Contrast-enhanced Ultrasound Perfusion Research Articles

Bowel contrast-enhanced ultrasound perfusion imaging in the evaluation of Crohn's disease patients undergoing anti-TNFα therapy

AimTo evaluate whether changes in bowel perfusion parameters measured by dynamic-CEUS (D-CEUS) can be used for monitoring response to therapy in active Crohn disease (CD). MethodsFifty-four CD patients were evaluated with d-CEUS before (T0) and after 2 (T1), 6 (T2) and 12 weeks (T3) of anti-TNFα therapy. Variations from baseline were calculated for: peak intensity, PI; area under the curve, AUC; slope of wash in, Pw; time to peak, TP; mean transit time, MTT (median percentage values) and were correlated with combined endoscopic/clinical response after 12 weeks and clinical relapse within 6 months. Results70% of patients achieved combined endoscopic/clinical response (responders). The reduction in PI, AUC, Pw and MTT between T1 and T0 was higher in responders. Relapsers (21%) showed significantly lower reduction in delta PI and Pw at T1 and T2. At T3 they showed a new increase in PI and lower reduction in delta Pw. In relapsers, AUC showed a significantly lower decrease at T2 and T3, TP showed a significant reduction at T3 and MTT showed a progressive increase at the different time-points, reaching the statistical significance at T3. Conclusionsd-CEUS might become a reliable predictor of combined endoscopic/clinical response and clinical relapse in CD.

Contrast-enhanced ultrasound perfusion patterns and serum lipid signatures of vulnerable carotid artery plaque in predicting stroke: A cohort study of carotid stenosis in Chinese patients.

Early identification of vulnerable plaques at risk of rupture could help prevent cerebral ischemic stroke in patients with carotid artery disease. To investigate the correlation between contrast-enhanced ultrasound (CEUS) perfusion patterns and serum lipid signatures of carotid artery plaques with the degree of carotid stenosis. A total of 80 patients with carotid artery plaques who underwent CEUS were included. All patients underwent CEUS, computed tomography angiography or digital subtraction angiography, and serum lipid testing. The contrast agent enhancement levels and the CEUS perfusion patterns in the plaques were associated with the degree of carotid stenosis (P < 0.05). Serum free fatty acid (FFA) was associated with the contrast agent enhancement levels (P < 0.05), but did not correlate with the degree of stenosis (P > 0.05). There was no significant difference in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides with respect to contrast agent enhancement levels (P > 0.05) or the degree of stenosis (P > 0.05). A high level of CEUS perfusion and increased serum FFA levels are indicative of vulnerable carotid plaques, which may be useful for the prediction of stroke in patients with carotid artery disease.

Assessment of neovascularization in atherosclerotic carotid sinus plaques using quantitative contrast-enhanced ultrasound perfusion imaging

Aim. To assess the prospects of using quantitative contrast-enhanced ultrasound perfusion imaging of atherosclerotic carotid sinus plaques. Material and methods. The study included 5 men and 1 woman (59-76 years old, median 72) with symptomatic coronary sinus atherosclerosis. The inclusion criterion was history of ischemic stroke due to internal carotid artery lesion (NASCET &gt;60%). We performed contrast-enhanced ultrasound perfusion imaging of the carotid arteries, endarterectomy, studying pathomorphology of the removed plaque with the calculation of the neovascular density and the total number of neovessels with a diameter &lt;40 μm. Neovascularization was assessed by quantitative contrast-enhanced ultrasound 20 seconds after the 1 ml infusion of Sonovia (Bracco, Italy) and subsequent application of the flash. The analysis of dynamics of ultrasonic signal intensity in the atherosclerotic plaque was carried out by creating the curves of the ultrasonic signal intensity (dB)/time (s) over 3 segments of the cross section of the internal carotid artery long axis. The automatic calculation of the intensity dynamics took into account the parameter values in the studied areas within 20 s after the flash. The calculated coefficients (A, B, β) of the exponential equation for 3 atherosclerotic segments were recorded. Results. Perfusion and neovascularization were assessed in 27 segments of atherosclerotic plaques. The correlation relationships between the ultrasonic parameters of plaque perfusion and the severity of neovascularization were assessed according to the histological data. Significant correlations of the exponential curve coefficient β and histological parameters characterizing the prevalence of “young” vessels (&lt;40 microns) in the atherosclerotic plaque were revealed. Spearman’s R for the density of neovessels was 0,54; for the number of neovessels with a diameter &lt;40 μm. —0,66 (p&lt;0,01). Conclusion. Diagnosis of atherosclerotic plaque neovascularization becomes possible to quantify, assessing not only the presence of neovascular vessels, but also the perfusion intensity. The novel approach replaces the qualitative and semi-quantitative method for calculating the number of carotid plaques neovessels in vivo.

