bluuebunny/crossref_metadata_2025 huggingface dataset:
VEGF‐mediated fusion in the generation of uniluminal vascular spheroids
Authors: Gentile Carmine , Fleming Paul A. , Mironov Vladimir , Argraves Kelley M. , Argraves W. Scott , Drake Christopher J.
Published: September 2008

Embryonic mouse allantoic tissue (E8.5) was cultured in hanging drops to generate a three‐dimensional vascular micro‐tissue. The resulting tissue spheroids had an inner network of small diameter vessels expressing platelet endothelial cell adhesion molecule‐1 (PECAM‐1) and an outer layer of cells expressing SMαA, SM22‐α, and SM‐MHC. In a subsequent phase of culture, the fusion‐promoting activity of vascular endothelial growth factor (VEGF) was used to transform the inner network of small diameter endothelial tubes into a contiguous layer of cells expressing PECAM‐1, CD34, and VE‐cadherin that circumscribed a central lumen‐like cavity. The blood vessel‐like character of the VEGF‐treated spheroids was further demonstrated by their physiologically relevant vasodilatory and contractile responses, including contraction induced by KCl and relaxation stimulated by high‐density lipoproteins and acetylcholine‐induced nitric oxide production. Developmental Dynamics 237:2918–2925, 2008. © 2008 Wiley‐Liss, Inc.
Leading edge‐secreted Dpp cooperates with ACK‐dependent signaling from the amnioserosa to regulate myosin levels during dorsal closure
Authors: Zahedi Baharak , Shen Weiping , Xu Xing , Chen Xi , Mahey Meena , Harden Nicholas
Published: September 2008

Dorsal closure of the Drosophila embryo is an epithelial fusion in which the epidermal flanks migrate to close a hole in the epidermis occupied by the amnioserosa, a process driven in part by myosin‐dependent cell shape change. Dpp signaling is required for the morphogenesis of both tissues, where it promotes transcription of myosin from the zipper (zip) gene. Drosophila has two members of the activated Cdc42‐associated kinase (ACK) family: DACK and PR2. Overexpression of DACK in embryos deficient in Dpp signaling can restore zip expression and suppress dorsal closure defects, while reducing the levels of DACK and PR2 simultaneously using mutations or amnioserosa‐specific knock down by RNAi results in loss of zip expression. ACK function in the amnioserosa may generate a signal cooperating with Dpp secreted from the epidermis in driving zip expression in these two tissues, ensuring that cell shape changes in dorsal closure occur in a coordinated manner. Developmental Dynamics 237:2936–2946, 2008. © 2008 Wiley‐Liss, Inc.
Analysis of the IKKβ/NF‐κB signaling pathway during embryonic angiogenesis
Authors: Hou Yanjun , Li Fu , Karin Michael , Ostrowski Michael C.
Published: September 2008

The nuclear factor‐κB (NF‐κB) signaling pathway regulates cellular growth, survival, differentiation and development. In this study, the functions of IκB kinase (IKK)β in angiogenesis during mouse development were examined. Conditional disruption of the Ikkβ locus in endothelial cells using the well‐characterized Tie2‐Cre transgene resulted in embryonic lethality between embryonic day (E) 13.5 and E15.5. Examination of the mutant embryos revealed that while deletion of Ikkβ occurred in endothelial cells throughout the embryo, only the vascular network in the fetal liver was affected. Disruption of the fetal liver vasculature was accompanied by decreased cell proliferation and increased apoptosis of hepatocytes, but hematopoiesis was not affected. Increased apoptosis was not observed outside of fetal liver in the mutant embryos. These results indicate that the IKKβ/NF‐κB pathway plays a previously unappreciated role in development of the sinusoidal vasculature in the fetal liver and additionally that this pathway is critical in the crosstalk between endothelial cells and hepatocytes during mouse development. Developmental Dynamics 237:2926–2935, 2008. © 2008 Wiley‐Liss, Inc.
Origin and fate of cardiac mesenchyme
Authors: Snarr Brian S. , Kern Christine B. , Wessels Andy
Published: September 2008

The development of the embryonic heart is dependent upon the generation and incorporation of different mesenchymal subpopulations that derive from intra‐ and extra‐cardiac sources, including the endocardium, epicardium, neural crest, and second heart field. Each of these populations plays a crucial role in cardiovascular development, in particular in the formation of the valvuloseptal apparatus. Notwithstanding shared mechanisms by which these cells are generated, their fate and function differ profoundly by their originating source. While most of our early insights into the origin and fate of the cardiac mesenchyme has come from experimental studies in avian model systems, recent advances in transgenic mouse technology has enhanced our ability to study these cell populations in the mammalian heart. In this article, we will review the current understanding of the role of cardiac mesenchyme in cardiac morphogenesis and discuss several new paradigms based on recent studies in the mouse. Developmental Dynamics 237:2804–2819, 2008. © 2008 Wiley‐Liss, Inc.
Fgf16 is required for cardiomyocyte proliferation in the mouse embryonic heart
Authors: Hotta Yuhei , Sasaki Sayaka , Konishi Morichika , Kinoshita Hideyuki , Kuwahara Koichiro , Nakao Kazuwa , Itoh Nobuyuki
Published: September 2008

