Showing papers in "Ultraschall in Der Medizin in 2010"
TL;DR: CEUS and MRI are of equal value for the differentiation and specification of newly discovered liver tumors in clinical practice and the characterization of metastases and HCC is also very reliable.
Abstract: PURPOSE: The aim of this prospective multicenter study was to assess the diagnostic role of CEUS in the diagnosis of newly discovered focal liver lesions in clinical practice. One important aspect is the comparison of CEUS with magnetic resonance imaging (MRI). MATERIALS AND METHODS: From 05 / 2004 to 12 / 2006, standardized CEUS was performed prospectively on 1349 patients with focal liver lesions that had been newly detected by fundamental ultrasound in order to determine tumor differentiation and tumor entity. 269 patients had a standardized MRI after CEUS. In typical liver hemangioma and focal nodular hyperplasia (FNH), the definitive diagnosis was based on the MRI as the ”diagnostic gold standard” and on clinical evidence and additional follow-up (subgroup A) or on histology (subgroup B). 262 patients met the diagnostic standard that had been set. RESULTS: In the subcollective (n = 262), the tumor differentiation (malignant or benign) of CEUS and MRI was concordant in 225 cases (85.9 %), and the assessment of tumor entity in 204 cases (77.9 %). In subgroup A (n = 180), concordant results for tumor differentiation were obtained in 169 (93.2 %) and for tumor entity in 160 (88.9 %) cases. Liver hemangiomas (n = 122) and FNH (n = 43) were most frequent. Subgroup B (n = 82) comprised mainly malignant liver lesions (n = 55), with only a few of hemangiomas (n = 8) or FNH (n = 5). Tumor differentiation was concordant in 56 (68.3 %) and tumor entity in 44 cases (53.7 %). There were no statistically proven differences between CEUS and MRI. CONCLUSION: CEUS and MRI are of equal value for the differentiation and specification of newly discovered liver tumors in clinical practice. CEUS and MRI are extremely reliable for the differentiation of benign and malignant lesions, the diagnosis of liver hemangiomas and FNH. The characterization of metastases and HCC is also very reliable.
175 citations
TL;DR: A German interdisciplinary council on carotid artery stenosis has recommended the implementation of the NASCET grading system (distal diameter reduction percentage) as the standard and a novel differentiation between main (primary) and additional (secondary) criteria has been proposed.
Abstract: Since 1986, German ultrasound criteria for grading carotid stenosis have followed the local diameter reduction percentage consistent with the definition used in the European Carotid Surgery Trial (ECST) definition. To overcome the confusion caused by the coexisting grading method used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET), a German interdisciplinary council on carotid artery stenosis has recommended the implementation of the NASCET grading system (distal diameter reduction percentage) as the standard. The multi-parametric German "DEGUM ultrasound criteria" consisting of combined Doppler and imaging criteria have consequently been revised and transferred to the NASCET definition. In addition, a novel differentiation between main (primary) and additional (secondary) criteria has been proposed. When these ultrasound criteria are combined, vascular sonography allows reliable grading of carotid disease.
147 citations
TL;DR: The data demonstrates that the complementary use of sonoelastography definitely improves the performance in breast diagnostics and can be integrated into daily practice.
Abstract: PURPOSE: Hitachi real-time tissue elastography (HI-RTE) is an ultrasound technique that facilitates the estimation of tissue elasticity. Our study evaluates whether sonoelastography improves the differentiation of benign and malignant breast lesions. MATERIALS AND METHODS: In a multicenter approach sonoelastography of focal breast lesions was carried out in 779 patients with subsequent histological confirmation. We present data from 3 study centers (Berlin, Bielefeld, Homburg/Saar) focusing on the sensitivity (SE), specificity (SP) and the positive (PPV) and negative predictive value (NPV) of sonoelastography. In addition we performed an analysis of the diagnostic performance, expressed by the pretest and posttest probability of disease (POD), in BI-RADS®-US 3 or 4 lesions as these categories can imply both malignant and benign lesions and a more precise prediction would be a preferable aim. RESULTS: Sonoelastography demonstrated an improved SP (89.5 %) and an excellent PPV (86.8 %) compared to B-mode ultrasound (76.1 % and 77.2 %). Especially in dense breasts ACR III-IV, the SP was even higher (92.8 %). In BI-RADS-US 3 lesions, a suspicious elastogram significantly modified the POD from 8.3 % to a posttest POD of 45.5 %. In BI-RADS-US 4 lesions, we found a pretest POD of 56.6 %. The posttest POD changed significantly to 24.2 % with a normal elastogram and to 81.5 % with a suspicious elastogram. CONCLUSION: Our data demonstrates that the complementary use of sonoelastography definitely improves the performance in breast diagnostics. Finally we present a protocol of how sonoelastography can be integrated into our daily practice.
140 citations
TL;DR: At present, liver elasticity evaluation by means of ARFI is not superior to TE for the assessment of liver fibrosis, but is an accurate test for the diagnosis of cirrhosis.
Abstract: Purpose To compare two methods of noninvasive assessment: transient elastography (TE) and acoustic radiation force impulse elastography (ARFI) Patients and methods Our study included 114 subjects: 38 healthy volunteers, (considered to have no fibrosis - F 0) and 76 patients with chronic liver disease: 53 who had undergone liver biopsy (LB) (7 with F 1, 24 with F 2, 22 with F 3 Metavir) and 23 previously diagnosed with cirrhosis (F4 Metavir) In each patient we performed a liver stiffness measurement by means of TE and ARFI ARFI (shear wave velocity quantification) was performed at 3 points: at 0 - 1 cm, at 1 - 2 cm and at 2 - 3 cm under the capsule For each depth, 5 valid measurements were made, and a median value was calculated, measured in m/sec Results A direct, strong, linear correlation (Spearman rho = 0848) was found between TE and the stage of fibrosis (p 0), TE had the best predictive value: optimized cut-off 565 kPa (AUROC -0898) For ARFI, the cut-offs were: 14 m/sec, AUROC -0747 (1 - 2 cm), and 126 m/sec AUROC -0721 (2 - 3 cm) For predicting cirrhosis (F = 4 Metavir), the optimized cut-offs were: TE -129 kPa (AUROC -0994); ARFI - 178 m/sec for measurements made 2 - 3 cm below the capsule, AUROC - 0951 Conclusion At present, liver elasticity evaluation by means of ARFI is not superior to TE for the assessment of liver fibrosis For ARFI, the most reliable results are obtained if measurements are made 1 - 2 and 2 - 3 cm below the liver capsule ARFI is an accurate test for the diagnosis of cirrhosis
139 citations
TL;DR: This study underscores the usefulness of ARFI as a quick method for assessing liver fibrosis or cirrhosis in patients with HBV or HCV and concludes that ARFI measurements of the liver should be performed via an intercostal access.
