Time balanced multi-mode primary imaging sequence for ultrasound contrast imaging

Abstract

Particular sequences of ultrasound emissions and corresponding reception of echoes enable the production of time-balanced amplitude-modulated (AM) signals and amplitude-modulated phase-inverted (AMPI) signals. Time balancing significantly reduces tissue artifacts caused by movement of tissue during the acquisition of ultrasound echoes. In addition, in combining selected echo signals to produce the AM signals and AMPI signals, and optionally in combining phase-inverted (PI) signals, each of the echo signals is equally weighted to promote amplitude balancing that avoids differentially affecting different echoes of the produced AM signals, AMPI signals, and PI signals.

Description

TECHNICAL FIELD

[0001] The present invention relates to the field of contrast-enhanced ultrasound (CEUS) imaging, and in particular to a method and system employing advanced pulse sequences that combine the advantages of multiple CEUS pulse schemes. BACKGROUND

[0002] Ultrasound images are created by transmitting ultrasound pulses at varying amplitudes and frequencies, receiving echoes corresponding to each transmitted pulse, and processing the echoes to create an image. Typically, ultrasound contrast agents are injected into the blood vessels of a subject to enhance the observation of blood flow through blood vessels and perfused tissue. Ultrasound contrast agents typically contain microbubbles, which greatly increase the intensity of the signal emanating from the blood, thus preferentially enhancing the signal emanating from blood relative to the signal received from tissue not perfused with blood.

[0003] However, ultrasound signals that provide strong acoustic pressure are capable of destroying microbubbles in the blood vessels. Therefore, the amplitude of the ultrasound signal is controlled to remain below a given limit, thereby minimizing microbubble destruction; correspondingly, the amplitude of the microbubble echoes is quite small. Thus, these low-amplitude microbubble echoes are often obscured by the larger echoes of the surrounding tissue.

[0004] Recognizing the benefits obtained by enabling ultrasound images to show blood flow in blood vessels as well as tissue perfusion, a variety of techniques have been developed to distinguish microbubble echoes from non-perfused tissue echoes based on the characteristics of the echoes. Tissue echoes typically exhibit a linear response, while microbubble echoes exhibit primarily a nonlinear response, and the distinction between microbubble echoes and tissue echoes is conventionally achieved by canceling the linear signal ("tissue cancellation") from the received echo signal.

[0005] Three techniques (or sub-modes) are generally available for tissue cancellation: pulse inversion (PI), amplitude modulation (AM), and amplitude modulation pulse inversion (AMPI). In conventional contrast imaging ultrasound systems, each of the three sub-modes PI, AM, and AMPI is used, alone or in combination, to create ultrasound images, as each of these sub-modes has its own set of advantages and disadvantages in terms of resolution, microbubble sensitivity, penetration, artifacts, etc.

[0006] USPA 2005 / 0256404, which is incorporated herein by reference, discloses a sequence of two pulses capable of providing each of a PI signal, an AM signal, and an AMPI signal.

[0007] Pulse inversion (PI) is illustrated in FIG. 1A. Two pulses P1, P2 are transmitted at opposite phases. Received echo signals E1, E2 are provided to unity (+1) gain amplifiers 110 and the echo signals E1, E2 are combined at summer 120. At summer 120, the opposite phase signals cancel each other, removing the linear component of the signal due to non-perfused tissue echoes. The remaining signal PI represents the nonlinear component due to contrast microbubble echoes from blood vessels and perfused tissue.

[0008] Amplitude modulation (AM) is illustrated in FIG. IB. Two pulses are transmitted, one pulse P1 at half amplitude and one pulse P2 at full amplitude, both at the same phase. Half amplitude echoes E1 are doubled via +2 gain amplifier 112, while full amplitude echoes E2 are inverted at negative (-1) unity gain amplifier 114. When these signals are summed 120, the resulting linear signal has zero amplitude, and the remaining signal AM is another representation of the nonlinear component (microbubble echoes).

[0009] Amplitude modulation pulse inversion (AMPI) is illustrated in FIG. 1C, combining the AM sub-mode with the PI sub-mode by setting the phase of the full aperture pulse P2 opposite the phase of the half aperture pulse P1 in the AM sequence described above. In this embodiment, the negative (-1) unity gain amplifier 114 is replaced by a positive (+1) unity gain amplifier 110, and the signals are combined 120. The resulting opposite phase linear signal has zero amplitude, and the remaining signal AMPI is another representation of the nonlinear component (microbubble echoes).

[0010] USPA 2005 / 0256404 also discloses that half-amplitude pulses can be obtained by activating half of the ultrasound transducer elements. The transducer elements can be numbered sequentially, and in an example embodiment, all odd-numbered transducer elements are activated to produce a half-amplitude pulse P1(o), while all even-numbered transducer elements are activated to produce a half-amplitude pulse P2(e), as shown in FIG. ID. Those skilled in the art will recognize that half-amplitude pulses can be obtained in various sequences, such as, for example, "enable the first N / 2 transducer elements, then enable the remaining N / 2 transducers"; or "repeat enabling every K transducer elements out of a group of N transducer elements, where N / K is an even integer" (e.g., N = 18, K = 3: Set 1 = {1, 2, 3, 7, 8, 9, 13, 14, 15}; Set 2 = {4, 5, 6, 10, 11, 12, 16, 17, 18}); or "randomly enable a group of N / 2 transducer elements, then enable the remaining N / 2 transducer elements", etc. For ease of reference and understanding, the terms "odd" (P1(o)) and "even" (P2(e)) are used hereinafter with respect to half-amplitude pulses to symbolize alternating groups of half transducer elements, regardless of how the groups are selected.