Fibroblast growth factor (Fgf) signaling plays important roles in development and metabolism. Mouse Fgf16 was predominantly expressed in cardiomyocytes. To elucidate the physiological roles of Fgf16, we generated Fgf16 knockout mice. Although the mice were apparently normal and fertile, heart weight and cardiomyocyte cell numbers were slightly decreased at 6 months of age. However, blood pressure, heart rate, and cardiac performance were essentially unchanged. In addition, the expression of most cardiac marker genes examined was also essentially unchanged. However, the expression of Bnp was significantly decreased, indicating potential roles of Fgf16 in the heart under pathological conditions. In contrast, the proliferation of embryonic cardiomyocytes was significantly decreased, indicating that Fgf16 is a growth factor for these cells. The embryonic heart phenotype is similar to that of the Fgf9 knockout heart, indicating Fgf9 and Fgf16 to synergistically act as growth factors for embryonic cardiomyocytes. Developmental Dynamics 237:2947–2954, 2008. © 2008 Wiley‐Liss, Inc.
Ultrafast Vibronic Processes in a Ru–Porphyrin Complex
Authors: Iwakura Izumi , Yabushita Atsushi , Kobayashi Takayoshi
Published: September 2008

The excited‐state dynamics of RuII(TPP)(CO)(acetone) (TPP = tetraphenylporphyrin) was investigated by using a sub‐5‐fs pulse. In previous studies, the fluorescence lifetime of RuII(TPP)(CO) could not be resolved and was reported to be <1 ps. Analysis of the six‐coordinate complexes of RuII(TPP)(CO)(acetone) showed that 1Qx(π,π*) had a lifetime of 140 ± 20 fs and the lifetime of 3(d,π*) was 560 ± 150 fs. Stimulated emission due to a spin‐forbidden transition from 3(π,π*) to the ground state was observed for the first time.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Controlling the Crystal Growth of Dodecasil 3C by Buffering with DL‐Histidine
Authors: Seral José J. , Uriel Santiago , Coronas Joaquín
Published: September 2008

Dodecasil 3C, a pure silica zeolite with an MTN‐type structure, was prepared by liquid‐phase hydrothermal synthesis in the presence of the amino acid dl‐histidine. This compound acts as a buffer and affects the growth of zeolite, in particular its aggregation behaviour and particle size. As a result of the alteration the amino acid exerts on the silica chemistry in aqueous solution, nucleation was lowered and dodecasil 3C was formed as large, single crystals with sizes up to 140 μm.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Organometallic Diiron Complex Chemistry Related to the [2Fe]H Subsite of [FeFe]H2ase
Authors: Capon Jean‐François , Gloaguen Frédéric , Pétillon François Y. , Schollhammer Philippe , Talarmin Jean
Published: September 2008

During the last decade, the structure of the subsite of [FeFe]H2ases (or Fe‐only hydrogenases) has inspired organometallic chemists to find out whether it was possible to build synthetic molecules, based on sulfur, iron, carbon monoxide and cyanide or surrogates, having the same efficiency for hydrogen production/uptake as that of the enzyme. A short nonexhaustive overview of recent advances in this chemistry is presented. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Unexpected Differences in the Coordination Behaviour of 1,2,4‐Triphosphaferrocenes towards CuIChloride
Authors: Deng Shining , Schwarzmaier Christoph , Vogel Ulf , Zabel Manfred , Nixon John F. , Scheer Manfred
Published: September 2008

The coordination behaviour of 1,2,4‐triphosphaferrocenes [FeCpR(η5‐P3C2tBu2)] [CpR= Cp (1), Cp″′ (2)] towards CuIchloride is significantly influenced by the substitution pattern of the cyclopentadienyl ring attached to iron. The dimeric copper complexes [{FeCp(η5:η1:η1‐P3tBu2C2)}{μ‐CuCl(MeCN)}]2(3) and [{FeCp″′ (η5:η1:η1‐P3tBu2C2)}(μ‐CuCl)]2(4), in which two 1,2,4‐triphosphaferrocenes are linked by two CuCl centres to form dimeric complexes were obtained in reactions using a 1:1 stoichiometry. Whereas in3a tetra‐coordinated Cu atom is revealed,4possesses a threefold‐coordinated Cu atom due to the steric influence of the bulkier Cp″′ ligand. However, if the reaction is carried out with an excess of CuCl in a 1:2 stoichiometry for the Cp derivative1the same product3is obtained, whereas in the case of a tri‐tert‐butyl‐substituted Cp″′ ligand complex2the triphospholyl ring is fragmented under mild conditions to a tetraphosphabutadiene moiety within an iron triple‐decker sandwich complex [{(FeCp″′)2(μ,η4:η4:η1:η1‐P4)}{μ‐CuCl(MeCN)}]∞(5) embedded in a CuCl polymer matrix.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Alcoholysis of Phosphaisocoumarins and Synthesis of 2‐(2‐Oxoalkyl)phenylphosphonates
Authors: Peng Ai‐Yun , Guo Yu‐Juan , Ke Zhi‐Hai , Zhu Shizheng
Published: September 2008

Phosphaisocoumarins do not undergo aminolysis, but instead they were found to be susceptible to alcoholysis in the presence of alcohols and primary amines. This paper examined this unexpected alcoholysis reaction and found that in the presence of Et3N or K2CO3, 4‐unsubstituted‐ and 4‐chlorophosphaisocoumarins underwent the alcoholysis reaction smoothly to give a series of 2‐(2‐oxoalkyl)phenylphosphonates in good yields, whereas 4‐iodo‐ and 4‐bromophosphaisocoumarins underwent a dehalogenation–alcoholysis tandem reaction. The possible mechanism for the alcoholysis reaction was discussed. In addition, direct access to 2‐(2‐oxoalkyl)phenylphosphonates was developed by the mercury(II)‐catalyzed hydration of 2‐(1‐alkynly)phenylphosphonates with high regioselectivity. In a preliminary study, the obtained novel keto phosphonates showed medium inhibitory activity towards α‐chymotrypsin. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Real‐time or current vintage: does the type of data matter for forecasting and model selection?
Authors: Feng Hui
Published: September 2008

