bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Sensitivity of 4‐Chlorophenol Detection by Use of Nitrobenzene as a Liquid Membrane over a Carbon Nanotube‐Modified Glassy Carbon Electrode
Authors: Phanthong Chatuporn , Somasundrum Mithran
Published: January 2008

The analytical utility of nitrobenzene as a liquid membrane for the detection of hydrophobic compounds was examined with a glassy carbon electrode, using 4‐chlorophenol as the model analyte. Electrochemical experiments indicated a large partition coefficient for the entry of 4‐chlorophenol into the nitrobenzene (7.6×102±1.5×102). This was combined with an increase in effective electrode area by coating with single‐walled nanotubes. Differential pulse voltammetry produced a linear response across the range 0.3 nM to 1.5 nM with a sensitivity of 1.1×10−5 A nM−1 cm−2. To the best of our knowledge, this limit of detection for phenol is lower than other nonenzymatic modifications of carbon.
High‐resolution computer simulation of the dynamics of isoelectric focusing: In quest of more realistic input parameters for carrier ampholytes
Authors: Mosher Richard A. , Thormann Wolfgang
Published: January 2008

The impact of the systematic variation of either ΔpKa or mobility of 140 biprotic carrier ampholytes on the conductivity profile of a pH 3–10 gradient was studied by dynamic computer simulation. A configuration with the greatest ΔpKa in the pH 6–7 range and uniform mobilities produced a conductivity profile consistent with that which is experimentally observed. A similar result was observed when the neutral (pI = 7) ampholyte is assigned the lowest mobility and mobilities of the other carriers are systematically increased as their pI's recede from 7. When equal ΔpKa values and mobilities are assigned to all ampholytes a conductivity plateau in the pH 5–9 region is produced which does not reflect what is seen experimentally. The variation in ΔpKa values is considered to most accurately reflect the electrochemical parameters of commercially available mixtures of carrier ampholytes. Simulations with unequal mobilities of the cationic and anionic species of the carrier ampholytes show either cathodic (greater mobility of the cationic species) or anodic (greater mobility of the anionic species) drifts of the pH gradient. The simulated cationic drifts compare well to those observed experimentally in a capillary in which the focusing of three dyes was followed by whole column optical imaging. The cathodic drift flattens the acidic portion of the gradient and steepens the basic part. This phenomenon is an additional argument against the notion that focused zones of carrier ampholytes have no electrophoretic flux.
Protein separations using polyelectrolyte multilayer coatings with molecular micelles in open tubular capillary electrochromatography
Authors: Luces Candace A. , Fakayode Sayo O. , Lowry Mark , Warner Isiah M.
Published: January 2008

Novel polyelectrolyte multilayer (PEM) coatings for enhanced protein separations in open tubular CEC (OT‐CEC) are reported. Use of four cationic polymers (poly‐L‐lysine, poly‐L‐ornithine, poly‐L‐lysine‐serine, and poly‐L‐glutamic acid‐lysine), and three anionic molecular micelles, sodium poly(N‐undecanoyl‐L‐leucyl‐alaninate) (poly‐L‐SULA), sodium poly(N‐undecanoyl‐L‐leucyl‐valinate) (poly‐L‐SULV), and sodium poly(undecylenic sulfate) (poly‐SUS) were investigated in PEM coatings for protein separations. The simultaneous effects of cationic polymer concentration, number of bilayers, temperature, applied voltage, and pH of the BGE on the separation of four basic proteins (α‐chymotrypsinogen A, lysozyme, ribonuclease A, and cytochrome c) were analyzed using a Box Behnken experimental design. The influence of NaCl on the run‐to‐run reproducibility was investigated for PEM coatings containing each cationic polymer. All coatings exhibited excellent reproducibilities with a %RSD of the EOF less than 1% in the presence of NaCl. Optimal conditions were dependent on both the cationic and anionic polymers used in the PEM coatings. Poly‐L‐glutamic acid‐lysine produced the highest resolution and longest migration time. The use of molecular micelles to form PEM coatings resulted in better separations than single cationic coatings. Chiral poly‐L‐SULA and poly‐L‐SULV resulted in higher protein resolutions as compared to the achiral, poly‐SUS. Furthermore, the use of poly‐L‐SULV reversed the elution order of lysozyme and cytochrome c when compared to poly‐L‐SULA and poly‐SUS.
An advanced application of the quantitative structure–activity relationship concept in electrokinetic chromatography of metal complexes
Authors: Oszwałdowski Sławomir , Timerbaev Andrei R.
Published: January 2008

The relevance of the quantitative structure–activity relationship (QSAR) principle in MEKC and microemulsion EKC (MEEKC) of metal–ligand complexes was evaluated for a better understanding of analyte migration mechanism. A series of gallium chelates were applied as test solutes with available experimental migration data in order to reveal the molecular properties that govern the separation. The QSAR models operating with n‐octanol–water partition coefficients or van der Waals volumes were found to be valid for estimation of the retention factors (log k′) of neutral compounds when using only an aqueous MEEKC electrolyte. On the other hand, consistent approximations of log k′ for both uncharged and charged complexes in either EKC mode (and also with hydro‐organic BGEs) were achievable with two‐parametric QSARs in which the dipole moment is additionally incorporated as a structural descriptor, reflecting the electrostatic solute–pseudostationary phase interaction. The theoretical analysis of significant molecular parameters in MEKC systems, in which the micellar BGE is modified with an organic solvent, confirmed that concomitant consideration of hydrophobic, electrostatic, and solvation factors is essential for explaining the migration behavior of neutral metal complexes.
Regular properties of simple electrophoretic BGEs with multiprotic weak acids: Discovery of complex hybrid system boundaries
Authors: Gebauer Petr , Malá Zdena , Šlampová Andrea , Boček Petr
Published: January 2008

