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In this study, we compared contrast-enhanced ultrasound perfusion imaging with magnetic resonance perfusion-weighted imaging or perfusion computed tomography for detecting normo-, hypo-, and nonperfused brain areas in acute middle cerebral artery stroke. We performed high mechanical index contrast-enhanced ultrasound perfusion imaging in 30 patients. Time-to-peak intensity of 10 ischemic regions of interests was compared to four standardized nonischemic regions of interests of the same patient. A time-to-peak >3 s (ultrasound perfusion imaging) or >4 s (perfusion computed tomography and magnetic resonance perfusion) defined hypoperfusion. In 16 patients, 98 of 160 ultrasound perfusion imaging regions of interests of the ischemic hemisphere were classified as normal, and 52 as hypoperfused or nonperfused. Ten regions of interests were excluded due to artifacts. There was a significant correlation of the ultrasound perfusion imaging and magnetic resonance perfusion or perfusion computed tomography (Pearson's chi-squared test 79.119, p < 0.001) (OR 0.1065, 95% CI 0.06-0.18). No perfusion in ultrasound perfusion imaging (18 regions of interests) correlated highly with diffusion restriction on magnetic resonance imaging (Pearson's chi-squared test 42.307, p < 0.001). Analysis of receiver operating characteristics proved a high sensitivity of ultrasound perfusion imaging in the diagnosis of hypoperfused area under the curve, (AUC = 0.917; p < 0.001) and nonperfused (AUC = 0.830; p < 0.001) tissue in comparison with perfusion computed tomography and magnetic resonance perfusion. We present a proof of concept in determining normo-, hypo-, and nonperfused tissue in acute stroke by advanced contrast-enhanced ultrasound perfusion imaging.

Transcranial brain sonography (TCS) has become a reliable and sensitive diagnostic tool in the evaluation of extrapyramidal movement disorders. Alterations of brainstem raphe (BR) have been depicted by TCS in major depression but not in bipolar disorder. The aim of our study was to evaluate BR echogenicity depending on the different conditions of bipolar patients. Echogenicities of dopaminergic basal ganglia structures were assessed for the first time in bipolar disorder. Thirty-six patients with bipolar I disorder (14 depressed, 8 manic, 14 euthymic) were compared to 35 healthy controls. Echogenicities were investigated according to the examination protocol for extrapyramidal disorders using a Siemens Sonoline® Elegra system. The sonography examiner was blinded for clinical rating scores. Six patients (16.7%) showed hyperechogenicity of the substantia nigra. The raphe was hypoechogenic in 13 (36.1%) of the patients. No significant differences were seen between the subgroups. Compared to the control group, frequency of altered echogenicities did not reach statistical significance. The width of third ventricle was significantly larger in the patient group (3.8±-2.1 mm vs. 2.7±1.2 mm). Depressed bipolar patients with reduced BR echogenicity showed significantly higher scores on the Hamilton Depression Rating Scale as well as the Montgomery-Åsberg Depression Rating Scale. In contrast to unipolar depression, sonographic findings of bipolar patients may generally indicate structural integrity of mesencephalic raphe structures. If bipolar disorder coexists with hypoechogenic raphe structure, depressive symptoms are more severe., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Severe internal carotid artery stenosis can cause constriction of cerebral perfusion. Different techniques of measuring brain perfusion are currently available. Ultrasound perfusion imaging (UPI) can differentiate hypoperfused and nonperfused cerebral tissue. Aim of this study was to compare the value of UPI and perfusion-weighted magnetic resonance imaging (pw-MRI) in the evaluation of cerebral perfusion in patients with severe internal carotid artery stenosis. Ten patients with severe internal carotid artery stenosis were included. UPI was performed with phase-inversion-harmonic-imaging and bolus application of contrast media for semiquantitative analysis of time-intensity curves. Time-to-peak intensity (TPI) values were compared with time-to-peak maps of pw-MRI examinations in predefined regions-of-interest (ROI). Further, a comparison of pre- and postoperative UPI data was performed in selected cases. Seven of 10 patients could be evaluated. Eighty ROIs were used for the comparison of UPI and pw-MRI, 37 ROIs were used for pre- and 36 ROIs for postoperative comparison of UPI data. There was no delay in any MRI ROI. In UPI, there were relevant delays in seven of 37 ROIs (18.9%) before and in nine of 36 ROIs (25.0%) after surgery. Eleven of these 16 ROIs (68.8%) were in the inner border zone. Compared with the established pw-MRI technique, UPI described possible subtle perfusion delays mainly of the inner border zone. These preliminary results suggest a possible diagnostic power of UPI as a noninvasive tool for the detection of hemodynamic relevance in severe internal carotid artery disease., (Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Transcranial sonography (TCS) identifies basal ganglia alterations in extrapyramidal movement disorders such as Parkinson's disease or dystonia. Although only rarely reported, TCS also reveals signal alterations of basal ganglia in several forms of hereditary and nonhereditary ataxia. Here, the examination procedure and its diagnostic value for the classification of ataxia are reviewed. Three TCS studies reported hyperechogenicity of substantia nigra (SN) as a frequent finding in spinocerebellar ataxia type 2, type 3, and type 17, indicating a vulnerability of the nigrostriatal system in SCA patients. A new "cerebellar examination plane" was proposed, allowing better visualization of fourth ventricle enlargement and nucleus dentatus hyperechogenicity as a characteristic finding in SCA3 patients. In sporadic Creutzfeldt-Jakob disease, a blurry inhomogeneous hyperechogenic signal pattern of lentiform nucleus was identified in all of the patients in a small case series. Furthermore, distinct bilateral hyperechogenicity of pallidostriatal regions have been described as a novel diagnostic feature in the sonographic differentiation of extrapyramidal and atactic movement disorders. TCS is a commonly available, noninvasive, and inexpensive diagnostic tool, which provides reliable information about the morphology of the brain in ataxias, even in agitated patients who do not tolerate other imaging techniques. Further neuropathological and multimodal imaging studies are needed to elucidate the precise morphological and pathogenetic background of the detected echosignal pathology, and also to correlate these findings to the various clinical features of this disease entity., (Copyright 2010 Elsevier Inc. All rights reserved.)

