Wash-in Perfusion Index Research Articles

Dynamic Contrast-Enhanced Magnetic Resonance Enterography and Dynamic Contrast-Enhanced Ultrasonography in Crohn's Disease: An Observational Comparison Study.

Purpose e Cross-sectional imaging methods are important for objective evaluationof small intestinal inflammationinCrohn'sdisease(CD).The primary aim was to compare relative parameters of intestinal perfusion between contrast-enhanced ultrasonography (CEUS) and dynamic contrast-enhanced magnetic resonance enterography (DCE-MRE) in CD. Furthermore, we aimed at testing the repeatability of regions of interest (ROIs) for CEUS. Methods This prospective study included 25 patients: 12 females (age: 37, range: 19-66) with moderate to severe CD and a bowel wall thickness>3mm evaluated with DCE-MRE and CEUS. CEUS bolus injection was performed twice for repeatability and analyzed in VueBox®. Correlations between modalities were described with Spearman's rho, limits of agreement(LoA) and intraclass correlation coefficient(ICC). ROIrepeatability for CEUS was assessed. Results s The correlation between modalities was good and very good for bowel wall thickness (ICC=0.71, P<0.001) and length of the inflamed segment (ICC=0.89, P<0.001). Moderate-weak correlations were found for the time-intensity curve parameters: peak intensity (r=0.59, P=0.006), maximum wash-in-rate (r=0.62, P=0.004), and wash-in perfusion index (r=0.47, P=0.036). Best CEUS repeatability for peak enhancement was a mean difference of 0.73 dB (95% CI: 0.17 to 1.28, P=0.01) and 95% LoA from -3.8 to 5.3 dB. Good quality of curve fit improved LoA to -2.3 to 2.8 dB. Conclusion The relative perfusion of small intestinal CD assessed with DCE-MRE and CEUS shows only a moderate correlation. Applying strict criteria for ROIs is important and allows for good CEUS repeatability.

Chronic liver disease: Quantitative MRI vsCEUS-based microperfusion.

To compare the diagnostic performance of MRI-based T1 relaxometry with dynamic contrast-enhanced ultrasound (CEUS)-based liver microcirculation for evaluation of liver function. 22 patients underwent Gd-EOB-DTPA-enhanced MRI with T1 relaxometry and previous or consecutive CEUS examinations. A transverse 3D VIBE sequence with an inline T1 calculation was acquired and the reduction rate of T1 relaxation time (rrT1) was evaluated. For CEUS measurements (1-6 MHz), a bolus injection of 1.4 ml sulfur hexafluoride microbubbles were administered and both cine loops and single images from arterial phase up to late phase were stored.Quantification of time to peak (TTP), rise time (RT), Wash- In Area Under the Curve (WiAUC), mean transit time (mTTI), the wash- in rate (WiR) and Wash-in perfusion index (WIPI)) was performed using a novel quantification software (VueBoxTM). To compare quantification parameters, patients were classified in patients representing a healthy population (rrT1 > 50%, n = 8) and those representing patients with liver disease (rrT1 < 50%, n = 14). Comparing perfusion parameters TTP, mTTI, and WiR were higher in patients without liver disease compared to patients with impaired liver function (p = 0.10-0.21). RT, WiAUC and WIPI were significantly lower in patients with impaired liver function (RT, 14.8±1.5 s; WiAUC, 17288±6179 a.u., WIPI, 1243±423) compared to patients without liver disease (RT, 21.2±2.6 s, p = 0.032; WiAUC, 71534±25600, p = 0.034; WIPI, 4286±1748, p = 0.04). In a simple linear regression model, none of the perfusion parameters correlated significantly with rrT1 (p = 0.08-0.63). Within the framework of this study, CEUS-based perfusion parameters were not able to assess severity of liver disease, however, WiAUC, RT and WIPI were significant perfusion parameters to make a rough assessment of liver function.

