Spatial analysis of acoustic noise transfer function with a human-body phantom in a clinical MRI scanner.

BACKGROUND: The acoustic noise in magnetic resonance imaging (MRI) potentially depends on the measurement position and presence of a patient inside the scanner bore. PURPOSE: To analyze the spatial characteristics of the acoustic noise by using the gradient-pulse-to-acoustic-noise transfer function (GPAN-TF) with and without a human-body phantom on the examination table. MATERIAL AND METHODS: Acoustic noise waveforms were acquired at 80 and 110 measurement positions with and without a phantom. The GPAN-TFs µPa/(mT/m) in the coils were calculated by deconvolution. The phantom effect on the spatial distribution of the acoustic noise was assessed using the peak sound pressure levels (SPLs), mean values, peak values, and peak frequencies of the GPAN-TFs. RESULTS: The peak SPLs in all positions for the X-, Y-, and Z-gradient coils were increased by 11.1 dB, 1.4 dB, and 6.1 dB, respectively, compared with the peak SPL of the magnetic isocenter. The maximum peak SPLs among all positions of the X-, Y-, and Z-gradient coils with the phantom were increased by 4.9 dB, 7.4 dB, and 6.9 dB, respectively, relative to those without the phantom. However, the peak SPLs decreased at some positions with the phantom placed on the table (X-gradient coil = 4.6 dB, Y-gradient coil = 5.0 dB, Z-gradient coil = 8.4 dB). The most common peak frequencies were in the range of 2000-3000 Hz. CONCLUSION: "Hotspot" areas with and without the phantom were associated with acoustic noise sources in the clinical MRI scanner and were enhanced by the phantom's presence.

Structure of the mouse sex peptide pheromone ESP1 reveals a molecular basis for specific binding to the class C G-protein-coupled vomeronasal receptor.

Exocrine gland-secreting peptide 1 (ESP1) is a sex pheromone that is released in male mouse tear fluids and enhances female sexual receptive behavior. ESP1 is selectively recognized by a specific class C G-protein-coupled receptor (GPCR), V2Rp5, among the hundreds of receptors expressed in vomeronasal sensory neurons (VSNs). The specific sensing mechanism of the mammalian peptide pheromone by the class C GPCR remains to be elucidated. Here we identified the minimal functional region needed to retain VSN-stimulating activity in ESP1 and determined its three-dimensional structure, which adopts a helical fold stabilized by an intramolecular disulfide bridge with extensive charged patches. We then identified the amino acids involved in the activation of VSNs by a structure-based mutational analysis, revealing that the highly charged surface is crucial for the ESP1 activity. We also demonstrated that ESP1 specifically bound to an extracellular region of V2Rp5 by an in vitro pulldown assay. Based on homology modeling of V2Rp5 using the structure of the metabotropic glutamate receptor, we constructed a docking model of the ESP1-V2Rp5 complex in which the binding interface exhibited good electrostatic complementarity. These experimental results, supported by the molecular docking simulations, reveal that charge-charge interactions determine the specificity of ESP1 binding to V2Rp5 in the large extracellular region characteristic of class C GPCRs. The present study provides insights into the structural basis for the narrowly tuned sensing of mammalian peptide pheromones by class C GPCRs.

Development and validation of an analysis method for pesticide residues by gas chromatography-tandem mass spectrometry in Daikenchuto.

Daikenchuto (DKT) is one of the most widely used "Kampo" in Japan as a representative of herbal medicine. Because DKT is made from a natural product like food, it requires the management of pesticides; therefore, an analysis of residual pesticides in Kampo is required. The World Health Organization (WHO) indicates that pesticide residue analysis by the U.S. Pharmacopeia (USP) is required. USP defines 107 compounds containing organochlorine pesticides and organophosphorus pesticides and their metabolites, which have a high residual risk. Accordingly, to guarantee the safety of herbal medicines according to global standards is a very important issue. In this study, we developed an analytical method for 91 compounds, which are listed in USP, using DKT as the subject. The method could extract pesticides from DKT with acetone, elute pesticides with acetonitrile using a SepPak C18 column (5 g) and with ethyl acetate using a DSC-NH2 column (2 g), and perform simultaneous analyses by gas chromatography-tandem mass spectrometry (GC-MS/MS). This method, which could quantify 88 compounds, was validated according to USP. A pesticide residue analysis method that meets USP requirements enables the analysis of pesticide residues with a high residue risk and contributes to improving the safety of "Kampo" and other herbal medicines.

