Influence of temporal insonation window quality on the assessment of cerebral autoregulation with transcranial Doppler sonography

Cerebral autoregulation can be assessed quickly and noninvasively using transcranial Doppler sonography (TCD). A poor transtemporal insonation window is a common limitation in TCD examinations. The effects of insonation quality on TCD autoregulation measurements have never been investigated. We developed two methods to quantitatively measure insonation quality. We also validated a model to artificially worsen the insonation window. This involves inserting a thin aluminium foil between the TCD probe and the skin. Forty-six healthy volunteers underwent TCD examination before and after artificial reduction of the transtemporal insonation quality. Two autoregulation parameters, the phase difference (PD) and a cross-correlation coefficient (Mx), were calculated from the recordings. The aluminium foil model realistically simulates poor insonation conditions, producing a decrease in the signal power from 36.4 +/- 2.8 dB to 32.0 +/- 1.5 dB. In corrupted insonation windows, the PD is artificially low (native: 34.2 +/- 9.3 degrees , corrupted: 29.9 +/- 9.7 degrees , p = 0.002), but the Mx is not significantly different. Insonation quality may introduce a systematic bias of clinically relevant magnitude into TCD-based cerebral autoregulation studies. This must be considered when studies of elderly patients are planned. This article discusses strategies to account for this bias.     

Determinants of myocardial hypoperfusion analyzed for the interventricular septum using power Doppler harmonic imaging with contrast echocardiography in humans: a methodologic approach for clinical practice.

BACKGROUND: To evaluate determinants of myocardial hypoperfusion using power Doppler harmonic imaging (PDHI) with myocardial contrast echocardiography (MCE) in clinical practice, a retrospective clinical study was performed comparing echocardiographic and angiographic data. Angiographic data of patients with a normal coronary angiogram (non-CAD) and symptomatic patients with low flow conditions caused by a stenosis of the left anterior descending coronary artery (LAD) or occlusion, or TIMI-II-flow in the LAD were compared with the PDHI data. METHODS AND RESULTS: In 32 patients, MCE was performed with a System Five Performance ultrasound system (GE Vingmed Ultrasound, Horten, Norway). Myocardial perfusion was semiquantitatively analyzed with the EchoPac 6.2b.134 software, bolus injection with Optison (0.35 mL with 5 mL saline flush), and continuous infusion with Levovist (400 mg/mL(-1); 3.5-5 mL/min(-1)) were performed (8 non-CAD patients, 8 CAD patients, respectively). After bolus injection, Doppler intensity (DI) kinetics showed a significant decrease of maximum DI wash-in rate (eg, apical septum [AS]: 4.9 +/- 3.3 vs 2.4 +/- 1.9 dB/s(-1)), of peak maximum DI (eg, AS: 25.3 +/- 6.3 vs 16.4 +/- 5.7 dB), and of DI determined 10 and 20 seconds after peak maximum DI (eg, AS: 22.1 +/- 4.9 vs 10.8 +/- 4.6 dB; AS: 20.4 +/- 5.3 vs 8.0 +/- 3.8 dB, respectively) using a trigger interval once every 3 cardiac cycles when normal perfused areas were compared with hypoperfused areas. During infusion coronary transit time (3.3 +/- 0.9 vs 7.0 +/- 3.6 seconds), maximum DI wash-in rate (eg, AS: 3.2 +/- 1.3 vs 1.3 +/- 0.8 dB/s(-1)) and DI-maximum plateau (eg, AS: 28.6 +/- 4.7 vs 18.3 +/- 6.4 dB) significantly decreased, respectively. CONCLUSION: Regional myocardial hypoperfusion at rest can be detected by using PDHI with MCE in clinical practice, according to a standardized methodologic protocol.     