Abstract: PURPOSE: The acoustic radiation force impulse (ARFI) technology is a novel ultrasound method that provides information about the local elasticity of tissue in real-time. ARFI is integrated in a conventional ultrasound system. The aim of this exploratory study was to evaluate this new technique in the assessment of liver fibrosis in a cohort with chronic viral hepatitis B and C and to ascertain the most reliable hepatic segment for measurements. MATERIALS AND METHODS: 57 patients (27 female, 30 male, mean age 54 years) with chronic viral hepatitis B and C underwent ARFI imaging and consecutively liver biopsy. The results were compared to the histological fibrosis degree (F), which served as the reference. 20 healthy volunteers received ARFI quantification of different segments of the liver. RESULTS: The best ARFI assessments with the lowest rate of invalid measurements were carried out by an intercostal approach to segment VII/VIII of the liver. The ARFI velocities of the healthy group had a mean of 1.09 m/s (range 0.79 - 1.32 m/s), the means of the patient group ranged from 0.83 to 4.19 m/s. ARFI quantification correlated significantly with the histological fibrosis stage (p < 0.001). The area under the receiver operating characteristic (ROC) curves for the accuracy of ARFI imaging was 85 %, 92 % and 87 % for the diagnosis of moderate fibrosis (≥ F2), severe fibrosis (≥ F3) and cirrhosis ( = F 4), respectively. CONCLUSION: This study underscores the usefulness of ARFI as a quick method for assessing liver fibrosis or cirrhosis in patients with HBV or HCV. ARFI measurements of the liver should be performed via an intercostal access. Increasing ARFI velocities correlate with higher degree of hepatic fibrosis.
124 citations
TL;DR: Even in this multi-center trial, CEUS proved to be an excellent method for clarifying liver lesions remaining unclear after native ultrasound.
Abstract: PURPOSE: To discuss the difficulties of contrast-enhanced ultrasound (CEUS) in a large multi-center trial. MATERIALS AND METHODS: CEUS was performed on 1349 liver lesions with an unclear diagnosis after native ultrasound using a standardized protocol (phase inversion; low MI 2 min. were documented. The diagnosis based on CEUS results was compared to the final diagnosis (histology: n = 1006; MRI: n = 269; CT: n = 269 – multiple examinations possible). RESULTS: Of the 1349 enclosed liver lesions, 20 could not be definitively diagnosed even using all diagnostic steps including histology (the others were proven to be benign n = 573 or malignant n = 756). Of the 1349 unclear liver lesions, 1257 could be differentiated with an accuracy of 90.3 % using CEUS. The sensitivity, specificity, and positive and negative predictive value for malignant liver lesions was 95.8 %, 83.1 %, 88.2 % and 93.7 % respectively. 92 liver lesions (6.8 %) could not be definitively diagnosed using CEUS. Most of them were benign (n = 67) on final diagnosis. The CEUS diagnosis was wrong for 39 lesions. However, only 8 lesions classified as benign by CEUS turned out to be malignant. In 3 cases HCC proven by histology was incorrectly diagnosed by CEUS as adenoma and 2 lesions incorrectly diagnosed by CEUS as FNH turned out to be an HCC and a metastasis. Two lesions diagnosed by CEUS as hemangiomas turned out to be an HCC and a metastasis. One lesion classified as benign by CEUS was ultimately diagnosed as a lymphoma. CONCLUSION: Even in this multi-center trial, CEUS proved to be an excellent method for clarifying liver lesions remaining unclear after native ultrasound. The CEUS diagnosis of benign was only incorrect in a few cases.
91 citations
TL;DR: This is the first study about CEH-EUS for the quantitative assessment of uptake after contrast injection which has shown that it can aid differentiation between benign and malignant masses but cannot replace EUS-FNA.
Abstract: PURPOSE: Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) for the assessment of microcirculation and the delineation of pancreatic tumors in order to characterize and stage them has only recently become available for commercial use, and few reports have been published. The purpose of the study was the qualitative and quantitative digital image analysis of pancreatic adenocarcinomas using conventional endoscopic ultrasonography (EUS) and CEH-EUS and the evaluation of whether contrast medium injection modified adenocarcinoma staging and patient management. MATERIALS AND METHODS: In each of 30 prospectively examined patients with suspected pancreatic solid lesions, CEH-EUS was performed using the same quantity of the contrast agent SonoVue and a low mechanical index (0.3 – 0.4), followed by EUS-FNA. The histology, based on EUS-FNA or surgery and 9 months of follow-up, was: pancreatic adenocarcinoma (n = 15), pseudotumoral chronic pancreatitis (n = 12), neuroendocrine tumor (n = 1), common bile duct tumor (n = 1), lymph node metastases of gastric cancer (n = 1). The quantitative analysis was based on histograms obtained from each CEH-EUS video recording. RESULTS: CEH-EUS showed a hypoenhanced pattern in 14 cases of adenocarcinoma and in 10 cases of chronic pancreatitis. The index of the contrast uptake ratio was significantly lower in adenocarcinoma than in mass-forming chronic pancreatitis. A cut-off uptake ratio index value of 0.17 for diagnosing adenocarcinoma corresponded to an AUC (CI 95 %) of 0.86 (0.67 – 1.00) with a sensitivity of 80 %, a specificity of 91.7 %, a positive predictive value of 92.8 %, and a negative predictive value of 78 %. The size of the pancreatic mass was assessed significantly more effectively by CEH-EUS but adenocarcinoma staging was not modified. CONCLUSION: The majority of cases of both pancreatic adenocarcinoma and chronic pancreatitis were hypoenhanced and visual discrimination was not possible. This is the first study about CEH-EUS for the quantitative assessment of uptake after contrast injection which has shown that it can aid differentiation between benign and malignant masses but cannot replace EUS-FNA. Neither tumor stage nor therapeutic management have changed after contrast medium injection during CEH-EUS.