In this paper we investigate the impact of data revisions on forecasting and model selection procedures. A linear ARMA model and nonlinear SETAR model are considered in this study. Two Canadian macroeconomic time series have been analyzed: the real‐time monetary aggregate M3 (1977–2000) and residential mortgage credit (1975–1998). The forecasting method we use is multi‐step‐ahead non‐adaptive forecasting. Copyright © 2008 John Wiley & Sons, Ltd.
Topographic analysis of individual activation patterns in medial frontal cortex in schizophrenia
Authors: Stern Emily R. , Welsh Robert C. , Fitzgerald Kate D. , Taylor Stephan F.
Published: September 2008

Individual variability in the location of neural activations poses a unique problem for neuroimaging studies employing group averaging techniques to investigate the neural bases of cognitive and emotional functions. This may be especially challenging for studies examining patient groups, which often have limited sample sizes and increased intersubject variability. In particular, medial frontal cortex (MFC) dysfunction is thought to underlie performance monitoring dysfunction among patients with schizophrenia, yet previous studies using group averaging to compare schizophrenic patients to controls have yielded conflicting results. To examine individual activations in MFC associated with two aspects of performance monitoring, interference and error processing, functional magnetic resonance imaging data were acquired while 17 patients with schizophrenia and 21 healthy controls (HCs) performed an event‐related version of the multisource interference task. Comparisons of averaged data revealed few differences between the groups. By contrast, topographic analysis of individual activations for errors showed that control subjects exhibited activations spanning across both posterior and anterior regions of MFC while patients primarily activated posterior MFC, possibly reflecting an impaired emotional response to errors in schizophrenia. This discrepancy between topographic and group‐averaged results may be due to the significant dispersion among individual activations, particularly in HCs, highlighting the importance of considering intersubject variability when interpreting the medial frontal response to error commission. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Brain activity during visual versus kinesthetic imagery: An fMRI study
Authors: Guillot Aymeric , Collet Christian , Nguyen Vo An , Malouin Francine , Richards Carol , Doyon Julien
Published: September 2008

Although there is ample evidence that motor imagery activates similar cerebral regions to those solicited during actual movements, it is still unknown whether visual (VI) and kinesthetic imagery (KI) recruit comparable or distinct neural networks. The present study was thus designed to identify, through functional magnetic resonance imaging at 3.0 Tesla in 13 skilled imagers, the cerebral structures implicated in VI and KI. Participants were scanned in a perceptual control condition and while physically executing or focusing during motor imagery on either the visual or kinesthetic components of an explicitly known sequence of finger movements. Subjects' imagery abilities were assessed using well‐established psychological, chronometric, and new physiological measures from the autonomic nervous system. Compared with the perceptual condition, physical executing, VI, and KI resulted in overlapping (albeit non‐identical) brain activations, including motor‐related regions and the inferior and superior parietal lobules. By contrast, a divergent pattern of increased activity was observed when VI and KI were compared directly: VI activated predominantly the occipital regions and the superior parietal lobules, whereas KI yielded more activity in motor‐associated structures and the inferior parietal lobule. These results suggest that VI and KI are mediated through separate neural systems, which contribute differently during processes of motor learning and neurological rehabilitation. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Time to stop ovarian cancer screening in BRCA1/2 mutation carriers?
Authors: van der Velde Nienke M. , Mourits Marian J.E. , Arts Henriëtte J.G. , de Vries Jacob , Leegte Beike K. , Dijkhuis Grieteke , Oosterwijk Jan C. , de Bock Geertruida H.
Published: September 2008

Women at high risk of ovarian cancer due to a genetic predisposition may opt for either surveillance or prophylactic bilateral salpingo‐oophorectomy (pBSO). Main objective of our study was to determine the effectiveness of ovarian cancer screening in women with a BRCA1/2 mutation. We evaluated 241 consecutive women with a BRCA1 or BRCA2 mutation who were enrolled in the surveillance program for hereditary ovarian cancer from September 1995 until May 2006 at the University Medical Center Groningen (UMCG), The Netherlands. The ovarian cancer screening included annual pelvic examination, transvaginal ultrasound (TVU) and serum CA125 measurement. To evaluate the effectiveness of screening in diagnosing (early stage) ovarian cancer sensitivity, specificity, positive and negative predictive values (PPV and NPV) of pelvic examination, TVU and CA125 were calculated. Three ovarian cancers were detected during the surveillance period; 1 prevalent cancer, 1 interval cancer and 1 screen‐detected cancer, all in an advanced stage (FIGO stage IIIc). A PPV of 20% was achieved for pelvic examination, 33% for TVU and 6% for CA125 estimation alone. The NPV were 99.4% for pelvic examination, 99.5% for TVU and 99.4% for CA125. All detected ovarian cancers were in an advanced stage, and sensitivities and positive predictive values of the screening modalities are low. Restricting the analyses to incident contacts that contained all 3 screening modalities did not substantially change the outcomes. Annual gynecological screening of women with a BRCA1/2 mutation to prevent advanced stage ovarian cancer is not effective. © 2008 Wiley‐Liss, Inc.
Endothelial function in patients with and without diabetes mellitus with different degrees of coronary artery stenosis
Authors: Simova Iana I. , Denchev Stefan V. , Dimitrov Simeon I. , Ivanova Raia
Published: September 2008

Purpose.

To evaluate endothelial function using flow‐mediated dilatation (FMD) of the brachial artery in patients with and without diabetes mellitus (DM) with different degrees of coronary artery stenosis.

Method.

We investigated 293 patients, 69 (23.6%) of whom had DM. FMD and coronary arteriography were performed.

Results.

