Acetazolamide vasoreactivity evaluated by transcranial power harmonic imaging and Doppler sonography.

BACKGROUND: Cerebral vasoreactivity (CVR) in the major cerebral arteries evaluated by transcranial Doppler sonography has shown some correlation with CVR in the brain tissue measured by other neuroradiological modalities. To clarify vasoreactive differences in the brain tissue and the major cerebral arteries, we have evaluated the relationship of acetazolamide (ACZ) CVR between transcranial ultrasonic power harmonic imaging (PHI) and color Doppler sonography (CDS), in cases ofparenchymal pathology with and without occlusive vascular lesions. MATERIALS AND METHODS: The subjects were 31 stroke patients with intraparenchymal pathologies, 15 with (occlusive group) and 16 without (non-occlusive group) occlusive carotid and/or middle cerebral artery lesions. CVR based on values before/after ACZ (angle-collected CDS velocity in the middle and posterior cerebral arteries, PHI contrast area size, peak intensity, time to peak intensity), and correlation of CVR between PHI and CDS were compared between the side with and without lesions in both groups. FINDINGS: (a) PHI CVR tended to be more disturbed than CDS CVR. CVR side differences were not significant. (b) CVR correlations between PHI and CDS were always lower in the pathological sides. CONCLUSIONS: CVR in brain tissue evaluated by PHI is susceptible to disturbance in comparison with CDS, due to both parenchymal and vascular occlusive pathologies.

Quantitative evaluation of cerebrovascular reactivity in brain tissue by a refill kinetic method of transcranial ultrasonic perfusion imaging: a comparison with Doppler sonography.

UNLABELLED: To confirm the reliability of a refill kinetic method of ultrasonic harmonic perfusion imaging (HPI) capable of quantifying separate parameters of microvascular blood flow velocity and volume in brain tissue, we evaluated acetazolamide (ACZ) cerebrovascular reactivity by transcranial HPI in comparison with Doppler sonography (TCD). Methods. HPI during continuous Levovist infusion with changing pulsing intervals (t) and TCD time-averaged maximum velocity (TAMX) in the middle and posterior cerebral arteries were evaluated before and after ACZ administration in 12 patients, 8 without and 4 with a temporal skull defect. Plateau value (A) and rise rate (beta) of intensity (I) represented by HPI time-intensity curves of I(t) = A(1 - e(-beta*t)) were analyzed on the axial diencephalic plane. RESULTS: 1) A significantly decreased in proportion to the region of interest location depth only in the intact skull cases. 2) Despite inter- and intra-individual data scattering, in correspondence with TAMX increases after ACZ, significant beta increases were more frequently identified than increases of A. CONCLUSIONS: Cerebral vasoreactivity analysis utilizing refill kinetics of transcranial HPI can potentially provide separate quantification based on microvascular blood velocity and volume (capillary patency) with consideration of depth-dependant ultrasound attenuation. This should be suitable for bedside evaluation of neurointensive care patients.

Acetazolamide vasoreactivity evaluated by transcranial harmonic perfusion imaging: relationship with transcranial Doppler sonography and dynamic CT.

UNLABELLED: To establish the reliability and clinical significance of transcranial ultrasonic harmonic perfusion imaging (HPI), we evaluated HPI's relationships with transcranial Doppler (TCD) and with dynamic CT (DCT), during acetazolamide (ACZ) vasoreactivity tests. METHODS: The subjects were 12 neurological patients. Time-averaged maximum velocity (TAVMX) in the middle (MCA) and posterior cerebral arteries was measured by TCD. Time-intensity (-density) curves of HPI (DCT) after bolus intravenous contrast injections were created in 3 regions of interest (ROI) on the axial plane involving the temporal lobe, basal ganglia, and thalamus on both sides. Assessments of vasoreactivity were based on comparisons conducted before and after ACZ administration in terms of: a) relative changes (%delta) of the TCD TAVMX, b) HPI contrast area enlargement, c) %delta of calculated cerebral blood volume and flow of the HPI and DCT. RESULTS: 1) TCD vasoreactivity decrease in the left MCA tended to correlate with lower frequency of HPI contrast area enlargement on the left side. 2) HPI and DCT vasoreactivity tended to be disturbed in the same side ROIs. CONCLUSIONS: Transcranial HPI achieves repeatable non-invasive bedside evaluation of cerebrovascular reserve capacity through qualitative and quantitative measurements of brain tissue perfusion, and will have clinical value in pathophysiological follow-up and therapeutic effectiveness determination of neurointensive care patients.