[0011] Also illustrated in FIG. ID are full-amplitude pulses P3 and P4 of opposite phase. As shown, the four pulses of this sequence are sufficient to provide each of the PI, AM, and AMPI signals. Because two half-amplitude echo signals E1(o), E1(e) are produced as a result of pulses P1(o) and P2(e), there is no need to double the received half-amplitude signals via the +2 gain amplifier 112 as in the examples of FIGS. IB and 1C.

[0012] Compared to acquiring PI, AM, and AMPI separately, the use of four pulses to provide each of the PI, AM, and AMPI signals reduces the time required to acquire the three sets of signals, but does not necessarily improve the efficacy of reducing the amount of non-perfused tissue included in the corresponding images, particularly in the presence of tissue motion. SUMMARY

[0013] It would be advantageous to provide systems and methods that improve the quality of contrast-enhanced ultrasound images by reducing the amount of non-perfused tissue (hereinafter referred to as "tissue clutter") that appears in the ultrasound images, particularly tissue artifacts caused by tissue motion.

[0014] To better address one or more of these concerns, in embodiments of the present application, a particular sequence of ultrasound emissions and corresponding echo receptions enables the production of a time balanced AM signal and AMPI signal. Time balancing significantly reduces tissue artifacts caused by movement of the tissue during the acquisition of the ultrasound echoes. Additionally, in combining selected echo signals to produce the PI signal, AM signal, and AMPI signal, each of the echo signals is weighted equally to promote amplitude balancing, which enables the production of ideal AM and AMPI summations.

[0015] In an example embodiment, the sequence of transmitted pulses includes: (+0.5o, +1, +0.5e, -1, +0.5o), where the sign + / - indicates the phase of the transmission and the numerical value indicates the amplitude, where o / e indicates complementary half-aperture transmissions.

[0016] To produce the PI signal, the second (+1) echo and the fourth (-1) echo are summed.

[0017] To produce a time balanced AM signal, the second echo (+1) is subtracted from the sum of the first (+0.50o) echo and the third echo (+0.5e).

[0018] To produce a time balanced AMPI signal, the third (+0.5e) signal, the fourth (-1) signal, and the fifth (-0.5o) signal are summed.

[0019] Images based on these PI signals, AM signals, and AMPI signals, alone or in combination, are displayed to a user. The combination can be based on the signal-to-noise ratio (SNR) of one or more of the signals and the spectral response of one or more of the signals to further enhance the display of blood flow and blood perfusion in the patient. BRIEF DESCRIPTION OF DRAWINGS

[0020] The present application will be further explained in detail with reference to the drawings, wherein:

[0021] FIGS. 1A-1D illustrate the transmission and reception of ultrasound pulses to produce PI signals, AM signals, and AMPI signals.

[0022] Figures 2A-2C FIG. 1A illustrates the impact of tissue motion on a prior art sequence of ultrasound pulses.

[0023] Figure 3 FIG. 1A illustrates the impact of tissue motion on a prior art sequence of ultrasound pulses.

[0024] Figures 4A-4C FIG. 1A illustrates the impact of tissue motion on a prior art sequence of ultrasound pulses.Figure 3 a combination of echo processors of PI signals resulting from echoes of sequences of

[0025] Figures 5A-5D ultrasound images of echo signals with and without AM and AMPI temporal balancing.

[0026] Figure 6 illustrates an example block diagram of an ultrasound system.

[0027] Figure 7 illustrates an example flowchart for creating pulse sequences that produce temporally balanced AM and AMPI signals.

[0028] Figure 8 is a block diagram illustrating an example processor in accordance with embodiments of the present disclosure.

[0029] Throughout the drawings, like reference numerals indicate similar or corresponding features or functions. The drawings are included to provide a thorough understanding of the concept of the invention and are not intended to limit the scope of the invention. DETAILED DESCRIPTION

[0030] In the following description, for purposes of explanation and not limitation, specific details are set forth, such as particular architectures, interfaces, techniques, etc., in order to provide a thorough understanding of the concept of the application. However, it will be apparent to those skilled in the art that the application can be practiced in other embodiments that depart from these specific details. In like manner, the use of

[0031] As described in detail above, prior art systems that employ PI sub- modes, AM sub-modes, and AMPI sub-modes to distinguish between tissue and blood flow and blood perfusion rely on pulse sequence transmissions that are in some way complementary, such that certain combinations of echo signals from these pulses result in cancellation of linear echo signals from stationary objects (tissue), while preserving the non-linear signals produced from microbubbles in blood vessels or perfused tissue. The premise of these sub-modes (PI, AM, and AMPI) is the assumption that the echoes from stationary objects are consistent over the duration of the pulse sequence.

[0032] However, known regular anatomical processes (e.g. respiratory cycles, cardiac cycles, etc.) and small movements introduced by the operator holding the ultrasound transducer often cause movement of the (relatively) stationary object. In some cases, such motion can be minimized (e.g. by requiring the patient to hold his / her breath), but in other cases such motion is beyond the patient's control. This tissue motion introduces a non-linear component to the linear echo signals from the stationary tissue. Conventional PI sub- modes, AM sub-modes or AMPI sub-modes fail to cancel out these non-linear echo signals, which results in partial appearance of residual tissue components (clutter) in the ultrasound images ("motion-induced tissue artifacts"). These artifacts reduce the clarity of the images recording blood flow and tissue perfusion, and in some cases also reduce the diagnostic information that can be extracted from such images.

