Quantitative Morphological Analysis Research Articles

Ultrastructural and proteomic profiling of mitochondria-associated endoplasmic reticulum membranes reveal aging signatures in striated muscle

Aging is a major risk for developing cardiac and skeletal muscle dysfunction, yet the underlying mechanism remains elusive. Here we demonstrated that the mitochondria-associated endoplasmic reticulum membranes (MAMs) in the rat heart and skeletal muscle were disrupted during aging. Using quantitative morphological analysis, we showed that the mitochondria-endoplasmic reticulum contacts (MERCs) were reduced by half over the lifespan with an early onset of accelerated thickening in the clefts. The ultrastructural changes were further validated by proteomic profiling of the MAM fractions. A combination of subcellular fractionation and quantitative mass spectrometry identified 1306 MAM-enriched proteins in both heart and skeletal muscle, with a catalog of proteins dysregulated with aging. Functional mapping of the MAM proteome suggested several aging signatures to be closely associated with the ER-mitochondria crosstalk, including local metabolic rewiring, calcium homeostasis imbalance, and impaired organelle dynamics and autophagy. Moreover, we identified a subset of highly interconnected proteins in an ER-mitochondria organization network, which were consistently down-regulated with aging. These decreased proteins, including VDAC1, SAMM50, MTX1 and MIC60, were considered as potential contributors to the age-related MAM dysfunction. This study highlights the perturbation in MAM integrity during the striated muscle aging process, and provides a framework for understanding aging biology from the perspective of organelle interactions.

New Geometric Models for Shape Quantification of the Dorsal View in Seeds of Silene Species.

The description of shape in Silene seeds is based on adjectives coined by naturalists in the 19th century. The expressions reniform, dorso plana, and dorso canaliculata were applied in reference to lateral or dorsal views of seeds, but the characters described can be submitted now to an analytical description by quantitative methods, allowing shape quantification and the comparison between species or populations. A quantitative morphological analysis is based on the comparison with geometric models that adjust to the shape of seeds. Morphological analysis of the dorsal view of Silene seeds based on geometric models is applied here to 26 seed populations belonging to 12 species. According to their dorsal views, the seeds are classified as convex and non-convex. New geometric models are presented for both types, including figures such as super-ellipses and modified ellipses. The values of J index (percent of similarity of a seed image with the model) are obtained in representative seed samples from diverse populations and species. The quantitative description of seed shape based on the comparison with geometric models allows the study of variation in shape between species and in populations, as well as the identification of seeds in Silene species. The method is of application to other plant species.

A Workflow for Three-Dimensional Reconstruction and Quantification of the Monkey Optic Nerve Head Vascular Network.

A comprehensive characterization of the three-dimensional (3D) vascular network of the optic nerve head (ONH) is critical to understanding eye physiology and pathology. Current in vivo imaging technologies, however, do not have simultaneous high spatial resolution and imaging depth to resolve the small vessels deep within the ONH. We describe a workflow for the 3D reconstruction and quantitative morphological analysis of the ONH vasculature. The vessels of a normal monkey ONH were perfusion labeled. Serial cryosections of the ONH were imaged using fluorescence microscopy (FM) and instant polarized light microscopy (IPOL) to visualize the labeled vessels and label-free collagen, respectively. The IPOL images were registered and used to form a stack of FM images from which the vessels were segmented and skeletonized to reconstruct the 3D vascular network. The network consisted of 12,966 vessel segments, 7989 branching points, and 1100 terminal points at the boundaries. For each vessel segment, we measured its length, tortuosity, inclination (θ), and polar orientation (φ). The length followed a lognormal distribution, whereas the distribution of the tortuosity followed an exponential decay. The vessels were mainly oriented toward the coronal plane (θ = 90 deg). For orientation, there were nearly as many vessels aligned circumferentially (φ = 90 deg) and radially (φ = 0 deg). Our results demonstrate the workflow for 3D eye-specific reconstruction and quantification of the monkey ONH vascular network. This is a critical first step to analyze the blood flow and oxygenation within the ONH, which will help understand the role of vascular dysfunction in glaucoma.

