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Vascular damage induced by type 2 diabetes mellitus as a risk factor for benign prostatic hyperplasia.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the relationship between benign prostatic hyperplasia (BPH) and arteriosclerosis shown in a model of type 2 diabetes in a trans-sectional population study using contrast-enhanced colour Doppler ultrasound for exact assessment of prostatic blood flow. METHODS: Contrast-enhanced transrectal colour Doppler ultrasound was performed using a microbubble-based ultrasound enhancer SonoVue for evaluating prostate vascularity (transitional zone [TZ] and peripheral zone [PZ]) in diabetic BPH patients, non-diabetic BPH patients and healthy subjects. Computer-assisted quantification of colour pixel intensity (CPI) was used to objectively evaluate the prostate vascularity. Resistive index measurements were obtained in the TZ and the PZ. Findings were compared between these three groups. RESULTS: TZ-CPI was significantly lower in diabetic patients than in non-diabetic BPH men (p=0.001), whereas the CPI of the PZ showed no difference between these two groups (p=0.978). TZ-CPI of patients with diabetic and non-diabetic BPH were significantly lower than in controls (p<0.001), but no difference was found between diabetic and healthy patients in the PZ (p=0.022) and borderline significance was seen when comparing patients of the BPH group with the control patients (p=0.019). Resistive index values of the TZ in diabetic patients showed significantly higher values (p<0.001) than the BPH and control groups. CONCLUSIONS/INTERPRETATION: The significantly lower CPI and higher resistive index values of the TZ in diabetic patients compared with patients with non-diabetic BPH and healthy subjects indicate considerable vascular damage in the TZ of these patients. Diabetic vascular damage may cause hypoxia and may contribute to the pathogenesis of BPH.

Adult↗

Comparison of echo-enhanced ultrasound with fluoroscopic MCU for the detection of vesicoureteral reflux in neonates.

BACKGROUND: Fluoroscopic micturating cystourethrography (MCU) is used for screening and grading of vesicoureteral reflux (VUR). It involves ionizing radiation. This study was designed to assess the efficacy of contrast-enhanced sonography in predicting the presence or absence of VUR. OBJECTIVE: To compare an ultrasound contrast agent for detection of VUR in at-risk infants, and to compare these findings with fluoroscopic MCU with the aim of determining whether echo-enhanced sonography could be used instead of fluoroscopic MCU to identify neonates who do not have VUR, thus avoiding the use of radiation in this group. MATERIALS AND METHODS: From August 1999 to August 2000, 97 neonates (69 male, 31 female), aged 28-90 days (mean 48 days), referred for MCU and renal ultrasonography for investigation of VUR were recruited consecutively. Echo-enhanced sonography using stabilized microbubbles was followed immediately by fluoroscopic MCU. VUR was diagnosed if transient hyperechogenicity appeared within the pelvicalyceal system or ureter. The mean number of micturitions was 2.7 (range 1-6). RESULTS: Reflux was detected in 19 kidneys (14 babies) by one or other technique. The findings were concordant in 181 kidneys (94.2%). Echo-enhanced sonography had a sensitivity of 64% (95% CI 35-87%), a specificity of 100% (95-100%), a positive predictive value of 100% (66-100%), and a negative predictive value of 94% (87-98%). CONCLUSIONS: The role of echo-enhanced sonography is limited at present in our neonatal population as a screening examination. Its ability to detect cases of high-grade reflux may make it an attractive alternative in follow-up of known cases of VUR, and may help to reduce radiation exposure in this group.

Contrast Media↗

Harmonic US imaging of vesicoureteric reflux in children: usefulness of a second generation US contrast agent.