Patients with DM had a significantly lower FMD (mean ± SD, 3.7 ± 3.8%) compared with patients without DM (mean ± SD, 5.2 ± 5.3%) (p < 0.05). When the results were broken down by the severity of coronary artery disease (CAD) (no significant coronary artery stenosis, 1‐vessel disease, 2‐vessel disease, and 3‐vessel disease) the only statistically significant difference between diabetics and nondiabetics was found in patients without significant coronary stenosis (mean FMD ± SD: 5.2 ± 4.4% in diabetics, 7.6 ± 5.4% in nondiabetics [p < 0.05]).

Conclusion.

In CAD patients, the presence of DM was associated with endothelial dysfunction. The difference in the FMD was clearly expressed between patients with and without DM in the subgroup without significant coronary stenosis, and was no longer present with advanced coronary atherosclerosis. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2009
A local structure theorem on 5‐connected graphs
Authors: Ando Kiyoshi
Published: September 2008

An edge of a 5‐connected graph is said to be contractible if the contraction of the edge results in a 5‐connected graph. Let x be a vertex of a 5‐connected graph. We prove that if there are no contractible edges whose distance from x is two or less, then either there are two triangles with x in common each of which has a distinct degree five vertex other than x, or there is a specified structure called a K4−‐configuration with center x. As a corollary, we show that if a 5‐connected graph on n vertices has no contractible edges, then it has 2n/5 vertices of degree 5. © 2008 Wiley Periodicals, Inc. J Graph Theory 60: 99–129, 2009
Terminal Modification with 1‐Adamantylamine to Endow Hyperbranched Polyamidoamine with Thermo‐/pH‐Responsive Properties
Authors: Guo Zhe , Zhang Yongwen , Huang Wei , Zhou Yongfeng , Yan Deyue
Published: September 2008

A novel terminal modification agent to endow hyperbranched polyamidoamine (HPAMAM) with thermo‐/pH‐responsive properties is reported. HPAMAM with terminal vinyl groups is first synthesized and then end‐capped by 1‐adamantylamine (ADA). The resulting hyperbranched polymer (HPAMAM‐ADA) shows interesting thermo‐responsive properties in aqueous solution, which have been investigated by UV‐vis spectroscopy, optical microscopy, and 1H NMR spectroscopy. The lower critical solution temperature can be controlled by adjusting the end‐capping ratio of ADA. In addition, HPAMAM‐ADA exhibits a pH‐dependent water solubility. This pH‐responsive behavior is also studied.

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Effects of MgCl2 Crystallographic Structure on Active Centre Formation in Immobilized Single‐Centre and Ziegler–Natta Catalysts for Ethylene Polymerization
Authors: Huang Rubin , Malizia Federica , Pennini Gianni , Koning Cor E. , Chadwick John C.
Published: September 2008

The ability of a MgCl2 support to activate a transition metal catalyst has been found to depend both on the crystallographic structure of the support and on the nature of the catalyst. A high degree of crystallographic disorder can be very effective for the immobilization and activation of titanium and vanadium complexes, but is not necessarily effective for zirconocene activation. A highly disordered support prepared by the reaction of MgBu2 with HCl gave high activity with TiCl4 but low activity with (n‐PrCp)2ZrCl2. High polymerization activities with the zirconocene were only obtained with supports of type MgCl2/AlRn(OEt)3−n prepared from the reaction of AlR3 with MgCl2 · 1.1EtOH. These supports are characterized by additional peaks in the X‐ray diffraction pattern, indicating the presence of a crystalline structure which is absent in the other supports and contains highly Lewis acidic sites able to generate the active metallocenium species.

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Novel Luminescent Electrospun Fibers Prepared From Conjugated Rod–Coil Block Copolymer of Poly[2,7‐(9,9‐dihexylfluorene)]‐block‐Poly(methyl methacrylate)
Authors: Kuo Chi‐Ching , Tung Yi‐Chih , Lin Chia‐Hung , Chen Wen‐Chang
Published: September 2008

Novel luminescent electrospun (ES) fibers have been successfully prepared from a conjugated rod–coil block copolymer, poly[2,7‐(9,9‐dihexylfluorene)]‐block‐poly(methyl methacrylate) (PF‐b‐PMMA) using a single‐capillary spinneret. Experiment results indicate that PF‐b‐PMMA ES fibers prepared from THF, THF/DMF (50/50), and DMF contain PF block aggregated structures of dot‐like (5–10 nm), line‐like (10–20 nm), and ellipse‐like structure (25–50 nm), respectively. Such variation of aggregation size leads to a red‐shift of the absorption or luminescence spectra. In addition, the fiber diameters decrease upon enhancing the DMF content. The present study demonstrates that blue light‐emitting ES fibers are successfully prepared from conjugated rod–coil diblock copolymers and their aggregate morphology and photophysical properties could be tuned through use of selective solvent.

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An Original Calix[4]arene‐Containing Oligomer/Polymer Catalyst for Homogeneous Hydroformylation
Authors: Mongrain Pascal , Harvey Pierre D.
Published: September 2008

The title compound (10) was prepared from the calix[4]arene precursor (11) to form the ligand 5,11‐bis(methyl(diphenylphosphino))‐25,26,27,28‐tetra‐n‐propoxy calix[4]arene (12), which was reacted with [Rh(COD)Cl]2 (COD = 1,5‐cyclooctadienyl) and TlPF6 as chloride scavenger, in 31% overall chemical yield. The dimer structure in solution was demonstrated by the measurements of the 31P NMR spin‐lattice relaxation time (T1) in comparison with the ligand itself. Computer modeling shows that the dimer macrocycle exhibits many possible conformers, including some with obvious steric hindrance about the Rh atom, but no apparent ring stress. 10 was tested for the catalytic homogeneous hydroformylation of hex‐1‐ene and compared with other closely related analogue systems recently reported in the literature.