[0033] To date, it has been assumed that the specific order of the pulses in the sequence is irrelevant to the resulting ultrasound images ("the pulses in [an ultrasound] sequence can be transmitted in any order" (USPA 2005 / 0124895, incorporated herein by reference,

[0021] ); however, the inventors have determined that the order of the pulse sequence in each sub-mode can have a significant effect on the size of the appearance of motion-induced tissue artifacts. For ease of understanding, the examples provided herein are primarily directed to AM sub-modes and AMPI sub-modes, and the skilled person will recognize that the same principles can be applied to PI sub-modes, as will be described in further detail below. In Figures 2A-2C The reason why the order of the pulses in the ultrasound transmission affects the size of the motion-induced artifacts is illustrated in

[0034] Figure 2A An example ideal reception of echo signals corresponding to transmission of two half-amplitude pulses (P1, P2 of Fig. 1 D) is illustrated, followed by two full-amplitude pulses (P3, P4) as these pulses are reflected from the stationary object at times T1, T2, T3 and T4. As illustrated, the AM signal from these echo signals totals E1 (o) + E2(e) - E3. In the ideal case, i.e. in the absence of any non-linear echoes, this sum is zero; thus, any residual signal corresponds to non-linear echoes; these are primarily the microbubble echoes of interest.

[0035] In Figure 2BIn this case, the dashed line 210 illustrates the motion. For the sake of illustration, the echoes received at times T1, T2, T3, T4 are superimposed on the motion line 210. Echo signal E2(e) differs from echo signal E1 (o) by a difference dl induced by the motion, and echo signal E3 differs from echo signal E2(e) by a difference d2 induced by the motion. Likewise, E4 will differ from E3. As mentioned above, the echoes are superimposed on the motion line 210 for the sake of illustration. The differences dl and d2 represent the difference in the received echo signals due to the motion of the tissue, which is assumed to be related to the distance moved by the tissue. That is, when the tissue moves continuously in one direction, the echo signals are monotonically affected (i.e. continuously increasing or continuously decreasing). The differences dl, d2 represent parameters of the echoes affected by the movement, rather than the distance moved by the tissue itself. For ease of reference, these parameters are referred to in the following as the size of the echoes, and can refer to the amplitude size of the echoes, the size of the frequency variation of the echoes, etc., depending on the technique used to process the echo signals. In a similar manner, the relative difference between the sizes of the echo signals can simply be referred to as "smaller" or "larger".

[0036] In this example, the motion introduces a decrease in the received signal strength over the time period corresponding to the transmitted pulse sequence. Thus, each subsequent echo is shown as being lower along the motion line 210 relative to its preceding pulse. However, in other cases, each subsequent echo can be higher along the motion line 210 relative to its preceding pulse.

[0037] In this simple illustrative example, relative to the centre of the three echoes E1 (o), E2(e) and E3 at T2, E1 (o) is larger than E2(e) by dl, and E3 is smaller than E2(e) by d2. Thus, as shown in the summation arrangement of Figure 2B , E1 (o) + dl, E2(e) and E3 - d2 would appear at their respective inputs. Thus, the resulting AM signal would be (E1 (o) + E2(e) - E3) + (dl + d2). The first term (E1 (o) + E2(e) - E3) is the same as the AM signal without motion as shown in Figure 2A ; thus, the motion-induced effect on the AM signal when it is produced by the P1 (o), P2(e), P3 pulse sequence totals (dl + d2).

[0038] In a similar manner, the AMPI signal produced by the combination of E1 (o), E2(3), E4 would be offset by a larger amount, since the difference between E2(e) and E4 in the case of the AMPI is larger than the distance d2 between E2(e) and E3 in the case of the AM.

[0039] Consider, for example, the case where the motion is a continuous movement in one direction, and the echo signals are received at times T1, T2, T3, T4, as shown in Figure 2CThe alternative shown, where the order of the pulses is: P1(o), P3, P2(e), this is relative to Figure 2B The change occurs. This change produces echo signals E1(o), E3, E2(e) in that order. Using the same interpretation as in Figure 2B T2 along the motion line 210, the received echo E1(o) is larger than E3 by d1, and the received echo E2(e) is smaller than E3 by d2. Correspondingly, the inputs to the summing arrangement would be represented as E1(o)+d1, E3, E2(e)-d2. Thus, the output AM signal using this reordered sequence would be (E1(o)-E3+E2(e))+(d1-d2). The (E1(o)-E3+E2(e)) term is equal to the AM signal as Figure 2A shown for no motion. Thus, the difference caused by the same motion when using the sequence P1(o), P3, P2(e) is (d1-d2) compared to the difference (d1+d2) caused by the motion when using the sequence P1(o), P2(e), P3.

[0040] It is noted that if the tissue motion has a relatively constant velocity (e.g., typically when the patient is inhaling or exhaling), the motion-induced differences d1 and d2 will be similar, and thus the difference (d1-d2) caused by the motion in the output AM signal using the sequence P1(o), P3, P2(e) will generally be much smaller than the difference (d1+d2) caused by the motion in the output AM signal using the prior art sequence P1(o), P2(e), P3. In Figure 5A , Figure 5B the images shown in

[0041] To explain which order of the pulse sequence is more or less effective in reducing motion-induced artifacts, the concept of "temporal balance" is introduced. As discussed above, the underlying principle behind tissue cancellation in contrast-enhanced ultrasound images is to use two complementary sets of signals to cancel each other's echoes as much as possible. With respect to motion-induced artifacts, the time of transmission of each pulse or the time of reception of each echo must be taken into account, because the size of the echo signal changes over time, as described in detail above with respect to Figures 2A-2C .

[0042] In Figure 2C , the AM signal is provided by using the pulse sequence P1(o), P2, P3(e), P4 and the combination E1(o), E2, E2(e), the P1(o) signal and the P3(e) signal form one complement, and the P2 signal forms a second complement. With respect to Figure 2BIn contrast, motion-induced artifacts of AM signals are reduced because the first complement of echoes (E1(o), E2(e)) occurs on either side of the other complement (E3), thereby providing a "balanced" application of these complementary signals. In effect, this means that the sum of E1(o) and E2(e) yields a signal with a similar average displacement as E3. Conversely, in Figure 2B In Figure 2C , the first complement of echoes (E1(o), E2(e)) occurs before the other complement (E3), so the effective displacement of the sum signal is different from E3.

