Ultrasound Contrast Agent Bolus Research Articles

V14-06 CETRUS; CONTRAST-ENHANCED TRANS-RECTAL ULTRASOUND TO MONITOR POST-TREATMENT RECURRENCE AFTER FOCAL HIFU OF PROSTATE

You have accessJournal of UrologyProstate Cancer (V14)1 Apr 2020V14-06 CETRUS; CONTRAST-ENHANCED TRANS-RECTAL ULTRASOUND TO MONITOR POST-TREATMENT RECURRENCE AFTER FOCAL HIFU OF PROSTATE Aliasger Shakir*, Atsuko Fujihara, Tsuyoshi Iwata, Alessandro Tafuri, Cacciamani Giovanni, Suzanne Palmer, Inderbir Gill, and Andre Luis Abreu Aliasger Shakir*Aliasger Shakir* More articles by this author , Atsuko FujiharaAtsuko Fujihara More articles by this author , Tsuyoshi IwataTsuyoshi Iwata More articles by this author , Alessandro TafuriAlessandro Tafuri More articles by this author , Cacciamani GiovanniCacciamani Giovanni More articles by this author , Suzanne PalmerSuzanne Palmer More articles by this author , Inderbir GillInderbir Gill More articles by this author , and Andre Luis AbreuAndre Luis Abreu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000982.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To assess the role of contrast enhanced trans-rectal ultrasound (CeTRUS) in the follow-up evaluation of patients who underwent focal High Intensity Focused Ultrasound (HIFU) for prostate cancer (PCa). METHODS: From our IRB-approved database (HS-17-00749), we identified 22 patients who underwent focal hemi-gland HIFU ablation of the prostate and had follow-up CeTRUS, mutiparametric MRI (mpMRI) and prostate biopsy (PBx) between 6 months to 1 year after HIFU. Salvage or whole-gland HIFU patients were excluded. CeTRUS was performed following a 2.5cc intravenous bolus of ultrasound contrast agent (LUMASON). Two-minute cine images of the regions of interest were recorded. CeTRUS findings were compared with mpMRI and the results of PBx. CeTRUS images were evaluated qualitatively. A PIRADS v2 score of 3 or higher was considered positive. Clinically significant PCa (csPCa) is defined as ISUP Grade Group (GG) ≥ 2 and non-csPCa is defined as ISUP Grade Group (GG) < 2. RESULTS: At baseline, median age and PSA was 65 year old and 5.1ng/ml. Six (26%) patients had low-risk, 13 (57%) had intermediate-risk and 3 (13%) had high-risk PCa. Post HIFU, median PSA nadir, and reduction in PSA were 1.0 ng/mL and 72%, respectively. On follow-up PBx with a median follow of 16M, 12 (55%) patients had cancer, 6 (27%) patients had csPCa, 3 (14%) patients had in-field recurrences, 9 (40%) patients had out-field recurrences, and 10 (45%) patients had a negative biopsy. Among them, three (14%) patients had in-field csPCa, 3 (14%) had out-field csPCa, 0 (0%) had in-field ncsPCa, and 6 (27%) had out-field ncsPCa. In the 3 patients with in-field csPCa (Table), MRI detected 2 (66%) lesions and CeTRUS detected 2 (66%) lesions. However, the patients with lesions detected by MRI and CeTRUS were not the same. One patient had a lesion detected by both MRI and CeTRUS, one patient had a lesion detected by MRI only and one patient had a lesion detected by CeTRUS only. Overall, among the 3 patients with in-field csPCa, 3 (100%) had lesions detected by either imaging modality. CONCLUSIONS: CeTRUS enhancement pattern showed high correlation with in-field csPCa on follow up PBx. CeTRUS and MRI were able to identify more csPCa compared to MRI alone. The addition of CeTRUS to MRI can be helpful in the follow up after focal HIFU and aid detection, and localization of csPCa. Source of Funding: This study was funded in part by the R01 grant CA205058-01 from the National Institutes of Health/ National Cancer Institute (M.C.S, I.S.G. and A.L.A.). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1307-e1308 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aliasger Shakir* More articles by this author Atsuko Fujihara More articles by this author Tsuyoshi Iwata More articles by this author Alessandro Tafuri More articles by this author Cacciamani Giovanni More articles by this author Suzanne Palmer More articles by this author Inderbir Gill More articles by this author Andre Luis Abreu More articles by this author Expand All Advertisement PDF downloadLoading ...

