B Factors (b + factor)

Distribution by Scientific Domains


Selected Abstracts


Comparison of the three-dimensional structures of a human Bence-Jones dimer crystallized on Earth and aboard US Space Shuttle Mission STS-95,

JOURNAL OF MOLECULAR RECOGNITION, Issue 2 2003
Simon S. Terzyan
Abstract Crystals of a human (Sea) Bence-Jones dimer were produced in a capillary by vapor diffusion under microgravity conditions in the 9 day US Space Shuttle Mission STS-95. In comparison to ground-based experiments, nucleation was facile and spontaneous in space. Appearance of a very large (8,,1.6,,1.0,mm) crystal in a short time period is a strong endorsement for the use of microgravity to produce crystals sufficiently large for neutron diffraction studies. The Sea dimer crystallized in the orthorhombic space group P212121, with a,=,48.9,, b,=,85.2,, and c,=,114.0,. The crystals grown in microgravity exhibited significantly lower mosaicities than those of ground-based crystals and the X-ray diffraction data had a lower overall B factor. Three-dimensional structures determined by X-ray analysis at two temperatures (100 and 293,K) were indistinguishable from those obtained from ground-based crystals. However, both the crystallographic R factor and the free R factor were slightly lower in the models derived from crystals produced in microgravity. The major difference between the two crystal growth systems is a lack of convection and sedimentation in a microgravity environment. This environment resulted in the growth of much larger, higher-quality crystals of the Sea Bence-Jones protein. Structurally, heretofore unrecognized grooves on the external surfaces of the Sea and other immunoglobulin-derived fragments are regular features and may offer supplementary binding regions for super antigens and other elongated ligands in the bloodstream and perivascular tissues. Copyright 2003 John Wiley & Sons, Ltd. [source]


The minimum crystal size needed for a complete diffraction data set

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2010
James M. Holton
In this work, classic intensity formulae were united with an empirical spot-fading model in order to calculate the diameter of a spherical crystal that will scatter the required number of photons per spot at a desired resolution over the radiation-damage-limited lifetime. The influences of molecular weight, solvent content, Wilson B factor, X-ray wavelength and attenuation on scattering power and dose were all included. Taking the net photon count in a spot as the only source of noise, a complete data set with a signal-to-noise ratio of 2 at 2, resolution was predicted to be attainable from a perfect lysozyme crystal sphere 1.2,m in diameter and two different models of photoelectron escape reduced this to 0.5 or 0.34,m. These represent 15-fold to 700-fold less scattering power than the smallest experimentally determined crystal size to date, but the gap was shown to be consistent with the background scattering level of the relevant experiment. These results suggest that reduction of background photons and diffraction spot size on the detector are the principal paths to improving crystallographic data quality beyond current limits. [source]


Structural consequences of hen egg-white lysozyme orthorhombic crystal growth in a high magnetic field: validation of X-ray diffraction intensity, conformational energy searching and quantitative analysis of B factors and mosaicity

