The introduction of transpulmonary stable echoenhancing agents offer new perspectives for transcranial ultrasound. Improving signal intensity and therefore signal to noise ratio enables to perform Doppler sonography according to established clinical criteria in patients with insufficient acoustic bone window. The complete asessment of the circle of Willis is achievable and the number of non-diagnostic scans is reduced. Echoenhancement also offers new perspectives, increasing the sensitivity of ultrasound scanning for low volume flow as in high grade stenosis, and for low velocity flow as in the cerebral venous system. These improvements support the analysis of vascular pathologies such as stenosis, occlusion, AV malformations, aneurysms and cavernomas. The vascularity of tumors, with low velocity and low flow volume, can be assessed, and new diagnostic opportunities arise from the transcranial analysis of the venous system for thrombosis. Additionally, new approches such as three-dimensional vascular imaging are enabled by the iv. application of echoenhancers. With an excellent safety profile, echoenhancers add to diagnostic capabilities of transcranial Doppler ultrasound, resulting in less non-diagnostic scans, improved accuracy of diagnosis and novel diagnostic opportunities.

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The present study was performed to examine the influence of head-up postural change on cerebral circulation in patients with internal carotid artery occlusion (ICAO) . Duplex ultrasonography was used to measure blood flow velocity (FV) and pulsatility index (PI) of the common carotid artery (CCA) in 11 men with unilateral ICAO (aged 63.0±7.2 yr) while they were lying flat, as well as standing up. In addition, the change in cerebral blood flow (CBF) after becoming upright was evaluated using SPECT. No patient showed any sign of orthostatic hypotension. FVs and PI on the nonoccluded side and systolic FV on the occluded side remained unchanged, while mean, end-diastolic (ED) FVs on the occluded side decreased, and the PI on the occluded side increased. Thus, the side-to-side ratio of EDFV (ED ratio) increased in all cases. A decrease in CBF was observed in 7 out of 9 patients when they were standing upright. The degree of the increase in the ED ratio was associated with worsening of hypoperfusion in upright SPECT. Our results suggest that head-up postural change increases the relative resistance of the CCA against the decrease in carotid arterial pressure due to gravity in carotid occlusive disease, and that cerebral dysautoregulation might then occur. Duplex ultrasonography and SPECT are both safe and useful methods for evaluating the hemodynamic influence of head-up postural change on cerebral circulation in such patients, and the upright test is helpful in diagnosing ICAO using Doppler sonography because of the conspicuous laterality of the FVs.

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Changes in cerebral blood flow in response to acetazolamide (ACZ) were evaluated using transcranial Doppler (TCD) as a parameter of cerebrovascular reserve capacity (CVR) in 9 patients who underwent carotid endarterectomy (5 cases, CEA group) and EC-IC bypass (4 cases of STA-MCA anastomosis, bypass group) . TCD data were obtained before and after intravenous administration of ACZ. The percentage change in mean flow velocity (%ΔMFV) was measured as CVR. TCD was performed before, 2 weeks after, and 4-6 months after surgery.
In the CEA group with high-grade stenosis, MFV did not change significantly before and after surgery, but % ΔMFV was significantly improved 2 weeks after surgery. In the bypass group, MFV and %ΔMFV did not change significantly before and 2 weeks after surgery, but %ΔMFV was significantly improved 4-6 months after surgery.
In conclusion, during the perioperative period after reconstruction surgery for occlusive cerebrovascular disease, measurement of %ΔMFV with TCD may be of great value for estimating the change in cerebrovascular reserve capacity, similarly to PET, SPECT, and Xe-CT.

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Activation studies of cerebral circulation are important for evaluation of cerebrovascular reactivity (CVR) . In this study, CVR was investigated in 52 healthy subjects, 25 patients with chronic severe hypertension and 16 patients with hyperlipidemia. All the patients had normal findings of neurological studies, brain CT and neck vessel echo-Doppler. The CVR was assessed by TCD recording of blood flow velocity in the middle cerebral artery (MCAFV) under resting conditions and at 5, 10, 15 and 20 min after i.v. injection of 1g Acz. Additionally, we performed an Acz-activated ¹³³Xe-CT study in 8 healthy patients (16 hemispheres) who had mild carotid stenosis on MR-angiography. The regional cerebral blood flow (rCBF) in the MCA territory was measured and the CVR was also analyzed. MCAFV and CVR determined by TCD study showed a non-significant tendency to be reduced in the group aged over 60 yr. The MCAFV under resting conditions was nearly the same in the normal controls and in the patients with hypertension, but the CVR was decreased in patients even without stroke. The normal value of CVR seemed to be 40-50% in this study. When planning surgical treatment for asymptomatic patients (e.g.; those with occlusive cerebrovascular disease and unruptured cerebral aneurysm) with decreased CVR, they should be treated carefully using prophylaxis for ischemic complications.

