bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of pharmaceuticals in drinking water by CD‐modified MEKC: Separation optimization using experimental design
Authors: Drover Vincent J. , Bottaro Christina S.
Published: October 2008

A suite of 12 widely used pharmaceuticals (ibuprofen, diclofenac, naproxen, bezafibrate, gemfibrozil, ofloxacin, norfloxacin, carbamazepine, primidone, sulphamethazine, sulphadimethoxine and sulphamethoxazole) commonly found in environmental waters were separated by highly sulphated CD‐modified MEKC (CD‐MEKC) with UV detection. An experimental design method, face‐centred composite design, was employed to minimize run time without sacrificing resolution. Using an optimized BGE composed of 10 mM ammonium hydrogen phosphate, pH 11.5, 69 mM SDS, 6 mg/mL sulphated β‐CD and 8.5% v/v isopropanol, a separation voltage of 30 kV and a 48.5 cm×50 μm id bare silica capillary at 30°C allowed baseline separation of the 12 analytes in a total analysis time of 6.7 min. Instrument LODs in the low milligram per litre range were obtained, and when combined with offline preconcentration by SPE, LODs were between 4 and 30 μg/L.
Dielectric cell separation of fine needle aspirates from tumor xenografts
Authors: Cristofanilli Massimo , Krishnamurthy Savitri , Das Chandra M. , Reuben James M. , Spohn William , Noshari Jamileh , Becker Frederick , Gascoyne Peter R.
Published: October 2008

As an approach to isolating tumor cells from fine needle biopsy specimens, we investigated a dielectric cell preparation method using an in vivo xenographic tumor model. Cultured human MDA‐MB‐435 tumor cells were grown as solid tumors in nude mice and fine needle aspiration biopsies were conducted. Biopsied cells were suspended in sucrose medium and collected on slides patterned with microelectrode arrays (electrosmears) energized by electrical signals in the range 10 to 960 kHz. The unlabeled cells adhered to characteristic regions of the slides in accordance with their morphology as a result of dielectric forces. Tumor cells were trapped between 40 and 60 kHz and were separated according to whether they were mitotic, large and complex, or small. Damaged tumor cells were captured at between 60 and 120 kHz; granulocytes between 70 and 90 kHz; lymphocytes between 85 and 105 kHz; healthy erythrocytes between 140 and 180 kHz, and damaged erythrocytes above 180 kHz. Using intrinsic cell characteristics, the electrosmear presented cell subpopulations from fine needle aspiration biopsy specimens in a manner that is compatible with automated slide‐based analysis systems. The approach has the potential to facilitate the analysis of the role of cell subpopulations in disease.
Comparison of performance of Chirobiotic T, T2 and TAG columns in the separation of β2‐ and β3‐homoamino acids
Authors: Pataj Zoltán , Ilisz István , Berkecz Robert , Misicka Aleksandra , Tymecka Dagmara , Fülöp Ferenc , Armstrong Daniel W. , Péter Antal
Published: October 2008

The enantiomers of eight unusual β2‐ and β3‐homoamino acids were separated on chiral stationary phases containing the macrocyclic glycopeptide antibiotic teicoplanin (Chirobiotic T or T2) or teicoplanin aglycone (Chirobiotic TAG) as chiral selectors. The effects of the organic modifier, the mobile phase composition, and temperature on the separations were investigated. Linear van't Hoff plots were observed in the studied temperature range, 280–318 K, and the changes in enthalpy, Δ(ΔH°), entropy, Δ(ΔS°), and free energy, Δ(ΔG°) were calculated. The values of the thermodynamic parameters depended on the nature of the selectors, the structures of the analytes, and especially the positions of the substituents on the analytes. A comparison of the separation performances of the macrocyclic glycopeptide stationary phases revealed that the Chirobiotic TAG column exhibited much better selectivity for β2‐homoamino acids, while the separation of β3‐homoamino acid enantiomers was better on Chirobiotic T or T2. The elution sequence was determined in some cases and was observed to be R < S.
Modeling GC‐ECD retention times of pentafluorobenzyl derivatives of phenol by using artificial neural networks
Authors: Asadpour‐Zeynali Karim , Jalili‐Jahani Naser
Published: October 2008

The depicted retention times (RTs) of an electron capture detection (ECD) system is predicted for a set of 37 pentafluorobenzyl (PFB) derivatives of phenol in a semi‐polar column, DB‐1701 (14% cyanopropylphenyl and 86% dimethyl‐polysiloxane). Among a large number of descriptors, four parameters categorized as electronic, topological, geometric, and hybrid (geometric and topological) descriptors are chosen using stepwise multiple regression technique. Each molecular descriptor in this model was disputed to unfold the relationship between molecular structures and their RTs. The descriptors occurring in the multiple linear regression (MLR) model were considered as inputs for developing the back propagation artificial neural networks (BPANN). The artificial neural network (ANN) model shows superiority over the MLR by decerning 91.9% for different classes of molecules in confusion matrix. This refers to the fact that the retention behaviors of molecules display nonlinear characteristics. The accuracy of 4‐4‐1 BPANN model was illustrated using leave‐one‐out (LOO), leave‐multiple‐out (LMO) cross‐validations, and Y‐randomization. Moreover, the mean effect of descriptors betrays that descriptor Ss is the most indispensable factor affecting the retention behavior of molecules.
Statistical and methodological issues in the analysis of complex sample survey data: Practical guidance for trauma researchers
Authors: West Brady T.
Published: October 2008