Effect of Levovist on splanchnic hemodynamics in cirrhotic patients

This study was aimed to assess the effect of Levovist on Doppler parameters of splanchnic hemodynamics. A total of 12 patients with cirrhosis and 12 healthy subjects underwent Doppler ultrasound (US) examination of the portal vein and of the hepatic, splenic and superior mesenteric arteries before, 5 to 8 and 12 to 15 min after the start of an 8-min long IV infusion of 2.5 g of Levovist. Mean velocity and mean diameter were calculated for the portal vein. Resistance index was determined for the arteries. A significant increase of resistance index was observed in the hepatic (0.80 +/- 0.07 vs. 0.71 +/- 0.06; p < 0.01) and splenic arteries (0.72 +/- 0.06 vs. 0.64 +/- 0.06; p < 0.01) 5 to 8 min after contrast agent injection in patients with cirrhosis, but not in controls. Neither portal vein diameter nor portal flow mean velocity changed during the test in both controls and cirrhotic patients. This effect might be related to a selective trapping of microbubbles in the altered hepatic and splenic microvasculature in patients with cirrhosis rather than being artefactual. It might have implications on harmonic imaging US protocols designed to image the cirrhotic liver in the early arterial phase.     

In vitro quantification of flow using continuous infusion of Levovist and pairs of harmonic power Doppler images

To evaluate the potential of harmonic power Doppler to quantify perfusion using a continuous infusion of contrast, two dialysis cartridges were perfused with different flow rates adjusted between 0 to 300 mL/min, corresponding to flow ratios comprised between 300:0 and 150:150. The contrast agent (Levovist, Schering) was injected at constant rates (0.6 to 5 g/h). Sequential pairs of images showing simultaneously the cross-sections of the two filters were acquired with a HDI 5000 (ATL) and the Doppler data were processed with HDI lab software (ATL). The absolute values of the signal in the different regions-of-interest (ROI) were not closely related to flow rate. At the opposite, the rapid signal decrease between the first and the second image of each pair was inversely proportional to the flow rate. An index of perfusion [PerI = image 1/(image 1 -- image 2)] was defined. It correlated closely with the absolute and relative flow rates. For the latter, the slopes of regression were found to be independent of the infusion rate of Levovist. Thus, the use of pairs of images combined with a continuous infusion of Levovist provide a quantification of perfusion.     

Contrast agent increases Doppler velocities and improves reproducibility of aortic valve area measurements in patients with aortic stenosis.

Observer variability may limit assessment of aortic stenosis by Doppler echocardiography. This study aimed to assess whether echocardiographic contrast agent improves reproducibility of aortic valve area (AVA) measurements for patients with aortic stenosis. In all, 20 patients with aortic stenosis (67 +/- 10 years old) underwent noncontrast and contrast Doppler echocardiography on 2 occasions, 3 weeks apart. Intraobserver and interobserver coefficients of reproducibility were 0.36 and 0.20 cm for left ventricular outflow tract (LVOT) diameter, and 0.38 and 0.24 cm(2) for AVA, respectively. Although intraobserver reproducibility was unaffected, contrast improved interobserver reproducibility for LVOT diameter (mean of differences -0.02 +/- 0.07 cm vs 0.01 +/- 0.10 cm, P <.05) and AVA (mean of differences 0.02 +/- 0.10 cm(2) vs 0.07 +/- 0.12 cm(2), P <.05). Prevalve and postvalve velocities were increased with contrast compared with noncontrast imaging (prevalve, 1.07 +/- 0.20 vs 0.94 +/- 0.19 m/s, P <.01; postvalve, 3.76 +/- 0.87 vs 3.47 +/- 0.78 m/s, P <.01). We conclude that contrast significantly increases Doppler velocities and produces modest improvements in reproducibility of LVOT diameter and AVA. We suggest that, when assessing patients with aortic stenosis, contrast agents should be considered in patients who are difficult to image with poor baseline LVOT images or Doppler studies, or where there is poor interobserver reproducibility.     