BACKGROUND: Contrast-enhanced voiding urosonography (VUS) is largely accepted both for the diagnosis and follow-up of vesicoureteric reflux (VUR) in children. OBJECTIVE: To evaluate the usefulness of contrast-enhanced second-harmonic VUS in the diagnosis and grading of VUR, using a second-generation contrast agent. MATERIALS AND METHODS: Eighty consecutive children were prospectively studied with contrast-enhanced second-harmonic VUS. All children received a second-generation contrast medium, constituted by phospholipid-stabilized microbubbles of sulphur-hexafluoride (SonoVue, Bracco, Milan, Italy). US monitoring of the bladder, of the retrovesical space and of the kidneys was performed using, alternatively, both tissue-harmonic and contrast-harmonic modes. In those young boys where VUR was depicted at VUS, examination was completed with transperineal, sagittal urethral exploration during micturition. VUR was graded in five steps and diagnoses were compared with voiding cystourethrography (VCUG). RESULTS: VUR was diagnosed in 52 reno-ureteral units with VUS. In 49 of these reno-ureteral units, VCUG confirmed the presence of VUR. In comparison to VUS, sensitivity and negative predictive value of VCUG were inferior. The grade of VUR detected at VUS was higher than that detected at VCUG in three units. In no case was the grade of VUR detected at VCUG higher than the one detected at VUS. The differences between VUS and VCUG in grading VUR were statistically significant (p=0.02). Imaging of the normal posterior urethra was skilfully demonstrated with US in 15 young boys with VUR. No statistically significant differences were found between tissue-harmonic and contrast-harmonic mode (p=0.102). CONCLUSIONS: Contrast-enhanced second-harmonic VUS is a sensitive and easy technique for the evaluation of VUR. A second-generation US contrast medium such as SonoVue, if available, should be the first choice as the dose required for one examination is much lower and consequently significant reduction of contrast agent cost is possible.

Child, Preschool↗

Diagnosis of vesicoureteric reflux with low-dose contrast-enhanced harmonic ultrasound imaging.

BACKGROUND: Harmonic US imaging has been shown to be better than conventional US for the detection and visualisation of microbubbles in contrast-enhanced voiding urosonography (VUS). OBJECTIVE: To determine the diagnostic efficacy of VUS using a reduced dose of the US contrast medium in comparison to voiding cystourethrography (VCUG). MATERIALS AND METHODS: Fifty-five children (17 boys, 38 girls; mean age 4 years) were recruited. All patients underwent VUS by harmonic imaging followed by VCUG. The dose of the US contrast medium (Levovist) administered intravesically was half of the recommended dose i.e. 5% of the bladder filling volume. RESULTS: A total of 114 kidney-ureter (K-U) units were available for evaluation. Vesicoureteric reflux (VUR) was detected in 29 K-U units by one or both examination modalities. There was a 91.2% concordance rate between VUS and VCUG. VUR in seven and three K-U units were detected only by VUS and VCUG, respectively. Taking VCUG as the reference method, VUS had the following diagnostic results: 86.4% sensitivity, 92.4% specificity, positive and negative predictive values of 73.1 and 96.6%, respectively. CONCLUSIONS: Even when the dose of US contrast medium is halved, the diagnostic efficacy of harmonic VUS is comparable to VCUG. Consequently, we recommend an US contrast medium dose of 5% of the bladder filling volume for the diagnosis of VUR using contrast-enhanced harmonic VUS.

Adolescent↗

Potential pediatric applications for US contrast agents: lessons from the laboratory.

OBJECTIVES: The goals of this review are to familiarize the reader with the physical basis for microbubble contrast effect and to summarize experimental studies exploring their potential pediatric applications. MATERIALS: Animal studies conducted over a 4-year period using an experimental US contrast agent for imaging the central nervous system, kidney, testes, hip joints, and malignant tumors are reviewed with respect to imaging efficacy of the agent, possible use for quantification of tissue blood flow, and potential non-vascular imaging applications. CONCLUSIONS: US contrast agents hold important potential for many clinical applications in imaging the pediatric patient.

Animals↗

Contrast-enhanced dynamic ultrasonography of the liver: optimization of hepatic arterial phase in normal volunteers.

