Wilko Wilkening

Contrast agent specific imaging modes for the ultrasonic assessment of parenchymal cerebral echo contrast enhancement.

Previous work has demonstrated that cerebral echo contrast enhancement can be assessed by means of transcranial ultrasound using transient response second harmonic imaging (HI). The current study was designed to explore possible advantages of two new contrast agent specific imaging modes, contrast burst imaging (CBI) and time variance imaging (TVI), that are based on the detection of destruction or splitting of microbubbles caused by ultrasound in comparison with contrast harmonic imaging (CHI), which is a broadband phase-inversion—based implementation of HI. Nine healthy individuals with adequate acoustic temporal bone windows were included in the study. Contrast harmonic imaging, CBI, and TVI examinations were performed in an axial diencephalic plane of section after an intravenous bolus injection of 4 g galactose-based microbubble suspension in a concentration of 400 mg/mL. Using time-intensity curves, peak intensities and times-to peak-intensity (TPIs) were calculated off-line in anterior and posterior parts of the thalamus, in the region of the lentiform nucleus, and in the white matter. The potential of the different techniques to visualize cerebral contrast enhancement in different brain areas was compared. All techniques produced accurate cerebral contrast enhancement in the majority of investigated brain areas. Contrast harmonic imaging visualized signal increase in 28 of 36 regions of interest (ROIs). In comparison, TVI and CBI examinations were successful in 32 and 35 investigations, respectively. In CHI examinations, contrast enhancement was most difficult to visualize in posterior parts of the thalamus (6 of 9) and the lentiform nucleus (6 of 9). In TVI examinations, anterior parts of the thalamus showed signal increase in only 6 of 9 examinations. For all investigated imaging modes, PIs and TPIs in different ROIs did not differ significantly, except that TVI demonstrated significantly higher PIs in the lentiform nucleus as compared with the thalamus and the white matter (P < 0.05). The current study demonstrates for the first time that CBI and TVI represent new ultrasonic tools that allow noninvasive assessment of focal cerebral contrast enhancement and that CBI and TVI improve diagnostic sensitivity as compared with CHI.

Contrast Burst Depletion Imaging (CODIM) A New Imaging Procedure and Analysis Method for Semiquantitative Ultrasonic Perfusion Imaging

Background and Purpose— Established methods of ultrasonic perfusion imaging using a bolus application of echo contrast agent provide only qualitative data because of various physical phenomena. This study was intended to investigate whether a new ultrasound perfusion imaging method termed contrast burst depletion imaging (CODIM) may provide semiquantitative measures of parenchymal perfusion independent of examination depth and acoustic energy distribution. Methods— In a system with a constant concentration of contrast agent, analyzing the decrease in image intensity that occurs with microbubble-destructive imaging modes yields parameters that are considered to correlate with tissue perfusion. This method was first evaluated with a perfusion model that showed that the main resulting parameter “perfusion coefficient” (PC) is a monotonic nonlinear function of flow velocity. Seventeen human volunteers were then scanned according to this method with the use of 2 different contrast agents. Results were correlated with those from perfusion-weighted MRI examinations. Results— The PC did not show significant differences in gray matter areas (ranging from 1.466×10−2 s−1 to 1.641×10−2 s−1) of the brain despite different insonation depths (eg, ipsilateral and contralateral thalamus). In contrast, white matter exhibited significantly lower perfusion values in both imaging modes (PC: 0.604×10−2 s−1 to 0.745×10−2 s−1;P <0.05). Conclusions— CODIM is a promising new tool of imaging parenchymal (brain) perfusion in healthy persons. The method provides semiquantitative and depth-independent perfusion parameters and in this way overcomes the limitations of the perfusion methods using a bolus kinetic. Further investigations must be done to evaluate the potential of the method in patients with perfusion deficits.

Comparison Between Echo Contrast Agent-Specific Imaging Modes and Perfusion-Weighted Magnetic Resonance Imaging for the Assessment of Brain Perfusion