Insonation facilitates plasmid DNA transfection into the central nervous system and microbubbles enhance the effect

Many of the diseases which affect the central nervous system are intractable to conventional therapies and therefore require alternative treatments such as gene therapy. Therapy requires safety, since the central nervous system is a critical organ. Choice of nonviral vectors such as naked plasmid DNA may have merit. However, transfection efficiencies of these vectors are low. We have investigated the use of 210.4 kHz ultrasound and found that 5.0 W/cm(2) of insonation for 5 s most effectively transfected a plasmid DNA into culture slices of mouse brain (147.68-fold increase compared with 0 W/cm(2) of insonation for 5 s). The effect was reinforced by combination with echo contrast agent, Levovist. One hundred fifty mg/mL of Levovist significantly increased gene transfection by ultrasound (5.23-fold when insonated at 5.0 W/cm(2) for 5 s). When DNA was intracranially injected, Levovist also enhanced gene transfection in newborn mice (4.49-fold increase when insonated at 5.0 W/cm(2) for 5 s). Since ultrasound successfully transfected naked plasmid DNA into the neural tissue and Levovist enhanced the effect, this approach may have a significant role in gene transfer to the central nervous system.     

Potential of gold-bound microtubules as a new ultrasound contrast agent

Contrast agents based on gas-filled microspheres share the problem of time limited opacification due to low stability of microbubbles. The aim of this study was to test if gold-bound microtubules provide backscattering that allows microtubules to be potentially useful as an ultrasound (US) contrast agent. Gold colloids were immobilized on protein microtubule walls. Latex balloons were filled with gold-bound microtubules or conventional left heart contrast agent and were ultrasonographically imaged in fundamental and harmonic modes. Feasibility of anti-beta-tubulin antibody conjugation to gold-bound microtubules was confirmed using immune fluorescence analysis. Gold particles were successfully bound to microtubules. Contrast intensities in latex balloons filled with gold-bound microtubules (141 +/- 35) were comparable to those with Levovist (180 +/- 35) and did not decrease significantly during continuous US imaging for 20 min (135 +/- 34 vs. Levovist 5.0 +/- 2.0). Anti-beta-tubulin antibodies were successfully conjugated to gold-bound microtubules. Gold-bound microtubules provide a persistent contrast effect, suggesting their use as an ultrasonic contrast agent with the feasibility of antibody conjugation.     

Feasibility of mitral flow assessment by echo-contrast ultrasound, part I: determination of the properties of echo-contrast agents

Data on the ultrasonic properties of commercially available contrast agents are limited by being instrument-dependent, especially with regard to their backscattering properties. The present work describes methods of measurements that provide instrument-independent estimations of a contrast agent's attenuation coefficient and integrated backscatter index and provide them as functions of its concentration. The two studied commercially available contrast agents were Albunex and Levovist SHU 508-A, both representative of agents in common use for echocardiography. The attenuation coefficients and integrated backscatter indices of both agents were found to be a linear function of their concentrations. Proportionality coefficients +/- their standard deviations are provided. Actually, square root values of the averaged backscatter indices normalized with respect to the rms of the reference signal were determined. The coefficients of proportionality were found to be: C(A) = 3.11+/-0.1813 dB/mm; C(L) = 0.07+/-0.005 dB/mm for attenuation coefficients of the Albunex and Levovist contrast agents, respectively, and the corresponding values for backscattering were: D(A) = 0.07+/-0.0054; D(L) = 0.02+/-0.0012. Being apparatus-independent, the findings of the study are important prerequisites for the use of these echo-contrast agents as an indicator in research for a quantitative assessment of blood flow.     

Assessment of no-reflow phenomenon after acute myocardial infarction with harmonic angiography and intravenous pump infusion with Levovist: comparison with intracoronary contrast injection.

