Abstract: A medical diagnostic ultrasound imaging method and system insonify a tissue containing a contrast agent with ultrasonic transmit signals at a fundamental frequency f. Backscattered ultrasonic receive signals are acquired and filtered to emphasize frequency components between the fundamental frequency f and the second harmonic frequency 2f, and the filtered receive signals are processed for display. This filtering enhances the ability of the method and system to discriminate between contrast agent and adjacent tissue.

Abstract: Reflectors such as microbubbles in a contrast agent introduced into a blood vessel of a patient are destroyed (or otherwise acoustically altered) using focused ultrasound at a modulation point according to an input modulation sequence. This creates “gaps” in the flowing contrast agent that are sensed at a downstream sensing point. The pattern of gaps is then matched in time with the input modulation sequence to determine a transit time for the gaps, which is also the flow velocity of the blood. The input modulation sequence creates at least two gaps, but may otherwise have any of several different forms, which include, among others, square-wave, maximal sequence, random binary patterns. Edge-detection and correlation techniques are used to match the input and sensed gap patterns. By triggering the input sequence off of a heart rate monitor, a flow velocity profile may also be calculated and displayed from one heart beat to the next.

Abstract: An ultrasonic diagnostic imaging system and method are provided for producing harmonic ultrasonic images at high line densities or frame rates of display. Scanlines are received from spatially adjacent fundamental frequency transmit beams of opposite phase or polarity. The received scanlines are summed on a spatially consistent basis to produce image lines of separated harmonic echo signals intermediate the adjacent scanlines. The received scanlines may be subtracted, or the polarity of alternately received scanlines inverted, to produce image lines of separated linear (fundamental frequency) echo signals. In preferred embodiments the received scanlines are combined by filter functions which reduce or eliminate artifacts which otherwise arise from the scanline combining process.

Abstract: Fluid flow rate and perfusion rate are measured using ultrasound techniques by introducing a contrast agent into a fluid stream and then selectively modifying the contrast agent particles within a target area by the application of a focused pulse of relatively low frequency ultrasonic energy, thus creating a zone of reduced backscatter in the target area. The restoration of the zone of reduced backscatter or the movement of the zone of reduced backscatter is monitored, preferably using high frequency ultrasound, to determine the flow rate or perfusion rate of the fluid. Spectral parameters of ultrasound return signals are evaluated to determine an estimate of contrast agent concentration and/or mean particle size.

Abstract: Plastics material-containing closed containers (e.g., elastomer-stoppered vials) for contrast agents and contrast agent precursors which incorporate or are adapted to incorporate a volatile substance (e.g., a gaseous halocarbon such as a perfluorocarbon), where the plastics material is pretreated by exposure to the volatile substance. Such containers may enhance the storage stability of the contrast agent or precursor content.

Abstract: A method and system for imaging contrast agent within human or animal tissue, organs and/or blood is provided. Contrast agents, such as perfluorocarbon gas-filled albumin microbubbles which exhibit momentary contrast enhancement when exposed to high intensity ultrasound are injected into a patient. Periodic images are generated to avoid reduction in the contrast provided by the contrast agents due to ultrasound destruction. Between the periodic images, an M-mode image is substantially continuously updated to allow the user to better locate and maintain imaging of a region of interest, determine dynamic movement within the region of interest, access attenuation, determine an appropriate trigger point, and view perfusion of the contrast agent between the periodic images while minimizing destruction of contrast agent. In one embodiment, an ultrasound system alternates between triggered firings of a two-dimensional B-mode image and substantially continuous updating of an M-mode image.

Abstract: Perfusion of tissue such as the myocardium by a microbubble contrast agent is imaged in realtime by a multiple pulse technique which uses low power transmit pulses which are sufficient to elicit a harmonic response from the microbubbles but are not high enough in power to cause substantial destruction to the microbubbles. In a preferred embodiment the realtime microbubble image sequence is displayed in color, overlaid with a grayscale image of the surrounding tissue in the region being imaged.

Abstract: A method of imaging blood with the use of contrast agents. A sequence or ensemble of imaging pulses is transmitted into a patient. Echo signals received in response to each of the imaging pulses are received and analyzed to determine if the echoes are produced by tissue or by the contrast agent. Echoes produced by the contrast agent are detected by an echo signal that changes in amplitude or a centroid frequency that changes with each imaging pulse. Once the location of the contrast agent has been determined, an image is created whereby the contrast agent is highlighted for view by a physician or sonographer.