Contrast-Enhanced Ultrasound to Detect Early Microvascular Changes in Skeletal Muscle after High-Dose Radiation Treatment.

The biological response of normal tissue to high-dose radiation treatment remains poorly understood. Alterations to the microenvironment, specifically the microvasculature, have been implicated as a significant contributor to tumoral cytotoxicity. We used contrast-enhanced ultrasound (CEU) perfusion imaging, which is uniquely suited to assess functional status of the microcirculation, to measure microvascular blood flow after high-dose irradiation to normal skeletal muscle tissue in a murine model. Proximal hindlimbs of wild-type C57Bl/6 mice were irradiated with a single fraction using 6 MV photons, 1 cm bolus and a dynamic wedge. Quantitative perfusion CEU imaging of the skeletal muscle was performed at days 1 and 8 postirradiation in three different regions of interest (ROIs): 1. 15 Gy external-beam irradiated leg; 2. 12 Gy irradiated 5 mm proximal area; 3. single ROI in the nonirradiated contralateral (CL) hindlimb. Perfusion imaging was also performed in the hindlimb of nonirradiated mice. CEU time-intensity data were analyzed to measure microvascular blood flow (MBF, also referred to as perfusion), and its parametric components of microvascular flux rate and functional microvascular blood volume (MBV). Plasma measurements of two potent vasoconstrictors, endothelin-1 and angiotensin II, were also performed to assess systemic response. CEU perfusion imaging values for the 12 and 15 Gy irradiated limb regions were pooled. At day 1, MBF in the irradiated limb was significantly lower than in the CL limb (P = 0.016) but quite similar to the nonirradiated mice. At day 8, both limbs of irradiated mice exhibited a trend towards lower MBF than the limbs of nonirradiated mice (28% decrease in mean MBF, P = 0.149 for CL; 39% decrease, P = 0.065 for irradiated limb). Compared to nonirradiated animals, the reduction in perfusion in irradiated limbs at day 8 may have been more influenced by the microvascular flux rate (25% decrease in the mean, P = 0.079) than the MBV (12% decrease in the mean, P = 0.328). Examination of vasoactive compounds revealed that the average plasma concentration for endothelin-1 at day 8 postirradiation was significantly higher in 14 irradiated animals than in 4 nonirradiated animals (3.07 pg/ ml vs. 2.51 pg/ml; P = 0.011). Up to day 8 after high-dose irradiation, flow deficits in irradiated muscle appear to be a consequence of increased vascular resistance more so than loss or functional de-recruitment of microvascular units.

