3-dimensional digital reconstruction of the murine coronary system for the evaluation of chronic allograft vasculopathy

Diagnostic Pathology

Yukako Yagi¹  Robert B Colvin¹  A Marcell Szász³  Divya P Sebastian¹  Martin Groher²  Evan A Farkash¹  Kazunobu Shinoda¹  László Fónyad⁴ 

[1] Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;microDimensions GmbH, Munich, Germany;2nd Department of Pathology, Semmelweis University, Budapest, Hungary;1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

关键词: Neointimal volume index;    Serial sectioning;    CAV;    3D;    Digital slides;   

Others  :  1175185
DOI  :  10.1186/s13000-015-0248-6

 received in 2014-10-28, accepted in 2015-03-11,  发布年份 2015

【 摘 要 】

Background

Chronic allograft vasculopathy (CAV) is a major mechanism of graft failure of transplanted organs in humans. Morphometric analysis of coronary arteries enables the quantitation of CAV in mouse models of heart transplantation. However, conventional histological procedures using single 2-dimensional sections limit the accuracy of CAV quantification. The aim of this study is to improve the accuracy of CAV quantification by reconstructing the murine coronary system in 3-dimensions (3D) and using virtual reconstruction and volumetric analysis to precisely assess neointimal thickness.

Methods

Mouse tissue samples, native heart and transplanted hearts with chronic allograft vasculopathy, were collected and analyzed. Paraffin embedded samples were serially sectioned, stained and digitized using whole slide digital imaging techniques under normal and ultraviolet lighting. Sophisticated software tools were used to generate and manipulate 3D reconstructions of the major coronary arteries and branches.

Results

The 3D reconstruction provides not only accurate measurements but also exact volumetric data of vascular lesions. This virtual coronary arteriography demonstrates that the vasculopathy lesions in this model are localized to the proximal coronary segments. In addition, virtual rotation and volumetric analysis enabled more precise measurements of CAV than single, randomly oriented histologic sections, and offer an improved readout for this important experimental model.

Conclusions

We believe 3D reconstruction of 2D histological slides will provide new insights into pathological mechanisms in which structural abnormalities play a role in the development of a disease. The techniques we describe are applicable to the analysis of arteries, veins, bronchioles and similar sized structures in a variety of tissue types and disease model systems.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3772457541477230 webcite.

【 授权许可】

   
2015 Fónyad et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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