Abstract: Detectable markers that may be introduced into a cavity created by removal of a biopsy specimen to mark the location of the biopsy site so that it may be located in a subsequent medical/surgical procedure. The markers remain present in sufficient quantity to permit detection and location of the biopsy site at a first time point (e.g., 2 weeks) after introduction but clear from the biopsy site or otherwise not interfere with imaging of tissues adjacent the biopsy site at a second time point (e.g., 5-7 months) after introduction.

Abstract: In order to obtain an image of a microballoon contrast agent with sharpness, the invention comprises means for generating ultrasound 522 by thermally exciting the microballoon contrast agent infused in a subject to cause the microballoons to resonate, and means for producing an image 514 based on the generated ultrasound.

Abstract: An ultrasound contrast medium which substantially consist of microbubbles is injected into a patient and contrast echo imaging is performed by a diagnostic ultrasound apparatus. In the apparatus, an ultrasound pulse signal is transmitted toward the patient's diagnostic region on the basis of a changeable transmitted sound pressure, an echoed component of the transmitted ultrasound pulse signal is received to produce a corresponding reception signal, a tomographic image using the reception signal is produced, and the transmitted sound pressure is optimized so as to maximize a value of the reception signal. The transmitted sound pressure is a representative of the transmission power condition. For example, the transmitted sound pressure optimized is displayed. The transmitted sound pressure is, by way of example, optimized based on the reception signal corresponding to the echoed component emanating from an overall region of interest in a cross section scanned by the ultrasound pulse signal.

Abstract: An ultrasound wave is transmitted to a target object through an ultrasound probe, and an echo signal returning from the target object is received through the ultrasound probe. In a fundamental wave mode, a fundamental wave component is extracted from the echo signal, and an image is generated based on the fundamental wave component. In a harmonics mode, a harmonics component is extracted, and an image is generated based on the harmonics component. The focal strength ratio of the ultrasound wave in the harmonica mode is changed between in the harmonics mode and in the fundamental wave mode. As a result, images with high quality can be obtained in both the fundamental wave mode and the harmonics mode.

Abstract: A medical diagnostic ultrasound imaging system and method modulate the image signal as a function of the ratio of the harmonic receive signal to the fundamental receive signal. Tissue harmonic backscatter differs substantially in spectral shape as compared to contrast agent backscatter, and this method allows improved discrimination between contrast agent and tissue backscatter.

Abstract: Medical diagnostic ultrasonic imaging systems and methods image at a fractional harmonic such as f.sub.0 /2 or 3f.sub.0 /2, where f.sub.0 is the fundamental frequency of the associated transmit beam. In order to improve fractional harmonic imaging, the transmit beam includes a fractional harmonic seed component, which may also have a center frequency of f.sub.0 /2 or 3f.sub.0 /2. Multiple pulse imaging methods using transmit beams having such fractional harmonic seed components further enhance fractional harmonic imaging.

Abstract: An ultrasound imaging system is programmed to acquire first ultrasonic image frames intermittently. These first frames, typically triggered frames synchronized with a selected portion of an ECG cycle, are optimized for high image quality of a contrast agent included in the tissue. The imaging system automatically acquires second ultrasonic image frames between at least some of the first frames. The second image frames are typically locator frames which are optimized for reduced degradation of the contrast agent. More of the second frames are acquired per unit time than first frames, and both the first and second frames are displayed, either superimposed over one another or in side-by-side relationship. In this way the user is provided with substantially continuous transducer locating information, yet contrast agent destruction between acquisitions of the first, triggered frames is reduced or eliminated.

Abstract: Coatings to enhance the echogenicity of materials are especially useful for medical devices wherein the practitioner desires to locate or visualize a device by ultrasonic imaging when the device is inserted into a body cavity. These coatings can be applied to any device of virtually any composition. To accomplish this, a polymer matrix is formed containing an entrapped gas in enclosed bubbles or open surface channels or cavities. Coated needles are visible in ultrasound when inserted in animals. A pre-coat or base coat may be applied to condition the surface to enhance adhesion. A finish coat or top coat may be applied to improve durability, smoothness, and biocompatibility, lubricity, antibiotic, antimicrobial, antithrombogenic activity, and other desirable properties for the finished product. Coating liquids and methods for preparing and applying such coatings are disclosed, including forming bubbles by chemical reaction during the coating process.

