Skip to main navigation menu Skip to main content Skip to site footer

Review article: Biomedical intelligence

Vol. 144 No. 5152 (2014)

Assessment of microcirculation by contrast-enhanced ultrasound: a new approach in vascular medicine

  • Mathias Kaspar
  • Sasan Partovi
  • Markus Aschwanden
  • Stephan Imfeld
  • Thomas Baldi
  • Heiko Uthoff
  • Daniel Staub
Cite this as:
Swiss Med Wkly. 2014;144:w14047


Contrast-enhanced ultrasound (CEUS) has emerged as a valuable imaging modality that complements and enhances standard vascular ultrasound imaging. Ultrasound contrast agents are gas-filled microbubbles that are injected intravenously and serve as intravascular tracers. Based on the properties to enhance and to quantify the macro- and microcirculation down to the capillary perfusion level in different vascular territories and organs, CEUS imaging has the potential to improve the diagnostic performance in the detection and characterisation of various vascular disorders reviewed in this article.

In carotid atherosclerotic disease, CEUS imaging provides additional information on plaque vulnerability by illustrating the presence and extent of intraplaque neovascularisation. This new imaging modality may be helpful for further risk stratification of arteriosclerotic lesions and for detecting patients at risk for vascular events, eventually leading to more specific individually tailored therapeutic recommendations. CEUS imaging is also a helpful tool for the diagnosis and for monitoring of inflammatory vascular diseases. It increases the diagnostic performance of ultrasound in detecting inflammatory changes of the vessel wall such as hypervascularisation and hyperaemia. Changes in vessel wall enhancement may also reflect the response to anti-inflammatory therapy. Moreover, CEUS imaging is also a valuable tool for the assessment of the microcirculation and the tissue perfusion in solid organs including native and transplanted kidneys. The technique provides more accurate information on perfusion deficits of the parenchyma in patients with kidney infarction, necrosis or graft dysfunction. CEUS also has great potential in the assessment of the microcirculation of the skeletal muscle, particularly in patients with peripheral artery disease or diabetic microangiopathy.

In the future, the use of targeted on site microbubbles could further enhance and expand the diagnostic capabilities of current vascular ultrasound by assessing specific molecular processes that play a role in the pathophysiology of vascular diseases. Furthermore, ultrasound-directed, site-specific drug and gene delivery using microbubble contrast agents could gain great clinical value in the future. The combination of CEUS for diagnosis and therapy will provide unique opportunities for vascular clinicians to image the microcirculation and directly treat vascular diseases.


