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PubMed2002

Diffusion-weighted imaging of the spinal cord: interleaved echo-planar imaging is superior to fast spin-echo.

PURPOSE: To compare and evaluate two novel diffusion-weighted sequences, based either on fast spin-echo (FSE) or interleaved echo-planar imaging (EPI) methods, as potential tools for investing spinal cord abnormalities. MATERIALS AND METHODS: Following recent improvements, both interleaved EPI (IEPI) and FSE techniques could be alternative approaches for rapid diffusion-weighted imaging (DWI). Therefore, a navigated diffusion-weighted multishot FSE sequence and a fat-suppressed navigated diffusion-weighted IEPI sequence with local shimming capabilities were tested. Both methods were compared in a consecutive series of five healthy volunteers and five patients with suspected intramedullary lesions. The sequences were graded qualitatively as either superior, inferior, or equal in quality, and also quantitatively by measuring the amount of ghosting artifacts in the background. Quantitative measurements of the diffusion coefficients within the spine were included. RESULTS: The overall image quality of IEPI was superior to FSE. Two out of five FSE scans were rated with poor image quality, whereas all IEPI scans were of sufficient quality. The ghosting levels ranged from approximately 3.3% to 6.2% for IEPI and from approximately 7.5% to 18.9% for FSE. Diffusion coefficients measured in healthy volunteers were similar for both IEPI and FSE, but showed higher fluctuations with the FSE technique. CONCLUSION: Despite potential advantages of FSE, the IEPI technique is preferable for DWI applications in the spinal cord.

Diffusion↗

PubMedDate not supplied

Determination of background gradients with diffusion MR imaging.

A new magnetic resonance (MR) imaging technique, opposite-polarity pulsed-field-gradient technique, with which the effects of background magnetic field gradients can be separated from the effects of diffusion, is described. It is based on the processing of two sets of diffusion-weighted images, the acquisition parameters of which differ only in the polarity of the applied diffusion pulses. The two effects can be separated because the cross term (bc) of the gradient factor function is antisymmetric with respect to reversal of the sign of the applied diffusion pulses. The technique permits simultaneous measurement of the spatial distribution of both the diffusion constants and background magnetic field gradients, with the same spatial resolution as the parent images from which they were derived. The technique has been validated with a phantom in which the spatial distribution of susceptibility-induced background gradients is known, the results showing excellent agreement with theory. The technique was applied to two systems in which the spatial distribution of the background gradient is unknown. Sources of error in the measurement of background gradients and (unrestricted) diffusion constants are analyzed, including the effects of voxel size, partial volumes, and interactions between background and imaging gradients.

Algorithms↗

PubMed2002

17beta-estradiol matrixpatch removal and reapplication in postmenopausal women: theoretical predictions with an oscillating diffusion coefficient model.

The pharmacokinetic performance of a matrix system for transdermal beta-estradiol (E(2)) delivery after multiple consecutive dosing in postmenopausal women undergoing hormone replacement therapy was investigated. The E(2) plasma profiles determined during the third application in 16 postmenopausal women were compared with results obtained in a published clinical study using the same patch in 24 postmenopausal women without E(2) pretreatment; they were compared with a theoretical diffusion/pharmacokinetic model. A conventional theoretical model with constant model parameter (CPM) obtained from in vitro mass balance experiments in a Franz cell type set up described successfully the transdermal E(2) bioavailability parameter AUC(0-96h) (4341.9 +/- 1513.1; calculated 4250.8) and C(average) (45.0 +/- 13.2; calculated 41.2). Also, experimentally, there was no significant drop in E(2) plasma values after patch removal and reapplication; this was corroborated by calculations. Accumulation of E(2) did not occur when several patches were applied consecutively over a period of 3 weeks. Steady state was achieved following application of the first patch. However, the differences between recorded E(2) plasma profiles and theoretical results detected at specific measurement points cannot be explained by the CPM model. Experimentally obtained plasma profiles were always lower in the morning and higher in the evening than predicted on the basis of the model. Measurements of in vivo skin temperature in the postmenopausal women showed oscillating temperature profiles in the form of a cosinor function: The temperature mesor of untreated postmenopausal women was 34.8 degrees C with an acrophase at 17.0 o'clock (95% CI: 14.30-19.30) and an amplitude of +/- 0.4 degrees C (p = 0.1). During the application of the patch the average temperature next to a patch rose 0.3 degrees C, which was statistically significant (p = 0.1). In the skin under the application of the matrix patch a mesor temperature was detected as 35.6 degrees C with an amplitude of +/- 0.5 degrees C with an acrophase at 17.51 o'clock (95% CI: 14.30-21.00) (p = 0.05). The temperature period was 24 h for all measurements and the maximum temperature was observed at about 16.30 h, and a minimum at about 5.00 h. A linear dependency was detected in in vitro experiments between the log of E(2) permeability and the temperature for stripped skin, epidermis/dermis layer, as well as for the matrix. Modeling of E(2) plasma profiles with oscillating diffusion coefficients (ODM1) with a sine wave function results in this equation: D(1) = D(0x) + Da(x).sin(k.t). D(0x) is the diffusion coefficient determined at 35.6 degrees C, k is 1/24 h, D(a) is the diffusion coefficient of the temperature amplitude, h is hour, and x stands for the respective diffusion layer. It was shown that the experimental E(2) plasma profile variations are more pronounced than can simply be explained by skin temperature variations alone (ODM1 model). A simplex fit with an oscillating diffusion coefficient in the form of a sine wave function for the stratum corneum (ODM2 model) resulted in a temperature amplitude of 1.1 degrees C, about twice as high as was determined in the in vivo measurements (ODM2 model). Therefore, other circadian parameterlike blood flow might superimpose the temperature profile. The improvement in data analysis by incorporating oscillating diffusion coefficients (ODM1 and 2) over CPM was judged from a comparison of experimental data with the calculated plasma profiles with the AIC, Akaikes model selection criterion, which allows ranking between models because it is independent of the scaling of the data points. ODM1 and ODM2 improved the data analysis over CPM by allowing better calculation of experimental C(max), t(max), the time to reach to C(max), and the fluctuation, f. No difference between CPM, ODM1, or ODM2 was found for the bioavailability parameter C(average) and AUC(0-96h).

