US006319203B1 (12) United States Patent (10) Patent N0.: US 6,319,203 B1 Averkiou (45) Date of Patent: Nov. 20, 2001

(54) ULTRASONIC NONLINEAR IMAGING AT 5,833,613 11/1998 Averkiou et al. . FUNDAMENTAL FREQUENCIES 5,848,968 12/1998 Takellchi~ 5,873,829 2/1999 Kamiyama et al. . (75) Inventor: Michalakis Averkiou, Kirkland, WA 5,879,303 3/1999 Averkiou et a1- - (Us) 6,048,316 4/2000 Zhao et al. . 6,186,949 * 2/2001 Hat?led et al...... 600/443 (73) Assigneez ATL Ultrasound, Bothell, WA (Us) 6,251,074 * 6/2001 Averkiou et al...... 600/447

* . . ( * ) Notice: Subject to any disclaimer, the term of this cued by exammer patent is extended or adjusted under 35 _ _ _ U S C 154(k)) by 0 days Prtmary Examtner—Marvm M. Lateef ' i i ' Assistant Examiner—Maulin Patel (21) Appl NO _ 09/627 918 (74) Attorney, Agent, or Firm—W. Brinton Yorks, Jr. . .. , (22) Filed: Jul. 28, 2000 (57) ABSTRACT 7 Nonlinear tissue or contrast agent effects are detected by (2;) ...... gbbyhlss?onos?g Combining echoes from multiple, differently modulated ( ) _' ' ' ’ transmit pulses beloW the second harmonic band. The Fleld Of Search ...... received eChoes may even Overlap the fundamental transmit 600/445’ 437’ 447’ 448’ 128/416 frequency band. The modulation may be amplitude modu , lation or phase or polarity modulation, and is preferably both (56) References Clted amplitude and phase or modulation. The present invention U_S_ PATENT DOCUMENTS affords the ability to utiliZe a majority of the transducer _ passband for both transmission and reception, and to trans lg ELOCk'FISh‘ZI ‘lat a1‘ ' mit pulses Which are less destructive to microbubble contrast , , apman e a . . 5,694,937 12/1997 Kamiyama . agents‘ 5,706,819 1/1998 Hwang et al. . 5,735,281 4/1998 Rafter et al. . 7 Claims, 5 Drawing Sheets

120 104 105’

T/R L 102 _/- Swltch. Beamformer B_

100 Freq. C t I . en r a 106/ Transmrtter Phase Controller

B Mode Processor ,‘ —,_., 172 180 \ 150 190 \ 170\ Dis Ia Video Scan Doppler p y Processor Conv. Processor (—,_" _/-160 _/_ 3DMemory Image <_ Rendering3D Image _\ Cgntrastignal 184 182 Processor U.S. Patent Nov. 20, 2001 Sheet 1 0f5 US 6,319,203 B1

FIG. 1

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12

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FIG. 2

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16 18 U.S. Patent Nov. 20, 2001 Sheet 2 0f5 US 6,319,203 B1

FIG. 3

Ampl. 1" 20

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Ampl. U.S. Patent Nov. 20, 2001 Sheet 3 0f5 US 6,319,203 B1

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.UER U.S. Patent Nov. 20, 2001 Sheet 4 0f5 US 6,319,203 B1 FIG. 8 Ampl.

