Power Doppler ultrasound phenotyping of expanding versus collapsed popliteal lymph nodes in murine inflammatory arthritis.

Power Doppler ultrasound phenotyping of expanding versus collapsed popliteal lymph nodes in murine inflammatory arthritis.
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DOI:
10.1371/journal.pone.0073766
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Schwarz EM
Schwarz EM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bouta EM;Ju Y;Rahimi H;de Mesy-Bentley KL;Wood RW;Xing L;Schwarz EM

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风湿性关节炎是一种慢性炎症性疾病,表现为受影响关节中的偶发性耀斑,这是一种具有挑战性的预测和治疗。肿瘤坏死因子转基因(TNF-Tg)小鼠炎症性关节炎的纵向对比增强MRI(CE-MRI)已经证明,在疾病的关节炎前“扩展”阶段,然后在膝关节外展时突然“塌陷”。考虑到这种关节炎发作生物标志物的潜力,我们的目的是开发一种使用超声(US)成像对PLN进行表型分型的更具成本效益的方法。最初,我们尝试通过皮下足垫注射US微泡(DEFINITY®)来概括PLN的CE-MRI。虽然这种方法允许通过量化PLN中的淋巴窦进行表型分型,其显示塌陷的PLN相对于扩张的或野生型(WT)PLN显著减少,但电子显微镜证实DEFINITY®注射也导致对PLN的淋巴管传入的破坏。相比之下,能量多普勒(PD)US对WT和TNF-Tg小鼠PLN内的血流无害并有效定量。PD-US证实,扩张PLN具有显著高于塌陷PLN的标准化PD体积(NPDV)(0.553±0.007对0.008±0.003; p<0.05)。此外,我们定义了该小鼠组群中的上(>0.030)和下(<0.016)四分位数NPDV,其分别作为表型PLN的保守阈值为扩张和塌陷。有趣的是,在通过两种方法进行表型分型的12个PLN中,在4个病例中存在不一致,其中通过CE-MRI确定它们正在扩张,并且通过PD-US确定它们正在塌陷。由于所有4例病例的相邻膝关节均有滑膜炎证据,因此我们得出结论,PD-US表型分型是正确的,并且该方法是目前将小鼠PLN表型作为关节炎发作生物标志物的最安全和最具成本效益的体内方法。
Rheumatoid arthritis is a chronic inflammatory disease manifested by episodic flares in affected joints that are challenging to predict and treat. Longitudinal contrast enhanced-MRI (CE-MRI) of inflammatory arthritis in tumor necrosis factor-transgenic (TNF-Tg) mice has demonstrated that popliteal lymph nodes (PLN) increase in volume and contrast enhancement during the pre-arthritic “expanding” phase of the disease, and then suddenly “collapse” during knee flare. Given the potential of this biomarker of arthritic flare, we aimed to develop a more cost-effective means of phenotyping PLN using ultrasound (US) imaging. Initially we attempted to recapitulate CE-MRI of PLN with subcutaneous footpad injection of US microbubbles (DEFINITY®). While this approach allowed for phenotyping via quantification of lymphatic sinuses in PLN, which showed a dramatic decrease in collapsed PLN versus expanding or wild-type (WT) PLN, electron microscopy demonstrated that DEFINITY® injection also resulted in destruction of the lymphatic vessels afferent to the PLN. In contrast, Power Doppler (PD) US is innocuous to and efficiently quantifies blood flow within PLN of WT and TNF-Tg mice. PD-US demonstrated that expanding PLN have a significantly higher normalized PD volume (NPDV) versus collapsed PLN (0.553±0.007 vs. 0.008±0.003; p<0.05). Moreover, we define the upper (>0.030) and lower (<0.016) quartile NPDVs in this cohort of mice, which serve as conservative thresholds to phenotype PLN as expanding and collapsed, respectively. Interestingly, of the 12 PLN phenotyped by the two methods, there was disagreement in 4 cases in which they were determined to be expanding by CE-MRI and collapsed by PD-US. Since the adjacent knee had evidence of synovitis in all 4 cases, we concluded that the PD-US phenotyping was correct, and that this approach is currently the safest and most cost-effective in vivo approach to phenotype murine PLN as a biomarker of arthritic flare.
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