71 citations
TL;DR: US appears to be a feasible method for evaluating cartilage thickness in JIA target joints, especially when age and sex-related references are defined, and no significant systematic joint size-related differences are found.
Abstract: Purpose In juvenile idiopathic arthritis (JIA), proliferative changes in the synovium and synovial fluid accumulation are pathological findings responsible for damage to the cartilaginous tissue and periarticular bone, which are late radiographic findings in conventional radiography. Early detection of these joint changes would allow the clinicians to initiate relevant therapies as is essential for the long-term outcome of JIA. Ultrasonography (US) has shown great potential for this purpose but validation in a pediatric setting is needed. The objective of this study was to validate US measurements of cartilage thickness in target joints in healthy children by comparing them with MRI. Materials and methods Twenty-five healthy Caucasian children (17 boys/ 8 girls), mean age 11.33 years, were examined with MRI (1.5 T, fat-suppressed T 1-weighted 3D sequences) and US (real-time Hitachi EUB 6500 CFM, B-mode 6 - 14 MHz linear transducer) in the right knee, ankle, wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. US was obtained according to the EULAR standard scans. Results All differences in cartilage thickness measurements between MRI and US were less than 0.5 millimeters. The coefficient of variation (CV) was found to be good (16 %) except for in the case of the wrist joint (20 %). Conclusion We found a good level of agreement and no significant systematic joint size-related differences in cartilage thickness measurements between MRI and US. US appears to be a feasible method for evaluating cartilage thickness in JIA target joints, especially when age and sex-related references are defined.
68 citations
TL;DR: FLL vary in ARFI elastometry, however, high ARFI values occur in benign as well as in malignant lesions and do not permit differentiation between them.
Abstract: PURPOSE: The technology of acoustic radiation force impulse (ARFI) represents an innovative method for the quantification of tissue elasticity. The aim of this prospective pilot study was to evaluate the role of ARFI elastometry of focal liver lesions (FLL) and the surrounding liver parenchyma. MATERIALS AND METHODS: All patients with unclear FLL in B-mode ultrasound were assigned to ARFI elastometry (m/sec). Measurement sites were located within the FLL, in the peritumoral tissue and in hepatic segment VIII (intercostal approach). Histology and CEUS served as the reference for the characterization of the lesions. RESULTS: A total of 81 patients were enrolled, of whom 62 patients (39 females, 23 males; mean age 54 years) had FLL measurable by means of ARFI. The lesions were: 38 benign (61 %) and 24 malignant FLL (39 %). The ARFI elastometric values of the FLL differed significantly from those of the liver parenchyma (p < 0.001). Elastometry of benign lesions and of malignant tumors showed statistically comparable results (p = 0.28). The lowest ARFI values were observed in focal fatty sparing and the highest in CCC. Only focal fatty sparing and HCC showed negative differences between FLL and peritumoral tissue or liver parenchyma. In 23 % of the hepatic lesions, no reliable quantitative ARFI results were obtainable due to false, inconsistent or technically failed measurements. CONCLUSION: FLL vary in ARFI elastometry. However, high ARFI values occur in benign as well as in malignant lesions and do not permit differentiation between them.
68 citations
TL;DR: CEUS is significantly more accurate than US and highly comparable with MDCT in the detection of liver metastases from colorectal cancer, and must be performed after contrast administration in the evaluation of patients with suspected hepatic metastases.
Abstract: PURPOSE: To compare ultrasound (US), low-mechanical index contrast enhanced US (CEUS) and multidetector-CT (MDCT) for the detection of hepatic metastases from colorectal cancer. METHODS AND MATERIALS: From January to June 2006, 110 patients (65 males, 45 females; mean age 62 years; range 39 - 78) with suspected hepatic lesions from colorectal cancer were prospectively evaluated with US, CEUS and MDCT by two independent readers. Intraoperative ultrasonography (IOUS, n = 45) or a follow-up up for at least 6 months by using MDCT or Gd-BOPTA-enhanced MRI was considered the gold standard. McNemar test was employed. RESULTS: Reference standards revealed 430 metastases in 110 patients. On a patient-by-patients analysis, CEUS improved US sensitivity from 67.4 - 71.6 % to 93.4 - 95.8 % (p < 0.05). On a lesion-by-lesion analysis, CEUS improved the sensitivity of US from 60.9 - 64.9 % to 85.3-92.8 % (p < 0.001). The specificity increased from 50 - 60 % to 76.7 - 83.3 %. No significant differences in sensitivity or specificity between CEUS and MDCT were found. Contrast- enhanced US was significantly more sensitive than baseline US in the detection of metastases smaller than 1 cm (p < 0.001) with an increase in sensitivity from 29.1 - 35 % to 63.3 - 76.6 % no significant statistical difference was identified when compared with MDCT (sensitivity of 73.3 - 75.8 %). CONCLUSIONS: CEUS is significantly more accurate than US and highly comparable with MDCT in the detection of liver metastases from colorectal cancer. Therefore, in the evaluation of patients with suspected hepatic metastases from colorectal tumour, US examination must be performed after contrast administration.
64 citations
TL;DR: Basic abdominal sonographic anatomy can be taught effectively by student tutors according to a pre/post-test design and limited data regarding its effectiveness.
Abstract: PURPOSE Ultrasound is a widely used diagnostic tool. In medical education, it can be used to teach sonographic anatomy as well as the basics of ultrasound diagnostics. Some medical schools have begun implementing student tutor-led teaching sessions in sonographic abdominal anatomy in order to meet the growing demand in ultrasound teaching. However, while this teaching concept has proven to be feasible and well accepted, there is limited data regarding its effectiveness. We investigated whether student tutors teach sonographic anatomy as effectively as faculty staff sonographers. MATERIALS AND METHODS 50 medical students were randomly assigned to one of two groups. 46 of these could be included in the analysis. One group was taught by student tutors (ST) and the other by a faculty staff sonographer (FS). Using a pre/post-test design, students were required to locate and label 15 different abdominal structures. They printed out three pictures in three minutes and subsequently labeled the structures they were able to identify. The pictures were then rated by two blinded faculty staff sonographers. A mean difference of one point in the improvement of correctly identified abdominal structures between the pre-test and post-test among the two groups was regarded as equivalent. RESULTS In the pre-test, the ST (FS) correctly identified 1.6 ± 1.0 (2.0 ± 1.1) structures. Both the ST and FS group showed improvement in the post-test, correctly identifying 7.8 ± 2.8 vs. 8.9 ± 2.9 structures, respectively (p < .0001 each). Comparing the improvement of the ST (6.2 ± 2.8 structures) versus the FS (6.9 ± 3.2) showed equivalent results between the two groups (p < .05 testing for equivalence). CONCLUSION Basic abdominal sonographic anatomy can be taught effectively by student tutors.
