Injection Of Microbubble Contrast Agent Research Articles

EFSUMB Technical Review - Update 2023: Dynamic Contrast-Enhanced Ultrasound (DCE-CEUS) for the Quantification of Tumor Perfusion.

Dynamic contrast-enhanced ultrasound (DCE-US) is a technique to quantify tissue perfusion based on phase-specific enhancement after the injection of microbubble contrast agents for diagnostic ultrasound. The guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published in 2004 and updated in 2008, 2011, and 2020 focused on the use of contrast-enhanced ultrasound (CEUS), including essential technical requirements, training, investigational procedures and steps, guidance regarding image interpretation, established and recommended clinical indications, and safety considerations. However, the quantification of phase-specific enhancement patterns acquired with ultrasound contrast agents (UCAs) is not discussed here. The purpose of this EFSUMB Technical Review is to further establish a basis for the standardization of DCE-US focusing on treatment monitoring in oncology. It provides some recommendations and descriptions as to how to quantify dynamic ultrasound contrast enhancement, and technical explanations for the analysis of time-intensity curves (TICs). This update of the 2012 EFSUMB introduction to DCE-US includes clinical aspects for data collection, analysis, and interpretation that have emerged from recent studies. The current study not only aims to support future work in this research field but also to facilitate a transition to clinical routine use of DCE-US.

Visualization of tumor angiogenesis using super-resolution ultrasound imaging

Super-resolution ultrasound imaging (SR-US) is a new technique that breaks the diffraction limit and allows visualization of microvascular structures down to tens of microns. The objective of this presentation is to briefly introduce SR-US imaging and use in various small animal models. Engineering challenges and ongoing opportunities will also be introduced. SR-US is predominantly a software advance that can be integrated with both clinical and preclinical US imaging platforms. After injection of an intravascular microbubble (MB) contrast agent, a time-series of contrast-enhanced ultrasound (CEUS) images are acquired. Spatiotemporal filtering of the CEUS images helps remove the tissue clutter signal and segmentation of the MB signal. Precise localization of the center of each agent is then determined. This process is repeated for each CEUS image in the time series. The resultant SR-US images depict fine microvascular detail typically unresolved using traditional CEUS imaging methods. During this presentation, we will explore use of methods to help improve the MB detection and localization process in space and time like with the use of motion correction and machine learning algorithms. We will also present a series of preclinical examples highlighting the potential of this new technology in cancer research. Results demonstrate that SR-US imaging depicts microvascular structures not visible using traditional CEUS methods. The utility of this new diagnostic tool will play more of a role in theranostics over the next decade.

Short-Term Efficacy of Transcranial Focused Ultrasound to the Hippocampus in Alzheimer's Disease: A Preliminary Study.

Preclinical studies have suggested that low-intensity transcranial focused ultrasound (tFUS) may have therapeutic potential for Alzheimer’s disease (AD) by opening the blood–brain barrier (BBB), reducing amyloid pathology, and improving cognition. This study investigated the effects of tFUS on BBB opening, regional cerebral metabolic rate of glucose (rCMRglu), and cognitive function in AD patients. Eight patients with AD received image-guided tFUS to the right hippocampus immediately after intravenous injection of microbubble ultrasound contrast agents. Patients completed magnetic resonance imaging (MRI), 18F-fluoro-2-deoxyglucose positron emission tomography (PET), and cognitive assessments before and after the sonication. No evidence of transient BBB opening was found on T1 dynamic contrast-enhanced MRI. However, immediate recall (p = 0.03) and recognition memory (p = 0.02) were significantly improved on the verbal learning test. PET image analysis demonstrated increased rCMRglu in the right hippocampus (p = 0.001). In addition, increases of hippocampal rCMRglu were correlated with improvement in recognition memory (Spearman’s ρ = 0.77, p = 0.02). No adverse event was observed. Our results suggest that tFUS to the hippocampus of AD patients may improve rCMRglu of the target area and memory in the short term, even without BBB opening. Further larger sham-controlled trials with loger follow-up are warranted to evaluate the efficacy and safety of tFUS in patients with AD.

Early Predictors of the Long-term Response to Therapy in Patients With Crohn Disease Derived From a Time-Intensity Curve Analysis After Microbubble Contrast Agent Injection.

