Diagnosis of intracerebral hemorrhage with transcranial ultrasound.

In acute stroke, different sonographic methods can be used to assess structural and hemodynamic compromise. Structural abnormalities of brain parenchyma such as primary intracerebral hemorrhage (ICH) and epiphenomena such as midline shift can be detected by native transcranial B-mode ultrasound. Moreover, transcranial Doppler provides a functional approach to intracranial hemodynamics and may assist in predicting ICH growth and global intracranial pressure increase. New ultrasound technologies allow the visualization of ultrasound contrast agents in the cerebral microcirculation. According to recent data, ultrasound perfusion imaging provides additional information for the diagnosis of ICH and may differentiate ischemic from hemorrhagic stroke. This review summarizes the impact of these different transcranial ultrasound methods on diagnosis and monitoring of ICH.

Detecting stripe artifacts in ultrasound images.

Brain perfusion diseases such as acute ischemic stroke are detectable through computed tomography (CT)-/magnetic resonance imaging (MRI)-based methods. An alternative approach makes use of ultrasound imaging. In this low-cost bedside method, noise and artifacts degrade the imaging process. Especially stripe artifacts show a similar signal behavior compared to acute stroke or brain perfusion diseases. This document describes how stripe artifacts can be detected and eliminated in ultrasound images obtained through harmonic imaging (HI). On the basis of this new method, both proper identification of areas with critically reduced brain tissue perfusion and classification between brain perfusion defects and ultrasound stripe artifacts are made possible.

Sonographic evaluation of hemorrhagic transformation and arterial recanalization in acute hemispheric ischemic stroke.

BACKGROUND AND PURPOSE: We conducted this prospective study to evaluate the time course of hemorrhagic transformation (HT) and arterial recanalization in the early phase of ischemic stroke using transcranial sonography (TCS). METHODS: Fifty-five patients with acute ischemic hemispheric stroke <32 hours after symptom onset were studied. A 2-MHz sector probe was used to evaluate brain tissue by TCS and basal cerebral arteries by transcranial color-coded sonography. Follow-up investigations were performed up to 6 days. Lesion size and localization were determined by cranial computed tomography. RESULTS: Of 20 patients with HT, 18 displayed by computed tomography could be identified by TCS. In 1 patient, TCS provided a wrong positive result, and in another 2 patients with small cortical HT, a wrong negative result was provided (sensitivity 90.0%, specificity 97.4%). HT was detected in the first 60 hours after symptom onset in 62.5% of patients treated with tissue plasminogen activator in comparison to 33.3% without thrombolysis. Recanalization of middle cerebral artery occurred earlier in tissue plasminogen activator-treated patients compared to those without tissue plasminogen activator treatment (in the first 60 hours after symptom onset: 78.5% vs 50.0%, respectively; P=0.34). There was a significant time difference between middle cerebral artery recanalization and HT occurrence (n=13, median time interval: 20 vs 60 hours; P=0.035). CONCLUSIONS: Transcranial ultrasound is a useful bedside method to depict and closely monitor HT in patients with acute hemispheric stroke. The strong influence of tissue plasminogen activator treatment on HT could be demonstrated. HT development is dependent on the time of artery recanalization.

Improved modelling of ultrasound contrast agent diminution for blood perfusion analysis.

Ultrasound contrast imaging is increasingly used to analyze blood perfusion in cases of ischemic or cancerous diseases. Among other imaging methods, the diminution harmonic imaging (DHI), which modells the diminution of contrast agent due to ultrasound pulses, is the most promising because of its speed. However, the current imaging quality of DHI is insufficient for reliable diagnoses. In this paper, we extend the mathematical DHI model to include the part of the intensity signal which is due to tissue reflections and other effects not based on the contrast agent and its concentration in the blood. We show in a phantom experiment with available perfusion ground truth the vast improvements in accuracy of the new model. Our findings also strongly support the theory of a linear relationship between the perfusion speed and the determined perfusion coefficient, which is a large step towards quantitative perfusion measurements.

Ultrasound cerebral perfusion analysis based on a mathematical model for diminution harmonic imaging.

