Intracranial hemorrhage as a complication of dobutamine stress echocardiography: case report and review of the literature.

Dobutamine stress echocardiography is a generally well-tolerated study to evaluate patients with suspected coronary artery disease. Rare but life-threatening complications of this study have been well described. Severe hypertensive responses are a known but uncommon adverse reaction to dobutamine infusion. The authors report a case of intracranial hemorrhage in the setting of severe hypertension as a complication of dobutamine stress echocardiography. The patient was on systemic anticoagulation with warfarin for a prosthetic mitral valve and had an international normalized ratio (INR) of 3.8 that was slightly over the therapeutic goal INR of 2.5-3.5. He had no predisposing intracranial lesions such as tumor, vascular malformation, or aneurysm. He suffered an intraparenchymal hemorrhage in three distinct areas of his brain. Intracranial hemorrhage related to dobutamine infusion has not been reported previously, but given the known risk of hypertension, life-threatening sequelae including intracranial hemorrhage are possible.

Thermal effects of diagnostic ultrasound in an anthropomorphic skull model.

PURPOSE: Exposure to diagnostic ultrasound (US) can significantly heat biological tissue although conventional routine examinations are regarded as safe. The risk of unwanted thermal effects increases with a high absorption coefficient and extended insonation time. Certain applications of transcranial diagnostic US (TC-US) require prolonged exposure. An anthropomorphic skull model (ASM) was developed to evaluate thermal effects induced by TC-US of different modalities. The objective was to determine whether prolonged continuous TC-US application results in potentially harmful temperature increases. MATERIALS AND METHODS: The ASM consists of a human skull with tissue mimicking material and exhibits acoustic and anatomical characteristics of the human skull and brain. Experiments are performed with a diagnostic US device testing four different US modalities: Duplex PW (pulsed wave) Doppler, PW Doppler, color flow Doppler and B-mode. Temperature changes are recorded during 180 minutes of insonation. RESULTS: All measurements revealed significant temperature increases during insonation independent of the US modality. The maximum temperature elevation of + 5.25° C (p < 0.001) was observed on the surface of the skull exposed to duplex PW Doppler. At the bone-brain border a maximum temperature increae of + 2.01 °C (p < 0.001) was noted. Temperature increases within the brain were < 1.23 °C (p = 0.001). The highest values were registered using the duplex PW Doppler modality. CONCLUSION: TC-US induces significant local heating effects in an ASM. An application duration that extends routine clinical periods causes potentially harmful heating especially in tissue close to bone. TC-US elevates the temperature in the brain mimicking tissue but is not capable of producing harmful temperature increases during routine examinations. However, the risk of thermal injury in brain tissue increases significantly after an exposure time of > 2 hours.

Clinical concerns in the ultrasound exposure of the developing central nervous system.

Neurosonography is used as a primary imaging modality worldwide for visualization of the developing brain and spinal cord in fetuses, infants and children. During the entire process of brain development, there is rapid cell turnover, a condition that is favorable for genetic mutations once external stimuli are applied. No clinical studies in humans have been performed specifically to discuss the long-term impact of postnatal ultrasound exposure of the central nervous system. Currently published studies concerning the prenatal and postnatal use of Doppler or of ultrasound contrast agent use and the developing central nervous system are insufficient to draw meaningful conclusions regarding safety. By instituting a standardized examination and following appropriate patient handling guidelines, the risk of an adverse outcome associated with neurosonography is minimized. This paper recommends adoption of the ALARA principle and offers suggestions as to how to minimize the risk of adverse effects in neurosonography.

The cooling effect of liquid flow on the focussed ultrasound-induced heating in a simulated foetal brain.

There is a need to investigate the thermal effects of diagnostic ultrasound (US) to assist the development of appropriate safety guidelines for obstetric use. The cooling effect of a single liquid flow channel was measured in a model of human foetal brain and skull bone heated by a focussed beam of simulated pulsed spectral Doppler US. Insonation conditions were 5.7 micros pulses, repeated at 8 kHz from a focussed transducer operating with a centre frequency of 3.5 MHz, producing a beam of -6 dB diameter of 3.1 mm at the focus and power outputs of up to 255 +/- 5 mW. Brain perfusion was simulated by allowing distilled water to flow at various rates in a 2 mm diameter wall-less channel in the brain soft tissue phantom material. This study established that the cooling effect of the flowing water; 1. was independent of the acoustic source power, 2. was more effective close to the flow channel, for example, there was a marked cooling at a distance of 1 mm and negligible cooling at a distance of 3 mm from the channel; and 3. initially increased at low flow rates, but further increase above normal perfusion had very little effect.

Changes in cerebral oxygenation and hemodynamics during cranial ultrasound in preterm infants.

OBJECTIVES: To evaluate whether application of a transducer on the anterior fontanelle during cranial ultrasound (US) examination effects cerebral hemodynamics and oxygenation in preterm infants. STUDY DESIGN*: During cranial US examination, changes in cerebral blood oxygenation (cHbD) and cerebral blood volume (CBV) were assessed using near infrared spectrophotometry (NIRS) in 76 infants (GA 30.7 (4.1)wk, BW 1423 (717)g) within two days after birth. Ten of these infants (GA 29.1 (1.6)wk, BW 1092 (455)g) were studied again at a postnatal age of one week. RESULTS*: We obtained stable and consistent NIRS registrations in 54 infants within the first two days after birth. Twenty-eight of these infants showed a decrease in cHbD (0.59 (0.54) micromol/100g) during the scanning procedure while CBV did not change. Twenty-four infants showed no changes in NIRS and 2 infants showed an atypical NIRS response during cranial US examination. At the postnatal age of one week, stable and consistent NIRS registrations were obtained in 7 infants. None of these infants showed changes in NIRS variables during cranial US examination. CONCLUSIONS: Application of an US transducer on the anterior fontanelle causes changes in cerebral oxygenation and hemodynamics in a substantial number of preterm infants. ( *values are expressed as median (interquartile range)).

