Detecting changes in ultrasound backscattered statistics by using Nakagami parameters: Comparisons of moment-based and maximum likelihood estimators.

The Nakagami distribution is an approximation useful to the statistics of ultrasound backscattered signals for tissue characterization. Various estimators may affect the Nakagami parameter in the detection of changes in backscattered statistics. In particular, the moment-based estimator (MBE) and maximum likelihood estimator (MLE) are two primary methods used to estimate the Nakagami parameters of ultrasound signals. This study explored the effects of the MBE and different MLE approximations on Nakagami parameter estimations. Ultrasound backscattered signals of different scatterer number densities were generated using a simulation model, and phantom experiments and measurements of human liver tissues were also conducted to acquire real backscattered echoes. Envelope signals were employed to estimate the Nakagami parameters by using the MBE, first- and second-order approximations of MLE (MLE1 and MLE2, respectively), and Greenwood approximation (MLEgw) for comparisons. The simulation results demonstrated that, compared with the MBE and MLE1, the MLE2 and MLEgw enabled more stable parameter estimations with small sample sizes. Notably, the required data length of the envelope signal was 3.6 times the pulse length. The phantom and tissue measurement results also showed that the Nakagami parameters estimated using the MLE2 and MLEgw could simultaneously differentiate various scatterer concentrations with lower standard deviations and reliably reflect physical meanings associated with the backscattered statistics. Therefore, the MLE2 and MLEgw are suggested as estimators for the development of Nakagami-based methodologies for ultrasound tissue characterization.

Cultural issues in post-disaster reconstruction: the case of Typhoon Morakot in Taiwan.

Most members of Taiwan's indigenous communities live in areas that are prone to natural disasters. Yet, due to their marginalised cultural, economic and political status, each time such calamities strike, any assistance they receive is usually provided without considering their actual needs. The areas hardest hit by Typhoon Morakot in August 2009 were the indigenous villages in the southern and eastern parts of the island. After the initial emergency relief efforts had been completed, there remained the highly challenging task of reconstruction and the resettlement of those who lost their homes and livelihoods. This paper examines the cultural conflicts that arose during the reconstruction process, with special emphasis on the participation of Taiwan's indigenous communities and their capacity for resilience. It was found that community participation and identification are key issues in effective disaster governance.

Changes in backscattered ultrasonic envelope statistics as a function of thrombus age: an in vitro study.

It is necessary to determine the age of thrombi in planning clinical treatment for thrombolysis. Ultrasound imaging can potentially be used to evaluate thrombus age in real time. The backscattered signals from thrombi may contain useful information regarding their age. On the basis of the randomness of ultrasound backscattering, this study explored changes in backscattered US statistics as a function of thrombus age. Porcine blood samples were used for the in vitro induction of fresh thrombi (day 0) with hematocrits ranging from 0%-40% and aged thrombi (days 0-8) with a hematocrit of 40%. Each thrombus was imaged using a pulse-echo ultrasound scanner equipped with a 7.5-MHz linear array transducer to acquire raw backscattered signals for B-mode and Nakagami imaging, by which the backscattered statistics were visualized. Hematoxylin and eosin staining and scanning electron microscopy were used to observe the histology of fresh and aged thrombi. The results indicated that a decrease in the number of red blood cells in the thrombus caused by the aging effect was observed in the in vitro model, indicating that the proposed model could simulate the structural changes in the thrombus during aging. Compared with fresh thrombi with various hematocrits, the aged thrombi exhibited a trend toward more substantial decreases in the Nakagami parameter with increasing thrombus age (the Nakagami parameter decreased from 1.1 to 0.6 as thrombus age increased from day 0 to day 8), indicating that thrombus aging causes the backscattered statistics to follow a pre-Rayleigh distribution to a high degree. This finding may be applied to the determination of thrombus age using conventional ultrasound imaging in the future.

Optical coherence tomography: a new strategy to image planarian regeneration.

The planarian is widely used as a model for studying tissue regeneration. In this study, we used optical coherence tomography (OCT) for the real-time, high-resolution imaging of planarian tissue regeneration. Five planaria were sliced transversely to produce 5 head and 5 tail fragments. During a 2-week regeneration period, OCT images of the planaria were acquired to analyze the signal attenuation rates, intensity ratios, and image texture features (including contrast, correlation, homogeneity, energy, and entropy) to compare the primitive and regenerated tissues. In the head and tail fragments, the signal attenuation rates of the regenerated fragments decreased from -0.2 dB/µm to -0.05 dB/µm, between Day 1 and Day 6, and then increased to -0.2 dB/µm on Day 14. The intensity ratios decreased to approximately 0.8 on Day 6, and increased to between 0.8 and 0.9 on Day 14. The texture parameters of contrast, correlation, and homogeneity exhibited trends similar to the signal attenuation rates and intensity ratios during the planarian regeneration. The proposed OCT parameters might provide biological information regarding cell apoptosis and the formation of a mass of new cells during planarian regeneration. Therefore, OCT imaging is a potentially effective method for planarian studies.