Early Changes in Contrast Enhanced Ultrasound Predict for Pathologic Response to Chemotherapy in an Animal Tumor Model

The purpose of this study was to examine CEUS whether could earlier predict pathologic response to chemotherapy than morphologic method in a MCF-7 tumor model. Twenty MCF-7 breast cancer bearing nude mice were included in this study. Animals received either adriamycin or a control substance were imaged before and after treatment with an ultrasound scanner after bolus injection of SonoVue. Dynamic contrast enhanced ultrasound was performed at pretherapy, Day 3, Day 5 and Day 7 after adriamycin administration. Regions of interest within the tumor were analyzed off-line to determine perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WIAUC), wash-in rate (WIR), wash-in perfusion index (WIPI) and quality of fit (QOF). The section equivalent to ultrasound imaging plane was stained with Hematoxylin and Eosin to allow for assessment of tumor cell density and Ki67 for situation of tumor proliferation, CD34 for tumor micro-vascular density. There were no significant differences in tumors perfusion and tumor volumes before treatment. Treatment with adriamycin resulted into a significant decrease in PE, WIAUC, WIR and WIPI in comparison with control group (P < 0.05) at Day 3, when there was no significant difference in tumor volume. The volume of treated tumors was significant smaller than that of control tumors (P < 0.05) at day 7. The tumor cell density estimated by pathology slice was significantly lower in treated tumors than in control tumors at day 7 (P < 0.05). The positive Ki67 cell density and CD34 estimated by pathology slice were also significantly lower in treated tumors than in control tumors at day 7 (P < 0.05). The correlation between micro-vascular and perfusion parameters was obvious (P < 0.05). Changes in tumor micro-vessel functionality as depicted by CEUS early on after starting adriamycin -based chemotherapy can predict final pathologic response. Contrast enhanced ultrasound will be a new way for evaluating tumor response to chemoth.

Contrast-Enhanced Ultrasound (CEUS) Determines Supraspinatus Muscle Atrophy after Cuff Repair

Muscle degeneration following rotator cuff tears is mainly assessed by MRI. Contrast-enhanced ultrasound (CEUS) as functional imaging can assess microvascular perfusion which represents muscle tissue vitality. In this cross-sectional study we evaluated the supraspinatus muscle perfusion after cuff repair and analyzed its association to the grade of echogenicity in B-mode ultrasound indicating fatty infiltration and the functional shoulder outcome. Patients that received unilateral refixation of the supraspinatus were invited for a single follow-up, functional scores such as Constant-Score (CS) were assessed. CEUS examination was performed bilaterally in an oblique sagittal plane of the supraspinatus fossa. Perfusion was quantified with parameters like Wash-in-Perfusion-Index (WiPI) and Peak Enhancement (PE) using VueBox quantification software. Function and perfusion were referenced to the contralateral shoulder and correlated. Echogenicity was classified in a three-point scale compared to the trapezius muscle. 67 patients were available with a mean follow-up of 38.0±18.5 months. The function of the operated shoulder was worse than contralaterally (relative CS: 80±19%). CEUS revealed diminished perfusion on the operated shoulder (WiPI, 55.1±40.2%, p<.001). A strong correlation could be demonstrated between the perfusion deficit and the functional impairment (relative WiPI and CS: rs= .644, p< .001). Higher grade of echogenicity was associated to lower perfusion. CEUS is able to visualize the impaired supraspinatus muscle perfusion after rotator cuff repair. With its ability to quantify microvascular perfusion as a surrogate parameter for muscle vitality and function, CEUS may serve as an ultrasound-based method to perioperatively evaluate rotator cuff muscles.

