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Rhodamine B diffusion in hair as a probe for structural integrity.

The aim of this work was to investigate the diffusion of Rhodamine B into bleached, photo bleached and abraded hair, treated or not with an emulsion of ceramide using two different techniques: spectrophotometry and fluorescence optical microscopy with image analysis. This comparison, combined with the Einstein-Smoluchowski equation, allowed validating a methodology that uses the apparent diffusion coefficient of a dye as an index for hair damage. Distinct behaviors of the dye were observed in the cuticle and in the cortex. For a bleached hair sample the apparent diffusion coefficient in the cuticle ranges from 8.2 x 10(-11) cm2 s(-1) to 10 x 10(-11)cm2 s(-1), while for the cortex this value drops to 4.0 x 10(-11) cm2 s(-1) to 4.2 x 10(-11) cm2 s(-1). The diffusion is always faster in the cuticle than in the cortex and the apparent diffusion coefficient shows up to a seven-fold decrease when the dye penetrates the cortex. The chemical, photochemical and physical treatments applied to hair significantly change the values of the apparent diffusion coefficients in the cuticle. The data also proved that the penetration of Rhodamine B into hair occurs via an intercellular path.

Biocompatible Materials↗

Postictal diffusion weighted imaging.

PURPOSE: Our aim was to determine whether diffusion weighted imaging can detect abnormalities of diffusivity after single seizures, and investigate the localisation and time course of any changes. METHODS: Twenty-one patients with intractable focal epilepsy were imaged interictally and after 23 seizures. Voxel-based statistical parametric mapping was used to detect postictal changes in mean diffusivity (MD), compared to the changes noted in 20 controls scanned twice. The time course and magnitude of the changes were evaluated by measuring MD in the areas of change identified by the voxel-based analysis. RESULTS: Thirty-four focal changes in MD (24 decreases, 10 increases) were detected after 12 of 23 seizures in 11 patients, after a median interval of 53 min from the time of seizure onset. Five patients had areas of both increased and decreased diffusion after seizures. In four patients, postictal changes in diffusion corresponded with the presumed seizure focus. Repeated postictal scanning, after a further interval of a median of 46 min in eight patients, showed that postictal changes in MD, both increases and decreases, were returning towards interictal values. CONCLUSIONS: Diffusion weighted imaging identified focal changes in MD after 52% of single complex partial and secondarily generalised seizures. Changes in MD corresponded to the putative seizure focus in a minority of cases suggesting that the technique is not promising as a method for localising seizure foci, but may indicate the networks involved in seizures.

Adult↗

Detection of age-dependent brain injury in a mouse model of brain amyloidosis associated with Alzheimer's disease using magnetic resonance diffusion tensor imaging.

Using magnetic resonance diffusion tensor imaging (DTI), the present study investigates changes in both gray and white matter in the APPsw transgenic mouse (Tg2576), a model of beta-amyloid plaque deposition associated with Alzheimer's disease (AD). DTI analyses were performed in cross-sectional groups of transgene-positive and -negative mice at 8, 12, 16, and 18 months of age to assess the magnitude of water diffusion in gray matter (i.e., Tr(D)) and changes in diffusion in white matter that may be indicative of axonal degeneration (i.e., reduced water diffusion parallel to axonal tracts, lambda(||)) and myelin degradation (i.e., increased water diffusion perpendicular to axonal tracts, lambda(perpendicular)). No appreciable changes in gray or white matter were observed between the APPsw and the age-matched control mice at 8 months of age. Reduced Tr(D) and lambda(||) were observed in gray and white matter, respectively, for the APPsw mice at ages greater than 8 months, which coincides with the time period when appreciable amyloid plaque accumulation was confirmed by ex vivo histopathological studies. The decreases in lambda(||) suggest the presence of axonal injury in multiple white matter tracts of APPsw mice. Unlike lambda(||), lambda(perpendicular) was unaltered between control and APPsw mice in most white matter tracts. However, in the corpus collosum (CC), lambda(perpendicular) increased at 16 and 18 months of age, suggesting the possibility of myelin damage in the CC at these later ages. This work demonstrates the potential for DTI as a noninvasive modality to detect evolving pathology associated with changes in tissue water diffusion properties in brain tissues.

