Evaluation of blood flow in the cerebral microcirculation: analysis of the refill kinetics during ultrasound contrast agent infusion.

By means of harmonic imaging, it is possible to display brain perfusion qualitatively using ultrasound (US) contrast agent (UCA) bolus injection. With UCA continuous infusion reaching a steady state, mean microbubble velocity can be measured, analyzing the reappearance rate after microbubble destruction by US (refill kinetics). We performed an animal pilot study to investigate this new method for the assessment of brain perfusion. Using harmonic grey-scale imaging, five sedated male beagle dogs were investigated through the intact skull with increasing pulsing intervals (250 to 8000 ms) and three UCA infusion rates (0.5, 1.0 and 1.5 mL/min of Optison). Cerebral blood flow was increased by acetazolamide (30 mg/kg BW). Intensity vs. pulsing interval curves were analyzed using an exponential curve fit [I(t) = A(1-e(-beta t))] and parameters of the curve were compared. We found that increasing the pulsing interval above 4000 ms led to no further increase of echo enhancement for infusion rates. Mean beta values were not influenced by infusion rate (p = 0.25 and p = 0.55). Mean F values increased nonsignificantly with rising infusion rate (p = 0.25 and p = 0.86). Acetazolamide led to an increase of mean beta and F values (p = 0.18 and p = 0.025, respectively). It is possible to evaluate changes in brain perfusion through the intact skull by analyzing the UCA refill kinetics after US-induced microbubble destruction.

Harmonic imaging of the human brain. Visualization of brain perfusion with ultrasound.

BACKGROUND AND PURPOSE: Through harmonic gray-scale imaging, it is possible to analyze brain tissue perfusion with different ultrasound methods. METHODS: In 12 healthy volunteers, 2 doses (0.5 and 1.5 mL) of Optison, a perfluoropropane-containing contrast agent, were injected intravenously and produced a strong increase of brightness in the brain parenchyma. We used harmonic imaging for quantification of ultrasound intensity in the thalamus, ipsilateral temporoparietal white matter (TPWM), and ipsilateral lateral fissure at both sides. Time-intensity curves were calculated, and peak increase (PI) of intensity and the area under the time-intensity curve (AUC) from baseline were compared. RESULTS: We found a significant dose dependence of the AUC in all regions at both sides. PI only showed a significant dose dependence in the TPWM but not in the ipsilateral thalamus and lateral fissure. No side differences for AUC and PI were detected in all regions and doses used. We found a significantly higher value of the PI insonating the thalamus from the ipsilateral side compared with the contralateral side. The same result was obtained for the AUC in the left thalamus for both doses and in the right thalamus for the high dose. Using 0.5 mL for insonation of the right thalamus AUC again showed a higher value for the insonation from the ipsilateral compared with the contralateral side but failed to show statistical significance (P=0.08, n=12). CONCLUSIONS: Harmonic gray-scale imaging with Optison showed a strong enhancement effect in the brain parenchyma. A quantitative analysis of perfusion seems difficult because of the depth dependence of the effect. The most robust parameter is the AUC.

Transcranial harmonic power duplex sonography for the evaluation of cerebral arteries.

Harmonic power-based duplex sonography is a new ultrasound method that improves the signal-to-noise ratio of extracranial vascular imaging. The authors evaluated this new method for transtemporal imaging of the basal cerebral arteries. Fundamental power-based duplex sonography (p-TCCS) and harmonic power-based duplex sonography (HI-p-TCCS) in combination with a novel perfluoropropane-containing ultrasound contrast agent (Optison) were investigated for the evaluation of the basal cerebral arteries in 12 healthy volunteers. The number of identified vascular segments and the blood flow velocities in the middle and posterior cerebral arteries were determined for p-TCCS and for two doses of Optison (0.5 and 1.5 mL) using HI-p-TCCS. Furthermore, the authors determined the time course of signal enhancement after Optison bolus injections. The results were compared using Friedman two-way ANOVA test. Significantly more arterial segments were visualized using HI-p-TCCS with enhancement of either 0.5 mL or 1.5 mL Optison (p < 0.01, each) than using p-TCCS. The spatial resolution was markedly increased with HI-p-TCCS, resulting in a striking difference in the detection of distal arterial segments and cortical and parenchymal branches. Except for the diastolic blood flow velocities (BFVs) in the M1 segment, the BFVs did not differ significantly between p-TCCS and HI-p-TCCS. Comparing HI-p-TCCS with 0.5 mL and 1.5 mL Optison, the authors found a small but significant reduction of the latency period (18.2 vs. 15.9 seconds, respectively; p < 0.01), a significant increase of the blooming phase (62.7 vs. 99.8 seconds, respectively; p < 0.0006) and a significant prolongation of the diagnostically useful signal enhancement (233.7 vs. 427.6 seconds, respectively; p < 0.004).

The influence of Doppler system settings on the clearance kinetics of different ultrasound contrast agents.

OBJECTIVE: To evaluate the influence of different Doppler system settings on time-intensity curves after ultrasound contrast agent (UCA) bolus injection. This is important for the comparison of different UCAs. METHODS: Six sedated dogs were investigated with a transcranial Doppler system and Doppler power, sample volume size and high pass filter settings were modified during the procedure. Mean time intensity curves were determined and peak values of mean intensity as well as the decrease in Doppler intensity were compared for the different system settings. Three different UCAs were used (SonoVue(TM), BY963 and Levovist(TM)). RESULTS: The Doppler time intensity curves showed a typical two phase decrease with a distribution phase alpha and an elimination phase beta with all three UCAs. Altering the system settings had a significant effect on the mean peak Doppler intensity for SonoVue(TM) (P=0.02) but not for BY963 or Levovist(TM) (P=0.07 and P=0.39, respectively), due to high variation of the Levovist(TM) and BY963 intensity values. There were no significant differences between the alpha slopes of BY963 and Levovist(TM) (P=0.96), or the beta slope of Levovist(TM) and SonoVue(TM) (P=0.62), when the results of all system settings were combined. CONCLUSION: Different Doppler system settings show no significant influence on the decrease of mean Doppler intensity, but have a significant effect on peak intensity.

The influence of different gases on acoustic properties of a spherosome-based ultrasound contrast agent (BY963). A transcranial Dopplersonography study.

Ultrasound contrast agents improve the signal-to-noise ratio of reflected ultrasound, enhancing the diagnostic value of transcranial Doppler (TCD). In dog studies, we investigated the time course of TCD signal amplitude after application of a phospholipid-containing ultrasound contrast agent (BY963) filled with different gases. The median time of Doppler amplitude enhancement exceeding 5 dB was determined using isoflurane-, isopentane-, trichlortrifluoroethane-, air-, argon-, and perfluoropentane-filled BY963 (69, 72, 75, 78, 88, and 245 seconds respectively). The decrease of time-intensity curve and the duration of signal enhancement showed significant differences comparing the different gases (p = 0.04 and 0.03, respectively). The time course of in vitro stability of BY963 agitated with the different gases measured by absorbance of light (500 nm) showed a retarded decay for perfluoropentane, a rapid decrease for air, isopentane, trichlortrifluoroethane, and argon, and a very rapid decrease using isoflurane. The time course of the different gases depended on the physiochemical properties (lipophilicity and the solubility in water) of the gas encoated in the phospholipid shell. Perfluoropentane-filled BY963 showed the highest in vitro stability and the longest duration of TCD enhancement compared with the other gases used.