Abstract: We prospectively compared hepatic transit time (HTT) measurements in subjects with liver metastases from colorectal cancer (group a) and healthy volunteers (group b) using contrast-enhanced ultrasound with BR1. The purpose of this study was to verify our hypothesis that the hemodynamic changes of the liver, which occur during metastasis seeding, would shorten the HTT, and we expect that such changes could be used for the detection of occult liver metastases from colorectal cancer in the future. The study had institutional review board approval and all subjects gave informed written consent. Group a and group b consisted of 22 subjects each. Baseline and post contrast images were acquired starting 10 s before and ending 40 s after administration of BR1, using nonlinear imaging at a frame rate of 5/s. The baseline images were used to determine the signal intensity without contrast enhancement as the reference signal. Arrival times (AT) of the contrast agent for the hepatic artery, the portal vein and one hepatic vein were determined using (i) quantitative analysis and (ii) subjective analysis by two blinded readers. HTT was calculated based on arrival time measurements. Quantitative and subjective analysis showed significantly shorter arterial to venous and portal to venous HTT in group a compared with group b (p < 0.001). Arterial to venous HTT (quantitative analysis) was </=9 s in 19 of 22 subjects of group a and >9 s in 18 of 22 subjects of group b (sensitivity 86%, specificity 82%, positive predictive value 83%, negative predictive value 86%, area under the curve [AUC] 0.87). Portal to venous HTT (quantitative analysis) was < 7 s in 21 of 22 subjects of group a and > 7s in 15 of 22 subjects of group b (sensitivity 95%, specificity 68%, PPV 75%, NPV 94%, AUC 0.85). There was an inverse relation with number of liver segments involved for arterial to venous and portal to venous HTT in group a (p < 0.05), but no correlation between HTT and overall volume of metastases (group a) or subject age (group b). From the results of our study, we conclude that HTT measurements using contrast-enhanced ultrasound with BR1 can detect hemodynamic changes caused by metastatic liver disease from colorectal cancer. However, comparison with the literature suggests that the use of other contrast agents might provide better results. Comparison of different contrast agents for the purpose of transit time analysis would therefore be useful before embarking on a prospective trial looking at the detection of occult liver metastases in patients with colorectal cancer.
Abstract: A 49 year old male with carcinoma of the esophagus was staged using conventional US of the abdomen. US revealed signs of cirrhosis and a hyporeflexive focal liver lesion of about 5 mm in diameter was found. Low-MI contrast-enhanced ultrasound (CEUS) with SonoVue (Bracco, Milano, Italy) showed an enhancement pattern which was typical for benign liver lesions while high-MI CEUS with Levovist (Schering, Berlin, Germany) revealed a contrast defect in the liver late phase (4:30 min p. i.) which is typical for a malignant lesion. Due to these findings the lesion was evaluated as a potentially malignant lesion and a biopsy was performed. Histology showed a benign biliary hamartoma and incomplete cirrhosis. The findings confirmed that liver-specific contrast agents have the ability to detect very small focal liver lesions not derived from hepatic tissue but may lead to a misinterpretation as a malignant lesion. Nevertheless biliary duct adenomas are benign lesions with almost the same perfusion properties as normal liver parenchyma. Therefore, while using SonoVue, such a misinterpretation of these very common but in most cases very small and not detectable lesions seems unlikely.
