Quantitative Contrast-enhanced Ultrasonography Research Articles

Role of early assessment of antiangiogenic treatment in metastatic colorectal cancer using quantitative contrast-enhanced ultrasonography

Objective To investigate the application of contrast-enhanced ultrasonograhy(CEUS) in the early assessment of antiangiogenic treatment in metastatic colorectal cancer. Methods Among 41 colorectal cancer patients with liver metastases enrolled in this study, 25 patients received treatment of antiangiogenic treatment(bevacizumab) combined with chemotherapy (BV group) and 16 patients received chemotherapy only (non-BV group). To assess the treatment responses in the liver lesions between and within these two groups, CEUS scans were performed before the treatment (T0 or baseline ), on the day 2 (T1), and on the day 7 (T2) after the treatment. The percentage differences were evaluated according to the CEUS quantitative parameters, such as rise time(RT), peak intensity(PI), mean transit time(MTT), area under the curve(AUC), time from peak to one half(TPH), wash in slope(WIS), and time to peak(TTP). Results On T1, both the RT and MTT increased within the BV group and decrease within the non-BV group, when compared with their own baselines, the differences were statistically significant (P 0.05). Conclusions CEUS can be used to assess the treatment response in liver metastatic patients with colorectal cancer, by monitoring the change of the tumor perfusion before and after the treatment. Key words: Contrast-enhanced ultrasonography; Colorectal neoplasms; Bevacizumab; Response evaluation

Accuracy of Contrast-enhanced US for Differentiating Benign from Malignant Solid Small Renal Masses.

To test the hypothesis that qualitative and quantitative features of contrast material-enhanced ultrasonography (US) can be used to differentiate benign from malignant small renal masses. This is an institutional review board approved, HIPAA-compliant prospective study with written informed consent. Patients with histologically characterized solid small renal masses, excluding lipid-rich angiomyolipomas, underwent qualitative contrast-enhanced US with a combination of three different US machines. A subgroup of patients underwent quantitative contrast-enhanced US. Patients received a bolus injection of 0.2 mL of contrast material for qualitative and quantitative evaluations and were followed for 3 minutes. Two radiologists independently reviewed videotaped qualitative contrast-enhanced US examinations and were blinded to the final diagnoses. Features that were evaluated included lesion vascularity relative to the adjacent cortex in the arterial phase, the presence of a capsule, homogeneity, the pattern of vascularity, and washout. One radiologist separately reviewed a subset of contrast-enhanced US examinations that were performed with all three machines. Parameters of a first-pass time intensity curve were calculated for quantitative analysis. The Mann-Whitney test was used for quantitative parameters, the χ(2) or Fisher exact test was used for qualitative parameters, and κ statistics and Fleiss methodology were used to determine interobserver and intermachine agreement. The study population consisted of 91 patients (35 women and 56 men) with 94 lesions. The mean age was 62 years ± 14 (range, 21-91). Three patients had two lesions each, which were evaluated at two different sessions. There were 26 benign small renal masses (including 18 oncocytomas, seven lipid-poor angiomyolipomas, and one hemangioblastoma) and 68 malignant masses (including 41 clear cell, 20 papillary, and seven chromophobe renal cell carcinomas [RCCs[) that were 1.1-4.0 cm in diameter (mean, 2.7 cm ± 0.9). All patients underwent contrast-enhanced US on the same one machine, and 68 patients were imaged on all three machines. Vascularity was present in all lesions (n = 94) at contrast-enhanced US. Lesion hypovascularity relative to the adjacent cortex in the arterial phase was seen in only malignant lesions by both reviewers; reviewer 1 saw hypovascularity in 24 of 94 lesions (P = .0001), and reviewer 2 saw hypovascularity in 21 of 94 lesions (P = .0006), for a specificity of 100% (95% confidence interval [CI]: 84, 100). This feature had κ values of 0.91 (95%CI: 0.82, 1.00) between the two reviewers and 0.85 (95% CI: 0.72, 0.99) between the three machines. Eighteen of 20 papillary RCCs were hypovascular. Quantitative parameters of area under the receiver operating characteristics curve, peak intensity, wash-in slope of 10%-90% and 5%-45%, and washout slope of 100%-10% and 50%-10% were significantly higher in malignant renal masses (P = .018, P = .002, P = .036, P = .016, P = .001, and P = .005, respectively) than in benign lesions. Excluding lipid-rich angiomyolipoma, hypovascularity-which has high interobserver and intermachine agreement-of solid small renal masses relative to the cortex in the arterial phase has 100% specificity (95% CI: 84, 100) for detecting malignancy, most often papillary RCC.