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Macromol. Rapid Commun. 19/2008
Authors: Kim GeunHyung , Son JoonGon , Park SuA , Kim WanDoo
Published: September 2008

Cover: The image shows a hybrid polymeric scaffold that was fabricated using a rapid prototyping (RP) method and electrospinning process. The panels clearly indicate that the layers of electrospun micro‐/nanofibers are located between the layers of dispensed poly(ε‐caprolactone) strands. Further details can be found in the article by G.‐H. Kim,* J.‐G. Son, S.‐A. Park, and W.‐D. Kim on page 1577.
Comparative reliability of proton spectroscopy techniques designed to improve detection of J‐coupled metabolites
Authors: Mullins Paul Gerald , Chen Hongji , Xu Jing , Caprihan Arvind , Gasparovic Charles
Published: September 2008

Improved detection of J‐coupled neurometabolites through the use of modified proton magnetic resonance spectroscopy (1H‐MRS) techniques has recently been reported. TE‐averaged point‐resolved spectroscopy (PRESS) uses the J modulation effects by averaging FIDs with differing echo times to improve detection of glutamate, while standard PRESS detection of glutamate can be improved by using an appropriate single echo determined from J‐modulation simulations. In the present study, the reliabilities of TE‐averaged PRESS, standard PRESS with TE = 40 ms, and standard PRESS with TE = 30 ms in detecting metabolite levels in the cingulate gyrus of the human brain at 3T were compared in six subjects. TE‐averaged PRESS measures showed a mean variability of 9% for N‐acetyl aspartate, choline, and creatine, compared with < 4% for the 30‐ and 40‐ms PRESS techniques. The coefficients of variation for glutamate were 10%, 7%, and 5% for TE‐averaged, 30‐ms, and 40‐ms PRESS, respectively. PRESS with a TE of 40 ms also demonstrated improved reliability for GABA and glutamine concentrations. These results show that with the appropriate selection of echo time standard PRESS can be a reliable 1H‐MRS technique for the measurement of J‐coupled neurometabolites in the human brain and, moreover, compares favorably with at least one J‐edited technique. Magn Reson Med 60:964–969, 2008. © 2008 Wiley‐Liss, Inc.
Three‐frequency RF coil designed for optimized imaging of hyperpolarized, 13C‐labeled compounds
Authors: Hancu Ileana , Wood S. James , Piel Joseph , Whitt David B. , Fish Kenneth M. , Rutt Brian K. , Tropp James , Dixon W. Thomas
Published: September 2008

Imaging exams involving hyperpolarized, 13C‐labeled compounds require novel RF coils for efficient signal utilization. While 13C coils are required for mapping the spatial distribution of the hyperpolarized compounds, imaging/pulsing at different frequencies is also needed for scan setup steps prior to the image acquisition. Imaging/pulsing at the 1H frequency is typically used for anatomical localization and shimming. Flip angle (FA) calibration, which is difficult or impossible to achieve at the 13C frequency, can be accurately performed at the 23Na frequency using the natural abundance signal that exists in any living tissue. We demonstrate here a single RF resonant structure that is capable of operating linearly at the 1H and 23Na frequencies for scan setup steps, and in quadrature at the 13C frequency for imaging. Images at the three resonant frequencies of this coil are presented from an exam involving hyperpolarized 13C compounds in vivo. Magn Reson Med 60:928–933, 2008. © 2008 Wiley‐Liss, Inc.
Effects of image noise in muscle diffusion tensor (DT)‐MRI assessed using numerical simulations
Authors: Damon Bruce M.
Published: September 2008

Diffusion tensor (DT)‐MRI studies of skeletal muscle provide information about muscle architecture, microstructure, and damage. However, the effects of noise, the diffusion weighting (b)‐value, and partial volume artifacts on the estimation of the diffusion tensor (D) are unknown. This study investigated these issues using Monte Carlo simulations of 3 × 9 voxel regions of interest (ROIs) containing muscle, adipose tissue, and intermediate degrees of muscle volume fractions (fM). A total of 1000 simulations were performed for each of eight b‐values and 11 SNR levels. The dependencies of the eigenvalues (λ1–3), mean diffusivity (λ), and fractional anisotropy (FA), and the angular deviation of the first eigenvector from its true value (α) were observed. For moderate b‐values (b = 435–725 s/mm2) and fM = 1, an accuracy of 5% was obtained for λ1–3, λ, and FA with an SNR of 25. An accuracy of 1% was obtained for λ1–3, λ, and FA with fM = 1 and SNR = 50. For regions with fM = 8/9, 5% accuracy was obtained with SNR = 40. For α, SNRs of ≥25 and ≥45 were required for ±4.5° uncertainty with fM = 1 and fM = 0.5, respectively; SNR ≥ 60 was required for ±9° uncertainty in single muscle voxels. These findings may influence the design and interpretation of DT‐MRI studies of muscle microstructure, damage, and architecture. Magn Reson Med 60:934–944, 2008. © 2008 Wiley‐Liss, Inc.
Myoinositol content in the human brain is modified by transcranial direct current stimulation in a matter of minutes: A 1H‐MRS study
Authors: Rango M. , Cogiamanian F. , Marceglia S. , Barberis B. , Arighi A. , Biondetti P. , Priori A.
Published: September 2008

