Ultraschall in der Medizin

Published by Thieme Publishing
Online ISSN: 1438-8782
Print ISSN: 0172-4614
The aim of the study was to assess the prevalence of thyroid enlargement by ultrasonic volume measurements. 1336 adults living in the iodine-deficient area of Aachen, West Germany (760 females, 576 males, mean age: 54.05 +/- 16.09 years) were included in the investigation. The ultrasonic examination was carried out in patients who did not suffer from thyroid disease at the time of study. The thyroid volume was age-dependent and varied from 13.3 +/- 10.4 ml in patients < 21 years to 29.9 +/- 24.3 ml in patients > 70 years. The prevalence of thyroid enlargement ranged from 14.3% in young people to 51.3% in the elderly. There was no difference in the volumes of the left and right thyroid lobe. The prevalence of thyroid enlargement was higher in females compared to males (p < 0.05). Retrosternal thyroid mass was detected in 25% of all patients > 70 years. There is evidence of a high prevalence of thyroid enlargement in iodine-deficient areas.
The Technical Quality Assurance group was initiated by the EFSUMB Board in 2007 and met firstly in 2008 to discuss and evaluate methods and procedures published for performing technical quality assurance for diagnostic ultrasound devices. It is the aim of this group of experts to advise the EFSUMB Board of effective and efficacious methods for routine use and to make recommendations regarding the technical aspects of EFSUMB by-law 9, parts 11.6. & 11.7. The group´s work focused on new developments and related European projects to establish a common guideline. There is a great need of a well established protocol and dedicated processing software for the performance testing of medical ultrasound equipment. The measurements should be user independent as much as physically possible. Only if these goals are achieved in an international (firstly European) context, the optimal quality of ultrasound imaging can be offered and maintained to the medical community. This guideline aims to offer and summarize suitable procedures and evaluation processes to lend support for an optimal Technical Quality Assurance (TQA) scheme. The content of this guideline was presented to the EFSUMB Board of Directors (delegates) and approved by the EFSUMB Executive Board (ExB) at the regular meeting during EUROSON 2012 in Madrid April 2012.
Purpose: Sonographic imaging techniques including 3 D volumetry were evaluated in women with missed abortion. Special emphasis was put on the impact of additional information regarding the etiology of the demise and improved visualization of embryonic and fetal anomalies due to the application of the latest imaging tools, e. g. HD live™. Parental acceptance of a more realistic display of the embryo/fetus in missed abortion was analyzed. Materials and methods: Between 09/2009 and 09/2012, 107 pregnancies with a missed abortion in the first trimester were included in this prospective survey. Using a transvaginal approach, all 2 D and 3 D studies were carried out with high-resolution 5 - 9 and 6 - 12 MHz probes. Results: The mean gestational age was 70.3 days (49 - 110 days). The difference between estimated gestational age and sonographic age at evaluation for missed abortion was 13.5 days (-13 - 40 days). Additional information via three-dimensional volume acquisition, like craniofacial deformities, clefts, neural tube defects, abdominal wall defects and caudal regression syndrome, could be documented in 23/107 cases (21.5 %). In 2/107 cases the parents disapproved of the 3 D visualization due to the more realistic presentation. Conclusion: 3 D ultrasound in cases of missed abortion can provide additional information regarding the presence of structural anomalies. It may give further details regarding the timing of embryonic/fetal demise in early pregnancy. Sufficient informational value is regularly obtained in cases having a CRL > 8 mm. In counseling parents, 3 D ultrasound is a useful tool and is generally well accepted.
Fetal weight is an important predictive parameter of neonatal morbidity and mortality. Precise estimation of fetal weight is therefore a valuable item of information for further prenatal and obstetric management. Many regression formulae for sonographic fetal weight estimation have been published during the last 30 years, which, unfortunately, generally show poor rates of accuracy. The aim of this study was to compare commonly used formulae in different birth weight groups in order to assess whether any of the formulae are more or less favourable. The second purpose was to estimate the role of examiners on the accuracy of fetal weight estimation. 11 different formulae were evaluated in a group of 1941 pregnancies. Each fetus underwent ultrasound examination with complete biometric parameters within seven days before delivery. The assessment was carried out by either experienced or inexperienced sonographers. Over the whole weight range and in the subgroup of newborns with a birth weight less than 2500 g (n = 160), two Hadlock regression formulae (including abdominal circumference, femur length, head circumference, biparietal diameter, and abdominal circumference, femur length, biparietal diameter, respectively) showed the best levels of accuracy. Infants with a birth weight between 2500 and 3999 g (n = 1570) were best estimated using the gender-specific Schild formula. Macrosomic newborns (n = 211) were best evaluated using Merz's regression formula. The more skilled sonographers were able to achieve much higher intraclass correlation coefficients for all formulae. Some regression formulae appear to be favourable within defined weight ranges. Accuracy of the formulae, however, is still unsatisfactory, and new formulae focusing on specific weight ranges (e. g., macrosomic fetuses) are needed. In addition, experience in obstetric ultrasound improves accuracy of fetal weight estimation.
Examination of fetal nasal bone (NB) by ultrasound between 11 + 0 and 13 + 6 gestation weeks has been proposed as an additional tool in the detection of trisomy 21 and therefore its application and implementation are used in a broad range. The study aimed at evaluating the interobserver feasibility of the measurement of fetal nasal bone length in comparison with experienced and inexperienced sonographers. The study population was comprised of women who chose to have first trimester screening (FTS) at the Fetal Medicine Unit of the University Medical School of Hannover. Two experienced (> 400 FTS examinations, sonographer 1 and 2) and one inexperienced sonographer (95 FTS examinations, sonographer 3) were asked to measure the nasal bone length consecutively and independently of each other. Statistical analysis was performed for any differences and variations in the results. The fetal profile was examined in 220 cases. The median nasal bone length by sonographer one was 2.4 cm, sonographer two 2.4 cm and sonographer three 2 cm. The differences between the results of sonographer 1 and 3 as well 2 and 3 were statistically significant. There were no significant variations between the results of sonographer 1 and 2. There was also no significant difference in the results concerning nuchal translucency and crown-rump length among the three examiners. The uncertainty and the difficulties of an inexperienced examiner with the presenting of the nasal bone, as shown by published data sets as well as by the variability of the measurement results of this study, with all the consequences in the risk calculation and counseling show that this tool should only be implemented by experienced and quality-controlled sonographers with a minimum amount of examinations. Because of its major impact in risk calculation and the importance of the nasal bone as a sonographic marker, documentation of the sonographer's skills is mandatory for the use of the nasal bones as an additional sonographic marker in first trimester screening.