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Cerebral hyperperfusion is a serious complication after carotid endarterectomy (CEA), because it often results in massive intracerebral hemorrhage and death. The cerebral hemodynamics following CEA were investigated using an electromagnetic flow meter and transcranial Doppler ultrasound (TCD) in 13 patients with severe unilateral stenosis of the carotid artery. The postoperative reactivity of the middle cerebral artery (MCA) flow velocity to CO2 was also measured in 7 intubated patients by increasing their ventilator minute volume.
Flow velocity in the MCA was highly correlated with volume flow in the internal carotid artery after CEA (r=0.87, p<0.01) . A significant increase in the MCA flow velocity was observed on the treated side during the 7 days after surgery. A blood pressure-dependent linear increase in the MCA flow velocity (i.e. dysautoregulation) was noticed after CEA, and this was improved by barbiturate therapy. The cerebrovascular reactivity to CO₂ was significantly increased on the treated side compared with the contralateral side (7.2 vs. 1.5%/mmHg, p<0.01) .
The present study indicated that cerebrovascular dysautoregulation, as well as cerebral hyperperfusion, could be produced by CEA in patients with severe stenosis of the carotid artery. Postoperative TCD monitoring of cerebral hemodynamics is required to prevent fatal intracerebral hemorrhage in these patients.

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Transcranial Doppler sonography is frequently used to monitor cerebral blood flow during open heart surgery. However, there is little information about cerebral blood flow velocity in patients under hypothermia.
In this study, mean flow velocities (FVs) in the middle cerebral artery (MCA) during the rewarming period were studied in 67 patients. In all cases, cardiac operations were performed with mild hypothermia and non-pulsatile cardiopulmonary bypass. The pump flow was fixed at 2.6 L/m²/min in all patients. MCA blood flow velocity changes on TCD records were compared with nasopharyngeal temperature (NPT) during the rewarming period. At first the patients were divided into two groups; 1) those with occlusive cerebrovascular attacks (CVA) (53 patients), and 2) those without occlusive CVA (14 patients) . In the patients without occlusive CVA, linear regression analysis demonstrated a relationship between NPT and FV of MCA (mean FV=-1.78+1.23 (NPT), R²=0.278) . There were no significant correlations between NPT and mean FV in patients with occlusive CVA. The patients without occlusive CVA were subdivided into two groups according to age (cut-off value, 70 years) . In the patients aged under 70 years (40 patients), there was a close correlation between NPT and mean FV (mean FV=0.211+1.33 (NPT), R² =0.278), whereas in the patients aged over 70 years (13 patients), there was a relationship between them (mean FV=10.80+0.649 (NPT), R² =0.114) . In the patients under 70 years old, there were 21 patients who received coronary artery bypass grafts (CABG group) and 19 who underwent closure of septal defects or replacement of heart valves (non-CABG group) . As in the CABG group, there was a linear correlation between NPT and mean FV (mean FV=5.77+0.911 (NPT), R² =0.290) . Non-CABG patients showed the strongest correlations between these parameters (mean FV= -2.73 + 1.38 (NPT), R²=0.357) .
It is concluded that flow velocity is reduced under hypothermia in proportion to the reduced NPT in patients aged under 70 years. TCD can provide an approximation of changes in cerebral circulation during mild hypothermia.

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We have developed a prototype second harmonic/flash echo imaging system for visualizing tissue perfusion. Second harmonic imaging is a new method that exploits the nonlinear properties of microbubble-containing ultrasound contrast agent. In phantom experiments, we obtained excellent harmonic images by eliminating the echoes from tissue-mimicking materials. The hepatic parenchyma was clearly enhanced in animal studies, and myocardial perfusion was visualized in studies using dogs.
Flash echo imaging (FEI) is a new contrast echo imaging technique. In FEI, the strong echoes that are momentarily induced by intermittent ultrasound transmission are detected. The results of our studies indicate that the harmonic mode of FEI is able to visualize microvessels which perfuse organ parenchyma.
The target blood flow can be changed by varying the suspension time for ultrasound transmission. FEI will be expected to visualize the flow rate of perfusion.
Second harmonic imaging and flash echo imaging are expected to expand the capabilities of diagnostic ultrasound systems for visualizing tissue perfusion.

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