TL;DR: Ultrasound as a widely available radiation-free imaging method would be preferable for assessing inflammatory activity of CD, particularly since the ultrasound findings correlate significantly with a histopathological scoring system.
Abstract: PURPOSE: Patients with Crohn's disease (CD) often undergo several radiological imaging studies, which - with the exception of MRI and US - subject patients to ionizing radiation. Thus, efforts have been made to identify the inflammation activity using ultrasound techniques. The aim of our study was to describe the perfusion pattern of the inflamed bowel wall in CD using contrast-enhanced ultrasound (CEUS) and specific quantification software for perfusion assessment. Moreover, we compared these findings with the operative macroscopic findings as well as with the transparietal histopathological findings of surgical specimens applying an advanced histopathological scoring system. MATERIALS AND METHODS: We prospectively performed CEUS in 20 consecutive patients with proven CD and planned bowel surgery due to CD within the next 15 days. We then applied the quantification software Qontrast® to obtain contrast-enhanced sonographic perfusion maps. The surgeon defined the clinical behavior of CD according to the Vienna classification. The resected segments were then assessed by a pathologist using an advanced scoring system. We compared the results of CEUS, macroscopic findings and histopathological scoring. RESULTS: We found a strong negative correlation (r = - 0.677, p < 0.01) between the histopathological score and the time-to-peak (TTP). Moreover, we detected a strong correlation between TTP and single parameters of the histopathological scoring system. CONCLUSION: Ultrasound as a widely available radiation-free imaging method would be preferable for assessing inflammatory activity of CD, particularly since the ultrasound findings correlate significantly with a histopathological scoring system.
TL;DR: The hepatic and splenic SWV measured by ARFI increase with the LF stage, and the hepatic SWV correlate well with SAPI, which might improve the accuracy of noninvasive liver fibrosis assessment.
Abstract: PURPOSE: To evaluate acoustic radiation force impulse imaging (ARFI) of the liver and spleen as a new method for the noninvasive assessment of liver fibrosis (LF). MATERIALS AND METHODS: Three groups of 58 examinees were studied: (A) 20 healthy volunteers; (B) 18 patients with chronic viral hepatitis (CVH) B or C having liver fibrosis stages F 1 - 4 (assessed by liver biopsy; Ishak classification); and (C) 20 patients with liver cirrhosis (LC). All participants were examined using the Siemens ACUSON S 2000 Ultrasound Virtual Touch Tissue Quantification™ system. Ten measurements were performed on both liver lobes and three measurements on the spleen, and the obtained mean values (shear wave velocities [SWV] expressed in m/s) were compared between the groups. In 20 patients the splenic artery pulsatility index (SAPI) was also measured and correlated to the liver and splenic ARFI and histological stage of LF. RESULTS: Hepatic ARFI measurements demonstrated a significant correlation to LB results (Spearman's ρ = 0.766; ρ < 0.001) and SWV cut-off values of 1.3 (AUC 0.96) and 1.86 (AUC 0.99) could reliably differentiate between healthy (A) and non-cirrhotic CVH (B), as well as between non-cirrhotic CVH (B) and LC (C). Splenic SWV cut-off value of 2.73 (AUC 0.82) could differentiate between the patients with LC and non-cirrhotic CVH. A significant correlation was also observed between the SAPI and liver ARFI results (ρ = 0.56; p = 0.013). CONCLUSION: The hepatic and splenic SWV measured by ARFI increase with the LF stage, and the hepatic SWV correlate well with SAPI. This new technology enables simultaneous morphological, Doppler and elastometric examinations and might improve the accuracy of noninvasive liver fibrosis assessment.
TL;DR: The majority of studies over the last 10 years, evaluating articular cartilage thickness with US, underestimated theCartilage thickness by not including the leading interface as part of the cartilage, and this error is substantial.
Abstract: Hintergrund: Theoretisch sollte der Ultraschall dank seiner hohen raumlichen Auflosung sehr geeignet sein, um Veranderungen der artikularen Knorpeldicke bei Osteoarthritis im Krankheitsverlauf darzustellen Voraussetzung hierfur ist allerdings, dass die Knorpelgrenzen gut identifizierbar sind und dass der Knorpel in orthogonaler Schnittfuhrung untersucht wird Wenn US-gestutzte Messungen mit anderen Untersuchungstechniken verglichen werden, sollte der hoheren Ultraschallgeschwindigkeit im Knorpel Rechnung getragen werden Ziel: Gepruft werden sollte, ob die Untersucher den artikularen Knorpel korrekt identifizierten, ob in orthogonaler Schnittfuhrung untersucht wurde und ob eine Korrektur fur die Schallgeschwindigkeit durchgefuhrt wurde Material und Methoden: Zeitlich auf die vergangenen 10 Jahre begrenzte Literaturrecherche zum Thema „US zur Messung der Knorpeldicke” Ergebnisse: 15 Studien zur Messung der Knorpeldicke wurden identifiziert, diese wiederum verwiesen auf 8 weitere Studien 11 der 15 Studien identifizierten die oberflachliche Knorpelgrenze nicht korrekt, in 6 Arbeiten wurde mittels schrager Schnittfuhrung untersucht In 2 der 15 Studien wurde eine Korrektur fur die Schallgeschwindigkeit durchgefuhrt In den weiteren 8 Studien wurde in einer die Messung der oberflachlichen Knorpelgrenze vermutlich adaquat durchgefuhrt, bei 4 Studien wurde in schrager Schnittfuhrung untersucht, und in keiner Arbeit wurde eine Korrektur fur die Schallgeschwindigkeit durchgefuhrt Schlussfolgerung: Wir konnten zeigen, dass in der Mehrzahl der Studien, die in den letzten 10 Jahren zum Thema US-gestutzte Knorpeldicke-Messung publiziert wurden, die Knorpeldicke systematisch unterschatzt wurde, da die zum Knorpel gehorende Grenzschicht nicht mitgemessen wurde Da der Knorpel relativ dunn ist, ist dieser Fehler betrachtlich Einige Autoren uberschatzten die Knorpeldicke, indem sie mit schragen Schnittfuhrungen arbeiteten Bei vielen Untersuchern kommt es durch fehlende Korrektur fur die hohe Schallgeschwindigkeit im Knorpel zu einer systematischen Unterschatzung der Knorpeldicke Background: Theoretically, the high spatial resolution of US makes it well suited to monitor the decrease in articular cartilage thickness in osteoarthritis A requirement is, however, that the borders of the cartilage are correctly identified and that the cartilage is measured under orthogonal insonation If US measurements are compared to measurements with other techniques, they should be corrected for the higher sound speed in cartilage Purpose: To study whether investigators correctly identify the articular cartilage, whether they insonate orthogonally, and whether they correct for sound speed Materials and Methods: A literature search limited to the last 10 years of studies applying US to measure cartilage thickness Results: 15 studies were identified and they referred to another 8 studies describing methods of thickness measurement 11 of the 15 studies identified the superficial cartilage border incorrectly, and 6 applied oblique insonation 2 of the 15 studies corrected for sound speed Of the further 8 studies, one might correctly identify the superficial cartilage border, 4 applied oblique insonation, and none corrected for sound speed Conclusion: We found that the majority of studies over the last 10 years, evaluating articular cartilage thickness with US, underestimated the cartilage thickness by not including the leading interface as part of the cartilage Since the cartilage is relatively thin, this error is substantial Some investigators also overestimated cartilage thickness by using oblique insonation of the cartilage By not correcting for the high sound speed in cartilage, most investigators underestimated the cartilage thickness
TL;DR: The use of linear data is the only mathematically valid methodology for determining a tumor's time-intensity curve and, in practice, it allows earlier demonstration of responses to antivascular drugs.
