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Quantitative Evaluation of the Peripheral Nerve Blood Perfusion with High Frequency Contrast-Enhanced Ultrasound

Rationale and Objectives

The blood perfusion of peripheral nerves plays an important role in regeneration after nerve injury. Previous studies have shown that it is possible to quantitatively assess the blood perfusion of the tissue using contrast-enhanced ultrasound (CEUS). The aim of this study was to evaluate the feasibility of CEUS for quantitative assessment of the blood perfusion of the sciatic nerve in normal New Zealand white rabbits and to compare these parameters to those of surrounding skeletal muscle and the main artery in the thigh.

Materials and Methods

CEUS of the bilateral sciatic nerves was performed in 12 normal New Zealand white rabbits after a bolus injection of SonoVue (0.13 mL/kg). Pulse-inversion harmonic imaging was used for real-time CEUS. The blood perfusion of the left sciatic nerve was compared to that of its surrounding muscle, the arterial branch in the thigh, and the contralateral side.

Results

The supplying arteries in the sciatic nerve could be demonstrated during the early phase of CEUS, followed by the homogeneous enhancement of the whole nerve. The area under the curve and the perfusion index of the sciatic nerve were higher than those of the surrounding muscle and lower than those of the arterial branch in the thigh (both P values = .000). The maximum intensity of the sciatic nerve was similar to that of skeletal muscle and lower than that of the arterial branch. The time to peak was not significantly different among the sciatic nerve, skeletal muscle, and arterial branch ( P = .551). There were no differences in area under the curve, mean transit time, perfusion index, maximum intensity, and time to peak between the left and right sciatic nerves ( P > .05).

Conclusions

CEUS may be a feasible method for the quantitative assessment of blood perfusion of the peripheral nerves.

Blood perfusion of the peripheral nerves plays an important role in regeneration after nerve injury. First, vascularized nerve grafts have been shown to be superior to nonvascularized nerve grafts with respect to healing, especially when used in the hypovascular and scarred recipient bed . Because of the presence of sufficient and uninterrupted blood supply to the nerve graft, Schwann cell viability could be high, which would result in successful nerve healing. Second, cytokines and gene therapy have been tried to promote the angiogenesis of peripheral nerves, and the results were promising . Using nerve grafts pretreated with vascular endothelial growth factor, both invasion of Schwann cells and neovascularization could be promoted, which are important during nerve regeneration . Studies using chambers containing vascular endothelial growth factor in a laminin-based gel to repair rat sciatic nerve defects also demonstrated an overall relationship between increased vascularization and enhanced nerve regeneration .

The current techniques that have been used to evaluate peripheral nerve blood perfusion include radioactive microspheres, microelectrode hydrogen clearance polarography, and laser Doppler flowmetry . However, these methods are not suitable for the noninvasive assessment of blood perfusion in the peripheral nerves in clinical practice. Because of its lower sensitivity for the detection of slow blood flow, color and power Doppler ultrasound cannot display the microcirculation in the tissue. Contrast-enhanced ultrasound (CEUS), which uses gas-filled microbubbles as the tracer in the bloodstream, can dynamically display the entire microcirculation, including the tiny vascular branches supplying organs and tissues and the related capillary network below the spatial resolution of transducer (in the form of tissue enhancement) . When combined with targeted microbubbles, CEUS can also provide a promising noninvasive tool to quantify the early angiogenesis of tumors and may provide insights into the biology of tumor angiogenesis . Yet few studies have been performed using CEUS to evaluate the blood perfusion of the peripheral nerves. We hypothesized that CEUS could be used to enhance the peripheral nerves and to provide quantitative information about the nerves’ blood perfusion. Thus, this study was performed to evaluate the feasibility of CEUS for quantitative assessment of the blood perfusion of the sciatic nerve in normal New Zealand white rabbits.

Materials and methods

Animals

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Sonographic Contrast Agent

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Equipment and CEUS Examination

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Offline Analysis

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Statistical Analysis

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Results

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Figure 1, Conventional ultrasound of the normal sciatic nerve. The left sciatic nerve (arrow) was demonstrated as a tubular echogenic structure with multiple parallel hypoechoic linear areas separated by hyperechoic bands on longitudinal sonography.

Figure 2, Contrast-enhanced ultrasound of the normal sciatic nerve. After the bolus injection of SonoVue, the sciatic nerve (arrow) was homogeneously enhanced because the capillary network was completely filled by microbubbles.

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Figure 3, Quantitative assessment of the blood perfusion of the sciatic nerve, its surrounding muscle, and the arterial branch. The time-intensity curve showed that the sciatic nerve (yellow curve) had a similar enhancement pattern with its surrounding muscle (white curve) and the arterial branch (purple curve), which included a rapid wash-in and a slow wash-out.

Figure 4, The area under the time-intensity curve of the sciatic nerve was higher than that of the skeletal muscle and lower than that of the arterial branch ( P = .000).

Figure 5, The perfusion index of the sciatic nerve was higher than that of the skeletal muscle and lower than that of the arterial branch ( P = .000).

Figure 6, There was a significant difference in the mean transit time among the sciatic nerve, the skeletal muscle, and the arterial branch ( P = .015).

Figure 7, The maximum intensity of the sciatic nerve was similar to that of the skeletal muscle ( P = .000).

Figure 8, There was no significant difference in the time to peak among the sciatic nerve, the skeletal muscle, and the arterial branch ( P = .551).

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Discussion

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Conclusions

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