Administration, Cutaneous↗

PubMed1980

Membrane transport of alkyl homologs: role of fluid flow in aqueous diffusion region.

Passive drug transport across a membrane involves the resistances in series offered by the membrane and the liquid layer immediately adjacent to it. The liquid layers generally are referred to as unstirred aqueous diffusion layers, suggesting that solute transport across these layers occurs solely by molecular diffusion. In accord with convective diffusion theory, recent studies showed that the transport from either a dissolving surface or a membrane surface depends not only on molecular diffusion but also on fluid convection inthe liquid adjacent to the membrane. Membrane permeation rates were determined for a series of alkyl p-aminobenzoates, and the results correlated with a model comprised of membrane diffusion and convective diffusion in the adjacent liquid region.

Aminobenzoates↗

PubMed1984

Physical model approach in the study of the transport of alkyl amines across a silicone rubber membrane in a two-chamber diffusion cell.

The transport of hexylamine and octylamine through a silicone rubber membrane was studied as a function of buffer (phosphate) concentration and pH. The results were interpreted using a physical model which assumed a steady-state rate of transport and which accounted for the simultaneous diffusion and rapid equilibrium of all the aqueous species, the possible diffusion of both the amine and its protonated form through the membrane, and the effect of a stagnant aqueous diffusion layer on each side of the membrane. The following conclusions were reached: The thickness of the aqueous diffusion layer is approximately 100 micron, which is about the same as that previously measured for benzoic acid in this system. Transport of octylamine at pH greater than or equal to 10 is approximately 90% aqueous diffusion layer controlled, whereas hexylamine is approximately 50% aqueous diffusion layer controlled at high pH. The membrane permeability of octylamine is approximately 15-20 times that of hexylamine. This gives an incremental pi constant for the partition coefficient of approximately 0.61, as compared with the previously reported value of 0.56. At low pH (less than or equal to 5), the transport of the protonated species becomes important. The membrane permeabilities of these ammonium ions are about four or five orders of magnitude less than the membrane permeabilities of the corresponding amines. The membranes were examined at 30,000X with the scanning electron microscope, and no evidence of holes was found.

Amines↗

PubMed1986

Evaluation of a tube method for determining diffusion coefficients for sparingly soluble drugs.

Evaluation of a non-steady state method using glass tubes for the determination of diffusion coefficients is the purpose of this study. Unlike capillaries, glass tubes accommodate a larger volume of solution, facilitating assay procedures. Tubes are more susceptible to convection than are capillaries, but this effect is anticipated and accounted for in experimental design and data treatment. Glass tubes, 66 or 90 mm in length and 2 mm outer diameter, were siliconized and then filled with aqueous drug solution and placed in a jacketed flask containing gently stirred solvent at 25 degrees C. Diffusion experiments were run from 140 to 168 hours. At the end of this time period, the tubes were removed from the flask, placed in an ultrasonic vibrator for one minute, and their contents assayed spectrophotometrically. Data collected using potassium chloride as the diffusant showed little tube-to-tube variability, demonstrating the precision of the tube method, while diffusion coefficients determined for benzoic acid and p-aminobenzoic acid using the tube method tested the accuracy of the method by comparing reasonably well with values obtained using standard methods such as the rotating disk, free boundary, and membrane cell. Experiments done with either hydrocortisone or sulfisoxazole as the diffusant demonstrated the appropriateness of the tube method for the study of the diffusion of sparingly soluble pharmaceutical solutes.