Abstract: PURPOSE: This study is intended to compare the value of uncompressed ultrasonic data, obtained after linear power detection of the ultrasonic radiofrequencies that we call linear data, with usual compressed video data for the quantification of tumor perfusion, particularly for monitoring antivascular therapy. MATERIALS AND METHODS: To form a clinically useful ultrasonic image, the detected power of the received signals (linear data) is compressed in a quasi-logarithmic fashion in order to match the limited dynamic range of the video monitor. The resulting reduced range of signals from an injected contrast agent may limit the sensitivity to changes in the time-intensity curves. Following a theoretical evaluation of the effects of compression on time-intensity curves and as an in vivo example, we measured at different times the effects of an antivascular drug administered to mice bearing melanoma tumors. The mean time-intensity curves within the tumors after bolus injection of a contrast agent were determined using both linear and video data. Linearized data was recovered using the inverse of the true scanner’s compression law, which was experimentally determined. Three features were extracted from the time-intensity curves: peak intensity (PI), time to peak intensity (TPI) and area under the curve in the wash-in phase (AUC wash-in ). When contrast reached its maximum value, the coefficient of variation reflecting the heterogeneity of the intensity of contrast uptake within the tumor, was computed using both data sets. RESULTS: TPI was found to be similar with either data set (r = 0.98, p < 0.05, factor of 1.09). Linear PI and AUC wash-in had significantly earlier decreases after drug administration than video data (p = 0.015 and p = 0.03, respectively). The coefficient of variation was significantly lower when using video rather than linear data (p < 10 -4 ). CONCLUSION: In conclusion, the use of linear data is the only mathematically valid methodology for determining a tumor’s time-intensity curve and, in practice, it allows earlier demonstration of responses to antivascular drugs.
TL;DR: If decisive anatomic structures are clearly depicted and the measuring points are set correctly, there is a good correlation between HRUS and MRI measurements of the optic nerve and the ONSD even on transbulbar sonography.
Abstract: PURPOSE: We performed a cadaver study to evaluate the accuracy of measurements of the optic nerve and the optic nerve sheath for high resolution US (HRUS) and magnetic resonance imaging (MRI). MATERIALS AND METHODS: Five Thiel-fixated cadaver specimens of the optic nerve were examined with HRUS and MRI. Measurements of the optic nerve and the ONSD were performed before and after the filling of the optic nerve sheath with saline solution. Statistical analysis included the calculation of the agreement of measurements and the evaluation of the intraobserver and interobserver variation. RESULTS: Overall a good correlation of measurement values between HRUS and MRI can be found (mean difference: 0.02 - 0.97 mm). The repeatability coefficient (RC) and concordance correlation coefficient (CCC) values were good to excellent for most acquisitions (RC 0.2 - 1.11 mm; CCC 0.684 - 0.949). The highest variation of measurement values was found for transbulbar sonography (RC 0.58 - 1.83 mm; CCC 0.615 / 0.608). CONCLUSION: If decisive anatomic structures are clearly depicted and the measuring points are set correctly, there is a good correlation between HRUS and MRI measurements of the optic nerve and the ONSD even on transbulbar sonography. As most of the standard and cut-off values that have been published for ultrasound are significantly lower than the results obtained with MRI, a reevaluation of sonographic ONSD measurement with correlation to MRI is necessary.
TL;DR: Strain ratio measurement of breast lesions is a standardized fast method for analyzing the stiffness inside the examined areas and used as an additional tool to B-mode ultrasound, it helps to increase the specificity of the examination.
Abstract: PURPOSE: The aim of this study was to evaluate the strain ratio measurement of breast lesions, to calculate the diagnostic value and to provide practically oriented recommendations concerning execution. MATERIALS AND METHODS: 117 breast lesions in 98 patients were included in the study. All lesions were examined by B-mode ultrasound and elastography using strain ratio measurement. The preinterventional findings of the different methods were compared to the final histopathological results. The sensitivity, specificity, positive and negative predictive value and the diagnostic accuracy were calculated for each method. RESULTS: There was a significant difference between the strain ratio of malignant (mean 6.50; sd 3.03; 95 %-CI 5.68 – 7.33) and benign (mean 1.79; sd 3.83; 95 %-CI 0.92 – 2.75) lesions. The strain ratio showed a sensitivity of 92.6 % (95 %-CI 82.1 – 97.9) and a specificity of 95.2 % (95 %-CI 86.7 – 99.0). The positive and negative predictive values were 94.3 % and 93.7 %. B-mode ultrasound achieved a sensitivity of 94.4 % (95 %-CI 84.6 – 98.8) and a specificity of 87.3 % (95 %-CI 76.5 – 94.3). The positive and negative predictive values were 86.4 % and 94.8 %. CONCLUSION: Strain ratio measurement of breast lesions is a standardized fast method for analyzing the stiffness inside the examined areas. Used as an additional tool to B-mode ultrasound, it helps to increase the specificity of the examination.