In electrophoresis, the introduction of a sample into the BGE creates two new zone boundaries, the front and rear boundary of the sample zone which is sandwiched between the BGE. During an electrophoresis run, these boundaries move and split into other new boundaries demarcating the zones of analytes. Besides the analyte zones migrating out of the original sample location, system zones may be also formed. Such zones are formed by the BGE components and differ from the BGE only in their concentrations. The front and rear boundaries of such system zones evolve during electromigration and may show sharp (S), dispersed (D), and/or hybrid character. This contribution brings the results of theoretical and experimental investigation of system properties of very simple BGEs formed by one weak acid and one weak or strong base provided that the acid is polyprotic. It is shown that system boundaries of the hybrid type occur even in these simple systems represented, e.g., by the very common phosphate buffer. Theory reveals that a phosphate buffer system (formed by phosphoric acid and a strong cation) may exhibit a very unusual complex shape of the electromigration dispersion velocity curve showing three turns. This leads to the formation of complex hybrid boundaries having D–S–D, S–D–S, or even S–D–S–D or D–S–D–S concentration profile types that have not been reported so far. The velocity diagram method allows theoretical analysis of such complicated profiles and the results are in good accordance with both computer simulation and experiments.
Changes in regional cerebral blood flow following antidepressant treatment in late‐life depression
Authors: Ishizaki Junko , Yamamoto Hideki , Takahashi Taro , Takeda Maki , Yano Madoka , Mimura Masaru
Published: January 2008

Objective

Reversible/irreversible abnormalities of regional cerebral blood flow (rCBF) are seen in patients with depression. However, in late‐life depression there is little evidence of a longitudinal change in rCBF through remission. We examined whether the decreased rCBF in individuals with late‐life depression resolves following treatment.

Methods

Twenty‐five depressed patients older than 55 years completed the Hamilton Rating Scale for Depression and single photon emission computed tomography before and after a mean of 13.7 weeks of pharmacotherapy. Quantitative analyses were performed using the Statistical Parametric Mapping procedure.

Results

Patients with depression demonstrated decreased rCBF in the anterior ventral and dorsal medial prefrontal cortex (PFC), including anterior cingulate cortices, bilateral ventrolateral PFC to temporal cortices, and bilateral medial to lateral parieto‐occipital lobes relative to healthy controls. No particular areas showed increased rCBF. Following pharmacotherapy, rCBF significantly increased in the left dorsolateral PFC to precentral areas and the right parieto‐occipital regions. However, decreased rCBF at baseline in the anterior ventral/dorsal medial PFC, bilateral ventrolateral PFC, bilateral temporal lobes, and bilateral parietal lobes did not show significant improvement after treatment.

Conclusions

Remarkable improvements in rCBF in the left dorsolateral PFC to precentral regions are consistent with the hypothesis that neuronetworks including the left frontal cortex may be functionally and reversibly involved in late‐life unipolar major depression (state‐dependent). In contrast, neural circuits including bilateral medial, dorsolateral, and parietal areas may reflect underlying and continuous pathognomonic brain dysfunction of depression (trait‐dependent). Copyright © 2008 John Wiley & Sons, Ltd.
Self‐organized criticality and the development of EEG phase reset
Authors: Thatcher Robert Wayne , North Duane Michael , Biver Carl John
Published: January 2008

Objectives: The purpose of this study was to explore human development of self‐organized criticality as measured by EEG phase reset from infancy to 16 years of age. Methods: The electroencephalogram (EEG) was recorded from 19 scalp locations from 458 subjects ranging in age from 2 months to 16.67 years. Complex demodulation was used to compute instantaneous phase differences between pairs of electrodes and the 1st and 2nd derivatives were used to detect the sudden onset and offset times of a phase shift followed by an extended period of phase locking. Mean phase shift duration and phase locking intervals were computed for two symmetrical electrode arrays in the posterior‐to‐anterior locations and the anterior‐to‐posterior directions in the α frequency band (8–13 Hz). Results: Log–log spectral plots demonstrated 1/f α distributions (α ≈ 1) with longer slopes during periods of phase shifting than during periods of phase locking. The mean duration of phase locking (150–450 msec) and phase shift (45–67 msec) generally increased as a function of age. The mean duration of phase shift declined over age in the local frontal regions but increased in distant electrode pairs. Oscillations and growth spurts from mean age 0.4–16 years were consistently present. Conclusions: The development of increased phase stability in local systems is paralleled by lengthened periods of unstable phase in distant connections. Development of the number and/or density of synaptic connections is a likely order parameter to explain oscillations and growth spurts in self‐organized criticality during human brain maturation. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Altered small‐world brain functional networks in children with attention‐deficit/hyperactivity disorder
Authors: Wang Liang , Zhu Chaozhe , He Yong , Zang Yufeng , Cao QingJiu , Zhang Han , Zhong Qiuhai , Wang Yufeng
Published: January 2008

