Jens Federlein

Knowing no fear.

People with brain injuries involving the amygdala are often poor at recognizing facial expressions of fear, but the extent to which this impairment compromises other signals of the emotion of fear has not been clearly established. We investigated N.M., a person with bilateral amygdala damage and a left thalamic lesion, who was impaired at recognizing fear from facial expressions. N.M. showed an equivalent deficit affecting fear recognition from body postures and emotional sounds. His deficit of fear recognition was not linked to evidence of any problem in recognizing anger (a common feature in other reports), but for his everyday experience of emotion N.M. reported reduced anger and fear compared with neurologically normal controls. These findings show a specific deficit compromising the recognition of the emotion of fear from a wide range of social signals, and suggest a possible relationship of this type of impairment with alterations of emotional experience.

Transient Response Harmonic Imaging An Ultrasound Technique Related to Brain Perfusion

BACKGROUND AND PURPOSE Gray-scale harmonic imaging is the first method to visualize blood perfusion and capillary blood flow with ultrasound after intravenous contrast agent application. The purpose of the present study was to evaluate the potential of transient response second harmonic imaging (TRsHI) to assess normal echo contrast characteristics in different brain areas by transcranial ultrasound. METHODS In 18 patients without cerebrovascular diseases, TRsHI examinations were performed bilaterally with the use of the transtemporal approach after application of 6.5 mL of a galactose-based microbubble suspension (400 mg/mL). The transmission rate was once every 4 cardiac cycles. Regional cerebral contrast was visually assessed and then quantified off-line with the use of time-intensity curves. In 4 different regions of interest (ROI) (posterior part of the thalamus [ROIa], anterior part of the thalamus [ROIb], lentiform nucleus [ROIc], and white matter [ROId]), the following parameters were evaluated: peak intensity, area under the curve (AUC), and time to peak intensity. AUC ratios for ROIc/a, d/a, c/b, and d/b were calculated. RESULTS In all patients parenchymal contrast enhancement was visually detectable. One hundred thirty-one characteristic time-intensity curves (baseline phase, peak contrast intensity, slow washout phase) were demonstrable in 144 ROIs. In ROIc and ROId, characteristic contrast curves could be observed most frequently (68/72 examinations), whereas time-intensity curves in ROIa and ROIb could not be evaluated because of inadequate contrast enhancement in 9 of 72 examinations. Time to peak intensity varied between 20 and 52 cardiac cycles; in 1 patient it was 88 cardiac cycles. In all individuals AUCs and in 16 of 18 subjects peak intensity in ROIc and ROId showed a 2- to 10-fold increase compared with ROIa and ROIb. In no examination did AUC ratios show a >2-fold side difference irrespective of the ROI. CONCLUSIONS The present study demonstrates for the first time that TRsHI produces accurate contrast in different brain areas and represents an ultrasonic tool related to brain perfusion. Absolute values of quantitative parameters show high variations caused by different temporal bone thicknesses and a complex relationship between echo contrast concentrations and measurements of optic intensities. Ratios between different ROIs help to compare contrast enhancement in different brain areas. Furthermore, because of the fact that attenuation of contrast enhancement in TRsHI depends strictly on the insonation depth, harmonic imaging studies of brain perfusion cannot be compared directly with other imaging techniques such as positron emission tomography.

Insufficient and absent acoustic temporal bone window: potential and limitations of transcranial contrast-enhanced color-coded sonography and contrast-enhanced power-based sonography.

The aim of this study was to investigate the diagnostic potential of contrast-enhanced transcranial color-coded sonography (CE-TCCS) and contrast-enhanced transcranial power-based sonography (CE-TPS) in patients with insufficient or absent acoustic bone windows (IABW). Due to temporal bone thickness, the basal cerebral circulation could not be insonated in 21 of 172 patients using unenhanced transcranial color-coded real-time sonography (TCCS) and transcranial power-based sonography. Additional CE-TCCS and CE-TPS were performed after application of 400 mg/ml galactose microbubble suspension. In both modalities, the use of echo-contrast agents allowed visualisation of the first segment of the middle cerebral artery (MCA) in all patients. The A1 segment of the anterior cerebral artery (67% in CE-TCCS; 81% in CE-TPS), P1 segment of the posterior cerebral artery (71% in CE-TCCS; 76% in CE-TPS) and the basilar artery (48% in CE-TCCS; 67% in CE-TPS) were depictable in the majority of the examinations. The M3 (5% in CE-TCCS; 33% in CE-TPS; p < 0.05), P2 (24% in CE-TCCS; 71% in CE-TPS; p < 0.005), P3 segments (0% in CE-TCCS; 43% in CE-TPS; p < 0.005) and the posterior communicating artery (5% in CE-TCCS; 33% in CE-TPS; p < 0.05) were detected in a significantly greater proportion of subjects using power Doppler. In conclusion, CE-TCCS and CE-TPS appear to be sensitive ultrasonic tools that provide reliable data regarding the basal cerebral circulation in patients with IABW. Furthermore, CE-TPS offers advantages over CE-TSSC in the identification of small-caliber arteries and vessels that run at unfavorable angels to the ultrasound beam. Both methods can overcome hyperostosis of the skull that is a major hindrance in transcranial ultrasonography, and may be helpful in the diagnosis of occlusive diseases of intracranial vessels.