Acetazolamide vasoreactivity in vascular dementia and persistent vegetative state evaluated by transcranial harmonic perfusion imaging and Doppler sonography.

To clarify the pathophysiological differences of the cerebrovascular reserve capacity in relation to cerebral cognitive impairments between vascular dementia (VaD) and persistent vegetative state (PVS), we evaluated acetazolamide (ACZ) vasoreactivity testing by transcranial harmonic perfusion imaging (HPI) and Doppler sonography (TCD). Sixteen patients (age: 29-85 years; mean: 62) were divided into three groups: 7 VaD, 4 PVS, and 5 nondementia patients. Mean velocity (Vm) in the middle and posterior cerebral artery (MCA, PCA) was measured, and time-intensity curves of the HPI were evaluated at three regions of interest-the bilateral temporal lobe (TL), basal ganglia (BG), and thalamus (Th). TCD and HPI were evaluated before (resting state) and after ACZ administration, and vasoreactivity was compared among the three groups in terms of resting values and relative changes (%Delta) of Vm, peak intensity (PI), area under curve (AUC), and mean transit time (MTT). Results of the resting state: Decreased Vm, PI, and AUC of the VaD and PVS groups were more obvious in the right side. Results of vasoreactivity: In the PVS group, %DeltaVm decreased in the left PCA and MCA; %DeltaPI and %DeltaAUC decreased in the left TL and bilateral BG. In the VaD group, %DeltaPI and %DeltaAUC decreased in the right TL; %DeltaMTT tended to increase in the left side. ACZ vasoreactivity tests by transcranial HPI and TCD allowed bedside, noninvasive quantitative evaluation of the pathophysiology of cognitive function impairment in relation to cerebrovascular reserve capacity in VaD and PVS.

Relationship between the pressure and diameter of the carotid artery in humans.

The purpose of this study was to examine the assumption of similarity between pressure and diameter-change waveforms in humans. We measured carotid arterial pressure and diameter change, simultaneously, in six patients with heart disease. In all patients, the carotid arterial pressure-diameter relationship could, in practice, be regarded as being linear.

Ultrasound facilitates transduction of naked plasmid DNA into colon carcinoma cells in vitro and in vivo.

One approach to improve the efficacy of in vivo gene therapy, with the aim at enhancing expression of the transgene, involves utilization of mechanical forces to facilitate transduction of DNA into cells. In this study, we evaluated the feasibility of mechanical insonation in gene transfers with naked DNA plasmid loading both in vitro and in vivo. We used an ultrasound probe, which can focus the ultrasonic beam in the exit zone of the probe. The reporter pcDNA3-lacZ plasmid, containing Escherichia coli lacZ or the beta-galactosidase gene (beta-gal), and the neomycin 3'-phosphotransferase gene (neo), was used for evaluation of transfer efficiency. Expression of beta-gal in MC38 murine colon carcinoma cells was measured after insonation of 20 W/cm2 with continuous 1.0-MHz wave exposure. In a transient assay, significant numbers of cells were transduced with the beta-galactosidase gene. After cells were treated with geneticin, we also observed a difference in colonogenicity between noninsonated and insonated groups. When MC38 cells were implanted in syngeneic mice and plasmid was injected, the insonation that followed facilitated beta-galactosidase expression. These results indicate that insonation represents a potential approach for gene therapy when combined with naked DNA plasmid injection.

Low-frequency ultrasound penetrates the cranium and enhances thrombolysis in vitro.