In this study, we investigated the changes in topological architectures of brain functional networks in attention‐deficit/hyperactivity disorder (ADHD). Functional magnetic resonance images (fMRI) were obtained from 19 children with ADHD and 20 healthy controls during resting state. Brain functional networks were constructed by thresholding the correlation matrix between 90 cortical and subcortical regions and further analyzed by applying graph theoretical approaches. Experimental results showed that, although brain networks of both groups exhibited economical small‐world topology, altered functional networks were demonstrated in the brain of ADHD when compared with the normal controls. In particular, increased local efficiencies combined with a decreasing tendency in global efficiencies found in ADHD suggested a disorder‐related shift of the topology toward regular networks. Additionally, significant alterations in nodal efficiency were also found in ADHD, involving prefrontal, temporal, and occipital cortex regions, which were compatible with previous ADHD studies. The present study provided the first evidence for brain dysfunction in ADHD from the viewpoint of global organization of brain functional networks by using resting‐state fMRI. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Functional connectivity of default mode network components: Correlation, anticorrelation, and causality
Authors: Uddin Lucina Q. , Clare Kelly A.M. , Biswal Bharat B. , Xavier Castellanos F. , Milham Michael P.
Published: January 2008

The default mode network (DMN), based in ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), exhibits higher metabolic activity at rest than during performance of externally oriented cognitive tasks. Recent studies have suggested that competitive relationships between the DMN and various task‐positive networks involved in task performance are intrinsically represented in the brain in the form of strong negative correlations (anticorrelations) between spontaneous fluctuations in these networks. Most neuroimaging studies characterize the DMN as a homogenous network, thus few have examined the differential contributions of DMN components to such competitive relationships. Here, we examined functional differentiation within the DMN, with an emphasis on understanding competitive relationships between this and other networks. We used a seed correlation approach on resting‐state data to assess differences in functional connectivity between these two regions and their anticorrelated networks. While the positively correlated networks for the vmPFC and PCC seeds largely overlapped, the anticorrelated networks for each showed striking differences. Activity in vmPFC negatively predicted activity in parietal visual spatial and temporal attention networks, whereas activity in PCC negatively predicted activity in prefrontal‐based motor control circuits. Granger causality analyses suggest that vmPFC and PCC exert greater influence on their anticorrelated networks than the other way around, suggesting that these two default mode nodes may directly modulate activity in task‐positive networks. Thus, the two major nodes comprising the DMN are differentiated with respect to the specific brain systems with which they interact, suggesting greater heterogeneity within this network than is commonly appreciated. Hum Brain Mapp 30:625–637, 2009. © 2008 Wiley‐Liss, Inc.
Diarylheptanoids from the Rhizomes of Alpinia officinarum
Authors: Sun Yi , Matsubara Hideki , Kitanaka Susumu , Yasukawa Ken
Published: January 2008

A novel dimeric diarylheptanoid, (5R,5′R)‐7,7′‐(6,6′‐dihydroxy‐5,5′‐dimethoxy[1,1′‐biphenyl]‐3,3′‐diyl)bis[5‐methoxy‐1‐phenylheptan‐3‐one] (1), and two new diarylheptanoids, (4E,6R)‐6‐hydroxy‐7‐(4‐hydroxy‐3‐methoxyphenyl)‐1‐phenylhept‐4‐en‐3‐one (2) and (4E,6R)‐6‐hydroxy‐1,7‐diphenylhept‐4‐en‐3‐one (3), together with seven known diarylheptanoids, were isolated from the rhizomes of Alpinia officinarum. Their structures were elucidated by application of extensive spectroscopic analyses and the modified Mosher method.
Two New Benzophenanthridine Alkaloids from Zanthoxylum nitidum
Authors: Cui Xin‐Gang , Zhao Qing‐Jie , Chen Qiao‐Ling , Xu Lei , Song Yan , Jin Yong‐Sheng , Xu Dan‐Feng
Published: January 2008

Two new benzophenanthridine alkaloids, named 8‐methoxysanguinarine (1) and 8‐methoxyisodecarine (2), were isolated from the EtOH extract of the rhizoma of Zanthoxylum nitidum. Their structures were determined on the basis of spectroscopic analysis.
A Novel One‐Pot Conversion of Allyl Alcohols into Primary Allyl Halides Mediated by Acetyl Halide
Authors: Kishali Nurhan , Polat M. Fatih , Altundas Ramazan , Kara Yunus
Published: January 2008

A new and simple method for the synthesis of the primary allyl chlorides and bromides 9–16 from the secondary or tertiary allyl alcohols 3–8 and acyl halide was developed (Scheme 2, Table 1). Non‐commercially available secondary and tertiary allyl alcohols were synthesized from the related ketones and aldehydes via the addition of vinylmagnesium chloride. Mechanistic studies indicate that the alcohols were first acetylated by the acetyl halide and then protonated prior to substitution by the halide, Cl− or Br−, via an SN2′ reaction, to yield the primary halides (Scheme 5).
Laminins and their roles in mammals
Authors: Miner Jeffrey H.
Published: January 2008

Laminins are α‐β‐γ heterotrimeric components of all basement membranes. Laminins are now known to play the central role in organizing and establishing the basement membrane. The diversity of laminins allows them to impart special structural and signaling properties to the basement membrane. Of the 12 known laminin chain genes, 10 have been either found to be mutated in humans or experimentally mutated in mice. This has led to great progress over the last several years towards understanding both the functions of laminins and the reasons for their great diversity. In this review, I will summarize the in vivo studies in mice and humans that have contributed to this new knowledge. Microsc. Res. Tech., 2008. © 2008 Wiley‐Liss, Inc.
Myocardial fibrosis of left ventricle: Magnetic resonance imaging in noncompaction
Authors: Alsaileek Ahmed A. , Syed Imran , Seward James B. , Julsrud Paul
Published: January 2008

