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Anomalous diffusion of proteins due to molecular crowding.

We have studied the diffusion of tracer proteins in highly concentrated random-coil polymer and globular protein solutions imitating the crowded conditions encountered in cellular environments. Using fluorescence correlation spectroscopy, we measured the anomalous diffusion exponent alpha characterizing the dependence of the mean-square displacement of the tracer proteins on time, r(2)(t) approximately t(alpha). We observed that the diffusion of proteins in dextran solutions with concentrations up to 400 g/l is subdiffusive (alpha < 1) even at low obstacle concentration. The anomalous diffusion exponent alpha decreases continuously with increasing obstacle concentration and molecular weight, but does not depend on buffer ionic strength, and neither does it depend strongly on solution temperature. At very high random-coil polymer concentrations, alpha reaches a limit value of alpha(l) approximately 3/4, which we take to be the signature of a coupling between the motions of the tracer proteins and the segments of the dextran chains. A similar, although less pronounced, subdiffusive behavior is observed for the diffusion of streptavidin in concentrated globular protein solutions. These observations indicate that protein diffusion in the cell cytoplasm and nucleus should be anomalous as well, with consequences for measurements of solute diffusion coefficients in cells and for the modeling of cellular processes relying on diffusion.

Biophysics↗

Determining diffusion coefficients in inhomogeneous tissues using fluorescence recovery after photobleaching.

Diffusion plays an important role in the transport of nutrients and signaling molecules in cartilaginous tissues. Diffusion coefficients can be measured by fluorescence recovery after photobleaching (FRAP). Available methods to analyze FRAP data, however, assume homogeneity in the environment of the bleached area and neglect geometrical restrictions to diffusion. Hence, diffusion coefficients in inhomogeneous materials, such as most biological tissues, cannot be assessed accurately. In this study, a new method for analyzing data from FRAP measurements has been developed, which is applicable to inhomogeneous tissues. It is based on a fitting procedure of the intensity recovery after photobleaching with a two-dimensional finite element analysis, which includes Fick's law for diffusion. The finite element analysis can account for distinctive diffusivity in predefined zones, which allows determining diffusion coefficients in inhomogeneous samples. The method is validated theoretically and experimentally in both homogeneous and inhomogeneous tissues and subsequently applied to the proliferation zone of the growth plate. Finally, the importance of accounting for inhomogeneities, for appropriate assessment of diffusivity in inhomogeneous tissues, is illustrated.

Algorithms↗

Diffusion of cholesterol and its precursors in lipid membranes studied by 1H pulsed field gradient magic angle spinning NMR.

Cholesterol content is critical for membrane functional properties. We studied the influence of cholesterol and its precursors desmosterol and lanosterol on lateral diffusion of phospholipids and sterols by1H pulsed field gradients (PFG) magic angle spinning (MAS) NMR spectroscopy. The high resolution of resonances afforded by MAS NMR permitted simultaneous diffusion measurements on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and sterols. The cholesterol diffusion mirrored the DPPC behavior, but rates were slightly higher at all cholesterol concentrations. DPPC and cholesterol diffusion rates decreased and became cholesterol concentration dependent with the onset of liquid-ordered phase formation. The activation energies of diffusion in the coexistence region of liquid-ordered/liquid-disordered phases are higher by about a factor of 2 compared to pure DPPC and to the pure liquid-ordered state formed at higher cholesterol concentrations. We assume that the higher activation energies are a reflection of lipid diffusion across domain boundaries. In lanosterol- and desmosterol-containing membranes, the DPPC and sterol diffusion coefficients are somewhat higher. Whereas the desmosterol rates are only slightly higher than those of DPPC, the lanosterol diffusion rates significantly exceed DPPC rates, indicating a weaker interaction between DPPC and lanosterol.

1,2-Dipalmitoylphosphatidylcholine↗

Multiple diffusion mechanisms due to nanostructuring in crowded environments.

