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Difference of optimal dose of contrast agent between gray-scale and power Doppler imaging in assessing graded coronary stenosis by myocardial contrast echocardiography.

RATIONALE AND OBJECTIVES: In myocardial contrast echocardiography (MCE), power Doppler imaging is more sensitive to contrast agent (microbubble) than gray-scale B-mode imaging; however, no data exist regarding the optimal contrast dose in power Doppler imaging. This study examined the optimal dose of contrast agent for power Doppler in assessing coronary stenosis. METHODS: Three grades of coronary stenosis were produced in 6 open-chest dogs. MCE was performed with gray-scale and power Doppler during continuous infusion of 0.2 mL/min FS-069. Thereafter, MCE was repeated with power Doppler during continuous infusion of 0.1 mL/min FS-069. RESULTS: Although the videointensity in the stenosed bed with power Doppler (214 +/- 14) was greater than gray scale (35 +/- 17) during 0.2 mL/min FS-069 infusion (P < 0.0001), power Doppler failed to identify milder coronary stenoses because videointensity in stenosed bed was quickly saturated with contrast agent. The videointensity in the stenosed bed with power Doppler (127 +/- 49) during 0.1 mL/min FS-069 infusion was greater than gray scale (35 +/- 17) during 0.2 mL/min FS-069 infusion (P < 0.0001), and all levels of stenosis were identified with power Doppler, even though the dose of contrast agent was half of that of gray scale imaging. The correlation between videointensity and myocardial blood flow was better in the case of power Doppler at 0.1 mL/min FS-069 infusion (r = 0.77, P < 0.0001) than in the case of gray scale imaging at 0.2 mL/min FS-069 infusion (r = 0.66, P < 0.01). CONCLUSIONS: These data support the need for a lower dose of contrast agent for power Doppler than for gray scale to detect milder coronary stenosis and avoid saturation of imaging fields.

Animals↗

Contrast-assisted ultrasound for sentinel lymph node detection in spontaneously arising canine head and neck tumors.

OBJECTIVES: We sought to evaluate a minimally invasive contrast-assisted ultrasound (US) technique for sentinel lymph node (SLN) localization. METHODS: Microbubble contrast medium was injected into peritumoral tissues in 10 dogs with spontaneous head or neck tumors. Regional lymph nodes (LNs) were imaged up to 20 minutes after contrast administration using power Doppler US. Comparative lymphoscintigraphy studies were performed in all dogs by peritumoral injection of 99mTc-sulfur colloid administered around the primary lesion. RESULTS: US contrast enhancement of SLN revealed sentinel nodes and associated lymphatics in 8 of 10 dogs. In each instance in which contrast-enhanced LN was identified with US, a corresponding SLN was detected by lymphoscintigraphy. Multiple SLNs were present in 2 dogs. Regional lymph nodes were positive for metastasis in 1 dog and reactive in 9 dogs. CONCLUSIONS: Contrast-assisted US is effective in localizing SLN. This technique could reduce or eliminate many of the limitations of current SLN detection procedures.

Animals↗

A revolution in liver ultrasound.

Liver ultrasound has been revolutionized by the development of microbubble contrast agents and multipulse software designed to detect their nonlinear resonances. The ability to visualize all parts of the liver's vasculature, including the sinusoids, at high spatial and temporal resolution gives unique insights into the haemodynamics of focal liver lesions. It has enabled ultrasound to detect and, as described by Celli N, et al.Eur J Gastroenterol Hepatol 2007; 3-14, to characterize such lesions with an accuracy comparable to multidetector computed tomography with consequent improvements in patient handling.

Contrast Media↗

Prostate ultrasound--for urologists only?

