iopromide and Neovascularization--Pathologic

Evaluation of transarterial chemoembolization (TACE) by using contrast-enhanced ultrasound (CEUS) and volume perfusion computed tomography (VPCT) as methods that display tumor vascularization.. To assess early results of TACE in patients with hepatocellular carcinoma (HCC) using CEUS and VPCT.. Twenty patients with HCC underwent CEUS and VPCT in the pre- and post-TACE setting (1 day). Hepatic perfusion index (HPI), arterial liver perfusion (ALP), blood flow (BF), and blood volume (BV) were measured with VPCT. Peak intensity (PI), time-to-peak (TTP), and regional blood flow (RBF) were measured with CEUS. Sensitivity, specificity, negative and positive predictive values, and cutoff values for these parameters were calculated. Immediate tumor response after TACE was classified as responder or non-responder. Results were compared with those at follow-up after 2 and 4 months (FU2mo/FU4mo) following modified RECIST.. CEUS and VPCT showed comparable immediate post-TACE results in 20/20 cases. Complete response was confirmed in 10/20 patients at FU2mo and in 9/20 at FU4mo. For responders, reduction in HPI, ALP, BV, and BF at day 1 post TACE proved significant (P < 0.001). For non-responders, the course of all VPCT parameters proved non-significant. A cutoff of 40% reduction in HPI and a reduction in ALP of >29.6%, in BV of >41.4%, or in BF of >53.1% was indicative of response according to FU2mo. For responders only, changes in PI (P < 0.001), TTP (P < 0.01), and BF (P < 0.01) proved significant whereas for non-responders, all CEUS parameters proved non-significant.. CEUS performs equally to VPCT for assessment of early response to TACE in HCC by a lesion-by-lesion assessment and showed prognostic value at mid-term.

Topics: Aged; Aged, 80 and over; Blood Volume; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cone-Beam Computed Tomography; Contrast Media; Female; Humans; Iohexol; Liver Neoplasms; Male; Middle Aged; Neovascularization, Pathologic; Predictive Value of Tests; Regional Blood Flow; Sensitivity and Specificity; Treatment Outcome; Ultrasonography

Hypoxia inducible factor-1 alpha (HIF-1α) plays a critical role in tumoral angiogenesis and HIF-1α overexpression is associated with an increased risk of patient mortality in many cancers. A number of studies have introduced perfusion computed tomography (CT) as a monitoring modality for antiangiogenic therapy.. To investigate significance of volumetric perfusion CT parameters in relationship to HIF-1α expression in VX2 tumor rabbit models.. Twenty VX2 carcinoma tumors of bilateral back muscles of 10 rabbits were evaluated with serial volumetric perfusion CT in 7, 10, and 14 days after tumor implantation. CT perfusion data were analyzed to calculate blood flow (BF), blood volume (BV), and permeability surface area product (PS) of whole tumor and non-necrotic peripheral area (periphery). Immunohistochemical analysis of HIF-1α expression and microvessel density (MVD) was performed.. HIF-1α was expressed in 12 tumors; two, three, and seven tumors classified as scores 1, 2 and 3, respectively. Mean MVD was 24.85 ± 13.7. PS of both the whole tumor and periphery showed positive correlations with HIF-1α score (r = 0.41, P = 0.046; r = 0.43, P = 0.002, respectively). BV of periphery showed a negative correlation with HIF-1α (r = -0.48, P = 0.040). There was strong positive correlation between HIF-1α expression and MVD (r = 0.82, P < 0.001).. In VX2 tumors, volumetric perfusion CT parameters were of limited value for the prediction of HIF-1α activity although HIF-1α expression was found to be weakly positively correlated with PS and negatively correlated with BV.

Topics: Animals; Cone-Beam Computed Tomography; Contrast Media; Disease Models, Animal; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Iohexol; Microvessels; Neovascularization, Pathologic; Rabbits; Soft Tissue Neoplasms