OBJECTIVES: Cerebral vascular diseases are detect- able by CT/MRI-based methods. Drawbacks of these methods are that they are expensive, time-consuming and intolerable to critically ill patients. Ultrasound, as an inexpensive bedside method, promises to become an alternative. Among other harmonic imaging methods, the diminution harmonic imaging (DHI) method is known, which determines perfusion-related parameters by analyzing ultrasound contrast agent (UCA) diminution kinetics based on constant UCA infusion. The shortcoming of DHI is that the used mathematical model can only determine these parameters by least squares fitting the model onto the data. METHODS: In this work, the underlying mathematical model is further developed such that it becomes possible to directly calculate the parameters from the image data. Furthermore, the new model offers an improved way to estimate the spatial distribution of the destruction coefficient necessary for accurately determining the destruction power of the ultrasound pulse on the contrast agent. RESULTS: The direct calculation of the perfusion coefficient is much faster than the former fitting of the model. Perfusion as well as destruction coefficients are displayed as color-coded images. In an example, a region with perfusion deficits (as shown in a MR image of the same patient) is clearly identifiable. CONCLUSIONS: Displaying the parameters as color-coded images facilitates result interpretation for the diagnosing physician. The results are preliminary and still have to be validated, but they suggest that the new DHI model improves the significance of ultrasound as a diagnostic help.

Ultrasound perfusion imaging: determination of thresholds for the identification of critically disturbed perfusion in acute ischemic stroke--a pilot study.

Ultrasound harmonic imaging of perfusion after ultrasound contrast agent (UCA) bolus injection (BHI) can detect cerebral perfusion deficits. In a pilot study, we evaluated the ability of time-intensity curve (TIC) measurements to differentiate between normal and hypoperfused brain areas in acute ischemic stroke. Ten patients with symptoms of acute middle cerebral artery infarction were investigated (SONOS 5500, Harmonic Imaging 1.6/3.8 MHz, diencephalic plane, 10 cm investigation depth, SonoVue 2.4 mL bolus). Peak signal increase (PSI), time-to-peak intensity (TPI) and area under the curve (AUC) were calculated for 60 regions-of-interest (ROIs) in each patient. Reference methods: Perfusion- and diffusion-weighted MRI (PWI/DWI) within 4 h before/after BHI (PWI threshold: 4 s). Receiver operating characteristics (ROC) analysis defined cut-off values for each TIC variable to distinguish between normal and affected brain areas as defined by PWI/DWI. In five patients, PWI showed a perfusion delay >4 s; seven patients had a DWI lesion. In three patients, both PWI and DWI findings showed pathology; one patient had a normal MRI of the insonation plane. Cut-off values for PWI delay: PSI: 5.53% (sensitivity .98, specificity .89); TPI: 4.04 s (sensitivity .74, specificity .69) and AUC: .63 (sensitivity .94, specificity .58). Referred to the mean value in unaffected brain areas the relative thresholds were 17.6%, 109.5% and 16.1%, respectively. Regarding DWI, only for PSI, a significant cut-off value was defined: 10.86%, sensitivity .84, specificity .60 (34.6% of mean). In conclusion, these thresholds distinguish between normal and affected brain areas in acute ischemic stroke.

Acute stroke: perfusion imaging.

Ultrasound perfusion imaging of the human brain is a bedside technique based on the detection of ultrasound contrast agent (UCA) in the cerebral microcirculation. In the last decade, ultrasound technology improved from single-pulse harmonic imaging to multiple-pulse technologies (pulse inversion or power modulation harmonic imaging as well as contrast pulse sequencing), with a further dramatic increase of the contrast-agent-to-tissue ratio. Different kinetic models for the qualitative assessment of brain perfusion have been evaluated so far in healthy subjects as well as in patients suffering from acute ischemic stroke. The analysis of the contrast bolus kinetics yields robust time-intensity curve parameters, which qualitatively describe regional brain perfusion. In the acute phase of ischemic stroke, the peak signal increase and the time-to-peak intensity are the most valuable curve parameters to predict the area of definite infarction and the outcome of the patient. Color-coded parametric imaging of these parameters facilitates the interpretation of contrast kinetics in analyzing brain perfusion. UCA-specific kinetic models, such as replenishment and diminution kinetics, are new modalities for the qualitative visualization of brain perfusion. The latter is more promising for acute ischemic stroke patients because of the faster imaging and processing time, leading to a lower vulnerability to movement artifacts.

Transcranial sonographic monitoring of hemorrhagic transformation in patients with acute middle cerebral artery infarction.