[Quantitative evaluation of Gd-EOB-DTPA uptake in phantom study for liver MRI].

Gd-EOB-DTPA is a new liver specific MRI contrast media. In the hepatobiliary phase, contrast media is trapped in normal liver tissue, a normal liver shows high intensity, tumor/liver contrast becomes high, and diagnostic ability improves. In order to indicate the degree of uptake of the contrast media, the enhancement ratio (ER) is calculated. The ER is obtained by calculating (signal intensity (SI) after injection-SI before injection) / SI before injection. However, because there is no linearity between contrast media concentration and SI, ER is not correctly estimated by this method. We discuss a method of measuring ER based on SI and T(1) values using the phantom. We used a column phantom, with an internal diameter of 3 cm, that was filled with Gd-EOB-DTPA diluted solution. Moreover, measurement of the T(1) value by the IR method was also performed. The ER measuring method of this technique consists of the following three components: 1) Measurement of ER based on differences in 1/T(1) values using the variable flip angle (FA) method, 2) Measurement of differences in SI, and 3) Measurement of differences in 1/T(1) values using the IR method. ER values calculated by these three methods were compared. In measurement made using the variable FA method and the IR method, linearity was found between contrast media concentration and ER. On the other hand, linearity was not found between contrast media concentration and SI. For calculation of ER using Gd-EOB-DTPA, a more correct ER is obtained by measuring the T(1) value using the variable FA method.

Nickel-Catalyzed Hydroarylation of in Situ Generated 1,3-Dienes with Arylboronic Acids Using a Secondary Homoallyl Carbonate as a Surrogate for the 1,3-Diene and Hydride Source.

The nickel-catalyzed hydroarylation of 1,3-dienes with arylboronic acids using a secondary homoallyl carbonate as a surrogate for the 1,3-diene and hydride source has been developed. The synthetic strategy allowed an efficient access to a wide array of hydroarylation products in high yields with high functional group compatibility without the use of an external hydride source. Mechanistic experiments indicated that the alkene-directed oxidative addition and subsequent ß-hydride elimination would be a critical process in this transformation.

Fast Phase-Contrast Cine MRI for Assessing Intracranial Hemodynamics and Cerebrospinal Fluid Dynamics.

We propose fast phase-contrast cine magnetic resonance imaging (PC-cine MRI) to allow breath-hold acquisition, and we compared intracranial hemo- and hydrodynamic parameters obtained during breath holding between full inspiration and end expiration. On a 3.0 T MRI, using electrocardiogram (ECG)-synchronized fast PC-cine MRI with parallel imaging, rectangular field of view, and segmented k-space, we obtained velocity-mapped phase images at the mid-C2 level with different velocity encoding for transcranial blood flow and cerebrospinal-fluid (CSF) flow. Next, we calculated the peak-to-peak amplitudes of cerebral blood flow (ΔCBF), cerebral venous outflow, intracranial volume change, CSF pressure gradient (ΔPG), and intracranial compliance index. These parameters were compared between the proposed and conventional methods. Moreover, we compared these parameters between different utilized breath-hold maneuvers (inspiration, expiration, and free breathing). All parameters derived from the fast PC method agreed with those from the conventional method. The ΔPG was significantly higher during full inspiration breath holding than at the end of expiration and during free breathing. The proposed fast PC-cine MRI reduced scan time (within 30 s) with good agreement with conventional methods. The use of this method also makes it possible to assess the effects of respiration on intracranial hemo- and hydrodynamics.

Decreased ID2 promotes metastatic potentials of hepatocellular carcinoma by altering secretion of vascular endothelial growth factor.