The preoperative evaluation of tumor grading and angiogenesis has important clinical implications in the treatment and prognosis of patients with colorectal cancers (CRCs). The aim of the present study was to assess tumor perfusion with 256-slice computed tomography (CT) using whole-volume perfusion technology before surgery, and to investigate the differences in the perfusion parameters among tumor grades and the correlation between perfusion parameters and pathologic results in CRC.. Thirty-seven patients with CRC confirmed by endoscopic pathology underwent whole-volume perfusion CT assessments with a 256-slice CT and surgery. Quantitative values for blood flow, blood volume, and time to peak were determined using commercial software. After surgery, resected specimens were analyzed immunohistochemically with CD105 antibodies for the quantification of microvessel density (MVD). The difference in CT perfusion parameters and MVD among different tumor differentiation grades was evaluated by the Student-Newman-Keuls test. The correlations between CT perfusion parameters and MVD were evaluated using the Pearson correlation analysis.. The mean blood flow was significantly different among well, moderately, and poorly differentiated groups (61.17 ± 17.97, 34.80 ± 13.06, and 22.24 ± 9.31 mL/minute/100 g, respectively; P < .05). The blood volume in the well-differentiated group was significantly higher than that in the moderately differentiated group (33.96 ± 24.81 vs. 16.93 ± 5.73 mL/100 g; P = .002) and that in the poorly differentiated group (33.96 ± 24.81 vs. 18.05 ± 6.01 mL/100 g; P = .009). The time to peak in the poorly differentiated group was significantly longer than that in the well-differentiated group (27.81 ± 11.95 vs. 17.60 ± 8.53 seconds; P = .016) and that in the moderately differentiated group (27.81 ± 11.95 vs. 18.94 ± 7.47 seconds; P = .028). There was no significant difference in the MVD among well, moderately, and poorly differentiated groups (33.47 ± 14.69, 28.89 ± 11.82, and 29.89 ± 11.02, respectively; P > .05). There was no significant correlation between CT perfusion parameters and MVD (r = 0.201, 0.295, and -0.178, respectively; P = .233, .076, and .292, respectively).. CT whole-volume perfusion technology has the potential to evaluate pathologic differentiation grade of CRC before surgery. However, preoperative perfusion CT parameters do not reflect the MVD of CRC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Colon; Colorectal Neoplasms; Contrast Media; Female; Humans; Image Processing, Computer-Assisted; Iohexol; Male; Microvessels; Middle Aged; Neoplasm Grading; Neovascularization, Pathologic; Prospective Studies; Radiographic Image Enhancement; Rectum; Tomography, X-Ray Computed

CT perfusion imaging has been used in diagnosis and classification of tumors widely and in assess tumor angiogenesis in some organs. However, there are few reports describing CT perfusion imaging of adrenal gland tumors.. This study aimed to evaluate the application of CT perfusion imaging in analysis of angiogenesis in adrenal tumors and in diagnosis of adrenal tumors.. Forty four patients with adrenal gland tumors (26 with adenomas and 18 with nonadenomas) were enrolled in this study. CT scan of adrenal glands was performed with the perfusion of non-ionic contrast medium Ultravist. The obtained images were processed with deconvolution algorithms-based perfusion software and then perfusion parameter maps and values (blood flow, blood volume, mean transit time, and permeability surface-area production) were generated and analyzed respectively.. Univariate multivariate logistic regression indicated that blood volume (OR: 1.261, 95% CI: 1.056, 1.505, P=0.010) was associated with the likelihood of adrenal adenoma. Receiver operating characteristic analysis showed that the blood volume value of ≥9.325 ml min(-1) 100 g(-1) predicted adrenal adenoma with sensitivity of 76.9% and specificity of 73.2%. In addition, permeability surface-area production in adenoma was higher than in non-adenoma (27.11±15.45 vs. 16.76±14.44 ml min(-1) 100 g(-1), P<0.05). The other parameters had no clear prognostic significance.. CT perfusion imaging can quantitatively distinguish adrenal gland tumors with different histological characteristics. Especially, blood volume can be used in differentiating adrenal adenomas from nonadenomas.

Topics: Adenoma; Adrenal Gland Neoplasms; Algorithms; Blood Volume; Contrast Media; Diagnosis, Differential; Female; Humans; Iohexol; Logistic Models; Male; Middle Aged; Neovascularization, Pathologic; Radiographic Image Interpretation, Computer-Assisted; ROC Curve; Sensitivity and Specificity; Software; Tomography, X-Ray Computed