Background and Purpose— Contrast burst imaging (CBI) and time variance imaging (TVI) are new ultrasonic imaging modes enabling the visualization of intravenously injected echo contrast agents in brain parenchyma. The aim of this study was to compare the quantitative ultrasonic data with corresponding perfusion-weighted MRI data (p-MRI) with respect to the assessment of brain perfusion. Methods— Twelve individuals with no vascular abnormalities were examined by CBI and TVI after an intravenous bolus injection of 4 g galactose-based microbubble suspension (Levovist) in a concentration of 400 mg/mL. Complementary, a dynamic susceptibility contrast MRI, ie, p-MRI, of each individual was obtained. In both ultrasound (US) methods and p-MRI, time-intensity curves were calculated offline, and absolute time to peak intensities (TPI), peak intensities (PI), and peak width (PW) of US investigations and TPI, relative cerebral blood flow (CBF) and relative cerebral blood volume (CBV) of p-MRI examinations were determined in the following regions of interest (ROIs): lentiform nucleus (LN), white matter (WM), posterior (PT), and anterior thalamus (AT). In addition, the M2 segment of the middle cerebral artery (MCA) was evaluated in the US, and the precentral gyrus (PG) was examined in the p-MRI examinations. In relation to a reference parenchymal ROI (AT), relative TPIs were compared between the US and p-MRI methods and relative PI of US investigations with the ratio of CBF (rCBF) of p-MRI examinations in identical ROIs. Results— Mean TPIs varied from 18.3±5.0 (AT) to 20.1± 5.8 (WM) to 17.2±4.9 (MCA) seconds in CBI examinations and from 19.4±5.3 (AT) to 20.4±4.3 (WM) to 17.3±4.0 (MCA) seconds in TVI examinations. Mean PIs were found to vary from 581.9±342.4 (WM) to 1522.9±574.2 (LN) to 3400.9± 621.7 arbitrary units (MCA) in CBI mode and from 7.5±4.6 (WM) to 17.5±4.9 (LN) to 46.3±7.1 (MCA) arbitrary units in TVI mode. PW ranged from 7.3±4.5 (AT) to 9.1±4.0 (LN) to 24.3±12.8 (MCA) seconds in CBI examinations and from 7.1±3.9 (AT) to 8.7±3.5 (LN) to 26.7±18.2 (MCA) seconds in TVI examinations. Mean TPI was significantly shorter and mean PI and mean PW were significantly higher in the MCA compared with all other ROIs (P <0.05). Mean TPI of the p-MRI examinations ranged from 22.0±6.9 (LN) to 23.0±6.8 (WM) seconds; mean CBF ranged from 0.0093± 0.0041 (LN) to 0.0043±0.0021 (WM). There was no significant difference in rTPI in any ROI between US and p-MRI measurements (P >0.2), whereas relative PIs were significantly higher in areas with lower insonation depth such as the LN compared with rCBF. Conclusions— In contrast to PI, TPI and rTPI in US techniques are robust parameters for the evaluation of cerebral perfusion and may help to differentiate physiological and pathological perfusion in different parenchymal regions of the brain.

Brain perfusion and ultrasonic imaging techniques.

Advances in neurosonology have generated several techniques of ultrasonic perfusion imaging employing ultrasound echo contrast agents (ECAs). Doppler imaging techniques cannot measure the low flow velocities that are associated with parenchymal perfusion. Ultrasonic perfusion imaging, therefore, is a combination of a contrast agent-specific ultrasound imaging technique (CAI) mode and a data acquisition and processing (DAP) technique that is suited to observe and evaluate the perfusion kinetics. The intensity in CAI images is a measure of ECA concentration but also depends on various other parameters, e.g. depth of examination. Moreover, ECAs can be destroyed by ultrasound, which is an artifact but can also be a feature. Thus, many different DAPs have been developed for certain CAI techniques, ECAs and target organs. Although substantial progress in ECA and CAI technology can be foreseen, ultrasound contrast imaging has yet to reliably differentiate between normal and pathological perfusion conditions. Destructive imaging techniques, such as contrast burst imaging (CBI) or time variance imaging (TVI), in combination with new DAP techniques provide sufficient signal-to-noise ratio (SNR) for transcranial applications, and consider contrast agent kinetics and destruction to eliminate depth dependency and to calculate semi-quantitative parameters. Since ultrasound machines are widely accessible and cost-effective, ultrasonic perfusion imaging techniques should become supplementary standard perfusion imaging techniques in acute stroke diagnosis and monitoring. This paper gives an overview on different CAI and DAP techniques with special focus on recent innovations and their clinical potential.

Transcranial Ultrasound Brain Perfusion Assessment With a Contrast Agent-Specific Imaging Mode Results of a Two-Center Trial

Background and Purpose— The purpose of this study was to assess brain perfusion with an ultrasound contrast-specific imaging mode and to prove if the results are comparable between 2 centers using a standardized study protocol. Methods— A total of 32 individuals without known cerebrovascular disease were included in the study. Perfusion studies were performed ipsilaterally in an axial diencephalic plane after intravenous administration of 0.75 mL of Optison. Offline time intensity curves (TIC) were generated in different anatomic regions. Both centers used identical study protocols, ultrasound machines, and contrast agent. Results— In both centers, the comparison of the parameter time to peak intensity (TPI) revealed significantly shorter TPIs in the main vessel structures compared with any parenchymal region of interest (ROI), whereas no significant differences were seen between the parenchymal ROIs. The parameter peak intensity (PI) varied widely interindividually in both centers, whereas the inter-ROI comparison revealed statistical significance (P<0.05) in most of the cases according to the following pattern: (1) lentiforme nucleus > thalamus and white matter region, (2) thalamus > white matter region, and (3) main vessel > any parenchymal structure. Similar results were achieved in both centers independently. Conclusion— The study demonstrates that brain perfusion assessment with an ultrasound contrast-specific imaging mode is comparable between different centers using the same study protocol.