Dynamic contrast-enhanced ultrasound and elastography assess deltoid muscle integrity after reverse shoulder arthroplasty

The outcome after reverse shoulder arthroplasty (RSA) depends on the condition of the deltoid muscle, which we assessed with new ultrasound modalities and electromyography (EMG). Contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) were applied to assess perfusion and elasticity of the deltoid muscle compared with the clinical and functional outcome. The study recruited 64 patients (mean age, 72.9 years) treated with RSA between 2004 and 2013. The deltoid muscle was examined with EMG and ultrasound imaging. Functional scores such as Constant score and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score were assessed. Among other CEUS parameters, the wash-in perfusion index, time to peak, and rise time were compared between the operated-on and contralateral shoulders as well as between patients with above-average and below-average outcome. The stiffness of the deltoid muscle was analyzed with ARFI. After RSA, deltoid perfusion (wash-in perfusion index, Δ = -12% ± 22%, P = .0001) and shoulder function (Constant score, Δ = -14 ± 24, P < .0001) were both inferior compared with the contralateral side. This perfusion deficit was associated with a limited range of motion (time to peak and anteversion: r = -0.290, P = .022). Deltoid perfusion was higher in patients with above-average outcome (rise time, Δ = 33% ± 13%, P = .038). The operated-on deltoid muscles showed higher stiffness than the contralateral muscles (ARFI, Δ = 0.2 ± 0.9 m/s, P = .0545). EMG excluded functionally relevant axillary nerve injuries in the study population. CEUS revealed reduced mean perfusion of the deltoid muscle after RSA. Reduced perfusion was associated with limited range of motion and below-average outcome. Functional shoulder impairment after RSA might be predicted by noninvasive CEUS as a surrogate parameter for the integrity of the deltoid muscle.

Quantitative dynamic contrast-enhanced ultrasound for the functional evaluation of the skeletal muscle microcirculation in systemic sclerosis.

The purpose was to evaluate skeletal muscle microcirculation by means of quantitative dynamic contrast-enhanced ultrasound (DCEUS) in patients with systemic sclerosis (SSc). DCEUS imaging of the gastrocnemius muscle was performed with phospholipid-stabilized microbubbles filled with sulfur hexafluoride in 12 patients with SSc and 12 healthy volunteers. The fitted time intensity curves (TIC) during the first 3 minutes after administration of the contrast agent bolus were analysed. Time course parameters of the TIC were compared between patients and healthy volunteers. Peak enhancement, wash-in area under the curve and was-out area under the curve was decreased in the patient group versus healthy volunteers (168 versus 248 AU p = 0.291; 2193 versus 3314 p = 0.198; 4948 AU x sec versus 8948 AU x sec p = 0.037). In the SSc patients the mean transit time and wash-in perfusion index were numerically, but not statistically lower than in the healthy volunteers, but rise and fall time were similar. On the microvascular level in SSc patients versus their healthy counterpart key parameters related to blood volume were decreased and perfusion parameters showed a slight diminishment in the patient population. These results suggest a component of impaired skeletal muscle microcirculation in SSc patients.

Quantitative perfusion analysis in pancreatic contrast enhanced ultrasound (DCE-US): a promising tool for the differentiation between autoimmune pancreatitis and pancreatic cancer.

In the work-up of focal pancreatic lesions autoimmune pancreatitis (AIP) is a rare differential diagnosis to pancreatic cancer (PC) with similar clinical constellations. The aim of our study was to compare differences between proven AIP and PC using transabdominal dynamic contrast enhanced ultrasound (DCE-US). Therefore we recorded 3-minute-clips of CEUS examinations and analyzed perfusion parameters with VueBox®-quantification software. To obtain DCE-US Parameters, Regions-of-Interest were selected within the lesions and the surrounding pancreas parenchyma, serving as reference tissue. We compared 3 patients with AIP (mean age: 58 years; lesion mean size: 40 mm) to 17 patients with PC (mean age: 68 years; lesion mean size: 35.9 mm). Significant differences between PC and parenchyma could be found in the following parameters: Peak-Enhancement (PE), Wash-in-and-Wash-out-AUC, Wash-in Perfusion-Index. PE of AIP was comparable to normal parenchyma. The relation of PE between parenchyma and lesion (ΔPE) AIP and PC was significantly different [AIP: 0.21 (±0.06); PC: 0.81 (±0.1); p<0.01]. PE of neoplastic lesions was significantly lower as AIP and normal parenchyma (p<0.01). Therefore perfusion analysis in DCE-US can help to differentiate hypovascular PC from AIP presenting nearly isovascular time intensity curves. Diagnostic accuracy of DCE-US in this setting has to be validated in future prospective studies in comparison to CT and MRI.