Standard methods for the analysis of survey data assume that the data arise from a simple random sample of the target population. In practice, analysts of survey data sets collected from nationally representative probability samples often pay little attention to important properties of the survey data. Standard statistical software procedures do not allow analysts to take these properties of survey data into account. A failure to use more specialized procedures designed for survey data analysis can impact both simple descriptive statistics and estimation of parameters in multivariate models. In this article, the author provides trauma researchers with a practical introduction to specialized methods that have been developed for the analysis of complex sample survey data.
Posttraumatic growth in adolescence: Examining its components and relationship with PTSD
Authors: Levine Stephen Z. , Laufer Avital , Hamama‐Raz Yaira , Stein Einat , Solomon Zahava
Published: October 2008

To address gaps in the literature, this study examined the components of posttraumatic growth, and the relationship between growth and posttraumatic stress disorder (PTSD). Participants were from a pooled sample of 4,054 Israeli adolescents exposed to terror of whom 210 (5.5%) met criteria for PTSD. Measures included the Child Post‐Traumatic Stress Reaction Index and Posttraumatic Growth Inventory. Principal components analysis showed two correlated components of outward and intrapersonal growth. Regression modeling showed that the relationship between the growth and PTSD measures was linear and curvilinear (inverted‐U). These results replicated accounting for heterogeneity in PTSD, exposure and subsamples. Collectively, the results imply that posttraumatic growth in adolescence is characterized by two robust components, and is greatest at moderate posttraumatic stress levels.
Avoidance symptoms and assessment of posttraumatic stress disorder in Arab immigrant women
Authors: Norris Anne E. , Aroian Karen J.
Published: October 2008

This study investigates whether the avoidance symptom criterion required for a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV; American Psychiatric Association, 1994) diagnosis of posttraumatic stress disorder (PTSD) is overly conservative. Arab immigrant women (N = 453), many of whom reported experiencing multiple traumatic events, completed the Posttraumatic Diagnostic Scale in Arabic as part of a face to face interview. Analyses indicated all but one avoidance symptom was reported less frequently than reexperiencing and arousal symptoms. However, those who fully met reexperiencing, avoidance, and arousal symptom criteria had worse symptom severity and functioning than those who fully met reexperiencing and arousal symptom criteria, but only partially met avoidance symptom criterion. Study findings support importance of the PTSD avoidance symptom criterion.
Adolescents' and parents' agreement on posttraumatic stress disorder symptoms and functioning after adolescent injury
Authors: Ghesquiere Angela , Fan Ming‐Yu , Berliner Lucy , Rivara Frederick P. , Jurkovich Gregory J. , Russo Joan , Katon Wayne , Zatzick Douglas F.
Published: October 2008

Few investigations have simultaneously assessed concordance between youth and parent ratings of posttraumatic stress disorder (PTSD) symptoms and functioning. Randomly sampled adolescent injury survivors ages 12–18 and their parents were assessed on the inpatient ward and again at 2, 5, and 12‐months postinjury (N = 99). Adolescent PTSD symptoms and functioning were rated by both adolescents and parents. Parent PTSD was also assessed; 27% of parents endorsed symptoms consistent with a diagnosis of PTSD over the course of the year after adolescent injury. The PTSD positive parents demonstrated significantly greater discordance in ratings of adolescent PTSD symptoms, family cohesion, and mental health functioning. These findings suggest caution in clinical and policy applications of parental ratings of adolescent symptomatic and functional outcomes after injury.
A pilot study of meditation for mental health workers following Hurricane Katrina
Authors: Waelde Lynn C. , Uddo Madeline , Marquett Renee , Ropelato Melanie , Freightman Sharifa , Pardo Adit , Salazar Jacqueline
Published: October 2008

This pilot study examined the effects of a manualized meditation intervention (called Inner Resources) for posttraumatic stress disorder (PTSD), depression, and anxiety symptoms among 20 African American and Caucasian mental health workers in New Orleans beginning 10 weeks after Hurricane Katrina. They participated in a 4‐hour workshop followed by an 8‐week home study program. Complete follow‐up data were available for 15 participants. Results of intention‐to‐treat analyses indicated that participants' PTSD and anxiety symptoms significantly decreased over the 8 weeks of the intervention; these improvements were significantly correlated with the total number of minutes of daily meditation practice. The majority of participants reported good treatment adherence and improvements in well‐being. These findings suggest that meditation may be a feasible, acceptable, and effective postdisaster intervention.
Noninferiority and equivalence designs: Issues and implications for mental health research
Authors: Greene Carolyn J. , Morland Leslie A. , Durkalski Valerie L. , Frueh B. Christopher
Published: October 2008

The terms noninferiority and equivalence are often used interchangeably to refer to trials in which the primary objective is to show that a novel intervention is as effective as the standard intervention. The use of these designs is becoming increasingly relevant to mental health research. Despite the fundamental importance of these designs, they are often poorly understood, improperly applied, and subsequently misinterpreted. In this article, the authors explain noninferiority and equivalence designs and key methodological and statistical considerations. Decision points in using these designs are discussed, such as choice of control condition, determination of the noninferiority margin, and calculation of sample size and power. With increasing utilization of these designs, it is critical that researchers understand the methodological issues, advantages, disadvantages, and related challenges.
Kinetics of the synthesis of propyl and butyl acrylates in the presence of some heteropolyacids as catalysts
Authors: Skrzypek Jerzy , Witczak Teresa , Grzesik Mirosław , Witczak Mariusz
Published: October 2008