One of the key questions regarding intracellular diffusion is how the environment affects molecular mobility. Mostly, intracellular diffusion has been described as hindered, and the physical reasons for this behavior are: immobile barriers, molecular crowding, and binding interactions with immobile or mobile molecules. Using results from multi-photon fluorescence correlation spectroscopy, we describe how immobile barriers and crowding agents affect translational mobility. To study the hindrance produced by immobile barriers, we used sol-gels (silica nanostructures) that consist of a continuous solid phase and aqueous phase in which fluorescently tagged molecules diffuse. In the case of molecular crowding, translational mobility was assessed in increasing concentrations of 500 kDa dextran solutions. Diffusion of fluorescent tracers in both sol-gels and dextran solutions shows clear evidence of anomalous subdiffusion. In addition, data from the autocorrelation function were analyzed using the maximum entropy method as adapted to fluorescence correlation spectroscopy data and compared with the standard model that incorporates anomalous diffusion. The maximum entropy method revealed evidence of different diffusion mechanisms that had not been revealed using the anomalous diffusion model. These mechanisms likely correspond to nanostructuring in crowded environments and to the relative dimensions of the crowding agent with respect to the tracer molecule. Analysis with the maximum entropy method also revealed information about the degree of heterogeneity in the environment as reported by the behavior of diffusive molecules.

Biophysics↗

Diffusion of the D.A.R.E and syringe exchange programs.

We examined the diffusion of the D.A.R.E program to reduce use of illicit drugs among school-aged children and youths and the diffusion of syringe exchange programs to reduce HIV transmission among injection drug users. The D.A.R.E program was diffused widely in the United States despite a lack of evidence for its effectiveness; there has been limited diffusion of syringe exchange in the United States, despite extensive scientific evidence for its effectiveness. Multiple possible associations between diffusion and evidence of effectiveness exist, from widespread diffusion without evidence of effectiveness to limited diffusion with strong evidence of effectiveness. The decision theory concepts of framing and loss aversion may be useful for further research on the diffusion of public health innovations.

Adolescent↗

Developing the molecular modelling of diffusion in zeolites as a high throughput catalyst screening technique.

Molecular modelling techniques have been used to screen zeolite catalysts for their suitability for organic synthesis. For example, we have used these techniques to study the alkylation of aromatic molecules which are important in the fine-chemical and drug industries. A survey of all such efforts is reviewed in this article. The application of molecular modelling techniques in a systematic manner is an efficient first step in the design of zeolite catalysts. As a qualitative screening tool, molecular graphics is used to visualize how well the reactant and product molecules fit inside the pores of the zeolites. Using a hybrid of several molecular modelling methods, which combines molecular dynamics (MD) and Monte Carlo methods with energy minimization, it is possible to determine the minimum energy locations of the molecules inside the zeolites cages. The minimum energy configurations determined by this hybrid method are taken as a starting point for diffusion of the molecules through the zeolite channels. When a molecule is allowed to diffuse through zeolite channel, the molecule attains some maxima and minima in its diffusion energy profile. From the differences between a maximum and a minimum energy configuration, the diffusion energy barrier for the molecule can be calculated in the zeolites. By comparing the diffusion energy barriers for various isomers of a molecule in different zeolites, it is possible to find out the most suitable zeolite for achieving the required shape-selectivity. In addition, factors influencing the diffusivity of the molecules and consequently the shape selectivity are derived. The list of factors and their relative importance are analysed to derive valuable guidelines to design shape-selective zeolite catalysts for a given reaction. Thus, the ultimate aim of these studies is to develop a high throughput computational screening process for the selection of shape-selective zeolite catalysts for various reactions. The dynamic behaviour of molecules inside the pores of zeolites can be studied using MD methods. Since MD is computationally time consuming, it is more efficient to screen the possible zeolite catalysts by energy minimization methods and then perform MD in specific zeolites. More accurate values of diffusivity of the molecules can be calculated using MD methods, and these values can be correlated with the shape-selectivity observed experimentally and /or derived from diffusion energy barrier calculations.

Catalysis↗

Diffusion MR imaging. Theory and applications.

Diffusion MR imaging provides a novel way to characterize tissues based on sensitivity to the microscope molecular motion of water. Clinical implementation requires strong, fast hardware and careful post-processing of diffusion parameters. It is important to recognize that diffusion images and derivatives such as the trace of the diffusion tensor are quite specific in reflecting the physical properties of diffusion, but are non-specific for pathology. Restricted diffusion is the earliest clinically detectable sign of ischemia, but similar diffusion changes can be seen with infection and some tumors. Diffusion MR techniques are providing new ways to study problems in oncology, epilepsy, white matter disorders, and infectious diseases, both for research and clinical applications.

Animals↗

Effect of concentration and hyaluronidase on albumin diffusion across rabbit mesentery.

