three Dimensional ◽  
3 Dimensional ◽  
3D Microstructure ◽  
Image Translation ◽  
Digital Correlation ◽  
On Line ◽  
Mechanical Stage ◽  
Projection Angle

Three-dimensional (3D) microstructure visualization on the electron microscope requires that the sample be tilted to different positions to collect a series of projections. This tilting should be performed rapidly for on-line stereo viewing and precisely for off-line tomographic reconstruction. Usually a projection series is collected using mechanical stage tilt alone. The stereo pairs must be viewed off-line and the 60 to 120 tomographic projections must be aligned with fiduciary markers or digital correlation methods. The delay in viewing stereo pairs and the alignment problems in tomographic reconstruction could be eliminated or improved by tilting the beam if such tilt could be accomplished without image translation.A microscope capable of beam tilt with simultaneous image shift to eliminate tilt-induced translation has been investigated for 3D imaging of thick (1 μm) biologic specimens. By tilting the beam above and through the specimen and bringing it back below the specimen, a brightfield image with a projection angle corresponding to the beam tilt angle can be recorded (Fig. 1a).

Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors

2003 ◽  
Vol 70 ◽  
pp. 201-212 ◽  
Author(s):  
Hideaki Nagase ◽  
Keith Brew
Keyword(s):  
Three Dimensional ◽  
Therapeutic Interventions ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Structural Basis ◽  
Structural Elements ◽  
Ridge Structure ◽  
Extracellular Matrix Components ◽  
Metalloproteinase Inhibitors ◽  
The Matrix ◽  
A Disintegrin And Metalloproteinase

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases.

Thermal characterization of ABS-Graphene blended three dimensional printed functional prototypes for electro chemical energy storage

2018 ◽  
Vol 1 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Kamaljit Singh Boparai ◽  
Rupinder Singh
Keyword(s):  
Energy Storage ◽  
Structural Changes ◽  
Fused Deposition Modeling ◽  
Morphological Changes ◽  
Three Dimensional ◽  
Thermal Characterization ◽  
Chemical Energy ◽  
Flow Index ◽  
Fused Deposition

This study highlights the thermal characterization of ABS-Graphene blended three dimensional (3D) printed functional prototypes by fused deposition modeling (FDM) process. These functional prototypes have some applications as electro-chemical energy storage devices (EESD). Initially, the suitability of ABS-Graphene composite material for FDM applications has been examined by melt flow index (MFI) test. After establishing MFI, the feedstock filament for FDM has been prepared by an extrusion process. The fabricated filament has been used for printing 3D functional prototypes for printing of in-house EESD. The differential scanning calorimeter (DSC) analysis was conducted to understand the effect on glass transition temperature with the inclusion of Graphene (Gr) particles. It has been observed that the reinforced Gr particles act as a thermal reservoir (sink) and enhances its thermal/electrical conductivity. Also, FT-IR spectra realized the structural changes with the inclusion of Gr in ABS matrix. The results are supported by scanning electron microscopy (SEM) based micrographs for understanding the morphological changes.

Analyzing the Impact of X-Ray Tomography on the Reliability of Integrated Circuits

2015 ◽  
Author(s):  
Halit Dogan ◽  
Md Mahbub Alam ◽  
Navid Asadizanjani ◽  
Sina Shahbazmohamadi ◽  
Domenic Forte ◽  
...  
Keyword(s):  
Integrated Circuits ◽  
Integrated Circuit ◽  
3D Imaging ◽  
Three Dimensional ◽  
Serial Sectioning ◽  
Promising Technique ◽  
Flash Memories ◽  
X Ray ◽  
3D Information ◽  
The Impact

Abstract X-ray tomography is a promising technique that can provide micron level, internal structure, and three dimensional (3D) information of an integrated circuit (IC) component without the need for serial sectioning or decapsulation. This is especially useful for counterfeit IC detection as demonstrated by recent work. Although the components remain physically intact during tomography, the effect of radiation on the electrical functionality is not yet fully investigated. In this paper we analyze the impact of X-ray tomography on the reliability of ICs with different fabrication technologies. We perform a 3D imaging using an advanced X-ray machine on Intel flash memories, Macronix flash memories, Xilinx Spartan 3 and Spartan 6 FPGAs. Electrical functionalities are then tested in a systematic procedure after each round of tomography to estimate the impact of X-ray on Flash erase time, read margin, and program operation, and the frequencies of ring oscillators in the FPGAs. A major finding is that erase times for flash memories of older technology are significantly degraded when exposed to tomography, eventually resulting in failure. However, the flash and Xilinx FPGAs of newer technologies seem less sensitive to tomography, as only minor degradations are observed. Further, we did not identify permanent failures for any chips in the time needed to perform tomography for counterfeit detection (approximately 2 hours).

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