Identification of Vascularised Carotid Plaques Using a Standardised and Reproducible Technique to Measure Ultrasound Contrast Uptake

Contrast-enhanced ultrasonography (CEUS) has been used to assess the vascularisation of carotid plaques. Our aim was to develop and validate a standardised semi-automated method for CEUS examination of plaques, and test if the technique could be used to identify vulnerable plaques. Study participants were a mixed population of symptomatic and asymptomatic subjects, selected if they had a plaque with height >2.5 mm and <10% acoustic shadowing. Participants received a bolus of ultrasound contrast agent and a 90-s cine-loop was captured. A Contrast Quantification Program (CQP) was developed and trained to identify extent of contrast uptake after motion correction and application of a noise reduction algorithm. The technique was validated by comparing CQP values with visual assessment of contrast uptake. CQP values were also compared with plaque echogenicity and history of clinical events. CQP values correlated with a visual, 5-scale classification of contrast uptake by two blinded, experienced sonographers. Repeated contrast injections showed high reproducibility. Participants with a history of ipsilateral stroke/TIA had significantly higher CQP values than asymptomatic participants. We present a reproducible, semi-automatic method to identify vascularisation of carotid plaques, which could be used in prospective studies to determine the clinical value of plaque vascularisation.

Volume quantification by contrast-enhanced ultrasound and thermodilution: an in vitro comparison

In clinical practice, blood volumes (BV) are typically measured by thermodilution. Recently, contrast-enhanced ultrasound (CEUS) has been proposed as an alternative minimally invasive approach for BV assessment [1]. This method measures BV using a single peripheral injection of a small bolus of ultrasound contrast agent (UCA) detected by an ultrasound scanner. By measuring the acoustic backscatter, two indicator dilution curves (IDCs) can be derived from two different sites in the circulatory system. IDC analysis permits deriving the mean transit time (MTT) the bolus takes to travel between the injection site and two measurement sites. Assessment of the BV between these sites is obtained by multiplying the difference in MTT (ΔMTT) by the blood flow. In this study, we compare different volumes in an in vitro set-up by CEUS with true set-up volumes and thermodilution acquired volumes.

Angiogenesis imaging by spatiotemporal analysis of ultrasound contrast agent dispersion kinetics

The key role of angiogenesis in cancer growth has motivated extensive research with the goal of noninvasive cancer detection by blood perfusion imaging. However, the results are still limited and the diagnosis of major forms of cancer, such as prostate cancer, are currently based on systematic biopsies. The difficulty in the detection of angiogenesis partly resides in a complex relationship between angiogenesis and perfusion. This may be overcome by analysis of the dispersion kinetics of ultrasound contrast agents. Determined by multipath trajectories through the microvasculature, dispersion permits a better characterization of the microvascular architecture and, therefore, more accurate detection of angiogenesis. In this paper, a novel dispersion analysis method is proposed for prostate cancer localization. An ultrasound contrast agent bolus is injected intravenously. Spatiotemporal analysis of the concentration evolution measured at different pixels in the prostate is used to assess the local dispersion kinetics of the injected agent. In particular, based on simulations of the convective diffusion equation, the similarity between the concentration evolutions at neighbor pixels is the adopted dispersion measure. Six measurements in patients, compared with the histology, provided a receiver operating characteristic curve integral equal to 0.87. This result was superior to that obtained by the previous approaches reported in the literature.

Contrast-Ultrasound Diffusion Imaging for Localization of Prostate Cancer

Prostate cancer is the most prevalent form of cancer in western men. An accurate early localization of prostate cancer, permitting efficient use of modern focal therapies, is currently hampered by a lack of imaging methods. Several methods have aimed at detecting microvascular changes associated with prostate cancer with limited success by quantitative imaging of blood perfusion. Differently, we propose contrast-ultrasound diffusion imaging, based on the hypothesis that the complexity of microvascular changes is better reflected by diffusion than by perfusion characteristics. Quantification of local, intravascular diffusion is performed after transrectal ultrasound imaging of an intravenously injected ultrasound contrast agent bolus. Indicator dilution curves are measured with the ultrasound scanner resolution and fitted by a modified local density random walk model, which, being a solution of the convective diffusion equation, enables the estimation of a local, diffusion-related parameter. Diffusion parametric images obtained from five datasets of four patients were compared with histology data on a pixel basis. The resulting receiver operating characteristic (curve area = 0.91) was superior to that of any perfusion-related parameter proposed in the literature. Contrast-ultrasound diffusion imaging seems therefore to be a promising method for prostate cancer localization, encouraging further research to assess the clinical reliability.