OBJECTIVE: To measure the diffusion coefficient of albumin through rabbit mesentery using the steady-state flux of radioactive tracer 125I-albumin. The effect of albumin concentration and testicular hyaluronidase were also studied. METHODS: Mesenteric tissue was bonded between two plates, exposing a 7 mm diameter surface, with two chambers on either side. One chamber was filled with a test solution of albumin containing the radioactive tracer and the other with lactated Ringer solution. The solutions in both chambers were stirred with small magnetic cylinders. The chamber filled with lactated Ringer solution was placed in a well-type NaI(Tl) detector, and the radiation emitted from the tracer that diffused across the mesentery was monitored continuously for 9 hours. The diffusion coefficient (D) was calculated using Fick's law of diffusion. The diffusion coefficient was measured at albumin concentration differences (delta C) between approximately 0 and 10 g/dL. The diffusion coefficient was also measured with testicular hyaluronidase at three different albumin-concentration differences. RESULTS: The diffusion coefficient increased significantly (P < 0.0001) approximately three-fold from a mean value of 2.2 x 10(-8) +/- 1.2 x 10(-8) (SD) cm2/s at 0-0.5 g/dL delta C to 5.9 x 10(-8) +/- 1.1 x 10(-8) (SD) cm2/s at 10 g/dL delta C. The values are much less than the free diffusion coefficient of albumin (6 x 10(-7) cm2/s). Testicular hyaluronidase added to the albumin solution decreased D by approximately 60%, but did not eliminate the increase in D with delta C. CONCLUSIONS: The increase in D with delta C and the reduced D with hyaluronidase were attributed to a reduced albumin-excluded volume caused by an interaction between albumin and hyaluronan. Further studies are required to define this interaction.

Albumins↗

Correction of sodium sieving for diffusion from the circulation.

Transcellular water transport (TCWT) can be estimated by Na- sieving. However, the assumption that the initial Na+ dialysate concentration (D0) is equal to the initial plasma concentration (P0) is not true for each patient. The difference leads to Na+ diffusion from the circulation to the dialysate, which diminishes the Na+ sieving. A model was developed to distinguish transcellular water transport from Na+ diffusion. We previously found evidence that the mass transfer area coefficient of urate (MTACurate) was similar to the MTACNa+. The MTAC is the product of the elimination constant (ke) and the volume of distribution (VD), the mean intraperitoneal volume. Because VD is known, the ke Na+ in each patient can be equated with the ke urate. The Na+ mass transfer from the circulation to the dialysate by diffusion can then be calculated for any time point during a dwell (Dt). Dt was subtracted from the measured Na+ dialysate concentration at 60 minutes. The corrected D/P Na+ then represents the actual Na+ sieving. Using 3.86% glucose dialysate, this approach was investigated in 15 stable peritoneal dialysis (PD) patients (normUF) and in 9 PD patients with low ultrafiltration (lowUF, < 400 mL/4 hours). The MTACurate was calculated according to Waniewski (W) and according to the Garred model (G). Similar calculations were also performed for the MTAC of creatinine (MTACcreat). Initial D/P Na+ was not different between the groups. When no diffusion correction was made, D/P60 Na+ in the lowUF group (median 0.898, range 0.870-0.949) was significantly higher (p < 0.025) than D/P60 Na+ in the normUF group (median 0.881, range 0.816-0.899). The difference disappeared after diffusion correction regardless of the correction model applied. However, at 240 minutes, D/P Na+ in the normUF group was significantly lower than in the lowUF group (median 0.880, range 0.839-0.952 vs median 0.942, range 0.866-0.987; p < 0.004). Even after correction, D/P Na+ in the normUF group was significantly lower: 0.847 normUF versus 0.893 lowUF (Wurate, p < 0.005); and 0.842 normUF versus 0.890 lowUF (Gcreat, p < 0.003). The correlation between the Wurate (the best theoretical diffusion correction) and Gcreat (the least) was: y = 0.99x + 0.0037. Furthermore, Bland and Altman analyses of Wurate and Gcreat at both 60 and 240 minutes resulted in random distribution around the means, with a slight overestimation in relation to the magnitude of Gcreat, as was expected. Gcreat can be used to make an accurate estimation of the contribution of Na+ diffusion in the time course of D/P Na+. It provides a simple way to more precisely determine Na+ sieving, and therefore TCWT. In conclusion, to avoid overestimation of impaired channel-mediated water transport, a Na+ diffusion correction should be made when D0 is not equal to P0 or in the case of a large vascular surface area.

