Search PubMed⌕ Search

Biomedical subjects

Stephen J Blackband

Publications and source records attributed to Stephen J Blackband.

At least 19 recordsLinked to original sources

Observation of anomalous diffusion in excised tissue by characterizing the diffusion-time dependence of the MR signal.

This report introduces a novel method to characterize the diffusion-time dependence of the diffusion-weighted magnetic resonance (MR) signal in biological tissues. The approach utilizes the theory of diffusion in disordered media where two parameters, the random walk dimension and the spectral dimension, describe the evolution of the average propagators obtained from q-space MR experiments. These parameters were estimated, using several schemes, on diffusion MR spectroscopy data obtained from human red blood cell ghosts and nervous tissue autopsy samples. The experiments demonstrated that water diffusion in human tissue is anomalous, where the mean-square displacements vary slower than linearly with diffusion time. These observations are consistent with a fractal microstructure for human tissues. Differences observed between healthy human nervous tissue and glioblastoma samples suggest that the proposed methodology may provide a novel, clinically useful form of diffusion MR contrast.

Algorithms↗

Structural insights from high-resolution diffusion tensor imaging and tractography of the isolated rat hippocampus.

The hippocampus is a critical structure for learning and memory formation injured by diverse neuropathologies such as epilepsy or Alzheimer's disease. Recently, clinical investigations have attempted to use diffusion tensor MRI as a more specific surrogate marker for hippocampal damage. To first better understand the tissue architecture of healthy hippocampal regions, this study characterized 10 rat hippocampi with diffusion tensor imaging (DTI) at 50-microm in-plane image resolution using a 14.1-T magnet. Chemical fixation of the dissected and straightened rat hippocampus provided a simple, effective way to reduce partial volume effects when segmenting hippocampal regions and improved mean signal-to-noise per unit time (e.g. 50.6+/-4.4 at b=1250 s/mm2 in 27 min). Contrary to previous reports that water diffusion is homogeneous throughout the nervous system, statistically different mean diffusivities were observed (e.g. 0.238+/-0.054 and 0.318+/-0.084 microm2/ms for the molecular and granule cell layers respectively) (ANOVA, P<0.05). Different hippocampal subregions had lower fractional anisotropy than uniformly fibrous structures like corpus callosum because of their complex architecture. DTI-derived color fiber orientation maps and tractography demonstrated most components of the trisynaptic intrahippocampal pathway (e.g. orientations in stratum lacunosum-moleculare were dominated by perforant and Schaffer fibers) and also permitted some assessment of connectivity in the rat hippocampus.

Animals↗

Resolution of complex tissue microarchitecture using the diffusion orientation transform (DOT).

This article describes an accurate and fast method for fiber orientation mapping using multidirectional diffusion-weighted magnetic resonance (MR) data. This novel approach utilizes the Fourier transform relationship between the water displacement probabilities and diffusion-attenuated MR signal expressed in spherical coordinates. The radial part of the Fourier integral is evaluated analytically under the assumption that MR signal attenuates exponentially. The values of the resulting functions are evaluated at a fixed distance away from the origin. The spherical harmonic transform of these functions yields the Laplace series coefficients of the probabilities on a sphere of fixed radius. Alternatively, probability values can be computed nonparametrically using Legendre polynomials. Orientation maps calculated from excised rat nervous tissue data demonstrate this technique's ability to accurately resolve crossing fibers in anatomical regions such as the optic chiasm. This proposed methodology has a trivial extension to multiexponential diffusion-weighted signal decay. The developed methods will improve the reliability of tractography schemes and may make it possible to correctly identify the neural connections between functionally connected regions of the nervous system.

Animals↗

Effects of temperature and aldehyde fixation on tissue water diffusion properties, studied in an erythrocyte ghost tissue model.