Quantitative Contrast-Enhanced Ultrasonic Imaging Reflects Microvascularization in Hepatocellular Carcinoma and Prognosis after Resection

Our aim was to evaluate the correlation between tumor vasculature detected by pre-surgical contrast-enhanced ultrasonography and the post-surgical prognosis of patients with hepatocellular carcinoma. One hundred ninety-five patients with hepatocellular carcinoma who had undergone curative resection and pre-operative contrast-enhanced ultrasonography were enrolled. Intra-tumoral microvessels were evaluated by immunohistochemical staining for anti-CD31 and anti-CD34. On the basis of the immunohistochemical staining and morphology patterns, tumors were divided into capillary-like and sinusoid-like microvessel subtypes. The rise time of tumors was shorter in the capillary-like microvessel subtype than in the sinusoid-like microvasculature subtype (p = 0.026). Intra-tumor microvascular density (p < 0.001, hazard ratio = 0.137) and rise time (p = 0.006, hazard ratio = 2.475) were independent factors corresponding to different microvasculature types. Microvascular density, vascular invasion and wash-in perfusion index were determined to be independent factors in recurrence-free survival and overall survival. In conclusion, contrast-enhanced ultrasonography may serve as a means of non-invasive assessment of tumor angiogenesis and may be associated with the survival of patients with hepatocellular carcinoma after resection.

Dose-response relationship in cisplatin-treated breast cancer xenografts monitored with dynamic contrast-enhanced ultrasound.

BackgroundExactly assessing tumor response to different dose of chemotherapy would help to tailor therapy for individual patients. This study was to determine the feasibility of dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of tumor vascular response to different dose cisplatin.MethodsMCF-7 breast cancer bearing mice were treated with different dose of cisplatin in group B (1 mg/kg) and group C (3 mg/kg). A control group A was given with saline. Sequential CEUS was performed on days 0, 3 and 7 of the treatment, in which time-signal intensity curves were obtained from the intratumoral and depth-matched liver parenchyma. Peak enhancement (PE), area under the curve of wash-in (WiAUC), wash-in rate (WiR) and wash-in perfusion index (WiPI) were calculated from perfusion time-intensity curves and normalized with respect to the adjacent liver parenchyma. Histopathological analysis was conducted to evaluate tumor cell density and microvascular density (MVD).ResultsSignificant decreases in tumor normalized perfusion parameters were observed on day 3 in the high dose group and on day 7 in the low dose group. On day 7, nPE, nWiAUC, and nWiPI significantly decreased in group C and group B as compared with group A (P < 0.05), and further decreased in group C as compared with group B (P < 0.05). Significant decreases of tumor cell density and MVD were seen in treated group (group B and C) compared to control group (P < 0.05) and further decrease in group C compared to group B (P < 0.05).ConclusionsDynamic CEUS for quantification of tumor perfusion could be used to evaluate tumor vascular response to different dose of chemotherapy.