Diffusion↗

Cerebral aneurysms treated by Guglielmi detachable coils: evaluation with diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: The most frequent and serious complications of endovascular treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs) are ischemic lesions caused by thromboembolic events. Diffusion-weighted MR imaging appears to be the most sensitive technique for detecting early ischemic phenomena. We evaluated this technique for the detection of brain changes in patients who underwent GDC treatment of aneurysms. METHODS: Twenty patients with a cerebral aneurysm were studied with diffusion-weighted imaging before and after endovascular treatment with GDCs. Aneurysms were located in the anterior (n = 16) or posterior (n = 4) circulation. Bleeding had occurred in 11 patients. MR studies, including fast fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted sequences, were scheduled before, 2 to 4 hours after, and 48 hours after treatment. MR images, including apparent diffusion coefficient (ADC) maps, were assessed for the presence of acute ischemic stroke lesions. RESULTS: In all patients, the aneurysm was excluded without neurologic worsening. In 18 patients, diffusion-weighted and FLAIR images showed no evidence of recent ischemic lesions after treatment. In one patient, an asymptomatic frontobasal hyperintense signal on diffusion-weighted images with a drop of ADC values corresponding to an acute ischemic lesion was observed. In another patient, multiple silent lesions were seen on diffusion-weighted images after embolization. These silent lesions were not all located in the vascular territory of the aneurysm's parent artery. CONCLUSION: This preliminary study suggests that diffusion-weighted MR imaging is a potentially useful tool for monitoring patients after endovascular treatment of a cerebral aneurysm. While small asymptomatic lesions can be observed on these images after embolization, their exact prevalence should be evaluated in a larger series.

Adult↗

Diffusion-weighted MR imaging in the acute phase of transient ischemic attacks.

BACKGROUND AND PURPOSE: Radiologic assessment of acute transient ischemic attacks (TIAs) has been handicapped by the low sensitivity of CT and conventional MR imaging for acute small-vessel infarction and the difficulty in differentiating between acute and chronic lesions by use of these methods. Our purpose was to evaluate the incidence of TIA-related infarction by using diffusion-weighted MR imaging to determine whether the presence of a diffusion imaging abnormality correlates with the duration of symptoms or cause of TIA. METHODS: We prospectively studied 58 consecutive patients with acute TIA by use of diffusion-weighted imaging. All MR imaging was performed with a 1.5-T whole-body system with 24-mT/m gradient strength and an echo-planar-capable receiver. All patients were imaged within 10 days of stroke onset. RESULTS: Thirty-nine patients (67%) manifested a diffusion imaging abnormality consistent with acute ischemia. Cortical lesions were identified in 54% of these patients; most of them associated with other acute ischemic lesions. Subcortical lesions were identified in 46%; most of them were isolated from other lesions. The mean duration of symptoms in patients with no TIA-related diffusion imaging abnormalities was 0.96 hours (median, 0.33 hours) compared with a mean of 6.85 hours (median, 1.53 hours) in patients with diffusion imaging abnormalities (P =.025, Mann-Whitney U test). This significant correlation between the duration of TIA symptoms and the presence of TIA-related abnormalities was lost when we excluded from the analysis patients whose symptoms lasted longer than 6 hours (P =.513, Mann-Whitney U test). No significant correlation was observed between the size of TIA-related lesions and the duration of symptoms or cause of TIA. CONCLUSION: Two thirds of our TIA patients showed focal abnormalities indicative of acute ischemic lesions on diffusion-weighted images. This incidence is higher than that previously reported in the literature. The presence of such abnormalities increased with increasing total symptom duration, but this relation was not observed when only patients whose symptoms lasted less than 6 hours were considered. No significant correlation was observed between the cause and presence of TIA-related lesions on diffusion-weighted MR images. These TIA-related lesions are probably irreversible and may lead to subsequent infarct.

Acute Disease↗

Study on protein adsorption kinetics to a dye-ligand adsorbent by the pore diffusion model.