Sonographic diagnostics are increasingly brought forward into the first trimenon. Lately, more and more expert studies have been published on echocardiography in the context of the Nuchal Translucency (NT) screening (gestational age 11-14 weeks). The aim of this study has been to evaluate the feasibility of early echocardiography on the occasion of first trimenon screening in the context of routine operation. From February 2003 to March 2004, an echocardiography was prospectively sought in 130 assigned, unselected pregnant women during the first trimenon screening. Three doctors with different OGUM/DEGUM (Austrian and German societies for ultrasound in medicine) qualifications at our ward tried to represent the four-chamber view (4CV) and the outflow tracts (OFT), each via B-mode and color Doppler. The study conditions were "routine", in particular they were temporally limited. In case no sufficient visual representation was achievable with the transabdominal examination, transvaginal sonography was also used. Via B-mode, 4CV was indicated as successful in 86/130, and OFTs in 37/130. Via color Doppler, on the other hand, it was possible to sufficiently represent 4CV in 75/130 and OFTs in 87/130. In routine screening, early heart examination is a big challenge and in many cases even with good equipment no complete diagnostic echocardiography can be achieved. The utilisation of the color Doppler is helpful particularly for the representation of the outflow tracts.
The Meckel-Gruber syndrome (MKS) is a rare autosomal recessive disorder that is characterized by typical sonographical findings: occipital encephalocele, postaxial polydactyly and cystic enlargement of the kidneys. Its recurrence risk of 25 % demands an exact diagnosis. Retrospective analysis of the sonographic characteristics in relation to the gestational age in eight cases with the pathologic diagnosis of MKS. The sonographic characteristics depend on the gestational age. The classic trias was solely seen in the case diagnosed before 14 (th) week of gestation. In the other seven cases, diagnosed between the 17 (th) and 20 (th) week of gestational age, only two of three characteristic signs of MKS could be visualised by US. Polydactyly was missed by ultrasound in all seven cases due to the marked oligohydramnion. The Meckel-Gruber syndrome can be confidently detected and diagnosed by sonography at the 11th to 14th gestational week. Later in the pregnancy, severe oligohydramnion makes it more difficult to establish the diagnosis by US alone. In these cases a meticulous autopsy is necessary to establish the diagnosis of MKS.
Evaluation of the diagnostic contribution of colour duplex sonography of the superficial temporal and the carotid arteries and Doppler sonography of the periorbital arteries by analysing the results in patients with giant cell arteritis with and without neuroophthalmological complications and patients with other diagnoses and neuroophthalmological complications. In a case control study, ultrasonographic findings in patients with neuroophthalmological complications (25 giant cell arteritis, 23 non giant cell arteritis) were compared to those of 62 patients suffering from giant cell arteritis without neuroophthalmological complications. Concentric hypoechogenic mural thickening (a so-called halo) was considered as an ultrasonographic finding typical of giant cell arteritis. Absent or retrograde signals not corresponding to carotid occlusive disease were classified as Doppler sonographic findings typical of giant cell arteritis of the periorbital arteries. There are higher rates of abnormalities in Doppler sonography of the periorbital arteries as well as halos in combination with stenosis of the temporal arteries in patients with giant cell arteritis with neuroophthalmological complications. This suggests that in patients with giant cell arteritis and neuroophthalmological complications, the haemodynamic situation is more severely disturbed. Patients suffering from giant cell arteritis with and without neuroophthalmological complications had the same rate of temporal artery abnormalities on colour duplex sonography (72 vs. 71 %), whereas abnormalities in the periorbital arteries were clearly different (40 vs. 8 %). Only 1 patient with giant cell arteritis without neuroophthalmological complication had anomalies of the carotid arteries typical of giant cell arteritis. In patients with other diagnoses and neuroophthalmological complications, the rate of anomalies in temporal artery colour duplex sonography and Doppler sonography of the periorbital arteries was 9 % and 0 %. Colour duplex sonography of the superficial temporal and carotid arteries and Doppler sonograpy of the periorbital arteries are complementary methods and should be part of the evaluation of all patients suspected to suffer from giant cell arteritis.
Purpose: Tissue defects are a common problem in trauma surgery and oncology. Flap transplantation is often the only therapy to cover such defects. Several monitoring systems are currently available but none has made it to the clinical routine. The aim of this study was to assess perfusion disturbances of local and free flaps using contrast-enhanced ultrasound (CEUS). Materials and methods: 112 patients were examined during the first 72 hours after operation. CEUS was performed by one experienced examiner with a linear transducer (6 - 9 MHz, LOGIQE9/GE) after a bolus injection of 2.4 ml sulfohexa-fluoride microbubbles (SonoVue®, Bracco, Italy). Retrospective vascular perfusion was quantified by evaluating the stored DICOM cine loops using the perfusion software QONTRAST® (Bracco, Italy). Over a total penetration depth of 3 cm, every centimeter was analyzed separately. 27 complications were observed. Complete flap loss was only seen in 4 cases, while 23 flaps had to undergo minor revision and survived. Results: Regarding the complete flap size, quantitative analysis showed significantly higher perfusion values in patients without complications compared to patients with complications: PEAK 16.5 vs. 10.0 (p = 0.001), TTP 32.6 vs. 22.2 (p = 0.001), RBV: 738.8 vs. 246.2 (p < 0.001), RBF 17.5 vs. 10.1 (p < 0.001) and MTT 43.1 vs. 29.5 (p = 0.001). Analysis of the correlation of the different flap types, age, sex and etiology of the tissue defect to the complication rate showed no statistical correlation. Conclusion: CEUS was capable of detecting vascular disturbances after flap transplantation. TTP, RBV and MTT seem to be the most accurately parameters and are not susceptible to malfunction during measurement.
