Ultrasound contrast agents (USCA)

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1 Ultrasound contrast agents (USCA) Jean-Yves Meuwly, MD, University Hospital Lausanne, Switzerland

2 Ultrasound contrast agents Initially developed in order to enhance the Doppler signal Increase in signal intensity ~ 20dB Detection of low flow Improvement of signal/noise ratio Sensitivity offset for low sensitivity ultrasound machines Forsberg F, Liu JB, Merton DA, Rawool NM, Goldberg BB. In vivo evaluation of a new ultrasound contrast agent. Proc IEEE Ultrason Symp, 1994;

3 Ultrasound contrast agents Gramiak and Shah, 1968 Shaked saline, containing air microbubbles, injected in the aortic root

4 Signal enhancement Density Compressibility Concentration Size

5 Prospects Increased life duration of the microbubbles Size Density Diffusion Solubility

6 Characteristics of microbubbles Size < 8 μm Dilatation and contraction produced by the ultrasound beam Asymmetrical movements Production of harmonics Microbubbles break down with high energy pulses

7 Oscillations of microbubbles Bubble Pressure peak Appearance half a cycle later Bubble Rarefaction zone Propagation direction

8 Behavior of microbubbles Very low acoustic energy Linear oscillations Low acoustic energy Non-linear oscillations Appearance of harmonic frequencies Preservation of microbubbles integrity High acoustic energy Destruction of microbubbles Intense and short harmonic signal

9 Fundamental imaging Low enhancement in B mode Detection of microbubbles in natural cavities Bladder Uterus Pyelocaliceal cavities Lowering of vascular contrast in B mode Increased contrast in Doppler ultrasound Enhancement of vessels Stimulated acoustic emission related to the destruction of the microbubbles

10 Fundamental imaging Sonohysterography demonstrates an endometrial polyp Contrast filled right ventricle

11 Fundamental Doppler imaging Without contrast With contrast

12 Identification of renal artery Without contrast

13 Identification of renal artery With contrast

14 Complicated cyst

15 Complicated cyst

16 Complicated cyst

17 Complicated cyst

18 Bosniak IV cyst

19 Mass or complicated cyst?

20 Mass or complicated cyst?

21 Mass or complicated cyst?

22 Mass or complicated cyst?

23 Mass or complicated cyst?

24 Mass or complicated cyst?

25 Aortic dissection

26 Aortic dissection

27 Aortic dissection

28 Aortic dissection

29 Aortic dissection

30 Testicular torsion

31 Testicular torsion

32 Testicular torsion

33 Testicular torsion

34 Harmonic imaging Based on the non-linear properties of microbubbles Single pulse with filtration Multipulses» Phase inversion» Contrast detection imaging» Amplitude modulation» Combination of phase and amplitude modulation

35 Pulse inversion: fundamental

36 Pulse inversion: harmonics

37 Amplitude modulation

38 Contrast pulse sequencing

39 Pattern-based classification of nhancement at arterio-portal phase Enhancement pattern HCC Hemangioma Cholangio- carcinoma Metastasis Fat spared Total Whole (art) Mosaic (art) Ring (art/port) Puddles (port) No focal sign Total Tanaka S, Ioka T, Oshikawa O, Hamada Y, Yoshioka F. Dynamic sonography of hepatic tumors. AJR Am J Roentgenol 2001;177(4):

40 Pattern-based classification of enhancement at parenchymal phase Enhancement pattern HCC Hemangioma Cholangio- carcinoma Metastasis Fat spared Total Clear defect Obscure defect Reticular Regional No focal sign Total Tanaka S, Ioka T, Oshikawa O, Hamada Y, Yoshioka F. Dynamic sonography of hepatic tumors. AJR Am J Roentgenol 2001;177(4):

41 Characterization of FNH Central spoke-wheel shaped enhancement Diffuse and rapid enhancement at arterial phase Persistent bubble uptake Late iso-echoic appearance Quaia E, Calderan L, Tona G, et al. Characterization of focal liver lesions using low transmit power ultrasound imaging and Sonovue. Eur Radiol 2004; 14 (supp 2) 157 Lencioni R, Franchini C, Cioni D, et al. Characterization of incidental liver lesions: Value of contrastenhanced ultrasound. Eur Radiol 2004; 14 (supp 2) 334

42 Tableau 2: Types et valeur diagnostique des prises de contraste en imagerie échographique non linéaire Fréquence % Artériel Porte Tardif Sensibilité % Spécificité % PPV % Angiome rare Élevé pour bénignité Elevé FNH 40* HCC Métastase 30 * Aspect transitoire avant la prise de contraste homogène en phase artérielle

43 Detection of metastases Imaging Nb of Sensibility False positive technique metastases Standard US % 1 Helical CT % 1 Per-operative 83 Reference Reference US Contraste US % 2 Albrecht T, Hoffmann CW, Schmitz SA, et al: Phase-inversion sonography during the liver-specific late phase of contrast enhancement: improved detection of liver metastases. AJR Am J Roentgenol 176: , 2001

44 Detection of metastases Imaging Nb of Sensibility False positive technique metastases Standard US % 1 Helical CT % 1 Per-operative 83 Reference Reference US Contrast US % 2 Albrecht T, Hoffmann CW, Schmitz SA, et al: Phase-inversion sonography during the liver-specific late phase of contrast enhancement: improved detection of liver metastases. AJR Am J Roentgenol 176: , 2001

45 Detection of metastases Imaging Nb of Sensibility False positive technique metastases Standard US % 1 Helical CT % 1 Per-operative 83 Reference Reference US Contrast US % 2 Albrecht T, Hoffmann CW, Schmitz SA, et al: Phase-inversion sonography during the liver-specific late phase of contrast enhancement: improved detection of liver metastases. AJR Am J Roentgenol 176: , 2001

46 Conventional / Contrast US Increasing in conspicuity Subjectively in 88 % of patients Objectively from 6.5 db to 17.3 db (P<.001)

47 Further application

48 Biopsy guidance Sufficient improvement in conspicuity to allow sampling Prolonged procedure time compared to conventional US Greater number of passes No difference in success and complications Meuwly JY, Gudinchet F, Schnyder P, et al: Pulse-inversion harmonic imaging improves lesion conspicuity during US-guided biopsy. J Vasc Intervent Radiol 14, 2003

49 Biopsy guidance

50 Present and future of USCA Direct visualization of blood flow Characterization of focal liver lesions Determination of vascular morphology Measurement transit time Quantification of perfusion Differentiation of tissues Detection of focal liver lesions Identification of the lesions before biopsy Detection solid organs trauma Tissular characterization with targeted microbubbles Gene and therapeutic agents transmission Microbulles as vector Sonoporation

51 Thank you for your attention!

RICCARDO LENCIONI,CLOTILDE DELLA PINA, LAURA CROCETTI,DANIA CIONI. Chapter 1

RICCARDO LENCIONI,CLOTILDE DELLA PINA, LAURA CROCETTI,DANIA CIONI Chapter 1 Impact of European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on the Use of Contrast