BACKGROUND AND PURPOSE: Previous studies indicate the potential of transcranial sonography (TCS) to detect cerebrovascular disease. The authors conducted this patient study to evaluate the diagnostic potential of gray-scale TCS in depicting hemorrhagic transformation (HT) in the early phase of middle cerebral artery infarction. METHODS: TCS was performed in 32 patients with acute ischemic stroke in the middle cerebral artery territory less than 12, 24 +/- 4, 72 +/- 6, and 120 +/- 12 hours after symptom onset (SONOS 5500, S4 probe, 16 cm investigation depth). Hemorrhagic transformation was identified as hyperechogenicity in the MCA territory, and the echogenicity of these areas was assessed. In addition, the dislocation of the third ventricle (midline shift, MLS) was assessed by TCS. Size and localization of infarction were determined by cranial computed tomography (CCT). RESULTS: In 10 of 11 patients, TCS detected HT as confirmed by CCT. In 1 patient, TCS provided a false-positive result. In another patient, TCS was unable to detect the hemorrhage (sensitivity, 91%; specificity, 95%). The echointensity of HT increased over time. MLS measurement failed to predict fatal outcome in 1 patient. CONCLUSIONS: TCS is a promising tool for depicting HT in patients with acute hemispheric stroke and might be suitable for monitoring purposes.

Ultrasound contrast agents for brain perfusion imaging and ischemic stroke therapy.

Stroke is one of the major causes of death and disabilities in industrialized countries. Ultrasound imaging is a largely wide spread bedside technique that is easily accessible and valuable in case of emergency but suffers from the fact that the ultrasound wave has to cross the skull for brain imaging. However, ultrasound contrast agents and new contrast-specific imaging modalities have helped to improve the diagnostic quality of transcranial ultrasonography. This review article surveys and discusses the current state of microbubbles technology and the use of contrast-enhanced transcranial ultrasound for the assessment of brain perfusion. Future aspects and expectations in contrast agent functionality, such as targeting and drug or gene delivery, acceleration of thrombolysis, and imaging technology, are also discussed.

Comparison of different mathematical models to analyze diminution kinetics of ultrasound contrast enhancement in a flow phantom.

Ultrasound (US) energy leads to intensity- and frequency-dependent destruction of US contrast agent (UCA) microbubbles. When applying repeated US pulses, this phenomenon can be detected as contrast diminution over time. Contrast diminution kinetics depend on the replenishment of UCA into the sample volume. Thus, it is related to organ perfusion. To analyze the contrast diminution kinetics following pulsed harmonic US application (SONOS 5500, 1.8-3.6 MHz, MI: 1.6, frame rates: 2, 4, and 6.67 Hz), we performed an in vitro study using SonoVue continuous infusion. Seven flow rates (4.5, 9, 13.5, 18, 22.5, 27 and 36 mL/min) were tested. Based on our results, three mathematical models (linear intensity decrease, exponential decay, and an exponential destruction/reperfusion model) describing diminution kinetics were compared. In 113 (89.7%) of 126 trials, a signal decrease was observed after US application. At higher flow rates (18 to 36 mL/min), curve fitting was not possible for the exponential models. For the linear model, intensity decrease depended significantly on the flow rate (p < or = 0.005, n = 7). A logistic model was fitted to the data, defining the slope in the dynamic range of quasilinear dependence for the different frame rates, as well as the inflection point: The higher the frame rate, the higher the flow rate at the point of inflection. For the exponential model, the contrast half-life was dependent on the flow rate (r = 0.95, p = 0.03, n = 6) only at the highest frame rate (6.67 Hz). The perfusion coefficient derived from the destruction/reperfusion model was not significantly related to the flow rate. In conclusion, the linear intensity decrease correlates well with the flow rate (i.e., flow velocity) and defines optimum frame rates for diminution imaging at different flow velocities. The exponential models, which required curve-fitting procedures, were determined to be inappropriate to describe flow in our phantom.

Ultrasound perfusion imaging in acute middle cerebral artery infarction predicts outcome.

BACKGROUND AND PURPOSE: Initial reports indicate that transcranial harmonic imaging after ultrasound contrast agent bolus injection (BHI) can detect cerebral perfusion deficits in acute ischemic stroke. We evaluated parametric images of the bolus washout kinetics. METHODS: Twenty-three patients with acute internal carotid artery infarction were investigated with perfusion harmonic imaging after SonoVue bolus injection < or =40 hour after the onset of symptoms. The findings were compared with those of cranial computed tomography (CCT) and clinical course 4 months after stroke. RESULTS: Images of pixel-wise peak intensity (PPI) and time to peak intensity could be calculated for all patients. Spearman rank correlations of r=0.772 (P<0.001) and r=0.572 (P=0.008) between area of PPI signal decrease and area of infarction in the follow-up CCT as well as outcome after 4 months were obtained, respectively. CONCLUSIONS: In the early phase of acute ischemic stroke, BHI after SonoVue bolus injection is a useful ultrasound tool for analyzing cerebral perfusion deficits at the patient's bedside. BHI data correlate with the definite area of infarction and outcome after 4 months.