scholarly journals Correlation of Micro-Computed Tomography Assessment of Valvular Mineralisation with Histopathological and Immunohistochemical Features of Calcific Aortic Valve Disease

2019 ◽  
Vol 9 (1) ◽  
pp. 29
Author(s):  
Guillermo Solache-Berrocal ◽  
Ana María Barral-Varela ◽  
Sheila Areces-Rodríguez ◽  
Alejandro Junco-Vicente ◽  
Aitana Vallina-Álvarez ◽  
...  

Aortic valve stenosis is a serious disease with increasing prevalence in developed countries. Research aimed at uncovering the molecular mechanisms behind its main cause, aortic valve calcification, is thus crucial for the development of future therapies. It is frequently difficult to measure the extent of mineralisation in soft tissues and some methods require the destruction of the sample. Micro-computed tomography (µCT), a non-destructive technique, was used to quantify the density and volume of calcium deposits on cusps from 57 explanted aortic valves. Conventional and immunostaining techniques were used to characterise valve tissue degeneration and the inflammatory and osteogenic stage with several markers. Although most of the analysed cusps came from severe stenosis patients, the µCT parameter bone volume/tissue volume ratio distinguished several degrees of mineralisation that correlated with the degree of structural change in the tissue and the amount of macrophage infiltration as determined by CD68 immunohistochemistry. Interestingly, exosomal markers CD63 and Alix co-localised with macrophage infiltration surrounding calcium deposits, suggesting that those vesicles could be produced at least in part by these immune cells. In conclusion, we have shown that the ex vivo assessment of aortic valve mineralisation with µCT reflects the molecular and cellular changes in pathological valves during progression towards stenosis. Thus, our results give additional validity to quantitative μCT as a convenient laboratory tool for basic research on this type of cardiovascular calcification.

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Ling Sun ◽  
John LeCluyse ◽  
Brian Robillard ◽  
Philippe Sucosky

INTRODUCTION: Calcific aortic valve disease (CAVD) is an active process presumably triggered by interplays between atherogenic risk factors, molecular signaling networks and hemodynamic cues. While our earlier work demonstrated that progressive alterations in fluid wall-shear stress (WSS) on the fibrosa could trigger leaflet inflammation, the mechanisms of CAVD pathogenesis secondary to side-specific WSS abnormalities are poorly understood. HYPOTHESIS: Supported by our previous studies, we hypothesize that valve leaflets are sensitive to both WSS magnitude and pulsatility and that abnormalities in either promote CAVD development. OBJECTIVE: This study aims at elucidating ex vivo the contribution of isolated and combined alterations in WSS magnitude and pulsatility to valvular calcification. METHODS: The fibrosa and ventricularis of porcine leaflets were subjected simultaneously to different combinations of WSS magnitude and pulsatility (i.e., physiologic, sub- and supra-physiologic levels) for 48 hours in a double-sided shear stress bioreactor. Endothelial activation (ICAM-1, VCAM-1), paracrine expression (TGF-β and BMP-4), and proteinase/collagenase expression (MMP-2, cathepsin L) were detected by immunohistochemistry, while osteogenic differentiation (α-SMA) was assessed via western blot. RESULTS: Regardless of the magnitude or frequency, non-physiologic WSS conditions did not result in endothelial activation. Tissue exposure to either supra-physiologic WSS magnitude or pulsatility significantly upregulated paracrine (74-fold increase), proteinase (4-fold increase), collagenase (5-fold increase) and α-SMA (23-fold increase) expressions relative to the levels measured under physiologic WSS. In contrast, combined alterations in WSS magnitude and pulsatility downregulated those responses. CONCLUSION: This study demonstrates the sensitivity of aortic valve leaflets to both WSS magnitude and pulsatility and the ability of supra-physiologic WSS magnitude or pulsatility to trigger events involved in early CAVD pathogenesis. The results provide new potential insights into the mechanisms of CAVD secondary to hypertension and Paget’s disease, which are associated with abnormal blood flow and leaflet WSS.


2016 ◽  
Vol 42 (4) ◽  
pp. 610-614 ◽  
Author(s):  
Thomas Gerhard Wolf ◽  
Frank Paqué ◽  
Maximilian Zeller ◽  
Brita Willershausen ◽  
Benjamín Briseño-Marroquín

2021 ◽  
Vol 11 (20) ◽  
pp. 9368
Author(s):  
Elise Doveri ◽  
Laurent Sabatier ◽  
Vincent Long ◽  
Philippe Lasaygues

Medical B-mode ultrasound is widely used for the examination of children’s limbs, including soft tissue, muscle, and bone. However, for the accurate examination of the bone only, it is often replaced by more restrictive clinical modalities. Several authors have investigated ultrasonic imaging of bone to assess cortical thickness and/or to estimate the wave velocity through the internal structure. The present work focuses on the transverse slice imaging process using reflection-mode ultrasound computed tomography (USCT). The method is valid for imaging soft tissues with similar acoustic impedances, but in the presence of bone, the higher contrasts alter the propagation of ultrasonic waves and reduce the contrast-to-noise ratio (CNR). There is a need to change the methods used for the processing of ultrasonic signals. Our group has developed a wavelet-based coded excitation (WCE) method to process information in frequency and time. The objective of this study is to use the method to improve reflection-mode USCT, at low ultrasonic intensities, to better address organ morphometry. Experimental results on a newborn arm phantom and on an ex vivo chicken drumstick are presented, and the usefulness of this WCE-mode USCT is discussed.


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