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2005
Shinya Saijo
A novel method has been developed to improve protein-crystal perfection during crystallization in a high magnetic field and structural studies have been undertaken. The three-dimensional structure of orthorhombic hen egg-white (HEW) lysozyme crystals grown in a homogeneous and static magnetic field of 10,T has been determined and refined to a resolution of 1.13, and an R factor of 17.0%. The 10,T crystals belonged to space group P212121, with unit-cell parameters a = 56.54,(3), b = 73.86,(6), c = 30.50,(2), and one molecule per asymmetric unit. A comparison of the structures of the 0,T and 10,T crystals has been carried out. The magnitude of the structural changes, with a root-mean-square deviation value of 0.75, for the positions of all protein atoms, is similar to that observed when an identical protein structure is resolved in two different crystalline lattices. The structures remain similar, with the exception of a few residues e.g. Arg68, Arg73, Arg128 and Gln121. The shifts of the arginine residues result in very significant structural fluctuations, which can have large effects on a protein's crystallization properties. The high magnetic field contributed to an improvement in diffraction intensity by (i) the displacement of the charged side chains of Arg68 and Arg73 in the flexible loop and of Arg128 at the C-terminus and (ii) the removal of the alternate conformations of the charged side chains of Arg21, Lys97 or Arg114. The improvement in crystal perfection might arise from the magnetic effect on molecular orientation without structural change and differences in molecular interactions. X-ray diffraction and molecular-modelling studies of lysozyme crystals grown in a 10,T field have indicated that the field contributes to the stability of the dihedral angle. The average difference in conformational energy has a value of ,578,kJ,mol,1 per charged residue in favour of the crystal grown in the magnetic field. For most protein atoms, the average B factor in the 10,T crystal shows an improvement of 1.8,2 over that for the 0,T control; subsequently, the difference in diffraction intensity between the 10,T and 0,T crystals corresponds to an increase of 22.6% at the resolution limit. The mosaicity of the 10,T crystal was better than that of the 0,T crystal. More highly isotropic values of 0.0065, 0.0049 and 0.0048 were recorded along the a, b and c axes, respectively. Anisotropic mosaicity analysis indicated that crystal growth is most perfect in the direction that corresponds to the favoured growth direction of the crystal, and that the crystal grown in the magnetic field had domains that were three times the volume of those of the control crystal. Overall, the magnetic field has improved the quality of these crystals and the diffracted intensity has increased significantly with the magnetic field, leading to a higher resolution. [source]


NF- ,B in liver diseases: a target for drug therapy

JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2009
Pablo Muriel
Abstract There are five nuclear factor- ,B (NF- ,B) transcription factors with important roles in innate immunity, liver inflammation, fibrosis and apoptosis prevention. Several inhibitors of NF- ,B, like caffeic acid, captopril, curcumin, pyrrolidine dithiocarbamate, resveratrol, silymarin and thalidomide, have demonstrated antinecrotic, anticholestatic, antifibrotic and anticancer activities in the liver. A link between inflammation and hepatocellular carcinoma through the NF- ,B pathway has been observed, providing ample experimental support for the tumor-promoting function of NF- ,B in various models of cancer. NF- ,B has been associated with the induction of proinflammatory gene expression and has attracted interest as a target for the treatment of inflammatory disease. However, despite much attention being focused on the deleterious effects of NF- ,B, activation of this factor during the resolution of inflammation is associated with the production of antiinflammatory molecules like interleukin (IL)-10 and the onset of apoptosis. This suggests that NF- ,B has an antiinflammatory role in vivo involving the regulation of the resolution of inflammation. Also, NF- ,B promotes liver regeneration by upregulating IL-6 and other molecules like hepatocyte growth factor. It has been postulated that the beneficial properties of NF- ,B are due to p50 homodimers, whose activation prevents cholestatic and chronic liver injury. More basic understanding on the function of the diverse NF- ,B factors is urgently needed in different physiological and pathological conditions, because depending on the subunit composition of the dimmer, the disease and the stage of the illness, inhibition of the factor may result in a beneficial or in a deleterious response. Copyright 2008 John Wiley & Sons, Ltd. [source]


A neutron crystallographic analysis of phosphate-free ribonuclease A at 1.7, resolution

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 9 2009
Daichi Yagi
A neutron crystallographic analysis of phosphate-free bovine pancreatic RNase A has been carried out at 1.7, resolution using the BIX-4 single-crystal diffractometer at the JRR-3 reactor of the Japan Atomic Energy Agency. The high-resolution structural model allowed us to determine that His12 acts mainly as a general base in the catalytic process of RNase A. Numerous other distinctive structural features such as the hydrogen positions of methyl groups, hydroxyl groups, prolines, asparagines and glutamines were also determined at 1.7, resolution. The protonation and deprotonation states of all of the charged amino-acid residues allowed us to provide a definitive description of the hydrogen-bonding network around the active site and the H atoms of the key His48 residue. Differences in hydrogen-bond strengths for the ,-helices and ,-sheets were inferred from determination of the hydrogen-bond lengths and the H/D-exchange ratios of the backbone amide H atoms. The correlation between the B factors and hydrogen-bond lengths of the hydration water molecules was also determined. [source]