Quantitative contrast-enhanced harmonic EUS in differential diagnosis of focal pancreatic masses (with videos)

The role of EUS with contrast agents can be expanded through the use of time-intensity curve (TIC) analysis and computer-aided interpretation. To validate the use of parameters derived from TIC analysis in an artificial neural network (ANN) classification model designed to diagnose pancreatic carcinoma (PC) and chronic pancreatitis (CP). Prospective, multicenter, observational trial-endoscopy units from Romania, Denmark, Germany, and Spain. A total of 167 consecutive patients with PC or CP. Contrast-enhanced harmonic EUS (CEH-EUS) and EUS-guided FNA (EUS-FNA), TIC analysis, andANN processing. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) for EUS-FNA, CEH-EUS, and the ANN. After excluding all of the recordings that did not meet the technical and procedural criteria, 112 cases of PCand 55 cases of CP were included. EUS-FNA was performed in 129 patients, and the diagnosis was confirmed by surgery (n= 15) or follow-up (n= 23) in the remaining cases. Its sensitivity and specificity were 84.82% and100%, respectively, whereas the PPV and NPV were 100% and 76.63%, respectively. The sensitivity of real-time quantitative assessment of CEH-EUS was 87.5%, specificity 92.72%, PPV 96.07%, and NPV 78.46%. Peak enhancement, wash-in area under the curve, wash-in rate, and the wash-in perfusion index were significantly different between the groups. No significant differences were found between rise time, mean transit time, and time to peak. For the ANN, sensitivity was 94.64%, specificity 94.44%, PPV 97.24%, and NPV 89.47%. Only PC and CP lesions were included. Parameters obtained through TIC analysis can differentiate between PC and CP cases and can beused in an automated computer-aided diagnostic system with good diagnostic results. ( NCT01315548.).

Preliminary results of contrast-enhanced sonography in the evaluation of the response of uveal melanoma to gamma-knife radiosurgery.

Our aim was to prospectively analyze the use of contrast-enhanced ultrasound (CEUS) in the quantitative assessment of the response of uveal melanoma (UM) to gamma-knife radiosurgery (GKR), investigating whether changes in tumor vascularization precede thickness reduction, which on average occurs at 12 months after GKR. Ten patients with UM treated with GKR underwent sonography (US) and CEUS at baseline and at 3, 6, and 12 months after GKR. The transverse diameter, thickness, and quantitative parameters of the UM (ie, area under the curve in the wash-in phase, wash-in perfusion index, peak enhancement, and wash-in rate) were calculated by using dedicated software and compared by using Wilcoxon's signed-rank test. The mean tumor thickness on US was significantly less at both 6 (6.6 mm) and 12 months after GKR (5.8 mm) than it was at baseline (8.3 mm; p < 0.05, both comparisons). Compared with baseline data, the median flow quantitative parameters on CEUS were significantly changed as follows: the peak enhancement (in arbitrary units [au]) at baseline was 5 × 10(6) ; 6 months after GKR, it was 2 × 10(1) (p < 0.05), and 12 months after GKR, it was 4 × 10(1) (p < 0.05). The wash-in rate (in au) at baseline was 1 × 10(6) ; 6 months after GKR, it was 2.1 (p < 0.05), and 12 months after GKR, it was 9.3 (p < 0.05). The wash-in perfusion index (in au) at baseline was 2 × 10(7) ; 6 months after GKR, it was 7 × 10(1) (p < 0.05), and 12 months after GKR, it was 1 × 10(2) (p < 0.05). The area under the curve during the wash-in phase (in au) at baseline was 1 × 10(8) ; 12 months after GKR, it was reduced to 6 × 10(2) (p < 0.05). At 6 months after GKR, a reduction of tumor thickness, as detected on US, occurred in 6 of the 10 patients, whereas a reduction in all the quantitative parameters measured on CEUS occurred in all 10 patients. However, a larger population is needed to investigate whether CEUS could become the first-choice technique for monitoring the response of UM to GKR.

Monitoring parotid gland tumors with a new perfusion software for contrast-enhanced ultrasound.