[0043] In Figure 2C , the first complement of echoes (E1(o), E2(e)) occurs before the other complement (E3), so the effective displacement of the sum signal is different from E3.

[0044] In contrast, in Figure 2B , the first complement of signals E1(o), E2(e) occurs at times T1 and T2, with an effective time of occurrence of this halfway point between T1 and T2, designated for convenience as T1.5. The second complement E3 occurs at time T3, which is far from T1.5. Thus, the sequence E1(o), E2(e), E3 can be said to be unbalanced in time by 1.5 time units (T3-T1.5 = 1.5 time units). The greater the difference between the effective times of occurrence of each complement, the greater the size of the motion-induced artifact. For example, by Figure 2B the combination of E1(o), E2(e), E4 yields an AMPI signal with an effective time of occurrence of T1.5 (the midpoint of E1(o), E2(e)) and T4 (a difference of 2.5 time units (T4-T1.5 = 2.5 time units)). This confirms the statement above: an AMPI signal with effective times of T1.5 and T4 using the sequence P1(o), P2(e), P3, P4 will exhibit a greater motion-induced artifact than an AM signal with effective times of T1.5 and T3 using this sequence.

[0045] However, Figure 2C the signals E1(o), E2(e), E4 used to produce an AMPI signal in Figure 2Bthe imbalance of the AMPI signal of the sequence in FIG. 1C (2.5 time units), but still not enough to greatly reduce motion-induced tissue artifacts in the AMPI signal.

[0046] It is noted that the four-pulse sequence commonly used in prior art systems, which includes two half-amplitude pulses and two full-amplitude pulses of opposite phase, cannot be arranged in any order to provide temporal balance of both the AM signal and the AMPI signal. It is also noted that the temporal balance of the PI signal using unity gain amplifiers requires at least four pulses (two pulses per phase) to create a point of temporal balance between each pair of pulses at each phase. For example, a sequence of full pulses at (phase 1, phase 2, phase 2, phase 1) results in an effective time for the phase 2 signal at the halfway point between the two pulses at phase 2, which is also an effective time for the phase 1 signal: the halfway point between the two pulses at phase 1. Two successive full pulses in a sequence (i.e., phase 2 in the above sequence) rarely, if ever, occur in prior art systems because redundant emissions are considered inefficient in regular cases.

[0047] Figure 3 An example five-pulse sequence is illustrated that provides temporal balance for the AM signal and the AMPI signal, and enables the production of a PI signal according to standard practice of those skilled in the art. The sequence is formed with three half-amplitude pulses P1(o), P3(e), P5(o) separated by two full-amplitude pulses P2 and P4. P2 and P4 have opposite phases to each other, while P1(o), P3(e), P5(o) are in phase with each other and with P2. In equivalent embodiments, P1(o), P3(e), and P5(o) can be in phase with P1. To facilitate illustration and understanding, the following notation is defined hereafter. "o" = half-amplitude odd; "e" = half-amplitude even; "+" = full-amplitude, phase 1; and "-" = full-amplitude, phase 2. Thus, Figure 3 The sequence of FIG. 1D can be referred to as the sequence (o, e, +, -), and the prior art sequence of FIG. 1C can be referred to as the sequence (o, +, e, -).

[0048] Figures 4A-4C An echo combination unit for providing PI, AM, and AMPI ultrasound signals using unity gain amplifiers 110, 114 and a summer 120 is illustrated.

[0049] Figure 4AA configuration for providing a PI signal based on the sum of full amplitude, opposite phase signals E2 and E4 is illustrated. As mentioned above, the balancing problem of the PI signal is not addressed with respect to this example; the temporal imbalance of the PI signal is two time units (T2-T4), i.e. the center of signal E2 is T2 and the center of signal E4 is T4.

[0050] Figure 4B A configuration for providing an AM signal based on the sum of two half amplitude echoes E1 (o), E3 (e) and a negative full amplitude echo -E2 is illustrated. The effective time of occurrence of this set of E1 (o), E3 (e) is T2 (signals E1 (o) and E3 (e) are uniformly shifted around the center point T2) and the effective time of occurrence of E2 is also T2 (the center of E2 is time T2), thereby providing a temporally balanced AM signal.

[0051] Figure 4C A configuration for providing an AMPI signal based on the sum of two half amplitude echoes E3 (e), E5 (o) and a full amplitude echo E4 of opposite phase is illustrated. The effective time of occurrence of this set of E3 (e) and E5 (o) is T4 (signals E3 (e) and E5 (o) are uniformly shifted around the center point T4) and the effective time of occurrence of E4 is also T4 (the center of E4 is time T4), thereby providing a temporally balanced AMPI signal.

[0052] As mentioned above, if the tissue motion is at a constant velocity and the pulse intervals are equal, this sequence will greatly reduce motion-induced tissue artifacts in AM and AMPI based images.

[0053] The PI signal is not balanced in time (T2, T4; 2 time units of imbalance) and will exhibit motion-induced artifacts. In embodiments of the present invention, the AM image or the AMPI image or both can be compared to or combined with the PI image to identify and reduce motion-induced tissue artifacts from the PI image.

[0054] Figures 5A-5D A significant improvement that can be achieved in ultrasound imaging by providing a temporally balanced pulse sequence to produce temporally balanced AM and AMPI signals is illustrated.