Semiquantitative Human Cerebral Perfusion Assessment With Ultrasound in Brain Space-Occupying Lesions

Transcranial Duplex ultrasound imaging with ultrasound contrast agents is an emerging technique for evaluating brain perfusion. The aim of this study was to evaluate cerebral perfusion with ultrasound in brain space-occupying lesions to identify different perfusion patterns. Twenty patients with brain space-occupying lesions underwent ultrasound assessment of brain perfusion with a contrast pulse sequencing nonharmonic ultrasound technique and an ultrasound contrast agent bolus. Data were analyzed with software for semiquantitative analysis. Contrast pulse sequencing imaging with the semiquantitative analysis software allowed identification of qualitative and semiquantitative brain perfusion. Brain hemorrhages showed lower or absent perfusion compared with normal tissue. Meningiomas and glioblastomas without large necrotic areas showed higher perfusion compared with normal tissue. Glioblastomas with large necrotic areas showed overall reduced perfusion compared with normal tissue but higher than that of brain hemorrhages. In glioblastomas with large necrotic areas, it was possible to distinguish between solid and necrotic tissue. This bedside ultrasound technique, if validated by larger-scale studies, may add helpful information in noninvasive staging of brain tumors. Further potential applications may be in follow-up imaging to evaluate postoperative tumor recurrence or the presence of radionecrosis.

On the Ability of Ultrasound Parametric Perfusion Imaging to Predict the Area of Infarction in AcuteIschemic Stroke

Cerebral perfusion deficits in acute ischemic stroke can be detected by means of transcranial harmonic imaging after ultrasound contrast agent bolus injection. We evaluated five different parameters of the bolus kinetics as parametric images and correlated areas of disturbed perfusion with the area of definite infarction. Perfusion harmonic imaging after SonoVue bolus injection (BHI) was used to investigate 22 patients suffering from acute internal carotid artery infarction. For each subject, we calculated five different images based on the following parameters from the time-intensity curve in each pixel: pixelwise peak intensity (PPI), area under the curve (AUC), positive gradient (PG), time to peak (TTP), and a three factor image from the factor analysis of medical image sequences (FAMIS). The findings in the diencephalic imaging plane were compared with the definite area of infarction, as diagnosed by cranial CT. In predicting the definite area of infarction in follow-up CT, we found the following sensitivities and positive predictive values (PPV): PPI (100 %/95 %), AUC (100 %/90 %), FAMIS (89 %/89 %), PG (84 %/94 %) and TTP (47 %/100 %). The areas of disturbed perfusion in all five types of parametric images correlated significantly with the area of infarction in CT. Images from the FAMIS algorithm and PPI images showed the highest Spearman rank correlation with the area of definite infarction as displayed in CT (both r = 0.76, p < 0.001). Images from the other parameters correlated as follows: PG: r = 0.62 (p = 0.003), AUC: r = 0.53 (p = 0.014), TTP: r = 0.50 (p = 0.021). BHI can detect disturbed perfusion in acute hemispheric stroke. In their ability to predict the development of an infarction, intensity-based parameters and FAMIS were determined to have a high sensitivity, and TTP was found to have a high PPV and specificity.

Ultrasound Perfusion Imaging of Cerebrovascular Disease

Ultrasound perfusion imaging of the cerebral microcirculation is a new semi-invasive bedside technique to evaluate human brain perfusion. Several approaches have been evaluated for the qualitative assessment of brain perfusion in healthy subjects and in patients suffering from acute ischemic stroke. The analysis of ultrasound contrast agent bolus kinetics yields various time-intensity curve parameters that qualitatively describe regional brain perfusion. In healthy subjects, there is a close correlation between the time to peak intensity measurements as performed by perfusion ultrasound and perfusion-weighted MRI. In the acute phase of ischemic stroke, the peak signal increase is the most useful curve parameter to predict the area of definite infarction. Ultrasound perfusion imaging performed in the early phase can predict the outcome of the individual stroke patient. Diminution and Replenishment kinetics are new modalities for the visualization of brain perfusion, the latter being more promising because of the fast imaging time resulting in a lower vulnerability to movement artifacts. The different approaches will have to be compared regarding their ability to provide valid thresholds for differentiation between normal and abnormal perfusion in the acute stroke situation. At present, the foremost limitations of transcranial ultrasound perfusion imaging are attenuation phenomena, caused by the temporal bone, which might be overcome by new imaging systems that are currently under development.