The aim of this study was to identify early predictors of the long-term response to therapy in patients with Crohn disease (CD) from time-intensity curves obtained after microbubble injection. One hundred fifteen consecutive patients with a proven diagnosis of CD involving the terminal ileal loop who were scheduled to begin pharmacologic therapy with biologics (infliximab or adalimumab) were scanned after sulfur hexafluoride-filled microbubble injection before the beginning and at the end of the sixth week of treatment. The absolute value and percentage change of each semiquantitative kinetic parameter (peak enhancement, time to peak enhancement, rise time, mean transit time, wash-in and wash-out rates, area under the curve [AUC] for the whole time-intensity curve, AUC during wash-in, AUC during wash-out, and wash-in perfusion index) as measured on the terminal ileal tract and adjacent reactive mesenteric fat were calculated from time-intensity curves. Patients were followed for at least 24 months with redetermination of the Crohn Disease Activity Index and with at least 1 endoscopy within 18 weeks after the beginning of pharmacologic treatment. The absolute values and percentage changes of kinetic parameters were assessed as potential predictors of the therapeutic outcome by a logistic regression analysis. The study group included 66 male and 49 female patients (mean age ± SD, 45.76 ± 11 years). The pretreatment values and percentage changes of the peak enhancement, AUC, AUC during wash-in, and AUC during wash-out were found to be predictors (P < .05) of the long-term therapeutic outcome. The analysis of time-intensity curves obtained after microbubble contrast agent injection provides early predictors of the long-term therapeutic outcome in patients with CD.

The Most Appropriate Time Delay after Microbubble Contrast Agent Intravenous Injection to Maximize Liver Metastasis Conspicuity on Contrast-Enhanced Ultrasound.

Purpose:To identify the most appropriate time delay after microbubble contrast agent injection to maximize liver metastasis conspicuity on contrast-enhanced ultrasound (CEUS).Methods:Twenty-five consecutive patients (12 male and 13 female; age: 50 ± 13 years) with a known primary tumor and evidence of liver metastases on unenhanced ultrasound (US) underwent CEUS. CEUS consisted of continuous liver parenchyma scanning during arterial (15–35 s after microbubble injection), portal venous (40–120 s), and late phase (from 120 s up to microbubble disappearance). Subjective conspicuity index (ranging from 1 to 5) and objective conspicuity index (Ilesion–Iliver/Iliver, I = signal intensity) were calculated on reference frames selected on arterial phase and every 20 s on portal venous and late phase.Results:A total number of 40 liver metastases were identified after microbubble injection. The highest liver metastasis conspicuity was observed on early portal venous phase (40–60 s after microbubble injection) both on visual (mean subjective conspicuity index ± standard deviation [SD] = 4.36 ± 0.75, reader 1; 4.25 ± 0.65, reader 2) and quantitative analysis (mean objective conspicuity index ± SD = −0.99 ± 0.001).Conclusion:The early portal venous phase (40–60 s after microbubble injection) provides the best liver metastases' conspicuity after microbubble contrast agent injection.

CEUS LI-RADS: algorithm, implementation, and key differences from CT/MRI.

Contrast-enhanced ultrasound (CEUS) is a specialized form of ultrasound (US) performed with an intravenous injection of microbubble contrast agents. It has been successfully used for a variety of applications including characterization of liver tumors. In April 2014, the American College of Radiology (ACR) convened a working group of international experts to develop ACR CEUS Liver Imaging Reporting and Data System (CEUS LI-RADS). An initial version of CEUS LI-RADS was published in August 2016. Although the CEUS LI-RADS concept and principles for liver lesion characterization, using dynamic contrast enhancement features, are similar to those for CT or MRI, there are significant differences between CT/MRI and CEUS LI-RADS. Therefore, CEUS LI-RADS has different diagnostic features and a unique characterization algorithm. The size of a lesion, the type and degree of arterial phase enhancement, the presence of washout, and the timing and degree of washout are the major features used for categorization. This paper describes key differences between CT/MRI and CEUS, and provides a diagnostic algorithm of CEUS LI-RADS with detailed, step-by-step instructions and imaging examples of CEUS LI-RADS categories.

