M.E. Frijlink

Brandaris 128: A digital 25 million frames per second camera with 128 highly sensitive frames

A high-speed camera that combines a customized rotating mirror camera frame with charge coupled device (CCD) image detectors and is practically fully operated by computer control was constructed. High sensitivity CCDs are used so that image intensifiers, which would degrade image quality, are not necessary. Customized electronics and instruments were used to improve the flexibility and control precisely the image acquisition process. A full sequence of 128 consecutive image frames with 500×292 pixels each can be acquired at a maximum frame rate of 25 million frames/s. Full sequences can be repeated every 20 ms, and six full sequences can be stored on the in-camera memory buffer. A high-speed communication link to a computer allows each full sequence of about 20 Mbytes to be stored on a hard disk in less than 1 s. The sensitivity of the camera has an equivalent International Standards Organization number of 2500. Resolution was measured to be 36 lp/mm on the detector plane of the camera, while under a microscope a bar pattern of 400 nm spacing line pairs could be resolved. Some high-speed events recorded with this camera, dubbed Brandaris 128, are presented.

Contrast harmonic intravascular ultrasound: A feasibility study for vasa vasorum imaging

Objective:We sought to investigate feasibility of vasa vasorum imaging using the novel technique of contrast harmonic intravascular ultrasound. Methods:Prototype intravascular ultrasound (IVUS) instrumentation was developed for the sensitive detection of microbubble contrast agents. The technique, “harmonic” imaging, involves transmitting ultrasound at 20 MHz (fundamental) and detecting contrast signals at 40 MHz (second harmonic). Phantom experiments were conducted to investigate the detection of a small vessel in the wall surrounding a larger vessel. In vivo experiments were conducted in atherosclerotic rabbit abdominal aortas. Results:The phantom experiments showed improved small vessel detection in harmonic mode relative to fundamental mode. For the in vivo experiments, harmonic imaging enabled the visualization of contrast agent outside the aortic lumen through a statistically significant (P < 0.001) enhancement of image power, consistent with the detection of adventitial microvessels. These microvessels were not detected in fundamental imaging mode. Conclusions:These results indicate the feasibility of contrast harmonic intravascular ultrasound as a new technique for vasa vasorum imaging.

Intravascular ultrasound tissue harmonic imaging in vivo

The feasibility of tissue harmonic imaging with a prototype intravascular ultrasound (IVUS) system using a conventional single-element rotating IVUS catheter was investigated. Hydrophone measurements showed fundamental peak pressures of 1.9 MPa on-axis of such a catheter in water. The second harmonic signal at 40 MHz built up to 0.55 MPa, corresponding to 11 dB below the peak fundamental pressure. Experiments performed in a tissue-mimicking phantom and in a rabbit aorta in vivo showed the feasibility of tissue harmonic imaging with a conventional IVUS catheter. When we applied averaging of four neighboring RF-lines in the in vivo acquisition, the signal-to-noise ratio of the harmonic image increased to 25 dB.

Vasa vasorum and molecular imaging of atherosclerotic plaques using nonlinear contrast intravascular ultrasound

There is increasing evidence that presence and location of neovascular vasa vasorum play an important role in atherosclerotic plaque pathogenesis and stability. This paper describes a method to detect vasa vasorum with high contrast and high spatial resolution. It uses second harmonic or subharmonic intravascular ultrasound, in combination with ultrasound contrast agents. The same technology in combination with targeted contrast agents is suited for molecular imaging. The potential for vasa vasorum imaging is illustrated using an atherosclerotic animal model and the potential for molecular imaging is illustrated using phantom experiments.

High frequency nonlinear scattering and imaging of a submicron contrast agent

We investigate high frequency nonlinear scattering and imaging of a contrast agent comprised of submicron bubbles. Agent characterization experiments conducted at 20 and 30 MHz transmit frequencies with a broadband PVDF transducer confirm the production of substantial amounts of energy in the subharmonic and second harmonic regions. Nonlinear contrast imaging with intravascular ultrasound (IVUS) is then explored with a prototype mechanically scanned system. Pulse-inversion techniques were employed with a 20 MHz transmit frequency (F20) for second harmonic imaging (H40), and with a 40 MHz transmit frequency (F40) for subharmonic imaging (SH20). H40 was found to produce improvements in contrast-to-tissue signal ratios (CTR) for low transmit amplitudes (<0.3 MPa). SH20 was demonstrated at a range of pressures (0.2 to 2.2 MPa). These results show the feasibility of using a submicron agent for high frequency (>15 MHz) nonlinear contrast imaging and suggest the potential application of these techniques in IVUS.