The aim of our study was to evaluate the efficacy of microwave (MW) ablation of liver metastases guided by B-mode ultrasound (US) and contrast-enhanced US (CEUS). 39 patients (17 women and 22 men) with a total of 125 liver metastases were treated with percutaneous or intraoperative CEUS-guided MW ablation. The primary tumor was colorectal cancer (n = 31), breast cancer (n = 6), carcinoid tumor (n = 1), and gastrointestinal stromal tumor (GIST) (n = 1). The median number of metastases ablated in the 45 treatment sessions was 2 (range 1 - 11). The median size (maximum diameter) of the 125 metastases was 1.5 cm (range, 0.6 - 4.0 cm). Nineteen (15 %) of the 125 metastases were bigger than 2 cm. Metastases smaller than 2 cm were treated with a single needle, metastases bigger than 2 cm were treated with 2 or 3 parallel needles. The 45 MW ablation sessions were performed percutaneously (n = 30), during laparotomy (n = 3), or during laparotomy combined with liver resection (n = 12). The 39 patients were followed up for at least 4 months with a median duration of 11 months (range, 4 - 20 months). The technical success rate was 100 %. The clinical effectiveness was 100 % with complete coverage of the metastasis by the avascular coagulation zone evaluated on immediate post-ablation CEUS. Local tumor progression (local recurrence) was seen in 12 (9.6 %) of the 125 treated metastases, and affected 10 (26 %) of the 39 patients. One major complication was observed in the form of a liver abscess that easily resolved after percutaneous drainage. Four minor complications were observed: Three cases of pain located at the puncture site and one case of ascites. CEUS was valuable in all phases of ablation including pre-ablation staging and procedure planning, placement of MW needles in the tumor, immediate post-ablation control of coagulation size, and finally in the long term follow-up regime. CEUS-guided MW ablation of liver metastases is an efficient and safe ablation technique with several advantages compared to other ablation modalities.
The recent development of a new multigate pulsed Doppler system used in conjunction with an A-mode scan allows real time display of the velocity profiles across the vessel and quantitative flow measurement. Experimental in-vitro and in-vivo studies showed an excellent correlation between flow measurements obtained by this noninvasive method and by direct timed collection. Preliminary results of the post-occlusive hyperaemic response in normals and in patients with iliac stenosis are presented. Although no statistical comparison is allowed, it appears that the hyperaemic response is diminished when an iliac stenosis is present. A non-invasive method of quantifying the haemodynamic significance of profunda femoris artery stenosis is described. Finally, the velocity profiles and the flow curves in PTFE grafts were studied and compared to the flow patterns of the normal superficial femoral artery. The differences observed between the two conditions might explain the low patency rate of the synthetic grafts. Other fields of application of the method are suggested. The future development of a Duplex scanner combining B-mode imaging and the multigate Doppler system will allow the exploration of vessels within the abdomen and thorax: portal vein, in situ or transplanted renal arteries, ascending and abdominal aorta.
Purpose: The aim of this study was to measure the two frontomaxillo-facial (FMF) angles: the FMF-vomer (FMF-v) and the FMF-palate (FMF-p), and to visualize the vomer in the 1(st) and early 2(nd) trimester, in order to ascertain whether they can be used as markers for trisomy 21 and trisomy 13. Materials and methods: A 2D ultrasound scan was performed in the 340 normal and 12 abnormal pregnancies, using the linear, convex and endovaginal probes. Results: We visualized the FMF angles within 1 to 5 minutes in 253 (72 %) of cases by using the linear probe. FMF-v angle was significantly smaller that the FMF-p angle (79.8° vs. 89.7°, 71.5° vs. 84.5° for the two trimesters, respectively), and that the value of both angles decreased in the second trimester. There was not one single case of trisomy in which vomer could be identified in the 1 (st) and early 2 (nd) trimester. The FMF-p angle failed to present difference between normal cases and the ones with trisomy (89.5°). There was not one single case of trisomy (21 or 13) in which vomer or FMF-v could be identified in the first or early second trimester. The diagnostic accuracy of vomer as a marker for trisomy was 0.985. Conclusion: If the vomer cannot be visualized in the 1 (st) and early 2 (nd) trimester, it is important to check the karyotype, and it is not necessary to measure the FMF-p angle. The high resolution probe (L 12 - 5 Mhz) enables easier assessment of the vomer.
Abb. 4 Vergleich der Sensitivitäten und Spezifitäten der unterschiedlichen diagnostischen Verfahren. Fig. 4 Comparison of sensitivity and specificity of the different diagnostic methods.  
Complementary diagnostic methods in early diagnosis of breast cancer are used to increase diagnostic accuracy and minimize unnecessary invasive diagnostic procedures. Aim of the following prospective, open multicenter clinical study was to define the value of high-frequency breast ultrasound with 13 MHZ transducers compared to standard breast ultrasound with 7.5 MHz. Data of 810 female patients, aged 45 to 60 years, with 819 suspicious breast lesions evaluated by four participating centres between October 1996 and December 1997. Standardised breast ultrasound was performed uniformly using a AU4 IDEA diagnostic ultrasound system by Esaote-Biomedica in addition to a standardised procedure of clinical examination and standard-2view-mammography. Analysis of all aquired data and the correlating histopathological findings was done by means of descriptive statistics on the basis of an access datafile (Version 2.0). The histopathological evaluation showed 435 benign and 384 malignant findings. Overall sensitivity and specificity of the clinical examination were 71.1 % and 88.9 % and for mammography 84.7 % and 76.5 %, respectively. Standard ultrasound with 7,5 MHz reached a sensitivity of 82,6 % and a specificity of 80.8 % high-frequency ultrasound with 13 MHz came to 87.2 % and 78.4 %, respectively. Regarding tumour size, mammography gave the highest sensitivity in detection of pre-invasive cancers (DCIS). High-frequency breast ultrasound (13 MHz) proved to have a higher diagnostic accuracy compared to standard breast ultrasound (7,5 MHz) regardless of tumour size. Sensitivity was especially improved in case of small invasive tumours (pT1a) with 78 % versus 56 %, respectively. We conclude that high-frequency ultrasound is a valueable additive tool especially in the diagnosis of small tumours, improving diagnostic safety and reducing unnecessary invasive diagnostic procedures.
