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ABSTRACT: Objectives The purpose of the study was to detect tumor blood flow changes after chemotherapy with contrast-enhanced destruction-replenishment sonography. Methods Twenty-four MCF-7 breast cancer-bearing nude mice were included in this study. Animals received either adriamycin or sterile saline and underwent contrast-enhanced sonography before and after treatment using a destruction-replenishment technique. A monoexponential function, y = A(1 - e(-βt)), was used to fit the replenishment kinetics, where the plateau signal intensity A reflects the percent blood volume; the time constant β reflects the average speed of blood; and their product A*β reflects the nutrient blood flow. Tumor blood perfusion was compared to measurements of cell density and microvascular density. Results Volumes of the treated tumors were significantly reduced after 7 days of adriamycin treatment compared with the control tumors (P < .001). Before adriamycin administration, there was no significant difference in blood perfusion between the treated and control groups (P > .05). Treatment with adriamycin resulted in a significant decrease in A, β, and A*β (P <.001) compared with the control tumors. The tumor cell density and microvascular density estimated by pathologic slices were significantly lower in the treated tumors than in the control tumors (P <.001). Conclusions Quantification of tumor blood flow using contrast-enhanced destruction-replenishment sonography shows the potential to evaluate tumor responses to chemotherapy.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 04/2013; 32(4):683-90. · 1.25 Impact Factor
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The British journal of radiology 02/2013; · 2.11 Impact Factor
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ABSTRACT: 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 (<0.01) 2 days after therapy. There were significant differences of tumor volumes between control and treated groups on day 6 (<0.001) while there were no significant differences in tumor volume on days 0, 2 and 4 (>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 (<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.
PLoS ONE 01/2013; 8(3):e58274. · 4.09 Impact Factor
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ABSTRACT: Portal vein embolization (PVE) has become a standard preoperative procedure to promote hypertrophy of the future remnant liver to reduce postoperative liver failure. Whether PVE accelerates tumor growth is still controversial. We developed a left PVE procedure and investigated its effect on liver hypertrophy and tumor growth in a rabbit liver tumor model.
VX2 tumors were implanted in both the external left and right middle lobe (the bilateral group) or in the external left lobe only (the unilateral group) of rabbit liver. Both groups were further divided into a PVE or a sham/control group. Tumor volume and tumor growth rate as volume relative increase were determined by ultrasound. Liver volume-to-body weight index, an index for liver volume, was compared. Serum HGF was measured by ELISA.
In the bilateral PVE group, tumor volume and relative increase value in the nonembolized lobe were significantly (71% and 65%, respectively) greater than those in the control group at 5 d post-PVE. In the unilateral PVE group, liver volume-to-body weight index of the nonembolized lobes was significantly increased by 17%. Increase of serum HGF level after PVE was correlated well with both tumor growth and liver hypertrophy.
Left PVE promoted both the growth of implanted tumors and liver hypertrophy in the nonembolized liver, in which serum HGF might play an important role.
Journal of Surgical Research 04/2012; 178(1):255-63. · 2.25 Impact Factor
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ABSTRACT: This paper introduces a new graph-based method for segmenting breast tumors in US images. BACKGROUND AND MOTIVATION: Segmentation for breast tumors in ultrasound (US) images is crucial for computer-aided diagnosis system, but it has always been a difficult task due to the defects inherent in the US images, such as speckles and low contrast.
The proposed segmentation algorithm constructed a graph using improved neighborhood models. In addition, taking advantages of local statistics, a new pair-wise region comparison predicate that was insensitive to noises was proposed to determine the mergence of any two of adjacent subregions.
Experimental results have shown that the proposed method could improve the segmentation accuracy by 1.5-5.6% in comparison with three often used segmentation methods, and should be capable of segmenting breast tumors in US images.