Contrast enhanced ultrasound (CE-US) is a promising imaging modality for non-invasive analysis of functional vascularisation. Lesions of the parotid gland are associated with a vascularisation that differs from normal gland tissue. The aim of this clinical study was to further analyse the perfusion in parotid gland lesions with CE-US. The new quantification software VueBox (Bracco, Italy) was used to assess the perfusion, based on DICOM datasets of CE-US examination. CE-US measurements were performed by intravenous application of a contrast agent (SonoVue, Bracco, Italy) before surgical tumor resection. From the analysis of a time sequence of 2D DICOM contrast images, area under time intensity curve (AUC), peak enhancement (PE), wash-in-rate (WiR) and wash-in-perfusion-index (WiPI) were calculated using VueBox. These were correlated with the histological analyses of the tumor tissue. Significant difference of area below intensity time curve (AUC), peak enhancement (PE), wash-in-rate (WiR) and wash-in perfusion index (WiPI) were observed in the malign lesions compared to benign tumors (p < 0,05) and in pleomorphic adenoma compared to cystadenolymphoma (p < 0,05). CE-US seems to be a quantitative and independent method for discriminating between malign and benign parotid gland tumors.

Contrast-enhanced US quantitatively detects changes of tumor perfusion in a murine breast cancer model during adriamycin chemotherapy

Currently used morphologic criteria have limitations in assessing tumor response to chemotherapy because of the relatively slow tumor shrinkage as measured by conventional morphologic imaging. Functional imaging techniques show promising results in early assessment of tumor response to treatment. To quantitatively detect changes in tumor perfusion during chemotherapy with contrast-enhanced ultrasound. Twenty-three MCF-7 breast cancer bearing nude mice treated by either adriamycin (n = 11) or sterile saline (n = 12) were imaged before and after treatment with an ultrasound scanner after bolus injection of SonoVue. Regions of interest within the tumor were analyzed offline to determine perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), rise time (RT), wash-in rate (WiR), wash-in perfusion index (WiPI), and quality of fit (QOF). Hematoxylin and eosin was used to assess tumor cell density and immunohistochemical analysis was performed for evaluation of microvascular density (MVD). Treatment with adriamycin significantly reduced tumor growth in comparison to the control group (P < 0.001). There was no significant difference in perfusion parameters before treatment. Treatment with adriamycin resulted in a significant decrease in PE, WiAUC, WiR, and WiPI in comparison with control group (P < 0.01). The tumor cell density estimated by pathology slice was significantly lower in treated tumors than in control tumors after treatment (P < 0.001). Immunohistochemistry showed significant decreases of MVD in treated tumors as compared with control tumors (P < 0.001) after treatment. Quantitative contrast-enhanced ultrasound can detect the change of tumor perfusion after chemotherapy, which may enable early assess tumor response to chemotherapy.

Assessment of Early Tumor Response to Cytotoxic Chemotherapy with Dynamic Contrast-Enhanced Ultrasound in Human Breast Cancer Xenografts

There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy. This study was to quantify tumor perfusion changes with dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of early tumor response to cytotoxic chemotherapy. Sixty nude mice bearing with MCF-7 breast cancer were administrated with either adriamycin or sterile saline. CEUS was performed on days 0, 2, 4 and 6 of the treatment, in which time-signal intensity (SI) curves were obtained from the intratumoral and depth-matched liver parenchyma. Four perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), wash-in rate (WiR) and wash-in perfusion index (WiPI) were calculated from perfusion curves and normalized with respect to perfusion of adjacent liver parenchyma. Histopathological analysis was conducted to evaluate tumor perfusion, tumor cell density, microvascular density (MVD) and proliferating cell density. Significant decreases of tumor normalized perfusion parameters (i.e., nPE, nWiAUC, nWiR and nWiPI) were noticed between adriamycin-treated and control groups (P<0.01) 2 days after therapy. There were significant differences of tumor volumes between control and treated groups on day 6 (P<0.001) while there were no significant differences in tumor volume on days 0, 2 and 4 (P>0.05). Significant decreases of tumor perfusion, tumor cell density, MVD and proliferating cell density were seen in adrianycin-treated group 2 days after therapy when compared to control group (P<0.001). Dynamic CEUS for quantification of tumor perfusion could be used for early detection of cancer response to cytotoxic chemotherapy prior to notable tumor shrinkage.