Chih-Wei Yu

Dynamic contrast-enhanced magnetic resonance imaging biomarkers predict survival and response in hepatocellular carcinoma patients treated with sorafenib and metronomic tegafur/uracil

BACKGROUND & AIMS Sorafenib plus metronomic tegafur/uracil therapy can induce tumor stabilization in advanced hepatocellular carcinoma (HCC) patients. This study evaluated the correlation of vascular response measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the clinical outcome. METHODS DCE-MRI was performed in advanced HCC patients treated with sorafenib (800 mg/d) plus tegafur/uracil (250 mg/m(2)/d based on tegafur) at baseline and after 14 days of treatment. An operator-defined region of interest was placed in the most strongly enhanced area of the tumor to measure the pharmacokinetic parameter K(trans). Changes in K(trans) after treatment were correlated with the best tumor response and survival. RESULTS Thirty-one patients were evaluable. There were one partial response (PR), 18 stable disease (SD), and 12 progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Baseline K(trans) was higher in patients with PR or SD (median 1215.2 × 10(-3)/min, range 582.5-4555.3 × 10(-3)/min) than patients with PD (median 702.0 × 10(-3)/min, range 375.2-1938.0 × 10(-3)/min, p = 0.008). After 14 days of study treatment, the median K(trans) change was -47.1% (range -87.0 to -18.0%) in patients with PR or SD, and 9.6% (range -44.8 to +81%) in those with PD (p<0.001). A vascular response, defined by a 40% or greater decrease in K(trans) after 14 days of study treatment, correlated with longer progression-free survival (median 29.1 vs. 8.7 weeks, p = 0.033) and overall survival (median 53.0 vs. 14.9 weeks, p = 0.016). Percentage of K(trans) change after treatment is an independent predictor of tumor response, progression-free survival, and overall survival. CONCLUSIONS K(trans) measured by DCE-MRI correlated well with tumor response and survival in HCC patients who received sorafenib plus metronomic tegafur/uracil therapy.

Dynamic contrast-enhanced magnetic resonance imaging with Gd-EOB-DTPA for the evaluation of liver fibrosis in chronic hepatitis patients

AbstractObjectivesTo develop a non-invasive MRI method for evaluation of liver fibrosis, with histological analysis as the reference standard.MethodsThe study protocol was approved by the Institutional Review Board for Human Studies of our hospital, and written informed consent was obtained from all subjects. Seventy-nine subjects who received dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA were divided into three subgroups according to Metavir score: no fibrosis (n = 30), mild fibrosis (n = 34), and advanced fibrosis (n = 15). The DCE-MRI parameters were measured using two models: (1) dual-input single-compartment model for arterial blood flow (Fa), portal venous blood flow, total liver blood flow, arterial fraction (ART), distribution volume, and mean transit time; and (2) curve analysis model for Peak, Slope, and AUC. Statistical analysis was performed with Student’s t-test and the nonparametric Kruskal-Wallis test.ResultsSlope and AUC were two best perfusion parameters to predict the severity of liver fibrosis (>F2 vs. ≦F2). Four significantly different variables were found between non-fibrotic versus mild-fibrotic subgroups: Fa, ART, Slope, and AUC; the best predictor for mild fibrosis was Fa (AUROC:0.701).ConclusionsDCE-MRI with Gd-EOB-DTPA is a noninvasive imaging, by which multiple perfusion parameters can be measured to evaluate the severity of liver fibrosis. Key Points • Dynamic Gd-EOB-DTPA contrast-enhanced-MRI can help evaluate the severity of liver fibrosis.• Slope and AUC were two best perfusion parameters to predict severity.• Absolute arterial blood flow was the best predictor for mild fibrosis.

Vandetanib in patients with inoperable hepatocellular carcinoma: A phase II, randomized, double-blind, placebo-controlled study

BACKGROUND & AIMS Inhibitors of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) have shown anti-tumor activities in advanced hepatocellular carcinoma (HCC). The present study evaluated the efficacy and safety of vandetanib, an oral inhibitor of both VEGFR and EGFR, in patients with unresectable advanced HCC. METHODS Eligible patients were randomized 1:1:1 to receive vandetanib 300mg/day, vandetanib 100mg/day, or placebo. Upon disease progression, all patients had the option to receive open-label vandetanib 300mg/day. The primary objective was to evaluate tumor stabilization rate (complete response+partial response+stable disease ⩾4months). Secondary assessments included progression-free survival (PFS), overall survival (OS) and safety. Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS Sixty-seven patients were randomized to vandetanib 300mg (n=19), vandetanib 100mg (n=25) or placebo (n=23) groups. Twenty-nine patients entered open-label treatment. Vandetanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels. In both vandetanib arms, tumor stabilization rate was not significantly different from placebo: 5.3% (vandetanib 300mg), 16.0% (vandetanib 100mg) and 8.7% (placebo). DCE-MRI did not detect significant vascular change after vandetanib treatment. Although trends of improved PFS and OS after vandetanib treatment were found, they were statistically insignificant. The most common adverse events were diarrhea and rash, whose incidence did not differ significantly between treatment groups. CONCLUSIONS Vandetanib has limited clinical activity in HCC. The safety profile was consistent with previous studies.

