Contrast enhanced ultrasound of breast cancer.

The importance of ultrasound examination in the diagnosis of breast cancer has been widely demonstrated. During the last few years, the introduction of ultrasound contrast media has been considered a promising tool for studying the vascular pattern of focal lesions within the breast. Our purpose was to assess whether contrast-enhanced (CE) ultrasound examination, performed using specific contrast imaging modes, can be helpful for detection and characterization of breast lesions, and for prediction of the response of breast cancer to therapy.

Serum liver enzymes in Turner syndrome.

UNLABELLED: Increased serum concentrations of liver enzymes are sometimes observed, in the absence of clinical symptoms of liver disease, in patients with Turner syndrome. The purpose of this study was to evaluate, in our Turner patients, serum liver enzyme levels and to find a cause for their increase. In 70 Turner patients, serum AST, ALT, GGT levels were evaluated every 6 months during a period of 0. 8-21.9 years. In patients in whom increased values of liver enzymes were found, serological markers for infectious hepatitis, serum hepatitis C virus RNA and virus genotype, IgG and IgA antibodies to gliadin and endomysium, coeruloplasmin, copper, alpha(1)-antitrypsin, total proteins and electrophoresis, IgG, IgA, IgM, fibrinogen, prothrombin, alkaline phosphatase, creatine kinase and total and direct bilirubin were also determined. Antinuclear, anti-smooth muscle and anti-liver-kidney microsome antibodies together with antithyroglobulin and anti-thyroid peroxidase antibodies were determined in all patients and in 166 age-matched female controls. In 22 patients, increased liver enzymes were observed, not related to karyotype. Follow-up showed that the hepatic disorder did not worsen with the time. Serological markers of hepatitis C virus were positive in three patients. When the serum liver enzyme increase was first observed in the other 19 patients with high enzyme levels (group A), 14 patients had never been submitted to hormonal treatment, 4 were on oestrogen/gestagen treatment and 1 was being treated with both growth hormone and oestrogen. Coeliac disease, alpha(1)-antitrypsin deficiency and Wilson disease were ruled out by appropriate investigations. In 8/19 group A patients, antinuclear and/or anti-smooth muscle antibodies were present versus 6/48 of patients with normal liver enzymes (group B). Thyroid antibodies were found in 8/19 patients in group A and in 13/48 in group B. Weight excess SDS was significantly higher in Turner girls with liver enzyme increase. Ultrasonography, performed in 17 patients of group A, showed mild hepatomegaly in 4 and increased echogenicity with fatty infiltration in 6. CONCLUSION: Hepatic abnormalities in Turner syndrome are not progressive. Oestrogen should not be considered the main cause of increased liver enzymes in Turner syndrome since most of our patients with this finding had not been previously treated with oestrogens. An auto-immune pathogenesis might be considered in some cases, whereas the association with weight excess seems the most frequent cause of liver disorder in Turner syndrome.

Ultrasound contrast agents: basic principles.

INTRODUCTION: Ultrasonography lacked substances to be administered to patients to improve or increase the diagnostic yield, which is peculiar considering that contrast agents have long been used with all the other imaging techniques. Fortunately some contrast agents, most of them consisting in gas microbubbles, have been recently introduced for ultrasound imaging too: this review will focus on their history, behavior, current applications and future developments. Echocontrast agent research is in progress and many new agents are expected to be marketed this and next year, to be added to Levovist by Schering AG (Berlin, Germany), to enhance the ultrasound signal safely and effectively. No definitive conclusions can be drawn yet on the actual merits of each contrast agent, but all of them seem to be both effective and safe, meaning that their future success will depend on the relative cost-effectiveness and peculiarities. THE BASIC PRINCIPLES OF ECHOCONTRAST AGENTS: The microbubbles act as echo-enhancers by basically the same mechanism as that determining echo-scattering in all the other cases of diagnostic ultrasound, namely that the backscattering echo intensity is proportional to the change in acoustic impedance between the blood and the gas making the bubbles. The different acoustic impedance at this interface is very high and in fact all of the incident sound is reflected, even though not all of it will of course go back to the transducer. But the acoustic wave reflection, though nearly complete, would not be sufficient to determine a strong US enhancement because the microbubbles are very small and are sparse in the circulation. Moreover, reflectivity is proportional to the fourth power of a particle diameter but also directly proportional to the concentration of the particles themselves. SECOND HARMONIC IMAGING: As we said above, the microbubbles reached by an ultrasound signal resonate with a specific frequency depending on microbubble diameter. However, the main resonance frequency is not the only resonance frequency of the bubble itself and multiple frequencies of the fundamental one are emitted, just like in a musical instrument. These harmonic frequencies have decreasing intensity, but the second frequency, known as the second harmonic, is still strong enough to be used for diagnostic purposes. The theoretical advantage of the harmonic over the fundamental frequency is that only contrast agent microbubbles resonate with harmonic frequencies, while adjacent tissues do not resonate, or else their harmonic resonation is very little. Thus, using a unit especially set to produce ultrasounds at a given frequency (3.5 MHz) and receive an ultrasound signal twice as powerful (7 MHz) it will be possible to show the contrast agent only, without any artifact from the surrounding anatomical structures, with a markedly improved signal-to-noise ratio. A similar effect to digital subtraction in angiography can thus be obtained, even though through a totally different process. Moreover, second harmonic imaging permits to show extremely small vessels (down to 40 microm) with very slow flow, which would be missed with a conventional method. B-mode imaging can also depict the microbubbles in the myocardium suppressing nearly all the artifacts from cardiac muscle motion. Recently a peculiar behavior of microbubbles has been observed which may permit contrast agent detection even in capillaries. This method is variously known as sonoscintigraphy, loss of correlation, stimulated acoustic emission and transient scattering. The contrast agent microbubbles reached by an ultrasound beam powerful enough explode producing a strong and very short backscatter echo which is read by the unit as a Doppler signal and results in a color pixel where the individual microbubble exploded. CONCLUSIONS: The microbubble contrast agents developed and introduced as safe and effective echo-enhancers in present-day clinical practice will open up new oppurtunities