This report describes a 24‐year‐old female with left ventricular noncompaction. Cardiovascular magnetic resonance (CMR) imaging demonstrated the characteristic features of noncompaction. We were also able to noninvasively document the presence and extent of myocardial fibrosis depicted on myocardial delayed enhancement (MDE). Magnetic resonance imaging can be performed simply and give much information about the morphologic and tissue characteristics of left ventricular wall in noncompaction. In particular, MDE imaging is useful to demonstrate the associated myocardial scaring that may result in heart failure and arrhythmia. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
Enhanced tumor MR imaging with gadolinium‐loaded polychelating polymer‐containing tumor‐targeted liposomes
Authors: Erdogan Suna , Medarova Zdravka O. , Roby Aruna , Moore Anna , Torchilin Vladimir P.
Published: January 2008

Purpose

To significantly enhance tumor MR imaging by using a contrast agent combining three components—a long‐circulating liposome, liposomal membrane‐incorporated polychelating amphiphilic polymer heavily loaded with gadolinium, and cancer‐specific monoclonal antibody 2C5 attached to the liposome surface.

Materials and Methods

Tumor‐bearing animals were imaged prior and 4, 24, and 48 hours after i.v. injection of 2C5‐modified and unmodified Gd‐PAP‐containing PEGylated liposomes. The faster and more specific accumulation of the novel contrast nanoparticles in tumors was also confirmed by 3D angiograms and by direct visualization of Gd‐immunoliposomes in tumor sections by confocal microscopy.

Results

2C5‐modified Gd‐PAP‐containing PEGylated liposomes allowed for fast and specific tumor imaging as early as 4 hours postinjection. T1 inversion recovery maps demonstrated a significant increase in tumor‐associated R1 in animals injected with antibody‐modified Gd‐loaded liposomes 4 hours postinjection, followed by a gradual decrease consistent with clearance of the agent from the tumor region. In control animals injected with antibody‐free liposomes the corresponding R1 values at all investigated timepoints were significantly smaller.

Conclusion

The results support the feasibility of using such multifunctional nanoparticular liposome‐based agents simultaneously providing prolonged circulation, heavy Gd load, and specific cancer cell recognition as a superior contrast for MR tumor imaging. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
CBF, BOLD, CBV, and CMRO2 fMRI signal temporal dynamics at 500‐msec resolution
Authors: Shen Qiang , Ren Hongxia , Duong Timothy Q.
Published: January 2008

Purpose

To investigate the temporal dynamics of blood oxygenation level‐dependent (BOLD), cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2) changes due to forepaw stimulation with 500‐msec resolution in a single setting.

Materials and Methods

Forepaw stimulation and hypercapnic challenge on rats were studied. CBF and BOLD functional MRI (fMRI) were measured using the pseudo‐continuous arterial spin‐labeling technique at 500‐msec resolution. CBV fMRI was measured using monocrystalline iron‐oxide particles following CBF and BOLD measurements in the same animals. CMRO2 change was estimated via the biophysical BOLD model with hypercapnic calibration. Percent changes and onset times were analyzed for the entire forepaw somatosensory cortices and three operationally defined cortical segments, denoted Layers I–III, IV–V, and VI.

Results

BOLD change was largest in Layers I–III, whereas CBF, CBV, and CMRO2 changes were largest in Layers IV–V. Among all fMRI signals in all layers, only the BOLD signal in Layers I–III showed a poststimulus undershoot. CBF and CBV dynamics were similar. Closer inspection showed that CBV increased slightly first (P < 0.05), but was slow to peak. CBF increased second, but peaked first. BOLD significantly lagged both CBF and CBV (P < 0.05).

Conclusion

This study provides important temporal dynamics of multiple fMRI signals at high temporal resolution in a single setting. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
Determination of transmural, endocardial, and epicardial radial strain and strain rate from phase contrast MR velocity data
Authors: Delfino Jana G. , Fornwalt Brandon K. , Eisner Robert L. , Leon Angel R. , Oshinski John N.
Published: January 2008

Purpose

To develop a method for computing radial strain (ε) and strain rate (SR) from phase contrast magnetic resonance (PCMR) myocardial tissue velocity data.

Materials and Methods

PCMR tissue velocity maps were acquired at basal and mid‐short‐axis slices in the myocardium in 10 healthy volunteers. An algorithm for computing radial strain and SR from PCMR tissue velocity data was developed. PCMR strain values were compared to values computed independently from contours drawn on cine steady‐state free procession (SSFP) images. Peak endocardial and epicardial strain and SR values from PCMR data were compared.

Results

Excellent agreement was observed between peak strain values computed by PCMR and cine SSFP contours (38.1 ± 5.4% vs. 38.1 ± 6.2%; P = not significant [NS]). The presence of an endocardial‐epicardial gradient was demonstrated in both strain and SR: peak endocardial values were larger than peak epicardial values in the basal and mid‐short‐axis slices (P < 0.05).

Conclusion

This study presents a method for determining radial strain and SR values from PCMR velocity data. This technique illustrates a difference in strain and SR across the myocardium with peak endocardial values being greater than peak epicardial values. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
Evaluation of quantitative magnetic resonance imaging, biochemical and mechanical properties of trypsin‐treated intervertebral discs under physiological compression loading
Authors: Mwale Fackson , Demers Caroline N. , Michalek Arthur J. , Beaudoin Gilles , Goswami Tapas , Beckman Lorne , Iatridis James C. , Antoniou John
Published: January 2008

Purpose

To investigate the influence of targeted trypsin digestion and 16 hours compression loading on MR parameters and the mechanical and biochemical properties of bovine disc segments.