Ultrasonic evaluation of pathological brain perfusion in acute stroke using second harmonic imaging

OBJECTIVE To evaluate the use of transient response second harmonic imaging (HI) by means of ultrasound to assess abnormalities of cerebral echo contrast agent enhancement in patients with acute stroke. METHODS The study comprised 25 patients with acute onset of hemispheric stroke (<24 h) with sufficient insonation conditions and 14 control subjects without cerebrovascular disease. All stroke patients had HI, extracranial and transcranial colour coded duplex examinations of the arteries supplying the brain, and clinical examinations (European stroke scale) performed in the acute phase, on day 2, and within 1 week. Acute CT was repeated within 1 week and facultatively accompanied by angiography. Examinations using HI were performed in an axial diencephalic plane of section using the transtemporal acoustic bone window. After bolus application of galactose based microbubbles, 61 ultrasound images with a cardiac cycling triggering frequency of once every 2 seconds were recorded and evaluated off line. Focal perfusion deficit was identified if no contrast enhancement was visualised in a circumscribed region of interest and insufficient temporal bone window was excluded. In cases of reappearance of contrast enhancement reperfusion was assessed. RESULTS Adequate cerebral contrast enhancement could be seen in 21 subjects. In seven, a large hemispheric deficit of contrast enhancement affecting the entire middle cerebral artery (MCA) territory was detectable; the lentiform nucleus was affected in three subjects. Assessment of cerebral contrast abnormalities was possible in two patients with superficial MCA infarctions but in none of the patients with lacunar ischaemias. None of the control persons had focal deficits of cerebral echo contrast enhancement. In all patients with complete MCA infarction and striatocapsular infarction, presumed ischaemic areas in HI examinations correlated with final CT findings. Overall sensitivity and specifity of HI examinations for predicting size and localisation of the infarction were 75 and 100%, respectively. During follow up, reappearance of contrast enhancement was determined in three patients, in two patients circulatory arrest due to malignant brain oedema with missing contrast enhancement in the entire cerebral hemisphere could be seen. Extent of contrast enhancement deficits significantly correlated with the clinical status on admission and after 1 week (p<0.01). CONCLUSIONS Second harmonic imaging is the first ultrasonic technique that enables visualisation of pathological cerebral echo contrast enhancement. Because this method identifies deficits of focal contrast enhancement in patients with acute stroke and allows estimation of the final infarct size and clinical prognosis, it may help to select and monitor patients for invasive therapies.

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.

Second Harmonic Imaging In Acute Middle Cerebral Artery Infarction Preliminary Results

BACKGROUND Second harmonic imaging (SHI) is a new ultrasound technique that is able to detect microbubbles in the tissue vascular space. The aim of this pilot study was to prove that this technique may detect focal abnormalities of cerebral echo-contrast enhancement in acute hemispheric stroke. CASE DESCRIPTIONS Two male patients (aged 72 and 64 years) were included who presented with acute onset of severe hemiparesis and no established demarcation of the ischemic area in CT scans. After bolus application of galactose-based microbubbles, axial SHI examinations in a diencephalic plane of sections were performed using the transtemporal approach. Ultrasound investigations were recorded and evaluated offline. In both individuals demarcated focal abnormalities of cerebral contrast enhancement were detectable: in patient 1 the region of the lentiform nucleus and the adjacent parts of the temporoparietal lobe was affected, and in patient 2 a large region including the lentiform nucleus and cortical white matter was involved for at least 24 hours. Follow-up CT scans demonstrated a striatocapsular infarct in patient 1 and complete MCA infarction in patient 2, correlating with the presumed ischemic area in acute ultrasound examinations. The patient with complete MCA infarction showed missing contrast enhancement in the entire hemisphere of the affected side in follow-up SHI examinations. He died of malignant space-occupying brain edema. In the patient with the striatocapsular infarction, reappearance of echo-contrast enhancement in the ischemic area was assessable after 1 week. CONCLUSIONS SHI may identify focal abnormalities of cerebral echo-contrast enhancement in acute hemispheric stroke. Furthermore, this technique helps to determine size, localization, and prognosis of the ischemic region and could be useful for bedside assessment of echo-contrast agent distribution related to brain tissue perfusion.

Recanalization of acute symptomatic occlusions of the internal carotid artery.