  1. Staub D, Partovi S, Imfeld S, Uthoff H, Baldi T, Aschwanden M, et al. Novel applications of contrast-enhanced ultrasound imaging in vascular medicine. Vasa. 2013;42(1):17–31.
  2. Feinstein S, Coll B, Staub D, Adam D, Schinkel A, ten Cate F, et al. Contrast enhanced ultrasound imaging. J Nucl Cardiol. 2010;17(1):106–15.
  3. Faez T, Emmer M, Kooiman K, Versluis M, van der Steen A, de Jong N. 20 years of ultrasound contrast agent modeling. IEEE Trans Ultrason Ferroelectr Freq Control. 2013;60(1):7–20.
  4. Clevert DA, D’Anastasi M, Jung EM. Contrast-enhanced ultrasound and microcirculation: efficiency through dynamics – current developments. Clin Hemorheol Microcirc. 2013;53(1–2):171–86.
  5. Piscaglia F, Nolsøe C, Dietrich CF, Cosgrove DO, Gilja OH, Bachmann Nielsen M, et al. The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): update 2011 on non-hepatic applications. Ultraschall Med. 2012;33(1):33–59.
  6. Staub D, Schinkel A, Coll B, Coli S, van der Steen A, Reed J, et al. Contrast-enhanced ultrasound imaging of the vasa vasorum: from early atherosclerosis to the identification of unstable plaques. JACC Cardiovasc Imaging. 2010;3(7):761–71.
  7. Piscaglia F, Bolondi L. The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations. Ultrasound Med Biol. 2006;32(9):1369–75.
  8. ten Kate GL, Renaud GG, Akkus Z, van den Oord SC, ten Cate FJ, Shamdasani V, et al. Far-wall pseudoenhancement during contrast-enhanced ultrasound of the carotid arteries: clinical description and in vitro reproduction. Ultrasound Med Biol. 2012;38(4):593–600.
  9. Dietrich CF, Averkiou MA, Correas JM, Lassau N, Leen E, Piscaglia F. An EFSUMB Introduction into Dynamic Contrast-Enhanced Ultrasound (DCE-US) for Quantification of Tumour Perfusion. Ultraschall Med. 2012;33(4):344–51.
  10. Tranquart F, Mercier L, Frinking P, Gaud E, Arditi M. Perfusion quantification in contrast-enhanced ultrasound (CEUS) – ready for research projects and routine clinical use. Ultraschall Med. 2012;33 Suppl 1:S31–8.
  11. Sillesen H. Carotid Intima-media Thickness and/or Carotid Plaque: What is Relevant? Eur J Vasc Endovasc Surg. 2014.
  12. Den Ruijter HM, Peters SA, Anderson TJ, Britton AR, Dekker JM, Eijkemans MJ, et al. Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis. JAMA. 2012;308(8):796–803.
  13. Ziegelbauer K, Schaefer C, Steinmetz H, Sitzer M, Lorenz MW. Clinical usefulness of carotid ultrasound to improve stroke risk assessment: ten-year results from the Carotid Atherosclerosis Progression Study (CAPS). Eur J Prev Cardiol. 2013;20(5):837–43.
  14. Nambi V, Chambless L, Folsom AR, He M, Hu Y, Mosley T, et al. Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: the ARIC (Atherosclerosis Risk In Communities) study. J Am Coll Cardiol. 2010;55(15):1600–7.
  15. Eyding J, Geier B, Staub D. Current strategies and possible perspectives of ultrasonic risk stratification of ischemic stroke in internal carotid artery disease. Ultraschall Med. 2011;32(3):267–73.
  16. Partovi S, Loebe M, Aschwanden M, Baldi T, Jäger KA, Feinstein SB, et al. Contrast-enhanced ultrasound for assessing carotid atherosclerotic plaque lesions. AJR Am J Roentgenol. 2012;198(1):W13–9.
  17. van den Oord SC, ten Kate GL, Sijbrands EJ, van der Steen AF, Schinkel AF. Effect of carotid plaque screening using contrast-enhanced ultrasound on cardiovascular risk stratification. Am J Cardiol. 2013;111(5):754–9.
  18. Sluimer J, Daemen M. Novel concepts in atherogenesis: angiogenesis and hypoxia in atherosclerosis. J Pathol. 2009;218(1):7–29.
  19. Hellings WE, Peeters W, Moll FL, Piers SR, van Setten J, Van der Spek PJ, et al. Composition of carotid atherosclerotic plaque is associated with cardiovascular outcome: a prognostic study. Circulation. 2010;121(17):1941–50.