Removing the invariant salt bridge of parvalbumin increases flexibility in the AB -loop structure

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2009
Franois Hoh
Parvalbumins (PVs) are calcium-buffer proteins that belong to the EF-hand family. Their N-terminal domain consists of two antiparallel helices A and B that make up a flat hydrophobic surface that is associated with the opposite side of the CD and EF binding sites. A single conserved Arg75,Glu81 salt bridge is buried in this hydrophobic interface. The structure of a rat PV mutant in which Arg75 was replaced by alanine was solved by molecular replacement. Unexpectedly, a large distance deviation of 7.8, was observed for the AB loop but not for the residues that flank the R75A mutation. The thermal stability of the calcium-loaded form is lower (Tm = 352.0,K; ,Tm = ,11.4,K) than that of the wild-type protein and the apo mutant is unfolded at room temperature. Weaker calcium or magnesium affinities were also measured for the R75A mutant (Ca2+: K1 = 4.21 107,M,1, K2 = 6.18 106,M,1; Mg2+: K1 = 2.98 104,M,1, K2 = 3.09 103,M,1). Finally, comparison of the B factors showed an increase in the flexibility of the AB loop that is consistent with this region being more exposed to solvent in the mutant. The mutant structure therefore demonstrates the role of the salt bridge in attaching the nonbinding AB domain to the remaining protein core. Normal-mode analysis indeed indicated an altered orientation of the AB domain with regard to the CD,EF binding domains. [source]


Crystallographic model quality at a glance

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2009
Ludmila Urzhumtseva
A crystallographic macromolecular model is typically characterized by a list of quality criteria, such as R factors, deviations from ideal stereochemistry and average B factors, which are usually provided as tables in publications or in structural databases. In order to facilitate a quick model-quality evaluation, a graphical representation is proposed. Each key parameter such as R factor or bond-length deviation from `ideal values' is shown graphically as a point on a `ruler'. These rulers are plotted as a set of lines with the same origin, forming a hub and spokes. Different parts of the rulers are coloured differently to reflect the frequency (red for a low frequency, blue for a high frequency) with which the corresponding values are observed in a reference set of structures determined previously. The points for a given model marked on these lines are connected to form a polygon. A polygon that is strongly compressed or dilated along some axes reveals unusually low or high values of the corresponding characteristics. Polygon vertices in `red zones' indicate parameters which lie outside typical values. [source]


Re-refinement from deposited X-ray data can deliver improved models for most PDB entries

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 2 2009
Robbie P. Joosten
The deposition of X-ray data along with the customary structural models defining PDB entries makes it possible to apply large-scale re-refinement protocols to these entries, thus giving users the benefit of improvements in X-ray methods that have occurred since the structure was deposited. Automated gradient refinement is an effective method to achieve this goal, but real-space intervention is most often required in order to adequately address problems detected by structure-validation software. In order to improve the existing protocol, automated re-refinement was combined with structure validation and difference-density peak analysis to produce a catalogue of problems in PDB entries that are amenable to automatic correction. It is shown that re-refinement can be effective in producing improvements, which are often associated with the systematic use of the TLS parameterization of B factors, even for relatively new and high-resolution PDB entries, while the accompanying manual or semi-manual map analysis and fitting steps show good prospects for eventual automation. It is proposed that the potential for simultaneous improvements in methods and in re-refinement results be further encouraged by broadening the scope of depositions to include refinement metadata and ultimately primary rather than reduced X-ray data. [source]


Structure of a bovine secretory signalling glycoprotein (SPC-40) at 2.1, resolution