Aging↗

The diffusion of medical technology, local conditions, and technology re-invention: a comparative case study on coronary stenting.

Innovation of medical technology is a major driving force behind the increase in medical expenditures in developed countries. Previous studies identified that the diffusion of medical technology varied across countries according to the characteristics of regulatory policy and payment systems. Based on Roger's diffusion of innovation theory, this study purported to see how local practice norms, the evolving nature of diffusing technology, and local clinical needs in addition to differences in politico-economic systems would affect the process of innovation diffusion. Taking a case of coronary stenting, an innovative therapeutic technology in early 1990s, we provided a case study of hospital-based data between two teaching high-tech hospitals in Japan and the US for discussion. Stenting began to be widely used in both countries when complementary new technology modified its clinical efficacy, but the diffusion process still differed between the two hospitals due to (1) distinctive payment systems for hospitals and physicians, (2) practice norms in favor of percutaneous intervention rather than bypass surgery that was shaped by payment incentives and cultural attitudes, and (3) local patient's clinical characteristics that the technology had to be tailored for. The case study described the diffusion of stent technology as a dynamic process between patients, physicians, hospitals, health care systems, and technology under global and local conditions.

Aged↗

Cross-linked high amylose starch derivatives for drug release III. Diffusion properties.

Acetate (Ac-), aminoethyl (AE-) and carboxymethyl (CM-) derivatives of cross-linked high amylose starch (HASCL-6) were previously shown to control the release of drugs over 20 h from highly loaded (up to 60% drug) monolithic tablets. This report presents a diffusion analysis, aimed to facilitate a better understanding of the mechanisms involved in the control of the drug release from these hydrogels. The diffusion was found to depend on the molecular weight of the diffusant, whereas the partition coefficient depended on the affinities of the diffusant for the polymers and for the dissolution media via attractive or repulsive ionic interactions. The diffusion was also affected by the swelling of CM-HASCL-6, which, unexpectedly, increased with the decrease of the ionic strength. This diffusion analysis completes the swelling studies of HASCL-6 and of its derivatives, allowing the prediction of release kinetics of various active agents.

Acetaminophen↗

Monitoring small molecule diffusion into hydrogels at various temperatures by fluorescence technique.

Steady state fluorescence technique was used to study small molecule diffusion into polyacrylamide (PAAm) gels at various temperatures. Pyranine (P(y)), dissolved in water was introduced as a probe and fluorescence emission (I(p)) from P(y) was monitored during diffusion. Scattered light intensities, I(sc) from PAAm gel was also monitored to observe structural variations during diffusion process. Increase in I(p) intensity was attributed to P(y) diffusion into PAAm gel. On the other hand decrease in I(sc) intensity was interpreted as the variation of the spatial heterogeneities in the system. Li-Tanaka and Fickian models were used to quantify the swelling and diffusion experiments and diffusion coefficients were produced in both cases. Related activation energies were also calculated from the corresponding physical processes.

Biophysics↗

Capability and limitations of first-order and diffusion approaches to describe long-term sorption of chlortoluron in soil.

This paper compares the capability of a first-order and a spherical diffusion model to describe and predict long-term sorption and desorption processes of chlortoluron in two soils. Chlortoluron sorption was investigated at different time scales utilizing one rate experiment (120 days) and two sorption/desorption experiments. Experimental periods for sorption and desorption were set to 1 day (five desorption steps) and 30 days (three desorption steps), respectively. Upon fitting, the two models satisfactorily described the whole set of data. The spherical diffusion model performed better than the first-order model. We then tested the predictive capability of the models by predicting 30-day sorption/desorption data using kinetic parameters fitted on 1-day sorption/desorption data only. While the spherical diffusion model was able to predict the 30-day data set, the first-order model failed completely. Fitting both models to subsets of the data corresponding to different experimental time scales revealed that the rate parameter as well as the Freundlich coefficient of the first-order model are strongly time-dependent--a property that is not shared by parameters of the spherical diffusion model. The apparent stability of the spherical diffusion model with regard to time dependency of its parameters indicates that sorptive uptake may be diffusion-controlled. This also explains the models greater predictive power across different time scales compared to the first-order model. Finally, we investigate the suitability of solute class specific log-linear relationships between the first-order rate parameter and the Freundlich coefficient presented by earlier researchers in the light of the time dependency observed for the parameters of the first-order model.