[0055] Figure 5A An ultrasound image obtained by a prior art (o, e, +, -) transmit sequence (Fig. ID) and using the o, e and + echo signals to provide an AM signal (Fig. ID) is illustrated.

[0056] Figure 5B A temporally balanced AM signal provided by an example sequence of the present invention (o, +, e, -, o) and using the first three echo signals (o, +, e) is illustrated.Figure 4B ) obtained by the prior art (o, e, +, -) transmit sequence.

[0057] Comparison Figure 5A and Figure 5B It can be seen that, for example, the region 520 in Figure 5B is improved compared to the region 510 in Figure 5A It can be seen that the ultrasound image of Figure 5A produced using the prior art (o, e, +, -) sequence introduces quite a lot of "tissue clutter" at 510, which is mainly due to the fact that the tissue has moved during the acquisition of the echo signals (motion-induced tissue artifacts). By providing the transmit sequence (o, +, e, -, o) which enables to reduce or eliminate motion-induced tissue artifacts by providing time-balanced echo signals (o, +, e) according to the present application, the region 520 exhibits much less tissue clutter compared to the region 510.

[0058] Figure 5C Fig. illustrates an ultrasound image obtained by the prior art (o, e, +, -) transmit sequence and using the o, e and - echo signals to provide an AMPI signal (Fig. ID). It can be seen, and as discussed above, that due to the time imbalance of the echo signals (T1.5-T4) used to produce the AMPI image of Figure 5C is larger than the time imbalance of the echo signals (T1.5-T3) used to produce the AM image of Figure 5A it can be identified that the degree of tissue clutter at region 530 in the AMPI image of Figure 5C is larger than the degree of tissue clutter at region 510 produced in the AM image of Figure 5A .

[0059] Figure 5D Fig. illustrates an ultrasound image obtained by the example sequence (o, +, e, -, o) of the present application and using the last three e, - and o echo signals to provide a time-balanced AMPI signal. It can be seen that the amount of tissue clutter at 540 in Figure 5D is much smaller than the amount of tissue clutter at 530 in Figure 5C .

[0060] Figure 6 Fig. illustrates an example block diagram of an ultrasound system 600 according to an aspect of the present application.

[0061] The scan head 610 includes a plurality of transducer elements 615 and a controller 630. The plurality of transducer elements 615 transmit and receive ultrasound signals. The controller 630 determines, via the switch 620, whether to provide a signal to the transducer elements for transmission or receive a signal from the transducer elements. The transducer elements are typically configured in a matrix, where each transducer is numbered in sequence; in this way, the transducer elements can provide half- amplitude signals by enabling either the odd-numbered transducer elements or the even-numbered transducer elements as described above.

[0062] When the switch 620 is in the transmit state, the transmitter 650 provides a sequence 655 of time-balanced pulses to the transducer elements. The transmitter 650 also informs the controller 630 which set of transducer elements (all, odd, even) should be enabled for each pulse in the sequence, and the controller 630 controls the transducer elements 615 accordingly.

[0063] In the receive mode, the received echoes are directed by the switch 620 to the beamformer 640, which then organizes the cancellation of the echoes to provide the PI, AM, and AMPI signals. The echo signals are processed in the canceller 660 in a conventional manner, except that, because the transmitted pulses are time-balanced, the results of the processing of the organized cancellation of the echoes at the canceller 660 via the AM or AMPI sub-modes will be greatly improved compared to the AM or AMPI processing of time- unbalanced echoes.

[0064] The PI, AM, and AMPI signals resulting from the tissue canceller 660 are provided to an image processor, which creates an image selectively based on each of the PI, AM, and AMPI signals or a combination of two or more of these signals. As described above, each of these organized cancellation PI, AM, and AMPI sub-modes has particular advantages and disadvantages. For example, each sub-mode PI, AM, and AMPI contains inherent frequency-dependent responses from microbubbles and tissue. Thus, in some embodiments, a mixing is done at each pixel or each region can be determined by the strongest attribute over several frequency bands. In some embodiments, the region and frequency band of each sub-mode containing the highest microbubble signal-to-noise ratio can be used to mix the pixels into a final image.

[0065] As described above, the sub-mode data can be used to identify regions of tissue clutter for a particular image, and the image can be masked or mixed to suppress unwanted tissue artifacts.

[0066] In the case where one sub-mode dominates in the arterial phase and another sub-mode dominates in the subsequent phase, in a similar manner, the changing bubble spectral response over depth / time can be used to vary the proportion of mixing. That is, for example, the AM output signal can exhibit less clutter during the arterial phase and the AMPI output can exhibit less clutter during the portal venous phase, and a composite image can be formed by selectively mixing the AM output and the AMPI output based on phase.

[0067] The images produced by the image processor 670 are communicated to a display device 680. At the display, various image combinations can be displayed, including, for example, displaying the images of each sub-mode PI, AM, and AMPI to the clinician simultaneously, so that the different information contained in each sub-mode can be evaluated. In a similar manner, images based on combinations of sub-mode signals can be selectively displayed with or without simultaneous display of the underlying sub-mode images.

[0068] As noted above, Figure 3 The pulse sequence of Figure 7 An example flowchart 700 for producing a time-balanced ultrasound pulse sequence(s) subject to a fixed number of pulses in the sequence is illustrated. The sequence provides time-balanced AM signals and AMPI signals, and as further detailed below, the sequence can also be extended to provide time-balanced PI signals. Those skilled in the art will recognize that alternative procedures can also be used.