Intra-observer and Device-Dependent Inter-observer Reliability of Contrast-Enhanced Ultrasound for Muscle Perfusion Quantification

Muscle perfusion quantification by contrast-enhanced ultrasound (CEUS) may facilitate treatment decisions in musculoskeletal disorders. Translation into clinical routine relies on high intra-observer and inter-observer reliability and transferability between ultrasound devices to enable validation and multicenter studies. This study evaluates these aspects for deltoid muscle perfusion quantification, including possible multicenter study setups. One hundred sixty-six CEUS quantifications were conducted on 42 shoulders. Intra-observer reliability revealed a high intra-class correlation coefficient (ICC, r = 0.91) and low coefficient of variation (CV, 10.28%). Inter-observer reliability revealed an ICC of .84 and a CV of 17.1%, but these values decreased when different ultrasound devices were used (ICC = .60, CV = 18.6%). Re-evaluating subgroups with high sectional plane concordance significantly increased reliability (intra-observer: ICC = .97, CV = 5.49%, inter-observer/same device: ICC = .98, CV = 5.83%, varying devices: ICC = .78, CV = 9.8%). CEUS perfusion quantification of the deltoid seems applicable for multicenter studies, yet pooling different ultrasound devices remains critical. Sectional plane concordance appears to be crucial for reliability and transferability of CEUS muscle perfusion quantifications.

Contrast-enhanced ultrasound detects changes in microvascular blood flow in adults with sickle cell disease

In patients with sickle cell disease (SCD), poor outcome measures compromise the potential success of clinical trials. Contrast-enhanced ultrasound (CEUS) is a technique that can non-invasively quantify deep tissue microvascular blood flow. We tested the hypothesis that CEUS of forearm skeletal muscle could be used to: 1) assess microvascular abnormalities that occur during vaso-occlusive crisis; and 2) test new therapies for SCD that are targeted to improving the status of the microcirculation. We performed a prospective study, CEUS perfusion imaging of resting forearm muscle was performed in adults with SCD: 1) during and after a pain episode, and 2) before, during, and after a 24-hour infusion of the investigative agent, regadenoson, an adenosine A2A agonist. CEUS destruction-replenishment time-intensity data were analyzed to measure microvascular blood flow, as well as its components, microvascular blood volume and flux rate. Serial CEUS measurements were obtained in 32 adults with SCD. For the studies during crisis, there was a 30% reduction in microvascular blood flow compared to steady-state (p = 0.031), a reduction that was largely due to microvascular flux rate. For the regadenoson group, a non-significant 25% increase in flux rate and 9% increase in microvascular blood flow compared to baseline were detected during infusion. In a study of adults with SCD, CEUS detected changes in microvascular blood flow associated with vaso-occlusive crises. No changes were found during an infusion of the adenosine A2A agonist, regadenoson. This study provides preliminary evidence that CEUS could detect blood flow changes consistent with SCD physiology.

Limb Perfusion During Exercise Assessed by Contrast Ultrasound Varies According to Symptom Severity in Patients with Peripheral Artery Disease

In patients with peripheral artery disease (PAD), the severity of symptoms correlates poorly with ankle-brachial index (ABI). The aim of this study was to test the hypothesis that limb perfusion assessed using contrast-enhanced ultrasound (CEU) during contractile exercise varies according to functional class in patients with PAD, particularly those with ABIs in the 0.4 to 0.6 range whose symptoms vary widely. Bilateral quantitative CEU perfusion imaging of the calf was performed in normal control subjects (n=10) and patients with PAD who had at least one limb with a moderately reduced ABI (0.4-0.6; n=17). Imaging was performed at rest and immediately after 30sec of modest periodic (0.3-Hz) plantar flexion (10W). In patients with PAD, Rutherford symptom classification for each limb varied widely, including in limbs with ABIs of 0.4 to 0.6 (n=6 with mild or no symptoms, n=14 with moderate to severe symptoms). CEU perfusion imaging parameters at rest were similar between control subjects and patients with PAD irrespective of ABI. In normal control subjects, limb flow increased on average by>20-fold after only 30sec of moderate exercise. In patients with PAD, muscle exercise perfusion for all limbs was reduced compared with control subjects and decreased according to the severity of ABI reduction, primarily from reduced microvascular flux rate. Even limbs with ABIs > 0.9 in patients with PAD had lower exercise perfusion than in control subjects (P=.03). In subjects with PAD, exercise perfusion was lower in those with moderate to severe versus mild symptoms when analyzed for all limbs (median, 30 IU/sec [interquartile range (IQR), 21-52 IU/sec] vs 84 IU/sec [IQR, 36-177 IU/sec]; P=.01) and limbs with ABIs of 0.4 to 0.6 (median, 26 IU/sec [IQR, 14-41 IU/sec] vs 54 IU/sec [IQR, 31-105 IU/sec]; P=.05). In patients with PAD, CEU exercise perfusion imaging detects differences in limb muscle perfusion that are likely to be responsible for differences in symptom severity and can detect the flow abnormalities from microvascular dysfunction even in limbs with normal ABIs.

