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. 2016 Jul;42(7):1531-40.
doi: 10.1016/j.ultrasmedbio.2016.02.001. Epub 2016 Apr 12.

Diagnostic Ultrasound High Mechanical Index Impulses Restore Microvascular Flow in Peripheral Arterial Thromboembolism

Thomas R Porter  1 , Stanley Radio  2 , John Lof  2 , Carr Everbach  3 , Jeffry E Powers  4 , Francois Vignon  5 , William T Shi  5 , Feng Xie  2
Affiliations

Diagnostic Ultrasound High Mechanical Index Impulses Restore Microvascular Flow in Peripheral Arterial Thromboembolism

Thomas R Porter et al. Ultrasound Med Biol. 2016 Jul.

Abstract

We sought to explore mechanistically how intermittent high-mechanical-index (MI) diagnostic ultrasound impulses restore microvascular flow. Thrombotic microvascular obstruction was created in the rat hindlimb muscle of 36 rats. A diagnostic transducer confirmed occlusion with low-MI imaging during an intravenous microbubble infusion. This same transducer was used to intermittently apply ultrasound with an MI that produced stable or inertial cavitation (IC) for 10 min through a tissue-mimicking phantom. A nitric oxide inhibitor, L-Nω-nitroarginine methyl ester (L-NAME), was pre-administered to six rats. Plateau microvascular contrast intensity quantified skeletal microvascular blood volume, and postmortem staining was used to detect perivascular hemorrhage. Intermittent IC impulses produced the greatest recovery of microvascular blood volume (p < 0.0001, analysis of variance). Nitric oxide inhibition did not affect the skeletal microvascular blood volume improvement, but did result in more perivascular hemorrhage. IC inducing pulses from a diagnostic transducer can reverse microvascular obstruction after acute arterial thromboembolism. Nitric oxide may prevent unwanted bio-effects of these IC pulses.

Keywords: Cavitation; Diagnostic ultrasound; Microvascular obstruction; Nitric oxide.

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Figures

Figure 1
Figure 1
Location of the diagnostic ultrasound transducers applying IC and SC impulses through a tissue mimicking phantom, and the passive cavitation detectors which verified the presence and intensity (in root mean square voltage) of IC.
Figure 2
Figure 2. Examples of improvement in microvascular blood volume in a rat treated with intermittent IC inducing pulses both in the presence and absence of L-NAME pre-treatment
A rat treated with non-destructive stable cavitation imaging alone (NSC) is shown along the left column.
Figure 3
Figure 3. Demonstration of the increase in skeletal MBV with inertial cavitation (IC) inducing ultrasound treatments
Error bars depict standard deviation. SC = stable cavitation; NSC = nondestructive stable cavitation; 3 cm = 3 cm phantom; 6 cm = 6 cm phantom. *<0.05 compared to before treatment; †<0.01 compared to before treatment. n = 6 for each group.
Figure 4
Figure 4. Effect of pretreatment with L-NAME on restoration of microvascular blood volume
Skeletal muscle intensity bar graphs after microembolization. The skeletal muscle intensity following IC inducing impulses (green bar graphs) increased to nearly the same level as in the absence of L-NAME pretreatment (blue histograms). *<0.01 compared to before treatment; †<0.001 compared to before treatment. n = 6 for each group.
Figure 5
Figure 5
An example of a residual thrombus (arrows) in a small vessel, seen in an L-NAME pre treated rat.
Figure 6
Figure 6. Examples of no, mild, and moderate peri-vascular hemorrhage
The arrows depict the red blood cells observed in extravascular foci. When two or more foci were observed in a 10x magnification plane, it was considered moderate hemorrhage.
See this image and copyright information in PMC

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