The value of ultrasound (US) in the diagnosis of prostate cancer has dramatically increased in the past decade. This is mainly related to the increasing incidence of prostate cancer, the most common cancer in men and one of the most important causes of death from cancer in men. The value of conventional gray-scale US for prostate cancer detection has been extensively investigated, and has shown a low sensitivity and specificity. Therefore conventional gray-scale US is mainly used by urologists for guiding systematic prostate biopsies. With the development of new US techniques, such as color and power Doppler US, and the introduction of US contrast agents, the role of US for prostate cancer detection has dramatically changed. Advances in US techniques were introduced to further increase the value of US contrast agents. Although most of these developments in US techniques, which use the interaction of the contrast agent with the transmitted US waves, are very sensitive for the detection of microbubbles, they are mostly unexplored, in particular for prostate applications. Early reports of contrast-enhanced US investigations of blood flow of the prostate have shown that contrast-enhanced US adds important information to the conventional gray-scale US technique. Furthermore, elastography or 'strain imaging' seems to have great potential in prostate cancer detection. Since these new advances in US are very sophisticated and need a long learning curve, radiologists, who are overall better trained with these new US techniques, will play a more important role in prostate cancer diagnosis. Current trends show that these new US techniques may allow for targeted biopsies and therefore replace the current 'gold standard' for prostate cancer detection--the systematic biopsy. Consequently the use of these new US techniques for the detection and clinical staging of prostate cancer is promising. However, future clinical trials will be needed to determine if the promise of these new US advances of the prostate evolves into clinical application.

Humans↗

Pulse-inversion-based fundamental imaging for contrast detection.

Pulse-inversion-based fundamental imaging was experimentally investigated for the enhancement of contrast detection. The pulse-inversion technique involves two firings with inverted waveforms. When the returning echoes from the two firings are summed, the residue signal is limited to even-order harmonics for tissue. However, when the returning echoes are from microbubbles, the fundamental signal is not completely cancelled because the reaction of the bubbles under compression is different from that under rarefaction. Thus, with the application of pulse-inversion technique, the fundamental signal can be used to enhance the contrast-to-tissue ratio. In this paper, B-mode, pulse-inversion-based fundamental images were constructed with various transmit waveforms. Motion artifacts also were studied. The results indicate that the contrast-to-tissue ratio was significantly enhanced compared to that obtained using either conventional, fundamental imaging or second-harmonic imaging. Longer transmit pulses resulted in a better signal-to-noise ratio, but did not noticeably affect the nonlinear response of the bubbles. In addition, the optimal ratio of the magnitude of the positive pulse to that of the negative pulse was unity, in terms of avoiding the uncancelled, third-order response in the fundamental frequency range. It also was found that the pulse-inversion fundamental technique is highly sensitive to tissue motion because the fundamental tissue signal is not cancelled when motion is present.

Artifacts↗

Predicting backscatter characteristics from micron- and submicron-scale ultrasound contrast agents using a size-integration technique.

In this paper, a computationally, inexpensive, size-integration method based on a modified Rayleigh-Plesset model is developed to predict backscatter spectra from groups of bubbles with various size distributions, incident acoustic amplitudes, and driving frequencies. The method was validated using experimentally measured spectra from contrast bubbles of various sizes: Optison, Levovist, ST68 microbubbles, and submicron bubbles. This method provides a computationally inexpensive means of examining backscatter spectrum from multiple bubbles, especially in predicting occurrence and relative amplitude of subharmonics and second harmonics.

Algorithms↗

Vascular damage as a risk factor for benign prostatic hyperplasia and erectile dysfunction.