Brain content of myoinositol (mI) has been shown to be altered in several neuropsychiatric conditions. Likewise, various forms of electric currents have been applied to the human brain for therapeutic purposes in neuropsychiatric diseases. In this study we aimed to depict the effects of low‐power transcranial direct current stimulation (tDCS) on brain mI by proton magnetic resonance spectroscopy (1H‐MRS). We studied two groups of five healthy subjects by 1H‐MRS: the first group was studied before and after both anodal and sham (placebo) tDCS over the right frontal lobe, and the second group was studied at the same intervals without undergoing either sham or anodal tDCS. Anodal tDCS induced a significant increase of mI content at 30 min after stimulation offset (141.5 ± 16.7%, P < 0.001) below the stimulating electrode but not in distant regions, such as the visual cortex, whereas sham tDCS failed to induce changes in mI. Neither N‐acetyl‐aspartate (NAA) nor the other metabolite contents changed after anodal or sham stimulation. 1H‐MRS represents a powerful tool to follow the regional effects of tDCS on brain mI and, possibly, on the related phosphoinositide system. Magn Reson Med 60:782–789, 2008. © 2008 Wiley‐Liss, Inc.
Quantitative MR susceptibility mapping using piece‐wise constant regularized inversion of the magnetic field
Authors: de Rochefort Ludovic , Brown Ryan , Prince Martin R. , Wang Yi
Published: September 2008

Magnetic properties characterized by susceptibility and chemical shift linearly modify the local magnetic field experienced by spins. A piece‐wise constant solution using magnetic resonance imaging is found to the challenging inversion problem from field to magnetic properties. The magnetic field shifts were estimated from MR phase images. The MR magnitude images were segmented into many regions of uniform magnetic properties. Standard linear regression using the calculated magnetic field from each region allowed accurate susceptibility quantification. The technique was experimentally validated on a variety of samples including water, vegetable oil, air, Gadolinium, and superparamagnetic iron oxides. Susceptibility was measured with a precision better than 0.1 ppm, in a range of 10 ppm. In vivo feasibility was shown on the forearm for which soft‐tissue, cortical bone, and bone marrow susceptibility, and chemical shift values in good agreement with literature data were obtained. Magn Reson Med 60:1003–1009, 2008. © 2008 Wiley‐Liss, Inc.
Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging
Authors: Zhou Jinyuan , Blakeley Jaishri O. , Hua Jun , Kim Mina , Laterra John , Pomper Martin G. , van Zijl Peter C.M.
Published: September 2008

Amide proton transfer (APT) imaging is a type of chemical exchange–dependent saturation transfer (CEST) magnetic resonance imaging (MRI) in which amide protons of endogenous mobile proteins and peptides in tissue are detected. Initial studies have shown promising results for distinguishing tumor from surrounding brain in patients, but these data were hampered by magnetic field inhomogeneity and a low signal‐to‐noise ratio (SNR). Here a practical six‐offset APT data acquisition scheme is presented that, together with a separately acquired CEST spectrum, can provide B0‐inhomogeneity corrected human brain APT images of sufficient SNR within a clinically relevant time frame. Data from nine brain tumor patients at 3T shows that APT intensities were significantly higher in the tumor core, as assigned by gadolinium‐enhancement, than in contralateral normal‐appearing white matter (CNAWM) in patients with high‐grade tumors. Conversely, APT intensities in tumor were indistinguishable from CNAWM in patients with low‐grade tumors. In high‐grade tumors, regions of increased APT extended outside of the core into peripheral zones, indicating the potential of this technique for more accurate delineation of the heterogeneous areas of brain cancers. Magn Reson Med 60:842–849, 2008. © 2008 Wiley‐Liss, Inc.
BOLD imaging in the mouse brain using a turboCRAZED sequence at high magnetic fields
Authors: Schneider Johannes T. , Faber Cornelius
Published: September 2008

Functional MRI (fMRI) based on the detection of intermolecular double‐quantum coherences (iDQC) has previously been shown to provide pronounced activation signal. For fMRI in small animals at very high magnetic fields, the essential fast gradient echo‐based readout methods become problematic. Here, rapid intermolecular double‐quantum coherence (iDQC) imaging was implemented, combining the iDQC preparation sequence with a Turbo spin echo‐like readout. Four‐step phase cycling and a novel intensity‐ordered k‐space encoding scheme with separate acquisition of odd and even echoes were essential to optimize signal to noise ratio efficiency. Compared with a single echo readout of iDQC signal, acceleration of factor 16 was achieved in phantoms using the novel method at 17.6 Tesla. In vivo, echo trains consisting of 32 echoes were possible and images of the mouse brain were obtained in 30 s. The blood oxygen level dependent (BOLD) effect in the mouse brain upon change of breathing gas was observed as average signal change of (6.3 ± 1.1)% in iDQC images. Signal changes in conventional multi spin echo images were (4.4 ± 2.3)% and (8.3 ± 3.8)% with gradient echo methods. Combination of T2*‐weighting with the fast iDQC sequence may yield higher signal changes than with either method alone, and establish fast iDQC imaging a robust tool for high field fMRI in small animals. Magn Reson Med 60:850–859, 2008. © 2008 Wiley‐Liss, Inc.
Validation of oxygen extraction fraction measurement by qBOLD technique
Authors: He Xiang , Zhu Mingming , Yablonskiy Dmitriy A.
Published: September 2008

Measurement of brain tissue oxygen extraction fraction (OEF) in both baseline and functionally activated states can provide important information on brain functioning in health and disease. The recently proposed quantitative BOLD (qBOLD) technique is MRI‐based and provides a regional in vivo OEF measurement (He and Yablonskiy, MRM 2007, 57:115–126). It is based on a previously developed analytical BOLD model and incorporates prior knowledge about the brain tissue composition including the contributions from grey matter, white matter, cerebrospinal fluid, interstitial fluid and intravascular blood. The qBOLD model also allows for the separation of contributions to the BOLD signal from OEF and the deoxyhemoglobin containing blood volume (DBV). The objective of this study is to validate OEF measurements provided by the qBOLD approach. To this end we use a rat model and compare qBOLD OEF measurements against direct measurements of the blood oxygenation level obtained from venous blood drawn directly from the superior sagittal sinus. The cerebral venous oxygenation level of the rat was manipulated by utilizing different anestheisa methods. The study demonstrates a very good agreement between qBOLD approach and direct measurements. Magn Reson Med 60:882–888, 2008. © 2008 Wiley‐Liss, Inc.
Measurement of myocardial frequency offsets during first pass of a gadolinium‐based contrast agent in perfusion studies
Authors: Ferreira Pedro , Gatehouse Peter , Bucciarelli‐Ducci Chiara , Wage Ricardo , Firmin David
Published: September 2008