Abstract: OBJECTIVE: The aim of the study was to assess the clinical value of contrast-enhanced intraoperative ultrasound (CE-IOUS) as a novel tool in the hepatic staging of patients undergoing liver resection. METHODS: Sixty patients scheduled to undergo liver resection for metastatic disease were studied. Preoperative staging with contrast-enhanced CT and/or MR scans was performed within 2 to 6 weeks of operation. Following exploration, intraoperative ultrasound (IOUS) was performed using an HDI-5000 scanner (Philips) and a finger-probe with pulse inversion harmonic (PIH) capability. CE-IOUS in the PIH mode was performed in a standardized protocol (low MI: 0.02-0.04) after intravenous injection of 3-4 mL of SonoVue (Bracco spa, Milan); all detected lesions on precontrast and postcontrast scans were counted and mapped. Any alteration in surgical management was documented following CE-IOUS compared with IOUS. RESULTS: Three patients were excluded due to disseminated disease on exploration. CE-IOUS was significantly more sensitive than CT/MR and IOUS in detecting liver metastases (96.1% versus 76.7% and 81.5%, respectively) (P<0.05); it altered surgical management in 29.8% (17 of 57) of cases, due to 1) additional metastases in 19.3% (11 of 57), 2) less metastases in 3.5% (2 of 57), 3) benign lesions wrongly diagnosed as metastasis on IOUS/CT in 5.3% (3 of 57), and 4) vascular proximity in 1.8% (1 of 57). Management was unchanged in 70.2% (40 of 57) despite additional lesions detected in 3.5% (2 of 57) and benign lesion wrongly diagnosed on IOUS and CT as metastasis in 1.8% (1 of 57). CE-IOUS altered combined IOUS/CT/MR staging in 35.1%. CONCLUSION: These preliminary results suggest CE-IOUS is an essential tool prior to liver resection for metastases.
Abstract: PURPOSE: To test whether a new quantitative measure, the tumor-to-vessel ratio, obtained from late post-iron-oxide-enhanced T1-weighted images allows for differentiating hemangiomas from liver metastases or all malignant liver lesions. MATERIAL AND METHODS: Twenty-six patients (mean 57, range 33-79 years) were prospectively studied at 1.5T magnetic resonance imaging (MRI) with a T1-weighted 2D fast low-angle shot (FLASH) sequence (repetition time/echo time/flip angle; 200 ms/4.8 ms/90 degrees ) and a T2-weighted turbo spin-echo sequence (4072 ms/99 ms/180 degrees ). Imaging was carried out before and at intervals up to 18 min after IV injection of Ferucarbotran (Resovist, Schering, Germany). In 19 patients, one representative malignant lesion was analysed. Eleven hemangiomas were evaluated in 7 patients. Two readers performed a consensus reading with a signal intensity measurement in a lesion, normal liver and hepatic veins, from which ratios were computed. RESULTS: On T1-weighted iron-oxide-enhanced MRI of 30 lesions, tumor-to-vessel signal intensity ratios were distinct in hemangiomas (median 1.04, range 0.99-1.10) as opposed to either metastases (0.64, 0.33-0.77; P < 0.05) or all malignant lesions taken together (0.64, 0.33-0.98; P < 0.05), while the tumor-to-liver ratio was not. CONCLUSION: The tumor-to-vessel ratio may help to differentiate between hemangiomas and metastases. A ratio greater than 0.98 allowed differentiating hemangiomas from metastases with a wide safety margin.
Abstract: AIM: SonoVue is the first ultrasound contrast agent which allows repeated continuous examination of the liver in real time. The aim of this study was to compare low mechanical index (MI) real time contrast enhanced ultrasound of the liver, using the contrast agent SonoVue, with conventional B-mode sonography for the detection of hepatic metastases. METHOD: 40 patients with known malignancy and at least one liver lesion on conventional B-mode sonography were included. Conventional B-mode sonography was performed followed by contrast enhanced ultrasound (CEUS) of the liver in the arterial (< 30 sec), portal-venous (40-120 sec) and delayed phase (> 120 sec) after injection of SonoVue. CEUS was performed using contrast specific imaging and low MI (< 0.3). Number, location and size of metastases on baseline and CEUS were compared with CT or MRI (blinded reader). RESULTS: 37 patients had 128 metastases on CT or MRI. Baseline US showed 74 metastases confirmed by reference examination (69%), while CEUS yielded 109 metastases (sensitivity 90%) (p < 0.001). On CEUS, 35 additional metastases not seen on baseline but confirmed by reference imaging were detected in 14 patients (36%). In 8 patients, CEUS showed 13 metastases not seen on reference imaging. CONCLUSION: Detection of hepatic metastases is substantially improved by low MI real time contrast enhanced ultrasound with SonoVue compared to conventional B-mode sonography.
Abstract: We report two children who sustained traumatic parenchymal splenic injury and were monitored with contrast-enhanced ultrasound (CEUS). In both cases, unenhanced US failed to diagnose splenic haematoma, but the injury was well demonstrated after injection of contrast agent. In one case agreement with CT was excellent; in the other, CT was not performed due to the comprehensive information provided by CEUS.