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 9 2006
Janesh Kumar
A recently discovered new class of 40,kDa glycoproteins forms a major component of the secretory proteins in the dry secretions of non-lactating animals. These proteins are implicated as protective signalling factors that determine which cells are to survive during the processes of drastic tissue remodelling. In order to understand its role in the remodelling of mammary glands, the detailed three-dimensional structure of the bovine signalling glycoprotein (SPC-40) has been determined using X-ray crystallography. SPC-40 was purified from bovine dry secretions and crystallized using the hanging-drop vapour-diffusion method. The crystals belong to the orthorhombic space group P212121, with unit-cell parameters a = 62.6, b = 67.4, c = 106.9,. The protein was also cloned in order to determine its complete amino-acid sequence. Its three-dimensional structure has been determined using data to 2.1, resolution. The amino-acid sequence determination of SPC-40 reveals two potential N-glycosylation sites at Asn39 and Asn345, but electron density for a glycan chain was only present at Asn39. The protein adopts a conformation with the classical (,/,)8 -barrel fold of triosephosphate isomerase (TIM barrel; residues 1,237 and 310,360) with the insertion of a small ,+, domain (residues 240,307) similar to that observed in chitinases. However, the substitution of Leu for Glu in the consensus catalytic sequence in SPC-40 caused a loss of chitinase activity. Furthermore, the chitin-binding groove in SPC-40 is considerably distorted owing to unfavourable conformations of several residues, including Trp78, Tyr120, Asp186 and Arg242. Three surface loops, His188,His197, Phe202,Arg212 and Tyr244,Pro260, have exceptionally high B factors, suggesting large-scale flexibility. Fluorescence studies indicate that various sugars bind to SPC-40 with low affinities. [source]


Structural consequences of hen egg-white lysozyme orthorhombic crystal growth in a high magnetic field: validation of X-ray diffraction intensity, conformational energy searching and quantitative analysis of B factors and mosaicity

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2005
Shinya Saijo
A novel method has been developed to improve protein-crystal perfection during crystallization in a high magnetic field and structural studies have been undertaken. The three-dimensional structure of orthorhombic hen egg-white (HEW) lysozyme crystals grown in a homogeneous and static magnetic field of 10,T has been determined and refined to a resolution of 1.13, and an R factor of 17.0%. The 10,T crystals belonged to space group P212121, with unit-cell parameters a = 56.54,(3), b = 73.86,(6), c = 30.50,(2), and one molecule per asymmetric unit. A comparison of the structures of the 0,T and 10,T crystals has been carried out. The magnitude of the structural changes, with a root-mean-square deviation value of 0.75, for the positions of all protein atoms, is similar to that observed when an identical protein structure is resolved in two different crystalline lattices. The structures remain similar, with the exception of a few residues e.g. Arg68, Arg73, Arg128 and Gln121. The shifts of the arginine residues result in very significant structural fluctuations, which can have large effects on a protein's crystallization properties. The high magnetic field contributed to an improvement in diffraction intensity by (i) the displacement of the charged side chains of Arg68 and Arg73 in the flexible loop and of Arg128 at the C-terminus and (ii) the removal of the alternate conformations of the charged side chains of Arg21, Lys97 or Arg114. The improvement in crystal perfection might arise from the magnetic effect on molecular orientation without structural change and differences in molecular interactions. X-ray diffraction and molecular-modelling studies of lysozyme crystals grown in a 10,T field have indicated that the field contributes to the stability of the dihedral angle. The average difference in conformational energy has a value of ,578,kJ,mol,1 per charged residue in favour of the crystal grown in the magnetic field. For most protein atoms, the average B factor in the 10,T crystal shows an improvement of 1.8,2 over that for the 0,T control; subsequently, the difference in diffraction intensity between the 10,T and 0,T crystals corresponds to an increase of 22.6% at the resolution limit. The mosaicity of the 10,T crystal was better than that of the 0,T crystal. More highly isotropic values of 0.0065, 0.0049 and 0.0048 were recorded along the a, b and c axes, respectively. Anisotropic mosaicity analysis indicated that crystal growth is most perfect in the direction that corresponds to the favoured growth direction of the crystal, and that the crystal grown in the magnetic field had domains that were three times the volume of those of the control crystal. Overall, the magnetic field has improved the quality of these crystals and the diffracted intensity has increased significantly with the magnetic field, leading to a higher resolution. [source]