Absorption↗

Effects of permeable boundaries on the diffusion-attenuated MR signal: insights from a one-dimensional model.

The local magnetization distribution M(x,t) and the net MR signal S arising from a one-dimensional periodic structure with permeable barriers in a Tanner-Stejskal pulsed-field gradient experiment are considered. In the framework of the narrow pulse approximation, the general expressions for M(x,t) and S as functions of diffusion time and the bipolar field gradient strength are obtained and analyzed. In contrast to a system with impermeable boundaries, the signal S as a function of the b-value is modeled well as a bi-exponential decay not only in the short-time regime but also in the long-time regime. At short diffusion times, the local magnetization M(x,t) is strongly spatially inhomogeneous and the two exponential components describing S have a clear physical interpretation as two "population fractions" of the slow- and fast-diffusing quasi-compartments (pools). In the long-diffusion time regime, the two exponential components do not have clear physical meaning but rather serve to approximate a more complex functional signal form. The average diffusion propagator, obtained by means of standard q-space analysis procedures in the long-diffusion time regime is explored; its structure creates the deceiving appearance of a system with multiple compartments of different sizes, while in reality, it reflects the permeable nature of boundaries in a system with multiple compartments all of the same size.

Diffusion Magnetic Resonance Imaging↗

Measurements and modeling of long range 3He diffusion in the lung using a "slice-washout" method.

In healthy lung tissue, pulsed-gradient-spin-echo (PGSE) methods reveal apparent diffusion coefficients (ADC) of the order 0.20 cm2 s(-1); for diffusion times of approximately 2 ms. For these short diffusion times the ADC is only sensitive to structures approximately (2Dt)1/2 approximately 0.6mm in size. Recent work, using magnetic tagging of the longitudinal magnetization has revealed much smaller ADC values for longer length scales. In this work, the in vivo ADC from within the air-spaces, was measured using a new technique. The signal from a series of images was analyzed from a slice that was repeatedly imaged. Diffusion tends to "top-up" the non-renewable polarization within the slice, which leads to a non-exponential decay in image signal. Image data were compared to 1D finite-difference simulations of diffusion to calculate a long range ADC value. The results yield values of the order 0.034 cm2 s(-1), which are nearly an order of magnitude smaller than those reported by PGSE measurements at shorter diffusion times.

Algorithms↗

Similar diffusibility of membrane proteins across the axon-soma and dendrite-soma boundaries revealed by a novel FRAP technique.

In polarized mature neurons, the asymmetrical distribution of proteins between axonal and somatodendritic plasma membrane (PM) domains may be maintained by a diffusion barrier at the axon-soma boundary. At the boundary, a complex containing membrane-associated and cytoskeletal proteins is formed, anchoring axonal membrane proteins and indirectly hindering the diffusion of other membrane proteins. We examined the latter case, i.e., secondary diffusion impedance by comparing the mobility of fluorescently labeled membrane proteins within the axon-soma and dendrite-soma boundaries. We performed fluorescence recovery after photobleaching (FRAP) experiments using mature cultured hippocampal neurons that had been labeled specifically at their PMs with fluorescent proteins (FPs). The maturation of these neurons was confirmed by immunolocalization with Ankyrin-G, which is thought to participate in the creation of the diffusion barrier at the axon-soma boundary. We developed a wide-field microscope equipped with a device (digital micromirror device) composed of 1024 x 768 binary mirrors at the field-stop, allowing free control of the illumination area and intensity. After the FPs in peripheral processes were photobleached, nonbleached FPs diffused into all the processes at equivalent speeds. These results indicate that the secondary diffusion barrier to exogenously overexpressed membrane proteins is not specific to the axon-soma boundary.