Esterification reactions of acrylic acid with n‐propanol and n‐butanol were carried out in the liquid phase in the presence of H3PW12O40 or H3PMo12O40 as a catalyst, at various temperatures, molar ratios of the reactants, and concentrations of the catalyst. The kinetic equations had a nonelementary form. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 41: 12–17, 2009
Kinetics and mechanism of hydrolysis of N‐(2′‐hydroxyphenyl)phthalamic acid (1) and N‐(2′‐methoxyphenyl)phthalamic Acid (2) in a highly alkaline medium
Authors: Sim Yoke‐Leng , Damit Emmy Fadhiza , Ariffin Azhar , Khan M. Niyaz
Published: October 2008

A kinetic study on hydrolysis of N‐(2′‐hydroxyphenyl)phthalamic acid (1), N‐(2′‐methoxyphenyl)phthalamic acid (2), and N‐(2′‐methoxyphenyl)benzamide (3) under a highly alkaline medium gives second‐order rate constants, kOH, for the reactions of HO− with 1, 2, and 3 as (4.73 ± 0.36) × 10−8 at 35°C, (2.42 ± 0.28) × 10−6 and (5.94 ± 0.23) × 10−5 M−1 s−1 at 65°C, respectively. Similar values of kOH for 3, N‐methylbenzanilide, N‐methylbenzamide, and N,N‐dimethylbenzamide despite the difference between pKa values of aniline and ammonia of ∼10 pK units are qualitatively explained. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 41: 1–11, 2009
Laser cooling of solids
Authors: Sheik‐Bahae M. , Epstein R.I.
Published: October 2008

We present an overview of solid‐state optical refrigeration also known as laser cooling in solids by fluorescence upconversion. The idea of cooling a solid‐state optical material by simply shining a laser beam onto it may sound counter intuitive but is rapidly becoming a promising technology for future cryocoolers. We chart the evolution of this science in rare‐earth doped solids and semiconductors.
On‐line separations combined with MS for analysis of glycosaminoglycans
Authors: Zaia Joseph
Published: October 2008

The glycosaminoglycan (GAG) family of polysaccharides includes the unsulfated hyaluronan and the sulfated heparin, heparan sulfate, keratan sulfate, and chondroitin/dermatan sulfate. GAGs are biosynthesized by a series of enzymes, the activities of which are controlled by complex factors. Animal cells alter their responses to different growth conditions by changing the structures of GAGs expressed on their cell surfaces and in extracellular matrices. Because this variation is a means whereby the functions of the limited number of protein gene products in animal genomes is elaborated, the phenotypic and functional assessment of GAG structures expressed spatially and temporally is an important goal in glycomics. On‐line mass spectrometric separations are essential for successful determination of expression patterns for the GAG compound classes due to their inherent complexity and heterogeneity. Options include size exclusion, anion exchange, reversed phase, reversed phase ion pairing, hydrophilic interaction, and graphitized carbon chromatographic modes and capillary electrophoresis. This review summarizes the application of these approaches to on‐line MS analysis of the GAG classes. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 28:254–272, 2009
A real‐option rationale for investing in excess capacity
Authors: Sarkar Sudipto
Published: October 2008

Excess capacity is expensive, yet persistent excess capacity is widely observed in the corporate sector. Using a real‐option approach to capacity planning, this paper shows that under certain conditions it is optimal to invest in long‐term (even permanent) excess capacity. This results from the asymmetric nature of operating flexibility resulting from excess capacity—the ability to increase output under favorable demand shocks. The model is used to identify conditions under which excess capacity is more likely to be optimal. The implications are generally consistent with existing empirical evidence from studies on excess capacity and capacity utilization. Copyright © 2008 John Wiley & Sons, Ltd.
Nanoparticle formulations in pulmonary drug delivery
Authors: Bailey Mark M. , Berkland Cory J.
Published: October 2008

The advent of nanotechnology has reignited interest in the lungs as a major route of drug delivery for both systemic and local treatments. The large surface area of the lungs and the minimal barriers impeding access to the lung periphery make this organ a suitable portal for a variety of therapeutic interventions. Nanoparticles provide new formulation options for both dispersed liquid droplet dosage forms such as metered dose inhalers and nebulizers, and dry powder formulations. Nanoparticle formulations have many advantages over traditional dosage forms, such as enhanced dissolution properties and the potential for intracellular drug delivery. Specifically, pure drug nanoparticles, polymeric nanoparticles, polyelectrolyte complexes, and drug‐loaded liposomes offer some encouraging results for delivering drugs to and through the lungs. Methods are also being investigated to produce nanoparticles with properties suitable for improving access to the peripheral lung. Traditional techniques such as spray drying and grinding, and more recent advances in supercritical fluid extraction, precipitation, and solvent extraction have been employed to produce nanoparticle formulations for pulmonary delivery. Here, the benefits of nanoparticle formulations and current progress are compared in light of the practical encumbrances of producing formulations, and possible toxicological effects of these materials. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 1, 196–212, 2009
Inhibitors and antagonists of bacterial quorum sensing
Authors: Ni Nanting , Li Minyong , Wang Junfeng , Wang Binghe
Published: October 2008

Bacteria can regulate community‐wide behaviors including biofilm formation, virulence, conjugation, sporulation, and swarming motility through a process called quorum sensing. Inhibitors and antagonists of bacterial quorum sensing are important research tools and potential therapeutic agents. In this review, we have summarized recent developments in this area. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 1, 65–124, 2009
Importance of Radical Transfer in Precipitation Polymerization: The Case of Vinyl Chloride Suspension Polymerization
Authors: Wieme Joris , D'hooge Dagmar R. , Reyniers Marie‐Françoise , Marin Guy B.
Published: October 2008