MRI of myocardial perfusion observed with an extracellular contrast agent has proven valuable for the detection of coronary artery disease. During contrast enhancement transient dark rim artifacts are sometimes visible, complicating diagnosis and quantification. In this work a quantification of the frequency offsets caused solely by the first pass of Gd‐DTPA in a typical perfusion setup was made in vivo and compared with both phantom work and numerical simulations data. The results show that numerically simulated and phantom data agree well with in vivo frequency offsets. During the first pass main field distortion occurs mainly in the subendocardium, and the same pattern is always observed: positive for posterior/anterior regions, negative for septal/lateral regions (from −69 to 85 Hz). The larger myocardial frequency offsets were measured for patients with greater angles between the long axis of the heart and the direction of the main field. From these results it would appear that the frequency offsets are too weak to cause dark rim artifacts due simply to intravoxel dephasing in a typical perfusion sequence. However, when added to other sources of off‐resonance it can cause dark rims in particular regions of the myocardium wall in balanced‐SSFP sequences. Magn Reson Med 60:860–870, 2008. © 2008 Wiley‐Liss, Inc.
Comparison of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) using inversion recovery and fast T1 mapping sequences
Authors: Mamisch Tallal Charles , Dudda Marcel , Hughes Timothy , Burstein Deborah , Kim Young‐Jo
Published: September 2008

The delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) technique has shown promising results in pilot clinical studies of early osteoarthritis. Currently, its broader acceptance is limited by the long scan time and the need for postprocessing to calculate the T1 maps. A fast T1 mapping imaging technique based on two spoiled gradient echo images was implemented. In phantom studies, an appropriate flip angle combination optimized for center T1 of 756 to 955 ms yielded excellent agreement with T1 measured using the inversion recovery technique in the range of 200 to 900 ms, of interest in normal and diseased cartilage. In vivo validation was performed by serially imaging 26 hips using the inversion recovery and the Fast 2 angle T1 mapping techniques (center T1 756 ms). Excellent correlation with Pearson correlation coefficient R2 of 0.74 was seen and Bland‐Altman plots demonstrated no systematic bias. Magn Reson Med 60:768–773, 2008. © 2008 Wiley‐Liss, Inc.
Macromolecular dynamic contrast‐enhanced (DCE)‐MRI detects reduced vascular permeability in a prostate cancer bone metastasis model following anti–platelet‐derived growth factor receptor (PDGFR) therapy, indicating a drop in vascular endothelial growth factor receptor (VEGFR) activation
Authors: Dafni Hagit , Kim Sun‐Jin , Bankson James A. , Sankaranarayanapillai Madhuri , Ronen Sabrina M.
Published: September 2008

The antivascular function of the platelet‐derived growth factor receptor (PDGFR) inhibitor imatinib combined with paclitaxel has been demonstrated by invasive immunohistochemistry. The purpose of this study was to 1) noninvasively monitor the response to anti‐PDGFR treatment, and 2) understand the underlying mechanism of this response. Thus, response to treatment was studied in a prostate cancer bone metastasis model using macromolecular (biotin–bovine serum albumin [BSA]–Gd‐diethylene triamine pentaacetic acid [GdDTPA]) dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). Human prostate cancer (PC‐3MM2) bone metastases that caused osteolysis and grew in neighboring muscle showed a high blood‐volume fraction (fBV) and vascular permeability (PS) at the tumor periphery compared to muscle tissue and intraosseous tumor. Imatinib alone or with paclitaxel significantly reduced PS by 35% (one‐tailed paired t‐test, P = 0.045) and 40% (P = 0.0003), respectively, whereas paclitaxel alone or no treatment had no effect. Based on changes in PS, we hypothesized that imatinib interferes with the signaling pathway of vascular endothelial growth factor (VEGF). This mechanism was verified by immunohistochemistry. It demonstrated reduced activation of both PDGFR‐β and VEGF receptor 2 (VEGFR2) in imatinib‐treated mice. Our study therefore demonstrates that macromolecular DCE‐MRI can be used to detect early vascular effects associated with response to therapy targeted to PDGFR, and provides insight into the role played by VEGF in anti‐PDGFR therapy. Magn Reson Med 60:822–833, 2008. © 2008 Wiley‐Liss, Inc.
Comprehensive quantification of signal‐to‐noise ratio and g‐factor for image‐based and k‐space‐based parallel imaging reconstructions
Authors: Robson Philip M. , Grant Aaron K. , Madhuranthakam Ananth J. , Lattanzi Riccardo , Sodickson Daniel K. , McKenzie Charles A.
Published: September 2008

Parallel imaging reconstructions result in spatially varying noise amplification characterized by the g‐factor, precluding conventional measurements of noise from the final image. A simple Monte Carlo based method is proposed for all linear image reconstruction algorithms, which allows measurement of signal‐to‐noise ratio and g‐factor and is demonstrated for SENSE and GRAPPA reconstructions for accelerated acquisitions that have not previously been amenable to such assessment. Only a simple “prescan” measurement of noise amplitude and correlation in the phased‐array receiver, and a single accelerated image acquisition are required, allowing robust assessment of signal‐to‐noise ratio and g‐factor. The “pseudo multiple replica” method has been rigorously validated in phantoms and in vivo, showing excellent agreement with true multiple replica and analytical methods. This method is universally applicable to the parallel imaging reconstruction techniques used in clinical applications and will allow pixel‐by‐pixel image noise measurements for all parallel imaging strategies, allowing quantitative comparison between arbitrary k‐space trajectories, image reconstruction, or noise conditioning techniques. Magn Reson Med 60:895–907, 2008. © 2008 Wiley‐Liss, Inc.
Exponential excitation pulses for improved water content mapping in the presence of background gradients
Authors: Preibisch Christine , Volz Steffen , Anti Sandra , Deichmann Ralf
Published: September 2008