PURPOSE: We aimed to explore the molecular and biological functions of Inhibitor of DNA binding/differentiation 2 (ID2), which was found to be responsible for portal vein invasion of hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: We measured ID2 mRNA levels in 92 HCC patients by real-time reverse transcription-PCR and examined the relation to clinicopathologic features. To clarify the precise roles of ID2, we did in vitro analysis with expression vectors and small interfering RNAs. Effects of ID2 on cell invasive potential and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1alpha were analyzed by Matrigel-coated invasion chamber, ELISA, and Western blot analysis, respectively. RESULTS: ID2 mRNA level correlated inversely with portal vein invasion (P < 0.001), tumor-node-metastasis stage (P < 0.001), tumor size (P < 0.001), and early intrahepatic recurrence (P < 0.05). When limited to a cohort of hepatitis C virus-related HCCs, patients with low levels of ID2 had significantly shorter disease-free survival time than those with high levels of ID2. Invasive potential of cells transfected with ID2 expression vector was lower than that of empty vector-transfected cells. Cells overexpressing ID2 also showed decreased VEGF secretion and hypoxia-inducible factor-1alpha protein levels. The results of ID2-knockdown experiments were opposite to those of ID2 overexpression experiments. CONCLUSIONS: On the basis of our clinical and in vitro data, we suggest that ID2 plays a significant role in the metastatic process during progression of HCC. This action might be explained, at least in part, by altered cell mobility due to decreased secretion of VEGF.

Glycolysis module activated by hypoxia-inducible factor 1alpha is related to the aggressive phenotype of hepatocellular carcinoma.

An increased level of glycolysis, an intracellular hallmark of neoplasms, enables cancer cells to survive under various conditions. To elucidate the role of increased glycolysis in the progression of hepatocellular carcinoma (HCC), we investigated the associations between the expression patterns of 14 glycolysis-related genes and clinicopathologic factors in 60 HCCs by using pooled transcriptome data. We then evaluated the therapeutic efficacy of the knockdown of ENO1, which is encoded by a glycolysis-related gene, in HCC cells. Among the 14 genes, levels of 8 genes (GPI, ALDOA, TPI1, GAPD, PGK, PGAM, ENO1 and PKM), all of which can be transcriptionally activated by hypoxia-inducible factor 1alpha (HIF-1alpha), were significantly higher in HCC with venous invasion (VI) than in HCC without VI. Our cluster analysis showed that HCC patients with activation of the 8 HIF-1alpha-regulated genes had significantly shorter overall survival (P=0.023) than did HCC patients without increased expression levels of these genes. The association between the levels of ENO1 and VI was confirmed in an independent sample set of 49 HCCs by real-time reverse-transcription PCR. The knockdown of ENO1 by small-interfering RNA significantly inhibited the proliferation of an HCC cell line (HLE cells) in both the glucose-rich and glucose-free conditions, accompanied by a decreased S phase and increased G2/M phase of the cell cycle. Collectively, these data suggest that activation of an HIF-1alpha-regulated glycolysis module is closely related to the aggressive phenotype of HCC, and that ENO1, a glycolysis module gene, might serve as a new target to circumvent HCC metastasis.

A three-gene predictor for early intrahepatic recurrence of hepatocellular carcinoma after curative hepatectomy.