Differentiation of Inflammatory from Fibrotic Ileal Strictures among Patients with Crohn's Disease through Analysis of Time–Intensity Curves Obtained after Microbubble Contrast Agent Injection

The aim of the study described here was to assess whether the analysis of time–intensity curves obtained after microbubble contrast agent injection could differentiate inflammatory from fibrotic ileal strictures among patients with Crohn's disease. Sixty-five consecutive patients (40 male and 25 female; mean age ± SD, 42.2 ± 12.22 y) with stricture of the terminal ileal loop from Crohn's disease were scanned after microbubble injection. Time–intensity curves were obtained from quantitative analysis, and peak enhancement, rise time, time to peak, area under the time–intensity curve (AUC), AUC during wash-in (AUCWI) and AUC during wash-out (AUCWO) were compared between patients with inflammatory strictures and patients with fibrotic strictures. Inflammatory (n = 40) and fibrotic (n = 25) strictures differed (p < 0.05) in peak enhancement, wash-in rate, wash-in perfusion index, AUC, AUCWI and AUCWO. The quantitative analysis of small bowel wall contrast enhancement after microbubble contrast agent injection may differentiate inflammatory from fibrotic ileal strictures in patients with Crohn's disease.

Contrast-enhanced ultrasound mapping of sentinel lymph nodes in oral tongue cancer-a pilot study.

To assess the usefulness of contrast-enhanced ultrasound (CEUS) with peritumoral injection of microbubble contrast agent for detecting the sentinel lymph nodes for oral tongue carcinoma. The study was carried out on 12 patients with T1-2cN0 oral tongue cancer. A radical resection of the primary disease was planned; a modified radical supraomohyoid neck dissection was reserved for patients with larger lesions (T2, n = 8). The treatment plan and execution were not influenced by sentinel node mapping outcome. The Sonovue™ contrast agent (Bracco Imaging, Milan, Italy) was utilized. After detection, the position and radiologic features of the sentinel nodes were recorded. The identification rate of the sentinel nodes was 91.7%; one patient failed to demonstrate any enhanced areas. A total of 15 sentinel nodes were found in the rest of the 11 cases, with a mean of 1.4 nodes for each patient. The sentinel nodes were localized in: Level IA-1 (6.7%) node; Level IB-11 (73.3%) nodes; Level IIA-3 (20.0%) nodes. No contrast-related adverse effects were observed. For oral tongue tumours, CEUS is a feasible and potentially widely available approach of sentinel node mapping. Further clinical research is required to establish the position of CEUS detection of the sentinel nodes in oral cavity cancers.

Development of complex tissue-mimicking phantoms for quantification of flow by the time-intensity method in contrast enhanced ultrasound imaging

Currently, there are few simple-to-construct in vitro, wall-less phantoms that have accurate acoustic properties while mimicking the complex normal and neoplastic geometries of the vascular network. The purpose of this study was to develop agar-based tissue-mimicking phantoms (TMP) to model such networks. Three types of vascular networks were considered: (1) single vessel, (2) multi-vessel with artery bifurcations, and (3) multi-vessel with artery bifurcations and structural abnormalities typical of diseased (tumor) vascular networks. Blood-flow related parameters were derived from the time-intensity curves obtained from the bolus injection of a lipid-based microbubble ultrasound contrast agent (UCA) under varying flow conditions relevant to our ongoing work in developing techniques to simultaneously quantify both the total volume and flow measurements within a tumor phantom. A Fukuda Denshi Ultrasound system was used with a linear probe (LG308-16A) positioned transversely and longitudinally to the direction of the flow. B-mode image acquisition was performed with 0.5 mL of UCA bolus injected into a 500 mL degassed water reservoir and then pumped through the vessels at rates ranging from 20 mL/min to 100 mL/min. Offline analysis of time-intensity curves in response to varied flow conditions indicated the TMP ability to yield easily reproducible simulations of vascular microcirculation.

Contrast-Enhanced Ultrasound of Focal Liver Lesions.

The purpose of this article is to discuss the use of contrast-enhanced ultra-sound (CEUS) in focal liver lesions. Focal liver lesions are usually detected incidentally during abdominal ultrasound. The injection of microbubble ultrasound contrast agents improves the characterization of focal liver lesions that are indeterminate on conventional ultrasound. The use of CEUS is recommended in official guidelines and suggested as a second diagnostic step after ultrasound detection of indeterminate focal liver lesions to immediately establish the diagnosis, especially for benign liver lesions, such as hemangiomas, avoiding further and more expensive examinations.