  20. Gallino A, Stuber M, Crea F, Falk E, Corti R, Lekakis J, et al. “In vivo” imaging of atherosclerosis. Atherosclerosis. 2012;224(1):25–36.
  21. Coli S, Magnoni M, Sangiorgi G, Marrocco-Trischitta M, Melisurgo G, Mauriello A, et al. Contrast-enhanced ultrasound imaging of intraplaque neovascularization in carotid arteries: correlation with histology and plaque echogenicity. J Am Coll Cardiol. 2008;52(3):223–30.
  22. Schinkel A, Krueger C, Tellez A, Granada J, Reed J, Hall A, et al. Contrast-enhanced ultrasound for imaging vasa vasorum: comparison with histopathology in a swine model of atherosclerosis. Eur J Echocardiogr. 2010.
  23. Shah F, Balan P, Weinberg M, Reddy V, Neems R, Feinstein M, et al. Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? Vasc Med. 2007;12(4):291–7.
  24. Hoogi A, Adam D, Hoffman A, Kerner H, Reisner S, Gaitini D. Carotid plaque vulnerability: quantification of neovascularization on contrast-enhanced ultrasound with histopathologic correlation. AJR Am J Roentgenol. 2011;196(2):431–6.
  25. Vavuranakis M, Sigala F, Vrachatis DA, Papaioannou TG, Filis K, Kavantzas N, et al. Quantitative analysis of carotid plaque vasa vasorum by CEUS and correlation with histology after endarterectomy. Vasa. 2013;42(3):184–95.
  26. van den Oord SC, Akkus Z, Bosch JG, Hoogi A, Ten Kate GL, Renaud G, et al. Quantitative Contrast-Enhanced Ultrasound of Intraplaque Neovascularization in Patients with Carotid Atherosclerosis. Ultraschall Med. 2014.
  27. Li C, He W, Guo D, Chen L, Jin X, Wang W, et al. Quantification of carotid plaque neovascularization using contrast-enhanced ultrasound with histopathologic validation. Ultrasound Med Biol. 2014;40(8):1827–33.
  28. Müller HF, Viaccoz A, Kuzmanovic I, Bonvin C, Burkhardt K, Bochaton-Piallat ML, et al. Contrast-enhanced ultrasound imaging of carotid plaque neo-vascularization: accuracy of visual analysis. Ultrasound Med Biol. 2014;40(1):18–24.
  29. Staub D, Partovi S, Schinkel AF, Coll B, Uthoff H, Aschwanden M, et al. Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US. Radiology. 2011;258(2):618–26.
  30. Staub D, Patel M, Tibrewala A, Ludden D, Johnson M, Espinosa P, et al. Vasa vasorum and plaque neovascularization on contrast-enhanced carotid ultrasound imaging correlates with cardiovascular disease and past cardiovascular events. Stroke. 2010;41(1):41–7.
  31. Xiong L, Deng Y, Zhu Y, Liu Y, Bi X. Correlation of carotid plaque neovascularization detected by using contrast-enhanced US with clinical symptoms. Radiology. 2009;251(2):583–9.
  32. Faggioli GL, Pini R, Mauro R, Pasquinelli G, Fittipaldi S, Freyrie A, et al. Identification of carotid “vulnerable plaque” by contrast-enhanced ultrasonography: correlation with plaque histology, symptoms and cerebral computed tomography. Eur J Vasc Endovasc Surg. 2011;41(2):238–48.
  33. Partovi S, Imfeld S, Aschwanden M, Bilecen D, Jaeger KA, Staub D. The use of contrast-enhanced ultrasound (CEUS) in chronic periaortitis. Ultraschall Med. 2012;Aug 7 [epub ahead of print].
  34. Steubl D, Thürmel K, Moog P, Essler M, Heemann U, Stock KF. Comparison of fluorine-18–deoxyglucose positron emission tomography/computed tomography and contrast-enhanced ultrasound in a patient with chronic periaortitis. Vasa. 2013;42(5):370–4.
  35. Magnoni M, Dagna L, Coli S, Cianflone D, Sabbadini MG, Maseri A. Assessment of Takayasu arteritis activity by carotid contrast-enhanced ultrasound. Circ Cardiovasc Imaging. 2011;4(2):e1–2.
  36. Giordana P, Baqué-Juston MC, Jeandel PY, Mondot L, Hirlemann J, Padovani B, et al. Contrast-enhanced ultrasound of carotid artery wall in Takayasu disease: first evidence of application in diagnosis and monitoring of response to treatment. Circulation. 2011;124(2):245–7.