Bone marrow angiogenesis magnetic resonance imaging in patients with acute myeloid leukemia: peak enhancement ratio is an independent predictor for overall survival.

Emerging evidence suggests that progression of hematologic malignancies is associated with angiogenesis. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can provide global and functional imaging of tumor angiogenesis. In this study, we performed bone marrow DCE-MRI prospectively at diagnosis and after induction chemotherapy in 78 de novo acute myeloid leukemia (AML) patients and correlated it with treatment outcome. An algorithm to assess bone marrow angiogenesis by measuring the DCE-MRI time-intensity curve pixel by pixel was developed using 3 distinct parameters: peak enhancement ratio (Peak) to indicate tissue blood perfusion; amplitude (Amp) to reflect vascularity; and volume transfer constant (K trans) to indicate vascular permeability. The Peak and Amp decreased significantly at remission status after induction chemotherapy. Patients with higher Peak or Amp at diagnosis had shorter overall survival and disease-free survival than others. Cox multivariate analysis identified higher Peak value (hazard ratio, 9.181; 95% confidence interval, 1.740-48.437; P = .009) as an independent predictor for overall survival in addition to unfavorable karyotype and old age. Our findings provide evidence that increased bone marrow angiogenesis measured by DCE-MRI can predict adverse clinical outcome in AML patients. DCE-MRI may help to select high-risk phenotype AML patients for tailored antiangiogenic therapy and to monitor treatment response.

Dynamic Contrast-enhanced MR Imaging Measurement of Vertebral Bone Marrow Perfusion May Be Indicator of Outcome of Acute Myeloid Leukemia Patients in Remission

PURPOSE To examine whether dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging measurement of bone marrow perfusion in acute myeloid leukemia (AML) patients in complete remission (CR) is associated with outcome and survival. MATERIALS AND METHODS After institutional review board approval and informed consent were obtained, from September 2004 to October 2007, 51 patients (29 women, 22 men; mean age, 43.5 years; range, 17-66 years) agreed to undergo DCE MR imaging to assess bone marrow perfusion, among 96 patients with newly diagnosed de novo AML who had received induction chemotherapy and achieved CR. Two semiquantitative parameters (peak and slope) and another three quantitative parameters (amplitude, K(ep) [efflux rate constant], and K(el) [elimination rate constant]) were calculated. Overall survival (OS) and relapse-free survival (RFS) were assessed with the Kaplan-Meier model, while differences between patient groups with high and low DCE MR imaging parameter values were assessed by using the two-sided log-rank test. RESULTS The median follow-up was 25.9 months. Univariate analysis results showed that high values of peak (≥0.42), slope (≥0.0235), amplitude (≥0.03), and K(ep) (≥0.0082) were associated with shorter OS (P = .004, 0.01, 0.034, and 0.026, respectively). Besides, a high value of K(ep) was also associated with shorter RFS (P = .008). When age, sex, and initial karyotype at diagnosis were included in multivariate Cox proportional hazards analysis, the results showed that only K(ep), but not other DCE MR imaging parameters, was an independent factor for OS (relative risk [RR], 30.305; P = .021) and RFS (RR, 6.477; P = .009). CONCLUSION Bone marrow perfusion measured with DCE MR imaging in AML patients in CR can be an indicator of outcome and survival. K(ep) measured with kinetic modeling was useful and significantly associated with RFS, while heuristic parameters (peak and slope) were not.

Mature cystic teratoma of the pancreas in a child

A cystic pancreatic tumour is rare in a child and a mature cystic teratoma of the pancreas is even rarer. This is the first demonstration of the CT appearance of such a tumour in a child. We present a 2-year-old boy who presented with a palpable abdominal mass. Abdominal CT revealed a huge cystic mass in the upper abdomen. Pathology disclosed a mature cystic teratoma originating from the pancreas.

Correlation between Pancreatic Microcirculation and Type 2 Diabetes in Patients with Coronary Artery Disease: Dynamic Contrast-enhanced MR Imaging