OBJECTIVE: To assess benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), both considered to be associated with urogenital ageing, in ageing men in a cross-sectional population study, comparing them with healthy controls by using symptom scores and contrast-enhanced colour Doppler ultrasonography (CDUS). PATIENTS, SUBJECTS AND METHODS: Transrectal CDUS and quantitative measurement of colour pixel intensity (CPI) are excellent minimally invasive techniques for assessing normal and pathological blood flow. CDUS was performed using the microbubble-based ultrasound enhancer for evaluating prostate, bladder neck and corpus cavernosum vascularity in young healthy men, men with BPH, and men with severe vascular damage (diabetes mellitus type 2). Resistive index measurements and computer-assisted quantification of CPI were used to objectively evaluate perfusion. The International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF) were applied to quantify the symptoms. RESULTS: In patients with BPH, perfusion of the transition zone (TZ) of the prostate was significantly lower and the resistive index of the TZ significantly higher (both P < 0.001) than in healthy controls. The perfusion patterns of men with BPH and those who also had severe vascular damage (diabetes mellitus type 2) showed that vascularity in the latter group was lower in the prostatic TZ and the corpora cavernosa. In patients with BPH the IPSS, quality-of-life and IIEF scores were significantly worse than in the control group. Men with concomitant atherosclerosis had even worse symptom scores. CONCLUSION: These results strongly support the hypothesis that age-related impairment of blood supply to the lower urinary tract is important in the development of BPH and ED. Vascular damage may cause chronic ischaemia and thus be a contributing factor in the pathogenesis of BPH and ED.

Adult↗

Almost perfect concordance between simultaneous transcranial Doppler and transesophageal echocardiography in the quantification of right-to-left shunts.

BACKGROUND AND PURPOSE: Transesophageal echocardiography (TEE) and transcranial Doppler (TCD) are the methods of choice to study patent foramen ovale (PFO), but there are discrepancies between the 2 concerning PFO detection. No study has analyzed right-to-left shunt (RLS) quantification concordance. The 2 methods are carried out in different hemodynamic states, and the Valsalva maneuver (VM) required in each also differs. The authors compared PFO detection and concordance of RLS quantification classifications performing the 2 studies simultaneously. METHODS: The authors prospectively included consecutive stroke patients undergoing TEE and applied the TCD protocol of the Consensus Conference. Echocardiographic PFO was diagnosed when at least 3 microbubbles (MBs) were detected in the left atrium within 3 heartbeats after opacification of the right atrium. RLS quantification was (1) TCD: minimum (1-10 MBs), moderate (11-25 MBs), and massive (>25 MBs) and (2) TEE: small (3-10 MBs), moderate (11-30 MBs), and large (>30 MBs). STATISTICS: contingency tables (chi(2) and K test). Results. The authors studied 110 patients whose mean age was 56.7 +/- 12.1 years, and 60.9% were men. PFO was detected at the first VM in 30% of patients with TCD and in 31.8% with TEE. At the second VM, both methods detected the same patients (32.7%). RLS was minimum (14), moderate (5), and massive (17) in TCD and small (13), moderate (3), and large (20) in TEE. There was an almost perfect concordance in RLS quantification (K = 0.928, P = .001), with only 4 discrepancies. CONCLUSIONS: Simultaneous study with TCD and TEE showed an almost perfect concordance in PFO detection and RLS quantification.

Adult↗

Noninvasive measurement of steady and pulsating velocity profiles and shear rates in arteries using echo PIV: in vitro validation studies.

Although accurate measurement of velocity profiles, multiple velocity vectors, and shear stress in arteries is important, there is still no easy method to obtain such information in vivo. We report on the utility of combining ultrasound contrast imaging with particle image velocimetry (PIV) for noninvasive measurement of velocity vectors. This method (echo PIV) takes advantage of the strong backscatter characteristics of small gas-filled microbubbles (contrast) seeded into the flow. The method was tested in vitro. The steady flow analytical solution and optical PIV measurements (for pulsatile flow) were used for comparison. When compared to the analytical solution, both echo PIV and optical PIV resolved the steady velocity profile well. Error in shear rate as measured by echo PIV (8%) was comparable to the error of optical PIV (6.5%). In pulsatile flow, echo PIV velocity profiles agreed well with optical PIV profiles. Echo PIV followed the general profile of pulsatile shear stress across the artery but underestimated wall shear at certain time points. However, error in shear from echo PIV was an order of magnitude less than error from current shear measurement methods. These studies indicate that echo PIV is a promising technique for noninvasive measurement of velocity profiles and shear stress.

Animals↗

The effect of surface agitation on ultrasound-mediated gene transfer in vitro.

