Tiffany Ting-Fang Shih

Blood perfusion of vertebral lesions evaluated with gadolinium-enhanced dynamic MRI: In comparison with compression fracture and metastasis

To investigate blood perfusion of vertebral lesions using dynamic Gd‐DTPA‐enhanced MRI.

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.

Solitary vertebral collapse: distinction between benign and malignant causes using MR patterns.

Differentiation of benign from malignant causes of vertebral compression fracture can be difficult at a single location. We studied 37 patients with solitary vertebral collapse (SVC) in the spine using magnetic resonance imaging (MRI). Sixteen of them were found to have a benign cause of SVC, while the remaining 21 were found to have malignancy. The following four MRI characteristics were investigated: ill‐ or well‐defined margin of the intravertebral lesion (P < 0.005); pedicle involvement (P < 0.05); MR enhancement pattern (P < 0.005); and paravertebral soft tissue lesion (PSL) (P < 0.025). It was found that cases of malignant SVC tended to have an ill‐defined margin, abnormal signal involvement of the pedicle, a marked and heterogenous MR enhancement pattern, and irregular nodular‐type PSL. Pedicle change with expansile lesion totally excluded a benign cause. By using these criteria, we were able to differentiate benign or malignant causes of SVC accurately.J. Magn. Reson. Imaging 1999;9:635–642.

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.

Association of epicardial adipose tissue with coronary atherosclerosis is region-specific and independent of conventional risk factors and intra-abdominal adiposity

OBJECTIVE To elucidate which measurement of epicardial adipose tissue (EAT) best reflects its atherogenic risk, we examined the associations between different EAT measurements and various atherosclerotic parameters of the entire coronary tree and individual coronary arteries. METHODS This study included 224 consecutive patients underwent multidetector computed tomography before diagnostic coronary angiography. Regional thickness, cross-sectional areas, and total volume of EAT were measured. Four atherosclerotic parameters, including severity score, extent score, calcium volume score, and number of coronary arteries with ≥50% luminal stenosis, of the entire coronary tree and individual coronary arteries were assessed. RESULTS Both total EAT volume and thickness of EAT in the left atrioventricular groove were unanimously associated with the presence of coronary atherosclerosis dichotomously defined by the 4 scoring systems. However, only EAT thickness in the left atrioventricular groove, but not total EAT volume, was significantly associated with all 4 parameters of coronary atherosclerosis in a dose-dependent manner, even after adjustments for conventional risk factors, body-mass index, waist circumference, C-reactive protein, and intra-abdominal visceral fat area. Using the receiver-operating-characteristic analysis, 12.2mm was the optimal cutoff point for left atrioventricular groove thickness to predict the presence of significant coronary stenosis (≥50% diameter stenosis). Among the three coronary arteries, left atrioventricular groove thickness was most strongly correlated with ≥50% diameter stenosis in the embedded left circumflex artery by multivariate regression model. CONCLUSIONS Thickness of EAT in the left atrioventricular groove provides a more accurate assessment of its atherogenic risk and is therefore a better coronary risk factor than total EAT volume.

In Vitro Study on Interaction Between Human Nucleus Pulposus Cells and Mesenchymal Stem Cells Through Paracrine Stimulation

Study Design. Coculture of human nucleus pulposus (NP) cells and mesenchymal stem cells (MSCs) using a noncontact system. Objective. To investigate the interaction between NP cells and MSCs through paracrine stimulation. Summary of Background Data. Cell-based therapies have a potential role in the treatment of intervertebral disc degeneration. Upregulating the viability of NP cells and differentiating MSCs into NP-like cells are potential alternatives to achieve viable cells. Methods. Culture plates and inserts were used to coculture MSCs and NP cells without direct contact or exchange of cellular components. Cellular proliferation and RNA expression of selected genes were then evaluated after coculture. Results. Coculturing slightly promoted the proliferation of MSCs, and expression of collagen I and Fas-associated death domain protein significantly decreased. MSCs, which initially expressed no collagen II, started to show collagen II expression after coculturing; the expression level was highest when the cells were cultured with a higher number of NP cells. On the converse, proliferation of NP cells significantly rose even after cocultured with a few MSCs. Increasing the number of cocultured MSCs did not further enhance proliferation of NP cells. Expression of aggrecan in the NP cells significantly increased when the cells were cultured with a higher number of MSCs. Conclusion. The results showed a possible mechanism of interaction between MSCs and NP cells mediated by secreted factors. The most significant effect on NP cells was enhancement of cellular proliferation when they were cocultured with even a small number of MSCs. To differentiate MSCs into NP-like cells with heightened collagen II expression, MSCs must be in an environment containing numerous NP cells.

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.