Abstract: Modern liver imaging of cancer patients requires an imaging modality that is not only highly sensitive in detecting lesions but also provides reliable characterisation of lesions and thus allows differentiation of metastases from frequently found benign lesions. Conventional ultrasound (US) has a relatively poor sensitivity and specificity for imaging liver metastases and US used to be inferior to CT and MRI mainly due to a lack of contrast agents. This has changed with the advent of microbubble contrast agents for US. The use of recent contrast agents such as SonoVue (Bracco, Italy) combined with low mechanical index contrast-specific imaging techniques such as Contrast Pulse Sequencing provides dynamic real time imaging of focal liver lesions in the arterial, portal venous and delayed phase. This improves lesion detection and characterisation. To investigate the benefit of SonoVue for detecting liver metastases we studied 40 cancer patients with liver lesions on reference imaging (CT or MRI), 37 of them had metastases. The mean number of reference confirmed metastases per patient increased from 1.85+/-1.79 on conventional ultrasound to 2.73+/-2.50 post SonoVue (p < 0.05). CEUS showed more individual metastases than baseline in 12 (34%) patients. Using CT or MRI as the reference, the mean sensitivity to individual metastases increased from 69% on baseline US to 90% post contrast (p < 0.0005). The role of SonoVue in characterisation of focal liver lesions was evaluated in 63 patients. One lesion was studied per patient. Based on standardised dynamic enhancement criteria for each lesion type, the number of correctly diagnosed lesions improved from 41 (65%) on baseline US to 58 (92%) post contrast (p < 0.001). On CEUS all 27 metastases were correctly diagnosed, while baseline US misinterpreted 2 of these. The number of correctly diagnosed benign lesions (n = 28) increased from 12 (43%) on baseline to 25 (89%) post SonoVue. In conclusion, detection and characterisation of focal liver lesions by US are markedly improved by the use of SonoVue. Contrast agents add a new dimension to sonography allowing it to rival CT and MRI, especially for lesion characterisation.
Abstract: In patients with known or suspected malignancy, ultrasonography (US) is often the first choice for liver imaging because of its widespread availability and low cost. Compared with contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), the sensitivity of conventional US for detecting hepatic metastases is relatively poor. The advent of microbubble contrast agents changed this situation. Sensitivity and specificity increased substantially with the use of these contrast agents and contrast-specific imaging modes in recent years. Currently, numerous US imaging methods exist, based on Doppler techniques or harmonic imaging. They exploit the complex nonlinear behavior of microbubbles in a sound field to achieve marked augmentation of the US signal. Although microbubble contrast agents are essentially blood pool agents, some have a hepatosplenic specific late phase. Imaging during this late phase is particularly useful for improving the detection of malignant liver lesions and allows US to perform similarly to spiral CT as shown by recent studies. In addition, this late phase imaging is very helpful for lesion characterization. Low mechanical index imaging with the newer perfluor agents permits real-time imaging of the dynamic contrast behavior during the arterial, portal venous, and late phases and is particularly helpful for lesion characterization. The use of US for hemodynamic studies of the liver transit time may detect blood flow changes induced by micrometastases even before they become visible on imaging. In this field of functional imaging, further research is required to achieve conclusive results, which are not yet available.
Abstract: Ultrasonography (US) is the first choice for screening patients with suspected liver lesions. However, due to a lack of contrast agents, US used to be less sensitive and specific compared with computed tomography (CT) and magnet resonance imaging (MRI). The advent of microbubble contrast agents increased both sensitivity and specificity dramatically. Rapid developments of the contrast agents as well as of special imaging techniques were made in recent years. Today numerous different US imaging methods exist which based either on Doppler or on harmonic imaging. They are using the particular behaviour of microbubbles in a sound field which varies depending on the energy of insonation (low/high mechanical index, MI) as well as on the properties of the agent themselves. Apart from just blood pool enhancement some agents have a hepatosplenic specific late phase. US imaging during this late phase using relatively high MI in phase inversion mode (harmonic imaging) or stimulated acoustic emission (SAE; Doppler method) markedly improves the detection of focal liver lesions and is also very helpful for lesion characterisation. With regards to detection, contrast enhanced US performs similarly to CT as shown by recent studies. Early results of studies using low MI imaging and the newer perfluor agents are also showing promising results for lesion detection. Low MI imaging with these agents has the advantage of real time imaging and is particularly helpful for characterisation of focal lesions based on their dynamic contrast behaviour. Apart from the techniques which based on the morphology of liver lesions there were some attempts for the detection of occult metastases or micrometastases by means of liver blood flow changes. Also in this field the use of US contrast agents appears to have advantages over formerly used non contrast-enhanced methods although no conclusive results are available yet.
