Jens Eyding

Contrast Burst Depletion Imaging (CODIM) A New Imaging Procedure and Analysis Method for Semiquantitative Ultrasonic Perfusion Imaging

Background and Purpose— Established methods of ultrasonic perfusion imaging using a bolus application of echo contrast agent provide only qualitative data because of various physical phenomena. This study was intended to investigate whether a new ultrasound perfusion imaging method termed contrast burst depletion imaging (CODIM) may provide semiquantitative measures of parenchymal perfusion independent of examination depth and acoustic energy distribution. Methods— In a system with a constant concentration of contrast agent, analyzing the decrease in image intensity that occurs with microbubble-destructive imaging modes yields parameters that are considered to correlate with tissue perfusion. This method was first evaluated with a perfusion model that showed that the main resulting parameter “perfusion coefficient” (PC) is a monotonic nonlinear function of flow velocity. Seventeen human volunteers were then scanned according to this method with the use of 2 different contrast agents. Results were correlated with those from perfusion-weighted MRI examinations. Results— The PC did not show significant differences in gray matter areas (ranging from 1.466×10−2 s−1 to 1.641×10−2 s−1) of the brain despite different insonation depths (eg, ipsilateral and contralateral thalamus). In contrast, white matter exhibited significantly lower perfusion values in both imaging modes (PC: 0.604×10−2 s−1 to 0.745×10−2 s−1;P <0.05). Conclusions— CODIM is a promising new tool of imaging parenchymal (brain) perfusion in healthy persons. The method provides semiquantitative and depth-independent perfusion parameters and in this way overcomes the limitations of the perfusion methods using a bolus kinetic. Further investigations must be done to evaluate the potential of the method in patients with perfusion deficits.

Comparison Between Echo Contrast Agent-Specific Imaging Modes and Perfusion-Weighted Magnetic Resonance Imaging for the Assessment of Brain Perfusion

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 M2 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.

Depression in patients with Huntington disease correlates with alterations of the brain stem raphe depicted by transcranial sonography

BACKGROUND Transcranial sonography (TCS) has become a new diagnostic tool in the evaluation of extrapyramidal disorders. Studies of TCS report alterations of the mesencephalic raphe in patients with depression. The aim of this study was to evaluate TCS findings in patients with Huntington disease in correlation with their neurologic and psychiatric status. METHODS We recruited patients with genetically confirmed Huntington disease. The neurological and psychiatric status of participants was assessed by independent physicians. Echogenicities were investigated according to examination protocol for extrapyramidal disorders using a Siemens Sonoline Elegra system. The sonography examiner was blinded for clinical data. RESULTS We included 39 patients in our study; 21 patients (53.8%) showed symptoms of depression at the time of evaluation and, of those, 15 (71.4%) had hypoechogenic raphe structures. Thirty patients (76.9%) had a history of depressive episodes, 19 (63.3%) of them with hypoechogenic raphe structures. All 9 patients without a history of depressive episodes showed normal echogenicity of raphe structures (sensitivity 63.3%, specificity 100%). Twelve (70.6%) of the 17 patients with Huntington disease who showed psychiatric disturbances prior to the occurrence of motor symptoms exhibited pathological raphe echogenicity (sensitivity 70.6%, specificity 68.2%). LIMITATIONS Most of the patients were taking antichoreatic medication, which particularly influences neurologic status. Thus, a meaningful interpretation of the correlation between TCS findings and neurologic features was limited. CONCLUSION As a novel finding, a relation between mesencephalic raphe echogenicity and depressive state could be identified in patients with Huntington disease. An alteration of the serotonergic brain stem raphe might be involved in the pathogenesis of depression in these patients.

Brain perfusion and ultrasonic imaging techniques.

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.