Animals↗

Role of potassium lateral diffusion in non-synaptic epilepsy: a computational study.

An increase of extracellular potassium ion concentration can result in neuronal hyperexcitability, and thus contribute to non-synaptic epileptiform activity. It has been shown that potassium lateral diffusion alone is sufficient for synchronization in the low-calcium epilepsy in-vitro model. However, it is not yet known whether the lateral diffusion can, by itself, induce seizure activity. We hypothesize that spontaneous sustained neuronal activity can be generated by potassium coupling between neurons. To test this hypothesis, neuronal simulations with 2-cell or 4-cell models were used. Each model neuron was embedded in a bath of K+ and surrounded by interstitial space. Interstitial potassium concentration was regulated by both K+-pump and glial buffer mechanisms. Simulations performed with two coupled neurons with parameter values within physiological range show that, without chemical and electrical synapses, potassium lateral diffusion alone can generate and synchronize zero-Ca2+ non-synaptic epileptiform activity. Simulations performed with a network of four zero-Ca2+ CA1 pyramidal neurons modeled in zero-calcium conditions also show that spontaneous sustained activity can propagate by potassium lateral diffusion alone with a velocity of approximately 0.93 mm/sec. This diffusion model used for the simulations is based on physiological parameters, is robust for various kinetics, and is able to reproduce both the spontaneous triplet bursting of non-synaptic activity and speed of propagation in low-Ca2+ non-synaptic epilepsy experiments. These simulations suggest that potassium lateral diffusion can play an important role in the synchronization and generation on non-synaptic epilepsy.

Calcium↗

Retrograde cerebral perfusion with intermittent pressure augmentation provides adequate neuroprotection: diffusion- and perfusion-weighted magnetic resonance imaging study in an experimental canine model.

OBJECTIVE: Diffusion- and perfusion-weighted magnetic resonance imaging can identify ischemic brain injury in the hyperacute stage. For neuroprotection during thoracic aortic surgery, we developed a novel retrograde cerebral perfusion with intermittent pressure augmentation. The purpose of this study was to assess the efficiency of this novel method for neuroprotection in real time by using diffusion- and perfusion-weighted magnetic resonance imaging. METHODS: Sixteen beagle dogs were randomly divided into 4 groups: the antegrade selective cerebral perfusion group (n = 4; antegrade selective cerebral perfusion at a flow rate of 10 mL x kg(-1) x min(-1)); the intermittent retrograde cerebral perfusion group (n = 4; retrograde cerebral perfusion at a baseline pressure of 15 mm Hg with intermittent pressure augmentation to 45 mm Hg every 30 seconds); the conventional retrograde cerebral perfusion group (n = 4; conventional retrograde cerebral perfusion at a fixed pressure of 25 mm Hg); and the circulatory arrest group (n = 4; only circulatory arrest). Diffusion- and perfusion-weighted magnetic resonance images were acquired during each session of cerebral perfusion. Regions of interest were defined, and the apparent diffusion coefficient and relative regional cerebral blood volume were calculated in these regions of interest. Finally, the brain was evaluated for its histopathologic damage score. RESULTS: The best apparent diffusion coefficient values were observed in the intermittent retrograde cerebral perfusion group in all the regions of interest, although the relative regional cerebral blood volume values were mostly lower than those in the antegrade selective cerebral perfusion group. The total Histopathologic Damage Score (0, normal; 32, worst) in the intermittent retrograde cerebral perfusion group (8.0 +/- 0.6) was significantly lower than that in the conventional retrograde cerebral perfusion (17.5 +/- 1.7; P < .01) and circulatory arrest (25 +/- 1.0; P < 0.01) groups and was equivalent to that in the antegrade selective cerebral perfusion group (7.8 +/- 0.8; P = .9). CONCLUSION: Intermittent retrograde cerebral perfusion provides adequate neuroprotection by allowing high apparent diffusion coefficient values to be maintained.