  37. Schinkel AF, van den Oord SC, van der Steen AF, van Laar JA, Sijbrands EJ. Utility of contrast-enhanced ultrasound for the assessment of the carotid artery wall in patients with Takayasu or giant cell arteritis. Eur Heart J Cardiovasc Imaging. 2014;15(5):541–6.
  38. Bertolotto M, Martegani A, Aiani L, Zappetti R, Cernic S, Cova MA. Value of contrast-enhanced ultrasonography for detecting renal infarcts proven by contrast enhanced CT. A feasibility study. Eur Radiol. 2008;18(2):376–83.
  39. McArthur C, Baxter GM. Current and potential renal applications of contrast-enhanced ultrasound. Clin Radiol. 2012.
  40. Fischer T, Filimonow S, Rudolph J, Morgera S, Budde K, Slowinski T, et al. Arrival time parametric imaging: a new ultrasound technique for quantifying perfusion of kidney grafts. Ultraschall Med. 2008;29(4):418–23.
  41. Grzelak P, Szymczyk K, Strzelczyk J, Kurnatowska I, Sapieha M, Nowicki M, et al. Perfusion of kidney graft pyramids and cortex in contrast-enhanced ultrasonography in the determination of the cause of delayed graft function. Ann Transplant. 2011;16(1):48–53.
  42. Aschwanden M, Partovi S, Jacobi B, Fergus N, Schulte AC, Robbin MR, et al. Assessing the end-organ in peripheral arterial occlusive disease-from contrast-enhanced ultrasound to blood-oxygen-level-dependent MR imaging. Cardiovasc Diagn Ther. 2014;4(2):165–72.
  43. Duerschmied D, Olson L, Olschewski M, Rossknecht A, Freund G, Bode C, et al. Contrast ultrasound perfusion imaging of lower extremities in peripheral arterial disease: a novel diagnostic method. Eur Heart J. 2006;27(3):310–5.
  44. Duerschmied D, Zhou Q, Rink E, Harder D, Freund G, Olschewski M, et al. Simplified contrast ultrasound accurately reveals muscle perfusion deficits and reflects collateralization in PAD. Atherosclerosis. 2009;202(2):505–12.
  45. Duerschmied D, Maletzki P, Freund G, Olschewski M, Bode C, Hehrlein C. Success of arterial revascularization determined by contrast ultrasound muscle perfusion imaging. J Vasc Surg. 2010;52(6):1531–6.
  46. Lindner J, Womack L, Barrett E, Weltman J, Price W, Harthun N, et al. Limb stress-rest perfusion imaging with contrast ultrasound for the assessment of peripheral arterial disease severity. JACC Cardiovasc Imaging. 2008;1(3):343–50.
  47. Amarteifio E, Wormsbecher S, Krix M, Demirel S, Braun S, Delorme S, et al. Dynamic contrast-enhanced ultrasound and transient arterial occlusion for quantification of arterial perfusion reserve in peripheral arterial disease. Eur J Radiol. 2012.
  48. Duerschmied D, Maletzki P, Freund G, Olschewski M, Seufert J, Bode C, et al. Analysis of muscle microcirculation in advanced diabetes mellitus by contrast enhanced ultrasound. Diabetes Res Clin Pract. 2008;81(1):88–92.
  49. Amarteifio E, Wormsbecher S, Demirel S, Krix M, Braun S, Rehnitz C, et al. Assessment of skeletal muscle microcirculation in type 2 diabetes mellitus using dynamic contrast-enhanced ultrasound: a pilot study. Diab Vasc Dis Res. 2013;10(5):468–70.
  50. Womack L, Peters D, Barrett EJ, Kaul S, Price W, Lindner JR. Abnormal skeletal muscle capillary recruitment during exercise in patients with type 2 diabetes mellitus and microvascular complications. J Am Coll Cardiol. 2009;53(23):2175–83.
  51. Lindner JR, Sinusas A. Molecular imaging in cardiovascular disease: Which methods, which diseases? J Nucl Cardiol. 2013;20(6):990–1001.
  52. Castle J, Butts M, Healey A, Kent K, Marino M, Feinstein SB. Ultrasound-mediated targeted drug delivery: recent success and remaining challenges. Am J Physiol Heart Circ Physiol. 2013;304(3):H350–7.

Most read articles by the same author(s)