We previously developed a DNA microarray-based system that out-performs traditionally used clinical parameters for prediction of early intrahepatic recurrence (IHR) of hepatocellular carcinoma (HCC). Because DNA microarray is too expensive for daily clinical use, we used a quantitative real-time reverse transcription-polymerase chain reaction (QRT-PCR) to develop a lower-cost predictor for early IHR. From the 12 early IHR-related genes integrated in the previous predictor, we selected 6 genes whose levels showed the strongest association between data from the 2 distinct DNA microarray platforms with the same sample set. Expression of these 6 genes relative to that of GAPDH was measured by QRT-PCR in 82 HCCs. Of the 82 HCCs, 39 and 43 were assigned to training and independent test sets, respectively. By searching all combinations (n=2-6) of the 6 genes, we found an optimal combination of 3 genes (HLADRA, DDX17 and LAPTM5) that minimized the leave-one-out error for prediction of early IHR in the training set. The 3-gene predictor constructed with the Fisher linear classifier correctly predicted early IHR or non-recurrence in 35 (81.4%) of 43 HCCs in the independent test set and had a high positive predictive value of 72.7% and a high negative predictive value of 84.4%. Multivariate analysis with the stepwise logistic regression showed that the 3-gene predictor [F(x)<0] was an independent risk factor for early IHR (risk ratio, 13.6; p=0.006), indicating its potential as an easy-to-use predictor for accurate prediction of early IHR of HCC.

[Influence of mechanical effect due to MRI-magnet on tattoo seal and eye makeup].

The purpose of our study was to assess the mechanical effect on tattoo seals and eye makeup caused by a spatial magnetic gradient in the magnetic resonance imaging (MRI) system. Seven kinds of tattoo seals and three kinds of eye makeup, i.e., mascara, eye shadow, and eyeliner were used. On a 3.0-Tesla MRI, we determined these deflection angles according to a method established by the American Society for Testing and Materials (ASTM) at the position that produced the greatest magnetically induced deflection. Eighty-five percent of the tattoo seals showed deflection angles greater than 45 degrees of the ASTM guidelines, and the mascara and eye shadow showed over 40 degrees. This was because these contained ferromagnetic pigments such as an iron oxide, but those translational forces were very small owing to slight mass. However, it is desirable that these should be removed before MRI examination to prevent secondary problems.

Involvement of c-myc-regulated genes in hepatocellular carcinoma related to genotype-C hepatitis B virus.

PURPOSE: The purpose of this study was to elucidate the molecular basis of hepatocellular carcinoma (HCC) caused by genotype-C hepatitis B virus (HBV). METHODS: We compared molecular profiles of 15 HCCs and five non-tumorous livers, all of which were associated with genotype-C HBV infection, using DNA microarray technology. RESULTS: Our supervised learning identified 237 genes whose expression differed between HCCs and non-tumorous livers. This result was validated by a false discovery rate of 0%. Levels of expression of 35 and 202 genes were higher and lower, respectively, in HCCs than in non-tumorous livers. Among the 237 genes, we highlighted the top 35 upregulated and top 35 down regulated genes in tumor. Interestingly, when overlapping genes were excluded, 12 (e.g., NM23-H2, MCM7, PARP1, YWHAH, HSPB1, and MSH2) of the top 34 upregulated genes and five (e.g., MT1A and MT3) of the top 33 downregulated genes were c-myc-regulated genes. The microarray data for five randomly selected genes (MCM7, UBE2L3, PPIA, CXCL12, and ASS) were confirmed by quantitative real-time reverse transcription-polymerase chain reaction. CONCLUSIONS: Our results indicate that many c-myc-regulated genes are involved in genotype-C-HBV-related HCC, suggesting that c-myc is related to the hepatocarcinogenic activity of genotype-C HBV.

Quantitative analysis of hepatic fat fraction by single-breath-holding MR spectroscopy with T2 correction: phantom and clinical study with histologic assessment.

The focus of this study was on the investigation of the accuracy of the fat fraction of the liver by use of single-breath-holding magnetic resonance spectroscopy (MRS) with T (2) correction. Single-voxel proton MRS was performed with several TE values, and the fat fraction was determined with and without T (2) correction. MRS was also performed with use of the point-resolved spectroscopy sequence in single breath holding. The T (2) values of both water and fat were determined separately at the same time, and the effect of T (2) on the fat fraction was corrected. In addition, MRS-based fat fractions were compared with the degree of hepatic steatosis (HS) by liver biopsy in human subjects. With T (2) correction, the MRI-derived fat fractions were in good agreement with the fat fractions in all phantoms, but the fat fractions were overestimated without T (2) correction. R (2) values were in good agreement with the preset iron concentrations in the phantoms. The MRI-derived fat fraction was well correlated with the degree of HS. Iron deposited in the liver affects the signal strength when proton MRS is used for detection of the fat signal in the liver. However, the fat signal can be evaluated more accurately when the T (2) correction is applied. Breath-holding MRS minimizes the respiratory motion, and it can be more accurate in the quantification of the hepatic fat fraction.