Abstract: A method and apparatus for performing harmonic imaging. Each transmit focal zone in the near-field is interrogated by two or more transmit firings of different phase, while each transmit focal zone in the far-field is interrogated by a single transmit firing. On receive, the respective near-field vectors are summed, thereby substantially canceling the fundamental signal components while isolating the (sub)-harmonic signal components. In the far-field, the single transmit firing has a fundamental frequency .function..sub.0. A filter isolates the signal component having a passband centered at a (sub)harmonic frequency, e.g., 2.function..sub.0. The near-field and far-field receive vectors at each scan angle are then stitched together to form a composite vector.

Abstract: A method and an apparatus for displaying three-dimensional images of ultrasound data having improved segmentation. This is accomplished by harmonic imaging. There are two types of harmonic imaging: (1) imaging of harmonics returned from contrast agents injected into the fluid; and (2) naturally occurring harmonics, generally referred to as "tissue harmonics". An ultrasound transducer array is controlled to transmit a beam formed by ultrasound pulses having a transmit center frequency and focused at a desired sample volume containing contrast agents. In the receive mode, the receiver forms the echoes returned at a multiple or sub-multiple of the transmit center frequency into a beam-summed receive signal. This process is repeated for each sample volume in each one of a multiplicity of scan planes. After filtering out the undesired frequencies in the receive signal, i.e.

Abstract: An ultrasonic diagnostic imaging method and apparatus are presented which separates broadband linear and nonlinear echo signal components while simultaneously distinguishing the effects of motion. The inventive method maps ultrasonic echo signals in the r.f. (time) domain to Doppler shift frequencies in the Doppler domain in a way that depends upon the linearity of the echoes. The inventive method does this by analyzing the phase shifts between successive echoes. Apparatus is described in which a Doppler echo ensemble is acquired by a transmit sequence of cyclically phase-varying waveforms. When the echoes of the ensemble are combined during Doppler processing, the resulting Doppler spectrum is divided into separate regions, with odd harmonics (e.g., linear signal components) residing in one region and even harmonics (e.g., second harmonic signal components) residing in another region.

Abstract: The present invention relates to a method of imaging using multiple doses of an echogenically persistent contrast agent. In particular, it relates to the use of ultrasound energy to eliminate residual echogenicity attributed to the first dose of contrast agent prior to administering a second dose of contrast agent for the purpose of acquiring more images.

Abstract: Methods for use of contrast agents with an acoustic echographic imaging system, including controlling the concentration of contrast agent in a region of interest by adjusting the acoustic imaging signal to increase or decrease depletion of the contrast agent to the linear range of response. Adjustment of the signal includes dividing the received signal level by a power reduction ratio to re-normalize the signal level and compensating the signal power level. A spectral processor detects the concentration of the contrast agent in a gate marker window as the averaged ratio of energy around the second harmonic of the return signal versus energy around the fundamental frequency of the return signal, and includes a boundary detector for detecting a point of greatest change in value of the averaged ratios as a boundary between regions of interest.

Abstract: An ultrasonic imaging technique is disclosed which uses microbubbles as echo contrast agents. In general the method employs maitenance of an ultrasound signal while the contrast agent is intravenously injected into a mammal. Once all the contrast agent has been injected and transmission of the signal is suspended for a period of time sufficient for the microbubbles perfuse the organ of interest. Transmission of the ultrasound signal is then resumed and peak contrast images are obtained which rival more complicated imaging procedures such as nuclear resonance imaging.

Abstract: A method of generating an ultrasound image comprising the steps of (i) introducing into the location to be imaged an ultrasound contrast agent obtained by spraying a solution or suspension of a wall forming material into a heated gas to form hollow microcapsules, (ii) exposing the microcapsules to ultrasound energy at an insonation frequency of less than 3.5 MHz and (iii) creating an image based on the scattering of the ultrasound energy by the microcapsules.