Early detection of liver fibrosis in rats using 3-D ultrasound Nakagami imaging: a feasibility evaluation.

We investigated the feasibility of using 3-D ultrasound Nakagami imaging to detect the early stages of liver fibrosis in rats. Fibrosis was induced in livers of rats (n = 60) by intraperitoneal injection of 0.5% dimethylnitrosamine (DMN). Group 1 was the control group, and rats in groups 2-6 received DMN injections for 1-5 weeks, respectively. Each rat was sacrificed to perform 3-D ultrasound scanning of the liver in vitro using a single-element transducer of 6.5 MHz. The 3-D raw data acquired at a sampling rate of 50 MHz were used to construct 3-D Nakagami images. The liver specimen was further used for histologic analysis with hematoxylin and eosin and Masson staining to score the degree of liver fibrosis. The results indicate that the Metavir scores of the hematoxylin and eosin-stained sections in Groups 1-4 were 0 (defined as early liver fibrosis in this study), and those in groups 5 and 6 ranged from 1 to 2 and 2 to 3, respectively. To quantify the degree of early liver fibrosis, the histologic sections with Masson stain were analyzed to calculate the number of fiber-related blue pixels. The number of blue pixels increased from (2.36 ± 0.79) × 10(4) (group 1) to (7.68 ± 2.62) × 10(4) (group 4) after DMN injections for 3 weeks, indicating that early stages of liver fibrosis were successfully induced in rats. The Nakagami parameter increased from 0.36 ± 0.02 (group 1) to 0.55 ± 0.03 (group 4), with increasing numbers of blue pixels in the Masson-stained sections (p-value < 0.05, t-test). We concluded that 3-D Nakagami imaging has potential in the early detection of liver fibrosis in rats and may serve as an image-based pathologic model to visually track fibrosis formation and growth.

Using ultrasound Nakagami imaging to assess liver fibrosis in rats.

This study explored the feasibility of using the ultrasound Nakagami image to assess the degree of liver fibrosis in rats. The rat has been widely used as a model in investigations of liver fibrosis. Ultrasound grayscale imaging makes it possible to observe fibrotic rat livers in real time. Statistical analysis of the envelopes of signals backscattered from rat livers may provide useful clues about the degree of liver fibrosis. The Nakagami-model-based image has been shown to be useful for characterizing scatterers in tissues by reflecting the echo statistics, and hence the Nakagami image may serve as a functional imaging tool for quantifying rat liver fibrosis. To validate this idea, fibrosis was induced in each rat liver (n=21) by an intraperitoneal injection of 0.5% dimethylnitrosamine. Livers were excised from rats for in vitro ultrasound scanning using a single-element transducer. The backscattered-signal envelopes of the acquired raw ultrasound signals were used for Nakagami imaging. The Metavir score determined by a pathologist was used to histologically quantify the degree of liver fibrosis. It was found that the Nakagami image could be used to distinguish different degrees of liver fibrosis in rats, since the average Nakagami parameter increased from 0.55 to 0.83 as the fibrosis score increased from 0 (i.e., normal) to 4. This correlation may be due to liver fibrosis in rats involving an increase in the concentration of local scatterers and the appearance of the periodic structures or clustering of scatterers that would change the backscattering statistics. The current findings indicate that the ultrasound Nakagami image has great potential as a functional imaging tool to complement the use of the conventional B-scan in animal studies of liver fibrosis.

Three-dimensional ultrasonic Nakagami imaging for tissue characterization.

The two-dimensional (2D) Nakagami image complements the ultrasound B-scan image when attempting to visualize the scatterer properties of tissues. The resolution of the Nakagami image is lower than that of the B-scan image, since the former is produced by processing the raw envelope data using a 2D sliding window with side lengths typically corresponding to three times the pulse length of the incident ultrasound. This paper proposes using three-dimensional (3D) Nakagami imaging for improving the resolution of the obtained Nakagami image and providing more complete information of scatterers for a better tissue characterization. The 3D Nakagami image is based on a voxel array composed of the Nakagami parameters constructed using a 3D sliding cube to process the 3D backscattered raw data. Experiments on phantoms with different scatterer concentrations were carried out to determine the optimal size of the sliding cube for a stable estimation of the Nakagami parameter. Tissue measurements on rat livers without and with fibrosis formation were further used to explore the practical feasibility of 3D Nakagami imaging. The results indicated that the side length of the cube used to construct the 3D Nakagami image must be at least two times the pulse length, which improved the resolution for each Nakagami image frame in the 3D Nakagami image. The results further demonstrated that the 3D Nakagami image is better than the conventional 2D Nakagami image for complementing the B-scan in detecting spatial variations in the scatterer concentration and classifying normal and fibrotic livers. This study suggests that 3D Nakagami imaging has the potential to become a new 3D quantitative imaging approach.