RealNeuralNetworks.jl: An Integrated Julia Package for Skeletonization, Morphological Analysis, and Synaptic Connectivity Analysis of Terabyte-Scale 3D Neural Segmentations.

Benefiting from the rapid development of electron microscopy imaging and deep learning technologies, an increasing number of brain image datasets with segmentation and synapse detection are published. Most of the automated segmentation methods label voxels rather than producing neuron skeletons directly. A further skeletonization step is necessary for quantitative morphological analysis. Currently, several tools are published for skeletonization as well as morphological and synaptic connectivity analysis using different computer languages and environments. Recently the Julia programming language, notable for elegant syntax and high performance, has gained rapid adoption in the scientific computing community. Here, we present a Julia package, called RealNeuralNetworks.jl, for efficient sparse skeletonization, morphological analysis, and synaptic connectivity analysis. Based on a large-scale Zebrafish segmentation dataset, we illustrate the software features by performing distributed skeletonization in Google Cloud, clustering the neurons using the NBLAST algorithm, combining morphological similarity and synaptic connectivity to study their relationship. We demonstrate that RealNeuralNetworks.jl is suitable for use in terabyte-scale electron microscopy image segmentation datasets.

Morphological Characterization of PE Blown Films by Atomic Force Microscopy

AbstractThe properties of blown polyethylene (PE) films depend on various factors, including crystallinity, morphology, and orientation, in addition to chemical composition. It has been shown that the optical properties are strongly influenced by surface morphology. In this work, non-contact atomic force microscopy (AFM) and polarized light microscopy (PLM) were used to visualize surface and bulk morphology. Various techniques, such as surface and line roughness, surface and line fractal dimension, pair-correlation function and nearest neighbor distance distribution function, are employed to quantify the description of morphology and to compare the morphological characteristics of a number of polyethylene (PE) films of commercial interest. A comprehensive quantitative analysis of surface topography has been performed. The co-monomer of the PE resins was found to play a significant role in the formation and the orientation of spherulite-like domains. The film cross-section microstructure has been evaluated qualitatively by using both AFM and PLM. However, quantitative analysis of bulk morphology cannot be obtained due to knife effects.

Quantitative Chemical Imaging of Bone Tissue for Intraoperative and Diagnostic Applications.

Bone is difficult to image using traditional histopathological methods, leading to challenges in intraoperative pathological evaluation that is critical in guiding surgical treatment, particularly in orthopedic oncology. In this study, we demonstrate that a multimodal quantitative imaging approach that combines stimulated Raman scattering (SRS) microscopy, two-photon fluorescence (TPF) microscopy, and second-harmonic generation (SHG) microscopy can provide useful diagnostic information regarding intact bone tissue fragments from surgical excision or biopsy specimens. We imaged bone samples from 17 patient cases and performed quantitative chemical and morphological analyses of both mineral and organic components of bone. Our main findings show that carbonate content combined with morphometric analysis of bone organic matrix can separate several major classes of bone cancer-associated diagnostic categories with an average accuracy of 92%. This proof-of-principle study demonstrates that quantitative multimodal imaging and machine learning-based analysis of bony tissue can provide crucial diagnostic information for guiding clinical decisions in orthopedic oncology. Moreover, the general methodology of morphological and chemical imaging combined with machine learning can be readily extended to other tissue types for tissue diagnosis in intraoperative and other clinical settings.

Quantitative Analysis of Urban Spatial Morphology Based on GIS Regionalization and Spatial Syntax

Quantitative Analysis of Urban Spatial Morphology Based on GIS Regionalization and Spatial Syntax

The neuronal retromer can regulate both neuronal and microglial phenotypes of Alzheimer's disease.