Ultrasonics 08/2011; 52(2):266-75. · 1.84 Impact Factor
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ABSTRACT: A rhamnolipid production strain newly isolated from oil-contaminated soil was identified as Pseudomonas aeruginosa GIM32 by its morphology and 16S rDNA sequence analysis. The effect of carbon source and carbon to nitrogen (C/N) ratio on rhamnolipids production was investigated. Palm oil was favorable as a carbon source for rhamnolipid production. The maximum biomass and rhamnolipid concentration were 8.24 g/L and 30.4 g/L, respectively, with an optimization medium containing 50 g/L palm oil and 5 g/L sodium nitrate. Molasses distillery wastewater as an unconventional substrate for rhamnolipid production was investigated. It was found that 2.6 g/L of rhamnolipids was produced; this amount was higher than that of past reports using wastewater as a substrate. In addition, 44% of the chemical oxygen demand of wastewater was removed at the same time under the optimization condition. Eleven kinds of different molecular weight rhamnolipid homologues were identified in the rhamnolipids obtained from molasses distillery wastewater by P. aeruginosa GIM32 by LC-MS analysis.
Applied biochemistry and biotechnology 03/2011; 163(5):600-11. · 1.94 Impact Factor
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ABSTRACT: To assess the validity of contrast-enhanced ultrasonic parametric perfusion imaging in the evaluation of antiangiogenic tumor treatment by using histology as the reference standard.
H22 hepatoma-bearing mice were treated with thalidomide or placebo by intraperitoneal injection. Contrast-enhanced ultrasound was performed on day 8 after bolus injection of SonoVue. Three different parametric perfusion images were calculated based on the following parameters: area under the curve (AUC), maximum intensity (IMAX) and perfusion index (PI). A score from 1 to 5 (1 = low, 5 = excellent) was used for analysis of parametric perfusion images by two independent readers. Immunohistochemical analysis was performed for evaluation of microvascular density (MVD).
Treatment with thalidomide resulted in a significant decrease in perfusion scores assigned to AUC, IMAX and PI parametric images as compared with control tumors (P < 0.001). Immunohistochemistry showed significant decreases of MVD in treated tumors as compared with control tumors (P = 0.002). MVD was positively correlated with the perfusion scores assigned to AUC parametric images (r = 0.568, P = 0.009), IMAX parametric images (r = 0.614, P = 0.004) and PI parametric images (r = 0.636, P = 0.003).
Contrast-enhanced ultrasonic parametric perfusion imaging provides a noninvasive tool to directly visualize tumor perfusion changes after antiangiogenic tumor treatment.
European journal of radiology 02/2011; 81(6):1360-5. · 2.65 Impact Factor
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ABSTRACT: The quantitative parameters in contrast-enhanced ultrasonography-time-intensity curve of hepatocellular carcinoma (HCC) were studied to explore their potential importance in monitoring the effects of anti-angiogenic therapy for HCC.
115 HCC patients were studied with contrast-enhanced ultrasonography-time-intensity curve (CEUS-TIC) and with immunohistochemical analysis of tissue sections. The CEUS images were analyzed off-line to obtained quantitative parameters including maximum of intensity (IMAX), rise time (RT), time to peak (TTP), mean transit time (mTT), rise slope (RS), and washout time (WT). Monoclonal antibodies specific for smooth muscle actin and anti-CD34 were used to observe unpaired arteries (UAs) and microvessel area (MVA) of sinusoidal capillarization, respectively. The UAs and MVA of 82 HCC cases were successfully stained.
The number of UAs had moderate correlation with RT (r=-0.446), TTP (r=-0.432), and RS (r=0.431) (P<0.05), and it had mild correlation with IMAX (r=0.303) and WT (r=0.285) (P<0.05). MVA of sinusoidal capillarization had no correlation with perfusion parameters.
Quantitative CEUS-TIC parameters reflecting hemodynamics of tumors are correlated with UAs, but not with MVA, and they might be used to monitor the effects of anti-angiogenic therapy on HCC.
European journal of radiology 02/2011; 81(3):e182-8. · 2.65 Impact Factor
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ABSTRACT: To quantify tumor blood flow by using contrast material-enhanced destruction-replenishment ultrasonography (US) to evaluate tumor response to different doses of an agent for antiangiogenic treatment in hepatoma-bearing mice, with histologic measurements of microvascular density (MVD) as the reference standard.