Abstract: A process for selective graphic representation and/or evaluation of the Doppler spectrum of objects limitedly resistant to sonic intensity, for example biological organs and tissues, by an ultrasonic process wherein a material is introduced in the examination area to be acoustically irradiated, nonlinear oscillations are produced in the examination area by irradiated ultrasonic waves and the signal is evaluated by an ultrasonic converter. Also, a circuit for carrying out the above process is disclosed.

Abstract: A method and an apparatus for enhancing edges in computer-generated images. Each image frame is divided into non-overlapping blocks of pixels. Each block is characterized by a value proportional to the contrast of the block. Each block is checked to see if its contrast is greater than a user-selectable contrast threshold. If the block contrast is greater than the threshold, a window level operation is performed upon that pixel block. This method restricts the window level edge enhancement function to just the set of pixel blocks that have a high contrast value and may contain an edge.

Abstract: Transverse notches in a surgical needle provide an increased reflecting area and enhanced response to ultrasonic probing to provide an enhanced image on an ultrasonic echo sensor. Having the notch cut through to the needle lumen entrains small air bubbles in the notch further enhancing ultrasonic reflection and ultimate imaging of the needle's position.

Abstract: A method and an apparatus for imaging the nonlinear components of an ultrasound signal returned from ultrasound scatterers in tissue or contrast agents in blood. The method employs a code-modulated wavelet for transmission combined with correlation filtering on reception. Coding methods are used to simultaneously manipulate the linear and nonlinear terms. The manipulations affect the magnitude and temporal arrangement of the resulting decoded waveforms. Among the simultaneous manipulations of linear and harmonic decoded signals are: orthogonal linear terms, finite linear terms, minimum sidelobe with optimal peak harmonic terms and optimally compressed harmonic terms.

Abstract: A method and an apparatus for increasing the contrast resolution of computer-generated images using fractal enhancement techniques. Each image frame is divided into blocks of pixels which are sorted into source and destination lists based on their distance from the transmit focal zone. The source list contains overlapping pixel blocks corresponding to ranges within a predetermined distance of the transmit focal zone (i.e., blocks of high resolution). The destination list contains non-overlapping blocks corresponding to ranges outside the focal zone area (i.e., blocks of lower resolution). For each low-resolution block, a computer searches for a high-resolution block having the same brightness and contrast classes, but having a greater block contrast. The high-resolution block meeting these criteria and having the greatest block contrast is substituted for the corresponding low-resolution block in the image frame.

Abstract: It has been discovered microparticles formed from natural or synthetic polymer with thicker walls have significantly enhanced echogenicity as compared with microparticles having thinner walls. The effect of wall thickness has been determined experimentally as well as inserted into a formula for use in predicting the optimum conditions. In the preferred embodiment, the polymers are synthetic biodegradable polymers and the wall thickness is between about 100 and 660 nm, although wall thicknesses from about 20 nm to in excess of 500 nm can be used. The microparticles are manufactured with a diameter suitable for the targeted tissue to be imaged, for example, with a diameter of between 0.5 and 8 microns for intravascular administration, and a diameter of between 0.5 and 5 mm for oral administration for imaging of the gastrointestinal tract or other lumens.

Abstract: A method for ultrasonic harmonic imaging is disclosed, which uses microbubbles particularly selected for their properties of reradiating ultrasound energy at frequencies other than the exciting frequency.

Abstract: A method and apparatus for quantifying and displaying ultrasound signals in an ultrasonic system are provided. A first signal value for each of at least one spatial location in a region of interest is acquired at a first time, and the signal values are summed to obtain a first surface integral value. A second signal value for each of said at least one spatial location in said region of interest is acquired at a second time, and the second signal values are summed to obtain a second surface integral value. The first surface integral value is summed with the second surface integral value to obtain a time based integral. The time based integral is displayed. Other quantities based on any of various ultrasound parameters, such as Doppler energy, Doppler velocity and B-mode intensity, are calculated and displayed as quantities or as waveforms as a function of time. Furthermore, various comparisons of quantities and waveforms are provided. Image plane data or other ultrasound data are used in the calculations.

Abstract: This invention relates to an oil-in-water emulsion that is of a water-insoluble gas-forming chemical and a stabilizer. The emulsion being capable of forming microbubbles of gas upon application of ultrasonic energy. This composition allows for site specific imaging as the image enhancing microbubbles can be released upon the application of ultrasonic energy at the specific location where the image is desired.

