CmyoSize: An ImageJ macro for automated analysis of cardiomyocyte size in images of routine histology staining

Silva, Flávio Santos da; Souza, Natália Caroline Santos Aquino de; Moraes, Marcus Vinícius de; Abreu, Bento João; Oliveira, Moacir Franco de

doi:10.1016/j.aanat.2022.151892

Cited by 8 publications

(4 citation statements)

References 39 publications

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“…HeartJ is created as a macro for ImageJ, not as a plugin, so it is much easier to customize for individual needs. Another previously published tool uses ImageJ macro for the analysis of hematoxylin and eosin-stained cardiac tissues [ 19 ]. This approach measures only cardiomyocytes in transnuclear cross section, which significantly reduces the number of measured cardiomyocytes, and does not provide any other parameters.…”

Section: Discussionmentioning

confidence: 99%

Semiautomated pipeline for quantitative analysis of heart histopathology

Droste,

Wong,

Hohl

et al. 2023

J Transl Med

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Background Heart diseases are among the leading causes of death worldwide, many of which lead to pathological cardiomyocyte hypertrophy and capillary rarefaction in both patients and animal models, the quantification of which is both technically challenging and highly time-consuming. Here we developed a semiautomated pipeline for quantification of the size of cardiomyocytes and capillary density in cardiac histology, termed HeartJ, by generating macros in ImageJ, a broadly used, open-source, Java-based software. Methods We have used modified Gomori silver staining, which is easy to perform and digitize in high throughput, or Fluorescein-labeled lectin staining. The latter can be easily combined with other stainings, allowing additional quantitative analysis on the same section, e.g., the size of cardiomyocyte nuclei, capillary density, or single-cardiomyocyte protein expression. We validated the pipeline in a mouse model of cardiac hypertrophy induced by transverse aortic constriction, and in autopsy samples of patients with and without aortic stenosis. Results In both animals and humans, HeartJ-based histology quantification revealed significant hypertrophy of cardiomyocytes reflecting other parameters of hypertrophy and rarefaction of microvasculature and enabling the analysis of protein expression in individual cardiomyocytes. The analysis also revealed that murine and human cardiomyocytes had similar diameters in health and extent of hypertrophy in disease confirming the translatability of our murine cardiac hypertrophy model. HeartJ enables a rapid analysis that would not be feasible by manual methods. The pipeline has little hardware requirements and is freely available. Conclusions In summary, our analysis pipeline can facilitate effective and objective quantitative histological analyses in preclinical and clinical heart samples.

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Section: Discussionmentioning

confidence: 99%

Semiautomated pipeline for quantitative analysis of heart histopathology

Droste,

Wong,

Hohl

et al. 2023

J Transl Med

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“…Images were analyzed using the CmyoSize plugin on ImageJ. This fully automated plugin standardizes cardiomyocyte size by filtering for cells that are regular and round in shape and that contain a central round nucleus and visible border ( 47 , 48 ).…”

Section: Methodsmentioning

confidence: 99%

Soft robotic platform for progressive and reversible aortic constriction in a small-animal model

Rosalia,

Wang,

Ozturk

et al. 2024

Sci. Robot.

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Our understanding of cardiac remodeling processes due to left ventricular pressure overload derives largely from animal models of aortic banding. However, these studies fail to enable control over both disease progression and reversal, hindering their clinical relevance. Here, we describe a method for progressive and reversible aortic banding based on an implantable expandable actuator that can be finely tuned to modulate aortic banding and debanding in a rat model. Through catheterization, imaging, and histologic studies, we demonstrate that our platform can recapitulate the hemodynamic and structural changes associated with pressure overload in a controllable manner. We leveraged soft robotics to enable noninvasive aortic debanding, demonstrating that these changes can be partly reversed because of cessation of the biomechanical stimulus. By recapitulating longitudinal disease progression and reversibility, this animal model could elucidate fundamental mechanisms of cardiac remodeling and optimize timing of intervention for pressure overload.

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“…Cross-sectional cardiomyocyte width was measured for over 50 cardiomyocytes in 15 images from three independent slides per animal stained with HE as previously reported [45] using CymoSize macro [46] and manually validated in randomly-selected images.…”

Section: Methodsmentioning

confidence: 99%

Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation Via Hexosamine Biosynthetic Pathway

Grilo,

Zimmerman,

Puppala

et al. 2023

Preprint

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Age is a prominent risk factor for cardiometabolic disease, and often leads to heart structural and functional changes. However, precise molecular mechanisms underlying cardiac remodeling and dysfunction resulting from physiological aging per se remain elusive. Understanding these mechanisms requires biological models with optimal translation to humans. Previous research demonstrated that baboons undergo age-related reduction in ejection fraction and increased heart sphericity, mirroring changes observed in humans.The goal of this study was to identify early cardiac molecular alterations that precede functional adaptations, shedding light on the regulation of age-associated changes.We performed unbiased transcriptomics of left ventricle (LV) samples from female baboons aged 7.5-22.1 years (human equivalent ∼30-88 years). Weighted-gene correlation network and pathway enrichment analyses were performed to identify potential age-associated mechanisms in LV, with histological validation. Myocardial modules of transcripts negatively associated with age were primarily enriched for cardiac metabolism, including oxidative phosphorylation, tricarboxylic acid cycle, glycolysis, and fatty-acid β-oxidation. Transcripts positively correlated with age suggest upregulation of glucose uptake, pentose phosphate pathway, and hexosamine biosynthetic pathway (HBP), indicating a metabolic shift towards glucose-dependent anabolic pathways. Upregulation of HBP commonly results in increased glycosaminoglycan precursor synthesis. Transcripts involved in glycosaminoglycan synthesis, modification, and intermediate metabolism were also upregulated in older animals, while glycosaminoglycan degradation transcripts were downregulated with age. These alterations would promote glycosaminoglycan accumulation, which was verified histologically. Upregulation of extracellular matrix (ECM)-induced signaling pathways temporally coincided with glycosaminoglycan accumulation. We found a subsequent upregulation of cardiac hypertrophy-related pathways and an increase in cardiomyocyte width.Overall, our findings revealed a transcriptional shift in metabolism from catabolic to anabolic pathways that leads to ECM glycosaminoglycan accumulation through HBP prior to upregulation of transcripts of cardiac hypertrophy-related pathways. This study illuminates cellular mechanisms that precede development of cardiac hypertrophy, providing novel potential targets to remediate age-related cardiac diseases.

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CmyoSize: An ImageJ macro for automated analysis of cardiomyocyte size in images of routine histology staining

Cited by 8 publications

References 39 publications

Semiautomated pipeline for quantitative analysis of heart histopathology

Semiautomated pipeline for quantitative analysis of heart histopathology

Soft robotic platform for progressive and reversible aortic constriction in a small-animal model

Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation Via Hexosamine Biosynthetic Pathway

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