Dorsoventral patterning of the Drosophila hindgut is determined by interaction of genes under the control of two independent gene regulatory systems, the dorsal and terminal systems.

Dorsoventral (DV) patterning in the trunk region of Drosophila embryo is established through intricate molecular interactions that regulate Dpp/Scw signaling during the early blastoderm stages. The hindgut of Drosophila, which derives from posterior region of the cellular blastoderm, also shows dorsoventral patterning, being subdivided into distinct dorsal and ventral domains. engrailed (en) is expressed in the dorsal domain, which determines dorsal fate of the hindgut. Here we show that a repressor Brk restricts en expression to the dorsal domain of the hindgut. Expression domain of brk during early blastdermal stages is defined through antagonistic interaction with dpp, and expression domains of dpp and brk in the early blastoderm include prospective hindgut domain. After stage 9, dpp expression in the dorsal domain of the hindgut primordium disappears, but, the brk expression in the ventral domain continues. It was found that Dorsocross (Doc), which is a targe gene of Dpp, is responsible for restricting brk expression to the ventral domain of the hindgut. On the other hand, activation of en is under the control of brachyenteron (byn) that is regulated independently of dpp, brk, and Doc. The cooperative interaction of common DV positional cues with byn during hindgut development represents another aspect of mechanisms of DV patterning in the Drosophila embryo.

[Influence of b value on the measurement of contrast and apparent diffusion coefficient in 3.0 Tesla breast magnetic resonance imaging].

Diffusion-weighted imaging (DWI) has been used to characterize not only the brain, but also the breast by implementation of faster imaging techniques and higher magnetic field strengths. However, the optimum b value, which is an important scan parameter for DW images contrast on 3 T breast magnetic resonance imaging (MRI) has not been established. The purpose of this study was to investigate the influence of different b value combinations on the image contrast and apparent diffusion coefficient (ADC) in patients with known invasive carcinoma, ductal carcinoma in situ (DCIS), and normal mammary gland in breast DWI. The analysis procedure consisted of the following methods: 1) T(2) correction of DW images with echo-planar imaging (EPI) T(2)-weighted images; 2) contrast measurement between normal mammary gland and tumor tissues; 3) ADC measurement of normal mammary gland and tumor tissues. In many cases, the highest contrast between normal mammary gland and tumor tissues was obtained using a b value of 1500 s/mm(2). Our results indicated that when only one b value is used, the b value in which signal intensities of normal mammary gland decreases down to noise level, and the contrast between normal mammary gland and tumor tissues is recommended. ADC value decreased with increasing b value. Therefore, when determining the ADC threshold level, it is important to perform the evaluation using ADC values calculated from DW images with the same b value in clinical studies.

[Method of correcting sensitivity nonuniformity using gaussian distribution on 3.0 Tesla abdominal MRI].

In the direction where the phased array coil used in parallel magnetic resonance imaging (MRI) is perpendicular to the arrangement, sensitivity falls significantly. Moreover, in a 3.0 tesla (3T) abdominal MRI, the quality of the image is reduced by changes in the relaxation time, reinforcement of the magnetic susceptibility effect, etc. In a 3T MRI, which has a high resonant frequency, the signal of the depths (central part) is reduced in the trunk part. SCIC, which is sensitivity correction processing, has inadequate correction processing, such as that edges are emphasized and the central part is corrected. Therefore, we used 3T with a Gaussian distribution. The uneven compensation processing for sensitivity of an abdomen MR image was considered. The correction processing consisted of the following methods. 1) The center of gravity of the domain of the human body in an abdomen MR image was calculated. 2) The correction coefficient map was created from the center of gravity using the Gaussian distribution. 3) The sensitivity correction image was created from the correction coefficient map and the original picture image. Using the Gaussian correction to process the image, the uniformity calculated using the NEMA method was improved significantly compared to the original image of a phantom. In a visual evaluation by radiologists, the uniformity was improved significantly using the Gaussian correction processing. Because of the homogeneous improvement of the abdomen image taken using 3T MRI, the Gaussian correction processing is considered to be a very useful technique.