Association between color doppler vascularity index, angiogenesis-related molecules, and clinical outcomes in gastric cancer.

PURPOSE: This study was conducted to evaluate the correlation between color Doppler vascularity index (CDVI), clinical outcomes and five angiogenesis-related molecules including vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and calreticulin (CRT) in gastric cancer, and to develop an effective model selected from these five molecules to predict patient survival. PATIENTS AND METHODS: CDVI could be obtained preoperatively by transabdominal ultrasound from 30 patients. Enzyme immunoassay was adopted to determine protein level of VEGF and PlGF, and immunohistochemistry was used to detect COX-2, iNOS and CRT expression. Correlation between CDVI and five individual molecules was assessed. Multiple molecules model was developed using classification and regression tree (CART) analysis from five molecules, and was tested for patient survival in another 45 patients. RESULTS: CDVI was significantly correlated with patient survival (P = 0.00907) and absolute number of metastatic lymph nodes (P = 0.01). There was no significant association between CDVI and any individual molecule. The model, developed by CART consisting of VEGF and PlGF, could differentiate high and low CDVI and survival in testing group (P = 0.00257). CONCLUSIONS: CDVI was associated with lymph node metastasis, combined VEGF and PlGF expression status and patient survival in gastric cancer.

Aggregation of human serum albumin during a thermal viral inactivation step.

A terminal pasteurization step has been used for some plasma-derived protein products such as human serum albumin (HSA), which consists of heating the protein in solution at 60 degrees C for 10 h. Native and denaturing SDS-PAGE and dynamic light scattering were used to follow the stability of HSA during this process. It appears that a thermally unstable fraction, comprised primarily of haptoglobin, is involved in the formation of soluble aggregates of HSA. Therefore, it appears that aggregation during heat treatment is not due to conformational instability of HSA itself, but arises from unfolding of a thermally labile protein impurity. As haptoglobin aggregates, it entraps some HSA, which is present at much higher concentrations. This study emphasizes that, in a complex mixture of naturally occurring proteins, one thermally labile species can trigger aggregation of more stable proteins.

Arterial pulse waveform analysis by the probability distribution of amplitude.

Augmentation index (AIx) calculated from the pressure waveform of an artery is widely used to quantify the arterial stiffness and evaluate the cardiovascular risk. The key for calculating AIx is to locate the inflection point on the waveform signal, which is caused by the wave reflection. This study applies the probability distribution of the pressure waveform to identify the inflection point for estimating AIx. The results show that the pulse wave probability analysis not only can estimate AIx with a better tolerance of noise interference, but also allows for simultaneously monitoring, locating and characterizing other physiologically significant points on the pressure waveform.

The interactions between GPR30 and the major biomarkers in infiltrating ductal carcinoma of the breast in an Asian population.

OBJECTIVE: G-protein-coupled receptor 30 (GPR30) has been reported to be a novel estrogen receptor alpha (ERalpha) in vitro. Therefore, the interactions among GPR30, ERalpha, progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2/neu), and their prognostic utilities in the infiltrating ductal carcinoma (IDC) of the breast were evaluated. MATERIALS AND METHODS: Messenger RNA (mRNA) levels of GPR30, ERalpha, PR and HER-2/neu in the tumor samples of 118 Taiwanese IDC patients and 27 non-tumor mammary tissues were measured via quantitative polymerase chain reaction analyses. The correlations of GPR30 mRNA levels with clinical parameters, i.e. tumor/non-tumor, ERalpha, PR, HER-2/neu, age, lymph node metastasis, lymph-vascular invasion, grade, stage and patient survival, were assessed by using appropriate statistical analyses. RESULTS: GPR30 expression was observed to be lower in IDC (p < 0.001) than in non-tumor mammary tissues. Importantly, GPR30 mRNA level was positively correlated with that of ERalpha (p = 0.001) and PR (p = 0.001) but not correlated with that of HER-2/neu when they were analyzed as continuous variables. However, lower GPR30 was noticed in tumors with HER-2/neu protein overexpression. GPR30 expression was not correlated with age, lymph node metastasis, lymph-vascular invasion, grade and stage in IDC. GPR30 expression was not an independent prognostic factor for patient survival. CONCLUSION: GPR30 expression is downregulated in IDC. GPR30 is preferentially co-expressed with ER and/or PR but is lowly expressed in HER-2/neu(+) tumors. The correlation of GPR30 expression with clinical parameters, including patient survival, was not evident in this cohort.