TL;DR: The US-guided perforation and lavage technique is an effective and safe treatment for rotator cuff calcifications as well as for other body tendons.
Abstract: PURPOSE: To analyze the effectiveness and complication rate of ultrasound (US)-guided perforation and lavage using a two-needle technique with 16 - 18 G needles in the treatment of patients with calcific tendinopathy in the shoulder, elbow, hip, and knee by radiological and clinical follow-up. MATERIALS AND METHODS: A retrospective chart review was performed and 40 patients (13 male, 27 female; mean age, 53.5 years; range 24 -74 years) were identified as having received US-guided perforation and lavage due to symptomatic calcific tendinopathy of the rotator cuff tendons, triceps, extensor and flexor tendons at the elbow, rectus femoris tendon and patellar tendons. The radiographic outcome was assessed by comparison of the size and quality of the calcification before and 6 weeks after the procedure. On US images, the quality of the acoustic shadow was assessed, together with other alterations of the tendon and surrounding tissue. Patients were interviewed by telephone to assess the clinical outcome regarding pre-treatment and post-treatment pain and tendon function. RESULTS: 34 shoulder tendons and 6 non-shoulder tendons were identified. The mean calcium reduction was 39.9 mm 2 (range, 0 - 215; p < 0.001), while 80 % of patient showed a resolution of more than 60 % resulting in good clinical improvement. A very low complication rate was found (1 partial tear). CONCLUSION: The US-guided perforation and lavage technique is an effective and safe treatment for rotator cuff calcifications as well as for other body tendons. Although the two-needle technique and large needles were used in this study, a very low complication rate was detected.
TL;DR: Contrary to frequent assumption, neovascularization is often found in tendons of asymptomatic runners, using modern power Doppler equipment, and the pathological relevance of single microvessels in asymPTomatic tendons must be critically discussed.
Abstract: AIM: The aim of this cross-sectional study was to assess the frequency of tendinopathy-typical Doppler sonographic changes in the Achilles tendons of long distance runners and to correlate these findings with anamnestic and anthropometric data of the subjects MATERIALS AND METHODS: 1906 Achilles tendons of 953 long distance runners were examined by ultrasound and power Doppler (Toshiba Aplio SSA-770A/ 80 12 MHz) Ultrasound images (spindle-shaped thickening, hypoechoic/hyperechoic lesions, neovascularizations) were analyzed in relation to the runners’ anthropometrical data and history of Achilles tendon complaints RESULTS: In asymptomatic runners as well as in the overall group, there was a statistically significant correlation between tendon thickness and age, height and weight (CC 024 - 038, p < 0001) Runners with current or healed Achilles tendon complaints displayed a statistically significant thickening of the tendons, as well as an increase in hypoechoic lesions and neovascularizations (p < 0001) While grayscale abnormalities were rarely found in asymptomatic runners (< 10 %), neovascularization was detected in 35 % of healthy test persons using the high-resolution power Doppler ”Advanced Dynamic Flow” CONCLUSION: Contrary to frequent assumption, neovascularization is often found in tendons of asymptomatic runners, using modern power Doppler equipment The pathological relevance of single microvessels in asymptomatic tendons must, therefore, be critically discussed
TL;DR: Transthoracic ultrasound of the lung might be a sensitive non-invasive tool to observe early stage interstitial lung disease in rheumatic diseases.
TL;DR: The most important factors that influence the final elastographic score, leading to false negative results, are the size of the region of interest, the initial compression and angulation of the transducer, while the frequency and amplitude of movement during the examination proved to be of no importance as long as the images were obtained within a range of assessment usefulness.
Abstract: PURPOSE: The aim of the study was to assess the influence of technical factors and/or lesion characteristics on the final elastographic score in solid breast nodules. MATERIALS AND METHODS: Patients with solid breast masses examined between May 2007 and May 2008 in the Radiology Department of Cluj District University Hospital were included in the study. All lesions were examined with conventional ultrasound, Doppler ultrasound and sonoelastography, according to a preset protocol. The influence of the following factors on the elastographic score was evaluated: type of section (sagittal versus transverse); size of region of interest (small versus large); amplitude and frequency of movement; initial compression (light versus strong); angulation (perpendicular versus angulated transducer); characteristics of the lesion (size and location). The reference diagnosis was the histopathology diagnosis and, in twenty cases, short-term follow-up. RESULTS: Ninety-two patients with a mean age of 48.11 years and 101 breast nodules were included in the study. The overall sensitivity and specificity for elastography were 79 % [68-88 %] and 79 % [65 - 89 %], respectively, with a negative predictive value of 74 % [60-85 %] and a positive predictive value of 84 % [72-91 %]. The following factors did not influence the elastographic score: type of section (scores on transverse and longitudinal section, Z = -0.641, p = 0.552); the amplitude and frequency of movements during the elastographic examination (Cochran's Q concordance = 0.706, p = 0.872); strong initial compression in the case of benign nodules (Z = 0.000, p = 1.000); size of the lesions. Of the elastographically benign nodules, 9 were false negative and of the 46 elastographically malignant nodules, 12 were false positive. The following factors influenced the elastographic scores: size of the region of interest (the scores were significantly different when small or large region of interest was used, Z = -0.671, p < 0.0001); transducer angulation (Z = -5.42, p < 0.0001); strong initial compression in the case of malignant nodules (Z = -6.044, p < 0.0001) and the location of the mass in the vicinity of the chest wall. CONCLUSION: The most important factors that influence the final elastographic score, leading to false negative results, are the size of the region of interest, the initial compression and angulation of the transducer, while the frequency and amplitude of movement during the examination proved to be of no importance as long as the images were obtained within a range of assessment usefulness. Changing the scanning parameters never led to false positive results in the case of malignant breast masses.
TL;DR: Die intensive Auseinandersetzung mit den sonografischen Moglichkeiten am Thorax in den letzten 30 Jahren hat gezeigt, dass insbesondere an der Thoraxwand and der Pleura sehr gute Bedingungen zur Ultraschalluntersuchung bestehen.