The importance of radical transfer between the reactive phases in precipitation polymerization processes is investigated with the vinyl chloride suspension polymerization as an example. A two‐film model that accounts for a mass transfer resistance in both the monomer‐rich and the polymer‐rich phase is constructed and applied. Equilibrium is assumed at the interphase boundary. Based on model calculations using intrinsic rate coefficients obtained by regression to experimental data the effect of accounting for radical transfer between the reactive phases on the simulated monomer conversion and total moments of the molar mass distribution is demonstrated. It is found that the effect of radical transfer between the reactive phases is most pronounced at low polymerization temperatures.

magnified image
Noninvasive mapping of human trigeminal brainstem pathways
Authors: Upadhyay Jaymin , Knudsen Jamie , Anderson Julie , Becerra Lino , Borsook David
Published: October 2008

The human trigeminal system mediates facial pain and somatosensory processing. The anatomic location of neuronal substrates and axonal pathways of the trigeminal system have previously been characterized with conventional in vitro methods. The present investigation implemented diffusion tensor imaging (DTI) and probabilistic tractography to first segment the peripheral trigeminal circuitry, trigeminal nerve branches (ophthalmic, maxillary, and mandibular nerves), ganglion, and nerve root. Subsequent segmentations involved the spinal trigeminal and trigeminal thalamic tracts, which respectively convey information to the spinal trigeminal nuclei and ventral thalamic regions. This latter procedure also identified 1) spinal thalamic (anterolateral [AL]) system pathways (propagating pain and temperature information from the body), 2) trigeminal lemniscus (TL; touch and face position), and 3) medial lemniscus (ML; touch and limb position). The anatomic location of the identified pain and somatosensory pathways compared well with previous functional findings in the human trigeminal system, as well as the tract position in human histological cross sections. Probabilistic tractography may be a useful method to further comprehend the functional and structural properties of trigeminal and other related systems. Application of DTI to map pain and somatosensory pathways in conjunction with a characterization of function properties of pain and somatosensory processing would further define the systematic changes that occur in trigeminal pathology. Magn Reson Med 60:1037–1046, 2008. © 2008 Wiley‐Liss, Inc.
Sliding‐window sensitivity encoding (SENSE) calibration for reducing noise in functional MRI (fMRI)
Authors: Law Christine S. , Liu Chunlei , Glover Gary H.
Published: October 2008

Functional magnetic resonance imaging (fMRI) at high magnetic field with parallel imaging (PI) has become increasingly popular for high‐resolution imaging. We present a method of self‐calibrated PI‐fMRI in which sensitivity profiles are calculated using a sliding window of fully sampled multishot imaging data. We show that by updating these sensitivity profiles in a sliding fashion, thermal noise is reduced in the reconstructed image time series. This is accomplished by retaining thermal noise in the sensitivity profiles; no spatial smoothing is performed. These noisy profiles actually provide a closer match to those required for thermal noise‐free reconstruction than conventional sensitivity map generation. Our proposed technique is especially applicable for acquiring high‐spatial‐resolution images, where thermal noise exceeds physiological noise. With conventional sensitivity calculation, PI‐fMRI sensitivity is preserved only when using a voxel size large enough such that physiological noise predominates. With small voxel size, our technique reveals activation from visual stimulation where conventional sensitivity calculation techniques falter. Our technique enhances fMRI detection, especially when higher spatial resolution is desired. Magn Reson Med 60:1090–1103, 2008. © 2008 Wiley‐Liss, Inc.
Accelerated radiation damping for increased spin equilibrium (ARISE): A new method for controlling the recovery of longitudinal magnetization
Authors: Huang Susie Y. , Witzel Thomas , Wald Lawrence L.
Published: October 2008

Control of the longitudinal magnetization in fast gradient‐echo (GRE) sequences is an important factor in enabling the high efficiency of balanced steady‐state free precession (bSSFP) sequences. We introduce a new method for accelerating the return of the longitudinal magnetization to the +z‐axis that is independent of externally applied RF pulses and shows improved off‐resonance performance. The accelerated radiation damping for increased spin equilibrium (ARISE) method uses an external feedback circuit to strengthen the radiation damping (RD) field. The enhanced RD field rotates the magnetization back to the +z‐axis at a rate faster than T1 relaxation. The method is characterized in GRE phantom imaging at 3T as a function of feedback gain, phase, and duration, and compared with results from numerical simulations of the Bloch equations incorporating RD. A short period of feedback (10 ms) during a refocused interval of a crushed GRE sequence allowed greater than 99% recovery of the longitudinal magnetization when very little T2 relaxation had time to occur. An appropriate application might be to improve navigated sequences. Unlike conventional flip‐back schemes, the ARISE “flip‐back” is generated by the spins themselves, thereby offering a potentially useful building block for enhancing GRE sequences. Magn Reson Med 60:1112–1121, 2008. © 2008 Wiley‐Liss, Inc.
Fast conjugate phase image reconstruction based on a Chebyshev approximation to correct for B0 field inhomogeneity and concomitant gradients
Authors: Chen Weitian , Sica Christopher T. , Meyer Craig H.
Published: October 2008