SUMMARYDisruption of retromer-dependent endosomal trafficking is considered pathogenic in late-onset Alzheimer’s disease (AD). Here, to investigate this disruption in the intact brain, we turn to a genetic mouse model where the retromer core protein VPS35 is depleted in hippocampal neurons, and then we replete VPS35 using an optimized viral vector protocol. The VPS35 depletion-repletion studies strengthen the causal link between the neuronal retromer and AD-associated neuronal phenotypes, including the acceleration of amyloid precursor protein cleavage and the loss of synaptic glutamate receptors. Moreover, the studies show that the neuronal retromer can regulate a distinct, dystrophic, microglia morphology, phenotypic of hippocampal microglia in AD. Finally, the neuronal and, in part, the microglia responses to VPS35 depletion were found to occur independent of tau. Showing that the neuronal retromer can regulate AD-associated pathologies in two of AD’s principal cell types strengthens the link, and clarifies the mechanism, between endosomal trafficking and late-onset sporadic AD.

Anatomic Considerations of the Distal Fibula: A Computed Tomography Guided Analysis

Category:Ankle; Basic Sciences/Biologics; Trauma; OtherIntroduction/Purpose:Ankle fractures are a common injury in the general population with nearly sixty thousand operations performed in California for fractures involving the tibiotalar joint over a 10-year span. Reestablishing anatomic fibular alignment after fracture reduction leads to improved patient outcomes by restoring ankle mortise congruence. An in-depth understanding of fibular morphology may aid in fracture reduction, preoperative planning, plate positioning and intra-operative contouring. The goal of this study is to perform quantitative morphologic analysis of distal fibular anatomy using computed tomography (CT).Methods:Using Nuance mPower Clinical Analytics software, a database of CT tibia-fibula reports for patients ages 18 through 35 performed at our institution were searched for the term 'normal.' Inclusion criteria was absence of any reported osseous pathology. Examinations were excluded if the fibula was incompletely imaged. Twenty CTs were collected and analyzed.Measurements were performed at 5 mm increments from the tip of the fibula extending proximally to 10 cm. At each level the following measurements were obtained: lateral and posterior border lengths, lateral to medial (LM) bicortical distances at ¼, ½, and ¾ the length of the lateral border, posteroanterior (PA) bicortical distance at the center of the posterior border, and the angles of the lateral and posterior borders relative to the PA axis of the tibia (figure 1). The location of the maximal bicortical distance in the LM direction was recorded at each level.Results:The posterior border of the fibula broadens from an apex distally to 8.4+-1.6 mm at 10 cm proximal while rotating an average of 97.5 degrees. The lateral border of the fibula rotates 6.3 degrees from distal to proximal and begins with a width of 12.8+-3.1 mm and comes to an apex at 9 cm. In the distal fibula, the ratio of the maximal LM to PA bicortical length is 0.56. By 3 cm proximal, the ratio approaches 1 and is 1.6 at 10 cm. The distal 1 cm of the fibula has the largest LM diameter anteriorly and medially but from 1.5 cm to 10 cm proximal the posterior ¼ has the largest LM diameter.Conclusion:The fibula has a complex distal geometry which changes with progression from the distal tip to 10 cm proximal. The posterior border of the fibula broadens and rotates over 90 degrees to become the lateral border proximally. The lateral border distally is broad but comes to an apex proximally with minimal rotation. The ratio of bicortical distances changes from distal to proximal as the distal posterior border rotates to face in a LM direction proximally. This information may aid in surgeons' understanding of the complex distal fibular morphology and assist with intra-operative decision making regarding hardware size, placement and manipulation.

Deep learning-based reconstruction of chest ultra-high-resolution computed tomography and quantitative evaluations of smaller airways.

The full-iterative model reconstruction generates ultra-high-resolution computed tomography (U-HRCT) images comprising a 1024×1024 matrix and 0.25mm thickness while suppressing image noises, allowing evaluating small airways 1-2mm in diameter. However, this technique imposes huge computational burdens and requires a long reconstruction time. This study evaluated whether a recently-established deep learning-based reconstruction, Advanced intelligent Clear-IQ Engine (AiCE), allows quantitative morphological analyses of smaller airways with equal or better quality than the full-iterative model reconstruction while shortening the reconstruction time. In phantom tubes mimicking small airways, the measurement error of 0.5-mm-thickness wall was smaller on the AiCE-based than the full-iterative model-based U-HRCT. Moreover, in five patients with chronic obstructive pulmonary disease, the AiCE-based U-HRCT decreased the reconstruction time approximately by 90% with a modest improvement in image noise, contrast, and sharpness compared to the full-iterative model-based U-HRCT. Therefore, the AiCE-based U-HRCT can be readily used clinically for morphologically evaluating peripheral small airways.