Abstract: PURPOSE: SonoVue is a new microbubble ultrasound contrast agent that for the first time allows continuous real time examination during the different phases of contrast enhancement using low transmission power, expressed as mechanical index (MI). This study investigates whether low MI real time phase inversion imaging with SonoVue can improve the characterization of focal liver lesions in comparison to unenhanced sonography and power Doppler sonography. MATERIALS AND METHODS: Sixty-three patients with 35 malignant and 28 benign liver lesions were studied with unenhanced ultrasound (US) including B-mode and power Doppler, followed by contrast-enhanced al MI (0.1 - 0.3) real time phase inversion US during arterial, portal-venous and delayed liver phase (> 2 min after injection). Findings of the scans obtained before and after administration of contrast agent were compared with each other and with reference examinations (biopsy, MRI, CT or intraoperative US). RESULTS: The number of correctly diagnosed lesions increased from 41 (65%) without contrast agent to 58 (92%) with contrast agent (p < 0.001). The differentiation of malignant from benign lesions improved from 43 (68 %) to 60 (95 %, p < 0.001). After administration of the contrast agent, all 35 malignant lesions were correctly recognized and 3 of the 28 benign lesions were misclassified. All 27 metastases showed little or no enhancement on portal-venous and delayed phase imaging, independent of their arterial features. All 6 hepatocellular carcinomas (HCC) enhanced markedly during arterial phase and 5 showed less contrast uptake than normal liver in the late phase. Ten of 11 hemangioma displayed arterial peripheral nodular enhancement followed by progressive centripetal fill-in. Nine of 11 focal nodular hyperplasias (FNHs) showed profuse arterial enhancement (5 with a transient "spokewheel") and contrast uptake similar to normal liver thereafter. One FNH showed a subtle central scar. CONCLUSION: Low MI real time US with SonoVue markedly improves the characterization of focal hepatic lesions in comparison with unenhanced sonography.
Abstract: Ultrasound contrast agents consist of tiny gas bubbles encapsulated by a stabilising membrane or shell. When combined with recent contrast-specific ultrasound techniques, they provide substantial enhancement of vessels and solid organs. The clinical use and the diagnostic value of ultrasound contrast agents are in principle comparable to those of contrast agents for CT and MRI. They add an additional dimension of information to sonography, which results in considerable improvement of diagnostic accuracy in many cases. This paper reviews the physicochemical properties of various microbubble contrast agents, discusses non-linear bubble behaviour and contrast-specific imaging techniques. An overview of the most important radiological clinical applications in the liver, kidney and spleen is given.
Abstract: Decreased, renormalized, or increased values of the calculated apparent diffusion coefficient (ADC) are observed in stroke models. A quantitative description of corresponding tissue states using ADC values may be extended to include true relaxation times. A histogram-based segmentation is well suited for characterizing tissues according to specific parameter combinations irrespective of the heterogeneity found for human healthy and ischemic brain tissues. In a new approach, navigated diffusion-weighted images and ADC maps were incorporated into voxel-based parameter sets of relaxation times (T1, T2), and T1- or T2-weighted images, followed by a supervised histogram-based analysis. Healthy tissues were segmented by incorporating T1 relaxation into the data set, ischemic regions by combining T2- or diffusion-weighted images with ADC maps. Mean values of healthy and pathologic tissues were determined, spatial distributions of the parameter vectors were visualized using color-encoded overlays. One to six days after stroke, ischemic regions exhibited reduced relative mean ADC values.