Materials and Methods

Twenty‐two 3‐disc bovine coccygeal segments underwent compression loading for 16 hours after the nucleus pulposus (NP) of each disc was injected with a solution of trypsin or buffer. The properties of the NP and annulus fibrosus (AF) tissues of each disc were analyzed by quantitative MRI, biochemical tests, and confined compression tests.

Results

Loading had a significant effect on the MR properties (T1, T2, T1ρ, MTR, ADC) of both the NP and AF tissues. Loading had a greater effect on the MR parameters and biochemical composition of the NP than trypsin. In contrast, trypsin had a larger effect on the mechanical properties. Our data also indicated that localized trypsin injection predominantly affected the NP. T1ρ was sensitive to loading and correlated with the water content of the NP and AF but not with their proteoglycan content.

Conclusion

Our studies indicate that physiological loading is an important parameter to consider and that T1ρ contributes new information in efforts to develop quantitative MRI as a noninvasive diagnostic tool to detect changes in early disc degeneration. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
New macromolecular polymeric MRI contrast agents for application in the differentiation of cancer from benign soft tissues
Authors: Cyran Clemens C. , Fu Yanjun , Raatschen Hans‐Juergen , Rogut Victor , Chaopathomkul Bundit , Shames David M. , Wendland Michael F. , Yeh Benjamin M. , Brasch Robert C.
Published: January 2008

Purpose

To compare three new macromolecular polyethylene glycol (PEG) ‐core dendrimeric gadolinium(Gd)‐based MRI contrast agents for their applicability in quantitative assays of endothelial leakiness and tissue vascular density for the differentiation of cancer from normal soft tissues.

Materials and Methods

Thirty‐two athymic rats with human breast cancer xenografts (MDA‐MB‐435) were imaged by dynamic MRI following enhancement with one of three new (Gd‐DOTA)‐conjugated PEG‐core dendrimer contrast agents (effective molecular weights 161 to 323 kDa). Results were compared with a prototype macromolecular contrast agent, albumin (Gd‐DTPA). Assays of permeabilities (KPS; μL/min · 100 cm3) and tumor fractional plasma volumes (%) based on a two‐compartment kinetic model were performed for skeletal muscle and tumors.

Results

The largest PEG‐core contrast agent, PEG20,000‐Gen4‐(Gd‐DOTA), leaked in breast tumors (KPS = 50 ± 23 μL/min · 100 cm3), while exhibiting no measurable transendothelial leak (KPS = 0 μL/min · 100 cm3) in normal soft tissue microvessels allowing successful differentiation (P < 0.05) of cancers from normal muscle. PEG12,000‐Gen4‐(Gd‐DOTA) leaked in tumors and in normal muscle (KPS = 51 ± 26 and KPS = 21 ± 18μL/min · 100 cm3, respectively). The smallest agent, PEG12,000‐Gen3‐(Gd‐DOTA) also showed a measurable leak in both normal and malignant microvessels.

Conclusion

MRI assays of vascular endothelial leakiness using new PEG‐core, (Gd‐DOTA)‐conjugated macromolecular contrast agents proved applicable for the differentiation of human breast cancer from normal soft tissue. The apparent threshold in effective molecular weight for a clear differentiation of cancer from normal muscle with no measurable leak in the muscle is between 194 and 323 kDa. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
Serial postmortem relaxometry in the normal rat brain and following stroke
Authors: Fagan Andrew J. , Mullin Jim M. , Gallagher Lindsay , Hadley Donald M. , Macrae I. Mhairi , Condon Barrie
Published: January 2008

Purpose

To investigate MRI for noninvasive autopsy by means of measurements of serial changes in relaxation parameters of the rat brain during the postmortem interval.

Materials and Methods

Postmortem relaxometry measurements were performed before and hourly after death for 24 h on five control rats and five rats that underwent middle cerebral artery occlusion. Analyses were performed on representative regions of gray, white, and mixed gray/white matter structures.

Results

Significant decreases in both T1 and T2 values were measured in all areas in the control group within 24 h of death. In the stroke animals, T2 differences between normal and ischemic striatal tissue decreased by 11 ± 4% (P < 0.01), with a complete convergence of T2 values observed between ischemic striatal tissue and nonischemic cortical tissue.

Conclusion

Lesion conspicuity and the ability to differentiate between different tissue compartments are significantly affected by postmortem interval, and alterations to pulse timing parameters will be necessary if the sensitivity of MRI to detect central nervous system diseases in postmortem tissue is to be maintained. Indeed in the case of stroke at least, convergence of T2 values with normal tissue post mortem indicates that T1‐weighted images may be more sensitive to the presence of such lesions. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
Navigation concepts for MR image‐guided interventions
Authors: Moche Michael , Trampel Robert , Kahn Thomas , Busse Harald
Published: January 2008

