Ultrasonic Nonlinear Imaging Tissue Harmonic Imaging 1 Conventional

Ultrasonic Nonlinear Imaging. Tissue Harmonic Imaging 1

Conventional B-mode image (AP 4 CH)

Fundamental THI

Fundamental THI

Tissue Harmonic Imaging 5

Tissue Nonlinear Imaging • Performance of ultrasound has been suboptimal on technically difficult bodies. • Most recent new developments have bigger impact on technically satisfactory bodies. • Poor image quality leads to uncertainty in diagnosis and costly repeat examinations. Tissue Harmonic Imaging 6

Tissue Harmonic Imaging • Methods to improve image quality: – Different acoustic window. – Lower frequency. – Adaptive imaging. – Non-linear imaging (or harmonic imaging). Tissue Harmonic Imaging 7

Origin of Tissue Non-linearity • Finite amplitude distortion: peaks of the waveform travels faster than the troughs. Tissue Harmonic Imaging 8

Tissue Non-Linearity • Signal Source – Finite amplitude distortion generated tissue harmonics Pressure Before distortion After distortion t Tissue Harmonic Imaging 9

Non-Linear Propagation Tissue Harmonic Imaging 10

Axial Amplitude Velocity(cm/sec) 80 Fundamental 2 nd Harmonic 60 40 20 0 0 20 40 60 80 Depth(mm) Tissue Harmonic Imaging 11

Tissue Non-Linearity • THI Characteristics transducer d. B transducer 4 MHz Beam Patterns Tissue Harmonic Imaging Lateral Position (mm) 12

Tissue Non-linearity • Tissue harmonics are virtually zero at the probe face. The intensity continues to increase until attenuation dominates. • The higher the intensity is, the more tissue harmonics are generated. • Such a mechanism automatically increase the difference between signal and acoustic noise. Tissue Harmonic Imaging 13

Advantages of Tissue Harmonic Imaging • Low sidelobes. • Better spatial resolution compared to fundamental imaging at the original frequency. • Less affected by tissue inhomogeneities – better performance on technically difficult bodies. Tissue Harmonic Imaging 14

Non-linear Parameter B/A • B/A defines non-linearity of the medium. The larger the B/A, the higher the nonlinear response. Tissue Harmonic Imaging 15

B/A Parameters: Measurements • Finite amplitude method: – B/A is related to the second harmonic generation. Thus, it can be found by relating the signal amplitude at the fundamental frequency to the second harmonic component. • Thermodynamic method: – The B/A value is determined by measuring the change of sound speed with pressure and temperature. Tissue Harmonic Imaging 16

B/A Parameters: Typical Values • Typical values: – – Water: 5. 5+/-0. 3. Liver: 7. 23. Fat: 10. 9. Muscle: 7. 5. • Results from both methods have excellent agreement. • B/A imaging may be used for tissue characterization. Tissue Harmonic Imaging 17

Image Analysis Issues • Low signal-to-noise ratio: coded excitation, simultaneous multiple transmit focusing. • Spectral leakage and image quality degradation. • Spatial covariance analysis for correlationbased processing. • Motion artifacts in pulse inversion imaging. Tissue Harmonic Imaging 18

Filter Based Image Formation • Fundamental and Harmonic Imaging Spectrum Fundamental Imaging Spectrum LPF MHz Transmit Signal MHz Harmonic Imaging Received Signal HPF Tissue Harmonic Imaging 19

Effects of Harmonic Leakage • Motive : MHz MHz 4 MHz Beam Patterns d. B – Contrast resolution degradation MHz Harmonic Imaging Transmit Spectrum Received Tissue Spectrum 20 Lateral Position (mm)

Sources of Harmonic Leakage • Designed transmit waveform. • System nonlinearity. • Electromechanical conversion. Waveform Generator High Voltage Amplifier & T/R Switch Tissue Harmonic Imaging Transducer 21

Designed Waveform (I) • Characteristics of transmit waveforms. Normalized Amplitude Waveforms s d. B Spectra MHz Tissue Harmonic Imaging 22

Designed Waveform (II) • Signal bandwidth. Spectrum of Transmit Signal Leakage Fundamental Harmonic band Tissue Harmonic band Imaging MHz 23