Although hepatocellular carcinoma (HCC) demonstrates characteristic hypervascularity, some HCCs have a hypovascular pattern on computed tomography (CT). Cytokeratin 19 (CK19) is a marker for the biliary phenotype reflecting a poor prognosis. We assessed the prognostic implications of tumor vascularity and its association with CK19 expression in HCC.. Patients that underwent surgical resection for HCC were included. Tumor vascularity was evaluated according to the arterial enhancement patterns on CT scans and CK19 expression was evaluated by using tissue microarray methods.. One hundred and forty patients were included. Their median follow-up duration was 55.0 months, and 92 (65.7%) patients had tumor recurrence. Forty-five patients (30.6%) had hypovascular HCC at the time of diagnosis, and they showed a significantly higher CK19 expression rate (32.5% vs. 8.2%, P = 0.001) and earlier recurrence rate within 6 months (hazard ratio (HR), 2.301; P = 0.025) compared to the patients with hypervascular HCCs. Hypovascularity (HR, 1.694; P = 0.045) was an independent risk factor for short overall survival.. Hypovascular HCCs were associated with early recurrence and short overall survival, and CK19 was more frequently expressed in hypovascular HCC than in hypervascular tumors. Therefore, tumor vascularity on CT images might be utilized in determining the prognosis of patients with HCCs.

Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Chi-Square Distribution; Contrast Media; Female; Humans; Iohexol; Keratin-19; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neovascularization, Pathologic; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome

To investigate the correlation between vascular endothelial cell growth factor (VEGF) expression and first-pass perfusion parameters at multidetector computed tomography (MDCT) using a low-dose technique, and to determine how to discriminate VEGF positivity from VEGF negativity by perfusion CT in oesophageal squamous cell carcinomas.. Thirty-two patients with oesophageal squamous cell carcinomas underwent first-pass perfusion with 64-section MDCT at 50 mAs. Perfusion parameters, including perfusion, peak enhanced density (PED), time to peak (TTP), and blood volume (BV), were measured. Postoperative specimens were assessed for VEGF expression. Correlation tests were performed to determine the associations between each CT perfusion parameter and VEGF expression. The cut-off values of perfusion parameters were obtained statistically to discriminate VEGF positivity from VEGF negativity.. Mean perfusion, PED, TTP, and BV were 38.47 ± 30.26 ml/min/ml, 24.68 ± 9.65 HU, 28.35 ± 9.03 s, and 11.82 ± 6.06 ml/100 g, respectively. PED or BV were significantly higher in the VEGF-positive group than in the VEGF-negative group (all p < 0.05), but no significant difference in perfusion or TTP was found between the VEGF-positive and VEGF-negative groups (all p > 0.05). In VEGF positivity, PED and BV were correlated with VEGF expression (r = 0.576 and 0.765, respectively; all p < 0.05), whereas perfusion and TTP were not (r = 0.361 and 0.239, respectively; all p > 0.05). A threshold of BV (10.23 ml/100 g) achieved a sensitivity of 94.4%, and a specificity of 92.9% for discriminating VEGF positivity from VEGF negativity.. BV could reflect tumour VEGF expression, and could be an indicator for evaluating angiogenesis in oesophageal tumours.

Topics: Adult; Aged; Aged, 80 and over; Blood Volume; Carcinoma, Squamous Cell; Contrast Media; Esophageal Neoplasms; Female; Humans; Iohexol; Male; Middle Aged; Multidetector Computed Tomography; Neovascularization, Pathologic; Prospective Studies; Radiographic Image Interpretation, Computer-Assisted; Vascular Endothelial Growth Factor A

The purpose of this article is to measure perfusion parameters, including transit constant (K(trans)), in untreated follicular and diffuse large B cell lymphoma using volume perfusion CT, to establish their discriminating role and to search for a possible histopathologic background.. Between January 2010 and June 2011, 46 consecutive patients with untreated histologically confirmed follicular lymphoma (n = 16) or diffuse large B cell lymphoma (n = 30) were enrolled. A 40-second volume perfusion CT of the tumor bulk using 6.9-cm z-axis coverage and a total of 26 volume measurements was performed. Blood flow (BF), blood volume (BV), and K(trans) were determined. Tumor size was recorded as the product of long- and short-axis diameters. In 13 of 46 patients, pathologic specimens of an appropriate size were available for assessment of microvessel density (MVD) and microvascular luminal diameter for comparison with volume perfusion CT measurements.. Mean BF, BV, and K(trans) values were significantly higher in follicular lymphoma than in diffuse large B cell lymphoma, even after controlling for patient age and tumor size (p < 0.05, respectively). Although MVD was slightly, but not significantly, higher in follicular lymphoma versus diffuse large B cell lymphoma (p > 0.05), microvascular luminal diameter was significantly larger in follicular lymphoma than in diffuse large B cell lymphoma (p < 0.05). We defined cutoff values for BF, BV, and K(trans). If the cutoff points are met for all three parameters, the overall accuracy for correctly identifying diffuse large B cell lymphoma and follicular lymphoma was 90.5% and 87.5%, respectively.. Volume perfusion CT allows assessment of differences in vascularity of follicular and diffuse large B cell lymphomas, reflecting vascular luminal variability and histopathologic anatomy.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Blood Flow Velocity; Blood Volume; Contrast Media; Female; Humans; Immunohistochemistry; Iohexol; Least-Squares Analysis; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Neovascularization, Pathologic; Tomography, X-Ray Computed