Abstract: Microcapsules are prepared by a process comprising the steps of (i) spray-drying a solution or dispersion of a wall-forming material in order to obtain intermediate microcapsules and (ii) reducing the water-solubility of at least the outside of the intermediate microcapsules.Suitable wall-forming materials include proteins such as albumin and gelatin.The microcapsules have walls of 40-500 nm thick and are useful in ultrasonic imaging. The control of median size, size distribution and degree of insolubilisation and cross-linking of the wall-forming material allows novel microsphere preparations to be produced.

Abstract: A method for ultrasonic harmonic imaging is disclosed, which uses microbubbles particularly selected for their properties of reradiating ultrasound energy at frequencies other than the exciting frequency.

Abstract: A method of generating an ultrasound image comprising the steps of (i) introducing into the location to be imaged an ultrasound contrast agent obtained by spraying a solution or suspension of a wall forming material into a heated gas to form hollow microcapsules, (ii) exposing the microcapsules to ultrasound energy of an intensity of at least 100 kPa and (iii) creating an image based on the scattering of the ultrasound energy by the microcapsules.

Abstract: A method and an apparatus for selectively performing contrast harmonic imaging, tissue harmonic imaging and B-mode flow imaging with an ultrasound imaging system utilizes phase-coded excitation on transmit and selective firing-to-firing, i.e., "slow-time", filtering on receive. "Slow-time" filtering in combination with transmit phases which change over the set of transmit firings results in different effective "slow-time" filters corresponding to the different harmonic modes within the reflected signal. The transmit phases and the "slow-time" filter weightings are designed to selectively enhance the desired modes while substantially suppressing other modes.

Abstract: Temporal variations in backscatter from an ultrasound contrast agent located in the vascular system and induced by movement of the scatterers are used to visualize the presence of contrast agent by determining areas where correlation between successive ultrasound images is poor. This low level of correlation from intravascular contrast agent movement permits distinction between stationary bulk tissue and moving bulk tissue since movement of the latter solid tissue scatterers is correlated.

Abstract: An ultrasonic transducer array for harmonic imaging including an ultrasonic transducer array having a plurality of transducer elements, each of said transducer elements having a first surface and a second surface opposite of said first surface, said second surface being non-planar in an elevation direction and said second surface facing away from a region of examination when the transducer is in use. Transmit circuitry is coupled to the transducer array and is operative to cause the transducer array to emit a signal having a bandwidth controlled such that substantially no harmonic energy is transmitted. Receive circuitry is coupled to the transducer array and selectively responsive to harmonic echo information.

Abstract: A patient is first injected with a contrast agent. A complete scan along a plurality of scan lines is then performed, resulting in the destruction of some contrast agent. While some of the contrast agent is destroyed, non-scanned portions of the target, and possibly the scan region, still include at least some contrast agent. A second scan is then sequentially performed sufficiently close in time to the first scan such that reflections from the anatomy remain unchanged. The second frame of data from the second scan will differ from the first frame of data from the first scan by only contrast agent effects. The second frame of data is subtracted from the first frame of data. The resulting data is used to image the contrast agent. By varying the time between each pair of scans, differences in the speed of the contrast agent motion within the body may be assessed. The collateral damage of contrast agents from ultrasound acoustic energy is minimized while the degradation due to various changes is also minimized.

Abstract: An improved retrograde coronary sinus perfusion catheter includes a flexible, tubular catheter body and an inflatable balloon. The catheter body has proximal and distal ends and an interior lumen. The inflatable balloon is located adjacent the distal end of the catheter body and has proximal and distal edges. The improvement includes an echogenicity enhancement embedded within the catheter body. The echogenicity enhancement is adapted to reflect ultrasonic waves at a characteristic different from the catheter body.

Abstract: An ultrasonic imaging system generates Doppler and B-mode image signals, and then uses a modulated, non-linear mapping function to combine the Doppler and B-mode image signals into an output signal. In another mode of operation the imaging system generates fundamental and harmonic frequency intensity values and maps these intensity values to display indicia, preferably with a modulated, non-linear mapping function.