Non-linear Propagation Wave at distance z angular spectrum method Linear propagation to z+Dz Nonlinear propagation at z+Dz frequency domain solution to Burgers’ equation Tissue Harmonic Imaging 24

Nonlinear Simulation Model • Model the Nonlinear Propagation Δf: fundamental frequency un： Sin(2π(nΔf)t) β：nonlinear parameter c：sound velocity Tissue Harmonic Imaging 25

Results: Effect of Bandwidth • Gaussian at 25% and 50% • Contrast v. s. Spatial Harmonic Beam Patterns 0 BW=25% BW=50% d. B -20 -40 -60 -10 -5 0 Tissue. Lateral Harmonic. Position Imaging 5 (mm) 10 26

Results: Signal Type • Sine, square and Gaussian wave, BW=25% • Smooth envelope has better contrast Harmonic Beam Patterns 0 Gaussian Gated sine Gated square d. B -20 -40 -60 -10 -5 0 5 Tissue Harmonic Imaging(mm) Lateral Position 10 27

Results: Signal Type – Gaussian, gated sine and gated square waves. – BW=50%. Integrated Harmonic Beam Patterns d. B Harmonic Beam Patterns Gaussian Gated sine Gated square 4 MHz linear Lateral Position (mm) Tissue Harmonic Imaging Lateral Position (mm)28

Effects of Harmonic Leakage • Tissue Inhomogeneities – Fat layer: 15 mm thick, B/A=10. – Aberrating plane: max. time delay error=30 ns, correlation length=5 mm. Phase Aberration Pattern 30 2. 5 (mm) 0 0 (ns) -2. 5 -10 -5 Tissue Harmonic Imaging 0 (mm) 5 -30 10 29

Results: Tissue Inhomogeneities – BW=50%. Integrated Harmonic Beam Patterns d. B Harmonic Beam Patterns Gaussian Gated sine Gated square 4 MHz linear Lateral Position (mm)Tissue Harmonic Imaging Lateral Position (mm) 30

Effects of Harmonic Leakage • Drive Voltage – Magnitude => nonlinearity Spectra Beam Patterns 1 Volt 5 Volt d. B Harmonic(1 Volt) Fundamental(1 Volt) Harmonic(5 Volt) Fundamental(5 Volt) Tissue Harmonic Imaging Frequency(MHz) 31 Lateral Position(mm)

Results: Bandwidth – Gaussian envelope, 1 Volt, 25% vs. 50%. Spectra Harmonic Beam Patterns BW=25% BW=50% d. B BW=25% BW=50% Frequency(MHz) Tissue Harmonic Imaging Lateral Position(mm) 32

Results: Drive Voltage – 1 Volt vs. 5 Volt. Beam Patterns Spectra Harmonic(1 Volt) 1 Volt 5 Volt Fundamental(1 Volt) Harmonic(5 Volt) d. B Fundamental(5 Volt) Frequency(MHz) Tissue Harmonic Imaging Lateral Position(mm) 33

Pulse Inversion Fundamental signal Positive driving pulse t Nonlinear propagation f Harmonic signal t f Negative driving pulse Tissue Harmonic Imaging ONLY harmonic signal 34

Pulse Inversion • Pulse inversion reduces sidelobe levels Fundamental Beam Gaussian pulse Harmonic Beam (Filtering) Tissue Harmonic Imaging Sine pulse Gaussian pulse Harmonic Beam (Pulse inversion) Sine pulse 35

Pulse Inversion • harmonic leakage could be avoided – all linearly propagated components are cancelled Harmonic Beam Patterns at 50% Bandwidth d. B Tissue Harmonic Imaging Lateral Position(mm) 36

Harmonic Leakage • Smooth envelopes provide lower sidelobes, but also require a more sophisticated transmitter. • Large bandwidths improve axial resolution, but also increase sidelobes. • Sidelobe differences decrease in the presence of tissue inhomogeneities. • Spectral leakage must be suppressed without affecting fundamental beams. • Pulse inversion technique is the most effective. Tissue Harmonic Imaging 37

Sound Velocity Inhomogeneities v 1 v 2 Array Transducer Tissue Harmonic Imaging 38