This article reports the effect of surface agitation of culture medium on ultrasound-mediated gene transfection in vitro and its possible mechanisms. The possibility of active induction of bubbles without using contrast microbubbles for effective gene transfer was also demonstrated. Cultured HeLa cells mixed with green fluorescent protein plasmid were exposed to 1.0 MHz ultrasound in 24-well culture plates. Up to 26% transfection efficiency in the survival cell population was achieved in samples exposed to 0.44 MPa ultrasound pulses with the presence of surface agitation. Inertial cavitation and bubble generation were observed throughout the ultrasound exposure. When surface agitation was suppressed by covering the medium surface with a thin membrane, bubble generation and gene transfection were significantly suppressed. Interestingly, transfection efficiency could be partially resumed by adding a small amount of culture medium onto the covering membrane to rebuild the surface agitation and bubble generation. Pressure fluctuation and transient high-pressure loci were found in samples with surface agitation. Numerical simulations of bubble dynamics showed that transient high pressures above the inertial cavitation threshold could generate bubbles, which might be subsequently stabilized at lower pressures by rectified diffusion, and exert strong shear forces that might create transient pores on cell membranes to facilitate gene transfer.

Cell Survival↗

Contrast-enhanced voiding US for grading of reflux in adult patients prior to antireflux ureteral implantation.

PURPOSE: To prospectively assess contrast material-enhanced voiding ultrasonography (US) for grading of vesicoureteral reflux (VUR) and to compare results with those of voiding cystourethrography (VCUG) in adult patients undergoing antireflux ureteral implantation. MATERIALS AND METHODS: Thirty-seven consecutive adult patients who had undergone renal transplantation with Politano-Leadbetter (18 patients) or Lich-Gregoire (19 patients) technique were included on the basis of previous urinary tract infections (UTIs) and time elapsed after renal transplantation. Exclusion criterion was current UTI. US was performed by one of two sonologists with injection of saline and microbubble suspension and was recorded on videotape. Sonologists assigned VUR diagnosis in consensus after videotape review. VCUG was performed by one of two radiologists immediately after US. Radiologists were blinded to US findings and assigned VCUG diagnoses in consensus. Contingency table was used to compare US and VCUG. Agreement between US and VCUG was determined with kappa statistics. RESULTS: With VCUG, VUR was diagnosed in 15 patients and not diagnosed in 22 patients. US and VCUG results were in agreement in 14 patients with VUR and 21 patients without VUR. US sensitivity and specificity for detection of VUR were 93% (14 true-positive results in 15 abnormal cases) and 95% (21 true-negative results in 22 normal cases), respectively. Agreement between US and VCUG was 95% (kappa = 0.89, P <.001). In 11 of 14 patients, VUR grades were in agreement for US and VCUG. In three of 14 patients, US indicated a higher grade than did VCUG. VUR was diagnosed in seven of 18 Politano-Leadbetter cases and eight of 19 Lich-Gregoire cases. CONCLUSION: A high rate of agreement was seen between voiding US and VCUG.

Adult↗

Ultrasound contrast agents for brain perfusion imaging and ischemic stroke therapy.

Stroke is one of the major causes of death and disabilities in industrialized countries. Ultrasound imaging is a largely wide spread bedside technique that is easily accessible and valuable in case of emergency but suffers from the fact that the ultrasound wave has to cross the skull for brain imaging. However, ultrasound contrast agents and new contrast-specific imaging modalities have helped to improve the diagnostic quality of transcranial ultrasonography. This review article surveys and discusses the current state of microbubbles technology and the use of contrast-enhanced transcranial ultrasound for the assessment of brain perfusion. Future aspects and expectations in contrast agent functionality, such as targeting and drug or gene delivery, acceleration of thrombolysis, and imaging technology, are also discussed.

Brain↗

Real-time blood-pool images of contrast enhanced ultrasound with Definity in the detection of tumour nodules in the liver.