Quantitative Analysis of Gross Morphology of Placenta in Normal and Hypertensive Patients

Background: Placenta is an important organ and the growth and development of fetus is dependent on it. The different pregnancy complications as antepartum haemorrhage, postpartum haemorrhage, coagulopathy etc. in mothers and IUGR (intrauterine growth retardation), prematurity etc. in foetus are reflected in the placenta & are associated with pregnancy induced hypertension (PIH) . They form the major causes of maternal and fetal mortality & morbidity.
 Objectives: Quantitative analysis of the changes in gross morphology of placenta in normal and hypertensive pregnancies.
 To study the resultant effect on the foetal outcome.
 Material & Methods: We had taken 100 placentas of normal & hypertensive group patients each for study .We collected them from the labour room & operation theatre of Dept. of Obstetrics & Gynaecology of our medical college. Gross morphological features of placentas like size, weight, no. of cotyledons , areas of infarction, retroplacental clot, calcification and insertion of umbilical cord etc. were noted and simultaneously the histological study was also done.
 Observations & Results: The gross morphological parameters like diameter, size, surface area, number of cotyledons and weight were reduced in hypertensive placentas than normal placentas while areas of infarction, retroplacental clot, calcification were more in hypertensive placentas than normal placentas. (p<0.005) The observed differences were statistically significant.

Variation in the Myotis keaysi complex (Chiroptera, Vespertilionidae), with description of a new species from Ecuador

Abstract The genus Myotis comprises a diverse group of vespertilionid bats with worldwide distribution. Twenty-eight Neotropical species are currently recognized. In this study, we evaluate molecular and morphological variation in the M. keaysi complex, a high elevation clade of Neotropical myotine bats characterized by complex taxonomy and high morphological variation. A phylogeny inferred with cytochrome-b sequences recovered two clades composed of samples traditionally assigned to M. keaysi, with 9% of genetic divergence between them. These clades were also suggested as putative distinct species by molecular species delimitation methods. Qualitative and quantitative morphological analyses indicated a phenotypic discontinuity between specimens from central Andes (including the holotype of M. keaysi) and western lowlands of Ecuador, showing strong congruence between molecular and morphological approaches. We therefore describe a new species for the Tumbes-Choco-Magdalena region, documenting their external and cranial diagnostic characters by comparing them with other Neotropical species. In addition, we provide an emended diagnosis for our new concept of M. keaysi.

Quantitative Morphologic Analysis of Cranial Vault in Twist1+/- Mice: Implications in Craniosynostosis.

The haploinsufficiency in the TWIST1 gene encoding a basic helix-loop-helix transcription factor is a cause of one of the craniosynostosis syndromes, Saethre-Chotzen syndrome. Patients with craniosynostosis usually require operative release of affected sutures, which makes it difficult to observe the long-term consequence of suture fusion on craniofacial growth. In this study, we performed quantitative analysis of morphologic changes of the skull in Twist1 heterozygously-deleted mice (Twist1+/-) with micro-computed tomographic images. In Twist1+/- mice, fusion of the coronal suture began before postnatal day 14 and progressed until postnatal day 56, during which morphologic changes occurred. The growth of the skull was not achieved by a constant increase in the measured distances in wild type mice; some distances in the top-basal axis were decreased during the observation period. In the Twist1+/- mouse, growth in the top-basal axis was accelerated and that of the frontal cranium was reduced. In the unicoronal suture fusion mouse, the length of the zygomatic arch of affected side was shorter in the Twist1+/- mouse. In one postnatal day 56 Twist1+/- mouse with bilateral coronal suture fusion, asymmetric zygomatic arch length was identified. The authors'results suggest that measuring the length of the left and right zygomatic arches may be useful for early diagnosis of coronal suture fusion and for estimation of the timing of synostosis, and that more detailed study on the growth pattern of the normal and the synostosed skull could provide prediction of the risk of resynostosis. The data from this study can be useful to better understand the cranial growth pattern in patients with craniosynostosis.

