Wash-in Area Under The Curve Research Articles

Assessing tumor angiogenesis in colorectal cancer by quantitative contrast-enhanced endoscopic ultrasound and molecular and immunohistochemical analysis.

Background and Objectives:Data on contrast-enhanced endoscopic ultrasound (CE-EUS) for colorectal cancer (CRC) evaluation are scarce. Therefore, we aimed to assess the vascular perfusion pattern in CRC by quantitative CE-EUS and compare it to immunohistochemical and genetic markers of angiogenesis.Patients and Methods:We performed a retrospective analysis of CE-EUS examinations of 42 CRC patients, before any therapy. CE-EUS movies were processed using a dedicated software. Ten parameters were automatically generated from the time-intensity curve (TIC) analysis: peak enhancement (PE), rise time (RT), mean transit time, time to peak (TTP), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-in perfusion index (WiPI), wash-out AUC (WoAUC), and wash-in and wash-out AUC (WiWoAUC). The expression levels of the vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2 genes were assessed from biopsy samples harvested during colonoscopy. Microvascular density and vascular area were calculated after CD31 and CD105 immunostaining.Results:Forty-two CE-EUS video sequences were analyzed. We found positive correlations between the parameters PE, WiAUC, WiR, WiPI, WoAUC, WiWoAUC, and N staging (Spearman r = 0.437, r = 0.336, r = 0.462, r = 0.437, r = 0.358, and r = 0.378, respectively, P < 0.05), and also between RT and TTP and CD31 vascular area (r = 0.415, and r = 0.421, respectively, P < 0.05). VEGFR1 and VEGFR2 expression did not correlate with any of the TIC parameters.Conclusions:CE-EUS with TIC analysis enables minimally invasive assessment of CRC angiogenesis and may provide information regarding the lymph nodes invasion. However, further studies are needed for defining its role in the evaluation of CRC patients.

Anti-angiogenic therapy with contrast-enhanced ultrasound in colorectal cancer patients with liver metastasis.

The aim of the study was to evaluate the efficacy of anti-angiogenic therapy with dynamic contrast-enhanced ultrasound (DCE-US) in colorectal cancer (CRC) patients with liver metastasis.A total of 50 CRC patients with liver metastasis who received bevacizumab (BEV)-based chemotherapy (BEV + FOLFOX6 protocol) were recruited into the present study. Before the study (d0), and 3, 7, 14, and 42 days (d3, d7, d14, and d42) after chemotherapy, DCE-US was performed, and tumor perfusion was evaluated quantitatively by retention time (RT), peak enhancement (PE), and wash-in area under the curve (WiAUC) on the basis of a contrast-uptake curve determined with original linear data.Routine ultrasonography was used to evaluate metastatic foci in the liver at baseline. A metastatic focus was selected for dynamic monitoring with ultrasound. The metastatic foci were 1.5 to 8 cm (median: 2.5 cm). The results of hemodynamics monitored at different time points, including RT, PE, and WiAUC, showed that RT at baseline was significantly different between groups (P < .001; Responder group: 10.54 seconds; nonresponder group: 15.33 seconds). The2 groups had opposite changes in RT (continuous increase in the responder group and transient reduction in the nonresponder). The RT of metastatic foci was normalized to that of adjacent normal liver as standard RT-quotient, a similar trend was observed, and no marked difference was noted in the standard RT-quotient between the 2 groups. The median progression-free survival was significantly higher in the increased-RT group (10.8 months) than the decreased-RT group (2.5 months) (P = .002). There were no significant differences in peak intensity and WiAUC between the 2 groups.DCE-US can be used to quantitatively evaluate the hemodynamics of liver metastasis in CRC patients who received bevacizumab-based chemotherapy.

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.

Postoperative evaluation of microvascularization in mandibular reconstructions with microvascular flaps – First results with a new perfusion software for contrast-enhanced sonography (CEUS)

Quantitative measurement of dynamic contrast values obtained by contrast-enhanced ultrasound (CEUS) for evaluating microvascularization in osseous and osseocutaneous free flaps used for maxillofacial reconstructions. 22 patients (6 women, 16 men, mean age: 57 years, range: 47 to 82 years) who had received mandibular reconstructions with 3 avascular and 19 microvascular free osseous or osseocutaneous transplants were included in this trial. 16 patients had received a microvascular osseocutaneous fibular flap, 2 patients a microvascular osseous fibular flap and 1 patient a microvascular osseous iliac crest flap. Patients were followed up for 12 months on average (range: 3 to 20 months). Ultrasound examination was carried out by one experienced examiner with a linear probe (6-9 MHz, LOGIQ E9, GE) after the intravenous bolus injection of 2.4 ml contrast agent (SonoVue®, BRACCO, Germany). Digital cine loops were analysed with a quantification software (VueBox™) for determining wash-in parameters: Rise Time (RT), Peak Enhancement (PE), Wash-in Area Under the Curve (WiAUC) and Wash-in Rate (WiR). Results were compared with the patients' postoperative clinical outcome. For the bone area the median of the RT was 10.0 s (range 3.1 to 65.0 s), for the ratio between bone tissue and soft tissue for the PE the median was 10.4% (range 2.6 to 29.8%), the median for the WiAUC was 11.1% (range 1.5 to 77.7%) and the median for the WiR was 5.7 %(range 0.7 to 61.1%). None of the patients with microvascular osseocutaneous and osseous flaps showed any signs of transplant bone loss, which corresponded with the qualitative CEUS assessment. The patients with microvascular re-anastomosed transplants showed widely varying values for the investigated parameters (RT, PE, WiAUC, WiR). For patients with avascular bone transplants, these parameters were reduced to zero values for the bone area resulting in a significant difference (p < 0.05) for the PE compared to the patients with microvascular bone transplants. CEUS allowed the qualitative assessment of bone microvascularization by observing the transition of the contrast agent from the periostal area into the bone. However, defining a critical lower border by quantification of bone perfusion was difficult because of the inconstant perfusion of the bone transplants used in the trial.