4-Aminobenzoic Acid↗

PubMed1987

Mass transport in dissolution kinetics. I: Convective diffusion to assess the role of fluid viscosity under forced flow conditions.

The quantitative influence of viscosity on dissolution kinetics is assessed under laminar flow conditions by utilizing a convective diffusion model for drug dissolution. Functional dependency of three types of viscosity inducing agents is established with respect to the parameters of fluid flow rate, diffusivity, and solubility. Studies of aqueous solutions of sucrose and of glycerol demonstrate that the decrease in dissolution rate of ethyl p-aminobenzoate is related to the decrease in solute diffusivity in these solutions, whereas the solubility change in the glycerol solutions has an additional independent simultaneous effect. Dissolution in hydroxypropyl cellulose solutions remains constant under fixed fluid flow conditions because of the negligible effect of the polymer upon the drug diffusivity. A change in fluid flow rate, however, alters the dissolution rate and correlates quantitatively with the rate of shear in the convective diffusion model. The interpretation of the effect of viscosity on dissolution kinetics with the convective diffusion model explains these phenomena quantitatively in terms of the fundamental mass transport processes.

Cellulose↗

PubMed2005

Polyacrylonitrile enzyme ultrafiltration and polyamide enzyme microfiltration membranes prepared by diffusion and convection.

Glucose oxidase (GOD) and catalase (CAT) were covalently immobilized onto three types of polyacrylonitrile (PAN 1, PAN 2, and PAN 3) ultrafiltration (UF) membranes with different pore sizes and one type of polyamide (PA) microfiltration (MF) membrane by the bifunctional reagent, glutaraldehyde. The initial membranes were pre-modified to generate active amide groups in the PAN membranes and active amino groups in the PA membranes. The PAN 3 membrane contained the highest amount of active groups, and the membrane PA the lowest. The modified membranes were enzyme-loaded by diffusion and convection (UF). The effect of membrane pore size and immobilization methods on enzymatic activity and bound protein were studied. The most effective immobilized system was prepared by diffusion using a PAN 3 membrane as a carrier (bound protein: 0.055 mg/cm(2), relative activity: 87.6%). This membrane had the highest pore size of all the PAN membranes. Despite the highest pore size of PA membrane, the enzyme PA membranes prepared by diffusion showed the lowest amount of bound protein (0.03 mg/cm(2)) and the lowest relative activity (35.38%). This correlates with the lowest amount of active groups found in these membranes. The relative activity was higher for all the enzyme systems loaded by diffusion. The systems prepared by convection of the enzyme solution contained higher amounts of enzymes (0.035-0.13 mg/cm(2) protein), which led to internal substrate diffusion resistance and a decrease in the GOD relative activity (21.55-68.5%) in these systems. The kinetic parameters (V(max) and K(m)) and the glucose conversion of the immobilized systems prepared by diffusion were also studied. [diagram in text].

Acrylic Resins↗

PubMed2002

Diffusion NMR methods applied to xenon gas for materials study.

We report initial NMR studies of (i) xenon gas diffusion in model heterogeneous porous media and (ii) continuous flow laser-polarized xenon gas. Both areas utilize the pulsed gradient spin-echo (PGSE) techniques in the gas phase, with the aim of obtaining more sophisticated information than just translational self-diffusion coefficients--a brief overview of this area is provided in the Introduction. The heterogeneous or multiple-length scale model porous media consisted of random packs of mixed glass beads of two different sizes. We focus on observing the approach of the time-dependent gas diffusion coefficient, D(t) (an indicator of mean squared displacement), to the long-time asymptote, with the aim of understanding the long-length scale structural information that may be derived from a heterogeneous porous system. We find that D(t) of imbibed xenon gas at short diffusion times is similar for the mixed bead pack and a pack of the smaller sized beads alone, hence reflecting the pore surface area to volume ratio of the smaller bead sample. The approach of D(t) to the long-time limit follows that of a pack of the larger sized beads alone, although the limiting D(t) for the mixed bead pack is lower, reflecting the lower porosity of the sample compared to that of a pack of mono-sized glass beads. The Pade approximation is used to interpolate D(t) data between the short- and long-time limits. Initial studies of continuous flow laser-polarized xenon gas demonstrate velocity-sensitive imaging of much higher flows than can generally be obtained with liquids (20-200 mm s-1). Gas velocity imaging is, however, found to be limited to a resolution of about 1 mm s-1 owing to the high diffusivity of gases compared with liquids. We also present the first gas-phase NMR scattering, or diffusive-diffraction, data, namely flow-enhanced structural features in the echo attenuation data from laser-polarized xenon flowing through a 2 mm glass bead pack.