Off‐resonance effects can cause image blurring in spiral scanning and various forms of image degradation in other MRI methods. Off‐resonance effects can be caused by both B0 inhomogeneity and concomitant gradient fields. Previously developed off‐resonance correction methods focus on the correction of a single source of off‐resonance. This work introduces a computationally efficient method of correcting for B0 inhomogeneity and concomitant gradients simultaneously. The method is a fast alternative to conjugate phase reconstruction, with the off‐resonance phase term approximated by Chebyshev polynomials. The proposed algorithm is well suited for semiautomatic off‐resonance correction, which works well even with an inaccurate or low‐resolution field map. The proposed algorithm is demonstrated using phantom and in vivo data sets acquired by spiral scanning. Semiautomatic off‐resonance correction alone is shown to provide a moderate amount of correction for concomitant gradient field effects, in addition to B0 imhomogeneity effects. However, better correction is provided by the proposed combined method. The best results were produced using the semiautomatic version of the proposed combined method. Magn Reson Med 60:1104–1111, 2008. © 2008 Wiley‐Liss, Inc.
Multiecho water‐fat separation and simultaneous R estimation with multifrequency fat spectrum modeling
Authors: Yu Huanzhou , Shimakawa Ann , McKenzie Charles A. , Brodsky Ethan , Brittain Jean H. , Reeder Scott B.
Published: October 2008

Multiecho chemical shift–based water‐fat separation methods are seeing increasing clinical use due to their ability to estimate and correct for field inhomogeneities. Previous chemical shift‐based water‐fat separation methods used a relatively simple signal model that assumes both water and fat have a single resonant frequency. However, it is well known that fat has several spectral peaks. This inaccuracy in the signal model results in two undesired effects. First, water and fat are incompletely separated. Second, methods designed to estimate T in the presence of fat incorrectly estimate the T decay in tissues containing fat. In this work, a more accurate multifrequency model of fat is included in the iterative decomposition of water and fat with echo asymmetry and least‐squares estimation (IDEAL) water‐fat separation and simultaneous T estimation techniques. The fat spectrum can be assumed to be constant in all subjects and measured a priori using MR spectroscopy. Alternatively, the fat spectrum can be estimated directly from the data using novel spectrum self‐calibration algorithms. The improvement in water‐fat separation and T estimation is demonstrated in a variety of in vivo applications, including knee, ankle, spine, breast, and abdominal scans. Magn Reson Med 60:1122–1134, 2008. © 2008 Wiley‐Liss, Inc.
Respiratory motion‐compensated radial dynamic contrast‐enhanced (DCE)‐MRI of chest and abdominal lesions
Authors: Lin Wei , Guo Junyu , Rosen Mark A. , Song Hee Kwon
Published: October 2008

Dynamic contrast‐enhanced (DCE)‐MRI is becoming an increasingly important tool for evaluating tumor vascularity and assessing the effectiveness of emerging antiangiogenic and antivascular agents. In chest and abdominal regions, however, respiratory motion can seriously degrade the achievable image quality in DCE‐MRI studies. The purpose of this work is to develop a respiratory motion‐compensated DCE‐MRI technique that combines the self‐gating properties of radial imaging with the reconstruction flexibility afforded by the golden‐angle view‐order strategy. Following radial data acquisition, the signal at k‐space center is first used to determine the respiratory cycle, and consecutive views during the expiratory phase of each respiratory period (34–55 views, depending on the breathing rate) are grouped into individual segments. Residual intrasegment translation of lesion is subsequently compensated for by an autofocusing technique that optimizes image entropy, while intersegment translation (among different respiratory cycles) is corrected using 3D image correlation. The resulting motion‐compensated, undersampled dynamic image series is then processed to reduce image streaking and to enhance the signal‐to‐noise ratio (SNR) prior to perfusion analysis, using either the k‐space‐weighted image contrast (KWIC) radial filtering technique or principal component analysis (PCA). The proposed data acquisition scheme also allows for high frame‐rate arterial input function (AIF) sampling and free‐breathing baseline T1 mapping. The performance of the proposed radial DCE‐MRI technique is evaluated in subjects with lung and liver lesions, and results demonstrate that excellent pixelwise perfusion maps can be obtained with the proposed methodology. Magn Reson Med 60:1135–1146, 2008. © 2008 Wiley‐Liss, Inc.
Novel solubility‐switchable MRI agent allows the noninvasive detection of matrix metalloproteinase‐2 activity in vivo in a mouse model
Authors: Lebel Réjean , Jastrzębska Beata , Therriault Hélène , Cournoyer Marie‐Michèle , McIntyre J. Oliver , Escher Emanuel , Neugebauer Witold , Paquette Benoit , Lepage Martin
Published: October 2008

A novel MRI proteinase‐modulated contrast agent (PCA) was developed to detect the activity of the proinvasive enzyme matrix metalloproteinase‐2 (MMP‐2) in vivo. The PCA2‐switch agent incorporates a solubility switch, where cleavage of a peptide substrate by MMP‐2 decreases the water solubility of the agent. Evidence suggests that this leads to an accumulation of cleaved PCA2‐switch in an MMP‐2‐positive, wild‐type, MC7‐L1 mammary carcinoma tumor in a Balb/c mouse model compared to a MC7‐L1 MMP‐2‐knockdown tumor. When a scrambled peptide sequence is inserted into the agent (PCA2‐scrambled), the in vitro cleavage efficiency of MMP‐2 is markedly reduced. In vivo, PCA2‐scrambled does not accumulate in the wild‐type tumor and the pharmacokinetics is similar in both tumors. In conclusion, in vivo cleavage of PCA2‐switch by MMP‐2 results in a significant accumulation of the cleaved PCA2‐switch in an MMP‐2‐positive tumor. Magn Reson Med 60:1056–1065, 2008. © 2008 Wiley‐Liss, Inc.
Myocardial T measurements in iron‐overloaded thalassemia: An in vivo study to investigate optimal methods of quantification
Authors: He Taigang , Gatehouse Peter D. , Smith Gillian C. , Mohiaddin Raad H. , Pennell Dudley J. , Firmin David N.
Published: October 2008