Abstract P2-01-06: In patients with breast cancer, pre-operative sentinel node biopsy using intradermal microbubbles and contrast enhanced ultrasound predicts volume of axillary metastases

Abstract Introduction In patients with early breast cancer, there is a trend towards conservative axillary surgery but there are concerns that patients with high volume axillary metastases may receive sub-optimal axillary treatment leaving them vulnerable to local recurrence. Determining the metastatic status of sentinel lymph nodes (SLN) in the pre-operative/ diagnostic period would allow focussed surgical planning and facilitate decisions regarding adjuvant therapy early in the patient pathway. Methods 654 patients with primary invasive breast cancer and a normal grey-scale axillary ultrasound were included in the analysis. Pre-operatively, patients received periareolar intra-dermal injection of microbubble contrast agent, breast lymphatics were visualised by ultrasound and followed to identify axillary SLN. Contrast-pulse sequencing and grey-scale ultrasound modalities were used to image SLN. Sentinel lymph nodes were then subjected to core biopsy. Patients subsequently underwent tumour excision and axillary node clearance (ANC) or surgical sentinel node biopsy (SNB) using blue-dye and isotope +/- completion ANC. Results Sentinel lymph nodes were clearly visualised in 605 patients and successfully (B2-B5) core biopsied in 555. The test identified 53% of all SLN metastases with 100% specificity. The negative predictive value was 88%. The prevalence of axillary lymph node metastases was 23%. Given a benign (B2) SLN biopsy result, the post-test probability that a patient had SLN metastases on subsequent surgical excision was 12%. Following ANC, 55% of patients with a malignant (B4/5) biopsy result were found to have high volume axillary disease (2 macro metastases or more) whereas 21% of patients with an initial benign (B2) biopsy result and metastatic cells found at SNB had high volume axillary disease identified after completion ANC (P value less than 0.001). In total, only 2% of patients with a benign (B2) SLN core biopsy result had high volume axillary metastases and half of these had either multifocal cancer or invasive lobular carcinoma. Conclusions SLN can be readily identified and biopsied in the breast clinic using intradermal microbubbles and CEUS. In patients with primary invasive breast cancer and a normal grey scale axillary ultrasound, a benign (B2) SLN core biopsy result may be highly predictive of either no metastases or low volume metastatic disease in the ipsilateral axilla. This group of patients is therefore likely to benefit from axillary conservation and in certain cases, it may be appropriate to completely omit a surgical SNB. Citation Format: Karina Cox, Jennifer Weeks, Ritchie Chalmers, Pippa Mills, David Fish, Ali Sever. In patients with breast cancer, pre-operative sentinel node biopsy using intradermal microbubbles and contrast enhanced ultrasound predicts volume of axillary metastases [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-06.

Contribution of Contrast–Enhanced Sonography in the Detection of Intrahepatic Cholangiocarcinoma

The purpose of this study was to evaluate the contribution of contrast-enhanced sonography in the diagnosis of intrahepatic cholangiocarcinoma up to 3 cm and analyze its dynamic enhancement patterns. Forty-five patients (29 male and 16 female; mean age ± SD, 61.3 ± 10.7 years; range, 38-79 years) with a preliminary diagnosis of intrahepatic cholangiocarcinoma by contrast-enhanced sonography were retrospectively analyzed. For each nodule, the enhancement pattern, level, and dynamic change during the arterial, portal, and late phases after the injection of a sulfur hexafluoride microbubble contrast agent were evaluated. Among the 35 patients with a histopathologic diagnosis of intrahepatic cholangiocarcinoma, 18 nodules showed hyperenhancement during the arterial phase, and 17 showed hypoenhancement. Heterogeneous, peripheral, and partial enhancement were found in 24, 8, and 2 nodules, respectively. However, only 1 nodule showed homogeneous enhancement. During the portal phase, 34 nodules showed hypoenhancement, and 1 showed isoenhancement. Hypoenhancement during the late phase was observed in all cases. Ten patients had a misdiagnosis of intrahepatic cholangiocarcinoma. Intrahepatic cholangiocarcinoma up to 3 cm may display a variety of arterial enhancement patterns on contrast-enhanced sonography. However, some other nodules may manifest findings similar to those of intrahepatic cholangiocarcinoma.