Correlation between microvessel density and contrast-enhanced ultrasound perfusion parameters in hepatocellular carcinoma

Correlation between microvessel density and contrast-enhanced ultrasound perfusion parameters in hepatocellular carcinoma

3434 The Study of Fetal Tracheal Occlusion to Treat Congenital Diaphragmatic Hernia in the EXTEND Model

OBJECTIVES/SPECIFIC AIMS: The goal of this project is to study fetal pulmonary vasculature in a CDH animal model, to understand how FETO affects developing vasculature, and to develop a modifiable fetal tracheal occlusive therapeutic device that avoids previously seen sequelae of FETO, like alveolar distension, decreased surfactant production, and decreased Type II Pneumocytes. The primary outcome is lung volume/kilogram. The secondary outcomes are contrast-enhanced ultrasound perfusion metrics (Time to Peak, Mean Transit Time, Wash-in Rate, Wash-in Perfusion Index), pulmonary vascular density, Lung Injury Histology Scores, and Lung Compliance upon ventilation. METHODS/STUDY POPULATION: Congenital diaphragmatic hernias will be modeled by surgical hernia creation via maternal laparotomy and hysterotomy at gestational age 72 - 74 days. The ewe will undergo a second laparotomy at 105 - 115 days gestational age. After a second hysterotomy is made, the fetus will be removed from the amniotic sac, though placental circulation will be maintained (EXIT Procedure). The animal is cannulated via the umbilical vein and arteries onto the pumpless ECMO circuit. The balloon and pressure sensor complex is placed into the trachea via direct laryngoscopy, and the fetus aseptically sealed into the Biobag. The wires of the tracheal occlusive device (balloon catheter and pressure sensor) will egress via the port of the Biobag. The fetus remains in the Biobag for fourteen days, with the tracheal occlusive device in place for ten days, followed by a four day recovery period. Daily contrast-enhanced ultrasounds and pulmonary artery dopplers are performed. Upon study completion, the fetus is intubated and placed on a conventional ventilator. A full necropsy is then performed, with perfusion fixation of the lungs via the pulmonary artery. RESULTS/ANTICIPATED RESULTS: Hypothesis 1: Modifiable Tracheal Occlusion will have statistically different effects on developing lung parenchyma, surfactant production, and abundance of Type II Pneumocytes Hypothesis 2: Modifiable Tracheal Occlusion will have lower levels of pulmonary hypertension than negative control animals, as measured by contrast-enhanced ultrasound (pulmonary artery velocity and washout time). DISCUSSION/SIGNIFICANCE OF IMPACT: This project will provide insight into the development of pulmonary hypertension in the CDH fetus. It will provide insight into the physiology of FETO, a novel therapy for congenital diaphragmatic hernias, and will demonstrate the utility of the EXTEND System for fetal treatments that are not possible in the maternal uterus.

Can Contrast-Enhanced Ultrasound Increase or Predict the Success Rate of Testicular Sperm Aspiration in Patients With Azoospermia?

