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骨关节炎大鼠模型中全软骨表面损伤的评估:利用微型计算机断层扫描的软骨粗糙度评分(CRS)

Assessment of whole cartilage surface damage in an osteoarthritis rat model: The Cartilage Roughness Score (CRS) utilizing microcomputed tomography.

作者信息

Kauppinen Sami, Fercher David, Barreto Gonçalo, Karjalainen Ville-Pauli, Virtanen Vesa, Baixauli-Marin Lucia, Fonti Marina, Zhang Shipin, Frondelius Tuomas, Weber Patrick, Saarakkala Simo, Zenobi-Wong Marcy, Finnilä Mikko A J

机构信息

Research unit of Health Sciences and Technology, University of Oulu, Finland.

Tissue Engineering and Biofabrication, ETH Zürich, Switzerland.

出版信息

Osteoarthritis Cartilage. 2025 Jan;33(1):134-145. doi: 10.1016/j.joca.2024.09.008. Epub 2024 Sep 30.

Abstract

OBJECTIVE

This study aims to establish an accurate and robust imaging biomarker for pre-clinical osteoarthritis (OA) research, focusing on early detection of cartilage surface degeneration.

METHOD

Using 50 male Wistar rats, this study aims to observe Collagenase-induced OA (CIOA) progression through microcomputed x-ray tomography (µCT), histopathological analysis, and gait analysis. A novel parameter, Cartilage Roughness Score (CRS), was developed for assessing cartilage structural damage from µCT data and was compared with histological OARSI Cartilage Degeneration Score (OARSI CDS). Additionally, as CRS maps the full surface, it was used to simulate the level of uncertainty in histological sampling.

RESULTS

CRS and OARSI CDS have a linear relationship. CRS for healthy cartilage is 2.75 (95% CI: 1.14-4.36), and with every 1 unit increase in OARSI, CRS is expected to increase by 0.64 (95% CI: 0.35-0.92). Cartilage degeneration due to CIOA was evident in both histopathological scoring and CRS. However, only CRS was sensitive enough to show consistent damage progression from day 10 to day 60. Furthermore, our simulation for histological sampling suggested that up to 16 coronal slices with 200 µm spacing would be needed to accurately represent the full extent of cartilage surface degeneration in a slice-wise manner. Gait analysis showed changes solely at eight days post-collagenase injection, normalizing by day 60.

CONCLUSION

The CRS analysis method emerges as a robust tool for cartilage surface damage assessment. This study demonstrates the potential of automatic 3D analysis over the traditional 2D histological approach when evaluating cartilage surface damage.

摘要

目的

本研究旨在建立一种准确且可靠的影像学生物标志物,用于临床前骨关节炎(OA)研究,重点关注软骨表面退变的早期检测。

方法

本研究使用50只雄性Wistar大鼠,旨在通过微型计算机X射线断层扫描(µCT)、组织病理学分析和步态分析观察胶原酶诱导的骨关节炎(CIOA)进展。开发了一种新参数——软骨粗糙度评分(CRS),用于从µCT数据评估软骨结构损伤,并与组织学OARSI软骨退变评分(OARSI CDS)进行比较。此外,由于CRS可绘制整个表面,因此用于模拟组织学采样中的不确定性水平。

结果

CRS与OARSI CDS呈线性关系。健康软骨的CRS为2.75(95%置信区间:1.14 - 4.36),OARSI每增加1个单位,CRS预计增加0.64(95%置信区间:0.35 - 0.92)。CIOA导致的软骨退变在组织病理学评分和CRS中均很明显。然而,只有CRS足够敏感,能显示从第10天到第60天一致的损伤进展。此外,我们对组织学采样的模拟表明,需要多达16个间距为200 µm的冠状切片,才能以切片方式准确呈现软骨表面退变的全部范围。步态分析显示仅在胶原酶注射后第8天出现变化,到第60天恢复正常。

结论

CRS分析方法是一种用于软骨表面损伤评估的可靠工具。本研究证明了在评估软骨表面损伤时,自动3D分析相对于传统2D组织学方法的潜力。

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