Contrast-enhanced ultrasound of the small bowel in Crohn’s disease

Crohn's disease (CD) is a chronic transmural inflammatory disease of the gastrointestinal tract characterized by episodes of inflammation alternating with periods of remission. Unenhanced grey-scale ultrasound may evaluate the localisation and the length of the affected intestinal segments and may detect transmural complications, including fistulas, abscesses and phlegmons, but it is less accurate to assess the CD activity. Contrast-enhanced ultrasound has become an important imaging modality in patients with CD for the grading of disease activity, the differentiation between small bowel stricture due to inflammation or mural fibrosis, and for the assessment of the response to specific therapy. New dedicated software packages allow the accurate quantification of the enhancement within the small bowel wall after microbubble contrast agent injection to obtain different kinetic semi-quantitative parameters-the percentage of the maximal enhancement, the time-to-the peak enhancement, and the area under the time-intensity curve-which are very useful to differentiate the inflammatory oedema from fibrosis and to differentiate responders from non-responders to the specific therapy among patients with CD.

Validation of a technique using microbubbles and contrast enhanced ultrasound (CEUS) to biopsy sentinel lymph nodes (SLN) in pre-operative breast cancer patients with a normal grey-scale axillary ultrasound

In patients with breast cancer, grey-scale ultrasound often fails to identify lymph node (LN) metastases. We aimed to validate the technique of contrast-enhanced ultrasound (CEUS) as a test to identify sentinel lymph node (SLN) metastases and reduce the numbers of patients requiring a completion axillary node clearance (ANC). 371 patients with breast cancer and a normal axillary ultrasound were recruited. Patients received periareolar intra-dermal injection of microbubble contrast agent. Breast lymphatics were visualised by CEUS and followed to identify and biopsy axillary SLN. Patients then underwent standard tumour excision and either SLN excision (benign biopsy) or axillary clearance (malignant biopsy) with subsequent histopathological analysis. The technique failed in 46 patients, 6 patients had indeterminate biopsy results and 24 patients were excluded. In 295 patients with a conclusive SLN biopsy, the sensitivity of the technique was 61% and specificity 100%. Given a benign SLN biopsy result, the post-test probability that a patient had SLN metastases was 8%. 35 patients were found to have SLN metastases and had a primary ANC (29 macrometastases and 6 micrometastases/ITC). There were 22 false negative results (10 macrometastases and 12 micrometastases). Macrometastases in core biopsy specimens correlated with LN macrometastases on surgical excision. Pre-operative biopsy of SLN reduced the numbers of patients requiring completion ANC. Despite the low sensitivity, only 22 patients (8%) with a benign SLN biopsy were subsequently found to have LN metastases. Without the confirmation of macrometastases on core biopsy specimens, patients with micrometastases/ITC may be inadvertently selected for primary ANC.

The value of time-intensity curves obtained after microbubble contrast agent injection to discriminate responders from non-responders to anti-inflammatory medication among patients with Crohn’s disease

To assess the value of time-intensity curves obtained after sulphur hefluoride-filled microbubble contrast agent injection to discriminate responders from non-responders among patients with Crohn's disease (CD). Forty-three patients (29 male and 14 female; mean age ± SD, 48.5 ± 17.17 years) with initial diagnosis of active CD were recruited. In each patient, the therapeutic outcome was assessed after 12 weeks from the beginning of pharmacologic treatment. The terminal ileal loop was scanned after sulphur hexafluoride-filled microbubble injection, and the digital cine-clip registered during the first-pass dynamic enhancement was quantified in gray-scale levels. The percentage of maximal enhancement, time to peak enhancement, and area under the time-intensity curve in responders vs. non-responders were compared by Mann-Whitney U non-parametric test. Responders (n = 25 patients) vs. non-responders (n = 18) differed in the area under the time-intensity curve (621.58 ± 374.53 vs. 1,199.64 ± 386.39 P < 0.05), while they did not differ in percentage of maximal enhancement (41.26 ± 15.22 vs. 43.17 ± 4.41, P = 0.25) and time to peak enhancement (11.31 ± 3.06 vs. 10.12 ± 3.47, P = 0.15). The area under the time-intensity curve obtained after microbubble injection was the only parameter to discriminate responders from non-responders among patients with CD during pharmacologic treatment. • Dynamic ultrasound using microbubble contrast agents can help assess inflammatory bowel disease • Time-intensity curves can assess therapeutic outcome in Crohn's disease (CD) • The area under the time-intensity curve differentiates responders from non-responders during pharmacological treatment.

