Probe classification of on-off type DNA microarray images with a nonlinear matching measure.

We propose a nonlinear matching measure, called counting measure, as a signal detection measure that is defined as the number of on pixels in the spot area. It is applied to classify probes for an on-off type DNA microarray, where each probe spot is classified as hybridized or not. The counting measure also incorporates the maximum response search method, where the expected signal is obtained by taking the maximum among the measured responses of the various positions and sizes of the spot template. The counting measure was compared to existing signal detection measures such as the normalized covariance and the median for 2390 patient samples tested on the human papillomavirus (HPV) DNA chip. The counting measure performed the best regardless of whether or not the maximum response search method was used. The experimental results showed that the counting measure combined with the positional search was the most preferable.

Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model.

BACKGROUND: Mesenchymal stem cells (MSCs) offer a novel therapeutic option in the treatment of acute myocardial infarction. MSCs are able to differentiate into myogenic cells after 5-azacytitdine treatment. However, 5-azacytidine might have genotoxic effects. Recently, it was reported that combined treatment with bone morphogenetic protein-2(BMP-2) and fibroblast growth factor-4(FGF-4) caused cardiac differentiation in non-precardiac mesoderm explants. Therefore, we investigated whether MSCs treated with combined BMP-2 and FGF-4 showed evidence of myogenic differentiation in vitro, and whether these cells resulted in sustained engraftment, myogenic differentiation, and improved cardiac function after implantation in infarcted myocardium. METHODS AND RESULTS: In vitro study: MSCs were treated with BMP-2 + FGF-4 (GF-MSCs) and myogenic phenotype was evaluated immunohistochemically. Cell growth curve was used to compare MSC proliferative capacity between the growth factors and 5-azacytidine treatments. In vivo study: two weeks after coronary artery occlusion, GF-MSCs (n=15), MSCs (n=5) labelled with PKH26 were injected into infarcted myocardium. Control animals (n=5) received a culture medium into the infarcted myocardium. Two weeks after implantation, some engrafted GF-MSCs or MSCs expressed sarcomeric-alpha-actinin and cardiac myosin heavy chain, as was observed in culture. Echocardiography showed that the GF-MSC group had a better (p < 0.05) left ventricular performance than the other groups. CONCLUSION: GF-MSCs induced myogenic differentiation in vitro. Moreover, GF-MSCs engrafted into the infarcted myocardium increased myogenic differentiation, prevented dilation of the infarcted region, and eventually improved heart function.

Computerized scheme for assessing ultrasonographic features of breast masses.

RATIONALE AND OBJECTIVE: To evaluate the ultrasonographic features of breast masses using a computerized scheme and to correlate the feature values with radiologists' grading. MATERIALS AND METHODS: One hundred and seventy-five breast ultrasound images (one to five images per subject) from 61 women (age 17-89 years, mean 43 years) were studied. Thirty-eight of the 157 images were from 11 women with malignant lesions, and the remaining 137 were from 50 patients with benign lesions. Two breast imaging radiologists participated in an observer performance study and were asked to grade, on a scale of 3, shape (1: regular, 3: very irregular), border (1: sharp, 3: ill-defined), internal texture (1: homogeneous, 3: very heterogeneous), width/depth ratio (1: flat, 3: tall), posterior enhancement (1: strong, 3: none), and lateral shadowing (1: strong, 3: none). The computerized scheme analyzed the breast region within a region of interest that was placed by a radiologist and quantified the following parameters: shape (jag count, disperse, convex hull depth, and lobulation count), border (acutance, average maximum ascending gradient, and sigmoid curve fitting), texture (edge density, co-occurrence matrix, and fractal dimension), width-depth ratio, posterior enhancement, and lateral shadowing. Correlations between the radiologists and the computerized scheme for assessing parameters in corresponding categories were computed. RESULTS: Good agreement was seen in posterior enhancement (P < .001, r = 0.45), lateral shadowing (P < .001, r = 0.38), width-depth ratio (P < .001, r = 0.33), and shape features (all P < .001): jag count (r = 0.38), disperseness (r = 0.55), and convex hull depth (r = 0.44). The remaining parameters demonstrated a poor or weak correlation (r < 0.30). CONCLUSION: The radiologists and the computerized scheme correlated best in analysis of shape features and posterior enhancement. We have yet to determine the significance of these features for the implementation of a computer-aided diagnosis program for characterizing breast ultrasound masses.