Abstract: 1. Kennenlernen der sonografischen Erscheinungsformen pleuraler Erkrankungen. 2. Sonografische Untersuchungstechnik bei Pleurauntersuchungen. 3. Integration der Sonografie in den diagnostischen Ablauf bei Verdacht auf eine pleurale Erkrankung. 4. Einschatzung der Grenzen der Sonografie an der Pleura. Seit mehr als 40 Jahren dient die Sonografie zum Nachweis von Pleuraergussen. Lange Zeit wurden allerdings daruber hinaus die diagnostischen Moglichkeiten der Sonografie an der Pleura kaum genutzt, da die untersuchungstechnischen Einschrankungen durch die Rippen und die lufthaltige Lunge keine weitere Aussage zuzulassen schienen [1]. Die intensive Auseinandersetzung mit den sonografischen Moglichkeiten am Thorax in den letzten 30 Jahren hat gezeigt, dass insbesondere an der Thoraxwand und der Pleura sehr gute Bedingungen zur Ultraschalluntersuchung bestehen. Erst die Totalreflexion an der Luft in der normalen Lunge verhindert das weitere Eindringen der Schallwellen.
TL;DR: SOS and a larger tumor size on RTE are specific characteristics of malignant breast lesions and EP, MV and distal mass border are further helpful signs to assess the malignancy of tumors.
Abstract: PURPOSE: Elastography is a new ultrasonographic method that has been examined as a diagnostic tool for breast lesions. This study was intended to create and define new elastographic criteria allowing assessment of whether breast lesions are malignant or benign. MATERIALS AND METHODS: 217 patients with a total of 245 breast lesions of unknown malignancy underwent ultrasound examination. The new eSie Touch Elasticity Imaging technology (Siemens, Erlangen, Germany) was used with a 10-MHz linear transducer (Acuson Antares). Lesions were examined using B-mode and real-time elastography (RTE). Each lesion was histologically assessed by core biopsy. Five RTE characteristics were examined: elasticity proportion (EP), different location on RTE in comparison with B-mode (MV), different contrast patterns (SOS), dorsal lesion limitation visibility and different size on RTE in comparison with B-mode. RESULTS: 54 malignant lesions (54 %) appeared inelastic, in contrast to the benign control group (34.5 %; P = 0.001). A completely elastic pattern was visible in 10 malignant (10 %) and 39 benign lesions (26.9 %). MV was identified in 23 cases, with 22 of the lesions being malignant and one benign. The SOS was negative in 89 malignant lesions (89 %) and positive in 100 benign lesions. The dorsal lesion limitation was visible on RTE without B-mode in 88 malignant lesions (88 %) and 27 benign lesions (18.6 %). The size was assessed as larger in 45 malignant lesions (45 %) and seven benign lesions (4.8 %). CONCLUSION: SOS and a larger tumor size on RTE are specific characteristics of malignant breast lesions. EP, MV and distal mass border are further helpful signs to assess the malignancy of tumors.
TL;DR: An easy-to-use algorithm should reduce the rate of inconclusive histology results mainly caused by sampling errors to an unrivaled minimum and improve the diagnostic yield of ultrasound-guided biopsy to 100%, which is at least rather promising.
Abstract: PURPOSE: We report on a novel approach to the work-up of musculoskeletal lesions with addition of an ultrasound contrast agent followed by focal ultrasound-guided biopsy. MATERIALS AND METHODS: In this pilot study 25 patients (age: 12 – 75) with unclear musculoskeletal tumors underwent grayscale ultrasound, color Doppler, contrast-enhanced ultrasound and subsequent ultrasound-guided biopsy. Grayscale and color Doppler ultrasound were performed with a 12 – 5 MHz broadband linear transducer and contrast-enhanced ultrasound with a 9 – 3 MHz broadband linear transducer (iU22®, Philips, USA) using a second-generation contrast agent (SonoVue®, Bracco, Italy). After the definition of the target area by contrast-enhanced ultrasound, guided biopsies were performed with a spring-loaded tru-cut™ biopsy needle using the coaxial technique. RESULTS: The definition of enhancing and viable tumor regions resulted in a diagnostic yield of the subsequent biopsy of 100 %. Seventeen tumors were classified as malignant and eight as benign, which was finally confirmed by histological work-up or the further clinical follow-up. CONCLUSION: This pilot study with a limited series of patients improved the diagnostic yield of ultrasound-guided biopsy to 100 %, which is at least rather promising. Our easy-to-use algorithm should reduce the rate of inconclusive histology results mainly caused by sampling errors to an unrivaled minimum.
TL;DR: The presence of vascularity within a lesion, by itself, is no longer a good predictor of malignancy because of the increase in Doppler sensitivity associated with improvements in ultrasound technology.
Abstract: PURPOSE: The aim of this study was to evaluate the use of vascular morphology, around and within the B-mode region of abnormality, for improving the diagnostic accuracy of two of the most common solid breast pathologies. MATERIALS UND METHODS: The B-mode and Doppler images of 117 breast cancers and 366 fibroadenomas and lesions with a fibroadenoma-like appearance were reviewed retrospectively and the morphology of the vascular pattern was evaluated. The ratio of external to internal color Doppler, the external vascular pattern and the connecting vessels to internal vessels were assessed and differentiated into benign and malignant vascular patterns. These patterns were correlated with the histological diagnosis. RESULTS: Vascularity was demonstrated in 95 % of cancers and in 46 % of benign lesions with a trend to increasing vascularity in cancers. This provided poor specificity for excluding cancer in fibroadenomas. Variations in vascular pattern were recorded. The observed benign vascular patterns were avascularity, vascularity in the periphery and peripheral marginal vessels connecting with internal vascularity. The observed malignant vascular patterns were radially aligned external vessels with internal vessels being more numerous than external vessels which connected to radial vessels. (Fisher exact test p < 0.0001). Analysis of the vascular morphology improved the sensitivity for identifying cancers from 97 % (B-mode) to 99 % (B-mode and color Doppler) with a minimal reduction in specificity (93.7 to 92.6 %) or accuracy (94.6 to 94.2 %). CONCLUSION: The presence of vascularity within a lesion, by itself, is no longer a good predictor of malignancy because of the increase in Doppler sensitivity associated with improvements in ultrasound technology. The color Doppler ultrasound vascular pattern morphology improves the accuracy and sensitivity of B-mode image diagnosis, breast cancers and fibroadenomas with a minimal loss of specificity. Any breast lesion with radial rather than marginal connecting vessels should be regarded with suspicion.