Ex vivo biological sample imaging can complement in vivo MRI studies. Since ex vivo studies are typically performed at room temperature, and samples are frequently preserved by fixation, it is important to understand how environmental and chemical changes dictated by ex vivo studies alter the physical and MR properties of a sample. Diffusion and relaxation time measurements were used to assess the effects of temperature change and aldehyde fixation on the biophysical and MR properties of a model biological tissue comprised of erythrocyte ghosts suspended in buffer or agarose gel. Sample temperature was varied between 10 degrees C and 37 degrees C. Diffusion MRI data were analyzed with a biophysically appropriate two-compartment exchange model. Temperature change resulted in a complex alteration of water diffusion properties due to the compartmental nature of tissues and alteration in membrane permeability. Formaldehyde, Karnovsky's solution, and glutaraldehyde all caused statistically significant changes to the biophysical and MR properties of the samples. Fixation caused large decreases in water proton T2, which was restored to near prefixation values by washing free fixative from the samples. Water membrane permeability was also significantly altered by fixation. This study demonstrates that relating in vivo MR data to chemically fixed ex vivo data requires an understanding of the effects of sample preparation.

Analysis of Variance↗

Translational neuroscience and magnetic-resonance microscopy.

Magnetic-resonance microscopy is a rapidly growing and a widely applied imaging method in translational neuroscience studies. Emphasis has been placed on anatomical, functional, and metabolic studies of genetically engineered mouse models of human disease and the need for efficient phenotyping at all levels. Magnetic-resonance microscopy is now implemented in many laboratories worldwide due to the availability of commercial high-field magnetic-resonance instruments for use in small animals, the development of accessories (including miniature radio-frequency coils), magnetic-resonance compatible physiological monitoring equipment, and access to adjustable anaesthesia techniques. Two of the major magnetic-resonance microscopy applications in the neurosciences-structural and functional magnetic-resonance microscopy-will be reviewed.

Animals↗

Diffusion tensor imaging of frontal white matter and executive functioning in cocaine-exposed children.

BACKGROUND: Although animal studies have demonstrated frontal white matter and behavioral changes resulting from prenatal cocaine exposure, no human studies have associated neuropsychological deficits in attention and inhibition with brain structure. We used diffusion tensor imaging to investigate frontal white matter integrity and executive functioning in cocaine-exposed children. METHODS: Six direction diffusion tensor images were acquired using a Siemens 3T scanner with a spin-echo echo-planar imaging pulse sequence on right-handed cocaine-exposed (n = 28) and sociodemographically similar non-exposed children (n = 25; mean age: 10.6 years) drawn from a prospective, longitudinal study. Average diffusion and fractional anisotropy were measured in the left and right frontal callosal and frontal projection fibers. Executive functioning was assessed using two well-validated neuropsychological tests (Stroop color-word test and Trail Making Test). RESULTS: Cocaine-exposed children showed significantly higher average diffusion in the left frontal callosal and right frontal projection fibers. Cocaine-exposed children were also significantly slower on a visual-motor set-shifting task with a trend toward lower scores on a verbal inhibition task. Controlling for gender and intelligence, average diffusion in the left frontal callosal fibers was related to prenatal exposure to alcohol and marijuana and an interaction between cocaine and marijuana exposure. Performance on the visual-motor set-shifting task was related to prenatal cocaine exposure and an interaction between cocaine and tobacco exposure. Significant correlations were found between test performance and fractional anisotropy in areas of the frontal white matter. CONCLUSIONS: Prenatal cocaine exposure, alone and in combination with exposure to other drugs, is associated with slightly poorer executive functioning and subtle microstructural changes suggesting less mature development of frontal white matter pathways. The relative contribution of postnatal environmental factors, including characteristics of the caregiving environment and stressors associated with poverty and out-of-home placement, on brain development and behavioral functioning in polydrug-exposed children awaits further research.

Child↗

Biochemical consequences of alginate encapsulation: a NMR study of insulin-secreting cells.