To assess correlations between whole tumour first-pass perfusion parameters obtained with 64-row multidetector computed tomography (MDCT), and microvessel density (MVD) in oesophageal squamous cell carcinoma.. Thirty-one consecutive patients with surgically confirmed oesophageal squamous cell carcinomas were enrolled into our study. All the patients underwent whole tumour first-pass perfusion scan with 64-row MDCT. Perfusion parameters, including perfusion (PF), peak enhanced density (PED), blood volume (BV), and time to peak (TTP) were measured using Philips perfusion software. Postoperative tumour specimens were assessed for MVD. Pearson correlation coefficient tests were performed to determine correlations between each perfusion parameter and MVD.. Mean values for PF, PED, BV and TTP of the whole tumour were 28.85 ± 20.29 ml/min/ml, 23.16 ± 8.09 HU, 12.13 ± 5.21 ml/100g, and 35.05 ± 13.85 s, respectively. Mean MVD in whole tumour at magnification (×200) was 15.75 ± 4.34 microvessel/tumour sample (vessels/0.723 mm(2)). PED and BV were correlated with MVD (r=0.651 and r=0.977, respectively, all p<0.05). However, PF and TTP were not correlated with MVD (r=0.070 and r=0.100, respectively, all p>0.05).. The BV value of first-pass perfusion CT could reflect MVD in oesophageal squamous cell carcinoma, and can be an indicator for evaluating the tumour angiogenesis.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Contrast Media; Esophageal Neoplasms; Female; Humans; Immunoenzyme Techniques; Iohexol; Male; Middle Aged; Multidetector Computed Tomography; Neoplasm Staging; Neovascularization, Pathologic; Radiographic Image Interpretation, Computer-Assisted; Reproducibility of Results

This study was designed to determine the optimal blending method and parameters to fuse computed tomography (CT) data sets with different energy levels in dual-energy CT (DECT) for the detection of hypervascular liver lesions.. A liver agar phantom containing 8 conical tubes with various concentrations of contrast material, was scanned using a Somatom Definition Dual Source CT (DSCT; Siemens, Forchheim, Germany) scanner in the dual energy mode at different current settings. CT data sets obtained at voltage potentials of 80 kVp and 140 kVp were fused using the linear blending method and nonlinear method with different weighting factors (0.1, 0.3, 0.5, 0.7, and 0.9) and different parameters sets (A--lambda: 20, omega: 430; B--lambda: 20, omega: 70; C--lambda: 250, omega: 430; D--lambda: 250, omega: 70). In 20 patients with hepatocellular carcinomas, multiphasic liver CT scans including arterial, portal, and equilibrium phases were performed. DECT was used only during the arterial phase but a voltage potential of 120 kVp was used for both the portal and equilibrium phases. For quantitative analyses of the phantom and patient study, the contrast-to-noise ratio (CNR) of the lesion to liver on arterial phase images, was measured. For qualitative analysis of the CT images of the 20 study patients, 5 radiologists, each with a different level of clinical experience, independently assessed the 5 types of image sets regarding lesion conspicuity and overall image quality. This study followed the guidelines of our hospital's institutional review board, and patient informed written consent was not required. Statistical comparisons were made using repeated measures ANOVA with Bonferroni correction for multiple comparisons.. For the phantom and patient studies, 2 linear images with weighting factors 0.5 and 0.7 and 2 nonlinear images with a wide width, showed a higher CNR of hyperattenuated lesions than a standard 0.3 weighting factor linear blended image (P < 0.05). For the patient study, a weighting factor 0.5 and a 0.7 linear mixing image had a 9.2% and an 11.8% increase in CNR, respectively, more than a 0.3 linear blended image (P < 0.05). Moreover, a nonlinear mixing image with parameters A and C had a 14.0% increase in CNR over that of a 0.3 linear blended image (P < 0.05). In a qualitative study performed by the 5 reviewers, the nonlinear blended image set with a low level and wide width, was estimated as the most preferred image set (55%-100%), whereas a weighting factor of a 0.3 linear blended image was determined as the least preferred image (65%-100%).. Linear blended images with a higher weighting factor than 0.5 and nonlinear blended images with a wide width are able to provide improved lesion-to-liver CNR over the standard linear blending method (with a weighting factor of 0.3). Furthermore, the linear blending method with a low level and a high width provided the most preferred image set for hypervascular hepatocellular carcinoma detection by our radiologists.