OBJECTIVE. The objective of our study was to determine whether contrast-enhanced ultrasound (CEUS) perfusion measurements obtained before testicular sperm aspiration (TESA) can improve or predict sperm retrieval (SR) outcomes of TESA in patients with azoospermia. SUBJECTS AND METHODS. Between May 2017 and January 2018, 70 patients with azoospermia (mean age, 29 years; age range, 22-41 years) underwent testes CEUS within 10 days before TESA. Major perfusion areas were visually chosen, and their ranges were recorded. The other areas were defined as minor perfusion. CEUS quantitative features were acquired for both the main perfusion area and whole testis. Testis tissue biopsies were taken for both major and minor perfusion areas by cognitive fusion, and SR outcomes were compared. Associations between testicular volume, quantitative CEUS features, and SR outcomes were analyzed. RESULTS. Twenty-four men were found to have obstructive azoospermia (OA), and the remaining 46 had nonobstructive azoospermia (NOA). All patients with OA had spermatozoa in biopsy. Only one patient with NOA had spermatozoa in the major perfusion area but not the minor perfusion area; the other patients with NOA had the same SR outcomes in both major and minor perfusion areas. In patients with NOA, both wash-in and washout CEUS features were correlated with the success of SR in TESA. CONCLUSION. CEUS-guided TESA with cognitive fusion cannot yield improved SR outcomes of TESA in patients with NOA, possibly because of imprecise correlation between biopsy sites and main perfusion area analyzed by CEUS; however, quantitative CEUS features can be useful predictors of the success of SR.

Value of Perfusion Parameters for Differentiating Hepatocellular Carcinoma and Liver Metastasis With Hypervascularity and a Normal Hepatic Background on Contrast-Enhanced Ultrasound Imaging.

To retrospectively evaluate the value of contrast-enhanced ultrasound (CEUS) perfusion parameters in the differential diagnosis of hepatocellular carcinomas (HCCs) and metastatic liver tumors (MLTs) with hypervascularity. Sixty-seven HCCs and 55 MLTs with arterial homogeneous/heterogeneous hyperenhancement on CEUS imaging and a normal liver background were included in this retrospective study. Six CEUS perfusion parameters were compared between HCCs and MLTs with different sizes and HCC differentiations: rise time (RT), time to peak (TTP), mean transit time, wash-out time (WT), maximum intensity (IMAX), and area under the curve (AUC). The area under the receiver operating characteristic curve (AUROC) was determined to compare the diagnostic efficacy of the parameters. The RT, TTP, and WT were significant longer and the IMAX and AUC were significantly higher in HCCs than in MLTs. In distinguishing between HCCs and MLTs, the AUROC was highest for the WT (0.922; sensitivity, 85.1%; specificity, 89.6%); the AUC and IMAX had the second and third highest AUROCs (AUC: 0.855; sensitivity, 76.1%; specificity, 80.6%; IMAX: 0.827; sensitivity, 76.1%; specificity, 77.6%). The AUROC was lowest for the TTP and RT (TTP: 0.719; sensitivity, 70.1%; specificity, 61.2%; RT: 0.707; sensitivity, 67.2%; specificity, 65.7%). In HCCs, both the tumor size and degree of differentiation affected the IMAX, AUC, and WT. In MLTs, perfusion parameters were not influenced by the tumor size. In HCCs and MLTs with hypervascularity and a normal liver background on CEUS imaging, various CEUS perfusion parameters, including IMAX, AUC, WT, RT, and TTP, differed significantly between tumor types. The WT may be the most useful parameter for differentiating between these tumors.

P256 Bowel contrast-enhanced ultrasound perfusion imaging in the evaluation of Crohn's disease patients

P256 Bowel contrast-enhanced ultrasound perfusion imaging in the evaluation of Crohn's disease patients

Contrast Enhanced Ultrasound Perfusion Imaging in Skeletal Muscle.