Identification of Paleoearthquakes and Coseismic Slips on a Normal Fault Using High-Precision Quantitative Morphology: Application to the Jiaocheng Fault in the Shanxi Rift, China

AbstractThe quantitative morphology of bedrock fault surfaces combined with aerial surveys and field identification is a useful approach to identify paleoearthquakes, obtain coseismic slips, and evaluate the seismogenic capacity of active faults in bedrock areas where traditional trenching methods are not applicable. Here, we report a case study of the Jiaocheng Fault (JCF) in the Shanxi Rift, China. Although several studies have been conducted on the JCF, its coseismic slip history and seismogenic capacity are still unclear. To address these problems, we investigated two bedrock fault surfaces, Sixicun (SXC) and Shanglanzhen (SLZ), on the JCF’s northern segment using quantitative morphological analysis together with aerial and field surveys. Quantitative fractal analysis based on the isotropic empirical variogram and moving window shows that both bedrock fault surfaces have the characteristics of vertical segmentation, which is likely due to periodic earthquakes, the coseismic slip of which can be determined by the height of the segments. Three seismic events at SXC, with a coseismic vertical slip of 1.74, 1.65, and 1.99 m, and three seismic events at SLZ, with a coseismic vertical slip of 1.32, 2.35, and 1.88 m, are identified. Compared with the previous studies, these three seismic events may occur in the Holocene, but it requires absolute dating ages to support, which is also the focus of our future work. Considering the seismologic capability (M>7.5) and the relationship between the recurrence interval of ~2.6 kyr and elapsed time of more than 3 kyr, the seismic hazard of the northern and middle segments of the JCF requires immediate attention.

Alzheimer's disease risk factor CD2AP functions at synapses via spinal F-actin.

In late-onset Alzheimer's disease (LOAD), the causal mechanisms of synaptic dysfunction underlying memory deficits that lead to dementia remain unclear. Genetic studies of LOAD patients identified gene variants associated with AD. Now it is necessary to translate the genotype into the mechanism of synaptic dysfunction. Here we investigated the impact of the putative LOAD risk factor CD2AP loss of function. We hypothesized that CD2AP might regulate spinal actin since CD2AP is a regulator of actin dynamics in non-neuronal cells, and the actin cytoskeleton dynamics is essential for spine plasticity. We have used wild-type mouse primary cortical neurons after differentiation for 15-21 DIV. To knockdown CD2AP, we infected primary neurons with lentivirus expressing GFP and shCD2AP or non-targeting shRNA as control. We used immunofluorescence microscopy, using epifluorescence and confocal microscopy, and quantitative morphologic and subcellular analysis using ICY and Imaris software to analyze CD2AP synaptic localization, synapses and spines density, as well as spinal F-actin. We discovered that CD2AP is present in spines. CD2AP knockdown reduced spines density. In contrast, CD2AP overexpression increased spine density. Morphologically, CD2AP overexpression enlarged spine heads. Synapses density was, like spines, reduced by CD2AP knockdown. Mechanistically, we found that spinal F-actin decreased by CD2AP knockdown and increased upon CD2AP overexpression. These results indicate that CD2AP regulates spine morphology and thus synapses, likely by regulating actin dynamics at spines. Overall CD2AP variants may contribute to LOAD development by directly interfering with synapses.

