Outline Ultrasound Contrast Imaging • History and background • Basics of Ultrasound Contrast Imaging • Application to liver lesion characterization Matthew Bruce Mike Averkiou Tony Brock-Fisher Patrick Rafter Jeff Powers Philips Ultrasound, Bothell, WA, USA • Quantification • Upcoming applications Bruce, Averkiou—AAPM 2004 1 Bruce, Averkiou—AAPM 2004 2 Blood Flow Imaging with Ultrasound Ultrasound Contrast Agents Color Doppler w/o contrast • Microbubbles Pulse Inversion with contrast – Heavy Gas/Air Mixture • PFC, SF6 – Encapsulated • Shell ~ lipid, Albumin, polymer – Diameters 2-10 µm • Administered – Intravenous Injection • Removed – Dissolve in circulation – Filtered by liver – Cleared ~ 15 minutes lesion Contrast and Red Blood Cells Spleen Bruce, Averkiou—AAPM 2004 3 Bruce, Averkiou—AAPM 2004 Hemangioma 4 1 Clinical Applications of Ultrasound Contrast History of Ultrasound Contrast Agents • LVO – Left Ventricular Opacification • Liver tumor detection and characterization – Shelled agents (galactose, albumin, lipid …) • Myocardial perfusion – With Heavy gases (PFC ..) • Kidney (transplants), breast, prostate, etc. • Stroke • Research for targeted/molecular imaging • Therapy guidance • First of microbubbles - Agitated Saline • Search for stabilization and passage through lungs led to: – Combined with drug delivery – RFA – Biopsy • Bruce, Averkiou—AAPM 2004 5 Bruce, Averkiou—AAPM 2004 6 Microbubble Response to Diagnostic Ultrasound Pressures Contrast Agent Status SonoVue $ Mouse imaging USA Canada Europe China Japan In trials Pending Yes YES In trials • Nonlinear oscillators Low MI – generate harmonic components Definity + Pending Yes Yes+ In trials No Optison † LVO LVO LVO No No Levovist* No Yes Yes Yes Yes Point Bio Pending for MCE No No No No – f0, 2f0, 3f0 ... • Transient nature – slow diffusion (after shell disruption) – bubble fragmentation into smaller bubbles $ SonoVue approved for macro / micro flow in heart, liver, renal High MI (after strong oscillation), and thus faster diffusion * Levovist available in 69 countries, including Latin America and Asia + Limited to UK, pending other European countries (LVO and GI) † Optison and Definity approved for Cardiology applications (LVO) in USA, Canada and Europe. Use in General Imaging requires “off-label” research agreement and IRB. Bruce, Averkiou—AAPM 2004 7 MI – Mechanical Index (High MI > 0.2) Bruce, Averkiou—AAPM 2004 Courtesy N. deJong, Erasmus University 8 2 Contrast in ventricle Harmonic Imaging • Contrast Imaging Techniques • • • Designed to extract nonlinear portion of returned signal Improved contrast to tissue ratio Single pulse techniques filter out fundamental on receive, but this limits the available bandwidth Triggered at High MI Fundamental Imaging – Intermittent image acquisitions Scanhead / beamformer frequency response Transmit Receive frequency frequency Led to Tissue Harmonic Imaging Amplitude • 1995 Harmonic Imaging Bruce, Averkiou—AAPM 2004 9 Harmonic Power Doppler • Decorrelated Doppler signals • Triggered at High MI Due to microbubble disruption (pulse to pulse) – High Frequency Doppler signals – – -40 0 2 3 4 5 6 3000 Tissue Doppler Signal 2000 1000 1 8000 4000 0 -4000 -8000 1 Bruce, Averkiou—AAPM 2004 1 Tissue Doppler Signal Optison Higher MI f 10 2 3 4 5 6 7 Bubble Doppler Signal 8 Bubble Doppler Signal 2 3 4 5 6 7 • Majority of microbubbles destroyed MI>0.4 – At real time frame rates (>10 Hz) Intermittent image acquisitions MI=1.1 trig. 1:4 2fo • Has highest SNRs RF Spectrum -20 End systole fo High MI Imaging RF Spectrum (dB) vs F (MHz) 0 – Bruce, Averkiou—AAPM 2004 • Limited visualization times – Destroy agent being imaged. – CV – ECG triggered imaging while skipping heart cycles – GI - Sweep through volume of interest or watch veil as agent is destroyed 8 More decorrelated Doppler signals 11 Bruce, Averkiou—AAPM 2004 12 3 Harmonic Power Doppler – High MI Harmonic Power Doppler – High MI Metastasis (from colorectal) – Levovist, high MI Bruce, Averkiou—AAPM 2004 13 Low MI - Real-time Contrast Imaging Bruce, Averkiou—AAPM 2004 Courtesy Dr. E. Leen, Royal Infirmary, Glasgow, UK 14 Pulse Inversion Processing • High MI techniques have high sensitivity but are in general difficult to use – Tissue harmonic component competes with bubble signals • Low MI – harmonics still generated – Does not destroy microbubbles (extends visualizaton time) • Does not require interval delay or sweeping – Low MI reduces harmonic tissue signals (tissue is removed) Real Time Imaging MI < 0.10 Frame Rate >15Hz Bruce, Averkiou—AAPM 2004 1999 Pulse Inversion 15 Bruce, Averkiou—AAPM 2004 16 4 Phase of the Harmonic Components of Pulse Inversion Nonlinear System Pulse 1 e jω o t ∞ m=1 Pulse 2 e jωo (t +T2 ) ωo = a1e jω o t + a 2e j 2ω o t + a 3e j 3ω o t xmit: (0.5, 1) rcv: (2, -1) + am pm(t) a1e( −jπ1e)ejωjoωt o+t a+2ae2j 21πeej 2j 2ωωoott ++aa33e( −j 31π)ee jj33ωωoto t++ Even Harmonics 2π T Gain (dB) where Power (Amplitude) Modulation Output Input a1 0 -20 a 2 -40 a3 a4 Bruce, Averkiou—AAPM 2004 π/2 Doppler Freq π 17 Clinical Example – Low MI 18 Clinical Examples – Low MI FNH Carotid Bruce, Averkiou—AAPM 2004 Bruce, Averkiou—AAPM 2004 19 Bruce, Averkiou—AAPM 2004 20 5 Clinical Examples Liver hemangioma Bruce, Averkiou—AAPM 2004 Liver Lesion Characterization Ultrasound Contrast Agents 21 Bruce, Averkiou—AAPM 2004 22 Flash Contrast Imaging Contrast Quantification • Contrast destruction provides method for perfusion quantification • Destroy contrast with high MI frame • Replenishment rate gives indication of microvascular flow rate Bruce, Averkiou—AAPM 2004 23 Bruce, Averkiou—AAPM 2004 24 6 MicroVascular Imaging Parametric Example • Some lesions have very low flow rates – bubbles can be seen in real-time, but not enough for good vessel conspicuity – Hold on to bubble signals as they traverse vasculature Stenosis 1 • Trace out resulting small-low velocity vessels Stenosis 2 Bruce, Averkiou—AAPM 2004 25 26 Mouse Heart Imaging MVI Rat Kidney Bruce, Averkiou—AAPM 2004 Bruce, Averkiou—AAPM 2004 27 Bruce, Averkiou—AAPM 2004 28 7 Mouse Perfusion Deficit Summary • History • Basics of Ultrasound Contrast Imaging • Application to Liver lesion characterization • Quantification LAD ligation Bruce, Averkiou—AAPM 2004 29 Bruce, Averkiou—AAPM 2004 30 8