The ability to accurately evaluate skeletal muscle microvascular blood flow has broad clinical applications for understanding the regulation of skeletal muscle perfusion in health and disease states. Contrast-enhanced ultrasound (CEU) perfusion imaging, a technique originally developed to evaluate myocardial perfusion, is one of many techniques that have been applied to evaluate skeletal muscle perfusion. Among the advantages of CEU perfusion imaging of skeletal muscle is that it is rapid, safe and performed with equipment already present in most vascular medicine laboratories. The aim of this review is to discuss the use of CEU perfusion imaging in skeletal muscle. This article provides details of the protocols for CEU imaging in skeletal muscle, including two predominant methods for bolus and continuous infusion destruction-replenishment techniques. The importance of stress perfusion imaging will be highlighted, including a discussion of the methods used to produce hyperemic skeletal muscle blood flow. A broad overview of the disease states that have been studied in humans using CEU perfusion imaging of skeletal muscle will be presented including: (1) peripheral arterial disease; (2) sickle cell disease; (3) diabetes; and (4) heart failure. Finally, future applications of CEU imaging in skeletal muscle including therapeutic CEU imaging will be discussed along with technological developments needed to advance the field.

Influencing factors of quality in contrast-enhanced ultrasound quantitative perfusion analysis for hepatocellular carcinoma and a reproducibility study

Objective To investigate the influencing factors of quality in contrast-enhanced ultrasound (CEUS) perfusion analysis for hepatocellular carcinoma (HCC) and the reproducibility of using CEUS perfusion analysis on HCC. Methods A total of 136 HCC lesions were undergone CEUS perfusion analysis. Maximum intensity (Imax), rise time (RT), time to peak (TTP), mean transit time (mTT) and quality of fit (QOF) of HCC lesion, top-enhanced region inside HCC lesion and adjacent liver parenchyma were measured. The quality of perfusion analysis was classified into three grades Good (QOF>75%), Common [QOF (50%-75%)], and Poor (QOF<75%). Ultrasound machine, patients′ age, tumor depth, tumor size and tumor location were recorded and compared among the three groups. 20 consecutive patients with 20 HCC lesions were received CEUS perfusion analysis by two operators and another 20 consecutive HCC lesions were received CEUS perfusion analysis by one operator at different time. Intra-class correlation coefficient (ICC) was used to evaluate the reproducibility of inter- and intra- observer. Results Fifty-six HCC lesions were classified as Good , 39 as Common and 39 as Poor , respectively. Tumor size (P=0.015) and tumor location (P=0.041) were significantly different among the three groups. Tumor size >3.0 cm and tumor located in S3, S4b, S5, S6 were apt to gain a better QOF. No significant difference was found for the different ultrasound machine, tumor depth and patients′ age. For all CEUS perfusion analysis parameters of both lesion and adjacent parenchyma, intra-class correlation coefficient of inter-and intra-observer were higher than 0.90, the reproducibility of CEUS perfusion analysis was good. For Imax, RT and TTP in top-enhanced region inside HCC lesion, ICC of inter- and intra- observer was all higher than 0.90 (good). For mTT in highest enhanced area inside HCC lesion, ICC of inter- and intra-observer were 0.459 (poor), 0.609 (common), respectively. Conclusions The parameters of HCC quantitative perfusion analysis were reproducible in peripheral liver parenchyma and tumor, but the mTT repeatability was poor in the highest enhancement area of the tumor. The size and location of the lesion were the factors affecting quantitative analysis. The quantitative analysis of >3.0 cm and the tumor located in S3, S4b, S5, S6 in the liver were satisfactory. Key words: Carcinoma, hepatocellular/US; Phlebography; Reproducibility of results

Lipoprotein Apheresis Acutely Reverses Coronary Microvascular Dysfunction in Patients With Severe Hypercholesterolemia