BACKGROUND: To optimize hepatic arterial phase timing in contrast-enhanced dynamic ultrasonography (US) of the liver. METHODS: Dynamic US was performed by using a microbubble-specific mode in 22 healthy volunteers after bolus injection of SH U 508A. Images were analyzed to determine whether hepatic arterial and portal venous phases could be temporally discriminated. Delay times to contrast enhancement at the hepatic artery (A(ini)) and portal vein (P(ini)) and the delay time until the signals between both vessels became inseparable (A(end)) were determined. RESULTS: The hepatic arterial and portal venous phases could be temporally discriminated in all subjects. A(ini), P(ini), and A(end) (mean +/- standard deviation) were 11.0 +/- 2.0, 14.8 +/- 3.6, and 22.6 +/- 5.1 s, respectively. CONCLUSION: In hepatic contrast-enhanced dynamic US, hepatic arterial phase scanning should be commenced earlier than 11 s and terminated after 23 s postinjection.

Adult↗

Focal liver lesions: evaluation with contrast-enhanced ultrasonography.

The development of contrast agents for ultrasound has significantly extended its clinical applications, particularly in the detection and characterization of focal liver lesions. Real-time evaluation of the vascular phase currently can be achieved by combining new microbubble-specific methods with second-generation contrast agents. The enhancement pattern in the vascular phase combined with the behavior in the liver-specific late phase allows characterization of the most frequent focal liver lesions, with an accuracy similar to those of dynamic computed tomography and magnetic resonance imaging.

Contrast Media↗

Vesicoureteral reflux in young patients: comparison of voiding color Doppler US with echo enhancement versus voiding cystourethrography for diagnosis or exclusion.

We assessed the accuracy of voiding color Doppler ultrasonography (US) with echo enhancement for diagnosis or exclusion of vesicoureteral reflux (VUR) versus voiding cystourethrography (VCUG) and evaluated patient tolerance of the echo-enhancing agent. One hundred twenty-two patients (ages range, 1 month to 17 years) with 244 ureterorenal units underwent voiding color Doppler US with echo enhancement, which was followed by VCUG on the same day. After US of the urinary tract, the bladder was filled with saline solution via catheter. Then an echo-enhancing agent was instilled, and color Doppler US was performed. Reflux was diagnosed when microbubbles appeared in the ureter or the pelvicaliceal system. VUR was detected in 98 units. All grades of reflux were identified. In 13 units (13.3%), grade I reflux diagnosed at voiding color Doppler US was not observed at VCUG. No reflux was detected in 146 units by either method. In 231 (94.2%) of the 244 ureterorenal units, there was concordance between the two methods. The echo-enhancing agent was well tolerated by all patients. Voiding color Doppler US with echo enhancement is useful for the diagnosis or exclusion of VUR, being as good as VCUG. Therefore, it may reduce the number of patients exposed to ionizing radiation.

Adolescent↗

How to detect hepatocellular carcinoma in cirrhosis.

Cirrhosis predisposes to hepatocellular carcinoma (HCC) which develops by sequential steps of de-differentiation of hepatocytes from regenerative nodules via borderline (dysplastic) nodules to frankly malignant HCC. Effective treatment depends on early recognition of HCC, so the key tasks for imaging are firstly recognising the presence of a suspicious lesion, and secondly differentiating between benign, borderline and malignant nodules. Screening of high-risk cirrhotic patients with sonography and measurement of alpha fetoprotein (AFP) is helpful but will not reliably differentiate small HCC from benign or dysplastic nodules. Large HCCs can usually be recognised by their characteristic morphology on imaging, but the appearances of smaller benign and malignant nodules show considerable overlap on unenhanced sonography, CT and MRI. Increasing degrees of histological malignancy are associated with increasing arterialisation and loss of portal blood supply, so the recognition of HCC requires the use of dynamic imaging with contrast-enhanced CT or T1-weighted MRI with gadolinium enhancement. Sonography with microbubble contrast media now offers another method for detecting arterialised nodules; however, some non-malignant nodules show arterial hypervascularity and a minority of HCCs are hypovascular, so the assessment of perfusion does not conclusively distinguish benign from malignant lesions. Kupffer cell function is another attribute of liver tissue which can be explored using MRI with superparamagnetic iron oxide particles (SPIO). Experience thus far suggests that uptake of SPIO is an effective discriminator between benign and malignant nodules. The combination of SPIO with gadolinium-enhanced MRI offers the opportunity for imaging characterisation of cirrhotic nodules by cellular function as well as by blood supply, and this approach is now proposed as the examination of choice for detecting HCC in cirrhosis.