The ongoing development of powerful magnetic resonance imaging techniques also allows for advanced possibilities to guide and control minimally invasive interventions. Various navigation concepts have been described for practically all regions of the body. The specific advantages and limitations of these concepts largely depend on the magnet design of the MR scanner and the interventional environment. Open MR scanners involve minimal patient transfer, which improves the interventional workflow and reduces the need for coregistration, ie, the mapping of spatial coordinates between imaging and intervention position. Most diagnostic scanners, in contrast, do not allow the physician to guide his instrument inside the magnet and, consequently, the patient needs to be moved out of the bore. Although adequate coregistration and navigation concepts for closed‐bore scanners are technically more challenging, many developments are driven by the well‐known capabilities of high‐field systems and their better economic value. Advanced concepts such as multimodal overlays, augmented reality displays, and robotic assistance devices are still in their infancy but might propel the use of intraoperative navigation. The goal of this work is to give an update on MRI‐based navigation and related techniques and to briefly discuss the clinical experience and limitations of some selected systems. J. Magn. Reson. Imaging 2008;27:276–291. © 2008 Wiley‐Liss, Inc.
Stem cell therapy: MRI guidance and monitoring
Authors: Kraitchman Dara L. , Gilson Wesley D. , Lorenz Christine H.
Published: January 2008

With the recent advances in magnetic resonance (MR) labeling of cellular therapeutics, it is natural that interventional MRI techniques for targeting would be developed. This review provides an overview of the current methods of stem cell labeling and the challenges that are created with respect to interventional MRI administration. In particular, stem cell therapies will require specialized, MR‐compatible devices as well as integration of graphical user interfaces with pulse sequences designed for interactive, real‐time delivery in many organs. Specific applications that are being developed will be reviewed as well as strategies for future translation to the clinical realm. J. Magn. Reson. Imaging 2008;27:299–310. © 2008 Wiley‐Liss, Inc.
Magnetic resonance guidance for radiofrequency ablation of liver tumors
Authors: Clasen Stephan , Pereira Philippe L.
Published: January 2008

Image‐guided thermal ablation of liver tumors is a minimally invasive treatment option. Techniques used for thermal ablation are radiofrequency (RF) ablation, laser interstitial thermotherapy (LITT), microwave (MW) ablation, high‐intensity focused ultrasound (HIFU), and cryoablation. Among these techniques RF ablation attained widespread consideration. Image guidance should ensure a precise ablation therapy leading to a complete coagulation of tumor tissue without injury to critical structures. Therefore, the modality of image guidance has an important impact on the safety and efficacy of percutaneous RF ablation. The current literature regarding percutaneous RF ablation mainly describes the use of computed tomography (CT) and ultrasonography (US) guidance. In addition, interventional MR systems offer the possibility to utilize the advantages of MR imaging such as excellent soft‐tissue contrast, multiplanar and interactive capabilities, and sensitivity to thermal effects during the entire RF ablation procedure. Monitoring of thermally induced coagulation by MR imaging is supportive to control the ablation procedure. MR imaging can be advantageously used to guide overlapping ablation if necessary as well as to define the endpoint of RF ablation after complete coverage of the target tissue is verified. Furthermore, monitoring of thermal effects is essential in order to prevent unintended thermal damage from critical structures surrounding the target region. Therefore, MR‐guided RF ablation offers the possibility for a safe and effective therapy option in the treatment of primary and secondary hepatic malignancies. The article summarizes the role of MR guidance for RF ablation of liver tumors. J. Magn. Reson. Imaging 2008;27:421–433. © 2008 Wiley‐Liss, Inc.
MR thermometry
Authors: Rieke Viola , Butts Pauly Kim
Published: January 2008

Minimally invasive thermal therapy as local treatment of benign and malignant diseases has received increasing interest in recent years. Safety and efficacy of the treatment require accurate temperature measurement throughout the thermal procedure. Noninvasive temperature monitoring is feasible with magnetic resonance (MR) imaging based on temperature‐sensitive MR parameters such as the proton resonance frequency (PRF), the diffusion coefficient (D), T1 and T2 relaxation times, magnetization transfer, the proton density, as well as temperature‐sensitive contrast agents. In this article the principles of temperature measurements with these methods are reviewed and their usefulness for monitoring in vivo procedures is discussed. Whereas most measurements give a temperature change relative to a baseline condition, temperature‐sensitive contrast agents and spectroscopic imaging can provide absolute temperature measurements. The excellent linearity and temperature dependence of the PRF and its near independence of tissue type have made PRF‐based phase mapping methods the preferred choice for many in vivo applications. Accelerated MRI imaging techniques for real‐time monitoring with the PRF method are discussed. Special attention is paid to acquisition and reconstruction methods for reducing temperature measurement artifacts introduced by tissue motion, which is often unavoidable during in vivo applications. J. Magn. Reson. Imaging 2008;27:376–390. © 2008 Wiley‐Liss, Inc.
Targeted drug delivery under MRI guidance
Authors: Arepally Aravind
Published: January 2008

The main goal of local drug delivery is to increase the concentration of a specific therapeutic agent in a target tissue with minimal nontarget distribution. Compared to systemic therapy, local drug delivery provides a high level of therapeutic efficacy with minimal systemic effects. The current primary imaging modality for drug delivery has been x‐ray angiography, but it has major limitations including anatomical ambiguity and inability to visualize the targeted tissues. Due to these inherent problems, MR guidance has been explored as an alternative imaging modality for guiding and monitoring of drug therapy. Recently, interventional MR (XMR) systems have been implemented that have both dual x‐ray and MRI capabilities in a single suite and allow for real‐time interventional procedures to be performed in a clinical setting. In cases where drug delivery is required, this system provides a significant leap for catheter‐based therapies. Although clinical drug delivery procedures utilizing MR guidance are still in the early stages of development and application, recent technological advances should help further promote the adoption of such procedures. This review covers the emerging techniques of drug delivery using MR guidance. J. Magn. Reson. Imaging 2008;27:292–298. © 2008 Wiley‐Liss, Inc.
MR systems for MRI‐guided interventions
Authors: Hushek Stephen G. , Martin Alastair J. , Steckner Michael , Bosak Elyakim , Debbins Josef , Kucharzyk Walter
Published: January 2008