Several water content mapping techniques are based on the acquisition of multiple gradient echoes (GE) with different echo times (TE). However, in the presence of linear magnetic field gradients Gsusc the signal decay is no longer exponential but in the case of a rectangular slice profile weighted by a sinc function, giving rise to erroneous initial amplitudes S0 in monoexponential fitting. Generally, it can be shown that the signal decay is weighted by the time profile of the excitation pulse. Thus, for an excitation pulse with an exponential time profile, i.e., a Lorentzian slice profile, the signal decay remains exponential and exponential fitting still yields the correct amplitude S0. Multiecho GE images of a gel phantom and five human volunteers were acquired at 3 T using a sinc‐shaped and an exponential excitation pulse. In addition, simulations were performed to investigate the influence of saturation effects due to distortion of the ideal Lorentzian slice profile. A considerable overestimation of S0 when using a sinc‐shaped excitation pulse was observed. Errors were greatly reduced with an exponential excitation pulse. We thus propose the use of excitation pulses with exponential time profile to obtain accurate estimates for S0 from exponential fitting. Magn Reson Med 60:908–916, 2008. © 2008 Wiley‐Liss, Inc.
Predictive modeling in glioma grading from MR perfusion images using support vector machines
Authors: Emblem Kyrre E. , Zoellner Frank G. , Tennoe Bjorn , Nedregaard Baard , Nome Terje , Due‐Tonnessen Paulina , Hald John K. , Scheie David , Bjornerud Atle
Published: September 2008

The advantages of predictive modeling in glioma grading from MR perfusion images have not yet been explored. The aim of the current study was to implement a predictive model based on support vector machines (SVM) for glioma grading using tumor blood volume histogram signatures derived from MR perfusion images and to assess the diagnostic accuracy of the model and the sensitivity to sample size. A total of 86 patients with histologically‐confirmed gliomas were imaged using dynamic susceptibility contrast (DSC) MRI at 1.5T. Histogram signatures from 53 of the 86 patients were analyzed independently by four neuroradiologists and used as a basis for the predictive SVM model. The resulting SVM model was tested on the remaining 33 patients and analyzed by a fifth neuroradiologist. At optimal SVM parameters, the true positive rate (TPR) and true negative rate (TNR) of the SVM model on the 33 patients was 0.76 and 0.82, respectively. The interobserver agreement and the TPR increased significantly when the SVM model was based on an increasing sample size (P< 0.001). This result suggests that a predictive SVM model can aid in the diagnosis of glioma grade from MR perfusion images and that the model improves with increasing sample size. Magn Reson Med 60:945–952, 2008. © 2008 Wiley‐Liss, Inc.
Advantage of sampling density weighted apodization over postacquisition filtering apodization for sodium MRI of the human brain
Authors: Stobbe Robert , Beaulieu Christian
Published: September 2008

For sodium imaging of the human brain, Gibbs' ringing can degrade image appearance and confound image analysis; k‐space filtering is generally required. In this work, the signal to noise ratio (SNR) advantage of sampling density weighted apodization (SDWA) over uniform k‐space sampling with postacquisition filtering apodization (UPFA) is quantified for sodium three‐dimensional (3D) twisted projection imaging (TPI) of the human brain. A direct comparison was conducted with the creation of two TPI projection data sets (each with an equal number of projections of equal length): one generating uniform sampling density, and the other a “generalized Hamming” sampling density that conformed to 3D‐TPI constraints for full k‐space sampling. In this work it is shown theoretically, and then experimentally with sodium imaging of the human brain, that an SNR advantage of 17% is associated with the use of SDWA over UPFA for the filter presented, along with a significant noise‐coloring benefit. Magn Reson Med 60:981–986, 2008. © 2008 Wiley‐Liss, Inc.
Gibbs tracking: A novel approach for the reconstruction of neuronal pathways
Authors: Kreher B.W. , Mader I. , Kiselev V.G.
Published: September 2008

Reconstruction of neuronal fibers using diffusion‐weighted (DW) MRI is an emerging method in biomedical research. Existing fiber‐tracking algorithms are commonly based on the “walker principle.” Fibers are reconstructed as trajectories of “walkers,” which are guided according to local diffusion properties. In this study, a new method of fiber tracking is proposed that does not engage any “walking” algorithm. It resolves a number of inherent problems of the “walking” approach, in particular the reconstruction of crossing and spreading fibers. In the proposed method, the fibers are built with small line elements. Each line element contributes an anisotropic term to the simulated DW signal, which is adjusted to the measured signal. This method demonstrates good results for simulated fibers. A single in vivo result demonstrates the successful reconstruction of the dominant neuronal pathways. A comparison with the diffusion tensor imaging (DTI)‐based fiber assignment with continuous tracking (FACT) method and the probabilistic index of connectivity (PICo) method based on a multitensor model is performed for the callosal fibers. The result shows a strong increase in the number of reconstructed fibers. These almost fill the total white matter (WM) volume and connect a large area of the cortex. The method is very computationally expensive. Possible ways to address this problem are discussed. Magn Reson Med 60:953–963, 2008. © 2008 Wiley‐Liss, Inc.