Transcranial Ultrasound Brain Perfusion Assessment With a Contrast Agent-Specific Imaging Mode Results of a Two-Center Trial

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

Outcome After Thrombectomy and Intravenous Thrombolysis in Patients With Acute Ischemic Stroke A Prospective Observational Study

Background and Purpose— In patients with ischemic stroke, randomized trials showed a better functional outcome after endovascular therapy with new-generation thrombectomy devices compared with medical treatment, including intravenous thrombolysis. However, effects on mortality and the generalizability of results to routine clinical practice are uncertain. Methods— In a prospective observational register-based study patients with ischemic stroke treated either with thrombectomy, intravenous thrombolysis, or their combination were included. Primary outcome was the modified Rankin scale score (0 [no symptoms] to 6 [death]) at 3 months. Ordinal logistic regression was used to estimate the common odds ratio as treatment effects (shift analysis). Propensity score matching was applied to compare patients treated either with intravenous thrombolysis alone or with intravenous thrombolysis plus thrombectomy. Results— Among 2650 recruited patients, 1543 received intravenous thrombolysis, 504 underwent thrombectomy, and 603 received intravenous thrombolysis in combination with thrombectomy. Later time-to-treatment was associated with worse outcomes among patients treated with thrombectomy plus thrombolysis. In 241 pairs of propensity score–matched patients with a proximal intracranial occlusion, thrombectomy plus thrombolysis was associated with improved functional outcome (common odds ratio, 1.84; 95% confidence interval, 1.32–2.57), and reduced mortality (15% versus 33%; P<0.0001) compared with intravenous thrombolysis alone. Results were similar in various sensitivity analyses accounting for missing outcome data and different analytic methods. Conclusions— Results from this large prospective registry show that also in routine clinical care thrombectomy plus thrombolysis compared with thrombolysis alone improved functional outcome and reduced mortality in patients with ischemic stroke. Earlier treatment was associated with better outcomes.

Evaluation of basal ganglia, brainstem raphe and ventricles in bipolar disorder by transcranial sonography

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.

Validation of the depletion kinetic in semiquantitative ultrasonographic cerebral perfusion imaging using 2 different techniques of data acquisition

Objective.To validate the potential of ultrasonographic depletion imaging for semiquantitatively visualizing cerebral parenchymal perfusion with contrast burst depletion imaging (CODIM) in comparison with phase inversion harmonic depletion imaging (PIDIM) in healthy volunteers. Methods.Thirteen healthy adults were examined with both CODIM and PIDIM in accordance with previously described criteria. In addition to the perfusion coefficient, the time to decrease image intensity to 10% above equilibrium intensity from the initial value and the relative error (deviation of measured data from the fitted model) were evaluated to compare the reliability of both techniques in 3 different regions of interest. Results.Perfusion coefficient values did not show significantly differing values in both groups (1.57–1.64 • 10−2 s−1 for CODIM and 1.42–1.58 • 10−2 s−1 for PIDIM). The relative error was significantly smaller in the PIDIM group (0.38–0.53 for CODIM and 0.18–0.25 for PIDIM; P < .002). Conclusions. Phase inversion harmonic depletion imaging proved to be more reliable than CODIM because values of the relative error were significantly lower in PIDIM even in this relatively small cohort. This is of interest because the underlying technique, phase inversion harmonic imaging, is more widely available than contrast burst imaging.

Outcome and periprocedural time management in referred versus directly admitted stroke patients treated with thrombectomy

Background: After thrombectomy has shown to be effective in acute stroke patients with large vessel occlusion, the potential benefit of secondary referral for such an intervention needs to be validated. Aims: We aimed to compare consecutive stoke patients directly admitted and treated with thrombectomy at a neurointerventional centre with patients secondarily referred for such a procedure from hospitals with a stroke unit. Methods: Periprocedure times and mortality in 300 patients primarily treated in eight neurointerventional centres were compared with 343 patients referred from nine other hospitals in a prospective multicentre study of a German neurovascular network. Data on functional outcome at 3 months was available in 430 (76.4%) patients. Results: In-hospital mortality (14.8% versus 11.7%, p = 0.26) and 3 months mortality (21.9% versus 24.1%, p = 0.53) were not statistically different in both patient groups despite a significant shorter symptom to groin puncture time in directly admitted patients, which was mainly caused by a longer interfacility transfer time. We found a nonsignificant trend for better functional outcome at 3 months in directly admitted patients (modified Rankin Scale 0–2, 44.0% versus 35.7%, p = 0.08). Conclusions: Our results show that a drip-and-ship thrombectomy concept can be effectively organized in a metropolitan stroke network. Every effort should be made to speed up the emergency interfacility transfer to a neurointerventional centre in stroke patients eligible for thrombectomy after initial brain imaging.

Transcranial Sonography in Huntington’S Disease

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 Huntingtons 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.