Local and reversible blood-brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications.

The purpose of this study was to test the hypothesis that burst ultrasound in the presence of an ultrasound contrast agent can disrupt the blood-brain barrier (BBB) with acoustic parameters suitable for completely noninvasive exposure through the skull. The 10-ms exposures were targeted in the brains of 22 rabbits with a frequency of 690 kHz, a repetition frequency of 1 Hz, and peak rarefactional pressure amplitudes up to 3.1 MPa. The total exposure (sonication) time was 20 s. Prior to each sonication, a bolus of ultrasound contrast agent was injected intravenously. Contrast-enhanced MR images were obtained after the sonications to detect localized BBB disruption via local enhancement in the brain. Brain sections were stained with H&E, TUNEL, and vanadium acid fuchsin (VAF)-toluidine blue staining. In addition, horseradish peroxidase (HRP) was injected into four rabbits prior to sonications and transmission electron microscopy was performed. The MRI contrast enhancement demonstrated BBB disruption at pressure amplitudes starting at 0.4 MPa with approximately 50%; at 0.8 MPa, 90%; and at 1.4 MPa, 100% of the sonicated locations showed enhancement. The histology findings following 4 h survival indicated that brain tissue necrosis was induced in approximately 70-80% of the sonicated locations at a pressure amplitude level of 2.3 MPa or higher. At lower pressure amplitudes, however, small areas of erythrocyte extravasation were seen. The electron microscopy findings demonstrated HRP passage through vessel walls via both transendothelial and paraendothelial routes. These results demonstrate that completely noninvasive focal disruption of the BBB is possible.

Auditory phenomena during transcranial Doppler insonation of the basilar artery.

During transcranial Doppler insonation of the basilar artery, 15 normal subjects heard high-frequency tones similar to tinnitus. The pitch of the tones equated with the PRF, and intensity equated with loudness. Alteration of pulse length did not change the tones heard, and the effect was highly dependent on probe position and direction. This is an example of ultrasonography acting as a sensory stimulus. The exact mechanism and implications of this effect will need to be clarified by further investigation. Although this phenomenon is not proved to be harmful, it would seem prudent to use the minimum transmitted power necessary to obtain a satisfactory signal from the basilar artery.

Effect of scanning pressure on intracranial hemodynamics during transfontanellar duplex US.

The purpose of this study was to determine the effect of transducer scanning pressure during duplex ultrasonographic evaluation of intracranial hemodynamics in newborns. Doppler spectra were obtained from the anterior cerebral artery with use of light and firm scanning pressure over the anterior fontanelle in 23 healthy infants and 20 infants with reduced cranial compliance due to ventricular dilatation, intracranial hemorrhage, diffuse cerebral edema, and extraaxial fluid. In healthy infants, the mean resistive index (RI) increased from 69.9 +/- 3 to 74.8 +/- 3 (P < .005), and mean time average velocity (TAV) decreased from 11.1 cm/sec +/- 1.3 to 8.6 cm/sec +/- 1.3 (P < .0001) with firm scanning pressure. In infants with decreased cranial compliance, mean RI increased from 67.8 +/- 4 to 85 +/- 5, and mean TAV decreased from 16.3 cm/sec +/- 2 to 10.7 cm/sec +/- 2 (P < .0001 for both comparisons). A significant alteration in RI with firm technique (> or = 20% increase in RI, or reversal of diastolic flow) was observed in 12 of 28 examinations in infants with decreased cranial compliance and in only one of 23 healthy infants (P < .005). These data show that scanning pressures during duplex ultrasonography can significantly affect intracranial hemodynamics, especially in infants with altered cranial compliance.

Cerebral Doppler studies in the fetus and newborn infant.

The goal of developing reliable commercial Doppler systems for measuring vessel diameter and velocity changes during the cardiac cycle appears to be near. Reaching this goal would enable us to obtain volume-flow information continuously. In animal experiments, continuous measurements of Doppler velocity, pressure, and flow add important insights into hemodynamic measurements. Incorporating Doppler methods in microcirculatory research could also provide a link between the microcirculatory and the macrocirculatory hemodynamic research. Although Doppler methods have been validated, Doppler findings in clinical research (using commercial systems) must be considered at best to reflect qualitative circulatory alterations indicating directions of change. Because of inherent technologic limitations and considerable intersubject and intrasubject variability, direct extrapolation of the numeric findings from one study to the other can lead to misleading conclusions. The Doppler results are also influenced by measurement conditions and equipment settings. However, Doppler-derived information can be used as an adjunct to clinical management in many of the diseases discussed above. As with any physiologic variable, serial measurements probably are of greater value than single measurements. With continued improvement in technology, Doppler methods hold promise of becoming an important adjunct in cerebral hemodynamic monitoring in perinatal-neonatal intensive care units.