A gene expression profile for vascular invasion can predict the recurrence after resection of hepatocellular carcinoma: a microarray approach.

BACKGROUND: Recurrence after hepatocellular carcinoma (HCC) resection is the major obstacle to improved survival. The presence of vascular invasion (VI) in pathology specimens is a well-known unfavorable prognostic factor for HCC recurrence. Though some VI-related genes have been reported, their association with recurrence-free survival is not known. We hypothesized that a gene expression profile for VI can predict the recurrence of HCC after liver resection. METHODS: Eighteen patients receiving complete HCC resection were included as a "training group". Genome-wide gene expression profile was obtained for each tumor using a microarray technique. Datasets were subjected to clustering analysis supervised by the presence or absence of VI to obtain 14 discriminative genes. We then applied those genes to execute pattern recognition using the k-Nearest Neighbor (KNN) classification method, and the best model for this VI gene signature to predict recurrence-free survival in the training group was obtained. The resulting model was then tested in an independent "test group" of 35 patients. RESULTS: A 14-gene profile was extracted which could accurately separate ten patients with VI and eight patients without VI in the "training group". In the "test group", significant difference in disease-free survival was found between patients predicted to have and not to have recurrence (P = .02823). In patients with stage_I disease, this model can also predict outcomes (P = .000205). CONCLUSIONS: Using the 14-gene expression profile extracted from microarrays based on the presence of VI can effectively predict recurrence after HCC resection. This approach might facilitate "personalized medicine" for HCC patients after surgical resection.

Gene expression profile predicts patient survival of gastric cancer after surgical resection.

PURPOSE: This study was conducted to characterize gene expression profile of survival in patients with surgically curable gastric cancer by using an in-house membrane microarray and developing a survival prediction model. MATERIALS AND METHODS: Data of cDNA microarrays were obtained from 18 pairs of cancerous and noncancerous gastric tissues. Nine patients who survived > 30 months were identified as good survival, and the other nine, who survived < 12 months, were identified as poor survival. Supervised analysis was performed to identify a gene expression profile by good and poor survival. Semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to confirm the microarray data in 10 patients with sufficient RNA. Using these 10 patients and another 10 patients selected randomly from 40 newly enrolled patients as the training group, the RT-PCR status of the confirmed genes was used for predicting good versus poor survival. Finally, the prediction model was tested in the remaining 30 newly enrolled gastric cancer patients. RESULTS: A survival prediction model consisting of three genes (CD36, SLAM, PIM-1) was developed. This model could correctly predict poor or good survival in 23 (76.7%) of 30 newly enrolled patients, and yielded a specificity of 80% and a sensitivity of 73.3%. The survival rate of the patients predicted to have good survival was significantly higher than that of those predicted to have poor survival in the test group as a whole (N = 30; P = .00531) and in stage III patients (n = 16; P = .04467). CONCLUSION: The semiquantitative RT-PCR gene expression profiling of three genes extracted from microarray study can accurately predict surgery-related outcome in gastric cancer patients.

Phylogenetic relationships and biochemical properties of the duplicated cytosolic and mitochondrial isoforms of malate dehydrogenase from a teleost fish, Sphyraena idiastes.

Unlike birds and mammals, teleost fish express two paralogous isoforms (paralogues) of cytosolic malate dehydrogenase (cMDH; EC 1.1.1.37; NAD+: malate oxidoreductase) whose evolutionary relationships to the single cMDH of tetrapods are unknown. We sequenced complementary DNAs for both cMDHs and the mitochondrial isoform (mMDH) of the fish Sphyraena idiastes (south temperate barracuda) and compared the sequences, kinetic properties, and thermal stabilities of the three isoforms with those of mammalian orthologues. Both fish cMDHs comprise 333 residues and have subunit masses of approximately 36 kDa. One cytosolic isoform, cMDH-S, was significantly more heat-stable than either the other cMDH (cMDH-L) or mMDH. In contradiction to the generally accepted model of vertebrate cMDH evolution, our phylogenetic analysis indicates that the duplication of the fish cytosolic paralogues occurred after the divergence of the lineages leading to teleosts and tetrapods. cMDH-L and cMDH-S differed in optimal concentrations of substrates and cofactors and apparent Michaelis-Menten constants, suggesting that the two paralogues may play distinct physiological roles. Differences in intrinsic thermal stability among MDH paralogues may reflect different degrees of stabilization in vivo by extrinsic stabilizers, notably protein concentration in the case of mMDH. Thermal stabilities of porcine mMDH and cMDH-L, but not cMDH-S, were significantly increased when denaturation was measured at a high protein (bovine serum albumin; BSA) concentration, but the BSA-induced stabilization reduced the catalytic activity.