Reproducible and accurate myocardial T measurements are required for the quantification of iron in heart tissue in transfused thalassemia. The aim of this study was to determine the best method to measure the myocardial T from multi‐gradient‐echo data acquired both with and without black‐blood preparation. Sixteen thalassemia patients from six centers were scanned twice locally, within 1 week, using an optimized bright‐blood T sequence and then subsequently scanned at the standardization center in London within 4 weeks, using a T sequence both with and without black‐blood preparation. Different curve‐fitting models (monoexponential, truncation, and offset) were applied to the data and the results were compared by means of reproducibility. T measurements obtained using the bright‐ and black‐blood techniques. The black‐blood data were well fitted by the monoexponential model, which suggests that a more accurate measure of T can be obtained by removing the main source of errors in the bright‐blood data. For bright‐blood data, the offset model appeared to underestimate T values substantially and was less reproducible. The truncation model gave rise to more reproducible T measurements, which were also closer to the values obtained from the black‐blood data. Magn Reson Med 60:1082–1089, 2008. © 2008 Wiley‐Liss, Inc.
Efficient fat suppression by slice‐selection gradient reversal in twice‐refocused diffusion encoding
Authors: Nagy Zoltan , Weiskopf Nikolaus
Published: October 2008

Most diffusion imaging sequences rely on single‐shot echo‐planar imaging (EPI) for spatial encoding since it is the fastest acquisition available. However, it is sensitive to chemical‐shift artifacts due to the low bandwidth in the phase‐encoding direction, making fat suppression necessary. Often, spectral‐selective RF pulses followed by gradient spoiling are used to selectively saturate the fat signal. This lengthens the acquisition time and increases the specific absorption rate (SAR). However, in pulse sequences that contain two slice‐selective 180° refocusing pulses, the slice‐selection gradient reversal (SSGR) method of fat suppression can be implemented; i.e., using slice‐selection gradients of opposing polarity for the two refocusing pulses. We combined this method with the twice‐refocused spin‐echo sequence for diffusion encoding and tested its performance in both phantoms and in vivo. Unwanted fat signal was entirely suppressed with this method without affecting the water signal intensity or the slice profile. Magn Reson Med 60:1256–1260, 2008. © 2008 Wiley‐Liss, Inc.
Linear phase‐error correction for improved water and fat separation in dual‐echo dixon techniques
Authors: Ma Jingfei , Slavens Zachary , Sun Wei , Bayram Ersin , Estowski Lloyd , Hwang Ken‐Pin , Akao James , Vu Anthony T.
Published: October 2008

Large and spatially‐linear phase errors along the frequency‐encode direction may be induced by several common and hard‐to‐avoid system imperfections such as eddy currents. For data acquired in dual‐echo Dixon techniques, the linear phase error can be more aggravated when compared to that acquired in a single echo and can pose challenges to a phase‐correction algorithm necessary for successful Dixon processing. In this work, we propose a two‐step process that first corrects the linear component of the phase errors with a modified Ahn‐Cho algorithm (Ahn CB and Cho ZH, IEEE Trans. Med. Imaging 6:32, 1987) and then corrects the residual phase errors with a previously‐developed region‐growing algorithm (Ma J, Magn. Res. Med. 52:415, 2004). We demonstrate that successive application of the two‐step process to data from a dual‐echo Dixon technique provides a “1‐2 punch” to the overall phase errors and can overcome local water and fat separation failures that are observed when the region‐growing–based algorithm is applied alone. Magn Reson Med 60:1250–1255, 2008. © 2008 Wiley‐Liss, Inc.
Cellular‐interstitial water exchange and its effect on the determination of contrast agent concentration in vivo: Dynamic contrast‐enhanced MRI of human internal obturator muscle
Authors: Buckley David L. , Kershaw Lucy E. , Stanisz Greg J.
Published: October 2008

The purpose of this study was to assess the effects of cellular‐interstitial water exchange on estimates of tracer kinetics parameters obtained using rapid dynamic contrast‐enhanced (DCE) MRI. Data from the internal obturator muscle of six patients were examined using three models of water exchange: no exchange (NX), fast exchange limit (FXL), and intermediate rate (shutter‐speed [SS]). In combination with additional multiple flip angle (FA) data, a full two‐pool exchange model was also used. The results obtained using the NX model (transfer constant, Ktrans = 0.049 ± 0.027 min–1, apparent interstitial volume, ve = 0.14 ± 0.04) were marginally higher than those obtained using the FXL model (Ktrans = 0.045 ± 0.025 min–1, ve = 0.13 ± 0.04), but the error bars overlapped in two‐thirds of these parameter estimate pairs. Estimates of Ktrans and ve obtained using the SS model exceeded those obtained using the NX model in half the patients, and many estimates, including all those of intracellular residence time of water, ti, were imprecise. Results obtained using the full two‐pool model fell between those obtained using FXL and NX models, and estimates of ti were also imprecise. The results suggest that data obtained using clinically relevant DCE‐MRI are exchange‐insensitive and unsuitable for the assessment of cellular‐interstitial water exchange. Magn Reson Med 60:1011–1019, 2008. © 2008 Wiley‐Liss, Inc.
Four‐pool modeling of proton exchange processes in biological systems in the presence of MRI–paramagnetic chemical exchange saturation transfer (PARACEST) agents
Authors: Li Alex X. , Hudson Robert H.E. , Barrett John W. , Jones Craig K. , Pasternak Stephen H. , Bartha Robert
Published: October 2008