Spatial Covariance Analysis • Sound velocity inhomogeneities are conventionally corrected by correlation-based methods. • The covariance of signals received at different positions is critical to correlation-based correction techniques (the van Cittert-Zernike theorem). • Is it possible to further improve the image by combining tissue harmonic imaging and phase aberration correction? • Optimal frequency selection for imaging and time delay estimation. Tissue Harmonic Imaging 39

Progress: Simulations • Transmit – beam formation by FDSBE • Receive – time-domain signal for each channel Tissue Harmonic Imaging a, b: length and width of channel 40

channel Correlation coefficient Progress: Simulations time channel Tissue Harmonic Imaging 41

Progress: Results • Harmonic covariance is generally similar to or lower than fundamental covariance 1 Spatial Covariance: Simulations 1 Spatial Covariance: Experiments Correlation Coefficient 2 MHz Fundamental 4 MHz Second Harmonic 0. 8 0. 6 0. 4 0. 2 0 0. 5 1 0 Tissue Harmonic Imaging Normalized Distance 3. 5 MHz Fundamental 7 MHz Second Harmonic 0. 5 42 1

Progress: Results • With sound velocity inhomogeneities Spatial Covariance: Simulations 1 Correlation Coefficient 2 MHz Fundamental 4 MHz Second Harmonic 1 3. 5 MHz Fundamental 7 MHz Harmonic 0. 8 0. 6 0. 4 0. 2 0 0. 5 Spatial Covariance : Experiments 1 0 Tissue Harmonic Imaging Normalized Distance 0. 5 43 1

Progress: Results • Effects of SNR Fundamental Spatial Covariance: Experiments Second Harmonic Spatial Covariance: Experiments 1 1 High SNR Low SNR Correlation Coefficient High SNR Low SNR 0. 8 0. 6 0. 4 0. 2 0 0. 5 1 0 Tissue Harmonic. Distance Imaging Normalized 0. 5 1 44

Spatial Covariance • When adequate SNR is available – Whether the sound velocity variations are present or not, the harmonic covariance is generally similar to or lower than fundamental covariance. • When SNR is low – Harmonic covariance is significantly affected. • Imaging at the second harmonic frequency, correlationbased correction at the fundamental frequency. Tissue Harmonic Imaging 45

Harmonic Interference • In contrast imaging, in which the tissue harmonic signals are un-desirable, the amplitude of the propagating wave needs to minimized. • Large apertures (smaller f-numbers) may be used. • It was reported that tissue harmonic signal can be reduced by 3 d. B by doubling the aperture size. Tissue Harmonic Imaging 46

Harmonic Interference • Harmonic cancellation system: non-linear propagation is reduced by using a new signal at the harmonic frequency. • Phase and magnitude of the signal may be pre-calculated, but on-line adjustment is necessary. • Due to attenuation, optimal effects may only be achieved locally. Tissue Harmonic Imaging 47

Ultrasonic Nonlinear Imaging. Contrast Harmonic Imaging Tissue Harmonic Imaging 48

Contrast Harmonic Imaging • Contrast agents are used to provide higher contrast. The three commonly seen contrast agents are backscatter, attenuation and sound velocity. • Contrast agents could be solid particles, emulsion, gas bubbles, encapsulated gas, or liquid. Tissue Harmonic Imaging 49

Contrast Harmonic Imaging • Primary clinical benefits: – Enhanced contrast resolution between normal and diseased tissues. – Outline of vessels or heart chambers. – Tissue characterization by using tissue specific agents. – Increasing blood flow signals. – Dynamic study using washout curve. Tissue Harmonic Imaging 50

Example Tissue Harmonic Imaging 51

Clinical Applications: Cardiology • • • Endocardial border detection. Left ventricle (LV) function. Valvular regurgitation quantification. LV flow patterns. Perfusion area of coronary artery. Assessment of surgery for ventricular septal defect. Tissue Harmonic Imaging 52

Clinical Applications: Others • • • Liver tumor enhancement. Uro-dynamics and kidney functions. Tubal function and placenta perfusion. Transcranial Doppler enhancement. LV pressure measurements. Tissue Harmonic Imaging 53