[0069] At 710, the number of different pulse forms available for emission (e.g., half-odd, half-even, full-phase 1, full-phase 2, or others) is identified, and the number of pulses forming the sequence (typically five or more) is selected. Based on the available pulse forms and the number of pulses forming the pulse sequence, the possible sequences of the K pulse forms (taking N pulse forms at a time in a repeating fashion) are determined, and at 715, filtered to eliminate any pulse sequences that do not enable the PI sub-mode, the AM sub-mode, and the AMPI sub-mode (e.g., all pulses of the same phase, no half-amplitude pulses, etc.).

[0070] Loop 720-785 processes each feasible sequence to determine whether time-balanced AM signals and time-balanced AMPI signals can be formed according to the sequence.

[0071] At 720, the loop starts and incrementally tests each of the potential sequences identified at 715 until (at 765) a time balanced sequence position is found. Alternatively, all potential sequences can be tested to create a set of time balanced sequences. The sequences in the set can be evaluated to select a preferred sequence based on some other criteria (the position in the sequence where the time balance point is located).

[0072] At 725, the (set or sets) of signals in the sequence that can be used to provide the AM signal are identified. The sequence can contain alternative arrangements (sets) of echoes to provide the AM signal. In loop 730-780, each of the sets of echoes in the sequence are processed to determine if the set is time balanced. At 730, the loop starts and incrementally selects each potential sequence set for use in generating the AM signal identified at 725. At 735, the time centers of each of the complementary signal sets (e.g., (half odd, half even), (all phase 1)) are determined and compared at 740. If the set of signals in the sequence cannot provide an AM time balance (NO at 740), the set is not suitable and the next AM set (if any) is processed.

[0073] If the sequence provides a time balanced AM signal at 740, then at 745 a set of signals in the sequence that provide the AM PI signal is identified and loop 750-775 determines if each of the AM PI sets also provide a time balanced AM PI signal. The time centers of the complementary signal sets (e.g., (half odd, half even), (all phase 2)) are determined at 755 and compared at 760. If the time centers are the same, then the sequence is suitable for providing both a time balanced AM signal and a time balanced AM PI signal and the sequence and set of AM pulse signals and AM PI pulse signals are selected at 765.

[0074] After a pulse sequence that provides a time balanced AM signal and AM PI signal is found, no further processing is required and the process terminates at 770. Since the possible sequences at 715 must be able to provide a PI signal, it is assured that the selected sequence also provides a PI signal.

[0075] If the signal set at 760 fails to provide a time-balanced AMPI signal, the next AMPI set (if any) is processed in loops 750-775. After determining that all AMPI sets in the sequence fail to provide a time-balanced AMPI signal, the next AM signal set (if any) is processed in loops 730-780. If the sequence fails to provide both a time-balanced AM and AMPI signal, the next sequence is evaluated in loops 720-785. If no sequence providing both a time-balanced AM and AMPI signal can be found, the process terminates at 770 without selecting a sequence.

[0076] Those skilled in the art will recognize that modifications are possible. Figure 7 The flowchart is used to find sequences of PI, AM, and AMPI signals that provide time balance.

[0077] If the sequence provides AM balance at 740 and AMPI balance at 760, the process can be modified to subsequently determine whether the sequence can also provide a balanced PI signal using the same technique as identifying pulse groups that can be used to provide a PI signal, and then evaluating whether one pulse in the pulse group provides a time-balanced PI signal. For example, by increasing N from five pulses in the sequence to eight pulses, the modified process will identify a sequence (o, +, e, -, o, -e, +) that will provide a time-balanced PI signal, AM signal, and AMPI signal. The PI signals {+}, {-}, {-}, {+} from the second, fourth, sixth, and eighth pulses are balanced at T5; the AM signals {o}, {+}, {e} from the first, second, and third pulses are balanced at T2; and the AMPI signals {e}, {-}, {o} from the third, fourth, and fifth pulses are balanced at T4. Optionally, another AMPI signal {o}, {-}, {e} can be obtained from the fifth, sixth, and seventh pulses, which is balanced at T6.

[0078] While increasing the sequence size consumes more time per sample, in some cases, the reduction or elimination of motion-induced artifacts in each sub-pattern within a sub-pattern may justify the extra time. Furthermore, since the AMPI signal can be provided by either an e, -, O signal (T4) or an o, -, e signal (T6), both signals can be generated and combined to potentially provide an improved AMPI signal.

[0079] Those skilled in the art will recognize that it can also be used Figure 7 The flowchart is used to provide signals with different time balances. For example, replace "PI" with... Figure 7 The "AMPI" block will generate a sequence of AM and PI signals that provide time balance;Figure 7 Replacing "AM" with "PI" would result in a sequence that provides a time balanced PI signal and an AM PI signal. In a similar manner, the test at block 725 can obviate the requirement that the sequence be able to produce the time unbalanced signal if it is not desired to use a time unbalanced signal (e.g., PI).

[0080] Those skilled in the art will also recognize that the principles of the present application can be applied to any set of signals subject to motion induced artifacts and using a complementary set of signals to cancel the underlying unwanted signal. That is, if different sub-patterns and / or different pulse types are found to cancel the underlying unwanted signal, then the following flowchart and examples can be applied Figure 7 flowchart and examples.

[0081] While the application has been illustrated and described in detail in the drawings and foregoing description, such illustration and description is to be considered illustrative or exemplary only and not restrictive; the application is not limited to the disclosed embodiments.

[0082] For example, the application can be operated in embodiments where the order of the sequences is reversed, the phases are reversed, etc., so long as the resulting sequence remains time balanced. That is, the use of the terms "positive" and "negative," "odd" and "even" are not absolute for purposes of understanding the application as disclosed in the claims, but are relative to one another.

