Ultrasound contrast agents (USCA)

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

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; 1555-1558

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

Signal enhancement Density Compressibility Concentration Size

Prospects Increased life duration of the microbubbles Size Density Diffusion Solubility

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

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

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

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

Fundamental imaging Sonohysterography demonstrates an endometrial polyp Contrast filled right ventricle

Fundamental Doppler imaging Without contrast With contrast

Identification of renal artery Without contrast

Identification of renal artery With contrast

Complicated cyst

Bosniak IV cyst

Mass or complicated cyst?

Aortic dissection

Testicular torsion

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

Pulse inversion: fundamental

Pulse inversion: harmonics

Amplitude modulation

Contrast pulse sequencing

Pattern-based classification of nhancement at arterio-portal phase Enhancement pattern HCC Hemangioma Cholangio- carcinoma Metastasis Fat spared Total Whole (art) 24 0 0 0 0 24 Mosaic (art) 29 0 0 2 0 31 Ring (art/port) 0 2 5 19 0 26 Puddles (port) 0 6 0 0 0 6 No focal sign 7 2 1 3 7 20 Total 60 10 6 24 7 107 Tanaka S, Ioka T, Oshikawa O, Hamada Y, Yoshioka F. Dynamic sonography of hepatic tumors. AJR Am J Roentgenol 2001;177(4):799-805.

Pattern-based classification of enhancement at parenchymal phase Enhancement pattern HCC Hemangioma Cholangio- carcinoma Metastasis Fat spared Total Clear defect 2 0 5 17 0 24 Obscure defect 37 1 1 5 0 44 Reticular 12 0 0 0 0 12 Regional 9 0 0 2 0 11 No focal sign 0 9 0 0 7 8 Total 60 10 6 24 7 107 Tanaka S, Ioka T, Oshikawa O, Hamada Y, Yoshioka F. Dynamic sonography of hepatic tumors. AJR Am J Roentgenol 2001;177(4):799-805.

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

Tableau 2: Types et valeur diagnostique des prises de contraste en imagerie échographique non linéaire Fréquence % Artériel Porte Tardif Sensibilité % Spécificité % PPV % Angiome 40-95 rare 18-60 100 Élevé pour bénignité 100 90 Elevé 100 100 FNH 40* 100 100 40-50 92 96 96 HCC 45-50 50 70 90 95 88 Métastase 30 * Aspect transitoire avant la prise de contraste homogène en phase artérielle

Detection of metastases Imaging Nb of Sensibility False positive technique metastases Standard US 47 70 % 1 Helical CT 61 80 % 1 Per-operative 83 Reference Reference US Contraste US 66 82 % 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 176:1191-8., 2001

Detection of metastases Imaging Nb of Sensibility False positive technique metastases Standard US 47 70 % 1 Helical CT 61 80 % 1 Per-operative 83 Reference Reference US Contrast US 66 82 % 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 176:1191-8., 2001

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

Further application

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

Biopsy guidance

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

Thank you for your attention!