Diagnosis of Total Internal Carotid Occlusions with Duplex Ultrasound and Ultrasound Contrast

It remains a significant technical challenge for duplex ultrasound to accurately differentiate between total and near total internal carotid artery (ICA) occlusions. We have evaluated the efficacy of an ultrasound contrast agent combined with improved imaging techniques in patients with suspected carotid artery occlusions. Patients identified by conventional duplex ultrasound between January and August 2003 as having a possible ICA occlusion were eligible for study. A 1 mL bolus of ultrasound contrast agent was injected into a 50 mL bag of normal saline and given intravenously at a rate of approximately 4-5 mL/minute. Ultrasound imaging and spectral Doppler analysis were done using tissue harmonic imaging for optimum contrast agent to soft tissue discrimination, or with the direct B-mode imaging of blood flow to maximize the brightness of the circulating contrast agent. Ten patients were identified, 6 men and four women with a mean age of 68.3 years. Nine suspected total ICA occlusions were unilateral and 1 was bilateral. Imaging with contrast agent confirmed occlusion of the ICA in 7 of 10 patients; 3 patients had near-total occlusion with flow detected in the distal ICA by spectral and color Doppler. All 3 of these near-total occlusions were ultimately confirmed by either conventional or magnetic resonance carotid angiography. The contrast agent was most beneficial in improving the detection of minimal flow beyond a severe stenosis and in evaluating flow dynamics in the presence of severely calcified plaque. We conclude that the use of an ultrasound contrast agent with newer duplex ultrasound imaging techniques can reliably distinguish total from near-total internal carotid artery occlusions. Future prospective studies should be able to define the efficacy of ultrasound contrast agents in improving the overall diagnostic accuracy of duplex ultrasound in technically difficult cases and in patients with complex peripheral vascular disease.

Identification of ultrasound contrast agent dilution systems for ejection fraction measurements

Left ventricular ejection fraction is an important cardiac-efficiency measure. Standard estimations are based on geometric analysis and modeling; they require time and experienced cardiologists. Alternative methods make use of indicator dilutions, but they are invasive due to the need for catheterization. This study presents a new minimally invasive indicator dilution technique for ejection fraction quantification. It is based on a peripheral injection of an ultrasound contrast agent bolus. Left atrium and left ventricle acoustic intensities are recorded versus time by transthoracic echocardiography. The measured curves are corrected for attenuation distortion and processed by an adaptive Wiener deconvolution algorithm for the estimation of the left ventricle impulse response, which is interpolated by a monocompartment exponential model for the ejection fraction assessment. This technique measures forward ejection fraction, which excludes regurgitant volumes. The feasibility of the method was tested on a group of 20 patients with left ventricular ejection fractions going from 10% to 70%. The results are promising and show a 0.93 correlation coefficient with echographic bi-plane ejection fraction measurements. A more extensive validation as well as an investigation on the method applicability for valve insufficiency and right ventricular ejection fraction quantification will be an object of future study.

Local and reversible blood–brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications

The purpose of this study was to test the hypothesis that burst ultrasound in the presence of an ultrasound contrast agent can disrupt the blood-brain barrier (BBB) with acoustic parameters suitable for completely noninvasive exposure through the skull. The 10-ms exposures were targeted in the brains of 22 rabbits with a frequency of 690 kHz, a repetition frequency of 1 Hz, and peak rarefactional pressure amplitudes up to 3.1 MPa. The total exposure (sonication) time was 20 s. Prior to each sonication, a bolus of ultrasound contrast agent was injected intravenously. Contrast-enhanced MR images were obtained after the sonications to detect localized BBB disruption via local enhancement in the brain. Brain sections were stained with H&E, TUNEL, and vanadium acid fuchsin (VAF)-toluidine blue staining. In addition, horseradish peroxidase (HRP) was injected into four rabbits prior to sonications and transmission electron microscopy was performed. The MRI contrast enhancement demonstrated BBB disruption at pressure amplitudes starting at 0.4 MPa with approximately 50%; at 0.8 MPa, 90%; and at 1.4 MPa, 100% of the sonicated locations showed enhancement. The histology findings following 4 h survival indicated that brain tissue necrosis was induced in approximately 70-80% of the sonicated locations at a pressure amplitude level of 2.3 MPa or higher. At lower pressure amplitudes, however, small areas of erythrocyte extravasation were seen. The electron microscopy findings demonstrated HRP passage through vessel walls via both transendothelial and paraendothelial routes. These results demonstrate that completely noninvasive focal disruption of the BBB is possible.