Sedimentary response of the deep eastern Mediterranean basin to the north African desertification, sea level variation and regional tectonics

AbstractThe buildup of a continental rise and its morphological patterns depend on sediment transport and deposition via downslope slumps, turbidity currents, along‐slope contourites and other deepwater currents. These delivery mechanisms are central to source‐to‐sink reconstructions, yet untangling their individual roles is not straightforward. The current study focuses on the sink section of the Nile system at the northern Levant continental rise (eastern Mediterranean). During the Pliocene, fluvial systems from northern Africa and the Levant margin supplied sediments to the study area. This supply decreased significantly during the Quaternary because of two processes: (a) The aridification of North Africa made the Nile River the predominant contributor to the basin; (b) the topographic rise of the Levant landmass severely limited fluvial supply. Meanwhile, on‐going counter‐clockwise marine currents became the prevalent supply system to the Levant margin, and downslope sediment‐transport became the only source to the northern Levant continental rise, which became a significant sink of the larger Nile system. These conditions provide an excellent natural laboratory for understanding the individual role of downslope sediment‐transport processes in building a continental rise. This research is based on single‐channel sparker seismic data, multibeam bathymetry and four 7–8 m long piston‐cores collected over the northern Levant continental rise at water depths of 1200–1800 m, together with available multibeam bathymetry and industrial multi‐channel seismic reflection data. The results show a major depositional changeover during the Pliocene‐Quaternary transition from concordant aggradation to repeated deposition of >12 sediment wave subunits, interpreted as upslope migrating cyclic steps. Quantitative analysis of the sediment wave morphology at the seafloor and subsurface, along with core data, indicates that the immediate sediment source was the nearby shelf. The supply was regulated by basinward‐landward shifts of the shore‐parallel marine currents during lowstand‐highstand conditions (respectively). Hence, this case study highlights the connection between sea‐level change and sedimentation patterns on a continental rise.

A new species of Myotis (Chiroptera, Vespertilionidae) from Uruguay

Abstract The genus Myotis comprises a diverse group of vesper bats with worldwide distribution. Twenty-eight neotropical species are currently recognized. Based on a morphological approach, we describe a new species of Myotis from the Uruguayan Pampas grasslands, an ecoregion under high anthropogenic pressure with a largely unknown bat fauna. Qualitative and quantitative morphological analyses support the recognition of the new species and we present a set of external and cranial diagnostic characters by comparing them with other neotropical Myotis species. The new species reassembles Myotis riparius, but can be distinguished by a set of qualitative and quantitative morphological traits, including its clearly bicolored dorsal fur, tricolored ventral fur, a pelage on the dorsal surface of uropatagium, sagittal crest lower, braincase lower in lateral view and overall smaller size.

Multi-path cascaded U-net for vessel segmentation from fundus fluorescein angiography sequential images

Background and ObjectiveFundus fluorescein angiography (FFA) technique is widely used in the examination of retinal diseases. In analysis of FFA sequential images, accurate vessel segmentation is a prerequisite for quantification of vascular morphology. Current vessel segmentation methods concentrate mainly on color fundus images and they are limited in processing FFA sequential images with varying background and vessels. MethodsWe proposed a multi-path cascaded U-net (MCU-net) architecture for vessel segmentation in FFA sequential images, which is capable of integrating vessel features from different image modes to improve segmentation accuracy. Firstly, two modes of synthetic FFA images that enhance details of small vessels and large vessels are prepared, and are then used together with the raw FFA image as inputs of the MCU-net. By fusion of vessel features from the three modes of FFA images, a vascular probability map is generated as output of MCU-net. ResultsThe proposed MCU-net was trained and tested on the public Duke dataset and our own dataset for FFA sequential images as well as on the DRIVE dataset for color fundus images. Results show that MCU-net outperforms current state-of-the-art methods in terms of F1-score, sensitivity and accuracy, and is able of reserving details such as thin vessels and vascular connections. It also shows good robustness in processing FFA images captured at different perfusion stages. ConclusionsThe proposed method can segment vessels from FFA sequential images with high accuracy and shows good robustness to FFA images in different perfusion stages. This method has potential applications in quantitative analysis of vascular morphology in FFA sequential images.

Immuno-histological detection of resistant columnar units and vulnerable networks in the rat retina after asphyxia-induced transient cardiac arrest.