[0083] Figure 8 is a block diagram illustrating an example processor 800 according to embodiments of the present disclosure. The processor 800 can be used to implement one or more processors described herein, such as the processor 102, the processor 202, the processor 302, the processor 402, the processor 502, the processor 602, the processor 702, the processor 802, and / or any or all of the processing elements shown. Figure 6 The processor 800 can be any suitable processor type, including but not limited to a microprocessor, a microcontroller, a digital signal processor (DSP), a field programmable array (FPGA) (where the FPGA has been programmed to form a processor), a graphics processing unit (GPU), an application specific integrated circuit (ASIC) (where the ASIC has been designed to form a processor), or a combination thereof.

[0084] The processor 800 can include one or more cores 802. The core 802 can include one or more arithmetic logic units (ALUs) 804. In some embodiments, the core 802 can include a floating point logic unit (FPLU) 806 and / or a digital signal processing unit (DSPU) 808 in addition to or instead of the ALU 804.

[0085] The processor 800 can include one or more registers 812 that are communicatively coupled to the core 802. The registers 812 can be implemented using dedicated logic gates e.g., flip-flops and / or any memory technology. In some embodiments, the registers 812 can be implemented using static memory. The registers can provide data, instructions, and addresses to the core 802.

[0086] In some embodiments, the processor 800 can include one or more levels of cache memory 810 that are communicatively coupled to the core 802. The cache memory 810 can provide computer-readable instructions for execution by the core 802. The cache memory 810 can provide data for processing by the core 802. In some embodiments, the cache memory 810 can be provided with computer-readable instructions by a local memory, e.g., a local memory attached to the external bus 816. The cache memory 810 can be implemented with any suitable cache memory type, e.g., metal-oxide semiconductor (MOS) memory such as static random access memory (SRAM), dynamic random access memory (DRAM), and / or any other suitable memory technology.

[0087] The processor 800 can include a controller 814 that can control input to the processor 800 from other processors and / or components included in the system, e.g., the components ROM 832, and / or output from the processor 800 to other processors and / or components included in the system, e.g., the components RAM 833. The controller 814 can control the data paths in the ALU 804, the FPLU 806, and / or the DSPU 808. The controller 814 can be implemented as one or more state machines, data paths, and / or dedicated control logic. The gates of the controller 814 can be implemented as standalone gates, FPGAs, ASICs, or any other suitable technology. Figure 8 The registers 812 and the cache memory 810 can communicate with the controller 814 and the core 802 via internal connections 820A, 820B, 820C, and 820D. The internal connections can be implemented as buses, multiplexers, crossbars, and / or any other suitable connection technology. Figure 8 The registers 812 and the cache memory 810 can communicate with the controller 814 and the core 802 via internal connections 820A, 820B, 820C, and 820D. The internal connections can be implemented as buses, multiplexers, crossbars, and / or any other suitable connection technology.

[0088] The registers 812 and the cache memory 810 can communicate with the controller 814 and the core 802 via internal connections 820A, 820B, 820C, and 820D. The internal connections can be implemented as buses, multiplexers, crossbars, and / or any other suitable connection technology.

[0089] Input and output for the processor 800 can be provided via a bus 816, which can include one or more wires. The bus 816 can be communicatively coupled to one or more components of the processor 800, e.g., the controller 814, the cache memory 810, and / or the registers 812. The bus 816 can be coupled to one or more components of a system, e.g., the previously mentioned components BBB and CCC.

[0090] Bus 816 can be coupled to one or more external memories. The external memories can include read only memory (ROM) 832. ROM 832 can be mask ROM, electronically programmable read only memory (EPROM), or any other suitable technology. The external memories can include random access memory (RAM) 833. RAM 833 can be static RAM, battery backed-up static RAM, dynamic RAM (DRAM), or any other suitable technology. The external memories can include electrically erasable programmable read only memory (EEPROM) 835. The external memories can include flash memory 834. The external memories can include magnetic storage devices such as a disk 836. In some embodiments, the external memories can be included in a system (e.g., the ultrasound imaging system 600) shown. Figure 6

[0091] Although processor 800 is shown as being distinct from external bus 816, memories 832, 834, 833, 835, and disk 836, in alternative embodiments some or all of these items can be part of "processor" 800. It will be appreciated that the term processor, processor system, computer, computer system controller, or controller system can refer to processor 800 alone or to the processor along with some or all of elements 816, 832, 834, 833, 835, and 836.

[0092] Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. In the claims, the word "comprising" does not exclude other elements or steps, and the words "a" or "an" do not exclude a plurality. A single processor or other unit can fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. The reference signs and symbols appearing in the claims should not be construed as limiting the scope of the claims. Computer programs can be stored / distributed on a suitable medium, such as an optical storage medium or a solid state storage medium supplied together with or as part of other hardware, but can also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems. Any reference signs in the claims should not be construed as limiting the scope of the claims.​

Claims

1. An ultrasound method for differentiating between non-perfused tissue and blood flow and / or blood perfusion, comprising: transmitting (650) a sequence of ultrasound signals (P1(o), P2, P3(e), P4, P5(o)) via a plurality of ultrasound transducer elements (615) into a patient; receiving (640) a sequence of echo signals (E1(o), E2, E3(e), E4, E5(o)) corresponding to a sequence of ultrasound images; combining (660) a selected first group of echo signals (E1(o), -E2, E3(e)) to produce an amplitude modulated (AM) signal, wherein the selected first group comprises a first subset (E1(o), E3(e)) forming a first complement and a second subset (-E2) forming a second complement, and wherein the combining of the selected first group of echo signals comprises combining the first complement and the second complement of the selected first group; combining (660) a selected second group of echo signals (E3(e), E4, E5(o)) to produce an amplitude modulated phase inversion (AMPI) signal, wherein the selected second group comprises a first subset (E3(e), E5(o)) forming a first complement and a second subset (E4) forming a second complement, and wherein the combining of the selected second group of echo signals comprises combining the first complement and the second complement of the selected second group; creating (670) at least one image based on at least one of the AM signal and the AMPI signal; displaying (680) the at least one image; wherein each of the selected first group of echo signals and the selected second group of echo signals is time balanced, time balanced meaning that for each of the selected first group of echo signals and the selected second group of echo signals, the order of the selected group of echo signals is such that the echo signals of the first complement occur on either side of the echo signals forming the second complement; wherein in each combination for producing the AM signal and the AMPI signal, each of the echo signals is equally weighted (110, 114).