OBJECTIVE: Refinements of treatment methods are sought to rapidly reduce the volume of intracranial clots and to decrease patient exposure to possible complications of thrombolytic therapy for intracranial hematomas. We assessed the possibility of adding ultrasonication using model systems including human blood clots and temporal bone in vitro. METHODS: The transmittance of ultrasound through temporal bone obtained at autopsy was compared between the frequencies 211.5 KHz and 1.03 MHz, using a meter to determine the power delivered. The frequency 211.5 KHz was chosen to assess the ultrasound effect on the weight of 24-hour-old clots prepared from human blood after exposures at 37 degrees C to 2 mg/ml urokinase with no additional treatment, ultrasound, or agitation during an interval of up to 12 hours. At these times, fibrin degradation products also were measured. RESULTS: The transmittance of low-frequency ultrasound (211.5 KHz) through temporal bone was approximately 40%, which is four times higher than that of high-frequency ultrasound (1.03 MHz). Ultrasound but not agitation significantly increased clot lysis (140% of lysis with urokinase alone), with correspondingly increased fibrin degradation products. CONCLUSION: We conclude that low-frequency ultrasound transmits well through human temporal bone and enhances thrombolysis in vitro. Clinically, this method may be promising for reducing dosages of thrombolytic agents and shortening the period of clot removal.

[Use of an accelerometer to measure coughing].

Coughing was detected by measuring body-surface acceleration. Twenty-seven patients with a chief complaint of coughing were studied. The sensor used is an apparatus for sound communication in aircraft, in which cranial vibrations that occur as the pilot speaks are converted into acceleration waves. An acceleration sensor was fixed to the body of each subject. The acceleration of the chest wall was recorded as a voltage change. Subjects rested in bed to exclude acceleration due to body movement. Acceleration waves of large amplitude were recognized during coughing. Conversation or laughter only caused very weak acceleration waves. Sound has often been used as an indicator of coughing, because coughing was thought to be one kind of human vocalization. However, distinguishing speaking from coughing was difficult, and complicated analysis was necessary. We regarded coughing as a movement causing acceleration of the body surface, and measured it without using sound. We plan to collect data on acceleration of the body surface in 3 dimensions simultaneously. After a continuous long-term recorder of coughing is developed the effects of antitussive drugs can be assessed.

Noninvasive measurement of aortic pressure waveform by ultrasound.

At present, the aortic pressure (Pa) waveform can only be measured invasively. In this paper, we describe a new noninvasive method of measuring Pa. The aortic diameter (Da) pulse waveform was measured noninvasively from the suprasternal fossa using an echo-tracking system that was applied to the anterior and posterior aortic wall echoes. To eliminate viscoelastic distortion, the measured Da was converted to an estimate of Pa, named P beta, using the stiffness parameter beta, which revealed the viscoelastic relationship between the vessel diameter and its internal pressure. P beta was then compared with the Pa pattern that was measured directly. Eight patients with ischemic heart disease who had undergone cardiac catheterization were examined by this method. Results showed that (1) the Da and Pa waveforms were similar; (2) the P beta waveform resembled the Pa waveform more closely than did the Da waveforms for a single cardiac cycle (r = 0.970); and (3) in particular, P beta resembled Pa most closely during the upslope phase of the ejection period (r = 0.996). Our results suggest that the Pa waveform can be accurately estimated from noninvasive measurements by this method.

Transvenous hemodynamic assessment of arteriovenous malformations and fistulas. Preliminary clinical experience in Doppler guidewire monitoring of embolotherapy.