In this study we explore the biochemical consequences of alginate encapsulation on betaTC3 cells. (13)C NMR spectroscopy and isotopomer analysis were used to investigate the effects of encapsulation on several enzymatic processes associated with the TCA cycle. Our data show statistically significant differences in various enzymatic fluxes related to the TCA cycle and insulin secretion between monolayer and alginate-encapsulated cultures. The principal cause for these effects was the process of trypsinization. Embedding the trypsinized cells in alginate beads did not have a compounded effect on the enzymatic fluxes of entrapped cells. However, an additional small but statistically significant decrease in insulin secretion was measured in encapsulated cells. Finally, differences in either enzymatic fluxes or glucose consumption as a function of bead diameter were not observed. However, differences in T(2), assessed by (1)H NMR microimaging, were observed as a function of bead diameter, suggesting that smaller beads became more organized with time in culture, while larger beads displayed a looser organization.

Alginates↗

MR microscopy of rat hippocampal slice cultures: a novel model for studying cellular processes and chronic perturbations to tissue microstructure.

Brain slices provide a useful nervous tissue model to investigate the relationships between magnetic resonance imaging (MRI) contrast mechanisms and tissue microstructure; yet, these acutely isolated tissues remain viable for only 10-12 h. To study slower biological processes, this work describes the first MRI microscopy characterization of organotypic rat hippocampal slice cultures that can be maintained for several weeks. Diffusion-weighted images of slice cultures acquired with a 14.1-T magnet demonstrated the laminar anatomy of the hippocampus with relatively high signal-to-noise ratios. Diffusion data analyzed using a two-compartment model with exchange indicated that cultured slices had a comparable microstructure to acute brain slices and to in vivo brain. Immunohistochemistry indicated that slice cultures tolerated the conditions required for MRI study well. MRI of cultured tissue slices is highly amenable to correlative microscopy techniques and offers great promise for future MRI investigations of pathological tissue reorganization, molecular imaging and stem cell therapies.

Animals↗

Noninvasive in vivo detection of glutathione metabolism in tumors.

Magnetic resonance spectroscopic imaging has been used to follow glutathione metabolism and evaluate glutathione heterogeneity in intact tumor tissue. Stable isotope-labeled glutathione was detected in s.c. implanted fibrosarcoma tumors in anesthetized rats following infusion of [2-13C]glycine. Using 1H-decoupled 13C magnetic resonance spectroscopy, the appearance of [2-13C]glycine at 42.4 ppm and the subsequent incorporation of this isotope label into the glycyl residue of glutathione at 44.2 ppm can be detected. The identity and relative concentrations of labeled metabolites observed in the in vivo spectrum were confirmed in studies of tissue extracts. The high level of isotopic enrichment and the concentration of glutathione in tumor tissue allow for collection of spatially localized spectra using 13C chemical shift imaging methods. These data provide the first direct images of glutathione in intact tumor tissue and show metabolic heterogeneity. This method may lead to the ability to monitor changes in tumor tissue redox state that may ultimately affect diagnosis, monitoring, and treatment.

Animals↗

A theoretical comparison of two optimization methods for radiofrequency drive schemes in high frequency MRI resonators.

In this paper, numerical simulations are used in an attempt to find optimal source profiles for high frequency radiofrequency (RF) volume coils. Biologically loaded, shielded/unshielded circular and elliptical birdcage coils operating at 170 MHz, 300 MHz and 470 MHz are modelled using the FDTD method for both 2D and 3D cases. Taking advantage of the fact that some aspects of the electromagnetic system are linear, two approaches have been proposed for the determination of the drives for individual elements in the RF resonator. The first method is an iterative optimization technique with a kernel for the evaluation of RF fields inside an imaging plane of a human head model using pre-characterized sensitivity profiles of the individual rungs of a resonator; the second method is a regularization-based technique. In the second approach, a sensitivity matrix is explicitly constructed and a regularization procedure is employed to solve the ill-posed problem. Test simulations show that both methods can improve the B(1)-field homogeneity in both focused and non-focused scenarios. While the regularization-based method is more efficient, the first optimization method is more flexible as it can take into account other issues such as controlling SAR or reshaping the resonator structures. It is hoped that these schemes and their extensions will be useful for the determination of multi-element RF drives in a variety of applications.

Computer Simulation↗

Fast orientation mapping from HARDI.