The threshold for brain damage in rabbits induced by bursts of ultrasound in the presence of an ultrasound contrast agent (Optison®)

The purpose of this study was to test the hypothesis that burst ultrasound (US) in the presence of a US contrast agent using parameters similar to those used in brain blood flow measurements causes tissue damage. The brains of 10 rabbits were sonicated in 3–8 locations with 1.5-MHz, 10-μs bursts repeated at a frequency of 1 kHz at temporal peak acoustic pressure amplitudes ranging from 2 to 12.7 MPa. The total sonication time for each location was 20 s. Before each sonication, a bolus of US contrast agent was injected IV. Contrast-enhanced magnetic resonance (MR) images were obtained after the sonications to detect local enhancement in the brain. Whole brain histological evaluation was performed, and the sections were stained with hematoxylin and eosin (H and E), TUNEL, and vanadium acid fuchsin (VAF) staining to evaluate tissue effects, including apoptosis and ischemia. Both the magnetic resonance imaging (MRI) contrast enhancement and histology findings indicated that brain tissue damage was induced at a pressure amplitude level of 6.3 MPa. The damage included vascular wall damage, hemorrhage and, eventually, necrosis. Mild vascular damage was observed localized in a few microscopic tissue volumes in about half of the sonicated locations at all pressure values tested (down to 2 MPa). However, these sonications did not induce any detectable tissue effects, including ischemia or apoptosis. As a conclusion, the study showed that the US exposure levels currently used for blood flow measurements in brain are below the threshold of blood-brain barrier opening or brain tissue damage. However, one should be aware that brain damage can be induced if the exposure level is increased.

Non-invasive diagnosis of hepatic cirrhosis by transit-time analysis of an ultrasound contrast agent

Hepatic cirrhosis is accompanied by several haemodynamic changes including arterialisation of the liver, intrahepatic shunts, pulmonary arteriovenous shunts, and a hyperdynamic circulatory state. We postulated that the hepatic first pass of a bolus of an ultrasound contrast agent injected into a peripheral vein is accelerated in patients with cirrhosis. We investigated this first pass in patients with diffuse liver disease and in normal controls to assess whether it provides useful differential diagnostic information. We enrolled 15 patients with biopsy-proven cirrhosis, 12 patients with biopsy-proven non-cirrhotic diffuse liver disease, and 11 normal controls. We carried out continuous spectral doppler ultrasonography of a hepatic vein from 20 s before to 3 min after a peripheral intravenous bolus injection of 2.5 g Levovist. The intensity of the doppler signal was measured and used to plot time-intensity curves. Patients with cirrhosis showed a much earlier onset of enhancement (arrival time; mean 18.3 s) and peak enhancement (mean 55.5 s) than controls (49.8 s and 97.5 s) or patients with non-cirrhotic diffuse liver disease (35.8 s and 79.7 s). All patients with cirrhosis had an arrival time of the bolus of less than 24 s, whereas the arrival time was 24 s or more in 22 of the 23 other participants. Peak enhancement was higher in patients with cirrhosis (mean 48.7 units) than in the other two groups (12.5 and 12.3 units, respectively). We found highly significant differences between the patients with cirrhosis and each of the other two groups for all variables (p<0.005), whereas we found no significant differences between non-cirrhotic patients and controls. Our preliminary study suggests that analysis of liver transit time of a bolus of ultrasound contrast agent provides useful information about haemodynamic changes in patients with cirrhosis. Measurement of the arrival time of the bolus allows discrimination of patients with cirrhosis from controls and from patients with non-cirrhotic diffuse liver disease, and has potential as a non-invasive test for cirrhosis.