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The aim was to evaluate phase-inversion harmonic imaging (PIHI) with respect to brain perfusion imaging using a novel "bilateral approach" (depth of examination: 150 mm) and established unilateral approach (100 mm). After bolus injection of two contrast agents (CA, Optison and SonoVue), perfusion-related parameters (time-to-peak intensity, Itpk, peak intensity, Ipk, and peak width, Wpk) were extracted by fitting a model function to time-intensity curves for different regions-of-interest (ROI) in 14 volunteers. In 207 (92%) of 224 ipsilateral ROIs and in 165 (98%) of 168 contralateral ROIs (372 or 95% of 392 altogether), parameters could be derived. Itpk and Wpk of gray matter ROIs did not vary in or between both CA groups (18.1-21.9 s and 7.9-14.2 s). ROIs within arteries showed significantly shorter Itpk (16.1-16.7 s) and longer Wpk (12.8-28.3 s). Level of significance was 0.05 (two-sided). Newer CAs are usable for nonlinear imaging over a wider range of acoustic intensities, so that sensitivity of PIHI is sufficient to image the brain bilaterally. This approach proves to be reliable in patients with adequate bone windows. For acute stroke patients, this implies that both hemispheres can be compared in one instead of two examinations, reducing time of examination by 50%. Furthermore, evaluation of regions close to the probe becomes possible. Thus, the "bilateral approach" should be considered as a new standard approach of acute ultrasonic perfusion imaging.

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.

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 M(2) 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.