Carcinoma, Hepatocellular↗

Impact of European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines on the use of contrast agents in liver ultrasound.

The introduction of microbubble contrast agents and the development of contrast-specific techniques have opened new prospects in liver ultrasound. Over the past few years several reports have shown that contrast ultrasound can substantially improve detection and characterization of focal liver lesions with respect to baseline studies. The advent of second-generation agents and low mechanical index real-time scanning techniques has been instrumental in improving the easiness and the reproducibility of the examination. With the publication of the guidelines for the use of contrast agents in liver ultrasound by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), contrast ultrasound enters into clinical practice. The guidelines define the indications and recommendations for the use of contrast ultrasound in focal liver lesion detection, characterization, and follow-up after tumor ablation procedures. We discuss the impact of EFSUMB guidelines on diagnostic protocols currently adopted in liver imaging.

Contrast Media↗

Comparison of contrast-enhanced ultrasonography versus baseline ultrasound and contrast-enhanced computed tomography in metastatic disease of the liver: diagnostic performance and confidence.

AIM: The aim of this study was to compare contrast-enhanced ultrasonography (CEUS) to baseline US and contrast-enhanced computed tomography (CT) in metastatic disease of the liver diagnosed or suspected by US during presurgical staging or postsurgical follow-up for primary malignancies. MATERIALS AND METHODS: Two hundred-fifty-three patients considered suitable for US due to the complete explorability of the liver and with one to five proven or suspected liver metastases at baseline US were included. All patients underwent US before and after microbubble injection, and multiphase contrast-enhanced CT. Independent panels of readers reviewed US and CT scans and recorded liver metastases according to a 5-grade scale of diagnostic confidence. Sensitivity, specificity (diagnostic performance) and area under the receiver operating characteristics (ROC) curve (diagnostic confidence) were calculated. RESULTS: Reference standards revealed no metastases in 57/253, more than five in 59/253, and one to five in 137/253 patients. In patients with one to five metastases, CEUS versus baseline US revealed more metastases in 64/137 and the same number in 73/137 patients while CEUS versus CT revealed more metastases in 10/137, the same number in 99/137, and lower number in 28/137. Sensitivity, specificity, and area under ROC curve of CEUS (83%, 84%, 0.929, respectively) differed from baseline US (40%, 63%, 0.579, respectively; P<0.01) while did not differ from CT (89%, 89%, 0.945, respectively; P>0.05). CONCLUSION: CEUS improved liver metastases diagnosis in comparison with baseline US while it revealed similar diagnostic performance and confidence to contrast-enhanced CT in patients considered suitable for US and with proven or suspected liver metastases at baseline US.

Aged↗

Ultrasound contrast agents and their use in urogenital radiology: status and prospects.

Ultrasound contrast agents (USCAs) for intravenous use are usually microbubbles with a mean diameter less than that of a red blood corpuscle and filled with gas. The USCAs may improve information about tissue characteristics and physiology by enhancing B-mode imaging, all Doppler modalities and by means of contrast-specific imaging, e.g. harmonic and stimulated acoustic imaging. Results from preclinical experiments have been promising, and several of these have been reproduced in clinical studies. This includes improved evaluation of renal vasculature and parenchyma, assessment of vesicoureteral reflux in children, assessment of tubal patency in women, and evaluation of prostate diseases and erectile dysfunction in men. Some of the physical limits of the ultrasound technology, as well as the operator-dependent factors, can probably never be overcome by the use of USCAs; however, the development of USCAs is now about to provide uroradiologists with potentially efficacious products for the benefit of the patient.

Animals↗

Ultrasound contrast agents: properties, principles of action, tolerance, and artifacts.