Myocardial contrast echocardiography (intracoronary application) has emerged as an accurate method to detect the "no-reflow phenomenon." To investigate the diagnostic value of harmonic angiography after intravenous infusion of Levovist in assessing "no-reflow," both intracoronary and intravenous contrast injections were performed in a group of patients with acute myocardial infarction. Seventeen consecutive patients with a successfully reperfused acute myocardial infarction within 6 hours of symptom onset were selected for this study. All patients underwent contrast echocardiography with harmonic angiography with Levovist (400 mg/mL, intravenous pump infusion, trigger intervals 1:4 to 1:8) and sonicated albumin (0.5 to 1 mL, intracoronary bolus) on day 1 after the achievement of a sustained coronary reflow. Myocardial perfusion was qualitatively assessed with a 12-segment model. The endocardial length of the residual contrast defect after reflow was also calculated. Forty-four of 204 segments were not analyzed after intravenous contrast echocardiography and 37 after intracoronary contrast echocardiography because of artifacts. Intracoronary and intravenous injections showed a perfusion defect in 31 (19%) segments, with a concordance of 89% (kappa coefficient, 0.72). Concordance in anteroseptal, anterolateral, and inferolateral segments was 95% (kappa = 0.92), 88% (kappa = 0.66), and 83% (kappa = 0.57), respectively. With intracoronary injection used as the reference method, intravenous injection had a sensitivity of 74% and a specificity of 93% for diagnosing contrast defects. The endocardial extent of no-reflow was 18 +/- 19 after intravenous and 21 +/- 17 after intracoronary contrast echocardiography (P = not significant). Intravenous contrast echocardiography with Levovist reliably identifies the no-reflow phenomenon after successful reperfusion, especially in acute anteroseptal myocardial infarction.     

Analysis of color Doppler signal intensity variation after levovist injection: a new approach to the diagnosis of thyroid nodules.

The objective of this study was to evaluate the usefulness of a galactose-based ultrasonographic contrast agent, Levovist (Schering AG, Berlin, Germany), in differentiating benign from malignant thyroid nodules by analysis of the time-intensity curves correlating the variation of the intensity signal value during the contrast transit time. Fifty-four patients scheduled for surgical removal of a nodule or the thyroid gland or both after cytologic examination were enrolled in this study; all of the nodules underwent a baseline color and power Doppler evaluation and then to a color Doppler examination after an intravenous bolus injection of Levovist. The time-intensity curves were analyzed with respect to the histologic results. Carcinomas showed a significantly earlier arrival time of Levovist than nodular hyperplastic benign nodules and adenomas (8.1 +/- 1.41 versus 19.6 +/- 2.2 and 16.1 +/- 2.8 seconds; P < .0001), although no significant difference occurred between hyperplastic benign nodules and adenomas; carcinomas and adenomas showed an earlier time to peak than hyperplastic benign nodules (14.6 +/- 1.2 and 23.1 +/- 3.8 versus 33.0 +/- 3.0 seconds; P < .0001). No significant difference was found in baseline, peak, final intensity signal, and percent variation of intensity signal among hyperplastic benign nodules, adenomas, and carcinomas. Although cytologic examination still remains the standard of reference for the presurgical diagnosis of thyroid nodules, the preliminary data of this pilot study demonstrate that the analysis of time-intensity curves after Levovist injection might provide useful, complementary, and quantitative information to differentiate benign from malignant thyroid nodules.     

Measurement of coronary flow velocity reserve in the posterior descending coronary artery by contrast-enhanced transthoracic Doppler echocardiography.

BACKGROUND: Although the measurement of coronary flow velocity (CFV) reserve (CFVR) in the left anterior descending coronary artery (LAD) by transthoracic Doppler echocardiography has been established, its success rate in the posterior descending coronary artery (PD) is still limited. OBJECTIVE: This study reports the feasibility and diagnostic accuracy of measuring CFVR in the PD by transthoracic Doppler echocardiography. METHODS: CFVR in both the distal LAD and the PD was measured in 151 consecutive patients before coronary angiography. PD flow was investigated under the guidance of a nondirectional Doppler color flow map with harmonic imaging in the modified apical 2-chamber view. Intravenous contrast agent, Levovist, was injected to enhance the CFV envelope at baseline and during hyperemia. RESULTS: CFVR was obtained in 145 patients in the LAD and 126 patients in the PD (P <.001). The success rate of CFVR measurement in the PD was significantly higher in the last 50 patients (88%) than it was in the first 50 patients (72%) (P <.05). CFVR in the PD was significantly lower for patients with significant stenosis of the artery supplying the PD than it was in those without stenosis (1.58 +/- 0.59 vs 2.45 +/- 0.72, P <.001). CFVR in the distal LAD was 1.40 +/- 0.62 in patients with significant LAD stenosis and 2.45 +/- 0.80 in those without stenosis (P <.001). If a cut-off value of CFVR < 2 was used, sensitivity, specificity, and accuracy for the diagnosis of significant (>50%) stenosis of the artery supplying the PD were 84%, 83%, and 83%, respectively, whereas for the LAD they were 91%, 75%, and 80%, respectively. CONCLUSIONS: Noninvasive measurement of CFVR in the PD could be obtained in the majority of unselected patients using a nondirectional Doppler color flow map and contrast-enhanced harmonic imaging. The diagnostic accuracy of CFVR in the PD is similar to that of the LAD and, hence, has a potential clinical use.     