Contrast-Enhanced Ultrasound in the Diagnosis of Gallbladder Diseases: A Multi-Center Experience

ObjectiveTo assess the usefulness of contrast–enhanced ultrasound (CEUS) in differentiating malignant from benign gallbladder (GB) diseases.MethodsThis study had institutional review board approval. 192 patients with GB diseases from 9 university hospitals were studied. After intravenous bonus injection of a phospholipid-stabilized shell microbubble contrast agent, lesions were scanned with low acoustic power CEUS. A multiple logistic regression analysis was performed to identify diagnostic clues from 17 independent variables that enabled differentiation between malignant and benign GB diseases. Receiver operating characteristic (ROC) curve analysis was performed.ResultsAmong the 17 independent variables, multiple logistic regression analysis showed that the following 4 independent variables were associated with the benign nature of the GB diseases, including the patient age, intralesional blood vessel depicted on CEUS, contrast washout time, and wall intactness depicted on CEUS (all P<0.05). ROC analysis showed that the patient age, intralesional vessels on CEUS, and the intactness of the GB wall depicted on CEUS yielded an area under the ROC curve (Az) greater than 0.8 in each and Az for the combination of the 4 significant independent variables was 0.915 [95% confidence interval (CI): 0.857–0.974]. The corresponding Az, sensitivity, and specificity for the age were 0.805 (95% CI: 0.746–0.863), 92.2%%, and 59.6%; for the intralesional vessels on CEUS were 0.813 (95% CI: 0.751–0.875), 59.8%, and 98.0%; and for the GB wall intactness were 0.857 (95% CI: 0.786–0.928), 78.4%, and 92.9%. The cut-off values for benign GB diseases were patient age <53.5 yrs, dotted intralesional vessels on CEUS and intact GB wall on CEUS.ConclusionCEUS is valuable in differentiating malignant from benign GB diseases. Branched or linear intralesional vessels and destruction of GB wall on CEUS are the CEUS features highly suggestive of GB malignancy and the patient age >53.5 yrs is also a clue for GB malignancy.

Ultrasound microbubble contrast agent-mediated suicide gene transfection in the treatment of hepatic cancer

The aim of this study was to investigate the role of ultrasound microbubble contrast agent-mediated suicide gene transfection in the treatment of hepatic cancer. We intratumorally injected KDR-TK, AFP-TK and microbubble contrast agent into nude mice prior to ultrasound treatment and administration of prodrugs (GCV and 5-FC). The tumor volume, tumor inhibition rate, survival time and apoptosis of tumor cells was determined. The sizes of subcutaneous hepatic cancers in mice receiving treatment were comparable to those in the control group, and the survival time was similar between the two groups (P>0.05). However, the tumor inhibition rate and the number of apoptotic cells in the treatment group was markedly higher compared with that in the control group (P<0.05). Evident tumor necrosis was absent in both groups, except at the needle tract. Ultrasound therapy following injection of suicide genes and microbubble contrast agents is able to inhibit cancer growth in vivo. This may be attributed to the induction of cancer cell apoptosis.

The Value of Small Bowel Wall Contrast Enhancement After Sulfur Hexafluoride-Filled Microbubble Injection to Differentiate Inflammatory from Fibrotic Strictures in Patients with Crohn's Disease