Abstract: A method for detecting the presence of contrast agent in the body of the patient initially transmits ultrasound pulses along respective acoustic scan lines, which pulses exhibit a fundamental transmission frequency. A set of returned signals are received along a respective scan line after each pulse transmission. The frequency content of each set of return signals is segregated into first and second groups, the first group positioned about the fundamental transmission frequency and the second group positioned about a harmonic frequency thereof. Thereafter, a relationship is determined as between the energy characteristics of the first group and the second group, for each set of return signals. The determined relationship for a scan line indicates a proportion of the return signal that is returned from contrast agent versus a proportion which is returned from tissue.

Abstract: A method and an apparatus for imaging the nonlinear components of an ultrasound signal returned from ultrasound scatterers in tissue or contrast agents in blood. The method employs a code-modulated wavelet for transmission combined with correlation filtering on reception. Transmit codes are used to modulate the phases of wavelets for successive transmit firings focused at the same transmit focal position. For example, for a first transmit firing a first transmit code is used to modulate a base wavelet to form a first coded wavelet and for a second transmit firing a second transmit code is used to modulate the same base wavelet to form a second coded wavelet. On reception, the receive signals resulting from the first and second transmit firings are decoded by correlating the receive signals with first and second receive codes respectively.

Abstract: An ultrasound imaging system is programmed to acquire first ultrasonic image frames intermittently. These first frames, typically triggered frames synchronized with a selected portion of an ECG cycle, are optimized for high image quality of a contrast agent included in the tissue. The imaging system automatically acquires second ultrasonic image frames between at least some of the first frames. The second image frames are typically locator frames which are optimized for reduced degradation of the contrast agent. More of the second frames are acquired per unit time than first frames, and both the first and second frames are displayed, either superimposed over one another or in side-by-side relationship. In this way the user is provided with substantially continuous transducer locating information, yet contrast agent destruction between acquisitions of the first, triggered frames is reduced or eliminated.

Abstract: Microspheres are prepared by a process comprising the steps of (i) spray-drying a solution or dispersion of a wall-forming material in order to obtain intermediate microspheres and (ii) reducing the water-solubility of at least the outside of the intermediate microspheres. Suitable wall-forming materials include proteins such as albumin and gelatin. The microsphere have walls of 40-500 nm thick and are useful in ultrasonic imaging. The control of median size, size distribution and degree of insolubilization and cross-linking of the wall-forming material allows novel microsphere preparations to be produced. In particular, the microspheres may be 15-20 .mu.m, targeted to selected areas of the body or of prolonged life in the circulation.

Abstract: The system described ultrasonically images a target with energy spreading transmissions. Generally, ultrasonic energy corresponding to a line focus is transmitted into a target at a fundamental center frequency. The target may or may not include contrast agents. In either case, echoes are received at a harmonic of the fundamental center frequency. Echoes are also received at the fundamental center frequency. The echoes received at the harmonic center frequency are efficiently compounding with the echoes received at the fundamental center frequency.

Abstract: Apparatus and methods are disclosed for the detection and imaging of ultrasonic harmonic contrast agents. The harmonic echo effect is detected through alternate polarity acquisition of harmonic contrast agent effects, which provides the benefits of suppressing the harmonic components of the transmitted signal while eliminating clutter.

Abstract: An ultrasonic imaging system uses first and second perpendicular arrays. The first array is operated at high power to selectively destroy contrast agent suspended in flowing blood in discrete regions. The second array is used to image the alternating bands of contrast agent depleted blood and contrast image containing blood in order to allow blood flow characteristics to be assessed.

Abstract: An ultrasonic imaging system uses first and second perpendicular arrays. The first array is operated at high power to selectively destroy contrast agent suspended in flowing blood in discrete regions. The second array is used to image the alternating bands of contrast agent depleted blood and contrast image containing blood in order to allow blood flow characteristics to be assessed.

Abstract: A wavefront compensation technique which approaches the performance of Inverse Filtering while demonstrating adequate stability and signal to noise ratio. The spectrum amplitude is compressed in combination with phase deaberration algorithms by compressing the amplitude distortion using an amplitude compression function, such as an Mth root function, which converges the amplitudes towards the ideal inverse filtering solution in conjunction with conventional phase deaberration algorithms. Wavefront compensation using the compressed amplitude distortion data in accordance with the invention provides substantial contrast improvement over conventional phase only deaberration algorithms. In experiments, the mainlobe diffraction shape has been restored down to a -30 dB level necessary for resolving small breast lesions.