PURPOSE Assessment of first-trimester combined screening for trisomy 18 and 13 with the combined use of the risk algorithms for trisomy 21, 18 and 13. MATERIALS AND METHODS First-trimester combined screening based on maternal and gestational age, fetal NT, PAPP-A and free β-hCG was assessed in 39 ,004 pregnancies. Patient-specific risks for trisomy 21, 18, 13 were computed based on the current FMF London algorithm. RESULTS The study population consisted of 38 ,751 singleton pregnancies including 39 cases with trisomy 18 or 13. In the aneuploid group, median delta NT was 0.72 mm, PAPP-A was 0.21 MoM and free β-hCG was 0.33 MoM. Although only 41 % of the NT measurements of fetuses with trisomy 18 or 13 were above the 95th percentile, the detection rates for trisomy 18 or 13 were 82 % with the trisomy 18/13 algorithm and 56.4 % with the trisomy 21 algorithm. The respective false-positive rates were 0.7 % and 4.7 %. The combination of the trisomy 18/13 and the trisomy 21 algorithm with the same cut-offs led to a detection rate of 94.9 % at an overall false-positive rate of 5.0 %. CONCLUSION Despite a substantial underestimation of the fetal NT, the combined use of the trisomy 18/13 and the trisomy 21 algorithm of the FMF London leads to a detection rate for trisomy 18/13 of about 95 % for a false-positive rate of 5.0 %. © Georg Thieme Verlag KG Stuttgart · New York.
Fibromatosis colli is the most common cause of congenital torticollis. Patients show a solid tumor in the region of the sternocleidomastoid muscle which has to be differentiated from other congenital space-occupying lesions in the cervical region. 13 infants (7 boys, 6 girls) with a mean age of 28 +/- 21 days with fibromatosis colli were examined with a high-resolution linear transducer via color-coded duplex sonography. The location of the tumor within the sternocleidomastoid muscle, delineation from surrounding structures, the echogenicity, and the vascularization were estimated. 3 tumors were surgically removed, and the other 10 infants were treated conservatively with physiotherapy. The tumors were located on the right side in 10 patients and on the left side in 3 infants. In 10 patients the tumor was located in the caudal part, in 3 in the middle part of muscle. All tumors showed a good delineation from the surrounding structures. The volume of the tumor was 5.4 +/- 2.7 ml. 8 tumors showed inhomogeneous echogenicity, and 5 showed homogenous echogenicity. 9 tumors had echopoor, 3 echogenic, 1 isoechogenic internal echoes compared to the contralateral healthy muscle. 13 tumors showed increased perfusion (10 diffusely, 3 focally) via color-coded Doppler sonography. Diagnosis of fibromatosis colli can be affirmed sonographically. The tumors are commonly located in the distal 2 / 3 of the sternocleidomastoid muscle and show good delineation from surrounding structures. Typically an inhomogeneous, echopoor tumor with increased perfusion can be shown. Additional diagnostic imaging modalities are usually not necessary. The treatment of choice is physiotherapy. In special cases with a lack of improvement, surgery is necessary.
The aim of the study was to characterize SonoVue enhancement in hepatocellular carcinoma in correlation to both lesion diameter and histological differentiation of the lesion. In a prospective study 130 patients (72 male, 58 female, 62 +/- 10 years) with HCC lesions detected by B-mode sonography were examined. After injection of 1.2 - 2.4 ml SonoVue, HCC lesions were examined continuously for up to 5 min using "low MI" sonography. Arterial hypervascularization was found in 72 % of the HCC lesions without correlation to the lesion diameter or histological grading, when analyzed for the total group. However, the analysis of the G 1 subgroup showed significant correlation between lesion diameter and arterial hypervascularization. Arterial hypervascularization was found in 95 % of the G 1 lesions > 3 cm but in only 43 % of the G 1 lesions < 3 cm (p < 0.001). In contrast, analysis of the remaining HCC lesions (without G 1) showed arterial hypervascularization in 69 % of the lesions < 3 cm and in 72 % of the lesions > 3 cm (n. s.) without correlation to the diameter. In the late phase in the G 1 subgroup, hypoechoic demarcation was found in 95 % of the G 1 lesions > 3 cm, but in only 64 % of the G 1 lesions < 3 cm (p < 0.001). In contrast, in the less differentiated HCC lesions (without G 1), hypoechoic demarcation was found in 91 % (HCC > 3 cm) and in 82 % (HCC < 3 cm) of the lesions (n. s.). In well-differentiated HCCs (G1) hyperechoic enhancement in the arterial phase and hypoechoic demarcation in the late phase correlate to the diameter.
To evaluate the incidence and diagnostic accuracy of tumor-specific vascularization pattern in contrast-enhanced ultrasound (CEUS) in the differential diagnosis of liver tumors in clinical practice. From May 2004 to December 2006 1349 patients (male 677, female 672) with a hepatic tumor lacking a definite diagnosis based on B-mode ultrasound and power Doppler ultrasound were examined at 14 hospitals by CEUS using a standardized protocol (pulse/phase inversion imaging, mechanical index < 0.4). Vascularity pattern and contrast enhancement pattern were analyzed in focal lesions during the arterial, portal, and late phase. The tumor-specific diagnosis established after CEUS was compared to histology (> 75 % cases) or in some cases to CT or MRI. The final diagnosis of 573 benign hepatic tumors included hemangiomas (n = 242) and focal nodular hyperplasia (n = 170), other benign lesions (n = 161). Tumor-specific vascularization pattern such as a wheel-spoke pattern and arterial hyperenhancement followed by isoenhancement in the late phase in FNH or a nodular peripheral enhancement and partial or complete fill-in pattern in hemangiomas could be assessed in the majority, but not all lesions. The diagnostic accuracy of CEUS was 83.1 % for all benign lesions and 82.2 % for hemangioma and 87.1 % for FNH. The final diagnosis of 755 malignant hepatic tumors included metastases n = 383, hepatocellular carcinoma n = 279 and other malignant lesions n = 93. Late phase hypoenhancement was seen in almost all liver metastases (94.7 %) The diagnostic accuracy of CEUS was 95.8 % for all malignant lesions and 91.4 % for liver metastases and 84.9 % for hepatocellular carcinomas. Tumor-specific vascularization pattern in CEUS have a high diagnostic impact on the overall high diagnostic accuracy of CEUS for the differential diagnosis of hepatic tumors in clinical practice.