Relationships between three potentiation effects of plyometric training and performance

This study measured the potentiation effects of plyometric training [normalized electromyography (EMG) in triceps surae, stiffness and elastic energy utilization of the Achilles tendon] and investigated the correlations between these effects and performances [voluntary electromechanical delay (EMD) and jump height]. Twenty‐one subjects were randomly assigned either to the control group (10 subjects: age 22.3±1.6 years) or to a training group (11 subjects: age 22.1±1.6 years) that performed 8 weeks of plyometric training. Results: As compared with the performances before training, normalized EMG in the soleus were significantly (P≤0.001) increased after 4 and 8 weeks of training. Tendon stiffness, elastic energy storage, release and jump height determined after training were significantly increased (P<0.05), with a concomitantly reduced voluntary EMD (P=0.01). These variables also showed significant differences vs the control group (all P<0.05). The other variables remained unchanged. Correlations were observed between tendon stiffness and either voluntary EMD (r=−0. 77, P=0.014) or jump height (r=0.54, P=0.031). Conclusions: Plyometric training specifically potentiated the normalized EMG, tendon stiffness and elastic energy utilization in the myotendinous complex of the triceps surae. Although these changes are possibly essential determinants, only increases of tendon stiffness were observed to correlate with performance improvements.

Correlation of bone marrow lipid water content with bone mineral density on the lumbar spine.

Study Design. Prospective study. Objectives. To assess the proton MR spectroscopy (1H MRS) of vertebral bone marrow and correlate the lipid water ratio (LWR) and spectral line width (LW) with bone mineral density (BMD) in female subjects. Summary of Background Data. The mechanism of bone marrow fat accumulation and bone mineral content is poorly understood. Proton MR spectroscopy was used to demonstrate the lipid and water spectra in the bone marrow. We try to assess the possible interaction between the bone marrow lipid content, aging, and BMD. Methods. Proton MRS and BMD of the lumbar spine were performed in 52 female subjects (mean age, 58 years; SD, 10 years). They were 13 premenopausal and 39 postmenopausal women. The BMD (g/cm2) was measured using dual energy radiograph absorptiometry at the lumbar spine. Single voxel 1H MRS was measured at L3 vertebral body by stimulated echo-acquisition mode (STEAM) sequence and demonstrated two major peaks (lipid and water). Comparisons of the differences between the two subgroups were made. Pearson’s correlation was also calculated to explore the association of 1H MRS measurements with age and BMD. Partial correlation was further conducted when controlling the variable such as age or BMD. Results. BMD and LWR had statistically significant difference between the pre- and postmenopausal subgroups (P < 0.001), while lipid LW had a borderline difference and water LW had no difference. LWR was positively correlated with age (r = 0.52 and P < 0.0001) and negatively correlated with BMD (r = −0.40 and P = 0.003) for all the subjects. Lipid LW was negatively correlated with age (r = −0.32 and P = 0.0197) and positively correlated with BMD (r = 0.67 and P < 0.0001). When controlling for BMD effect, only LWR is statistically correlated with age (partial r = 0.39, P = 0.0045), while only the lipid LW is statistically correlated with BMD when controlling for age (partial r = 0.63, P < 0.0001). None of the correlations between water LW and age or BMD was significant. In the subgroups, only the lipid LW is significantly correlated with BMD (r = 0.78, P = 0.0016 in premenopausal women; r = 0.62, P < 0.0001 in postmenopausal women). Conclusion. The LWR had a positive correlation with the age, while the lipid LW had a positive correlation with BMD, even after controlling the age factor. The bone marrow lipid water content and metabolism acted as important roles in the internal environment of bone and influenced bone mineralization.

Evaluation of the diagnostic performance of infrared imaging of the breast: a preliminary study

BackgroundThe study was conducted to investigate the diagnostic performance of infrared (IR) imaging of the breast using an interpretive model derived from a scoring system.MethodsThe study was approved by the Institutional Review Board of our hospital. A total of 276 women (mean age = 50.8 years, SD 11.8) with suspicious findings on mammograms or ultrasound received IR imaging of the breast before excisional biopsy. The interpreting radiologists scored the lesions using a scoring system that combines five IR signs. The ROC (receiver operating characteristic) curve and AUC (area under the ROC curve) were analyzed by the univariate logistic regression model for each IR sign and an age-adjusted multivariate logistic regression model including 5 IR signs. The cut-off values and corresponding sensitivity, specificity, Youdens Index (Index = sensitivity+specificity-1), positive predictive value (PPV), negative predictive value (NPV) were estimated from the age-adjusted multivariate model. The most optimal cut-off value was determined by the one with highest Youdens Index.ResultsFor the univariate model, the AUC of the ROC curve from five IR signs ranged from 0.557 to 0.701, and the AUC of the ROC from the age-adjusted multivariate model was 0.828. From the ROC derived from the multivariate model, the sensitivity of the most optimal cut-off value would be 72.4% with the corresponding specificity 76.6% (Youdens Index = 0.49), PPV 81.3% and NPV 66.4%.ConclusionsWe established an interpretive age-adjusted multivariate model for IR imaging of the breast. The cut-off values and the corresponding sensitivity and specificity can be inferred from the model in a subpopulation for diagnostic purpose.Trial RegistrationNCT00166998.