Background Little is known about the natural course of internal carotid artery (ICA) occlusion and its possible recanalization. The present study was designed to evaluate recanalization rates of extracranial ICA occlusions in acute stroke patients by means of color-coded duplex sonography (CCDS). Methods 305 patients with acute ischemia in the territory of the middle cerebral artery were included in this study. All patients had a neurological examination on admission and on discharge and were rated by means of the European Stroke Scale (ESS). Extracranial color-coded duplexsonography, transcranial Doppler sonography and cranial computed tomography were immediately performed after admission and within 7 days. Results 254 patients showed no sign of hemodynamic relevant stenosis greater than 70 % of the ICA. 21 patients had symptomatic high grade ICA stenosis. 20 patients had an acute occlusion and 10 patients an old ICA occlusion as judged by duplex sonographic criteria. Six patients (5 male, 1 female; age range 57 to 77 years) with an acute atherothrombotic or cardioembolic occlusion showed a recanalization of the ICA in the follow-up ultrasonography. Two patients with cardiogenic embolic occlusion of the ICA had the most favorable outcome and these patients showed no residual stenosis. 4 patients who had ultrasound findings consistent with atherosclerosis on follow-up examination (2 high-grade stenosis, 2 with carotid plaques) did not show a notable improvement of their ESS-score. Patients with carotid plaques developed complete MCA infarctions; the other 4 patients had partial anterior circulation infarction on follow-up CT. Conclusions The present study showed that recanalization of the occluded ICA in acute stroke patients is more frequent than generally presumed. CCDS should be routinely performed in the follow-up of stroke patients as spontaneous recanalization may influence clinical outcome.

Diagnosis and Monitoring of Middle Cerebral Artery Occlusion with Contrast-Enhanced Transcranial Color-Coded Real-Time Sonography in Patients with Inadequate Acoustic Bone Windows

Transcranial color-coded real-time sonography (TCCS) is an emerging diagnostic technique that allows noninvasive imaging of intracranial vessels within parenchymal structures. However, in some patients, transcranial ultrasound is particularly hindered by insufficient ultrasound penetration through the temporal bone. The present study evaluates whether or not application of an echo-contrast agent in ultrasound-refractory patients with middle cerebral artery (MCA) trunk occlusion enhances image acquisition enough to yield accurate diagnoses. Contrast-enhanced (CE) TCCS examinations, computed tomography scans and angiographic studies were performed in 20 patients with clinical symptoms suggestive of MCA occlusion within 12 h of the onset of symptoms. For comparison, 20 control persons without history or clinical signs for cerebrovascular diseases were examined using CE-TCCS. In none of the patients or control subjects did unenhanced TCCS investigations depict any color-coded vascular signal of an intracranial vessel. After application of 9 mL of 400 mg/mL galactose-based microbubbles, CE-TCCS was performed. In subjects with MCA occlusion, CE-TCCS examinations were repeated within 24 h, 48 h and 5 days after stroke. In stroke patients (n = 20), CE-TCCS showed an occluded MCA main stem in 11 patients, and this vessel was clearly demonstrable on the unaffected side. On the affected side, the posterior cerebral artery (PCA) and anterior cerebral artery (ACA) could be visualized in 8 of 11 subjects; in 3 patients, at least 1 of these vessels was detectable. Angiographic studies confirmed the diagnosis of MCA trunk occlusion in all 11 individuals. In follow-up investigations, 3 stroke patients had angiographic and CE-TCCS examinations consistent with vessel reperfusion. Nine stroke patients had a patent MCA shown in angiographic and CE-TCCS examinations. In the control group, the MCA trunk could be visualized in all subjects by CE-TCCS. CE-TCCS is a sensitive and specific ultrasound method for the diagnosis of MCA trunk occlusion that overcomes the anatomical hindrance of inadequate acoustic bone window. This technique may help to identify patients suitable for thrombolytic therapies and monitor their response.

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.

Comparison of transcranial power Doppler and contrast-enhanced color-coded sonography in the identification of intracranial arteries.

Power‐based transcranial color‐coded sonography and contrast‐enhanced transcranial color‐coded sonography are ultrasonographic techniques that allow improved visualization of vascular structures. The present study was designed to investigate and compare the diagnostic capacity and applicability of both methods in the assessment of intracranial vessels of the circle of Willis (33 patients) and the vertebrobasilar system (21 patients). Compared to conventional transcranial color‐coded sonography, both power‐based and contrast‐enhanced transcranial color‐coded sonography improved the diagnostic sensitivity in identifying peripheral segments and small vessels of the circle of Willis. Contrast‐enhanced transcranial color‐coded sonography was significantly superior to power‐based transcranial color‐coded ultrasonography in the depiction of the second segment of the middle cerebral artery (66 of 66 versus 60 of 66, P < 0.005), both segments of the anterior cerebral artery (66 of 66 versus 56 of 66 for the A1 segment, P < 0.005; 61 of 66 versus 44 of 66 for the A2 segment, P < 0.005), the first segment of the posterior cerebral artery (66 of 66 versus 55 of 66, P < 0.005), and the basilar artery using the transtemporal approach (21 of 21 versus 15 of 21, P < 0.05). Using the transforaminal approach contrast‐enhanced transcranial color‐coded real‐time sonography did not increase fine resolution of the vertebrobasilar system compared to power Doppler sonography. In conclusion, contrast‐enhanced transcranial color‐coded real‐time sonography further improves the diagnostic potential of power Doppler sonography in the identification of vascular structures of the circle of Willis. Contrast‐enhanced transcranial color‐coded sonography and power Doppler sonography are equally effective in visualizing the vertebrobasilar system with branches.