Near-atomic resolution crystal structure of an A-DNA decamer d(CCCGATCGGG): cobalt hexammine interaction with A-DNA

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 1 2003
Boopathy Ramakrishnan
The structure of the DNA decamer d(CCCGATCGGG) has been determined at 1.25, resolution. The decamer crystallized in the tetragonal space group P43212, with unit-cell parameters a = b = 44.3, c = 24.8, and one strand in the asymmetric unit. The structure was solved by the molecular-replacement method and refined to Rwork and Rfree values of 16.3 and 18.5%, respectively, for 5969 reflections. The decamer forms the A-form DNA duplex, with the abutting crystal packing typical of A-DNA. The crystal packing interactions seem to distort the local conformation: A5 adopts the trans/trans conformation for the torsion angles , and , instead of the usual gauche,/gauche+ conformations, yielding G*(GC) base triplets. The highly hydrated [Co(NH3)6]3+ ion adopts a novel binding mode to the DNA duplex, binding directly to phosphate groups and connecting to N7 and O6 atoms of guanines by water bridges. Analysis of thermal parameters (B factors) shows that the nucleotides involved in abutting crystal packing are thermally more stable than other nucleotides in the duplex. [source]


Structural flexibility, an essential component of the allosteric activation in Escherichia coli glucosamine-6-phosphate deaminase

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 1 2002
E. Rudio-Piera
A new crystallographic structure of the free active-site R conformer of the allosteric enzyme glucosamine-6-phosphate deaminase from Escherichia coli, coupled with previously reported structures of the T and R conformers, generates a detailed description of the heterotropic allosteric transition in which structural flexibility plays a central role. The T conformer's external zone [Horjales et al. (1999), Structure, 7, 527,536] presents higher B values than in the R conformers. The ligand-free enzyme (T conformer) undergoes an allosteric transition to the free active-site R conformer upon binding of the allosteric activator. This structure shows three alternate conformations of the mobile section of the active-site lid (residues 163,182), in comparison to the high B values for the unique conformation of the T conformer. One of these alternate R conformations corresponds to the active-site lid found when the substrate is bound. The disorder associated with the three alternate conformations can be related to the biological regulation of the Km of the enzyme for the reaction, which is metabolically required to maintain adequate concentrations of the activator, which holds the enzyme in its R state. Seven alternate conformations for the active-site lid and three for the C-terminus were refined for the T structure using isotropic B factors. Some of these conformers approach that of the R conformer in geometry. Furthermore, the direction of the atomic vibrations obtained with anisotropic B refinement supports the hypothesis of an oscillating rather than a tense T state. The concerted character of the allosteric transition is also analysed in view of the apparent dynamics of the conformers. [source]


A systematic case study on using NMR models for molecular replacement: p53 tetramerization domain revisited

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 12 2000
Yu Wai Chen
Molecular replacement using search models derived from nuclear magnetic resonance (NMR) spectroscopy has often proved problematic. It has been known for some time that the overall differences in atomic positions (r.m.s.d.) between the crystalline and the solution states of the same protein are of the order of 1,2, and approach the limit of molecular replacement. In most cases, this structural difference is a result of calculating the NMR structure with insufficient data, yielding an NMR structure of limited accuracy. A systematic case study was performed to investigate the use of NMR models for molecular replacement on the p53 tetramerization domain: NMR search models of varying degrees of accuracy were employed to solve phases for the 1.5, X-ray diffraction data. An approximate correlation was found between the accuracy of the NMR search model and the clarity and quality of the molecular-replacement solution. It was found that ensemble models perform better than single averaged models and have a larger tolerance in model inaccuracy. Also, distance-derived B factors can improve the performance of single models. [source]