Investigation of the frequency of various solid focal liver lesions (SFLL) in noncirrhotic and cirrhotic livers with focus on the frequency of metastasis in cirrhotic livers. The patient collective in the DEGUM multicenter study (n = 1349) was reevaluated and divided in subcollective A without (n = 1067) and B with cirrhosis (n = 282). 74.6 % of the various tumor entities were confirmed histologically (n = 1006). In subcollective A there were 385 patients with metastases (36.4 %) and 65 with HCC (6.1 %), whereas the most common benign lesions were hemangioma, with 237 cases (22.4 %) and FNH, with 170 cases (16.1 %). In subcollective B there were 216 cases of HCC (76.6 %) and 12 metastases (4.3 %), as well as 42 benign lesions (14.9 %). CCC was rare in both subcollective A (3.3 %) and subcollective B (2.5 %). A positive oncological history increased the probability of a malignant SFLL in subcollective A by 1.8 times, but did not do so in subcollective B. The frequency of various tumor entities is different in patients with and without cirrhosis of the liver. In noncirrhotic livers, malignant and benign SFLL are equally common. The most common forms are metastases, hemangiomas and FNH, CCC is rare. A positive history of extrahepatic malignancy increases the probability of a malignant SFLL. In cirrhosis, HCC dominates, HCC is 18 times as common as metastases. Benign SFLL and CCC are rare.
Transcutaneous ultrasound enables visualization of pleural based lesions but with a poor correlation to specific pathology. Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use. Up to date there are no data about the use of contrast enhanced sonography (CES) in a large series of pleural based pulmonary lesions. From August 2004 to August 2005, 137 consecutive patients with pleural based pulmonary lesions on B-mode sonography were studied by CES using a transcapillary second-generation contrast agent (SonoVue(R)). The following CES parameters were retrospectively evaluated. Time to enhancement (TE) of contrast agent after i. v. application was determined and classified as short TE (< = 6 sec) vs. delayed TE (> 6 sec). Extent of enhancement (EE) was evaluated during the arterial phase (2 - 30 sec) and the parenchymal phase (1 - 5 minutes) by using the normal splenic tissue as an in vivo reference, and classified in reduced EE (anechoic/hypoechoic) vs. marked EE (isoechoic/hyperechoic) during both phases. Homogeneity of enhancement (HE) was classified as homogeneous vs. inhomogeneous. 60 patients had histologically confirmed malignant lesions due to central lung cancer (n = 31), and peripheral malignant lesions (n = 29). 77 patients had benign pleural based lesions including pneumonia (n = 32), pulmonary embolism (n = 20), compression atelectasis (17), and other benign pleural based lesions (n = 8). Malignant and benign lesions did not vary significantly regarding TE, EE, and HE. However, there were highly significant differences in the ratio of short vs. delayed TE and reduced vs. marked EE between the six disease groups. Characteristic patterns were short TE with marked EE in all compression atelectasis cases and in 62 % of patients with pneumonia. Delayed TE and reduced EE was seen in all patients with pulmonary embolism and in 62 % of patients with peripheral malignant lesions. Central lung cancer and benign nodules did not present with such specific patterns. No significant differences in HE were seen between subgroups. Pulmonary lesions are characterized by different CES-patterns of arterial supply as evidenced by TE and EE which depends on underlying causes, but CES does not allow to distinguish benign from malignant pleural based lesions in general.
Purpose: The aim of this study was to assess different aspects of reliability in high-resolution ultrasonography (HRUS) of the peripheral nerves and to establish reference values for the most frequently examined nerve segments. Materials and methods: A nerve size parameter, the cross-sectional area (CSA) of the C5, C6 and C7 cervical roots, the median, ulnar, radial, superficial radial, peroneal, tibial, and the sural nerves was measured using HRUS at a total of 14 predefined anatomical sites in two different cohorts of healthy subjects (n = 56), and the inter-rater, intra-rater and inter-equipment reliability of measurements was assessed. Results: The mean CSA of the 14 nerve segments ranged from 2 to 10 mm(2). The intra-rater, inter-rater and inter-equipment reliability was high with intraclass correlation coefficients of 0.93, 0.98, and 0.86, respectively. The CSA values showed no consistent correlation with age, height, and body weight, but males had significantly larger values than females for nerve segments on the arm after correcting for age, weight and height in multivariate analysis. CSA values did not differ when two independent cohorts were compared. Conclusion: Peripheral nerve ultrasonography is a reliable and reproducible diagnostic method in the hands of experienced examiners. Normal values for several upper and lower extremity nerves are provided by our study.
Longitudinal section through the lower right abdomen shows multiple regional lymph nodes measuring 3.28 ” 1.25 cm due to mesenteric lymphadenopathy. 
a Longitudinal section through the appendix (A) shows a 6.4 mm measuring round hypoechoic tumour at the tip of the appendix (arrows). 
b Cross section through the appendix shows an eccentrically growing mass (arrows) with destruction of the wall layers of the appendix. 
Histological examination of the tumour showing a solid and trabecular growth pattern of small monomorphic tumour cells with strong expression of synaptophysin (immunhistochemical staining for synaptophysin, 400 ” ). 
Carcinoid tumours of the appendix are rare tumours of the bowel which occasionally are found histologically in resected appendices. There are no publications on the sonographic diagnosis of carcinoid tumours of the appendix in children. We report on the sonographic examination of a carcinoid tumour in a 14-year-old boy. Sonography showed a hypoechoic tumour located at the apex of the appendix with eccentric growth. Histology revealed a carcinoid tumour with invasion of the regional lymphatic vessels.
To describe B-mode sonographic patterns of splenic metastases and to evaluate clinical data regarding tumour staging, kind of tumour and survival of patients with splenic metastases. From 1988 till October 2002, about 168 000 abdominal examinations were performed in an internal ultrasound laboratory. During this time, n = 59 patients with splenic metastases were detected who qualified for the retrospective study design. The following data were evaluated: echomorphology of splenic metastases, tumour staging, kind of underlying tumour, and survival rates of patients with splenic metastases. The median age of patients was 61.8 years (SD +/- 10.9). Lesions were hypoechoic n = 19 (32%), isoechoic n = 15 (25.5%), hyperechoic n = 10 (17%) und complex n = 15 (25.5%). A hypoechoic rim was found in n = 18 patients (31 %). An additional spread into other organs was seen in 56 cases (95%). Underlying cancers were carcinoma of unknown primary tumours (CUP) n = 12 (20.3%), lung cancer n = 11 (18.6 %), ovarian cancer n = 7 (11.9%), colorectal cancer n = 6 (10.2%), breast cancer n = 6 (10.2%), malignant melanoma n = 5 (8.4 %), and others n = 12 (20.3%). The median survival time for all patients was 8.7 months. The worst prognosis within the subgroup analysis was found for patients with CUP-syndrome who had a median survival time of 2.7 months. The sonographic pattern of splenic metastases is variable. Metastases to the spleen indicate a terminal stage cancer disease and is associated with an extremely short survival time. 20 % of underlying cancers were CUP-syndromes with the worst prognosis of all subgroups.