Value of contrast-enhanced ultrasound on assessment of limb muscle crush injury: an animal experiment

Objective To explore the diagnostic value of quantitative contrast-enhanced ultrasonography(CEUS) for crush injury in the hind limb muscle of rabbits. Methods A totle of 120 New Zealand white rabbits were randomized to receive compression on the left hind limb for either 2 h(n=56) or 4 h(n=56) to induce muscle crush injury, another 8 animals were not injured and served as normal controls. CEUS parameters such as peak intensity(PI), area under curve(AUC), ascending slop(AS) and descending slop(DS) were measured at 0.5 h, 2 h, 6 h, 24 h, 3 d, 7 d, 14 d after decompression. Results Compared with the uninjured muscle, reperfusion of the injured muscles showed early and high enhancement in CEUS. The time-intensity curve showed a trend of rapid lift and gradual drop. The PI and AUC values differed significantly among the three groups and were positively correlated with serum and tissue biomarkers. Rabbits of the 4 h compression group showed significantly higher PI and AUC values compared with the 2 h compression group at each time points. Conclusions CEUS can effectively detect muscle crush injury and monitor dynamic changes of the injured muscle in rabbits.PI and AUC are promising diagnostic parameters for this disease. CEUS might play an important role in the pre-hospital and bedside settings for the diagnosis of muscle crush injury. Key words: Ultrasonography; Microbubbles; Muscle; Crush injury

A novel simple noninvasive index to predict renal transplant acute rejection by contrast-enhanced ultrasonography.

This study aimed to evaluate the application of quantitative contrast-enhanced ultrasonography (CEUS) in the assessment of renal allograft dysfunction and to establish a new noninvasive index to predict acute rejection (AR). Fifty-seven renal transplant recipients were enrolled in this prospective study. Before renal allograft biopsy, CEUS examinations were performed.The biopsy results proved 23 cases of AR (AR group), 10 cases of acute tubular necrosis (ATN group), and 24 with normal evolution (stable group). Contrast-enhanced ultrasonography parameters including rising time (RT), time to peak (TTP), and the delta-time among regions of interest (ΔRT and ΔTTP) were analyzed. In the AR group, RT and TTP of interlobar artery and medulla (RTi, RTm, TTPi, and TTPm) as well as ΔRT and ΔTTP between medulla and cortex (ΔRTm-c and ΔTTPm-c) were significantly higher compared with those in the stable group. RTm and TTPm as well as ΔRTm-c and ΔTTPm-c were remarkably higher compared with those in the ATN group. ΔRTm-c and estimated glomerular filtration rate (eGFR) were identified as independent predictors by multivariate analysis (P = 0.008 and P = 0.024). On the basis of the multivariate analysis results and area under the receiver operating characteristic curves of individual markers, we constructed a new simple index, P = -0.587 + 0.286 ×ΔRTm-c − 0.028 × eGFR; new index = e(P)/(1 + e(P)), to discriminate AR, which had better area under the receiver operating characteristic curves than eGFR or individual CEUS parameters. Contrast-enhanced ultrasonography parameters are reliable markers for differentiating the perfusion status of transplanted kidneys. Furthermore, the new simple index can easily predictAR with a high degree of accuracy.

The effect of anesthesia with propofol and sedation with butorphanol on quantitative contrast-enhanced ultrasonography of the healthy feline kidney

Contrast-enhanced ultrasonography of the left kidney was performed using a commercial contrast agent in six healthy adult purpose-bred cats. A cross-over design was used to compare three protocols: (1) awake, (2) butorphanol (0.4 mg/kg IM), and (3) propofol (3.5–7.7 mg/kg IV boluses to effect). Time–intensity curves were created from two regions-of-interest drawn in the renal cortex. The curves were analyzed for blood flow parameters representing blood volume (base intensity, peak intensity, area-under-curve) and blood velocity (arrival time, time-to-peak, wash-in/out).There was no difference in the subjective enhancement pattern between the three protocols. No significant effect of butorphanol was observed in any of the perfusion parameters (P > 0.05). Propofol did not influence the most important perfusion parameter, area-under-the-curve, and is adequate for use in contrast-enhanced ultrasound studies.

Differential diagnosis of nonpalpable testicular lesions: qualitative and quantitative contrast-enhanced US of benign and malignant testicular tumors.