Transcranial sonography (TCS) has become a reliable and sensitive diagnostic tool in the evaluation of extrapyramidal movement disorders, especially in the differentiation of Parkinsonian syndromes. Although only rarely reported, TCS reveals also signal alterations of basal ganglia in Huntington's disease (HD). Distinct findings are related to all of the three symptom domains of the clinical triad of the disease. The TCS finding of substantia nigra hyperechogenicity was related to higher clinical disease severity. A poorer cognitive performance correlated with larger width of third ventricle. Moreover, widths of frontal horns of lateral ventricles measured with TCS corresponded closely to diameters estimated by CT imaging. Depressive symptoms were found to be associated with abnormal echogenicity of mesencephalic raphe structures. Furthermore, a larger number of CAG repeats in the huntingtin gene correlated with presence of SN hyperechogenicity. This review provides information about the examination procedure and its diagnostic value in HD. Possible morphological and pathophysiological mechanisms leading to changes in the reflection of ultrasound waves are discussed in the context of established neuroimaging modalities., (Copyright 2010 Elsevier Inc. All rights reserved.)

The present paper summarizes recommendations on transcranial sonography (TCS) application in neurodegenerative diseases, resulting from a consensus meeting of the European Society of Neurosonology and Cerebral Hemodynamics. TCS of distinct infra- and supratentorial brain structures detects characteristic changes in several movement disorders, such as abnormal hyperechogenicity of substantia nigra (SN) in Parkinson's disease and of lenticular nucleus in dystonia, Wilson's disease and atypical Parkinsonian disorders. In healthy adults, the TCS finding of marked SN hyperechogenicity indicates a subclinical functional impairment of the nigrostriatal dopaminergic system. The finding of marked SN hyperechogenicity in combination with normal lenticular-nucleus echogenicity discriminates idiopathic Parkinson's disease from multiple-system atrophy and progressive supranuclear palsy with a positive predictive value of more than 90%. As TCS is a quick and noninvasive method, using the same duplex-ultrasound machines as for investigation of intracranial vessels, applicable even in agitated patients, this method has a great potential to be more widely used.

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., Conclusions: The study demonstrates that brain perfusion assessment with an ultrasound contrast-specific imaging mode is comparable between different centers using the same study protocol.