TL;DR: Sonoelastography is easily performed and not very time-consuming, but when used in conjunction with B-mode ultrasonography, the latter's sensitivity was increased, albeit at the expense of specificity.
Abstract: PURPOSE: This prospective study aimed to compare sonoelastography, B-mode ultrasonography, and mammography in terms of their ability to distinguish benign from malignant breast lesions. We also assessed how the diagnostic value of sonoelastography differs between palpable and clinically occult lesions. MATERIALS AND METHODS: Evaluation revealed a total of 97 lesions (66 benign; 31 malignant) without histological confirmation at the time of the initial examination. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) as well as efficiency were calculated. These parameters were separately assessed for palpable lesions and for non-palpable lesions. We subsequently compared these results. RESULTS: Sonography had a sensitivity of 97 % and a specificity of 82 % (PPV: 71 %, NPV: 98 %, efficiency: 87 %). For mammography, the respective figures were 84 % and 89 % (PPV: 79 %, NPV: 92 %, efficiency: 88 %). Sonoelastography had a sensitivity of 71 % and a specificity of 48 % (PPV: 39 %, NPV: 78 %, efficiency: 56 %). The combination of sonography and sonoelastography yielded a sensitivity of 100 % and a specificity of 38 % (PPV: 43 %, NPV: 100 %, efficiency: 58 %). The sensitivity and specificity were not statistically different between the groups of palpable and non-palpable lesions. CONCLUSION: Sonoelastography is easily performed and not very time-consuming. Used by itself, the method is not more efficacious than alternative techniques. When used in conjunction with B-mode ultrasonography, the latter’s sensitivity was increased, albeit at the expense of specificity.
TL;DR: CEUS can be helpful in demonstrating or excluding metastases in cancer patients with MDCT evidence of subcentimetric, indeterminate focal liver lesions.
Abstract: PURPOSE: To evaluate whether the use of contrast-enhanced ultrasound (CEUS) could improve the characterization of indeterminate subcentimetric focal liver lesions (FLLs) seen with multidetector computed tomography (MDCT) in cancer patients. MATERIALS AND METHODS: For 12 months all patients with extrahepatic tumors showing small (< 10 mm), indeterminate focal liver lesions on whole-body or abdominal computed tomography (CT) underwent immediate, targeted ultrasound (US) to rule out a cystic lesion. Whenever unenhanced US demonstrated a non-cystic lesion or failed to recognize any focal abnormality within the suspected area, CEUS was carried out. During the arterial phase, CEUS was focused on the area reflecting the CT finding, while the entire organ was explored during the portal-sinusoidal phase. RESULTS: Among the 132 patients with MDCT evidence of indeterminate, subcentimetric focal liver lesions (206 lesions), US proved the cystic nature of 138 lesions in 87 patients. In 45 cases US failed to recognize any abnormality or cystic image and these subjects underwent CEUS. The CEUS results were confirmed by further assessment or follow-up for 43 / 45 patients (3 cysts, 8 hemangiomas, 47 metastases, 2 areas of focal steatosis, 2 eosinophilic necroses, 1 granuloma, 1 abscess, 1 fistula). CEUS failed to detect 3 lesions (1 metastasis and 2 benign lesions). In 8 cases CEUS recognized additional liver metastases. CONCLUSION: CEUS can be helpful in demonstrating or excluding metastases in cancer patients with MDCT evidence of subcentimetric, indeterminate focal liver lesions.
TL;DR: CEUS is a reliable noninvasive method for differentiating low- and high-grade bladder carcinomas since it provides typical enhancement patterns as well as specific contrast-sonographic perfusion curves, but further studies involving larger patient populations is mandatory to confirm these promising results.
Abstract: PURPOSE: To assess the efficacy of low-mechanical index contrast-enhanced ultrasonography (CEUS) in the differentiation of a series of histologically proven bladder lesions identified via conventional cystoscopy and biopsied. MATERIALS AND METHODS: 36 patients (mean age: 62 years; range 45 – 72 years) with bladder lesions previously detected by color power Doppler ultrasonography (CDUS) were prospectively examined with low-mechanical index contrast-enhanced US after bolus administration of 2.4 ml of Sonovue (Bracco, Milan, Italy). All lesions were evaluated in real-time continuous scanning for 2 minutes and the videos were registered. Two ultrasound (US) experts evaluated the videos by consensus and assigned a score to the enhancement pattern. Subsequently, a specific sonographic quantification software (Qontrast, Bracco, Milan, Italy) based on pixel by pixel signal intensity over time was used to obtain contrast-enhanced sonographic perfusion maps for each lesion. Time-intensity curves (TICs) of each lesion were then extracted from the region of interest positioned within the lesion and in the closest bladder wall. The sensitivity and specificity of CDUS and CEUS were compared using McNemar’s test. All patients subsequently underwent conventional cystoscopy with biopsy or transurethral resection. RESULTS: 22 high-grade and 14 low-grade transitional cell carcinomas (TCCs) were histologically diagnosed (mean diameter 2.1 cm; range: 1 – 4.5 cm). The sensitivity and specificity of CDUS were 86.4 % (19 / 22; 95 % CI = 66.7 – 95.3 %) and 42.9 % (6 / 14; 95 % CI = 21.4 – 67.4 %), respectively. The sensitivity and specificity of CEUS were 90.9 % (20 / 22; 95 % CI = 72.2 – 97.5 %) and 85.7 % (12 / 14; 95 % CI = 60.1 – 95.9 %), respectively. The sensitivity and specificity of CEUS using TICs were 95.4 % (21 / 22; 95 % CI = 78.2 – 99.2 %) and 85.7 % (12 / 14; 95 % CI = 60.1 – 95.9 %), respectively. There was no significant difference between the sensitivity of CDUS versus CEUS, CDUS versus TIC, and CEUS versus TIC (p > 0.05; McNemar’s test). The specificity of CEUS and TIC was significantly higher than that of CDUS (p < 0.05; McNemar test). CONCLUSION: CEUS is a reliable noninvasive method for differentiating low- and high-grade bladder carcinomas since it provides typical enhancement patterns as well as specific contrast-sonographic perfusion curves. However, further studies involving larger patient populations is mandatory to confirm these promising results.