The concept of contrast imaging was introduced to ultrasound almost 30 years ago. The development of ultrasound contrast agents (USCAs), initially slowed by technical limitations, has become more dynamic during the past decade. The ideal USCA should be non-toxic, injectable intravenously, capable of crossing the pulmonary capillary bed after a peripheral injection, and stable enough to achieve enhancement for the duration of the examination. While satisfying cost-benefit requirements, it should provide not only Doppler but also gray-scale enhancement. Already, Doppler examinations are improved by using USCAs when studying deep and small vessels, vessels with low or slow flow, or vessels with a non-optimal insonation angle. Ultrasound contrast agents also enhance detection of flow within abnormal vessels, including tumor vascularization and stenotic vessels, and provide better delineation of ischemic areas. Research is focusing on the development of specific contrast imaging sequences that allow detection of tissue enhancement similar to that obtained with CT or MRI. These sequences take advantage of the nonlinear behavior of the microbubbles within the ultrasound field, bringing real-time perfusion imaging for liver, kidney, and the myocardium into reach. New objectives include targeted agents that could further widen USCA applications to specific delivery of active drugs such as anticoagulants or cytotoxic compounds. The combination of new generations of USCAs and new ultrasound image sequences appears to be very promising and currently represents a significant part of ultrasound research.

Albumins↗

Ultrasound contrast agents: clinical applications.

Ultrasound contrast agents (USCA) for intravenous injections are usually gas-filled microbubbles with a mean diameter less than that of a red blood corpuscle. There are only a few products on the market at the time of this writing, but several companies have various agents under development. This paper covers both established USCA on the market, and some new agents under clinical evaluation. The potential of improving ultrasound imaging using USCA depends on several factors. These factors include the pharmacokinetic and pharmacodynamic properties of the products, which determine the effects they have on various ultrasound imaging techniques. Furthermore, the proper clinical application of the agents requires a combination of technical and medical knowledge by the examiner, dedicated equipment, a disease that can be diagnosed or characterised by ultrasound and USCA, and a cooperative patient. Taking into account these factors, USCA can be used for improving the detection, characterisation and follow-up of diseases of several vascular beds and parenchymal organs from head to foot.

Blood Vessels↗

Ultrasound of focal liver lesions.

This paper gives a comprehensive overview of ultrasound of focal liver lesions. Technical aspects such as examination technique and the use of Doppler modes as well as recent developments such as tissue harmonic imaging and microbubble contrast agents are discussed. The clinical significance and sonographic features of various liver lesions such as haemangioma, focal nodular hyperplasia, adenoma, regenerative nodule, metastasis, hepatocellular carcinoma and various types of focal infections are described. With the exception of cysts and typical haemangiomas, definitive characterisation of a liver lesion is often not possible on conventional ultrasound. This situation has changed with the recent advent of ultrasound contrast agents, which permit definitive diagnosis of most lesions. Contrast-enhanced sonography using recently developed contrast-specific imaging modes dramatically extends the role of liver ultrasound by improving its specificity in the detection and characterisation of focal lesions to rival CT and MRI.

Adenoma↗

[Contrast echocardiography].

The intravenous application of an ultrasound contrast agent induces enhanced display of blood in all its pathways. Within cardiology, this principle is mainly utilized for signal enhancement of color Doppler and spectral Doppler in order to improve quantification of congenital and acquired valvular lesions and also for improved endocardial delineation during stress tests and in the evaluation of LV function. The new domaine of myocardial perfusion imaging by contrast echocardiography, however, needed profound technical developments before realization of the clinical potential could even be conceived. These are based on the complex reactions of microbubbbles in the acoustic field in order to allow the sensitive and bubble specific display of intramyocardial contrast effects. The presently available acquisition techniques, second harmonic imaging and harmonic power Doppler, demonstrate significant improvements if compared to traditional fundamental 2-d echocardiography; however, they are still subjected to important limitations. There are many anatomical, physiological, and technical reasons for insufficient display of intramyocardial microbubbles, the most important one being attenuation. It is hoped that the most recently developed imaging modality, pulse inversion technique, allows the necessary diagnostic accuracy and reproducibility in myocardial perfusion imaging.