Stroke-related loss of vision is one of the residual impairments, restricting the quality of life. However, studies of the ocular manifestations of asphyxia cardiac arrest/resuscitation (ACA/R) have reported very heterogeneous results. We aimed to evaluate the ACA/R-induced degeneration pattern of the different retinal cell populations in rats using different immuno-histological stainings. The staining pattern of toluidine blue and the ganglion cell markers β-III-tubulin and NeuN; the calcium-binding protein parvalbumin, indicating ganglion, amacrine, and horizontal cells; calretinin D28k, indicating ganglion and amacrine cells; calbindin, indicating horizontal cells; Chx 10, indicating cone bipolar cells; PKCα, indicating ON-type rod bipolar cells; arrestin, indicating cones; and rhodopsin, a marker of rods, as well as the glial cell markers GFAP (indicating astroglia and Müller cells) and IBA1 (indicating microglia), were evaluated after survival times of 7 and 21 days in an ACA/R rat model. Moreover, quantitative morphological analysis of the optic nerve was performed. The ACA/R specimens were compared with those from sham-operated and completely naïve rats. ACA/R-induced effects were: (i) a significant reduction of retinal thickness after long-term survival; (ii) ganglion cell degeneration, including their fiber network in the inner plexiform layer; (iii) degeneration of amacrine and cone bipolar cells; (iv) degeneration of cone photoreceptors; (v) enhanced resistance to ACA/R by rod photoreceptors, ON-type rod bipolar and horizontal cells, possibly caused by the strong upregulation of the calcium-binding proteins calretinin, parvalbumin, and calbindin, counteracting the detrimental calcium overload; (vi) significant activation of Müller cells as further element of retinal anti-stress self-defense mechanisms; and (vii) morphological alterations of the optic nerve in form of deformed fibers. Regardless of the many defects, the surviving neuronal structures seemed to be able to maintain retinal functionality, which can be additionally improved by regenerative processes true to the "use it or lose it" dogma.

Quantitative analysis of morphological and functional features in Meibography for Meibomian Gland Dysfunction: Diagnosis and Grading.

BackgroundTo explore the performance of quantitative morphological and functional analysis in meibography images by an automatic meibomian glands (MGs) analyser in diagnosis and grading Meibomian Gland Dysfunction (MGD).MethodsA cross-sectional study collected 256 subjects with symptoms related to dry eye and 56 healthy volunteers who underwent complete ocular surface examination was conducted between January 1, 2019, and December 31, 2020. The 256 symptomatic subjects were classified into MGD group (n = 195) and symptomatic non-MGD group (n = 61). An automatic MGs analyser was used to obtained multi-parametric measurements in meibography images including the MGs area ratio (GA), MGs diameter deformation index (DI), MGs tortuosity index (TI), and MGs signal index (SI). Adjusted odds ratios (ORs) of the multi-parametric measurements of MGs for MGD, and the area under the receiver operating characteristic (AUC-ROC) curves of multi-parametric measurements for MGD diagnosing and grading were conducted.FindingsWhen consider age, sex, ocular surface condition together, the estimated ORs for DI was 1.62 (95% CI, 1.29-2.56), low-level SI was 24.34 (95% CI, 2.73-217.3), TI was 0.76(95% CI, 0.54-0.90), and GA was 0.86 (95% CI, 0.74-0.92) for MGD. The combination of DI-TI-GA-SI showed an AUC = 0.82 (P < 0.001) for discriminating MGD from symptomatic subjects. The DI had a higher AUC in identifying early-stage MGD (grade 1-2), while TI and GA had higher AUCs in moderate and advanced stages (grade 3-5). Merging DI-TI-GA showed the highest AUCs in distinguish MGD severities.InterpretationThe MGs area ratio, diameter deformation, tortuosity and signal intensity could be considered promising biomarkers for MGD diagnosis and objective grading.FundingThis work was supported by the Key-Area Research and Development Program of Guangdong Province (No. 2019B010152001), the National Natural Science Foundation of China under Grant (81901788) and Guangzhou Science and Technology Program (202002030412).