BACKGROUND AND PURPOSE: Transvenous monitoring of blood flow through intracranial vascular malformations was performed with an intravascular Doppler guidewire to assess hemodynamic changes during endovascular embolotherapy. METHODS: Flow velocity was assessed in the intracranial venous sinuses of two patients with arteriovenous malformations and seven patients with dural arteriovenous fistulas. In all cases, the Doppler guidewire was positioned in the dural sinuses coaxially through a 2.1F microcatheter. The Doppler guidewire was then advanced to the site of arteriovenous shunting for sampling of venous average peak velocity (APV) and pulsatility index. In two cases, simultaneous feeding artery flow velocity was monitored by transcranial color-coded duplex sonography. RESULTS: Before embolotherapy, the flow pattern in the venous sinuses was pulsatile, with a mean (+/-SD) APV of 39.0 +/- 22.5 cm/s. Total or near-total embolization was achieved in six of the nine cases. After embolization, the flow pattern became less pulsatile and the APV was reduced to a mean of 21.2 +/- 14.6 cm/s (P = .0123, one-tailed paired t test). The pulsatility index was used to calculate the maximum minus the minimum peak velocity (MxPV-MnPV). This was reduced from an average of 27.0 +/- 8.7 cm/s to 13.5 +/- 8.3 cm/s after treatment (P = .0456). A parallel reduction in APV of the feeding arteries was observed with embolization. CONCLUSIONS: Preliminary clinical experience indicates that transvenous assessment of two parameters, APV and MxPV-MnPV, is useful in the hemodynamic evaluation of intracranial arteriovenous shunts. This valuable hemodynamic information may be used for objective and quantitative monitoring during embolotherapy of intracranial vascular malformations.

Evaluation of the thrombolytic effect of tissue-type plasminogen activator with ultrasonic irradiation: in vitro experiment involving assay of the fibrin degradation products from the clot.

Previous studies show that the combined method using thrombolytic drugs and ultrasonic irradiation enhances the effect of thrombolysis in in vitro and in vivo experiments. However, the mechanism of the clot lysis was unclear. In previous studies the evaluation of the clot lysis effect was determined by the rate of decrease in clot weight or the decrease in radioisotope-labeled fibrinogen in the clot. However, it was unclear whether or not the fibrinogen in the clot was degraded. We measured quantitatively the fibrin degradation product, D-dimer (FDP-DD), produced from clots subjected to recombinant tissue-type plasminogen activator (rt-PA, 2.0 micrograms/ml), with and without ultrasonic irradiation. Two levels of continuous ultrasound were used, 300 kHz (100 V, 0.07 W/cm2) and 1 MHz (20 V, 0.4 W/cm2). The quantity of FDP-DD produced was 1.74 times at 300 kHz and 1.80 times at 1 MHz, greater than that measured in rt-PA solution without ultrasonic irradiation; clot lysis was not observed in normal saline with ultrasonic irradiation. Our experiment clarifies that the mechanism of clot lysis when subjected to a combination of drug and ultrasound leads to degradation of fibrin, allowing a quantitative measurement of the enhancement of clot lysis. A high correlation was observed between the FDP-DD produced from the clots and the rate of decrease in clot weight.

[Coronary artery blood flow velocity non-invasively measured using a vessel-tracking pulsed Doppler system].

A newly-developed noninvasive method was used to measure left coronary blood flow during phantom experiments. Two techniques were used in which: (1) the sample position can always be set in a fluctuating vessel using a wall echo-tracking method with a phase-locked-loop, and (2) the Doppler reference signal was generated separately synchronous with the wall echo signal. These techniques were combined, using a commercially available pulsed Doppler apparatus (SSH-40B: Toshiba). Basic experiments were performed using a blood vessel phantom to verify the validity of these systems. Blood flow velocity in the fluctuating tube could be measured clearly using a vessel-tracking method. The blood flow velocity of the left anterior descending artery was measured in three normal subjects and in seven patients from the third intercostal space along the left sternal border. The velocity pattern was characterized by a crescendo-decrescendo shape in diastole. The peak velocity which appeared in diastole ranged from 19 to 69 cm/sec, with no difference by disease entity. However, in all cases, the blood flow velocity signals were marred by extraneous signals, making it impossible to measure blood flow velocity during systole. Further improvement of the system is mandatory in order to use this flowmeter clinically.

[Cardiac function noninvasively evaluated by phasic pattern analysis of ventricular power during ejection].