A simulation study on tissue harmonic imaging with a single-element intravascular ultrasound catheter

Recently, in vivo feasibility of tissue harmonic imaging with a mechanically rotated intravascular ultrasound (IVUS) catheter was experimentally demonstrated. To isolate the second harmonic signal content, a combination of pulse inversion and analog filtering was used. In this paper the development of a simulation tool to investigate nonlinear IVUS beams is reported, and the influence of transducer rotation and axial catheter-to-tissue motion on the efficiency of PI signal processing is evaluated. Nonlinear beams were simulated in homogeneous tissue-mimicking media at a transmit frequency of 20 MHz, which resulted in second harmonic pressure fields at 40 MHz. The competing effects of averaging and decorrelation between neighboring rf lines on the signal-to-noise ratio (SNR) were studied for a single point scatterer. An optimal SNR was achieved when lines were combined over 3 degrees - 3.75 degrees. When the transducer was rotated with respect to point scatterers, simulating the acoustic response of tissue, the fundamental frequency suppression using PI degraded rapidly with increasing interpulse angles. The effect of axial catheter-to-tissue motion on the efficiency of pulse inversion seemed to be of less influence for realistic motion values. The results of this study will aid in the optimization of harmonic IVUS imaging systems.

Nonlinear imaging of targeted microbubbles with intravascular ultrasound

The nonlinear detection of targeted microbubbles at high ultrasound frequencies was investigated. A prototype nonlinear intravascular ultrasound (IVUS) system was employed using a 20 MHz fundamental frequency (F20) to examine 40 MHz second harmonic (H40) signals and a 40 MHz fundamental frequency (F40) to examine 20 MHz subharmonic (SH20) signals. An experimental biotinated micron to submicron lipid encapsulated agent was targeted to avidin coated agar-based tissue mimicking phantoms. An examination of bound bubble acoustic signatures demonstrated the feasibility of initiating H40 and SH20 signals. Imaging experiments showed improvements in contrast-to-tissue ratios (CTR) using both H40 and SH20 relative to fundamental frequency imaging. These results indicate the potential of high frequency nonlinear imaging as a means of improving the detection of targeted microbubbles.

A 20-40 MHz ultrasound transducer for intravascular harmonic imaging

Recent studies have suggested the feasibility of tissue harmonic imaging (THI) with intravascular ultrasound (IVUS). This paper describes the design, fabrication and characterization of a piezoelectric transducer optimized for tissue harmonic IVUS. Ideally, such a transducer should efficiently transmit a short acoustic pulse at the fundamental transmission frequency and should be sensitive to its second harmonic echo, for which we have chosen 20 MHz and 40 MHz, respectively. The intravascular application limits the transducer dimensions to 0.75 mm by 1 mm. The transducer comprises of a single piezoelectric layer design with additional passive layers for tuning and efficiency improvement, and the Krimholtz-Leedom-Matthaei (KLM) model was used to find iteratively optimal material properties of the different layers. Based on the optimized design a prototype of the transducer was built. The transducer was characterized by water-tank hydrophone measurements and pulse-echo measurements. These measurements showed the transducer to have two frequency bands around 20 MHz and 40 MHz with -6dB fractional bandwidths of 30% and 25%, and round-trip insertion losses of -19 dB and -34 dB, respectively.

Pulse inversion sequences for mechanically scanned transducers

Mechanically scanned transducers are currently used for tissue harmonic imaging (THI) and nonlinear microbubble imaging at high frequencies. The pulse inversion (PI) technique is widely used for suppressing the fundamental signal, but its effectiveness is reduced by relative tissue/ transducer motion. In this paper, we investigate multipulse inversion (MPI) sequences that achieve a significant improvement on the fundamental suppression for mechanically scanned single-element transducers. MPI was subsequently applied on simulated and measured RF-data and relative fundamental suppression was compared with the 2-pulse PI technique. Simulations showed, for example, an increased fundamental suppression of 6 and 10 dB for MPI-sequences that combined 3 and 7 pulses, respectively, for a rotating intravascular ultrasound transducer with an interpulse angle of 0.15deg. Initial application of MPI sequences on RF-data from in vivo acquisitions resulted in similar fundamental suppression levels. The investigated MPI technique will help to reduce relative tissue/transducer motion effects and might lead to improved sensitivity and spatial resolution in nonlinear tissue imaging and improved microbubble detection in contrast imaging for mechanically scanned transducers.

High frequency harmonic imaging in presence of intravascular stents

High frequency second harmonic imaging was compared with fundamental imaging when highly reflective stents were present in the near field of a spherically focused PVDF transducer. Hydrophone measurements of the harmonic beam at 40 MHz showed a relative lower signal strength in the near field compared to the fundamental modes at 20 and 40 MHz. The beam width (-3dB) of the fundamental 40 MHz and the harmonic 40 MHz, measured in the focal plane were both 80 microns. It was found that harmonic 40 MHz imaging mode suppressed reverberations from the stent by up to 14 dB compared to fundamental 20 MHz imaging.