Contrast enhancing agents in ultrasonography: clinical applications.

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.

Color Doppler imaging of liver metastases. The value phase-III of a US contrast agent: SH U 508 A (Levovist) Schering.

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.

[Echographic assessment of the hand: normal anatomy and pathologic patterns]. / Studio ecografico della mano: anatomia normale e quadri patologici.

Ultrasonography (US) can ben used to study the hand thanks to small-parts probes whose frequency ranges 7.5 MHz to 20 MHz. Due to the complex hand anatomy, the clinician often needs further data relative to periskeletal soft tissues and vessels, which are provided by color Doppler US. Our personal series included 465 patients and a group of 20 healthy volunteers. A silicon pad was used to ensure max. adhesion to probe surface, given the uneven surface of the examined structures. Besides normal anatomic patterns, US demonstrated pathologic features in tendons, sheaths and muscles. As for tendons, stenosing and hypertrophic-exudative tenosynovites were depicted, as well as cysts and ruptures. As for muscles, the main findings were ruptures and, rarely, tumors. Relative to joints, arthrogenous ganglia and rheumatism were observed. Finally, the carpal tunnel syndrome was accurately investigated, where US revealed tenovaginalitis with sheath thickening and deformed and compressed median nerve in the carpal tunnel. Also the benign and malignant masses whose primary location is the nervous tissue are easily demonstrated on US, their typical shape being ovalar. To conclude, US proved extremely accurate in all the surgical patients, exhibiting 100% sensitivity in all of them; its specificity ranged from 84% for tendons, to 81% for muscles, 79% for nervous tissues and finally 82% for joint disorders.

[Echography in the study of periskeletal soft tissues: technique, normal and pathologic pictures]. / L'ecografia nello studio dei tessuti molli perischeletrici: tecnica, quadri normali e patologici.

Ultrasonography (US) is the method of choice in the study of normal soft tissue patterns thanks to its intrinsic features. The exam must be performed following strict directions relative to US units (last-generation), to probes (high-frequency, high axial and lateral resolution, focusing), the type of scan (orthogonal and oblique scans), the use of silicon pads. Exam reporting and the exact knowledge of possible image artifacts are of the utmost importance. Normal patterns in the skin, subcutaneous tissue, striate muscles, tendons and bursae, nerves, vessels and bone are reported and correlated with the corresponding US patterns in pathologic conditions. In inflammatory processes, muscles and tendons exhibit blurred, irregular and poorly-defined outlines; neither the anatomical structures nor the tissues nearby are infiltrated. Similar patterns are observed in some benign tumors, while in malignant lesions soft tissue echostructure is more or less alterated and the adjacent tissues are infiltrated. Color-Doppler US yields morphologic and functional information as to pathologic vascularization; typical findings, similar to those obtained by means of angiography, are seen in malignant lesions.

[Role of color coded duplex sonography in the study of thyroid pathology. Personal experience]. / Ruolo della colour coded duplex sonography nello studio della patologia tiroidea. Esperienza personale.

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.