The field of MR imaging has grown from diagnosis via morphologic imaging to more sophisticated diagnosis via both physiologic and morphologic imaging and finally to the guidance and control of interventions. A wide variety of interventional procedures from open brain surgeries to noninvasive focused ultrasound ablations have been guided with MR and the differences between diagnostic and interventional MR imaging systems have motivated the creation of a new field within MR. This review discusses the various systems that research groups and vendors have designed to meet the requirements of interventional MR and suggest possible solutions to those requirements that have not yet been met. The common requirements created by MR imaging guidance of interventional procedures are reviewed and different imaging system designs will be independently considered. The motivation and history of the different designs are discussed and the ability of the designs to satisfy the requirements is analyzed. J. Magn. Reson. Imaging 2008;27:253–266. © 2008 Wiley‐Liss, Inc.
MR‐guided biopsy: A review of current techniques and applications
Authors: Weiss Clifford R. , Nour Sherif Gamal , Lewin Jonathan S.
Published: January 2008

Biopsy has become a cornerstone of modern medicine and most modern biopsies are performed percutaneously using image guidance, typically computed tomography or ultrasound. MR‐guided biopsy offers many advantages over these more traditional modalities, and the recent development of interventional MR imaging techniques has made MR‐guided percutaneous biopsies and aspirations a clinical reality. As the field of MR‐guided procedures continues to expand and to attract more attention from radiologists, it is important to understand the concepts, techniques, applications, advantages, and limitations of MR‐guided biopsy/percutaneous procedures. Radiologists should also recognize the need for their significant involvement in the technical aspects of MR‐guided procedures, since several user‐defined parameters can alter device visualization in the MR imaging environment and affect procedure safety. This article reviews the prerequisites, systems, and applications of MR‐guided biopsy. J. Magn. Reson. Imaging 2008;27:311–325. © 2008 Wiley‐Liss, Inc.
Bone marrow stromal cells protect oligodendrocytes from oxygen‐glucose deprivation injury
Authors: Zhang Jing , Li Yi , Zheng Xuguang , Gao Qi , Liu Zhongwu , Qu Runjiang , Borneman Jade , Elias Stanton B. , Chopp Michael
Published: January 2008

Oligodendrocyte (OLG) damage leads to demyelination, which is frequently observed in ischemic cerebrovascular diseases. In this study, we investigated the effect of bone marrow stromal cells (BMSCs) on OLGs subjected to oxygen‐glucose deprivation (OGD). N20.1 cells (mouse OLG cell line) were transferred into an anaerobic chamber for 3 hr in glucose‐free and serum‐free medium. After OGD incubation, OLG cultures were divided into the following groups: 1) OGD alone, 2) OLG cocultured with BMSCs, 3) treatment with the phosphoinostide 3‐kinase (PI3k) inhibitor LY294002, 4) LY294002‐treated OLGs with BMSC cocultured, and 5) anti‐p75 antibody‐treated OLGs. After an additional 3 hr of reoxygenation incubation, OLG viability and apoptosis were measured. The mRNA expression in the BMSCs and OLGs was analyzed using quantitative real‐time PCR (RT‐PCR). Serine/threonine‐specific protein kinase (Akt), phosphorylated Akt (p‐Akt), p75, and caspase 3 protein expressions in OLGs were measured by Western blot. Our results suggest that BMSCs produce growth factors, activate the Akt pathway, and increase the survival of OLGs. BMSCs also reduce p75 and caspase 3 expressions in the OGD‐OLGs, which leads to decreased OLG apoptosis. BMSCs participate in OLG protection that may occur with promoting growth factors/PI3K/Akt and inhibiting the p75/caspase pathways. Our study provides insight into white matter damage and the therapeutic benefits of BMSC‐based remyelinating therapy after stroke and demyelinating diseases. © 2008 Wiley‐Liss, Inc.
Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone
Authors: Xu Hongmin , Hu Furong , Sado Yoshikazu , Ninomiya Yoshifumi , Borza Dorin‐Bogdan , Ungvari Zoltan , LaGamma Edmund F. , Csiszar Anna , Nedergaard Maiken , Ballabh Praveen
Published: January 2008

Germinal matrix is selectively vulnerable to hemorrhage in premature infants, and use of prenatal betamethasone is associated with a lower occurrence of germinal matrix hemorrhage. Because the major components of extracellular matrix of the cerebral vasculature—laminin, fibronectin, collagen IV, and perlecan—provide structural stability to blood vessels, we examined whether the expression of these molecules was decreased in the germinal matrix and affected by betamethasone. In both human fetuses and premature infants, fibronectin was significantly lower in the germinal matrix than in the cortical mantle or white matter anlagen. Conversely, laminin α1 gene expression was greater in the human germinal matrix compared with the cortical mantle or white matter. Expression of α1‐ and α2(IV) collagen chains increased with advancing gestational age. Low‐dose prenatal betamethasone treatment enhanced fibronectin level by 1.5–2‐fold whereas a high dose reduced fibronectin expression by 2‐fold in rabbit pups. Because fibronectin provides structural stability to the blood vessels, its reduced expression in the germinal matrix may contribute to the fragility of germinal matrix vasculature and the propensity to hemorrhage in premature neonates. © 2008 Wiley‐Liss, Inc.
Expression of polyalanine stretches induces mitochondrial dysfunction
Authors: Toriumi Kazuya , Oma Yoko , Kino Yoshihiro , Futai Eugene , Sasagawa Noboru , Ishiura Shoichi
Published: January 2008