We analysed the value of contrast-enhanced ultrasound to differentiate inflammatory from fibrotic ileal strictures in patients with Crohn's disease (CD). Twenty-eight patients (17 male and 11 female; mean age ± SD, 48.5 ± 17.17 years) with a biopsy-proven diagnosis of CD were included. In each patient, the terminal ileal loop was scanned by a convex-array probe (2–5 MHz) before and after sulphur hexafluoride-filled microbubble injection. The digital cine-clip registered after microbubble injection during the first-pass dynamic enhancement was quantified in gray-scale levels by a dedicated software through manually drawn regions-of-interest (ROIs) encompassing the anterior bowel wall. Time-intensity curves from patients with inflammatory and fibrotic ileal strictures, fitted according to the theoretical gamma variate curve, were compared. Inflammatory vs. fibrotic ileal strictures differed in the percentage of maximal enhancement (45.86 ± 5.32 vs. 37.33 ± 16.24%; p < 0.05) and area under the enhancement curve (1168.25 ± 437.65 vs. 570.47 ± 323.08; p < 0.05), whereas the difference in time to peak enhancement was found not significant (9.25 ± 4.21 vs. 12.01 ± 7.34 s; p > 0.05). The quantitative analysis of small bowel wall contrast enhancement after microbubble contrast agent injection may differentiate inflammatory from fibrotic ileal strictures in patients with CD.

Solid focal liver lesions indeterminate by contrast-enhanced CT or MR imaging: the added diagnostic value of contrast-enhanced ultrasound

The main clinically recognized application of contrast-enhanced US (CEUS) with microbubble contrast agents is the characterization of incidental focal liver lesions. CEUS with low transmit power insonation allows the real-time assessment of contrast enhancement in a focal liver lesion after microbubble contrast agent injection, during the arterial (10-25 s), portal venous (from 35 s up to 2 min) and late phase (4-6 min after microbubble injection). During the portal venous and late phase benign lesions appear hyper or iso-enhancing in comparison to the adjacent liver parenchyma, while malignant lesions prevalently present contrast washout with hypo-enhancing appearance. CEUS may provide an added diagnostic value in those incidental focal liver lesions in which contrast-enhanced CT or MR imaging are not conclusive. In particular, CEUS may provide an added diagnostic value in those focal liver lesions appearing indeterminate on single-phase CT scan, or on CT scans performed by an incorrect delay time or also after injection of a low dose of iodinated contrast agent, or also in those focal liver lesions revealing equivocal enhancement patterns on contrast-enhanced CT or MR imaging. CEUS may have an added diagnostic value also in hepatocellular nodules in a cirrhotic liver and can be considered a complementary imaging technique to CT.

Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling

What's known on the subject? and What does the study add? Transrectal gray-scale ultrasonography guided prostate biopsy sampling is the method for diagnosing prostate cancer (PC) in patients with an increased prostate specific antigen level and/or abnormal digital rectal examination. Several imaging strategies have been proposed to optimize the diagnostic value of biopsy sampling, although at the first biopsy nearly 10-30% of PC still remains undiagnosed. This study compares the PC detection rate when employing Colour Doppler ultransongraphy with or without the injection of SonoVue™ microbubble contrast agent, versus the transrectal ultrasongraphy-guided systematic biopsy sampling. The limited accuracy, sensitivity, specificity and the additional cost of using the contrast agent do not justify its routine application in PC detection. • To compare prostate cancer (PC) detection rate employing colour Doppler ultrasonography with or without SonoVue™ contrast agent with transrectal ultrasonography-guided systematic biopsy sampling. • A total of 300 patients with negative digital rectal examination and transrectal grey-scale ultrasonography, with PSA values ranging between 2.5 and 9.9 ng/mL, were randomized into three groups: 100 patients (group A) underwent transrectal ultrasonography-guided systematic bioptic sampling; 100 patients (group B) underwent colour Doppler ultrasonography, and 100 patients (group C) underwent colour Doppler ultrasonography before and during the injection of SonoVue™. • Contrast-enhanced targeted biopsies were sampled into hypervascularized areas of peripheral, transitional, apical or anterior prostate zones. • All the patients included in Groups B and C underwent a further 13 systematic prostate biopsies. The cancer detection rate was calculated for each group. • In 88 (29.3%) patients a histological diagnosis of PC was made, whereas 22 (7.4%) patients were diagnosed with high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. • No significant differences were found among the three groups for cancer detection rate (P= 0.329). • Additionally, low sensitivity, specificity and accuracy of colour Doppler with or without SonoVue™ contrast agent were found. • Prostate cancer detection rate does not significantly improve with the use of colour Doppler ultrasonography with or without SonoVue™. • Although no collateral effects have been highlighted, the combined use of colour Doppler ultrasonography and SonoVue™ determines adjunctive costs and increases the mean time for taking a single prostate biopsy.