Qualitative near-infrared vascular imaging system with tuned aperture computed tomography.

We developed a novel system for imaging and qualitatively analyzing the surface vessels using near-infrared (NIR) radiation using tuned aperture computed tomography (TACT(®)). The system consisted of a NIR-sensitive CCD camera surrounded by sixty light emitting diodes (with wavelengths alternating between 700 or 810 nm). This system produced thin NIR tomograms, under 0.5 mm in slice thickness. The venous oxygenation index reflecting oxygen saturation levels calculated from NIR tomograms was more sensitive than that from the NIR images. This novel system makes it possible to noninvasively obtain NIR tomograms and accurately analyze changes in oxygen saturation.

Acoustic noise transfer function in clinical MRI a multicenter analysis.

RATIONALE AND OBJECTIVES: Acoustic noise both in terms of its magnitude and frequency during magnetic resonance imaging (MRI) scan is influenced by imaging parameters and pulse sequences. It varies because of many different factors such as structure, materials, and magnetic field strength. The purpose of our study is to evaluate the characteristics of acoustic noise independent of MRI scan protocol by measuring a gradient-pulse-to-acoustic-noise transfer function (GPAN-TF) at various MRI scanners. MATERIALS AND METHODS: We measured sound pressure levels in the frequency domain in a 0.4-T, seven 1.5-T, and three 3.0-T clinical MRI systems when applying a simple narrower trapezoidal gradient pulse. We calculated a GPAN-TF [µPa/(mT/m)] in each gradient coil (ie, X, Y, and Z-axis) by the deconvolution process. RESULTS: GPAN-TF at a high-frequency range (1000-10,000 Hz) was larger than that at low frequency for all MRI (P<0.01) scanners except for a low static field machine. For high frequency (>1000 Hz), the 3.0-T MRI scanner had a larger GPAN-TF than that of 0.4-T and 1.5-T (P < .01). MR scanner with a vacuum chamber reduced GPAN-TF at a lower frequency (P < .01), but this effect decreased at higher frequency. CONCLUSION: GPAN-TF analysis makes it possible to obtain more detailed information on acoustic noise properties among MRI scanners.

Drosophila Tbx6-related gene, Dorsocross, mediates high levels of Dpp and Scw signal required for the development of amnioserosa and wing disc primordium.

Regional differentiation along the dorsoventral (DV) axis of the Drosophila embryo primarily depends on a graded BMP signaling activity generated by Decapentaplegic (Dpp) and Screw (Scw). We have identified triplicated Dpp and Scw target genes Dorsocross1, 2 and 3 (Doc1, 2, 3) that have a conserved T-box domain related to the vertebrate Tbx6 subfamily and act redundantly to induce dorsal structures. Doc genes are expressed in the dorsal region in the early blastoderm. After gastrulation, newly expressed Doc appears in a segmental pattern in the ectoderm. This expression correlates spatially with the second phase of Dpp expression in the ectoderm. Doc expression in the early blastoderm is abolished in either dpp or scw mutant embryos, whereas the ectodermal segmented expression depends only on Dpp. Inactivation of Doc genes with RNAi dramatically affected the development of amnioserosa and wing disc primordia, both of which depend on high levels of BMP signaling, although leg disc primordium, which depends on low levels of BMP, remained intact. Doc1 mRNA expressed in Xenopus embryos induced ventral mesoderm, suppressed activin-induced events and induced Xvent genes, which are analogous to the effects of native Tbx6 and its upstream regulator, BMP-4. These results suggest that the Tbx6 subfamily act in the BMP signaling pathway required for embryonic patterning in both animals.