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US 6,319,203 B1 1 2 ULTRASONIC NONLINEAR IMAGING AT embodiment the nonlinear signals are detected by an ampli FUNDAMENTAL FREQUENCIES tude modulated tWo (or more) pulse technique. Preferably the transmit pulse Waveforms are of opposite phase and This invention relates to ultrasonic diagnostic imaging polarity and of different amplitudes. Upon reception the systems and, in particular, to ultrasonic diagnostic imaging echoes are normaliZed for the different transmit amplitudes systems Which image nonlinear signals in the fundamental and combined and the signals Within the fundamental band frequency band. are used for imaging. US. Pat. No. 5,879,303, of Which I am a co-inventor, In the draWings: describes methods and apparatus for doing harmonic ultra FIG. 1 illustrates conventional transmit and harmonic sound imaging. As eXplained in my patent, an ultrasonic receive spectra Within a transducer passband; Wave can be transmitted at a fundamental frequency to give FIG. 2 illustrates the location of a harmonic spectrum at rise to harmonic echo signals, in particular at the second the upper limit of the transducer passband; harmonic, from tWo distinct sources. One is the nonlinear FIG. 3 illustrates the fundamental transmit and second behavior of microbubble contrast agents. When these harmonic receive spectra of an embodiment of the present microbubble agents are insoni?ed by the transmit Wave, they 15 invention; Will oscillate or resonate nonlinearly, returning a spectrum of FIG. 4 illustrates the spectrum of fundamental nonlinear echo signals including those at the second harmonic of the echo signals resulting from the transmit spectrum of FIG. 3; transmit frequency. The strong harmonic echo components FIG. 5 illustrates receive passbands for the nonlinear uniquely distinguish echoes returning from the echo signals of FIG. 4; microbubbles, Which can be used to form B mode or FIGS. 6a—6g depict Waveforms illustrating the principle Doppler images of the blood?oW infused by the contrast of pulse inversion harmonic separation; agent. The other source of harmonic echo signals is the FIGS. 7a—7g depict Waveforms illustrating the principle nonlinear distortion Which ultrasonic Waves undergo as they of nonlinear echo signal detection in the fundamental band travel through tissue. The echoes returned from these dis in accordance With the principles of the present invention; torted Waves manifest harmonic components developed by 25 FIG. 8 illustrates the transmit and receive passbands of this distortion. one embodiment of the present invention; My aforementioned US. patent describes tWo Ways in FIG. 9 illustrates the transmit and receive passbands of Which the harmonic components of these echo signals may another embodiment of the present invention; and be detected. One is by use of a highpass ?lter, Which Will FIG. 10 illustrates an ultrasonic imaging system con pass signals in the harmonic band While attenuating the structed in accordance With the principles of the present stronger echo components in the fundamental band. The invention. other Way is by transmitting tWo or more pulses of opposite Referring ?rst to FIG. 1, typical fundamental and har phase or polarity and combining the echoes received in monic spectra of an ultrasound system are shoWn. This response from the tWo pulses. The fundamental components, draWing illustrates a passband 10 of an ultrasonic being of opposite phase or polarity by reason of that char 35 transducer/beamformer Which transmits the fundamental acteristic of the transmit pulses, Will cancel. The harmonic frequency pulses or Waves, and receives the harmonic echo components of the combined echoes, being quadratic in signals. In this eXample the transducer has a passband nature, Will additively combine, leaving the separated sec extending from 1 to 3 MHZ. When the same transducer is to ond harmonic signals. be used for both transmission and reception, both the fun As discussed in my aforementioned patent, harmonic damental transmit pulse and the harmonic receive echoes signals are advantageous in many imaging situations must be encompassed Within the passband 10 of the trans because of the distinctive Way in Which they identify echoes ducer. In this eXample the transmit pulse eXhibits a passband returned from harmonic contrast agents. When used Without 12 Which is centered around 1.25 MHZ. Second harmonic contrast agents the tissue harmonic signals are advantageous echo signals Will be received in a passband 14 centered because their development Within the body eliminates much 45 around 2.5 MHZ. It is seen that because the transmit band 12 of the clutter caused by near?eld effects. HoWever, harmonic is at the loWer end of the transducer passband 10, the signals are of a signi?cantly loWer amplitude than the harmonic receive passband Will fall in the upper portion of fundamental signal echoes, providing loWer signal to noise the passband 10 and thus both transmission and reception ratios and requiring greater ampli?cation. In addition, har can be performed by this particular transducer. monic signals require the use of relatively loW frequency As FIG. 1 shoWs, in order to get both the fundamental transmit pulses so that the second harmonic echo signal Will band 12 and the harmonic band 14 Within the same trans be of a frequency Which can be received Within the trans ducer passband it is often necessary to ?t one or the other or ducer’s passband. Generally, the transmit signal Will be both of the transmit or receive passbands at one of the cutoff centered at the loWer end of the transducer’s passband so eXtremes of the transducer passband. FIG. 2 shoWs another that the second harmonic return signal Will be beloW the 55 eXample of this, in Which the fundamental transmit band 16 upper cutoff of the transducer passband. This can place the is centered about a frequency of 