In recent years, several novel types of disorders have been characterized, including what have been termed polyalanine diseases, in which patients have expanded triplet repeats in specific genes, resulting in the translation of aberrantly elongated polyalanine stretches. In this study, we showed that yellow fluorescent protein (YFP)‐fused elongated polyalanine stretches localized exclusively to the cytoplasm and formed aggregates. Additionally, the polyalanine stretches themselves were toxic. We sought to identify proteins that bound directly to the polyalanine stretches, as factors that might be involved in triggering cell death. Many mitochondrial proteins were identified as polyalanine‐binding proteins. We showed that one of the identified proteins, succinate dehydrogenase subunit A, was decreased in the mitochondria of cells expressing polyalanine stretches; as a result, succinate oxidative activity was decreased. Furthermore, the polyalanine stretches also associated directly with mitochondria. This suggests that polya‐lanine stretches might directly induce cell death. Additionally, the mitochondrial membrane potential was reduced in cells expressing polyalanine stretches. We propose a novel mechanism by which polyalanine stretches may cause cytotoxicity through mitochondrial dysfunction. This may be a common mechanism underlying the pathogenesis of all polyalanine diseases. © 2008 Wiley‐Liss, Inc.
Ciliary neurotrophic factor and interleukin‐6 differentially activate microglia
Authors: Krady J. Kyle , Lin Hsiao‐Wen , Liberto Christina M. , Basu Anirban , Kremlev Sergey G. , Levison Steven W.
Published: January 2008

Studies have shown that cytokines released following CNS injury can affect the supportive or cytotoxic functions of microglia. Interleukin‐6 (IL‐6)‐family cytokines are among the injury factors released. To understand how microglia respond to IL‐6 family cytokines, we examined the effects of ciliary neurotrophic factor (CNTF) and IL‐6 on primary cultures of rat microglia. To assess the functional state of the cells, we assayed the expression of tumor necrosis factor‐α (TNFα), interleukin‐1β (IL‐1β), and cyclooxygenase 2 (COX‐2) following stimulation. We show that CNTF reduces COX‐2 levels, whereas IL‐6 increases the expression of IL‐1β, TNFα, and Cox‐2. We also examined trophic factor expression and found that CNTF enhances glial cell‐line derived neurotrophic factor (GDNF) mRNA and protein secretion, whereas IL‐6 has no effect. Correspondingly, conditioned media from CNTF‐stimulated microglia promote motor neuron survival threefold beyond controls, whereas IL‐6‐stimulated microglia decrease neuronal survival twofold. To understand better the signaling mechanisms responsible for the opposite responses of these IL‐6‐family cytokines, we examined STAT‐3 and ERK phosphorylation in CNTF‐ and IL‐6‐stimulated microglia. IL‐6 markedly increases STAT‐3 and ERK phosphorylation after 20 min of treatment, whereas these signal transducers are weakly stimulated by CNTF across a range of doses. We conclude that CNTF modifies microglial activation to support neuronal survival and that IL‐6 enhances their capacity to do harm, as a result of different modes of intracellular signaling. © 2008 Wiley‐Liss, Inc.
Ischemia‐induced ribosomal protein S3 expressional changes and the neuroprotective effect against experimental cerebral ischemic damage
Authors: Hwang In Koo , Yoo Ki‐Yeon , Kim Dae Won , Kim So Young , Park Jun Hong , Ryoo Zae Young , Kim Joon , Choi Soo Young , Won Moo‐Ho
Published: January 2008

Some ribosomal proteins are important regulators of development and DNA repair. However, few studies have been conducted on ribosomal protein S3 (rpS3) in the ischemic hippocampus. In the present study, we investigated ischemia‐induced changes in rpS3 immunoreactivity, rpS3 mRNA, and protein levels in the hippocampal CA1 region of Mongolian gerbil after 5 min of transient forebrain ischemia. RpS3 immunoreactivity and its protein level were found to be significantly elevated at 6 hr after ischemia/reperfusion and then continuously decreased with time. RT‐PCR analysis also showed that rpS3 mRNA levels were significantly elevated in CA1 at 6 hr after transient ischemia. In addition, during the course of this study, we developed a delivery vector (Pep‐1) and its rpS3 fusion protein (Pep‐1–rpS3) to elucidate the role of rpS3 in ischemia‐induced damage. Pep‐1–rpS3 administration to ischemic animals significantly and dose dependently increased neuronal survival in the stratum pyramidale of CA1. Moreover, Pep‐1–rpS3 treatment reduced terminal deoxynucleotidyl dUTP nick‐end labeling‐positive CA1 pyramidal cell numbers in the stratum pyramidale. To elucidate how Pep‐1–rpS3 ameliorates ischemic damage, changes in 4‐hydroxy‐2‐nonnenal (HNE; an indicator of lipid peroxidation) immunoreactivity and protein levels were investigated. HNE levels and immunoreactivities in Pep‐1–rpS3‐treated ischemic animals were lower than in corresponding Pep‐1‐treated ischemic animals. These results indicate that rpS3 has a neuroprotective effect in the brain exposed to ischemia. © 2008 Wiley‐Liss, Inc.