The bolus kinetic in ultrasonic cerebral perfusion imaging is the most favored data acquisition and processing technique. However, there has not yet been convincing evidence for the potential to (semi-) quantitatively describe perfusion. Aim of this study was to determine the intraindividual range of relevant perfusion parameters to describe individual physiological cutoff scores. In 20 healthy volunteers, cerebral perfusion was evaluated using the bilateral approach with phase inversion harmonic imaging and the bolus kinetic. Relevant parameters (time-to-peak intensity, TPI; peak width, PW) were derived in 14 regions-of-interest in both hemispheres. The median and quartile deviation (QD) of these values were individually calculated. Within the 20 individuals, the mean QD of TPI was 0.68 s, and there was no case in which any TPI exceeded the mean more than 2 s. With PW, the mean QD was 1.2 s, and the mean was not exceeded by more than 6 s. Intraindividual perfusion parameters, especially TPI, show a considerable small range. Thus, the bolus kinetic derives reliable semiquantitative information once intraindividual comparison can be accomplished. We therefore propose that bilateral examination with the unaffected hemisphere as referential region should be performed in acute stroke. Future studies have to evaluate the potential of this approach of discriminating ischemia and hypoperfusion in the affected hemisphere.

Background and Purpose: Contrast burst depletion imaging (CODIM) visualizes cerebral perfusion by destruction of microbubbles and observation of image intensity course. Because of its complexity, artifacts occur. Criteria of reliability to improve diagnostic significance were created and validated., Methods and Results: Eighteen healthy volunteers were examined with 2 echo contrast agents (ECAs) and 3 frame rates in 3 regions of interest (ROIs). Perfusion coefficient (PC), Tmin (time to decrease intensity to 10% of its max), and relative error (RE) (deviation of measured data from fitted model) were determined. PC differed significantly neither between CA nor between frame rates (overall mean = 1.60 +/- 0.21 x 10(-2) s-1). Tmin differed significantly between frame rate groups (P < .001, 33.4 +/- 11.2 s/0.5 Hz; 3.6 +/- 2.5 s/5 Hz) since it is related to destruction of microbubbles that occurs with each frame and to the perfusion rate. RE was higher in the Optison group and tended to decrease in ROIs closer to the probe., Conclusions: PC was independent of frame rate and ECA. Tmin was shorter with higher frame rates. Due to a very rapid decay at 5 Hz, the ideal frame rate should be about 1 Hz, that is, because the number of frames acquired within Tmin and therefore signal-to-noise ratio is higher at 1 Hz. Since the algorithm is complex (high RE) and more artifacts should occur in patients (insufficient bone window, etc), a triggering of the insonations by, for example, heart rate could decrease artifacts and increase diagnostic power of CODIM.

Background: Transcranial sonography (TCS) identifies hyperechogenic basal ganglia in extrapyramidal disorders such as Parkinson's disease or dystonia and reveals brain atrophy reflecting the stage of degeneration in Huntington's disease. Aim of the present study was to evaluate the diagnostic potential of TCS in spinocerebellar ataxia type 3 (SCA3), a neurodegenerative disease affecting the cerebellum, multiple pontine nuclei, substantia nigra, pallidum, putamen, caudate nucleus and long spinal tracts., Methods: 15 patients with a molecular diagnosis of SCA3 and 15 age- and sex-matched healthy control individuals were examined with TCS. Echogenicity of the substantia nigra, caudate nucleus, pallidum, putamen, dentate nucleus and cerebellar white matter were determined quantitatively (substantia nigra by measuring the area of incresed echogenicity) or semiquantitatively (0 = none, 1 = mild, 2 = marked) on both sides and compared with the echotexture of defined brain structures. Additionally, the width of the lateral ventricles, the 3rd and 4th ventricle was measured in both groups., Results: SCA3 patients exhibited hyperechogenicities of the cerebellar white matter (57%), substantia nigra (40%), the dentate nucleus (54%), putamen (40%) and pallidum (40%) significantly more frequently (p <0.05) than controls (20%, 13%, 9%, 0%, and 0% in the corresponding areas). In none of the healthy individuals a marked signal increase could be observed, whereas 53% of SCA3 subjects had at least one region with marked echogenicity. Cerebellar atrophy as demonstrated by an enlarged 4th ventricle was observed in all SCA3 patients whereas this structure could not be differentiated from surrounding parenchyma due to its small size in healthy individuals. 3rd and lateral ventricles were significantly larger in SCA patients as compared to controls (p < 0.05)., Conclusions: TCS is a suitable and non-invasive bed-side method to detect basal ganglia hyperechogenic lesions and posterior fossa abnormalities in SCA3 patients. The pattern of echotexture alterations and brain atrophy most likely reflects distribution and morphology of the neurodegenerative process.

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.