To evaluate cardiac function, ventricular power during ejection (power) and the rate of change of power (dPower/dt) were assessed noninvasively. Power was determined from the product of aortic flow (Fa(t] and brachial arterial pressure (Pa(t]. Fa(t) was measured at the suprasternal notch using an ultrasonic pulsed Doppler flowmeter with a 2 MHz carrier frequency and 10 KHz repetition frequency. The maximum detectable blood velocity was 380 cm/sec. Pa(t) was measured using a newly-developed method based on indirect unloading techniques and an air pressure system. There were 21 normal subjects and seven patients with coronary artery disease in this study. The following results were obtained. There was no significant difference between power patterns calculated by Pa(t) and Pao(t) (aortic pressure measured by catheter). The average peak dPower/dt was 160.2 J/sec2 in normal subjects, 145.2 L/sec2 in patients with ejection fractions greater than 50%, and 93.5 J/sec2 in patients with ejection fraction less than 50%. Peak dPower/dt was significantly decreased in patients with the lower ejection fraction (p less than 0.005). The results indicated that this index is clinically useful in evaluating cardiac contractility.

[Continuous measurement of cardiac output during ergometer exercise using an ultrasonic pulsed Doppler flowmeter].

A method for determining cardiac output was developed, which provided the product of the absolute blood flow rate at the aortic arch (as measured non-invasively from the suprasternal notch by an ultrasonic pulsed Doppler flowmeter: UPDF) and the cross-sectional area of the aorta at that level, as estimated from two-dimensional echograms. Using this method, non-invasive continuous measurements of cardiac output were made during bicycle ergometer exercise. The results were summarized as follows: Resting cardiac output values obtained by this method correlated reasonably well with those by the thermodilution method (correlation coefficient r = 0.76). Eight healthy male volunteers exercised for 2 min on a bicycle ergometer at 250 kpm/min, and serial cardiac outputs were determined by this method for five of these subjects during and after the loading. The cardiac output curves thus obtained clearly demonstrated abrupt increases in cardiac outputs initially, followed by rapid returns to resting cardiac output levels after the end of exercise. We intend to conduct additional studies for larger groups of subjects to further evaluate and to establish this method for use in cardiac examinations.

Non-invasive quantitative evaluation of aortic regurgitation using an ultrasonic pulsed Doppler flowmeters.

The severity of aortic regurgitation (AR) is usually evaluated using cineaortography, but this procedure cannot be carried out easily because of its invasive nature. For estimating the severity of AR non-invasively as well as quantitatively, we measured the blood flow in the aortic arch using an ultrasonic pulsed Doppler flowmeter (UPDF) from a suprasternal notch. The rugurgitant ratio was calculated from the waves of relative flow volume and compared with the severity determined cineaortographically. The following results were obtained: 1) Reproducible waves of the aortic arch flow were recorded in all normal subjects and also in 19 out of 23 patients with AR. 2) Distinctive waves of the regurgitant flow, which could not be seen in normal subjects, were recorded in AR except for some mild cases. 3) The regurgitant ratio obtained from the UPDF corresponded well with the severity based on the cineaortogram. It may be concluded that the UPDF is clinically useful and reliable for quantifying AR non-invasively.

Non-invasive and quantitative measurement of volume flow-rate at internal and external carotid and vertebral arteries.

A non-invasive and quantitative system to measure the volume flow-rate, velocity and diameter in the internal and external carotid arteries and vertebral artery was developed. It was verified from the model experiment and clinical applications that this system could provide quite useful flow informations in small and sinuous artery within 8% error.

[Non-invasive quantitative evaluation of aortic regurgitation by ultrasonic pulsed Doppler flowmeter (author's transl)].

A usefulness of non-invasive and quantitative evaluation of aortic regurgitation (AR) was investigated by measuring the aortic arch flow from the suprasternal notch with ultrasonic pulsed Doppler flowmeter (UPDF). Measurement of the blood flow was made on 19 patients with AR, calculating the regurgitant ratio from the waves of relative flow volume, and the estimated grade of AR was compared with the severity judged from the cineaortogram. The results were as follows: 1) The aortic arch flow was recorded in 17 out of 19 patients with AR. 2) Except mild cases, the diastolic regurgitant flow was recorded in patients with AR. 3) The regurgitant ratio obtained by the UPDF correlated well with the grade of the severity of AR judged from the cineaortogram.