Effect of shell type on the in vivo backscatter from polymer-encapsulated microbubbles

This study compared in vivo enhancement from four different polymer-encapsulated ultrasound (US) contrast agents. The agents were produced with a rigid shell composed of the biodegradable block copolymer poly[D,L-lactide-co-glycolide] (PLGA) with the lactic and glycolic acid ratios 50:50, 75:25, 85:15 and 100:0 (i.e., increasingly hydrophobic shell compositions). Approximately the same bubble diameter (1.2 microm) and concentration (0.4 g/mL) were obtained for each agent. In four rabbits, audio Doppler signals were acquired from a 10 MHz cuff transducer placed around a surgically exposed vessel (contrast dose: 0.0125 to 0.15 mL/kg). In vivo dose responses were calculated off-line (in dB). Nine rabbit kidneys were imaged during contrast administration (0.1 mL/kg) in power Doppler and grey-scale pulse inversion harmonic (PIHI) modes using an HDI 5000 scanner (Philips Medical Systems, Bothell, WA). Time-intensity curves were produced and the time-to-peak, peak intensity, slope, area under the curve (AUC) and total duration of enhancement for each agent were compared. All agents produced marked Doppler enhancement with increasing duration from the 50:50 agent (48 +/- 10 s) to the 75:25 agent (166 +/- 46 s), the 85:15 agent (403 +/- 83 s) and with the 100:0 agent (603 +/- 93 s) lasting longest (p < 0.02). No other parameters changed significantly, except the AUC of the 85:15 agent, which was greater than that of the 50:50 agent (190.75 vs. 61.58; p = 0.02). The in vivo dose-response curves were similar for all agents, with mean enhancement up to 20.6 +/- 1.11 dB (p = 0.17). In conclusion, contrast duration increases by an order of magnitude as the lactic acid component in the polymer-encapsulated bubbles increases and the shell, thus, becomes increasingly hydrophobic.     

Echocardiographic contrast imaging of the human right heart: a multicenter study of the efficacy, safety, and reproducibility of intravenous SHU-454.

The contrast agent SHU-454 was intravenously injected in 103 patients during echocardiography: 37 mL/patient +/- 7 ml/patient. The quality of the contrast effect was optimal in 13, good in 51, sufficient in 30, and poor in 9 patients; reproducibility was optimal in 38, good in 46, sufficient in 17, and poor in 2 patients. Taste sensation, arm discomfort, or atypical chest pain occurred in 5 patients, premature ventricular contractions in 3. An isolated anginal attack occurred in 1 patient with frequent episodes at rest. A slight reduction in hematologic indices was attributed to hemodilution. Thus, SHU-454 produces a good and reproducible contrast effect with tolerable side effects.     

The Carotid Artery as an Alternative Site to the Middle Cerebral Artery for Reproducible Estimates of Autoregulation Index

Temporal insonation is not always possible for the middle cerebral artery (MCA) for blood flow velocity (BFV) measurements, to estimate cerebral autoregulation. We compared BFV and cerebral autoregulation estimates from the common-carotid (CCA) and internal-carotid arteries (ICA) with the MCA. BFV was measured at the CCA, ICA and MCA, synchronously with blood pressure, heart rate and end-tidal CO₂ and was recorded onto a data acquisition system. The autoregulation index (ARI) estimated using the Tiecks model. Eleven healthy volunteers (7 women, 33 ± 9 years old) were recruited. BFVs in the MCA, CCA and ICA were 60.3 ± 8.9, 64.4 ± 6.5 and 69.2 ± 4.8 cm/s, respectively. ARI estimates were not significantly different (5.6 ± 0.8, 6.0 ± 1.1 and 5.9 ± 0.5, respectively). Good reproducibility over repeated measurements was evidenced by low coefficient of variation of standard error of measurement for BFV and ARI. The CCA and ICA are alternatives to the MCA, where insonation is impossible, because of an absent trans-temporal window or where it cannot be tolerated, such as in patients with head injury.     