Signal loss due to magnetization transfer (MT) from the macromolecular protons of biological tissues is an important consideration for the in vivo detection of paramagnetic chemical exchange saturation transfer (PARACEST) agents. In this study, a four‐pool model is presented that is based on the modified Bloch equations and incorporates terms for the proton exchange processes that occur in biological systems in the presence of MRI‐PARACEST contrast agents. The effect of the exchangeable proton chemical shift and PARACEST agent concentration are modeled in the presence of macromolecule‐derived MT. Experimental validation of the model was performed at 9.4 Tesla using Eu3+‐DOTAM‐glycine (Gly)‐phenylalanine (Phe) in both aqueous solution and samples containing 10% bovine serum albumin (BSA). The model was then used to measure the agent‐bound‐water chemical shift and the transverse relaxation time of macromolecular protons of a sample of Vero (nonhuman primate) cells labeled with Eu3+‐DOTAM‐Gly‐Phe and a phantom containing mouse brain tissue and 7 mM Eu3+‐DOTAM‐Gly‐Phe. In the brain tissue phantom, a chemical shift map with standard deviation (SD) < 0.7 ppm and a T2 map with SD < 0.6 μs were obtained. The results demonstrate the feasibility of in vivo temperature measurement based on the bound‐water chemical shift of Eu3+‐DOTAM‐Gly‐Phe in combination with this four‐pool model despite the inherent MT effect. Magn Reson Med 60:1197–1206, 2008. © 2008 Wiley‐Liss, Inc.
Comparison of BOLD and direct‐MR neuronal detection (DND) in the human visual cortex at 3T
Authors: Chow Li Sze , Dagens Andrew , Fu Ying , Cook Greg G. , Paley Martyn N.J.
Published: October 2008

Direct‐MR neuronal detection (DND) of transient magnetic fields has recently been investigated as a novel imaging alternative to the conventional BOLD functional MRI (fMRI) technique. However, there remain controversial issues and debate surrounding this methodology, and this study attempts clarification by comparing BOLD responses in the human visual system with those of DND. BOLD relies on indirectly measuring blood oxygenation and flow changes as a result of neuronal activity, whereas the putative DND method is based on the hypothesis that the components of the in vivo neuronal magnetic fields, which lie parallel to the B0 field, can potentially modulate the MR signal, thus providing a means of direct detection of nerve impulses. Block paradigms of checkerboard patterns were used for visual stimulation in both DND and BOLD experiments, allowing detection based on different frequency responses. This study shows colocalization of some voxels with slow BOLD responses and putative fast DND responses using General Linear Model (GLM) analysis. Frequency spectra for the activated voxel cluster are also shown for both stimulated and control data. The mean percentage signal change for the DND responses is 0.2%, corresponding to a predicted neuronal field of 0.14 nT. Magn Reson Med 60:1147–1154, 2008. © 2008 Wiley‐Liss, Inc.
Inhibition of carbohydrate oxidation during the first minute of reperfusion after brief ischemia: NMR detection of hyperpolarized 13CO2 and H13CO
Authors: Merritt Matthew E. , Harrison Crystal , Storey Charles , Sherry A. Dean , Malloy Craig R.
Published: October 2008

Isolated rat hearts were studied by 31P NMR and 13C NMR. Hyperpolarized [1‐13C]pyruvate was supplied to control normoxic hearts and production of [1‐13C]lactate, [1‐13C]alanine, 13CO2 and H13CO was monitored with 1‐s temporal resolution. Hearts were also subjected to 10 min of global ischemia followed by reperfusion. Developed pressure, heart rate, oxygen consumption, [ATP], [phosphocreatine], and pH recovered within 3 min after the ischemic period. During the first 90 s of reperfusion, [1‐13C]alanine and [1‐13C]lactate appeared rapidly, demonstrating metabolism of pyruvate through two enzymes largely confined to the cytosol, alanine aminotransferase, and lactate dehydrogenase. 13CO2 and H13CO were not detected. Late after ischemia and reperfusion, the products of pyruvate dehydrogenase, 13CO2 and H13CO were easily detected. Using this multinuclear NMR approach, we established that during the first 90 s of reperfusion PDH flux is essentially zero and recovers within 20 min in reversibly‐injured myocardium. Magn Reson Med 60:1029–1036, 2008. © 2008 Wiley‐Liss, Inc.
A human ferritin iron oxide nano‐composite magnetic resonance contrast agent
Authors: Uchida Masaki , Terashima Masahiro , Cunningham Charles H. , Suzuki Yoriyasu , Willits Deborah A. , Willis Ann F. , Yang Philip C. , Tsao Philip S. , McConnell Michael V. , Young Mark J. , Douglas Trevor
Published: October 2008

Macrophages play important roles in the immunological defense system, but at the same time they are involved in inflammatory diseases such as atherosclerosis. Therefore, imaging macrophages is critical to assessing the status of these diseases. Toward this goal, a recombinant human H chain ferritin (rHFn)‐iron oxide nano composite has been investigated as an MRI contrast agent for labeling macrophages. Iron oxide nanoparticles in the form of magnetite (or maghemite) with narrow size distribution were synthesized in the interior cavity of rHFn. The composite material exhibited the R2 relaxivity comparable to known iron oxide MRI contrast agents. Furthermore, the mineralized protein cages are readily taken up by macrophages in vitro and provide significant T2* signal loss of the labeled cells. These results encourage further investigation into the development of the rHFn‐iron oxide contrast agent to assess inflammatory disease status such as macrophage‐rich atherosclerotic plaques in vivo. Magn Reson Med 60:1073–1081, 2008. © 2008 Wiley‐Liss, Inc.
Steady state free precession magnetization transfer imaging
Authors: Bieri Oliver , Mamisch Tallas C. , Trattnig Siegfried , Scheffler Klaus
Published: October 2008