To evaluate the diagnostic accuracy of unenhanced and quantitative contrast-enhanced ultrasonography (US) in the differential diagnosis of small nonpalpable testicular lesions. The local review board approved the protocol, and all patients provided written informed consent. One hundred fifteen patients (median age, 34 years; age range, 14-61 years) with nonpalpable testicular lesions were consecutively enrolled between 2006 and 2012 and underwent unenhanced scrotal US, contrast-enhanced US, surgical enucleation, and at least 18 months of follow-up. Clinical and histologic features were recorded, and qualitative and quantitative analysis of contrast-enhanced US time-intensity curves were performed. Logistic regression analysis was performed to explore features of malignancy. Receiver operating characteristic ( ROC receiver operating characteristic ) curves were developed for cumulative unenhanced and contrast-enhanced US scores. All lesions were 1.5 cm or smaller. Forty-four of the 115 patients (38%) had malignant tumors, 42 had benign tumors (37%), and 29 (25%) had nonneoplastic lesions. The features at unenhanced US that enabled the best differentiation of tumors versus nonneoplastic lesions and benign versus malignant tumors were parenchymal microlithiasis (26 of 86 patients with tumors vs five of 29 patients with nonneoplastic lesions [P = .178]; four of 42 patients with benign lesions vs 22 of 44 patients with malignant tumors [P < .001]), irregular margins (26 of 86 patients with tumors vs three of 29 patients with nonneoplastic lesions [P < .001]; eight of 42 patients with benign lesions vs 18 of 44 patients with malignant tumors [P < .001]), and internal vascularization (70 of 86 patients with tumors vs seven of 29 patients with nonneoplastic lesions [P < .001]; 28 of 42 patients with benign lesions vs 42 of 44 patients with malignant tumors [P < .001]). For contrast-enhanced US, the rapidity of wash-in (34 of 44 patients vs 15 of 42 patients, P < .001) and washout (33 of 44 patients vs five of 42 patients, P < .001) were the parameters that best differentiated malignant from benign tumors, with a typical prolonged washout observed in Leydig cell tumors (12 of 21 patients, P < .001 when compared with seminomas). Overall, the combination of unenhanced and contrast-enhanced US achieved a high accuracy in the diagnosis of small testicular malignancies (area under the ROC receiver operating characteristic curve performance: 0.927; 95% confidence interval: 0.872, 0.981). Benign testicular tumors are frequent incidental findings. Quantitative scrotal contrast-enhanced US is a noninvasive diagnostic tool that could improve the differential diagnosis and individualized management of small testicular lesions.

Use of quantitative contrast-enhanced ultrasonography to detect diffuse renal changes in Beagles with iatrogenic hypercortisolism

To determine the feasibility of quantitative contrast-enhanced ultrasonography (CEUS) for detection of changes in renal blood flow in dogs before and after hydrocortisone administration. 11 Beagles. Dogs were randomly assigned to 2 treatment groups: oral administration of hydrocortisone (9.6 mg/kg; n = 6) or a placebo (5; control group) twice a day for 4 months, after which the dose was tapered until treatment cessation at 6 months. Before treatment began and at 1, 4, and 6 months after, CEUS of the left kidney was performed by IV injection of ultrasonography microbubbles. Images were digitized, and time-intensity curves were generated from regions of interest in the renal cortex and medulla. Changes in blood flow were determined as measured via contrast agent (baseline [background] intensity, peak intensity, area under the curve, arrival time of contrast agent, time-to-peak intensity, and speed of contrast agent transport). Significant increases in peak intensity, compared with that in control dogs, were observed in the renal cortex and medulla of hydrocortisone-treated dogs 1 and 4 months after treatment began. Baseline intensity changed similarly. A significant increase from control values was also apparent in area under the curve for the renal cortex 4 months after hydrocortisone treatment began and in the renal medulla 1 and 4 months after treatment began. A significant time effect with typical time course was observed, corresponding with the period during which hydrocortisone was administered. No difference was evident in the other variables between treated and control dogs. Quantitative CEUS allowed detection of differences in certain markers of renal blood flow between dogs treated orally with and without hydrocortisone. Additional studies are needed to investigate the usefulness of quantitative CEUS in the diagnosis of diffuse renal lesions.