PURPOSE To evaluate pancreatic perfusion by using dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with pharmacokinetic modeling in coronary artery disease (CAD) patients with and those without type 2 diabetes to determine which perfusion parameter alterations might be associated with type 2 diabetes. MATERIALS AND METHODS This prospective study was approved by the responsible institutional review board. Written informed consent was obtained from all patients. All patients studied had CAD documented at conventional angiography. DCE MR with a two-dimensional T1-weighted fast low-angle shot sequence in oblique axial planes was used to assess pancreatic microcirculation in patients with and those without type 2 diabetes (age +/- standard deviation, 60.8 years +/- 11.2 and 61.8 years +/- 11.2, respectively; 20 men and five women in each group). Microcirculatory quantitative parameters, including volume transfer constant (K(trans), in min(-1)), extravascular extracellular space volume per unit volume of tissue (v(e)), and plasma volume per unit volume of tissue (v(p)) were compared between groups by using independent-sample t tests. RESULTS Patients with diabetes had a significantly higher K(trans) (0.977 vs 0.696, P = .031) and a lower v(p) (0.057 vs 0.084, P = .005) compared with patients without diabetes. A borderline difference in v(e) was found between the diabetes and nondiabetes groups (0.141 vs 0.103, P = .05). Among the 25 patients with diabetes, those who had the condition for more than 10 years (n = 11) had significantly higher K(trans) and v(e) than did those who had diabetes for less than 10 years (n = 14) (1.145 vs 0.783 and 0.174 vs 0.108; P = .04 and .02, respectively). CONCLUSION DCE MR imaging demonstrated increased endothelial permeability and decreased plasma volume in the pancreas in CAD patients with type 2 diabetes; patients with a history of diabetes for more than 10 years showed further increase in endothelial permeability.

Unusual Manifestations of Vertebral Osteomyelitis: Intraosseous Lesions Mimicking Metastases

BACKGROUND AND PURPOSE: Vertebral osteomyelitis can have different imaging manifestations. The purpose of this study was to demonstrate the unusual MR imaging patterns of vertebral osteomyelitis with intraosseous lesions mimicking metastases. MATERIALS AND METHODS: From September 2000 to August 2007, 7 patients were selected from our data base of 214 patients with confirmed vertebral osteomyelitis and MR images. All of those having misinterpreted MR imaging reports and unusual imaging patterns were analyzed. The presence of a peripheral curvilinear area of low signal intensity in an osseous lesion (the rim sign) and a peripheral rim of high signal intensity on T2-weighted images around an osseous lesion (the halo sign) was evaluated. Follow-up MR imaging studies were performed in all patients. RESULTS: The patients were 5 men and 2 women, with an age range of 42–80 years. MR imaging findings of those with vertebral osteomyelitis showed a solitary lesion in 2 and multiple lesions in 5 patients. The intraosseous lesions revealed low signal intensity on T1-weighted images, mixed or high signal intensity on T2-weighted images, high signal intensity on short τ inversion recovery images, and global or marginal enhancement. The rim sign was found in 6 (86%) patients; halo sign, in 7 (100%); preserved intervertebral disks, in 7 (100%); and limited paraspinal or epidural inflammation, in 6 (86%). Images of all patients demonstrated healing or almost healed changes on the follow-up MR imaging studies. CONCLUSION: Vertebral osteomyelitis can have MR imaging patterns mimicking osseous metastases. Recognition of these unusual imaging manifestations, together with clinical and histopathologic analysis, may aid in reaching the correct diagnosis.

Demonstration of extensive mesenteric venous thrombosis and intestinal infarction with multidetector row CT: value of curved planar reformations

We describe a case of extensive mesenteric venous thrombosis with small bowel infarction. Multidetector row computed tomography with curved planar reformation clearly demonstrated the full extents of the mesenteric venous thrombus and the infarcted bowel loops. The length of infarcted segment could be estimated from the curved planar reformatted image and correlated well with operative findings. To our knowledge, this is the first presentation and measurement of infarcted bowel loops on curved planar reformation.

Clinical and histologic implications of delayed hepatobiliary enhancement on magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic Acid.

PurposeThe aim of this study was to evaluate the serial signal changes in hepatobiliary enhancement on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid or gadoxetic acid (Gd-EOB-DTPA)–enhanced magnetic resonance imaging and its correlation with clinical parameters. MethodUnder institutional review board approval, Gd-EOB-DTPA-enhanced magnetic resonance imaging was performed in 77 subjects (21 healthy volunteers and 56 biopsy-proven chronic hepatitis patients), and the signal intensities of the liver and common hepatic ducts (CHD) were measured every 2 minutes up to 50 minutes postcontrast. The associations among hepatic and CHD signals, physiological and hematological variables, histological activity index, and Metavir scores were analyzed with Pearson correlation and multiple linear stepwise regressions. The predictive ability of contrast enhancement index (CEI) of the liver with histological activity index and fibrosis scores at different time points were studied using nonparametric receiver operating characteristic curves. ResultsAmong the clinical parameters, body weight and body mass index had the highest negative correlation with hepatobiliary enhancement between 2 and 50 minutes postcontrast (P < 0.001). Multiple regressions showed that creatinine level, body weight, and body mass index were independent predictors for both mean hepatic and CHD signal intensity (P < 0.05). Patients with more severe fibrosis or moderate necrosis tended to have lower CEIs than other patients were. The predictive ability of CEI for the best differentiation between no fibrosis and any fibrosis (F ≥ 1) was at 10 minutes postcontrast (area under the receiver operating characteristic curve, 0.797). ConclusionsDelayed hepatobiliary enhancement with Gd-EOB-DTPA could be possibly used for staging liver fibrosis. Contrast enhancement index of the liver at 10 minutes is useful for differentiating between no fibrosis and any degree of fibrosis in chronic hepatitis patients.