Experimental evaluation of photoacoustic coded excitation using unipolar golay codes

Q-switched Nd:YAG lasers are commonly used as light sources for photoacoustic imaging. However, laser diodes are attractive as an alternative to Nd:YAG lasers because they are less expensive and more compact. Although laser diodes deliver about three orders of magnitude less light pulse energy than Nd:YAG lasers (tens of microjoules compared with tens of millijoules), their pulse repetition frequency (PRF) is four to five orders of magnitude higher (up to 1 MHz compared with tens of hertz); this enables the use of averaging to improve SNR without compromising the image acquisition rate. In photoacoustic imaging, the PRF is limited by the maximum acoustic time-of-flight. This limit can be overcome by using coded excitation schemes in which the coding eliminates ambiguities between echoes induced by subsequent pulses. To evaluate the benefits of photoacoustic coded excitation (PACE), the performance of unipolar Golay codes is investigated analytically and validated experimentally. PACE imaging of a copper slab using laser diodes at a PRF of 1 MHz and a modified clinical ultrasound scanner is successfully demonstrated. Considering laser safety regulations and taking into account a comparison between a laser diode system and Nd:YAG systems with respect to SNR, we conclude that PACE is feasible for small animal imaging.

Ultrasonic assessment of perfusion conditions in the brain and in the liver

The assessment of perfusion conditions is of great importance for e.g. the diagnosis of ischemic lesions in the brain of stroke patients or of tumors in the liver. Contrast agents in combination with contrast specific imaging techniques offer the chance to visualize perfusion conditions based on an evaluation of time-intensity curves (TICs), where these curves reflect the concentration of microbubbles in the blood pool, the perfusion rate, and the destruction of microbubbles by ultrasound. For two very different applications, namely perfusion imaging in the brain and in abdominal organs, we have developed perfusion imaging strategies. They differ in terms of the contrast agent imaging technique, the administration of the agent, and the data processing.

Phase-coded pulse sequence for non-linear imaging

Nonlinear imaging modes are of great interest for perfusion imaging with contrast agents and for tissue harmonic imaging, i.e. a technique that provides improved spatial and contrast resolution. For both applications, many tradeoffs have to be made concerning transmit power, imaging depth, resolution, frame rate etc. because of the non-linear nature of the effects used for imaging. Time domain and spatial domain phase inversion (pulse inversion) techniques have been successfully introduced. Longer pulse sequences in combination with phase inversion allow for lower acoustic peak intensities or higher penetration depth. However, phase inversion eliminates all spectral components that are related to odd order non-linearities. We propose a phase-coded 5-pulse sequence that overcomes this limitation while providing the desired increase in SNR.

Spatial compounding with tissue harmonic images and monostatic synthetic aperture reconstruction

A high precision mechanical add-on module was realized to implement a transmission tomography system around a commercial analog ultrasound system. The modular nature of the add-on lets it be used, however, more universally. Without enormous effort the module could be programmed to be coupled to a fully digital high end commercial ultrasound system. A Siemens Antares was used for this work, which allows the acquisition of RF data of high quality B-scans and tissue harmonic imaging (THI) over the Axius Direct Ultrasound Research Interface (URI). This possibility was exploited to explore some more intricate processing options for image compounding in addition to the conventional spatial compounding approach. Several compounding schemes were implemented. One of the two new strategies for compounding consists of calculation of a compound image from the THI data, as the latter is known to possess a better contrast and lateral resolution. While the RF data acquired from various transducer positions provides all the essential input for monostatic synthetic aperture focusing (SAFT), the other strategy was to implement SAFT imaging. The effect of inhomogeneous speed of sound was studies carefully and two different schemes were implemented to overcome the problems of image registration arising from it. The algorithms were tested on polypropylene fiber phantoms in water and ethylene glycol. While the monostatic synthetic aperture reconstruction technique was found to be best in enhancing signal to noise ratio, the speckle reduction was notably better for the THI compounding scheme than that of the conventional compounding strategy. The resulting spatial resolution of the compound images was comparable for the latter two cases and the former technique outperformed the other ones in this respect.

Validation of the depletion kinetic in semiquantitative ultrasonographic cerebral perfusion imaging using 2 different techniques of data acquisition

Objective.To validate the potential of ultrasonographic depletion imaging for semiquantitatively visualizing cerebral parenchymal perfusion with contrast burst depletion imaging (CODIM) in comparison with phase inversion harmonic depletion imaging (PIDIM) in healthy volunteers. Methods.Thirteen healthy adults were examined with both CODIM and PIDIM in accordance with previously described criteria. In addition to the perfusion coefficient, the time to decrease image intensity to 10% above equilibrium intensity from the initial value and the relative error (deviation of measured data from the fitted model) were evaluated to compare the reliability of both techniques in 3 different regions of interest. Results.Perfusion coefficient values did not show significantly differing values in both groups (1.57–1.64 • 10−2 s−1 for CODIM and 1.42–1.58 • 10−2 s−1 for PIDIM). The relative error was significantly smaller in the PIDIM group (0.38–0.53 for CODIM and 0.18–0.25 for PIDIM; P < .002). Conclusions. Phase inversion harmonic depletion imaging proved to be more reliable than CODIM because values of the relative error were significantly lower in PIDIM even in this relatively small cohort. This is of interest because the underlying technique, phase inversion harmonic imaging, is more widely available than contrast burst imaging.