ObjectivesThis study evaluated whether lipoprotein apheresis produces immediate changes in resting perfusion in subjects with severe hypercholesterolemia, and whether there is a difference in the response between peripheral and coronary microcirculations. BackgroundLipoprotein apheresis is used in patients with severe hypercholesterolemia to reduce plasma levels of low-density lipoprotein cholesterol. MethodsQuantitative contrast-enhanced ultrasound perfusion imaging of the myocardium at rest and skeletal muscle at rest and during calibrated contractile exercise was performed before and immediately after lipoprotein apheresis in 8 subjects with severe hypercholesterolemia, 7 of whom had a diagnosis of familial hypercholesterolemia. Myocardial perfusion imaging was also performed in 14 normal control subjects. Changes in myocardial work and left ventricular function were assessed by echocardiography. Ex vivo ovine coronary and femoral artery ring tension assays were assessed in the presence of pre- and post-apheresis plasma. ResultsApheresis acutely decreased low-density lipoprotein cholesterol (234.9 ± 103.2 mg/dl vs. 67.1 ± 49.5 mg/dl; p < 0.01) and oxidized phospholipid on apolipoprotein B-100 (60.2 ± 55.2 nmol/l vs. 47.0 ± 24.5 nmol/l; p = 0.01), and acutely increased resting myocardial perfusion (55.1 [95% confidence interval: 77.2 to 73.1] IU/s vs. 135 [95% confidence interval: 81.2 to 189.6] IU/s; p = 0.01), without changes in myocardial work. Myocardial longitudinal strain improved in those subjects with reduced pre-apheresis function. Skeletal muscle perfusion at rest and during contractile exercise was unchanged by apheresis. Acetylcholine-mediated dilation of ex vivo ovine coronary but not femoral arteries was impaired in pre-apheresis plasma and was completely reversed in post-apheresis plasma. ConclusionsLipoprotein apheresis produces an immediate improvement in coronary microvascular function, which increases myocardial perfusion and normalizes endothelial-dependent vasodilation. These changes are not observed in the periphery. (Acute Microvascular Changes With LDL Apheresis; NCT02388633)

Quantitative Evaluation of Hepatic Microvascular Perfusion after Ischemia–Reperfusion Injury in Rabbits by Contrast-Enhanced Ultrasound Perfusion Imaging

The aim of this study was to evaluate microvascular perfusion after liver ischemia–reperfusion injury (IRI) in rabbits using the “flash-replenishment” method of contrast-enhanced ultrasound (CEUS) perfusion imaging. Twenty-eight rabbits underwent either 30, 60 or 90 min of ischemia and 120 min of reperfusion. CEUS perfusion imaging was performed using the “flash-replenishment” model, and hepatic microvascular perfusion parameters, including peak intensity (PI), area under the curve (AUC), and hepatic artery-to-vein transit time (HA-HVTT), were calculated. Prolonged ischemia upregulated intracellular adhesion molecule-1 (ICAM-1), alanine transaminase (ALT) and aspartate transaminase (AST) levels. Longer ischemia decreased PI and AUC, but increased HA-HVTT. The perfusion parameters were significantly correlated with Suzuki's pathology scores and ALT and AST levels. The “flash-replenishment” method of CEUS perfusion imaging is an accurate and non-invasive method for evaluating hepatic microvascular perfusion and provides a valuable experimental basis for early prediction of liver IRI damage after liver transplantation or liver resection.

Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion.

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

Skeletal and myocardial microvascular blood flow in hydroxycarbamide-treated patients with sickle cell disease.

In sickle cell disease (SCD), abnormal microvascular function combined with chronic anaemia predisposes patients to perfusion-demand mismatch. We hypothesized that skeletal muscle and myocardial perfusion, normalized to the degree of anaemia, is reduced at basal-state compared to controls, and that this defect is ameliorated by hydroxycarbamide (HC; also termed hydroxyurea) therapy. Twenty-one SCD patients, of whom 15 were treated with HC, and 27 controls underwent contrast-enhanced ultrasound (CEU) perfusion imaging of the forearm as well as the myocardium. HC treatment was associated with lower white cell and reticulocyte counts, and higher fetal haemoglobin and total haemoglobin levels. When corrected for the degree of anaemia in SCD patients, skeletal flow in HC-treated patients was significantly higher than in untreated SCD patients (217·7±125·4 vs. 85·9±40·2, P=0·018). Similarly, when normalized for both anaemia and increased myocardial work, resting myocardial perfusion was also significantly higher in HC-treated patients compared with untreated SCD patients (0·53±0·47 vs. 0·13±0·07, P=0·028). Haemoglobin F (HbF) levels correlated with skeletal muscle microvascular flow (r=0·55, P=0·01). In conclusion, patients with SCD not on HC therapy have resting flow deficits in both skeletal muscle and myocardial flow. HC therapy normalizes flow and there is a direct correlation with HbF levels. Clinical trial registration ClinicalTrials.gov Identifier: NCT01602809; https://clinicaltrials.gov/ct2/show/NCT01602809?term=sACHDEV&rank=9.