Experiments were approved by the regional animal care committee. Mice bearing subcutaneous H22 hepatoma were treated with different doses of thalidomide, 100 mg/kg in group B and 200 mg/kg in group C. Group A (control group) was treated with 0.5% carboxylmethylcellulose. Treatment groups and the control group included 10 mice each. Contrast-enhanced US was used to evaluate the percentage of nonenhanced area, and contrast-enhanced destruction-replenishment US was used to evaluate tumor blood flow. Tumor blood flow was compared with measurements of MVD. Comparisons were made by using one-way analysis of variance and the post hoc least significant difference test for multiple comparisons.
Contrast-enhanced gray-scale US showed significant increases in the percentage of nonenhanced area in group C (mean, 10.56% ± 7.25 [standard deviation]), as compared with groups A (mean, 2.40% ± 3.12; P = .004) and B (mean, 3.75% ± 5.55; P = .012). Contrast-enhanced destruction-replenishment US showed significant decreases of tumor blood flow in groups B and C, as compared with group A (P = .003 and P < .001, respectively), and the blood flow in group C was significantly lower than that of group B (P = .01). Immunohistochemical analysis revealed significant decreases of MVD in groups B and C, as compared with MVD in group A (P = .002 and P < .001, respectively); however, there was no significant difference in MVD between groups B and C (P = .21).
Quantification of tumor blood flow by using contrast-enhanced destruction-replenishment US shows the potential to guide drug dosage during antiangiogenic therapy.
Radiology 02/2011; 259(2):406-13. · 5.73 Impact Factor
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ABSTRACT: The purpose of this study was to quantify tumor blood perfusion with contrast-enhanced gray-scale ultrasound in the evaluation of tumor response to chemotherapy.
Mice bearing H22 hepatoma were treated with cisplatin or placebo by intraperitoneal injection. Contrast-enhanced gray-scale ultrasound was performed on day 8 after bolus injection of a lipid-based ultrasound contrast agent. Regions of interest within the tumor were analyzed offline to determine area under the curve, maximum intensity, perfusion index, mean transit time, time to peak, and quality of fit. Immediately after imaging, mice were euthanized, and tumor tissue was removed for fixation in 10% formalin solution. Microvascular density was measured after anti-CD34 staining.
The volume of treated tumors was significantly smaller than that of control tumors (p < 0.001). Treatment with cisplatin resulted in a significant decrease in perfusion index and maximum intensity compared with control tumors (p < 0.05). There were no significant differences between control and treated tumors (p > 0.05) with respect to area under the curve, mean transit time, and time to peak. The microvascular density of treated tumors was significantly lower than that of control tumors (p < 0.001).
Quantitative analysis of tumor blood perfusion with contrast-enhanced ultrasound can be used for noninvasive assessment of functional changes in tumors after chemotherapy.
American Journal of Roentgenology 01/2011; 196(1):W13-7. · 2.78 Impact Factor
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Guo-Liang Huang,
Bin-Kui Li,
Mei-Yin Zhang,
Hui-Zhong Zhang,
Rong-Rong Wei,
Yun-Fei Yuan,
Ming Shi,
Xiao-Qian Chen,
Long Huang, An-Hua Li,
Bi-Jun Huang,
Hong-Hua Li,
Hui-Yun Wang
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ABSTRACT: To investigate genes around the locus D4S2964 affected by loss of heterozygosity (LOH) and their clinical implications.
Four hundred and forty single nucleotide polymorphisms (SNPs) located at 49 genes around D4S2964 were selected from the National Center for Biotechnology Information website for the SNPs microarray fabrication. LOH of SNPs markers in 112 cases of hepatocellular carcinoma (HCC) tissues and paired adjacent liver tissues were investigated by the SNPs microarray. The correlation between allelic losses with clinicopathological features and overall survival was analyzed.
A fine map of LOH of SNPs in genes around D4S2964 was plotted. The average frequency of LOH in genes was 0.39. A correlation between cirrhosis and the FAL index (fractional allelic loss) was found (P = 0.0202). Larger tumor size was found to be significantly associated with LOH in genes ADP-ribosyltransferase 3 (ART3), nucleoporin 54 kDa (NUP54), scavenger receptor class B, member 2 (SCARB2) and coiled-coil domain containing 158 (CCDC158) (P = 0.043, P = 0.019, P = 0.001, P = 0.037, respectively). Kaplan-Meier analysis showed that patients with LOH in ARD1 homolog B (ARD1B) and septin 11 (SEPT11) had a significantly lower survival rate than those with retention (P = 0.021 and P = 0.004, respectively). A Cox regression model suggested that LOH in ARD1B and SEPT11, respectively, were predictors of the overall survival in HCC (P = 0.006 and P = 0.026, respectively).