Topics: Adult; Aged; Analysis of Variance; Carcinoma, Hepatocellular; Contrast Media; Female; Humans; Iohexol; Liver Neoplasms; Male; Middle Aged; Neovascularization, Pathologic; Phantoms, Imaging; Radiographic Image Interpretation, Computer-Assisted; Tomography, X-Ray Computed

Volumetric computed tomography (VCT) is a technology in which area detectors are used for imaging large volumes of a subject with isotropic imaging resolution. We are experimenting with a prototype VCT scanner that uses flat-panel X-ray detectors and is designed for high-resolution three-dimensional (3D) imaging. Using this technique, we have demonstrated microangiography of xeno-transplanted skin squamous cell carcinomas in nude mice. VCT shows the vessel architecture of tumors and animals with greater detail and plasticity than has previously been achieved, and is superior to contrast-enhanced magnetic resonance (MR) angiography. VCT and MR images correlate well for larger tumor vessels, which are tracked from their origin on 3D reconstructions of VCT images. When compared with histology, small tumor vessels with a diameter as small as 50 microm were clearly visualized. Furthermore, imaging small vessel networks inside the tumor tissue improved discrimination of vital and necrotic regions. Thus, VCT substantially improves imaging of vascularization in tumors and offers a promising tool for preclinical studies of tumor angiogenesis and antiangiogenic therapies.

Topics: Animals; Barium Sulfate; Histological Techniques; Iohexol; Iopamidol; Magnetic Resonance Imaging; Mice; Mice, Nude; Neoplasms; Neovascularization, Pathologic; Tomography, Spiral Computed

The aim of this work was to study the vascularization of hepatocellular carcinoma (HCC) by means of dynamic CT and to demonstrate the existence of optimal temporal windows for visualization of HCC in order to develop new protocols for helical CT of the liver. We studied, by means of dynamic CT, 42 histologically proved HCCs in 30 patients after injecting contrast medium (100 ml, 3 ml/s). We performed a time-density analysis of the aorta, liver, portal vein, spleen and lesion. We identified three temporal curves of attenuation of the neoplastic tissue. Curve 1 was three-phasic: hyperattenuation, isoattenuation and hypoattenuation; curve 2 was two-phasic: hyperattenuation and isoattenuation; curve 3 was two-phasic: isoattenuation and hypoattenuation. Thirty-two lesions were homogeneous (curve 1 in 22 cases, 68.7 %; curve 2 in 7 cases, 21.8 %; curve 3 in 3 cases, 9.4 %), whereas 10 lesions were non-homogeneous. Two optimal temporal windows were identified: the first, with predominantly hyperattenuating lesions (range 29-65 s, 90.4 % sensitivity); the second, with predominantly hypoattenuating lesions (range 132.1-360 s, 76.1 %). There is an interposed time range of reduced visualization (range 62-127 s, 54.7 %) in which lesions are isoattenuating. Combined CT study during the first and second temporal windows improves the detection of HCCs especially for homogeneous and small lesions. The intermediate isoattenuation time range does not increase lesion detection rate.

Topics: Aged; Aorta, Abdominal; Carcinoma, Hepatocellular; Contrast Media; Evaluation Studies as Topic; Female; Humans; Infusions, Intravenous; Iohexol; Liver Neoplasms; Male; Middle Aged; Neovascularization, Pathologic; Portal Vein; Radiographic Image Enhancement; Retrospective Studies; Spleen; Tomography, X-Ray Computed