Lower mechanical index (MI) technique with newer microbubble agents has been introduced into clinical practice as a newer ultrasound (US) imaging. However, the efficacy in detecting tumour nodules has not been proven scientifically. The aim of this study was to elucidate the efficacy of a blood-pool image of real-time contrast-enhanced US under low MI in detecting liver tumours. 15 rabbits with VX-2 tumour were used; the number of implantations was none in two rabbits, one in four, two in five and three in four. US equipment was APLIO (Toshiba) with linear probe (3.5/7.0 MHz). The number, location and size of tumour nodules were examined by non-contrast tissue harmonic imaging (NC-US) or contrast-enhanced pulse subtraction harmonic imaging (C-US) under extra-low MI (MI 0.065) with the injection of Definity (30 microl kg(-1)). The number of tumour nodules detected by both NC-US and C-US were consistent with the histopathological results in five rabbits - two with none, two with one nodule and one with two nodules. In the other 10 rabbits, C-US showed all the implanted tumours and small daughter nodules around them that were confirmed by histopathology. However, NC-US failed to demonstrate two implanted nodules and all the daughter nodules. On the basis of the histopathological results, detectability of implanted tumour was not significantly different between NC-US (24/26, 92.3%) and C-US (26/26, 100%). However C-US was superior to NC-US in delineating the nodules and in detecting small daughter nodules. The sizes of the implanted tumour nodules measured by histopathology correlated closely with those measured by C-US. Real-time blood-pool images by pulse subtraction harmonic imaging under extra-low MI with Definity will contribute to the improvement of the ultrasound delineation and detection of liver tumours.

Animals↗

Biological effects of low intensity ultrasound: the mechanism involved, and its implications on therapy and on biosafety of ultrasound.

The biological effects of low intensity ultrasound (US) in vitro; the mechanisms involved; and the factors that can enhance or inhibit these effects are reviewed. The lowest possible US intensities required to induce cell killing or to produce free radicals were determined. Following sonication in the region of these intensities, the effects of US in combination with either hyperthermia, hypotonia, echo-contrast agents (ECA), CO2, incubation time, high cell density or various agents were examined. The results showed that hyperthermia, hypotonia and microbubbles are good enhancers of the bioeffects, while CO2, incubation time and high cell density are good inhibitors. Cellular membrane damage is pivotal in the events leading to cell death, with the cellular damage-and-repair mechanism as an important determinant of the fate of the damaged cells. The optimal level of apoptosis (with minimal lysis) and optimal gene transfection efficiency were attained using a pulsed low intensity US. In summary, the findings suggest that low intensity US is potentially useful in therapy, while on the other hand, they also call for further investigation of such clinical scenarios as high-grade fever, edema or use of ECA which may lead to the lowering of the threshold for bioeffects with diagnostic US.

Animals↗

Focused ultrasound for blood-brain disruption and delivery of therapeutic molecules into the brain.

Noninvasive, transient and local image-guided blood-brain barrier disruption can be accomplished using focused ultrasound exposure with intravascular injection of preformed microbubbles. MRI-guided blood-brain barrier disruption has been demonstrated and has been shown to heal in within a few hours after exposure. The delivery of several marker molecules has been demonstrated in different animal models with minimal or no damage to the brain tissue. Most notably, the delivery of antibodies and liposomal doxorubicin has been shown. The method may potentially open a new era in CNS drug delivery and perhaps also aid in molecular imaging and targeting. However, effective clinical devices and methods need to be developed further and the clinical feasibility demonstrated.

Animals↗

Second-generation sonographic contrast agent for differential diagnosis of perisplenic lesions.

OBJECTIVE: On contrast-enhanced sonography, second-generation contrast media have shown a spleen-specific uptake of the microbubble contrast agent. To date, there is little data about the diagnostic value of contrast-enhanced sonography in perisplenic lesions. CONCLUSION: In patients with a perisplenic tumor of unknown cause, contrast-enhanced sonography enables the diagnosis or exclusion of accessory spleens.

Adult↗

Characterization of hepatic tumors: value of contrast-enhanced coded phase-inversion harmonic angio.

