1. Feasibility of Targeting Atherosclerotic Plaques by High-Intensity–focused Ultrasound: An In Vivo Study 
Islam A. Shehata, MD, MSc, John R. Ballard, PhD, Andrew J. Casper, PhD, Dalong Liu, PhD, Mitchell Troutman , DVM, MS, Emad S. Ebbini, PhD 
Journal of Vascular and Interventional Radiology 
Volume 24, Issue 12, Pages e2 (December 2013)
DOI: /j.jvir
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2. Figure 1
Skin marking and positioning of the dual-mode US array. (a) Blue lines are drawn on the skin over the left groin, corresponding to the best visualization of the atherosclerotic plaque on longitudinal (L) and transverse (T) US scan. The point of intersection (arrow) represents the point of best visualization of the plaque, upon which the dual-mode US array was centered. (b) Dual-mode US array is centered over the plaque, and a metallic frame holds thin membrane sealed to the skin by glue. Degassed water contained by the membrane provides acoustic coupling of the transducer to the skin.
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3. Figure 2
Imaging during treatment (from swine 2). (a) Conventional diagnostic scan (transverse) conveyed through the diagnostic transducer within the central fenestration of the integrated dual-mode US array. Imaging is conducted through degassed water (W), and different anatomic structures can be identified: subcutaneous fat (S.C), muscles (M), femoral artery (A), and femoral vein (V). (b) Synthetic aperture imaging of the dual-mode US array showing the femoral artery (A) and femoral vein (V). This image is completely registered with the therapeutic high-intensity–focused US beam.
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4. Figure 3
High-intensity–focused US-induced thermal damage in arterial walls (from swine 1). (a) H&E staining of the targeted arterial segment shows distinct region of mural injury outlined in (b). Mural injury is characterized by separated or individualized smooth muscle cells, which exposed the surrounding lightly basophilic extracellular matrix. Injured smooth muscle cells also showed hypereosinophilic cytoplasm and condensed or shrunken darkly basophilic nuclei. The intimal endothelial lining overlying the mural injury appears totally intact and confluent.
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5. Figure 4
Histologic appearance of a high-intensity–focused US lesion in atherosclerotic plaque (from swine 2). (Reprinted with permission from Ballard JR, Casper AJ, Liu D, et al. Dual-mode ultrasound arrays for image-guided targeting of atheromatous plaques. AIP Conf Proc 2012; 1503:124–128. Copyright © 2012, American Institute of Physics Publications.) (a) H&E stain (objective magnification, × 10) shows a discrete high-intensity–focused US lesion within the targeted plaque (outlined). Arrows point to the intact corresponding endothelial lining. (b) Image at objective magnification × 20 shows a thermally injured aggregate of lipid-laden macrophages with condensed or shrunken darkly basophilic nuclei and ruptured cell walls. Small numbers of neutrophils infiltrate and partially encircle the injured plaque.
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6. Figure 5
High-intensity–focused US-induced thermal injury within atherosclerotic plaque (from swine 3). Confluent area of thermal damage is seen within the substance of the plaque (outlined by green line).
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7. Figure 6
Histologic analysis of high-intensity–focused US-induced thermal damage within atherosclerotic plaque (from swine 4). (a) H&E staining of targeted plaque shows evidence of thermal damage and mural thrombosis (outlined). (b) Magnified view (objective magnification, × 20) of the outlined area shows mural thrombus covered by an intact and confluent layer of endothelium and subjacent inflammation within plaque. (c) Thrombosis of vasa vasorum within the atherosclerotic plaque (plane II).
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8. Figure E1
Integrated dual-mode US array system: 3.5-MHz dual-mode US array transducer with a central fenestration through which a linear diagnostic transducer is applied.
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9. Figure E2
Longitudinal US scan of the left femoral artery of swine 4 with a 7.5-MHz transducer shows a non–hemodynamically significant atherosclerotic plaque along the posterior wall of the artery (arrows).
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10. Figure E3
Muscle marker. H&E staining of a skeletal muscle shows evidence of muscle injury in the form of moderate variation in skeletal cells diameter, a thickened or fibrotic perimysium, vacuolation of muscle fibers, tinctorial changes in eosinophilic staining, separation of muscle cells from surrounding endomysium, and multiple nuclei not located at the cell periphery.
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11. Figure E4
Focal hemorrhage within targeted atherosclerotic plaque (from swine 3). Gross pathologic evaluation of the targeted arterial wall shows focal mural hemorrhage (arrow). No luminal thrombosis identified.
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12. Figure E5
High-intensity–focused US-induced thermal injury within atherosclerotic plaque (from swine 4). H&E staining (objective magnification, × 2) of the targeted plaque shows inflamed atherosclerotic plaque secondary to thermal injury, with inflammation extension into the subjacent tunica media.
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13. Figure E6
Histologic examination of high-intensity–focused US-induced thermal damage within atherosclerotic plaque (from swine 4). H&E staining of the targeted plaque shows hemorrhage within the targeted plaque and presumptive central area of thermal necrosis.
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14. Figure E7
Histology of high-intensity–focused US-induced thermal damage within atherosclerotic plaque. H&E staining of the targeted plaque shows an area of thermally altered extracellular lipid or thermal necrosis of lipid-laden macrophages.
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