1.5 MHZ and occupies the transmit and receive signals at the eXtremes Where broad entire loWer half of the transducer passband 10. The transmit band signals Will experience attenuating rolloff. It also band 16 thus is for a more broadband transmit signal than mandates loWer frequency transmit signals, Which can be that Which is transmitted by the passband 12 in FIG. 1, more disruptive to microbubble contrast agents than higher providing improved image detail and quality. HoWever the transmit frequencies Would be. Accordingly it is desirable to second harmonic receive passband 18 for this transmit pulse be able to overcome these de?ciencies and limitations of is centered at 3 MHZ at the upper eXtreme of the transducer harmonic imaging. passband 10. In this eXample the center of the harmonic In accordance With the principles of the present band is at the upper cutoff of the transducer band, resulting invention, the nonlinear signals returned from tissue and 65 in signi?cant attenuation of signals in the upper portion of contrast agents are detected in the fundamental frequency the band 18. Thus, broadband harmonic imaging is limited band rather than at harmonic frequencies. In a preferred by this transducer passband. US 6,319,203 B1 3 4 The passbands used in a ?rst embodiment of the present have been separated from the fundamental frequency com invention is shown in FIGS. 3—5 using the same transducer ponents of the echo signals. passband 10 as in the previous drawings. TWo or more FIG. 7 shoWs Waveforms illustrating the principles of the differently modulated broadband transmit pulses having a present invention. Like pulse inversion the technique of the passband 20 are transmitted along each scanline in the image present invention uses multiple, differently modulated trans ?eld as shoWn in FIG. 3. As this draWing shoWs, the mit pulses to separate nonlinear signal components. FIGS. fundamental transmit pulses centered at 2 MHZ Will elicit 7a and 7b shoW tWo exemplary transmit pulses 70 and 80 second harmonic echo signals in a band 22 centered at 4 Which are of different amplitudes. In this example the ?rst MHZ. These harmonic echo frequencies are outside the transmit pulse 70 is tWice the amplitude of the second transducer passband 10 and hence Will be beyond the 10 transmit pulse 80, although other amplitude relationships frequency range of the transducer. HoWever the transmit may be employed. In this example the tWo transmit pulses pulses Will also elicit echoes in the fundamental frequency are also of opposite phase or polarity. Transmit pulse 70 band 20 and beyond, as shoWn by the dashed line receive elicits different fundamental frequency echo signal charac passband 24 in FIG. 4. As Will be discussed beloW, these teristics from nonlinear and linear targets. For instance, if the fundamental frequencies can exhibit varying degrees of 15 echo is returned from a nonlinear contrast agent, the non linear and nonlinear characteristics depending upon the linear behavior of the microbubbles When insoni?ed Will presence of nonlinear re?ectors such as contrast agents in return a fundamental frequency echo Waveform 72 as shoWn the image ?eld. The nonlinear characteristics are extracted in FIG. 76 Which is nonlinearly related to the transmit and the linear fundamental components canceled by com Waveform. If the echo is returned from a linear re?ector such bining the echo signals in a chosen receive passband such as as tissue, a fundamental frequency echo 74 as shoWn in FIG. receive bands 30, 32 or 34 as shoWn in FIG. 5. The receive 7c results, Which is seen to be linearly related to the transmit band can start at the higher frequency location 32 at the pulse. initial reception of shalloW depth echoes, then be moved The second transmit pulse Will elicit fundamental fre dynamically to the loWer frequency position 34 during quency echo returns from nonlinear and linear re?ectors as reception to account for the effects of depth dependent 25 shoWn in FIGS. 7f and 7d. A nonlinear system such as a frequency attenuation. By virtue of the modulation of the microbubble Will return an echo 82, Which is nonlinearly transmit pulses and the nonlinearity of the re?ectors the related to the transmit Waveform 80. Since the transmit pulse correlated linear characteristics in the fundamental band Will 80 is of a lesser amplitude than the ?rst pulse, the cancel and the uncorrelated nonlinear characteristics in the microbubble Will behave differently by reason of the differ fundamental band Will not, leaving an echo signal compo ent level of insoni?cation. A linear re?ector returns an echo nent Which is a measure of the nonlinearity of the funda 84 Which is seen to be linearly related to the lesser amplitude mental frequency echoes. Thus, nonlinear components are transmit pulse 80. detected Which are beloW the second harmonic frequency. The ?rst and second echo signals are normalized to The use of these nonlinear components beloW the second account for the different transmit pulse amplitudes. When harmonic frequency provide several advantages. For one, 35 the tWo transmit pulses differ by a factor of tWo as they do most or even all of the transducer passband can be used for in this example, the echoes from the second pulse Would be transmission. This enables the use of broadband transmit ampli?ed by a factor of tWo, for instance. When the corre pulses Which Will result in broadband echo signals for ?ner sponding echoes are combined after normaliZation, it can be and more subtle image detail. There is no need to constrain seen that the linear echoes Will cancel as shoWn by line 94 the transmit pulses to a narroW range of the transducer in FIG. 7g. The echoes returned from the nonlinear re?ectors passband. Another advantage is that the transmit and receive Will partially cancel but leave a difference Which is a passbands can both be more centered in the transducer