NMR solution structure of the isolated Apo Pin1 WW domain: Comparison to the x-ray crystal structures of Pin1

BIOPOLYMERS, Issue 2 2002
Jennifer A. Kowalski
Abstract The NMR solution structure of the isolated Apo Pin1 WW domain (6,39) reveals that it adopts a twisted three-stranded antiparallel ,-sheet conformation, very similar to the structure exhibited by the crystal of this domain in the context of the two domain Pin1 protein. While the B factors in the apo x-ray crystal structure indicate that loop 1 and loop 2 are conformationally well defined, the solution NMR data suggest that loop 1 is quite flexible, at least in the absence of the ligand. The NMR chemical shift and nuclear Overhauser effect pattern exhibited by the 6,39 Pin1 WW domain has proven to be diagnostic for demonstrating that single site variants of this domain adopt a normally folded structure. Knowledge of this type is critical before embarking on time-consuming kinetic and thermodynamic studies required for a detailed understanding of ,-sheet folding. 2002 John Wiley & Sons, Inc. Biopolymers 63: 111,121, 2002 [source]


Molecular Dynamics Simulations of Na+/Cl, -Dependent Neurotransmitter Transporters in a Membrane-Aqueous System

CHEMMEDCHEM, Issue 6 2007
Anne Marie Jrgensen
Abstract We have performed molecular dynamics simulations of a homology model of the human serotonin transporter (hSERT) in a membrane environment and in complex with either the natural substrate 5-HT or the selective serotonin reuptake inhibitor escitalopram. We have also included a transporter homologue, the Aquifex aeolicus leucine transporter (LeuT), in our study to evaluate the applicability of a simple and computationally attractive membrane system. Fluctuations in LeuT extracted from simulations are in good agreement with crystallographic B factors. Furthermore, key interactions identified in the X-ray structure of LeuT are maintained throughout the simulations indicating that our simple membrane system is suitable for studying the transmembrane protein hSERT in complex with 5-HT or escitalopram. For these transporter complexes, only relatively small fluctuations are observed in the ligand-binding cleft. Specific interactions responsible for ligand recognition, are identified in the hSERT,5HT and hSERT,escitalopram complexes. Our findings are in good agreement with predictions from mutagenesis studies. [source]


Introduction to diffusion tensor imaging mathematics: Part III.

CONCEPTS IN MAGNETIC RESONANCE, Issue 2 2006
Tensor calculation, noise, optimization, simulations
Abstract The mathematical aspects of diffusion tensor magnetic resonance imaging (DTMRI, or DTI), the measurement of the diffusion tensor by magnetic resonance imaging (MRI), are discussed in this three-part series. Part III begins with a comparison of different ways to calculate the tensor from diffusion-weighted imaging data. Next, the effects of noise on signal intensities and diffusion tensor measurements are discussed. In MRI signal intensities as well as DTI parameters, noise can introduce a bias (systematic deviation) as well as scatter (random deviation) in the data. Propagation-of-error formulas are explained with examples. Step-by-step procedures for simulating diffusion tensor measurements are presented. Finally, methods for selecting the optimal b factor and number of b = 0 images for measuring several properties of the diffusion tensor, including the trace (or mean diffusivity) and anisotropy, are presented. 2006 Wiley Periodicals, Inc. Concepts Magn Reson Part A 28A: 155,179, 2006 [source]