LOH in genes around D4S2964 may play an important role in HCC development and progression. LOH in ARD1B and SEPT11 could serve as novel prognostic predictors in HCC patients.
World Journal of Gastroenterology 04/2010; 16(16):2046-54. · 2.47 Impact Factor
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ABSTRACT: To evaluate the ability of contrast enhanced ultrasound (CEUS) in monitoring percutaneous thermal ablation procedure in patients with hepatocellular carcinoma (HCC) in comparison with contrast enhanced computed tomography (CECT) and/or magnetic resonance imaging (CEMRI). A total of 151 patients were enrolled in the study. Before the radio-frequency (RF) or microwave ablation treatment, tumor vascularity was assessed in 139 patients with three imaging modalities i.e., US (139 exams), CEUS (139 exams) and CECT (103 exams)/CEMR (36 exams). CEUS examination was performed using a sulphur hexafluoride-filled microbubble contrast agent (SonoVue((R)), Bracco, Milan, Italy) and real-time contrast-specific imaging techniques. Within 30 +/- 7 d after the ablation procedure, 118/139 patients were monitored to assess the tumor response to treatment. Before ablation, contrast enhancement within tumor was observed in 129/139 (92.8%) patients with CEUS and 133/139 (95.7%) patients with CECT/CEMRI. Compared with CECT/CEMRI, CEUS sensitivity and accuracy in detecting tumor vascularity were 97.0% and 94.2%, respectively. One month after treatment, no enhancement was seen in 110/118 (93.2%) both on CEUS and CECT/CEMRI. Concordance between CEUS and CECT/CEMR on the presence of residual vascularization was obtained in four patients (true positive). The specificity and accuracy of CEUS in detecting tumor vascularity were 98.2% and 96.6%, respectively. The periprocedural impact of SonoVue administration on the assessment of treatment extent was also evaluated in a subgroup of patients and CEUS showed its superiority compared with baseline US in defining treatment outcome. In conclusion, in the detection of HCC tumor vascularity and assessment of response to thermal ablation after 1 month, real time CEUS provided results comparable to those obtained with CECT/CEMRI. CEUS examination proved to be a safe and easy to access procedure, with potential for diagnostic impact in the clinical practice.
Ultrasound in Medicine & Biology 12/2007; 33(11):1736-49. · 2.29 Impact Factor
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ABSTRACT: Color Doppler flow imaging (CDFI) has been widely applied to the diagnosis of breast neoplasms. But combined use of CDFI and imaging changes of breast fascia and ligament (superficial and deep fascia, and Cooper's ligament) on the differential diagnosis of small breast neoplasms (< or =2 cm) has rarely been reported. This study was to explore the value of combined use of CDFI and imaging changes of breast fascia and ligament in differential diagnosis of small breast neoplasms.
CDFI was performed on 110 patients with small breast neoplasms. Among them, 52 cases were diagnosed to be benign by pathologic examination after surgery, while the rest 58 were malignant. The blood flow and Doppler image inside and around the breast lesions were analyzed. Four grades were classified according to blood flow imaging. The infiltration of breast fascia and ligament was also considered. The CDFI result was compared with that of pathologic examination.
The correct diagnosis rates of CDFI in diagnosing benign and malignant small breast neoplasms were 90.4% and 84.5%, respectively. The false-positive and false-negative rates of CDFI were 9.6% and 15.5%, respectively. There were obvious differences in blood flow grading, systolic maximum velocity (V(max)), resistance index (RI), and imaging changes of superficial, deep fascia and Cooper's ligament between benign and malignant small breast neoplasms.
Combination of CDFI with imaging changes of breast fascia and ligament is valuable in clinical diagnosis and differential diagnosis of small breast neoplasms.
Ai zheng = Aizheng = Chinese journal of cancer 04/2006; 25(3):339-42.