Observation on the integrity of the blood-brain barrier after microbubble destruction by diagnostic transcranial color-coded sonography.

OBJECTIVE: To investigate alteration of the blood-brain barrier from ultrasonic contrast agent destruction by diagnostic transcranial color-coded sonography using gadolinium-enhanced magnetic resonance imaging. METHODS: Healthy male volunteers received 10 mL (400 mg/dL) of Levovist (SH U 508A; Schering AG, Berlin, Germany; n = 6) or 3 mL of Optison (FS069; Mallinckrodt Inc, St Louis, MO; n = 4) followed by 0.3 mmol/kg magnetic resonance imaging contrast agent (Magnevist; Schering) intravenously. Then transcranial color-coded sonography was performed with a conventional color duplex sonographic system, which insonated the brain in a slightly angulated axial plane with temporal average intensity of less than 700 mW/cm2 or acoustic pressure amplitude of less than 2.69 MPa, attenuated by the temporal bone. Before, immediately after, and 2 hours after insonation, T1-weighted axial magnetic resonance imaging was performed. All magnetic resonance images were individually assessed, and T1 signal intensities were measured in 2 regions of interest in both hemispheres at the 3 time points. RESULTS: No focal contrast enhancement or damage to the brain and no significant difference between T1 signal intensities in the right and left brain regions could be detected during early or late phases when either ultrasonic contrast agent was used. CONCLUSIONS: This bioeffects study gives further evidence of the safety of ultrasonic destruction of Levovist and Optison microbubbles by diagnostic transcranial color-coded sonography. However, more subtle local effects may have been missed by gadolinium-enhanced magnetic resonance imaging. Studies on diagnostic contrast-enhanced transcranial color-coded sonography as well as microbubble-based drug delivery strategies should consider ultrasonic contrast agent microbubble characteristics and concentration as well as ultrasound transmission power levels.     

Contrast-enhanced transvaginal sonography of benign versus malignant ovarian masses: preliminary findings.

OBJECTIVE: The aim of this prospective study was to evaluate differences in contrast enhancement and contrast enhancement kinetics in benign versus malignant ovarian masses with pulse inversion harmonic transvaginal sonography. METHODS: Seventeen consecutive patients with 23 morphologically abnormal ovarian masses (solid or cystic with papillary excrescences, focally thickened walls, or irregular solid areas) smaller than 10 cm received a microbubble contrast agent intravenously while undergoing pulse inversion harmonic transvaginal sonography. The following parameters were assessed in all tumors: detectable contrast enhancement, time to peak enhancement (wash-in), peak contrast enhancement, half wash-out time, and area under the enhancement curve. Tumor histologic analysis was used to distinguish benign from malignant ovarian tumors. RESULTS: Fourteen benign masses and 9 malignancies were studied. There was a statistically significant difference in the peak enhancement (mean +/- SD, 23.3 +/- 2.8 versus 12.3 +/- 3.9 dB; P < .01), half wash-out time (139.9 +/- 43.6 versus 46.3 +/- 19.7 seconds; P < .01), and area under the enhancement curve (2012.9 +/- 532.9 versus 523.9 +/- 318 seconds(-1); P < .01) in malignant masses compared with benign disease. There was no statistically significant difference in the time to peak enhancement (26.1 +/- 6.3 versus 24.9 +/- 7.6 seconds; P = .07). CONCLUSIONS: Overall, our data showed a significant difference in the contrast enhancement kinetic parameters between benign and malignant ovarian masses.     