This paper introduces a new, accurate and fast method for fiber orientation mapping using high angular resolution diffusion imaging (HARDI) data. The approach utilizes the Fourier relationship between the water displacement probabilities and diffusion attenuated magnetic resonance (MR) signal expressed in spherical coordinates. The Laplace series coefficients of the water displacement probabilities are evaluated at a fixed distance away from the origin. The computations take under one minute for most three-dimensional datasets. We present orientation maps computed from excised rat optic chiasm, brain and spinal cord images. The developed method will improve the reliability of tractography schemes and make it possible to correctly identify the neural connections between functionally connected regions of the nervous system.

Algorithms↗

Water diffusion measurements in perfused human hippocampal slices undergoing tonicity changes.

Diffusion MRI has the potential to probe the compartmental origins of MR signals acquired from human nervous tissue. However, current experiments in human subjects require long diffusion times, which may confound data interpretation due to the effects of compartmental exchange. To investigate human nervous tissue at shorter diffusion times, and to determine the relevance of previous diffusion studies in rat hippocampal slices, water diffusion in 20 perfused human hippocampal slices was measured using a wide-bore 17.6-T magnet equipped with 1000-mT/m gradients. These slices were procured from five patients undergoing temporal lobectomy for epilepsy. Tissue viability was confirmed with electrophysiological measurements. Diffusion-weighted water signal attenuation in the slices was well-described by a biexponential function (R(2) > 0.99). The mean diffusion parameters for slices before osmotic perturbation were 0.686 +/- 0.082 for the fraction of fast diffusing water (F(fast)), 1.22 +/- 0.22 x 10(-3) mm(2)/s for the fast apparent diffusion coefficient (ADC), and 0.06 +/- 0.02 x 10(-3) mm(2)/s for the slow ADC. Slice perturbations with 20% hypotonic and 20% hypertonic artificial cerebrospinal fluid led to changes in F(fast) of -8.2% and +10.1%, respectively (ANOVA, P < 0.001). These data agree with previous diffusion studies of rat brain slices and human brain in vivo, and should aid the development of working models of water diffusion in nervous tissue, and thus increase the clinical utility of diffusion MRI.

Analysis of Variance↗

NMR properties of alginate microbeads.

Alginates are a family of unbranched polysaccharides with properties that vary widely depending on their composition. In the presence of multivalent cations (frequently Ca2+), alginates form a gel. Consequently, alginates have been used to encapsulate a variety of biological materials, including cells. In this study, we present NMR relaxation and diffusion data from alginate microbeads with similar size and properties to those used in the development of a bioartificial pancreas. Our data demonstrate that the transverse relaxation time (T2) of water within the gel depends on the guluronic acid content of the alginate, whereas the longitudinal relaxation time (T1) and the apparent diffusion coefficient of water do not. Our data further suggest that the diffusion of Ca2+ ions is hindered by the presence of a poly-L-lysine layer, a layer commonly added to provide mechanical support to the beads and immunoprotection to the encapsulated cells in the event of implantation. The impact of these data on our understanding of the role of alginate gels in the development of a bioartificial pancreas is discussed.

Alginates↗

In vivo prostate magnetic resonance imaging and magnetic resonance spectroscopy at 3 Tesla using a transceive pelvic phased array coil: preliminary results.

Magnetic resonance (MR) systems operating at 3 Telsa (T) and above have demonstrated considerable potential in human studies, offering improved signal-to-noise ratio and spectral resolution. However, because of radiofrequency limitations and concerns, and the lack of large volume body coils, most studies have been limited to the head. In this study we describe the design and construction of a transceive pelvic phased array coil with which MR images and spectra of the human prostate at 3 T have been obtained. Comparison with 1.5 T instruments with different hardware configurations is difficult; however, in a preliminary comparison the signal-to-noise ratio is improved in phantoms and humans when compared with a 1.5 T receive-only pelvic phased array coil, and high quality spectral resolution is demonstrated through the delineation of the citrate quadruplet in localized 1H prostate spectra. Higher fields offer the potential for MR prostate studies without the use of an endorectal coil.

