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INTRODUCTION: As ultrasound remains a poorly sensitive method, echocontrast agents make a real difference. At least 29 echocontrast agents are currently on trial worldwide; their chemical composition, mechanisms of action and possible clinical applications are different. The state of the art of echocontrast agents is discussed: their established applications, those expected in the near future and finally their hypothetical, ideal applications. POTENTIAL CLINICAL APPLICATIONS: An extravascular and a vascular domain can be considered. The former includes the gastrointestinal tract and body cavities--both the normal (bladder, uterus, tubes and so on) and the abnormal (abscesses, fistulas, pericardium, peritoneum and so on) ones. Echocontrast agents can: (1) create or improve an acoustic window; (2) distend some organs and fill them with a liquid, with homogenous attenuation of the ultrasound beam; (3) displace the air-containing intestinal loops; (4) depict the walls, the shape and the contours of a normal or abnormal cavity; (5) detect abnormal communications, fistulas and drainages; and (6) evaluate the amount of fluid in the pleural, pericardial or peritoneal cavities. As for vascular applications, this domain sees the highest number of echocontrast agents on trial or on the market. The best know of them are: Levovist (Schering AG, Berlin, Germany), BR1 (Bracco, Milan, Italy) and EchoGen (Abbott, USA). All these act by enhancing arteries, veins and capillaries. The clinical applications validated in clinical trials mainly regard studies in intracranial and neck vessels and the vascularity of upper and especially lower limbs of renal vessels. Tumor macrovascularity (and in the future, hopefully microvascularity) can also be studied in parenchymatous and/or glandular organs, as well as in intra- and extra-abdominal parenchymatous organs in the periskeletal soft tissues. Clinical validation has also been obtained in the follow-up of tumors submitted to ablation therapy (chemoembolization, ethanol injection, thermal ablation) and in echocardiography, both for morphological studies in the cardiac cavities and for the cardiac wall perfusion. CONCLUSIONS: In a subgroup of 513 out of 1275 patients examined Europe-wide, the contrast agent Levovist increased the diagnostic confidence from 27.4 +/- 22.5 to 77.2 +/- 22.5%. Such data encourage further trials to validate current preliminary results.

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Venous thrombosis is a well-known complication of permanent cardiac pacemaker implantation, particularly, chronic occlusion of the subclavian vein is reported to occur in 20-33% of the cases where the percutaneous approach is performed. We examined 135 asymptomatic patients with digital venography to asses the frequency of venous thromboses causing stenosis and occlusion of the subclavian or anonymous arteries in pacemaker carriers. We considered both one- (44) and two-chamber (91) pacemakers and investigated a possible statistically significant difference between them: we found 21 venous thromboses (15%), seven of them in one-chamber pacemakers (15.9%) and 14 two-chambers pacemakers (15.3%). None of our 94 male and 41 female patients was on anticoagulants or had any evidence of coagulation disorders. Venography was performed 39.3 months (mean) after pacemaker implantation (range: 3-120 months). We conclude that digital venography is a simple and relatively noninvasive method permitting better depiction of subclavian, anonymous and caval veins than Doppler US and also showing some vascular abnormalities which may complicate pacemaker implantation.

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In a phase-III multicenter clinical trial, the color Doppler vascular patterns were studied of 34 liver metastases in 18 patients before and after the i.v. injection of SH U 508 A (Levovist), with different US units and probes. The patients were selected as having poor color Doppler signals at unenhanced examinations. Lesion size ranged .8 to 9 cm (mean: 3.5 cm). The primary lesion site was the colon in 14 cases, the breast in 8 cases, the lung in 4, the stomach in 4 cases, the ovary in 3 and finally unknown in 4 cases. Each patient received two to four contrast agent injections, with suggested doses and concentrations (10 ml x 300 mg/ml, 8 ml x 400 mgr/ml). No adverse reactions were observed. Thirteen of 34 lesions exhibited no vascular signals at baseline examinations, 10 exhibited some perilesional color spots or small vessel branches, 5 some internal color spots or vessels and 4 small internal and peripheral vessels. After contrast agent infusion, the vascular patterns were better demonstrated in 28/34 lesions and the signal-to-noise ratio was markedly improved, in a concentration-dependent manner, from 40 to 240s. Five lesions remained avascular, 11 exhibited "basket"-like vascular patterns, 10 "internal flow" patterns and finally 10 lesions exhibited both. No major correlation was observed between vascular pattern and lesion size. To conclude, the use of the intravenous contrast agent SH U 508 A (Levovist) appears to be a promising technique to improve the color Doppler demonstration of focal metastatic liver lesions. Nonetheless, further studies on larger series of cases are needed to differentiate the different primary sites of the metastases.

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The authors reviewed 463 hysterosalpingographies from a series of patients examined for primary infertility. 25.5% of them had been studied with echotomography and 4.1% with therapeutic and explorative laparoscopy. Hysterosalpingographic results were compared with positive findings at clinical examination and with various pathologic associations: the method proved to be extremely valuable in the diagnosis of the primary causes of female infertility, and even showed secondary, sometimes unsuspected, causes--e.g., iatrogenic and inflammatory. Moreover, high agreement (50%) was observed with echotomographic findings. The examination was carried out on an outpatient basis, and proved less dangerous and cheaper than other invasive techniques, its cost being more or less the same as that of US, which however is still the least dangerous and expensive method for the diagnosis of female infertility. Therefore, the authors suggest that diagnostic laparotomy be a second choice and be employed only in the cases where it can have therapeutic purposes. In all the extant cases, combined hysterosalpingography and US are still recommended.

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The authors examined 110 patients with suspected pathologic conditions of the thyroid by means of color-coded duplex US. In addition to the information yielded by conventional US, this technique allows organ vascularization to be demonstrated. Five normal patients were considered as a control group: no tissue vascularization was demonstrated in these cases. In 8 patients presenting with carcinoma or recurrences, vascularization was markedly increased both peripheral and central to the nodule. A few doubts are still to be solved as to the diagnostic value of color-coded duplex US in the evaluation of non-carcinomatous nodular pathologic conditions. As a matter of fact, non-functioning avascular adenomas can be demonstrated only in a very low percentage of cases (66%). Color-coded duplex US proved extremely sensitive and specific in depicting malignant neoplasms. Moreover, the use of fine-needle biopsy could be optimized and subsequently reduced. Color-coded duplex US proved to be markedly superior to other methods and techniques in the study of thyroid diseases, especially thyroiditis and multiple pathologic conditions. The simultaneous presence of hypocapture at scintigraphy and peripheral and central vascularization in a single nodule or within multinodular struma at color-Doppler was highly suggestive of malignant thyroid neoplasm. Color-coded duplex US is a low-cost technique, which can be performed on an outpatient basis. Moreover, it is not invasive, nor does it damage the thyroid. That is why its use is almost mandatory in the study of pathologic conditions of the thyroid.

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104 selective bronchial arteriographies were performed in 25 patients with bronchopulmonary neoplasia, 11 with mediastinal tumours, 15 with bronchopulmonary inflammation, and 53 with haemoptysis. An assessment is made of the diagnostic value of the information obtained. It is felt that this form of examination is particularly useful in detecting the site of bleeding cases of haemoptysis, and in the provision of treatment by means of embolisation.

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