Contrast Media↗

[Myocardial contrast echocardiography with harmonic power Doppler and lung traversing SHU 563A ultrasound contrast medium for imaging myocardial perfusion disorders].

The current approach for the assessment of myocardial perfusion using contrast echocardiography involves black-and-white gray scale imaging in b-mode. For better appreciation of perfusion abnormalities, off-line postprocessing techniques including color encoding are used. In this study, we examined whether we could exploit the contrast microbubble response to high ultrasound amplitude--the phenomenon of stimulated acoustic emission--that could be recorded with harmonic power Doppler (HPD) in color to identify myocardial perfusion defects. To assess the potential of HPD, we occluded branches of the left coronary artery for 2-3 h followed by 1 h reperfusion in 10 dogs. After transvenous administration of the new air-filled contrast agent SHU 563A, echocardiographic imaging was performed with ECG-triggered harmonic b-mode (HBM) and the harmonic power Doppler (HPD) approach in different short (SAX) and long axis (LAX) views. Post-mortem TTC staining was performed to verify infarction. HBM, HPD and TTC data were analyzed by independent observers. During coronary occlusion, HPD with SHU 563A showed perfusion defects in 10 dogs in all SAX and LAX views. HBM demonstrated perfusion defects in all dogs in SAX and in 8 dogs in LAX. The correlation of perfusion defect size between HPD and HBM images was good (SAX: r = 0.9, p < 0.001, LAX: r = 0.7, p < 0.01). One hour after reperfusion, both HPD and HBM showed perfusion defects with SHU 563A in 7 dogs. Five dogs showed TTC evidence of infarction. Perfusion defect size by HPD correlated well with residual infarct size (r = 0.8, p < 0.01), while defect size by HBM showed poor correlation (r = 0.3, p = ns). Myocardial contrast echocardiography with HPD and contrast agent SHU 563A identifies perfusion defects in acute coronary occlusion as reliably as HBM. After reperfusion HPD and SHU 563A accurately portray the site and size of residual myocardial infarction on line, in color. This approach has excellent potential for clinical application.

Animals↗

Contrast-enhanced ultrasound in dermatomyositis- and polymyositis.

OBJECTIVE: To evaluate prospectively contrast-enhanced ultrasound (CEUS) in patients suspected of having dermatomyositis or polymyositis. METHODS: In 35 patients (23 women, 12 men; mean age, 51 years+/-16 years) who were suspected of having dermatomyositis or polymyositis, perfusion in clinically affected skeletal muscles was quantified with contrast-enhanced intermittent power Doppler ultrasound. By applying a modified model that analyzed the replenishment kinetics of microbubbles, the perfusion-related parameters blood flow, local blood volume and blood flow velocity were measured. Findings were compared with muscle biopsy appearances and with the results of MRI that was performed with a 1.5-Tesla unit. Receiver operating characteristic analysis was performed and optimum thresholds for diagnosis of myositis were determined. RESULTS: Eleven patients had histologically confirmed dermatomyositis or polymyositis and showed significantly higher blood flow velocity (P=.01 for dermato- and P<.001 for polymyositis), blood flow (P<.001 for dermato- and polymyositis), and blood volume (P=.007 for dermato- and P<.001 for polymyositis) on contrast-enhanced ultrasound than those who did not have myositis. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis. MRI had a sensitivity, specificity, positive (PPV), and negative predicting values (NPV) of 100%, 88%, 77%, and 100% for diagnosis of myositis, respectively. CEUS blood flow was the best ultrasound measure for diagnosis of dermato- or polymyositis with sensitivity, specificity, PPV, and NPV of 73%, 91%, 80%, and 88%, respectively. CONCLUSIONS: Increased skeletal muscle perfusion measured by CEUS could serve as an additional measurer for the diagnosis of an inflammatory myopathy.

Adult↗