Animals↗

Diffusion-weighted three-dimensional MP-RAGE MR imaging.

The advantages of three-dimensional (3D) acquisition are that you obtain thinner and more slices with better profiles, and better signal-to-noise ratio for an equivalent slice thickness. Three-dimensional acquisition is preferable for obtaining contiguous thin-slice MR images. However, the acquisition time extends compared with the two-dimensional acquisition because the second phase-encode axis is applied by the 3D acquisition. Therefore, 3D acquisition should be a high-speed imaging method. In this paper, a new diffusion-sensitive 3D magnetization-prepared rapid gradient-echo (3D MP-RAGE) sequence was studied. In this sequence, a preparation phase with a 90 degrees RF-motion proving gradient (MPG): MPG-180 degrees RF-MPG-90 degrees RF pulse train (diffusion-weighted driven-equilibrium Fourier transform) was used to sensitize the magnetization to diffusion. Centric k-space acquisition order is necessary to minimize saturation effects from tissues with short relaxation times. From phantom experimental results, the effect of the diffusion weighting was changed by the centric vs. sequential k-space acquisition order. The effect of centric k-space acquisition order was larger than the effect of sequential k-space acquisition order. The contrast of centric k-space acquisition order became equal to the contrast of conventional diffusion-weighted spin echo. From rat experimental results, small isotropic diffusion-weighted image data (voxel size: 0.625 x 0.625 x 0.625 mm3) were obtained. This sequence was useful in vivo.

Acetone↗

Analysis of the distribution of diffusion coefficients in cat brain at 9.4 T using the inverse Laplace transformation.

In this work, the usefulness of the inverse Laplace transformation (ILT) in the characterization of diffusion processes in the brain has been investigated. The method has been implemented on both phantom and in vivo cat brain data acquired at high resolution at 9.4 T. The results were compared with monoexponential and biexponential analyses of the same data. It is shown that in the case of diffusion restricted by white matter axonal tracts, the resulting diffusograms are in good agreement with the biexponential model. In gray matter, however, the non-monoexponential decay does not lead to a bimodal distribution in the ILT, even though the data can be fitted to a biexponential. This finding suggests the possibility of a distribution of diffusion coefficients rather than a discrete biexponential behavior. It is shown that this distribution is sensitive, for example, to experimental parameters such as the diffusion time. Thus, the ILT offers the possibility of implementing a unique tool for the analysis of heterogeneous diffusion, that is, the analysis of the diffusion coefficient distribution, which has the yet unexplored potential of being a valuable parameter in the characterization of tissue structure.

Animals↗

Mapping the parameter space of a T2-dependent model of water diffusion MR in brain tissue.

We present a new model for describing the diffusion-weighted (DW) proton nuclear magnetic resonance signal obtained from normal grey matter. Our model is analytical and, in some respects, is an extension of earlier model schemes. We model tissue as composed of three separate compartments with individual properties of diffusion and transverse relaxation. Our study assumes slow exchange between compartments. We attempt to take cell morphology into account, along with its effect on water diffusion in tissues. Using this model, we simulate diffusion-sensitive MR signals and compare model output to experimental data from human grey matter. In doing this comparison, we perform a global search for good fits in the parameter space of the model. The characteristic nonmonoexponential behavior of the signal as a function of experimental b value is reproduced quite well, along with established values for tissue-specific parameters such as volume fraction, tortuosity and apparent diffusion coefficient. We believe that the presented approach to modeling diffusion in grey matter adds new aspects to the treatment of a longstanding problem.

Adult↗

Trace of diffusion tensor differentiates the Parkinson variant of multiple system atrophy and Parkinson's disease.