Antiangiogenic effects of pazopanib in xenograft hepatocellular carcinoma models: evaluation by quantitative contrast-enhanced ultrasonography

BackgroundAntiangiogenesis is a promising therapy for advanced hepatocellular carcinoma (HCC), but the effects are difficult to be evaluated. Pazopanib (GW786034B) is a pan-vascular endothelial growth factor receptor inhibitor, the antitumor effects or antiangiogenic effects haven't been investigated in HCC.MethodsIn vitro direct effects of pazopanib on human HCC cell lines and endothelial cells were evaluated. In vivo antitumor effects were evaluated in three xenograft nude mice models. In the subcutaneous HCCLM3 model, intratumoral blood perfusion was detected by contrast-enhanced ultrasonography (CEUS), and serial quantitative parameters were profiled from the time-intensity curves of ultrasonograms.ResultsIn vitro proliferation of various HCC cell lines were not inhibited by pazopanib. Pazopanib inhibited migration and invasion and induced apoptosis significantly in two HCC cell lines, HCCLM3 and PLC/PRF/5. Proliferation, migration, and tubule formation of human umbilical vein endothelial cells were inhibited by pazopanib in a dose-dependent manner. In vivo tumor growth was significantly inhibited by pazopanib in HCCLM3, HepG2, and PLC/PRF/5 xenograft models. Various intratumoral perfusion parameters changed over time, and the signal intensity was significantly impaired in the treated tumors before the treatment efficacy on tumor size could be observed. Mean transit time of the contrast media in hotspot areas of the tumors was reversely correlated with intratumoral microvessel density.ConclusionsAntitumor effects of pazopanib in HCC xenografts may owe to its antiangiogenic effects, and the in vivo antiangiogenic effects could be evaluated by quantitative CEUS.

New frontiers in pediatric oncologic imaging

As imaging technologies advance, a paradigm shift is emerging in the assessment of tumor response to therapy. The traditional method of measuring tumor size may not reflect changes in tumor viability induced by chemotherapy and radiation therapy. Today's oncologists and radiologists seek objective methods for assessing tumor metabolism and blood flow, measures that provide earlier, more accurate information about treatment effects. Pediatric imaging presents unique challenges not encountered in adult imaging, including the need for sedation and consideration of the long-term effects of radiation exposure in a growing child. Therefore, the potential risks and benefits of new imaging approaches for monitoring anticancer treatment in children require careful consideration. Several new imaging techniques are currently under investigation for use in pediatric oncology. These include dynamic enhanced magnetic resonance imaging and quantitative contrast-enhanced ultrasonography for assessment of blood flow in solid tumors such as osteosarcoma and neuroblastoma, and nuclear imaging, including positron emission tomography–computed tomography, for assessment of pediatric musculoskeletal tumors and neuroblastoma. The potential value, relative advantages, and limitations of these new methods in monitoring anticancer therapy in children are discussed.

Pathologic Skeletal Muscle Perfusion in Patients with Myositis: Detection with Quantitative Contrast-enhanced US—Initial Results

To prospectively determine whether contrast material-enhanced ultrasonography (US) can depict inflammation-induced changes in muscle perfusion for patients suspected of having dermatomyositis or polymyositis and to compare these findings with those of magnetic resonance (MR) imaging and muscle biopsy. Institutional review board approval and informed consent were obtained. Perfusion in skeletal muscles was quantified with contrast-enhanced intermittent power Doppler US by applying a modified model that analyzed the replenishment kinetics of microbubbles. In 22 patients (16 women, six men; mean age, 52 years +/- 17) who were suspected of having myositis and in 10 healthy volunteers (two women, eight men; mean age, 28 years +/- 4), contrast-enhanced US of the clinically affected right biceps muscle was performed to measure blood flow, blood volume, and blood flow velocity. Additionally, the right upper arm was examined with a 1.5-T unit by using three different MR imaging techniques. Findings were compared with the results of clinical examinations and muscle biopsy. Data for perfusion-related parameters obtained at contrast-enhanced US were analyzed by using a nonparametric Mann-Whitney U test. Eight patients had histologically confirmed myositis and showed significantly higher blood flow velocity (P = .01), blood flow (P = .001), and blood volume (P = .002) at contrast-enhanced US than did patients who did not have myositis. Blood flow velocity (P = .001) and blood flow (P = .002) were significantly higher in patients with myositis than in volunteers. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis, while contrast material enhancement on fat-suppressed T1-weighted MR images was found in only four of seven patients with myositis. Initial results show that contrast-enhanced US is a feasible method for noninvasively demonstrating increased perfusion in the involved muscle groups in patients with myositis.