In vivo evaluation of the pulsatile ECLS system.

Extracorporeal life support (ECLS) systems have been increasingly applied to groups of patients with cardiorespiratory failure, including pediatric and adult patients with respiratory failure. Current pulsatile ECLS systems use a single pulsatile blood pump that generates a high inlet pressure in the membrane oxygenator. To minimize this high inlet pressure, we have developed a new and improved ECLS system, twin pulse life support (T-PLS). To analyze the advantages of T-PLS, we have compared T-PLS with a single pulsatile ECLS system. An acute heart failure model was constructed by using a pulmonary artery banding technique. Fourteen pigs (22-31 kg) were used, with cardiac outputs of 2.0 l/min and a V/Q ratio set at 1. Cannulae of 28 Fr and 18 Fr were used in the right atrium and aorta, respectively. A polypropylene hollow-fiber membrane oxygenator and four polymer valves 30 mm in diameter were used in the T-PLS system. In the single pulsatile ECLS system, Medtronic Hall monostrut valves were used. To evaluate blood cell trauma in both pulsatile ECLS systems, plasma free hemoglobin (fHb) was measured while the systems were in use. The results show that fHb levels in T-PLS are lower than fHb levels in the single pulsatile ECLS system. There is a possibility that T-PLS could be used as an ECLS system for emergency situations.

Heparin monitoring in sheep by activated partial thromboplastin time.

Heparin anticoagulation is utilized during and after vascular surgery in animals to reduce the risk of acute or chronic thromboembolic problems. In this study, we examined variation of activated partial thromboplastin time APTT) after the intravenous bolus IV bolus) and subcutaneous SC) heparin injection in order to monitor heparin therapy in sheep. Nine healthy sheep were assigned to 3 groups A, B, and C) according to their body weights: less than 40 kg, 40 to 80 kg, and more than 80 kg, respectively. All animals were treated with heparin 300 IU/kg body weight) through two routes, and the APTT, fibrinogen, and platelet count were measured before and every hour after treatment. This showed that the APTT was increased significantly between 1 to 4 hours after IV bolus injection and between 2 to 6 hours after SC injection P < 0.05). The APTT was returned to baseline values 6 and 10 hours after the respective treatments. The APTT in Group C was consistently higher than in Group A and B after heparin treatment by the two routes. The APTT ratio entered the subtherapeutic range 5 and 8 hours after IV bolus and SC injection, respectively. The APTT ratio was maintained in the therapeutic range for about 1 and 4 hours after IV bolus and SC injection, respectively. The highest APTT ratio in Group C after SC injection of heparin was significantly higher than that in Groups A and B P < 0.05). The mean platelet counts in Groups A, B, and C before the injection were 3197 +/- 365.6, 2886 +/- 78.2, and 1861 +/- 298.0 102/microL, respectively. The mean platelet count gradually decreased without significant variation after IV bolus and SC injection. These results produced elementary data for monitoring in sheep using APTT, and suggested that heparin should be administrated by the SC route at 4-hour intervals in order to remain in the therapeutic range, after an initial IV bolus dose.

Classification of malignant and benign tumors using boundary characteristics in breast ultrasonograms.

We evaluated various spiculate and jagged margin shape features. These are known to be malignant characteristics in breast sonograms. A total of 79 breast ultrasonograms (60 benign, 19 malignant) containing solid breast nodules were evaluated. To determine the boundary of lesions, Markov random field segmentation was used. Our goal was to classify benign and malignant lesions on the breast sonogram. Our algorithm consisted of two steps: segmentation and classification. In the first step, a breast sonogram was segmented using low resolution and Gaussian-Markov random field. The fuzzy clustering method algorithm was then applied to the preprocessed image to initialize the segmentation. Next, to discriminate benign and malignant tumors three types of lesion characteristics were investigated: jag count, compactness, and acutance. Jag count was calculated based on the derivative of curvature, acutance was defined as gray-level variations across the lesion boundary, and compactness was defined as the ratio of boundary complexity to the enclosed area. Sensitivity of the three boundary features (jag count, compactness, and acutance) was 95.1, 94.1, and 81.1%, respectively, and their specificities were 97.2, 92.0, and 78%, respectively. The jag count performed best among the three boundary features. Our results indicate that computerized analysis of boundary characteristics can be an effective method for classifying solid breast nodules in ultrasonograms as malignant or benign. We found that curvature analysis was the best shape features. The curvature method classifies better than the compactness or acutance methods.