Contrast-Enhanced Ultrasound of Mouse Models of Hindlimb Ischemia Reveals Persistent Perfusion Deficits and Distinctive Muscle Perfusion Patterns

IF 2.4 3区医学 Q2 ACOUSTICS

Ultrasound in Medicine and Biology Pub Date : 2024-10-18 DOI:10.1016/j.ultrasmedbio.2024.08.013

Alyssa B. Becker , Lanlin Chen , John A. Hossack , Alexander L. Klibanov , Brian H. Annex , Brent A. French

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Abstract

Objective

Mouse models of hindlimb ischemia (HLI) are used to study peripheral arterial disease and evaluate novel therapies. Contrast-enhanced ultrasound (CEUS) is a noninvasive perfusion measurement technique that is increasingly being employed in these models. The objective of this study was to evaluate two models of severe HLI by CEUS to characterize perfusion recovery and muscle perfusion patterns.

Methods

Mice undergoing double femoral artery ligation were measured by CEUS and laser Doppler perfusion imaging (LDPI) at baseline and 1–150 d postsurgery. A second group undergoing femoral artery ligation and excision was measured 1–28 d postsurgery.

Results

By LDPI, both surgeries showed robust perfusion recovery by 14 d postsurgery. However, by CEUS only a ∼40% perfusion recovery plateau was reached in either group. These results are consistent with our previous work, employing a less severe single femoral artery ligation, that showed perfusion in the ischemic limb does not return to normal by 150 d postsurgery. Cluster analysis of muscle perfusion patterns indicated 3–5 different patterns at day 1 postsurgery. The double ligation model yielded significantly less variable perfusion patterns, suggesting that it can provide more reproducible results.

Conclusion

Contrary to LDPI, perfusion as measured by CEUS never fully recovers after hindlimb surgery, even when followed 28–150 d postsurgery. Individual mice can manifest different patterns of muscle perfusion to the same surgery, but these patterns are conserved within and between different surgical techniques. These results may have significant implications for the evaluation of novel therapeutics to treat PAD in mice.

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后肢缺血小鼠模型的对比增强超声显示持续的灌注缺陷和独特的肌肉灌注模式

目的：后肢缺血（HLI）小鼠模型用于研究外周动脉疾病和评估新型疗法。对比增强超声（CEUS）是一种无创灌注测量技术，越来越多地被用于这些模型中。本研究的目的是通过 CEUS 评估两种严重 HLI 模型，以确定灌注恢复和肌肉灌注模式的特征：方法：对接受双股动脉结扎的小鼠在基线和术后 1-150 d 通过 CEUS 和激光多普勒灌注成像（LDPI）进行测量。第二组接受股动脉结扎和切除术的小鼠在术后1-28 d接受测量：结果：通过 LDPI，两种手术在术后 14 d 都显示出强劲的灌注恢复。然而，通过 CEUS，两组患者的血流灌注恢复都只达到了 40% 左右。这些结果与我们之前采用较轻的单股动脉结扎术的研究结果一致，即缺血肢体的血流灌注在术后150 d仍未恢复正常。肌肉灌注模式的聚类分析显示，术后第1天有3-5种不同的模式。双结扎模型产生的灌注模式变化明显较少，这表明它能提供更多可重复的结果：结论：与 LDPI 相反，通过 CEUS 测定的灌注在后肢手术后从未完全恢复，即使在手术后 28-150 d 也是如此。个体小鼠对同一手术会表现出不同的肌肉灌注模式，但这些模式在不同手术技术内部和之间是一致的。这些结果可能对评估治疗小鼠PAD的新型疗法具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ultrasound in Medicine and Biology 医学-核医学

CiteScore

6.20

自引率

6.90%

发文量

325

审稿时长

70 days

期刊介绍： Ultrasound in Medicine and Biology is the official journal of the World Federation for Ultrasound in Medicine and Biology. The journal publishes original contributions that demonstrate a novel application of an existing ultrasound technology in clinical diagnostic, interventional and therapeutic applications, new and improved clinical techniques, the physics, engineering and technology of ultrasound in medicine and biology, and the interactions between ultrasound and biological systems, including bioeffects. Papers that simply utilize standard diagnostic ultrasound as a measuring tool will be considered out of scope. Extended critical reviews of subjects of contemporary interest in the field are also published, in addition to occasional editorial articles, clinical and technical notes, book reviews, letters to the editor and a calendar of forthcoming meetings. It is the aim of the journal fully to meet the information and publication requirements of the clinicians, scientists, engineers and other professionals who constitute the biomedical ultrasonic community.