Diffusion↗

PubMed2003

Fiber tracking using magnetic resonance diffusion tensor imaging and its applications to human brain development.

Diffusion tensor imaging is unique in its ability to noninvasively visualize white matter fiber tracts in the human brain in vivo. Diffusion is the incoherent motion of water molecules on a microscopic scale. This motion is itself dependent on the micro-structural environment that restricts the movement of the water molecules. In white matter fibers there is a pronounced directional dependence on diffusion. With white matter fiber tracking or tractography, projections among brain regions can be detected in the three-dimensional diffusion tensor dataset according to the directionality of the fibers. Examples of developmental changes in diffusion, tracking of major fiber tracts, and examples of how diffusion tensor tractography and functional magnetic resonance imaging can be combined are provided. These techniques are complimentary and allow both the identification of the eloquent areas of the brain involved in specific functional tasks, and the connections between them. The noninvasive nature of magnetic resonance imaging will allow these techniques to be used in both longitudinal developmental and diagnostic studies. An overview of the technique and preliminary applications are presented, along with its current limitations.

Anisotropy↗

PubMed2002

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

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 x mm(-2) so that the signal is dominated by the fast diffusing fraction. In this study b factors up to 3500 s x 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.

Anisotropy↗

PubMed2003

Increased diffusion sensitivity with hyperechos.

It is shown that the introduction of a 180 degrees refocusing pulse into a standard diffusion weighted stimulated echo sequence is equivalent to the simplest hyperecho sequence with identical diffusion weighting but equal or greater signal-to-noise (SNR) and thus equal or greater diffusion contrast. For high b-value imaging, the hyperecho sequence thus possesses the high diffusion contrast in the presence of small T(1)/T(2) ratios characteristic of stimulated echo sequences but with less than the 50% loss in SNR that is associated with the stimulated echo. For low b-value imaging, the hyperecho signal converges to that of the standard spin echo. The advantages of the two-pulse diffusion weighted hyperecho sequence are demonstrated theoretically. Experimental results are shown in the application to high angular resolution diffusion encoding (HARD) in normal human brain.

Anisotropy↗

PubMed2003

Circular spectrum mapping for intravoxel fiber structures based on high angular resolution apparent diffusion coefficients.

A method is presented for mapping intravoxel fiber structures using spectral decomposition onto a circular distribution of measured apparent diffusion coefficients (ADCs). The zeroth-, second-, and fourth-order harmonic components of the ADC distribution on the circle spanned by the major and median eigenvectors of the diffusion tensor can be used to provide quantitative indices for isotropic, linear, and fiber-crossing diffusion, respectively. A diffusion-weighted MRI technique with 90 encoding orientations was implemented to estimate the circular ADC distribution and calculate the circular spectrum. A digital phantom was used to simulate various diffusion patterns. Comparisons were made between the circular spectrum and regular DTI-based index maps. The results indicated that the zeroth- and second-order circular spectrum maps exhibited a strong consistency with the DTI-based mean diffusivity and linear indices, respectively, and the fourth-order circular spectrum map was able to identify the fiber crossings. MRI experiments were performed on seven healthy human brains using a 3T scanner. The in vivo fourth-order maps showed significantly higher densities in several brain regions, including the corpus callosum, cingulum bundle, superior longitudinal fasciculus, corticospinal tract, and middle cerebellar peduncle, which indicated the existence of fiber crossings in these regions.

Adult↗

PubMed2003

Statistical model for diffusion attenuated MR signal.

A general statistical model that can describe a rather large number of experimental results related to the structure of the diffusion-attenuated MR signal in biological systems is introduced. The theoretical framework relies on a phenomenological model that introduces a distribution function for tissue apparent diffusion coefficients (ADC). It is shown that at least two parameters--the position of distribution maxima (ADC) and the distribution width (sigma)--are needed to describe the MR signal in most regions of a human brain. A substantial distribution width, on the order of 36% of the ADC, was found for practically all brain regions examined. This method of modeling the MR diffusion measurement allows determination of an intrinsic tissue-specific ADC for a given diffusion time independent of the strength of diffusion sensitizing gradients. The model accounts for the previously found biexponential behavior of the diffusion-attenuated MR signal in CNS.