Changes in intracranial pressure and cerebral autoregulation in patients with severe traumatic brain injury

BACKGROUND: Impaired cerebral autoregulation is frequent after severe traumatic head injury. This could result in intracranial pressure fluctuating passively with the mean arterial pressure. OBJECTIVE: This study examines the influence of autoregulation on the amplitude and direction of changes in intracranial pressure in patients with severe head injuries during the management of cerebral perfusion pressure. DESIGN: Prospective study. SETTING: Neurosurgical intensive care unit PATIENTS: A total of 42 patients with severe head injuries. INTERVENTIONS: Continuous recording of cerebral blood flow velocity, intracranial pressure, and mean arterial pressure during the start or change of continuous norepinephrine infusion. MEASUREMENTS AND MAIN RESULTS: Cerebrovascular resistance was calculated from the cerebral perfusion pressure and middle cerebral artery blood flow velocity. The strength of autoregulation index was calculated as the ratio of the percentage of change in cerebrovascular resistance by the percentage of change in cerebral perfusion pressure before and after 121 changes in mean arterial pressure at constant ventilation between day 1 and day 18 after trauma. The strength of autoregulation index varied widely, indicating either preserved or severely perturbed autoregulation during hypotensive or hypertensive challenge in patients with or without intracranial hypertension at the basal state (strength of autoregulation index, 0.51 +/- 0.32 to 0.71 +/- 0.25). The change in intracranial pressure varied linearly with the strength of autoregulation index. There was a clinically significant change in intracranial pressure (> or =5 mm Hg) in the same direction as the change in mean arterial pressure in five tracings of three patients. This was caused by the mean arterial pressure dropping below the identified lower limit of autoregulation in three tracings for two patients. It seemed to be caused by a loss of cerebral autoregulation in the remaining two tracings for one patient. CONCLUSION: Cerebral perfusion pressure-oriented therapy can be a safe way to reduce intracranial pressure, whatever the status of autoregulation, in almost all patients with severe head injuries.     

Rapid quantitative assessment of myocardial perfusion: spectral analysis of myocardial contrast echocardiographic images.

We described a novel rapid spectral analysis technique performed on raw digital in-phase quadrature (IQ) data that quantitatively differentiated perfused from nonperfused myocardium based on the simultaneous comparison of local fundamental and harmonic frequency band intensity levels. In open-chest pigs after ligation of the left anterior descending coronary artery (LAD) and continuous venous contrast infusion, the fundamental-to-harmonic intensity ratio (FHIR) for samples placed within the left ventricular (LV) cavity (10.8 +/- 1.7 dB) and perfused myocardium (13.7 +/- 1.6 dB) were significantly (P <.001) lower than for nonperfused myocardium (27.1 +/- 2.9 dB). In attenuated images, the FHIR for the LV cavity and perfused myocardium were also significantly (P <.05) lower than for the nonperfused myocardium (21.4 +/- 3.0 dB, 34.4 +/- 3.2 dB, and 40.2 +/- 4.4 dB, respectively). Spectral properties of contrast microbubbles, as characterized by the FHIR, allow for rapid quantitative assessment of myocardial perfusion from data contained in a single-image frame, without requiring background image subtraction and image averaging.     

The repeatability of cerebral autoregulation assessment using sinusoidal lower body negative pressure

A forced periodic variation in blood pressure produces a similar variation in cerebral blood velocity. The amplitudes and phases of the pressure and velocity waveforms are indicative of the dynamic response of the cerebral autoregulation. The phase of the velocity leads the pressure; the greater the phase difference the faster the autoregulation response. Various techniques have been employed to oscillate arterial blood pressure but measurement reproducibility has been poor. The purpose of this study was to assess the reproducibility of phase measurements when sinusoidal lower body negative pressure is used to vary blood pressure. Five healthy volunteers were assessed at two vacuum levels on each of eight visits. For each measurement a 12 s sinusoidal cycle was maintained for 5 min. The Fourier components of blood pressure and the middle cerebral artery velocity were determined at the oscillation frequency. The phase of velocity consistently led the pressure. The mean phase difference was 42+/-13 degrees for the stronger vacuum and 36+/-42 degrees for the weaker vacuum. The variation given is the within-subjects standard deviation estimated from a one-way analysis of variance. Sinusoidal lower body negative pressure is a useful stimulus for investigating autoregulation; it has advantages over other methods. High vacuums show good reproducibility but are too uncomfortable for patient use.