MR Imaging of Peripheral Nerves Using Targeted Application of Contrast Agents: An Experimental Proof-of-Concept Study.

MR Imaging of Peripheral Nerves Using Targeted Application of Contrast Agents: An Experimental Proof-of-Concept Study.
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DOI:
10.3389/fmed.2020.613138
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发表时间:
2020
影响因子:
3.9
通讯作者:
Aszmann OC
Aszmann OC
中科院分区:
医学3区
文献类型:
--
作者:
Tereshenko V;Pashkunova-Martic I;Manzano-Szalai K;Friske J;Bergmeister KD;Festin C;Aman M;Hruby LA;Klepetko J;Theiner S;Klose MHM;Keppler B;Helbich TH;Aszmann OC

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介绍:目前周围神经的成像方式显示神经的结构,但不是它的功能。基于神经轴突运输的能力,可以通过靶向应用造影剂并通过放射成像评估分布来可视化,从而揭示神经的连续性。这一概念尚未被探索,然而,可能潜在地指导周围神经损伤的治疗。在这项实验性概念验证研究中,我们在给予钆基造影剂后通过MRI测试成像,然后逆行转运。研究方法:我们合成了由顺磁剂和各种轴突运输促进剂(HSA-DTPA-Gd、壳聚糖-DTPA-Gd或PLA/HSA-DTPA-Gd)组成的MRI造影剂。首先,我们在体外测量了它们的弛豫率值,以评估它们的放射适用性。随后,切断24只大鼠的坐骨神经并用其中一种造影剂标记,以实现沿神经的逆行分布沿着。手术后一周,采集脊髓和坐骨神经,使用7 T MRI观察相应造影剂的分布。在术后第1、3和7天使用9.4 T MRI进行体内MRI测量。放射成像后,使用电感耦合质谱法(ICP-MS)分析收获样品中的钆浓度。结果:所有造影剂均表现出高弛豫率值,范围为12.1 - 116.0 mM− 1 s −1。HSA-DTPA-Gd和PLA/HSA-DTPA-Gd应用导致在离体MRI中椎管和坐骨神经中的信号增强。在体测量显示,在应用HSA-DTPA-Gd和壳聚糖-DTPA-Gd后的第3天和第7天,坐骨神经中的信号显著增强(p < 0.05)。化学评价显示,HSA-DTPA-Gd(5.218 ± 0.860 ng/mg)和壳聚糖-DTPA-Gd(4.291 ± 1.290 ng/mg)在坐骨神经中的钆浓度较高。讨论:在这项研究中,实施了一种新的成像方法来评价周围神经的完整性。这些发现提供了造影剂沿大鼠坐骨神经沿着成功摄取及其在椎管内分布的放射学和化学证据。这种新的概念可能有助于在未来的周围神经损伤的诊断过程。
Introduction: Current imaging modalities for peripheral nerves display the nerve's structure but not its function. Based on a nerve's capacity for axonal transport, it may be visualized by targeted application of a contrast agent and assessing the distribution through radiological imaging, thus revealing a nerve's continuity. This concept has not been explored, however, may potentially guide the treatment of peripheral nerve injuries. In this experimental proof-of-concept study, we tested imaging through MRI after administering gadolinium-based contrast agents which were then retrogradely transported. Methods: We synthesized MRI contrast agents consisting of paramagnetic agents and various axonal transport facilitators (HSA-DTPA-Gd, chitosan-DTPA-Gd or PLA/HSA-DTPA-Gd). First, we measured their relaxivity values in vitro to assess their radiological suitability. Subsequently, the sciatic nerve of 24 rats was cut and labeled with one of the contrast agents to achieve retrograde distribution along the nerve. One week after surgery, the spinal cords and sciatic nerves were harvested to visualize the distribution of the respective contrast agent using 7T MRI. In vivo MRI measurements were performed using 9.4 T MRI on the 1st, 3rd, and the 7th day after surgery. Following radiological imaging, the concentration of gadolinium in the harvested samples was analyzed using inductively coupled mass spectrometry (ICP-MS). Results: All contrast agents demonstrated high relaxivity values, varying between 12.1 and 116.0 mM−1s−1. HSA-DTPA-Gd and PLA/HSA-DTPA-Gd application resulted in signal enhancement in the vertebral canal and in the sciatic nerve in ex vivo MRI. In vivo measurements revealed significant signal enhancement in the sciatic nerve on the 3rd and 7th day after HSA-DTPA-Gd and chitosan-DTPA-Gd (p < 0.05) application. Chemical evaluation showed high gadolinium concentration in the sciatic nerve for HSA-DTPA-Gd (5.218 ± 0.860 ng/mg) and chitosan-DTPA-Gd (4.291 ± 1.290 ng/mg). Discussion: In this study a novel imaging approach for the evaluation of a peripheral nerve's integrity was implemented. The findings provide radiological and chemical evidence of successful contrast agent uptake along the sciatic nerve and its distribution within the spinal canal in rats. This novel concept may assist in the diagnostic process of peripheral nerve injuries in the future.
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