The formerly proposed concept for magnetization transfer imaging (MTI) using balanced steady‐state free precession (SSFP) image acquisitions is in this work extended to nonbalanced protocols. This allows SSFP‐based MTI of targets with high susceptibility variation (such as the musculoskeletal system), or at ultra‐high magnetic fields (where balanced SSFP suffers from considerable off‐resonance related image degradations). In the first part, SSFP‐based MTI in human brain is analyzed based on magnetization transfer ratio (MTR) histograms. High correlations are observed among all different SSFP MTI protocols and thereby ensure proper conceptual extension to nonbalanced SSFP. The second part demonstrates SSFP‐based MTI allowing fast acquisition of high resolution volumetric MTR data from human brain and cartilage at low (1.5T) to ultra‐high (7.0T) magnetic fields. Magn Reson Med 60:1261–1266, 2008. © 2008 Wiley‐Liss, Inc.
Detection of targeted perfluorocarbon nanoparticle binding using 19F diffusion weighted MR spectroscopy
Authors: Waters Emily A. , Chen Junjie , Yang Xiaoxia , Zhang Huiying , Neumann Robert , Santeford Andrea , Arbeit Jeffrey , Lanza Gregory M. , Wickline Samuel A.
Published: October 2008

Real‐time detection of targeted contrast agent binding is challenging due to background signal from unbound agent. 19F diffusion weighted MR spectroscopy (DWS) could selectively detect binding of angiogenesis‐targeted perfluorocarbon nanoparticles in vivo. Transgenic K14‐HPV16 mice with epidermal squamous carcinomas exhibiting up‐regulated neovasculature were used, with nontransgenic littermates as controls. Mice were treated with αvβ3‐integrin targeted perfluorocarbon nanoparticles. 19F DWS (b‐values from 0 to 16,000 s/mm2) was performed on mouse ears in vivo at 11.74 Tesla. Progressive decay of 19F signal with increased diffusion weighting at low b‐values (< 1500 s/mm2) was observed in ears of both K14‐HPV16 and control mice, demonstrating suppression of background 19F signal from unbound nanoparticles in the blood. Much of the 19F signal from ears of K14‐HPV16 mice persisted at high b‐values, indicating a stationary signal source, reflecting abundant nanoparticle binding to angiogenesis. 19F signal in controls decayed completely at high b‐values (> 1500 s/mm2), reflecting a moving signal source due to absence of angiogenesis (no binding sites). Estimated ADCs of nanoparticles in K14‐HPV16 and control mice were 33.1 ± 12.9 μm2/s and 19563 ± 5858 μm2/s (p < 0.01). In vivo 19F DWS can be used for specific detection of bound perfluorocarbon nanoparticles by selectively suppressing background 19F signal from nanoparticles flowing in blood. Magn Reson Med 60:1232–1236, 2008. © 2008 Wiley‐Liss, Inc.
Focal reversible deactivation of cerebral metabolism affects water diffusion
Authors: Khachaturian Mark H. , Arsenault John , Ekstrom Leeland B. , Tuch David S. , Vanduffel Wim
Published: October 2008

The underlying biophysical mechanisms which affect cerebral diffusion contrast remain poorly understood. We hypothesized that cerebral metabolism may affect cerebral diffusion contrast. The purpose of this study was to develop the methodology to reversibly deactivate cerebral metabolism and measure the effect on the diffusion MRI signal. We developed an MRI‐compatible cortical cooling system to reversibly deactivate cortical metabolism in rhesus monkey area V1 and used MR thermometry to calculate three‐dimensional temperature maps of the brain to define the extent of deactivated brain in vivo. Significant changes in the apparent diffusion coefficient (ADC) wereonlyobserved during those experiments in which the cortex was cooled below the metabolic cutoff temperature of 20°C. ADC decreases (12–20%) were observed during cortical cooling in regions where the temperature did not change. The normalized in vivo ADC as function of temperature was measured and found to be equivalent to the normalized ADC of free water at temperatures above 20°C, but was significantly decreased below 20°C (20–25% decrease). No changes in fractional anisotropy were observed. In future experiments, we will apply this methodology to quantify the effect of reversible deactivation on neural activity as measured by the hemodynamic response and compare water diffusion changes with hemodynamic changes. Magn Reson Med 60:1178–1189, 2008. © 2008 Wiley‐Liss, Inc.
Antitussiva und Expektorantien. Medizinisch‐chemische Aspekte
Authors: Sander Kerstin , Zettl Heiko , Schubert‐Zsilavecz Manfred , Stark Holger
Published: October 2008

Husten – ein weit verbreitetes Symptom von unterschiedlicher Genese – resultiert am häufigsten als Folge von viralen und bakteriellen Infekten der oberen Atemwege. Je nach Ausprägung sind zur Behandlung dieses Symptoms Antitussiva und/oder Expektorantien indiziert. Trotz des großen Bedarfs an medikamentöser Therapie sind sowohl im verschreibungspflichtigen als auch im OTC‐Bereich die Möglichkeiten auf dem deutschen Markt eher übersichtlich und hinsichtlich einer signifikanten Wirksamkeit einiger Substanzgruppen kritisch zu beurteilen.