Analysis of Contrast-Enhanced Ultrasound Perfusion Patterns and Time-Intensity Curves for Metastatic Lymph Nodes From Lung Cancer: Preliminary Results.

To retrospectively summarize the similarities and differences in contrast-enhanced ultrasound (US) findings for lymph node metastasis from adenocarcinoma, squamous carcinoma, and small cell lung cancer. Patients who had received contrast-enhanced US examinations and had a histologic diagnosis of supraclavicular lymph node metastasis from lung cancer were included. The perfusion patterns on contrast-enhanced US images and time-intensity curve parameters were analyzed for the different pathologic types. The microvascular density and microvascular diameter were evaluated. Totally, 61 patients were enrolled in this study, including 26 cases with lung squamous carcinoma, 26 with lung adenocarcinoma, and 9 with small cell lung cancer. Contrast-enhanced US perfusion showed no significant differences in enhancement uniformity during the arterial phase and in the presence of unenhanced areas of metastatic lymph nodes with the 3 different pathologic origins (P > .05), but fewer unenhanced areas could be seen in metastatic lymph nodes from adenocarcinoma. The analysis of the time-intensity curve parameters showed that there were significant differences in the peak intensity between metastatic lymph nodes from lung squamous carcinoma and lung adenocarcinoma (P < .05). The microvascular density of metastatic lymph nodes from adenocarcinoma was significantly higher than that of metastatic lymph nodes from squamous carcinoma and small cell lung cancer (P < .001; P = .0444), whereas the microvascular diameter of metastatic lymph nodes from adenocarcinoma was significantly smaller than that from squamous carcinoma and small cell lung cancer (P = .0277; P < .001). Effects of the pathologic diagnosis should be considered when analyzing quantitative parameters of metastatic lymph nodes during contrast-enhanced US examinations, even in the same organ.

Exercise versus vasodilator stress limb perfusion imaging for the assessment of peripheral artery disease.

Our aim was to determine whether pharmacologic vasodilation is an alternative to exercise stress during limb perfusion imaging for peripheral artery disease (PAD). Quantitative contrast-enhanced ultrasound (CEU) perfusion imaging of the bilateral anterior thigh and calf was performed in nine control subjects and nine patients with moderate to severe PAD at rest and during vasodilator stress with dipyridamole. For those who were able, CEU of the calf was then performed during modest plantar flexion exercise (20watts). CEU time-intensity data were analyzed to quantify microvascular blood flow (MBF) and its parametric components of microvascular blood volume and flux rate. Thigh and calf skeletal muscle MBF at rest was similar between control and PAD patients. During dipyridamole, MBF increased minimally (<twofold) for all groups and there were only nonsignificant trends for a reduction in calf MBF in those with PAD (13.5±6.9, 10.0±4.7, and 8.2±6.1IU/s, for controls, moderate, and severe PAD, respectively; P=.11). In contrast, MBF during modest planar flexion exercise increased markedly in controls but not PAD patients (87.9±79.9 vs 15.2±12.9 IU/s, P<.05). In three moderate PAD patients restudied after undergoing surgical revascularization, MBF during dipyridamole did not change, whereas exercise MBF increased by an average of sevenfold. Resting limb skeletal muscle MBF in patients with moderate to severe PAD is similar to that in normal subjects. However, differences in hyperemic flow during contractile exercise but not during dipyridamole allow evaluation of the degree of flow impairment from PAD and the degree of improvement with revascularization.