Principal clinical parameters studied for the evaluation group. 
regression formulas for estimating fetal weight that were con- sidered in the evaluation group. 1 
In addition to gestational age, fetal weight is an important predictive parameter for neonatal morbidity and mortality in very small fetuses. In order to improve weight estimation, specific weight formulas for fetuses under 1500 g have been introduced by several authors. The aim of the present study was therefore to compare specific weight equations for fetuses under 1500 g with widely used methods that were designed for the whole fetal weight range. 459 pregnancies were included in order to evaluate six widely used formulas and four formulas specifically designed for very small fetuses. The inclusion criteria were a singleton pregnancy, birth weight equal to or less than 1500 g, ultrasound examination with complete biometric parameters during the 7 days prior to delivery, and an absence of structural or chromosomal malformations. All formulas, except the Hadlock equations, demonstrated a significant systematic error. Regarding the random error, it was similar for most of the methods. The Scott formula showed the narrowest limits of agreement. At a discrepancy level of 5 % and 10 % between estimated fetal weight and actual birth weight, one of the Hadlock formulas included the most cases. Weight formulas, specifically designed for very small fetuses, do not improve sonographic weight estimation substantially. Among these formulas, the Scott equation was the most accurate one. However compared to the widely used Hadlock formulas, it was not favorable.
Diagnosis-relevant laboratory findings in 17 patients with AIP. 
B-mode ultrasound in 17 patients with autoimmune pancreatitis. 
ERCP in 14 patients with autoimmune pancreatitis. 
Purpose: Autoimmune pancreatitis (AIP) is an independent, underdiagnosed, rare form of chronic pancreatitis. The goal of this study is to document ultrasound findings in histologically confirmed AIP in order to determine the diagnostic value of ultrasound. Materials and methods: 6 of 74 DEGUM instructors for internal medicine (level 3 and 2) provided anonymized clinical and sonographic data from 17 patients with histologically confirmed AIP. Results: 9/17 patients had diffuse AIP, 8/17 had focal AIP, 14/17 suffered from upper abdominal pain, 9/17 had jaundice, and 3/9 had an elevated IgG4 level. Ultrasound showed diffuse hypoechoic organ enlargement in 9/17 cases and a hypoechoic tumor with an unclear border in 8/17 cases. AIP was verified by ultrasound-guided percutaneous core biopsy in 14 cases, by biopsy of the bile duct in 1 case, and by surgical biopsy in 2 cases. Involvement of the hepatobiliary system was present in 7/17 patients and autoimmune cholangitis was verified in 5 cases. All patients experienced remission after immunosuppressive treatment. The pancreatic duct had a normal width in 11 cases, was dilated in 5 cases, and was stenosed over a long stretch in 3 cases. Contrast-enhanced ultrasound did not show uniform signal increase but also no significantly reduced or absent perfusion. Conclusion: Ultrasound can be diagnostically useful if the clinical manifestations of AIP are known. While the diffuse form allows an ad-hoc suspected diagnosis, the focal form can only be suspected in the case of additional extrapancreatic involvement. Contrast-enhanced ultrasound (CEUS) contributes greatly to the differentiation from ductal adenocarcinoma in the case of focal AIP.
Bei der Routine-Ultraschalluntersuchung in der 17. Schwangerschaftswoche wird ein Epignathus diagnostiziert. Epignathi sind Teratome in der Mundhöhle. Nach unserem Wissen wurden bisher nur 3 derartige, in der ersten Schwangerschaftshälfte diagnostizierte Mißbildungen publiziert. Meistens besteht ein Polyhydramnion und ein erhöhtes Alfafetoprotein, gelegentlich eine intrazerebrale Ausbreitung des Teratoms. Bei fehlender zerebraler Beteiligung ist eine radikale Operation nach der Geburt möglich, falls keine Komplikationen im Schwangerschaftsverlauf auftreten. Bei Diagnose in der ersten Schwangerschaftshälfte ist ein Abbruch der Schwangerschaft zu diskutieren.
Purpose: The aim of the present study was to calculate new Doppler reference ranges for systolic, intensity-weighted mean, and end-diastolic blood flow velocities (Vmax, Vmean, Vmin) and fetal heart rate and impedance indices (PI, RI) of the umbilical artery by automatic waveform analysis. Materials and methods: A cross-sectional prospective study of 1926 low-risk pregnancies was performed at 18 - 42 weeks of gestation. The measurements were carried out in the region of a free floating loop of cord. Reference ranges for the individual measuring parameters were constructed based on a growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle. The intraobserver reliability was also assessed. Results: A significant increase in umbilical blood flow velocity was observed at 18 - 42 weeks of gestation (Vmax = 33.7 cm/sec to 65 cm/sec (p < 0.001), Vmean = 18.2 cm/sec to 38.7 cm/sec (p < 0.001) and Vmin = 8.2 to 31 cm/sec (p < 0.001). Reference curves for the pulsatility and the resistance index were associated with significant decreases with increasing gestational age (PI: 18 weeks: 1.3; 28 weeks: 1.1; 42 weeks: 0.8 and RI: 18 weeks: 0.7; 28 weeks: 0.6; 42 weeks: 0.5). The fetal heart rate decreased from 147 - 134 bpm. The intraobserver reliability was low, but of no clinical relevance. Conclusion: The reference ranges for blood flow velocities and resistance indices in the umbilical artery calculated by the authors serve as the basis for Doppler ultrasound antenatal examinations in a normal patient population and enable the early diagnosis of fetal risk.
In spite of its prevalence in neonates, an inguino-scrotal hernia is a rarely detected condition in prenatal life. The sonographic findings, i. e., a scrotal mass with intestinal peristalsis, the differential diagnosis, and possible associations between a scrotal hernia and chromosomal aberrations are described by presenting the case of a fetus with trisomy 18 and major structural anomalies. Georg Thieme Verlag KG Stuttgart, New York.