Current Contrast Agents • • • Echovist. Albunex. Levovist. Echogen. Quantison. Many more, … Tissue Harmonic Imaging 54

Contrast Mechanisms • Strong backscattering produced by air bubbles. • The backscatter increases roughly linearly with the number of micro-bubbles. • A bubble in liquid acts as a harmonic oscillator. Acoustic resonance provides the major echo enhancement. In addition, strong harmonics are produced. Tissue Harmonic Imaging 55

Contrast Mechanisms • Acoustic attenuation of soft tissues is typically represented by a constant (e. g. , 0. 5 d. B/cm/MHz). • Since contrast agents significantly change the scattering properties, attenuation measurements can also be used for contrast enhancement. Tissue Harmonic Imaging 56

Contrast Mechanisms • Sound velocity is primarily determined by density and compressibility. Apparently, micro-bubble based contrast agents alter sound velocity. • Contrast enhancement based on sound velocity variations is still academic. Tissue Harmonic Imaging 57

Contrast Mechanisms • Micro-bubbles produce strong harmonics when insonified near the resonance frequency. • If such harmonics are stronger than tissue harmonics, contrast can be improved. • Second harmonic signal is most useful due to limited transducer and system bandwidth. Tissue Harmonic Imaging 58

Desired Characteristics of Contrast Agents • • • Efficient backscattering. Small size for pulmonary transport. Long half-life. Low toxicity. Possibility of attenuation contrast. Possibility of speed of sound contrast. Tissue Harmonic Imaging 59

Imaging Consideration • • Low peak acoustic amplitude. Low average acoustic power. ECG triggering. Frequency control. Tissue Harmonic Imaging 60

System Requirements • Similarities to tissue harmonic imaging: – Minimal harmonics on transmit. – Maximal fundamental suppression on receive. – Configurable beamformer. – Wide transducer and system bandwidths. – Alternate phasing and pulse inversion may both be applicable. Tissue Harmonic Imaging 61

System Requirements • Differences from tissue harmonic imaging: – Low harmonic generation during propagation, i. e. low fundamental amplitude through a small depth of field. – The fundamental amplitude may be significantly lower than regulatory limits. Tissue Harmonic Imaging 62

System Requirements • Transmitter: minimal harmonic signals. • Propagation: minimal harmonic generation. • Receiver: maximal fundamental rejection. Tissue Harmonic Imaging 63

System Requirements • Adequate dynamic range. • Configurable beam former. • Sufficient system bandwidth. • Wide transducer bandwidth. Tissue Harmonic Imaging 64

Imaging Techniques • The phasing pattern across the array can be varied to reduce the signals at a certain frequency. • Alternate phasing is applicable to contrast harmonic imaging. • Alternate phasing on transmit is not ideal. Tissue Harmonic Imaging 65

Imaging Techniques • Alternate phasing for receive: 00000 0 p 0 p 0 p • Alternate phasing for transmit 0 0. 5 p 0 Tissue Harmonic Imaging 0. 5 p 0 0. 5 p 66

Imaging Techniques • Difference imaging technique: contrast agents can be viewed as a “modulator”. When two different frequencies, say f 1 and f 2, are used on transmit, the contrast agents generate f 1+f 2 and f 1 -f 2. • f 1 and f 2 can be properly chosen to increase the rejection ratio. Tissue Harmonic Imaging 67

Imaging Techniques • Subtraction mode: Two pulses with different signs are transmitted consecutively. By adding two images together, linear components cancel while second order components remain. • This technique is susceptible to motion artifacts. Tissue Harmonic Imaging 68

Pulse Inversion Doppler • An extension for the subtraction mode to Doppler imaging, i. e. , pulse inversion with multiple firings. • There exists a nonlinear Doppler spectrum completely separate from the linear spectrum. • Potential increase in agent to tissue contrast. Tissue Harmonic Imaging 69

Problems in Flow Estimation • Radiation force tends to move the contrast agents to a direction independent of the flow direction. • Bubble break down causes image artifacts. • Excessive backscatter produces “color blooming”. • Spectral broadening at high acoustic pressures. Tissue Harmonic Imaging 70