Brain↗

PubMed2003

Effects of barrier-induced nuclear spin magnetization inhomogeneities on diffusion-attenuated MR signal.

The spatial distribution of the transverse nuclear spin magnetization, appearing in a single compartment with impermeable boundaries in a Stejskal-Tanner gradient pulse MR experiment, is analyzed in detail. At short diffusion times the presence of diffusion-restrictive barriers (membranes) reduces effective diffusivity near the membranes and leads to an inhomogeneous spin magnetization distribution (the edge-enhancement effect). In this case, the signal reveals a quasi-two-compartment behavior and can be empirically modeled remarkably well by a biexponential function. The current results provide a framework for interpreting experimental MR data on various phenomena, including water diffusion in giant axons, metabolite diffusion in the brain, and hyperpolarized gas diffusion in lung airways.

Animals↗

PubMed2004

The existence of biexponential signal decay in magnetic resonance diffusion-weighted imaging appears to be independent of compartmentalization.

It is generally believed that the apparent diffusion coefficient (ADC) changes measured by diffusion-weighted imaging (DWI) in brain pathologies are related to alterations in the water compartments. The aim of this study was to elucidate the role of compartmentalization in DWI via biexponential analysis of the signal decay due to diffusion. DWI experiments were performed on mouse brain over an extended range of b-values (up to 10,000 mm(-2) s) under intact, global ischemic, and cold-injury conditions. DWI was additionally applied to centrifuged human erythrocyte samples with a negligible extracellular space. Biexponential signal decay was found to occur in the cortex of the intact mouse brain. During global ischemia, in addition to a drop in the ADC in both components, a shift from the volume fraction of the rapidly diffusing component to the slowly diffusing one was observed. In cold injury, the biexponential signal decay was still present despite the electron-microscopically validated disintegration of the membranes. The biexponential function was also applicable for fitting of the data obtained on erythrocyte samples. The results suggest that compartmentalization is not an essential feature of biexponential decay in diffusion experiments.

Animals↗

PubMed2001

Improved diffusion-weighted single-shot echo-planar imaging (EPI) in stroke using sensitivity encoding (SENSE).

Diffusion-weighted single-shot EPI (sshEPI) is one of the most important tools for the diagnostic assessment of stroke patients, but it suffers from well known artifacts. Therefore, sshEPI was combined with SENSitivity Encoding (SENSE) to further increase EPI's potential for stroke imaging. Eight healthy volunteers and a consecutive series of patients (N = 8) with suspected stroke were examined with diffusion-weighted SENSE-sshEPI using different reduction factors (1.0 < or = R < or = 3.0). Additionally, a high-resolution diffusion-weighted SENSE-sshEPI scan was included. All examinations were diagnostic and of better quality than conventional sshEPI. No ghostings or aliasing artifacts were discernible, and EPI-related image distortions were markedly diminished. Chemical shift artifacts and eddy current-induced image warping were still present, although to a markedly smaller extent. Measured direction-dependent diffusion-coefficients and isotropic diffusion values were comparable to previous findings but showed less fluctuation. We have demonstrated the technical feasibility and clinical applicability of diffusion-weighted SENSE-sshEPI in patients with subacute stroke. Because of the faster k-space traversal, this novel technique is able to reduce typical EPI artifacts and increase spatial resolution while simultaneously remaining insensitive to bulk motion.

Adult↗

PubMed1989

The influence of flow and motion in MRI of diffusion using a modified CE-FAST sequence.

Severe motion and flow artifacts are a problem in MRI of diffusion in vivo due to the application of strong magnetic field gradients. Here it is shown that image artifacts can be removed by using a modified fast-scan MRI sequence (CE-FAST) in conjunction with averaging of diffusion-weighted images. In phantom studies slow (coherent) flow (less than 1 mm s-1) in the presence of strong diffusion gradients is shown to cause signal losses in diffusion-weighted images that depend on the relative orientations of the flow direction and the diffusion gradient. On the other hand, pulsatile motions of macroscopic dimensions (e.g., 1 mm, 1 Hz, in-plane) lead to smearing and ghosting of signal intensities along the phase-encoding direction of the images. In both phantoms and rabbit brains in vivo motion artifacts were found to be reducible by averaging 8-16 images. Unfortunately, the resulting image contrast no longer represents a "true" diffusion contrast but is affected by additional signal losses due to motion averaging. All experiments were performed on a 40-cm-bore 2.35-T Bruker Medspec system.

Animals↗