The goal of the present study was to establish new Doppler reference ranges for maternal heart rate, intensity-weighted mean blood flow velocities (Vmean) and impedance indices (PI, RI) for the uterine artery by automated waveform analysis. A cross-sectional prospective study of 921 low-risk pregnancies was performed at 18 - 42 weeks of gestation. Uterine blood flow velocities were derived with pulsed-wave color Doppler. Measurements were carried out 1 to 2 cm above the crossing of the uterine and external iliac arteries. Reference ranges for the individual measuring parameters were constructed based on a growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle. A significant increase in intensity-weighted mean uterine blood flow velocities was observed at 18 - 42 weeks of gestation (Vmean = 43 cm/s to 50 cm/s (p < 0.001)). Reference curves for the pulsatility and resistance indices (PI, RI) significantly decreased with progressing gestation (PI: 18 weeks: 0.89; 42 weeks: 0.65 and RI: 18 weeks: 0.45; 42 weeks: 0.35). No significant PI and RI differences were observed when different placental locations were compared. The maternal heart rate decreased from 88 bpm to 77 bpm. Normal ranges for blood flow velocities and impedance indices in the uterine artery were established by Doppler ultrasound antenatal examinations of a large population of low-risk pregnancies. The data are proposed as reference curves to allow the early diagnosis of maternal and fetal risks.
Unlabelled: Objective of our study is qualitative and quantitative comparison of contrast enhanced ultrasound (CEUS) and 18F-FDG PET-CT in monitoring hepatic alveolar echinococcosis (HAE). Parasitic liver lesions were examined regarding number, size, morphology, vascularization and metabolic activity. Patients, methods: 36 patients with medically-treated HAE were included in this prospective clinical study. Abdominal ultrasound and CEUS were carried out using ultrasound contrast amplifier SonoVue®. As part of monitoring, patients were examined by 18F-FDG-PET-CT. Quantitative analysis of CEUS was performed using the Software VueBox™ Quantification Toolbox. Maximum contrast enhancement in lesions peak enhancement (PE) was used as parameter. For quantification of 18F-FDG PET-CT, maximum Standardized Uptake Value (SUVmax) of lesions was specified and statistically compared with PE. Results: 18F-FDG uptake in parasitic liver lesions was diagnosed by 18F-FDG PET-CT in 32 of 36 patients. Vascularization of liver lesions was detected by CEUS in 22 of 32 FDG-positive patients with sensitivity of 69% and specificity of 100%. Mean maximum diameter of lesions was 69.5mm in CEUS and 63.7mm in B-scan ultrasound (p < 0.0001). No significant correlation was found between SUVmax and PE (p = 0.8879). Conclusion: In comparison to FDG PET-CT, the gold standard for detecting viable lesions by depicting metabolism, CEUS detects viable lesions with high specificity and moderate sensitivity by showing vascularization. CEUS must be regarded as an important tool in monitoring HAE. Dimensions of parasitic lesions are displayed more precisely through CEUS than in B-scan. With currently available methods, CEUS quantification has no benefit in monitoring HAE lesions in daily clinical practice.
Purpose: To assess the risk of malignancy of thyroid incidentalomas found on 18F-FDG PET/CT by US features and cytologic results, and to evaluate the clinical usage of a combination of US features and cytology for post-FNA management of thyroid incidentalomas on 18F-FDG PET/CT. Materials and methods: From September 2006 to December 2008, 132 patients with 134 thyroid incidentalomas detected on 18F-FDG PET/CT who had undergone US and US-FNA were included in this study. We evaluated the malignancy rate of thyroid incidentalomas in different subgroups subdivided by US features and US-FNA cytology results. Several variables were compared between the benign and malignant group. Results: The risk of malignancy was 58.2 % (78/132) in thyroid incidentalomas on 18F-FDG PET/CT. Age, gender, and tumor size were not significantly different between the malignant and benign group. Malignancy rate of thyroid incidentalomas was significantly higher in the suspicious malignant (88.9 %) than in the probably benign group (11.3 %) on US (p < 0.001). Malignancy rates were high in thyroid nodules with "malignancy", "suspicious for malignancy", or "follicular neoplasm" on cytologic results, regardless of US features. However, malignancy rates of thyroid incidentalomas with "unsatisfactory" or "benign" results on cytology were higher in the suspicious malignant (75 %, 12.5 %, respectively) than in the probably benign (0 %) group on US. Conclusions: This study demonstrated that the risk of malignancy was high in thyroid incidentalomas on 18F-FDG PET/CT even without suspicious US features. However, there was no malignancy in nodules with no suspicious US features and benign cytology. Based on these results, we concluded that US may not replace FNA in the diagnosis of PET incidentalomas, and that a follow-up may be considered of thyroid incidentalomas with benign cytology and no suspicious US features.
The purpose of this study was to evaluate the efficiency of first trimester screening for chromosomal abnormalities using the sonographically determined thickness of nuchal translucency (NT) combined with maternal age. Risk screening was offered to all patients with a fetal crown rump length (CRL) between 45 and 84 mm after extensive counselling. For the risk assessment the software provided by the Fetal Medicine Foundation was used. In accordance with the recommendation of the Swiss Working Group on First Trimester Screening a cut-off risk of 1 : 400 was chosen. A total of 1980 consecutive pregnancies participating in the risk screening programme with due dates prior to May 1, 2001 were included. Mean maternal age was 30.1 yrs and 522 (26.4 %) patients were 35 yrs or older. A positive risk screening result was obtained in a total of 219 (11.1 %) pregnancies including 33 of the 37 (1.9 %) cases with unbalanced chromosomal abnormalities. The detection rate for unbalanced chromosome abnormalities in general (89.2 %) as well as the one for trisomy 21 (93.3 %) in particular are very high with a moderate false-positive rate (9.6 %) in this series. As a comparison in the series presented here, traditional "maternal age screening" (cut-off age 35 yrs) would have yielded detection rates of 64.9 % for all unbalanced chromosome abnormalities and 73.3 % for trisomy 21 at a false-positive rate of 25.0 %. Reducing the false-positive rate by raising the cut-off age to 38 yrs would yield detection rates of 40.5 % for all unbalanced chromosome abnormalities and 46.7 % for trisomy 21 at a false-positive rate of 8.9 %. The number of invasive procedures performed to detect one unbalanced chromosome count may be calculated as 21.75 using the cut-off age of 35 yrs as compared to 6.4 using NT measurement and maternal age. The outcome of this ongoing study is in good accordance with the earlier observation that the main benefit of the addition of first trimester NT measurements to the risk screening protocol is a very high detection rate at a moderate false-positive rate.