OBJECTIVE: Our purpose was to evaluate the value of contrast-enhanced coded phase-inversion harmonic imaging in showing the characteristic intranodular hemodynamics of hepatic tumors. SUBJECTS AND METHODS. Using a microbubble contrast agent we performed coded harmonic angio in 163 patients with 192 hepatic tumor nodules: 153 hepatocellular carcinomas, 13 metastases, 14 hemangiomas, eight dysplastic nodules, and four focal nodular hyperplasias. After injecting Levovist, we performed real-time scanning, interval-delay fast low-angle shot imaging, and sweep scanning in the early arterial phase, late vascular phase, and postvascular phase, respectively. RESULTS: On contrast-enhanced coded harmonic angio, the typical hemodynamic pattern of hepatocellular carcinomas was shown as abundant tumor vessels supplied from the periphery to the center of the tumor and dense parenchymal tumor staining with fast washout (sensitivity, 92.8%; specificity, 92.3%). The characteristic hemodynamic pattern of metastases was peripheral tumor vessels with a rim parenchymal stain in the vascular phase followed by a perfusion defect in the postvascular phase (sensitivity, 69.2%; specificity, 100%). Hemangiomas were hypovascular in the early arterial phase with gradual spotty or cotton-wool pooling continuing to the late vascular phase (sensitivity, 92.9%; specificity, 100%). Dysplastic nodules were shown as having no early arterial supply with isovascularity in the late vascular phase (sensitivity, 75%; specificity, 100%). Focal nodular hyperplasias were shown to have a spoked wheel pattern of blood vessels accompanied by dense staining in interval-delay scanning (sensitivity, 100%; specificity, 100%). CONCLUSION: Contrast-enhanced coded harmonic angio is a promising method to provide useful information for the differential diagnosis of hepatic tumors.

Adult↗

Contrast ultrasonographic assessment of cerebral perfusion in patients undergoing decompressive craniectomy for traumatic brain injury.

OBJECT: The aims of this study were to determine whether contrast-enhanced ultrasonography (CEU) could be used for noninvasive evaluation of cerebral perfusion in patients with traumatic brain injury (TBI) and to assess the effect of decompressive surgery on cerebral perfusion as measured by CEU. METHODS: Contrast-enhanced ultrasonography with intravenous administration of a microbubble contrast agent was performed in six patients with TBI undergoing decompressive craniectomy. Contrast-enhanced ultrasonography was performed through a bur hole before craniectomy and through the calvarial defect immediately after craniectomy and on postoperative Days 1 and 2. For the latter two studies, patients were placed in the recumbent position and at a 35 degrees incline to investigate changes in perfusion produced by modulation of intracranial pressure (ICP). Cerebral microvascular blood flow increased by almost threefold immediately after craniectomy, from a mean of 7.5 +/- 6.9 (standard deviation [SD]) to 20.9 +/- 11.6 (p < 0.05), and further improved on postoperative Day 1 (mean 37.1 +/- 13.9 [SD], p < 0.05, compared with postcraniectomy microvascular blood flow) without subsequent change on Day 2. The change in microvascular perfusion correlated inversely with the initial ICP (p < 0.01), indicating less recovery of flow when preoperative ICP was markedly elevated. On postoperative Days 1 and 2, head-of-bed elevation produced an increase in microvascular perfusion on CEU (mean 37 +/- 11 compared with 51 +/- 20, p < 0.05) and a small decrease in ICP (mean 16 +/- 5 mm Hg compared with 12 +/- 4 mm Hg, p < 0.05). In patients with parenchymal hematoma, CEU provided spatial information on perfusion abnormalities in the hemorrhagic core and surrounding tissues. CONCLUSIONS: Contrast-enhanced ultrasonography has potential for the intraoperative and bedside assessment of cerebral perfusion in patients with TBI. The technique may be appropriate for evaluating responses to therapies aimed at preventing secondary ischemia and for assessing regional perfusion abnormalities.

Adolescent↗