We have recently shown that diffusion-weighted magnetic resonance (MR) imaging (DWI) discriminates patients with the Parkinson variant of multiple system atrophy (MSA-P) from those with Parkinson's disease (PD) by regional apparent diffusion coefficients (rADC) in the putamen. Because rADCs measured in one direction may underestimate diffusion-related pathologic processes, we investigated the diffusivity in different brain areas by trace of diffusion tensor (Trace(D)) in a new cohort of patients with MSA-P and PD. We studied 11 MSA-P, 17 PD patients, and 10 healthy volunteers matched for age and disease duration. Regional ADCs in three orthogonal directions and Trace(D) values were determined in selected brain regions including the basal ganglia, gray matter, white matter, substantia nigra, and pons. MSA-P patients had significantly higher putaminal and pallidal rTrace(D) values as well as rADCs in y- and z-direction than both PD patients and healthy volunteers. Moreover, putaminal Trace(D) discriminated completely MSA-P from both PD and healthy volunteers. The rADCs in the y- and z-direction provided a complete or near complete separation. In conclusion, our study confirms the results of previous studies of our group that patients with MSA-P show an increased putaminal diffusivity due to neuronal loss and gliosis. Because rADCs in one direction are dependent on the slice orientation relative to the directions of fiber tracts, Trace(D) imaging appears to be more accurate in the separation of MSA-P from PD.

Aged↗

Comparing microstructural and macrostructural development of the cerebral cortex in premature newborns: diffusion tensor imaging versus cortical gyration.

This study assessed microstructural development in four regions of the human cerebral cortex during preterm maturation using diffusion tensor imaging (DTI), compared to the macrostructural development of cortical gyration evaluated using three-dimensional volumetric T1-weighted MR imaging. Thirty-seven premature infants of estimated gestational age (EGA) ranging from 25 to 38 weeks were prospectively enrolled and imaged in an MR-compatible neonatal incubator with a high-sensitivity neonatal head coil. Cortical gyration was measured quantitatively as the ratio of gyral height to width on the volumetric MR images in four regions bilaterally (superior frontal, superior occipital, precentral, and postcentral gyri). Mean diffusivity (D(av)), fractional anisotropy (FA-the fraction of D(av) that is anisotropic), and the three DTI eigenvalues (components of diffusivity radial and tangential to the pial surface of cortex) were measured in the same cortical regions. Cortical gyration scores, FA, and radial diffusivity were all significantly correlated with EGA (P < 0.0001). However, in multivariate analysis, no significant relationship (P > 0.05) was found between DTI parameters and cortical gyration beyond their common association with estimated gestational age. Pre- and postcentral gyri had significantly lower anisotropy than the superior occipital and superior frontal gyri (P < 0.05), indicating that DTI is sensitive to regional heterogeneity in cortical development. Maturational changes in the DTI eigenvalues of cortical gray matter were found to differ from those that have previously been described in developing white matter, with a significant age-related decline in the radial diffusivity (P < 0.0001) but not in the tangential diffusivities (P > 0.05).

Algorithms↗

Progression of putaminal degeneration in multiple system atrophy: a serial diffusion MR study.

By using diffusion-weighted imaging (DWI), we have recently shown abnormal diffusivity in the putamen of patients with the Parkinson variant of multiple system atrophy (MSA-P) which also correlated with disease severity, indicating the capability of putaminal diffusivity to serve as a marker for disease progression. We therefore performed a serial DWI study in 10 patients with MSA-P compared to 10 patients with Parkinson's disease (PD) to evaluate the dynamic evolution of diffusion properties in the basal ganglia including putamen, caudate nucleus and globus pallidum by means of the trace of the diffusion tensor (Trace(D)). For comparison, we have also analyzed the frequency and semiquantitative grading of MSA-P-related structural changes on conventional MRI including putaminal atrophy, lateral hyperintense margination of the putamen and putaminal signal hypointensity relative to the globus pallidum on T2 MR images. None of the Trace(D) values in the basal ganglia regions in the PD group changed significantly at follow-up compared to baseline. In MSA-P, a significant increase of the Trace(D) was found in the putamen, which correlated with motor progression as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). No significant change of any of the abnormal putaminal findings on routine MRI was obtained. We suggest that abnormal diffusivity in the putamen is sensitive to change over time in MSA-P and correlates with motor progression indicating that DWI may serve to monitor disease progression in MSA-P in an objective and quantitative manner.

Aged↗