manifestation of the different nonlinearities of the echoes as passband, aWay from the rolloff at the extremes of the shoWn by Waveform 92 in FIG. 7h. That is because the transducer passband. Higher transmit pulse frequencies and nonlinear characteristics of echoes 72 and 82 are not equal shorter duration pulse bursts may also be used, providing 45 iZed by the linear normaliZing and Will leave a residual advantages in the form of reduced microbubble destruction. signal after combining because of the decorrelation of the FIG. 6 illustrates the principles of pulse inversion trans tWo nonlinear echo signals. The nonlinear effects in the mission and reception. A?rst transmit pulse 40 (FIG. 6a) has echoes are not linearly related to the difference in pulse a ?rst phase or polarity characteristic and a second transmit amplitude of the tWo transmit pulses. This means that the pulse 50 has an second phase or polarity characteristic (FIG. normaliZation, Which Will equaliZe the tWo linear echoes 74 6b). In this example both pulses are shoWn as a single cycle and 84 and result in cancellation, Will not equaliZe the of a Waveform and the second pulse 50 is the inverse of the echoes from the nonlinear re?ectors. The oscillation of ?rst. The ?rst transmit pulse 40 returns echo signals from a microbubbles When insoni?ed by pulses of different ampli nonlinear system such as a microbubble Which have a tudes is nonlinear and more complex than just the amplitude fundamental frequency component 42 (FIG. 6c) Which fol 55 difference. Furthermore, the microbubbles can be disrupted loWs the phase or polarity modulation of the transmit pulse, by the ?rst pulse so that the microbubbles interrogated by the and a second harmonic component 44 (FIG. 66). The second second pulse have a different character than those encoun transmit pulse 50 returns echo signals from the nonlinear tered by the ?rst pulse. The combination of these different system Which have a fundamental frequency component 52 nonlinear and behavioral characteristics of a nonlinear sys (FIG. 6d) Which also folloWs the phase or polarity of the tem provide the ability to clearly distinguish echoes from transmit pulse, and a second harmonic component 54 (FIG. nonlinear systems in the fundamental frequency band. 6]‘). When the echo signals from the tWo transmit pulses are FIG. 8 illustrates the passbands of another embodiment combined the fundamental frequency components Will can of the present invention. The fundamental frequency trans cel each other and the harmonic components Will additively mit pulse band is shoWn by the lined passband 200 centered reinforce each other by reason of the quadratic nature of 65 at 2 MHZ. The receive band 202 is centered at 2.7 MHZ and harmonics, leaving a detectable second harmonic compo greatly overlaps the transmit passband to receive echoes in nent 60 (FIG. 6g). Thus, the second harmonic components a portion of the received echo band 204. In the prior art great US 6,319,203 B1 5 6 pains Were taken to transmit pulses in a band Which did not ?lters 126 and 136. In a preferred embodiment these ?lters overlap the receive band so that the second harmonic signals are quadrature bandpass ?lters as described in my afore could be cleanly separated from the fundamental frequency mentioned patent, to produce quadrature signal components signals. In the present invention, Where it is nonlinear and also bandpass ?ltering for the receive passband. components at and around the fundamental band Which are The echo signals may be processed by a B mode pro of interest, this is not a problem. cessor 140, a Doppler processor 150, and/or a contrast signal FIG. 9 illustrates yet another embodiment of the present processor 160. The B mode processor Will amplitude detect invention Where the receive band 212 is beloW the transmit the echo signals in the production of image signals, and the pulse band 210. In this example the transmit band is a high Doppler processor Will process ensembles of echo signals to produce image signals of tissue or How motion. The contrast frequency band centered about 3.3 MHZ. The high fre 10 quency transmit signals result in better resolution in the echo signal processor is similar to the previous processors, gen signals. Locating the transmit band at the upper end of the erally With a threshold Which separates contrast harmonic transducer passband 10 obviously cannot be done When signals from tissue harmonic signals. Contrast agents can be trying to contain both the fundamental and second harmonic displayed in either Doppler or B mode format. Image signals from the three processors are coupled over an image signal bands in the transducer passband. Thus, the present inven 15 tion Will afford better image resolution than prior art har bus 172 to a scan converter 170, Which interpolates the monic systems. The receive band 212 encompasses some of image signals and puts the scanlines in the desired image the echo signal frequencies in the echo signal band 214 and format. The image information can be applied to a video is centered at 2.7 MHZ in this embodiment. shoW, the processor 180 for display of a tWo dimensional image on a duration of the 3.3 MHZ pulse is considerably less than that display 190. The image information can also be formed into of the loWer frequency burst, causing less microbubble three dimensional presentations by 3D image rendering 182. disruption. The 3.3 MHZ pulse, being of a higher frequency, Three dimensional images are stored in a 3D image memory Will also cause less disruption than the loWer frequency 184 and displayed on the display 190 by Way of the video pulse for this additional reason. Furthermore, the loWer processor 180. Other variations Will be apparent. While the embodiment amplitude transmit pulse (FIG. 7b) Will cause less disruption 25 than the higher amplitude transmit pulse. While the different of FIG. 10 provides the obvious bene?t of 2>