Endogenous functional CBV contrast revealed by diffusion weighting

NMR IN BIOMEDICINE, Issue 8 2006
Todd B. Harshbarger
Abstract Functional MRI (fMRI) based on the blood oxygenation level dependent (BOLD) contrast often suffers from a lack of specificity because of the vascular spread of oxygenation changes. It is suggested from the optical imaging and animal fMRI literature that cerebral blood volume (CBV) changes are more closely tied to the smaller vessels. As such, fMRI contrast based on CBV changes will have improved spatial specificity to the neuronal activities as they are immediately adjacent to the smaller vessels. In this paper, an endogenous contrast mechanism based on a diffusion weighting strategy that could detect functional CBV changes is presented. Initially, a theoretical framework is presented to model the functional signal changes as a function of CBV under diffusion weighting, which predicts peak CBV sensitivity at various vessel,tissue mixtures. It was found that a b factor over 1500,s/mm2 would be necessary to achieve dominant CBV contrast. Further, two sets of experimental results are also presented. In the first experiment, diffusion weighting at a set of b factors ranging from 300 to 600,s/mm2 was used. The results indicated that while the positive activation (predominantly BOLD signal) continued to reduce in magnitude and spatial extent, the negative activation (predominantly CBV signal) remained virtually constant with increasing b factors. The second experiment used a b factor of 1600,s/mm2 and showed extensive negative activation in the visual cortex and greatly reduced positive activations compared with images with no diffusion weighting. The time course of negative activation showed a faster time to peak and return to baseline than the positive BOLD activity, consistent with the small vessel origin of the signal changes. These results suggest that appropriate diffusion weighting could be used to measure activation related CBV changes. Copyright 2006 John Wiley & Sons, Ltd. [source]


In vivo mapping of the fast and slow diffusion tensors in human brain

MAGNETIC RESONANCE IN MEDICINE, Issue 4 2002
Chris A. Clark
Abstract Recent studies have shown that the diffusional signal decay in human brain is non-monoexponential and may be described in terms of compartmentalized water fractions. Diffusion tensor imaging (DTI), which provides information about tissue structure and orientation, typically uses b values up to 1000 s mm,2 so that the signal is dominated by the fast diffusing fraction. In this study b factors up to 3500 s mm,2 are utilized, allowing the diffusion tensor properties of the more slowly diffusing fraction to be mapped for the first time. The mean diffusivity (MD) of the slow diffusion tensor was found to exhibit strong white/gray matter (WM/GM) contrast. Maps depicting the principal direction of the slow tensor indicated alignment with the fast tensor and the known orientation of the WM pathways. Magn Reson Med 47:623,628, 2002. 2002 Wiley-Liss, Inc. [source]


Endogenous functional CBV contrast revealed by diffusion weighting

NMR IN BIOMEDICINE, Issue 8 2006
Todd B. Harshbarger
Abstract Functional MRI (fMRI) based on the blood oxygenation level dependent (BOLD) contrast often suffers from a lack of specificity because of the vascular spread of oxygenation changes. It is suggested from the optical imaging and animal fMRI literature that cerebral blood volume (CBV) changes are more closely tied to the smaller vessels. As such, fMRI contrast based on CBV changes will have improved spatial specificity to the neuronal activities as they are immediately adjacent to the smaller vessels. In this paper, an endogenous contrast mechanism based on a diffusion weighting strategy that could detect functional CBV changes is presented. Initially, a theoretical framework is presented to model the functional signal changes as a function of CBV under diffusion weighting, which predicts peak CBV sensitivity at various vessel,tissue mixtures. It was found that a b factor over 1500,s/mm2 would be necessary to achieve dominant CBV contrast. Further, two sets of experimental results are also presented. In the first experiment, diffusion weighting at a set of b factors ranging from 300 to 600,s/mm2 was used. The results indicated that while the positive activation (predominantly BOLD signal) continued to reduce in magnitude and spatial extent, the negative activation (predominantly CBV signal) remained virtually constant with increasing b factors. The second experiment used a b factor of 1600,s/mm2 and showed extensive negative activation in the visual cortex and greatly reduced positive activations compared with images with no diffusion weighting. The time course of negative activation showed a faster time to peak and return to baseline than the positive BOLD activity, consistent with the small vessel origin of the signal changes. These results suggest that appropriate diffusion weighting could be used to measure activation related CBV changes. Copyright 2006 John Wiley & Sons, Ltd. [source]