In a retrospective study of our hospital of the years 1983 to 1989 we diagnosed a hepatocellular carcinoma (HCC) in 30 patients. The diagnosis was confirmed by histology or cytology, ultrasound and clinical symptoms. The tumours presented sonomorphologically different patterns. Some were hypoechoic (n = 9), some hyperechoic (n = 16) and 5 had a mixed pattern. Nine of the hyperchoic lesions looked like a metastasis with a halo. 13 patients had multiple tumours or diffuse infiltration of the liver. Due to the variable sonomorphology only 16 patients were assumed to have a HCC, no definite diagnosis by ultrasound being possible. The concomitant cirrhosis of the liver was sonomorphically detected in 19 patients and was suspected in 2 further patients. Four patients had no cirrhosis; in 3 patients, the available information was insufficient. Because of the variable sonomorphology of HCC no definite diagnosis by ultrasound can be achieved. The combination of liver tumour and cirrhosis or elevated serumfetoprotein leads to the diagnosis. The diagnosis of HCC must be confirmed by histology.
Endoscopic ultrasound (EUS) allows for intraluminal sonographic imaging of the oesophagus, stomach, pancreatobiliary duct system, the papilla of Vater, as well as the colon and rectum. EUS has proved valuable for diagnosis and staging of tumours of the upper intestinal tract. EUS can also provide valuable additional information concerning lesions that cannot be immediately classified. As doing this involves, first, removal of the conventional endoscope and, second, insertion of the echo endoscope, EUS is not suitable for routine examinations. Therefore EUS has remained an independent endoscopic diagnostic modality. Moreover, due to their diameter conventional echoendoscopes cannot be inserted into the pancreatobiliary duct system. Fine calibre high frequency ultrasound probes promise a resolution of less than 2 mm in diameter. The following report is a summary of a one-day workshop which took place in Muenster, Germany on Oct. 28, 1995. Its goal was to define the current state of the art of miniaturised endoscopic ultrasound probes in the field of gastroenterology. During this workshop, possible clinical applications for diagnosis, therapy, as well as follow-up were described and discussed. The potential of miniaturised endoscopic ultrasound probes was explored in terms of possible future technical developments.
The diagnostic value and the complication rate of transabdominal chorionic villi and placental sampling was compared with standard amniocenteses. The method ist especially helpful in cases with conspicuous fetal sonographic findings. The results of 475 biopsies were retrospectively compared with 983 amniocenteses and chorionic villi samplings (CVS). 64% of chorionic villi samplings (CVS) were performed in the first, 30% in the second and 6% in the third trimester. The indications were advanced maternal age (45%) and psychological problems (14%) in the first trimester and conspicuous maternal serum markers (11%) or fetal ultrasound anomalies (12%) in the second and third trimester, respectively. 10 out of 20 aneuploid cytogenetic results were found in fetuses with sonographic anomalies. In 4 cases we found confined placental mosaicism, which was clarified by means of amniocentesis and cordocentesis. We had 8 miscarriages in a total of 475 CVS procedures; 6 in 304 before the 15th week of gestation (1.97%). The natural abortion rate in this gestational age is about 1%, the CVS-related abortion rate therefore is near 1%. Transabdominal CVS is a low risk method for rapid karyotyping during the entire pregnancy.
To investigate the risk of congenital malformations for newborn of obese women (BMI > or = 30) compared with women of average prepregnancy weight. We performed a prospective, population-based case-control study of 20,248 newborn born in the city of Mainz. A total of 1,451 infants (cases) with and 8,088 without congenital malformations (controls) were analysed. The relative risks of associations between obesity and malformations were calculated as odds ratios (OR) with 95% confidence intervals (CI). The prevalence of malformations in children of obese mothers is 11.1% and thus approximately 4% higher than those of the total study population. There is a significant odds ratio for major malformations (OR 1.3; KI 1.0-1.7). Statistically significant associations were calculated for malformations of the internal urogenital system (OR 1.7; 1.1-2.8), the eyes (OR 5.0; 1.3-20.0) and for orofacial clefts (OR 1.7; 1.1-2.8). Among the specific malformations the highest associations occurred for encephalocele (OR 7.3; 1.1-50.6), common truncus arteriosus (OR 6.3; 1.6-24.8) and Potter sequence (OR 6.3; 1.6-24.8). Adjustment for confounding factors (e.g. maternal diabetes mellitus and age) did not change the odds ratios. Our data demonstrate that newborn of obese mothers are at an increased risk for malformations. An adequate prenatal examination of these pregnancies should include ultrasound screening by specially trained ultrasonographers in tertiary units (DEGUM II/DEGUM III) and serum alpha-fetoprotein measurements. Public health campaigns for prevention are advised.
Evaluation of tubal patency is usually assessed with hysterosalpingography (HSG) or laparoscopy including chromopertubation. Sonographical visualisation with Echovist 200 (hysterosalpingo-contrast sonography-HyCoSy) provides a new noninvasive tool. Therefore we conducted a prospective controlled study to compare sonographic and radiological evaluation of the fallopian tube. Main test parameters were accuracy of both methods and patient discomfort. 50 patients were enrolled in this study. All patients were examined by both techniques; the sequence was randomly chosen. The results of HSG and HyCoSy were compared. Patient discomfort was assessed with a standardised questionnaire using a visual analog scale (0-10). Diagnosis of tubal patency identifying proximal or distal blockage was the primary end point using HSG as standard technique. Proximal and distal patency by HSG was sonographically confirmed in 82.9% (63/76) and 82.1% (46/56) tubes respectively. If HSG revealed proximal or distal occlusion, identical results were obtained in 91.7% (22/24) or 60% (12/20) by HyCoSy. No significant differences were found in patient discomfort. However a significant correlation was demonstrated between tubal patency and discomfort. The lowest score was obtained in patients with open tubes (4.6) increased in patients with distal occlusion (6.0) and reached a maximum with proximal pathology (8.7). Compared to conventional HSG, HyCoSy provides a highly efficient evaluation of tubal pathology and can be successfully used as a noninvasive screening method.
Top-cited authors
Christoph F Dietrich
  • Kliniken Hirslanden Beau Site & Salem und Permanence Bern
Fabio Piscaglia
  • University of Bologna
Odd Helge Gilja
  • Haukeland University Hospital
David Cosgrove
  • Imperial and King's Colleges London
Adrian Saftoiu
  • Universitatea de Medicina si Farmacie Craiova