Adult↗

Diffusion magnetic resonance imaging study of a rat hippocampal slice model for acute brain injury.

Diffusion magnetic resonance imaging (MRI) provides a surrogate marker of acute brain pathology, yet few studies have resolved the evolution of water diffusion changes during the first 8 hours after acute injury, a critical period for therapeutic intervention. To characterize this early period, this study used a 17.6-T wide-bore magnet to measure multicomponent water diffusion at high b-values (7 to 8,080 s/mm(2)) for rat hippocampal slices at baseline and serially for 8 hours after treatment with the calcium ionophore A23187. The mean fast diffusing water fraction (Ffast) progressively decreased for slices treated with 10-microM/L A23187 (-20.9 +/- 6.3% at 8 hours). Slices treated with 50-micromol/L A23187 had significantly reduced Ffast 80 minutes earlier than slices treated with 10-microM/L A23187 (P < 0.05), but otherwise, the two doses had equivalent effects on the diffusion properties of tissue water. Correlative histologic analysis showed dose-related selective vulnerability of hippocampal pyramidal neurons (CA1 > CA3) to pathologic swelling induced by A23187, confirming that particular intravoxel cell populations may contribute disproportionately to water diffusion changes observed by MRI after acute brain injury. These data suggest diffusion-weighted images at high b-values and the diffusion parameter Ffast may be highly sensitive correlates of cell swelling in nervous issue after acute injury.

Acute Disease↗

Simultaneous diffusion MRI measurements from multiple perfused rat hippocampal slices.

Rat brain slices provide a controllable tissue model in which to investigate the biophysical basis of diffusion-weighted magnetic resonance (MR) signal changes observed clinically in nervous tissue after ischemic injury. This study describes a new multislice perfusion chamber that allows for the simultaneous acquisition of diffusion-weighted MR images from multiple perfused rat hippocampal slices (eight slices in the present study). These images had a signal-to-noise ratio (SNR) of 48 +/- 3 at b = 8080 s/mm(2), which was sufficient to analyze the multicomponent diffusion properties of water in rat hippocampal slices. The tissue water diffusion parameters (f(fast) = 0.527 +/- 0.041, D(fast) = 1.268 +/- 0.087 x 10(-3) mm(2)/s, and D(slow) = 0.060 +/- 0.003 x 10(-3) mm(2)/s) were stable for at least 8 hr after slice procurement (ANOVA, P > 0.05), suggesting that it may be possible to study the acute temporal evolution of diffusion changes in multiple brain slices following experimental perturbation.

Analysis of Variance↗

Human erythrocyte ghosts: exploring the origins of multiexponential water diffusion in a model biological tissue with magnetic resonance.

A tissue model composed of erythrocyte ghosts was developed to study the effects of compartmentation on the MR signal acquired from biological tissues. This simple and flexible model offers control over the biophysical parameters that contribute to multicomponent signals arising from cellular systems. Cell density, size, intra- and extracellular composition, and membrane permeability can be independently altered. The effects of cell density and cell size on water diffusion properties were assessed. The data demonstrate non-monoexponential water diffusion in ghost cell suspensions of 17-67% cell density. Data were analysed with the widely employed two-compartment (biexponential) model, and with a two-compartment model that accounted for exchange between compartments. Water exchange between the intra- and extracellular compartments appeared to be significant over the range of diffusion times studied (7-35 ms). The biexponential fit to the ghost data appeared to be underparameterised as the ADCs and relative fractions of the fast and slow components were dependent on the experimental acquisition parameters, specifically the diffusion time. However, both analysis methods proved effective at tracking changes in the ghost model when it was perturbed. This was demonstrated with cell density variation, cell swelling and shrinkage experiments, and reduction of membrane water permeability using a water channel blocker (pCMBS). We anticipate that this model system could be used to investigate compartmental diffusion effects to simulate a range of pathologies, especially ischemic stroke.

4-Chloromercuribenzenesulfonate↗