2. The method of claim 1, wherein, the sequence of ultrasound signals comprises a sequence of a first signal, a second signal, a third signal, a fourth signal, and a fifth signal; wherein the first signal and the fifth signal correspond to transmissions with a first phase through a first half of the plurality of ultrasound transducer elements; wherein the second signal corresponds to a transmission with the first phase through the plurality of transducer elements; wherein the third signal corresponds to a transmission with the first phase through a second half of the plurality of ultrasound transducer elements, wherein the second half is a complement of the first half; and wherein the fourth signal corresponds to a transmission with a second phase through the plurality of transducer elements, wherein the second phase is a complement of the first phase.

3. The method of claim 2, wherein the first signal corresponds to the echo signal E1(o), wherein the second signal corresponds to the echo signal E2, wherein the third signal corresponds to the echo signal E3(e).

4. The method of claim 2 or 3, wherein, The AMPI signal comprises a sum of the third signal, the fourth signal and the fifth signal.

5. The method of any one of claims 2 to 4, wherein, The method comprises summing the second signal and the fourth signal to provide a phase inversion (PI) signal, and wherein the at least one image is also based on the phase inversion signal.

6. The method of claim 5, wherein, The phase inversion signal is time balanced.

7. The method of any one of claims 1-6, wherein, The at least one image is also based on a spectral response of at least one of the AM signal and the AMPI signal.

8. The method of any one of claims 1-7, wherein, The at least one image is also based on a signal-to-noise ratio of at least one of the AM signal and the AMPI signal.

9. The method of any one of claims 1-8, wherein, The creating at least one image comprises creating at least two images, and wherein the method comprises simultaneously displaying the at least two images, and / or wherein the at least one image comprises a combined image based on both the AM signal and the AMPI signal.

10. The method of any one of claims 1-9, wherein, For each of the selected first set of echo signals and the selected second set of echo signals: The first subset of echo signals forms the first complement with a first time center; The second subset of echo signals forms the second complement with a second time center; and wherein the first time center is equal to the second time center.

11. The method of claim 10, wherein, The time center of each of the first complement and the second complement corresponds to an average occurrence time of the echo signals forming the respective complement.

12. The method of any one of claims 1-11, wherein, The at least one image shows the flow of contrast-enhanced microbubbles injected in a blood vessel of the patient through the patient.

13. An ultrasound system comprising: a plurality of transducer elements (615) that emit a sequence of ultrasound pulses (P1(o), P2, P3(e), P4, P5(o)) and receive a sequence of echo signals (E1(o), E2, E3(e), E4, E5(o)) in response to the sequence of ultrasound pulses; and processing circuitry that generates (650) the sequence of ultrasound pulses and processes (660) the sequence of echo signals in accordance with any one of claims 1-12.

14. A non-transitory computer readable medium comprising a program which, when executed by a processing system, causes the processing system to: emit (650) a sequence of ultrasound signals (P1(o), P2, P3(e), P4, P5(o)) via a plurality of ultrasound transducer elements (615) into a patient; receive (640) a sequence of echo signals corresponding to a sequence of ultrasound images; The selected first set of echo signals (E1(o), -E2, E3(e)) is combined (660) to produce an amplitude modulated (AM) signal, wherein, the selected first set comprises a first subset (E1(o), E3(e)) forming a first complement and a second subset (-E2) forming a second complement, and wherein the combining of the selected first set of echo signals comprises combining the first complement and the second complement of the selected first set; the selected second set comprises a third subset (E2) forming a third complement and a fourth subset (-E4) forming a fourth complement, and wherein the combining of the selected second set of echo signals comprises combining the third complement and the fourth complement of the selected second set; and the first complement and the second complement are combined to provide a first combined signal; and the third complement and the fourth complement are combined to provide a second combined signal. combining (660) a selected second set of echo signals (E3(e), E4, E5(o)) to produce an amplitude modulated phase inverted (AMPI) signal, wherein the selected second set comprises a first subset (E3(e), E5(o)) forming a first complement and a second subset (E4) forming a second complement, and wherein the combining of the selected second set of echo signals comprises combining the first complement and the second complement of the selected second set; creating (670) at least one image based on at least one of the AM signal and the AMPI signal; displaying (680) the at least one image; wherein each of the selected first set of echo signals and the selected second set of echo signals is time balanced, meaning that for each of the selected first set of echo signals and the selected second set of echo signals, the order of the selected set of echo signals is such that the echo signals of the first complement occur on either side of the echo signals forming the second complement; wherein in each combination for producing the AM signal and the AMPI signal, each of the echo signals is equally weighted (110, 114).

15. The medium of claim 14, wherein: the sequence of ultrasound signals comprises a sequence of a first signal, a second signal, a third signal, a fourth signal, and a fifth signal; the first signal and the fifth signal correspond to emissions with a first phase by a first half of the plurality of ultrasound transducer elements; the second signal corresponds to emissions with the first phase by the plurality of transducer elements; the third signal corresponds to emissions with the first phase by a second half of the plurality of ultrasound transducer elements, wherein the second half is a complement of the first half; and the fourth signal corresponds to emissions with a second phase by the plurality of transducer elements, wherein the second phase is a complement of the first phase.

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