Adsorption kinetics of bovine serum albumin (BSA) and bovine hemoglobin (bHb) to Cibacron Blue 3GA (CB) modified Sepharose CL-6B has been studied. The effects of liquid-phase ionic strength and CB coupling density on the uptake rates of these two proteins in Tris-HCl buffer (pH 7.5) were evaluated by effective pore diffusivity derived from a pore diffusion model. The results showed that despite their similar molecular masses and sizes, the effects of aqueous-phase ionic strength and CB density on the effective pore diffusivities of BSA and bHb were distinctly different. The effective pore diffusivity of BSA to CB-Sepharose increased significantly with decreasing CB density and increasing liquid-phase ionic strength. This was considered due to the decrease in electrostatic repulsion between the BSA and CB molecules of like charge. That is, the increase in ionic strength and the decrease in CB coupling density reduced the electrostatic hindrance effect on BSA diffusion to CB-Sepharose, facilitating the hindered pore diffusion. In contrast, because of the higher isoelectric point of bHb (7.0) compared to BSA (4.7), bHb suffered little electrostatic hindrance effect during its diffusion to CB-Sepharose. Therefore, the effective pore diffusivity of bHb was unchanged with the change in liquid-phase ionic strength and CB coupling density.

Adsorption↗

Diffusion-tensor MR imaging of gray and white matter development during normal human brain maturation.

BACKGROUND AND PURPOSE: Conventional MR imaging findings of human brain development are thought to result from decreasing water content, increasing macromolecular concentration, and myelination. We use diffusion-tensor MR imaging to test theoretical models that incorporate hypotheses regarding how these maturational processes influence water diffusion in developing gray and white matter. METHODS: Experimental data were derived from diffusion-tensor imaging of 167 participants, ages 31 gestational weeks to 11 postnatal years. An isotropic diffusion model was applied to the gray matter of the basal ganglia and thalamus. A model that assumes changes in the magnitude of diffusion while maintaining cylindrically symmetric anisotropy was applied to the white matter of the corpus callosum and internal capsule. Deviations of the diffusion tensor from the ideal model predictions, due to measurement noise, were estimated by using Monte Carlo simulations. RESULTS: Developing gray matter of the basal ganglia and developing white matter of the internal capsule and corpus callosum largely conformed to theory, with only small departures from model predictions in older children. However, data from the thalamus substantially diverged from predicted values, with progressively larger deviations from the model with increasing participant age. CONCLUSION: Changes in water diffusion during maturation of central gray and white matter structures can largely be explained by theoretical models incorporating simple assumptions regarding the influence of brain water content and myelination, although deviations from theory increase as the brain matures. Diffusion-tensor MR imaging is a powerful method for studying the process of brain development, with both scientific and clinical applications.

Basal Ganglia↗

Inter-sequence and inter-imaging unit variability of diffusion tensor MR imaging histogram-derived metrics of the brain in healthy volunteers.

BACKGROUND AND PURPOSE: Diffusion tensor MR imaging has the potential to improve our ability to monitor several neurologic conditions. As a preliminary step to the assessment of the role of diffusion tensor MR imaging in the context of longitudinal and multicenter studies, we evaluated the effect of sequence-, imaging unit-, and imaging-reimaging-induced variations on diffusion tensor MR imaging quantities derived from histogram analysis of a large portion of the central brain of healthy volunteers. METHODS: Each of eight healthy volunteers underwent imaging on two MR imaging units using three different pulsed gradient spin-echo single shot echo-planar pulse sequences (each of them having a different diffusion gradient scheme). Four additional healthy participants underwent imaging twice on the same imaging unit to assess imaging-reimaging variability. RESULTS: For mean diffusivity histograms, the differences between inter-sequence and inter-imaging unit coefficients of variation were significant for all the considered quantities with P values ranging from.003 to <.001. Also, the inter-imaging unit coefficient of variation for average fractional anisotropy was significantly higher than the corresponding inter-sequence coefficient of variation (P =.002). In general, inter-sequence mean diffusivity histogram-derived metrics (coefficients of variation ranging from 1.72% to 5.56%) were more reproducible than were fractional anisotropy histogram-derived metrics (coefficients of variation ranging from 5.45% to 7.34%). Imaging-reimaging variability was found to fall in the range of inter-sequence coefficients of variation for all the considered quantities. CONCLUSION: This study shows that inter-sequence, imaging-reimaging, and inter-imaging unit variabilities of diffusion tensor MR imaging-derived measurements are relatively low, suggesting that diffusion tensor MR imaging might provide additional measures of outcome with which to assess the evolution of brain structural damage in large scale studies of various neurologic conditions.

Analysis of Variance↗

[Self-diffusion of water into silk fibers from magnetic field pulse gradient data].

Self-diffusion of water was studied in fibers of natural silk (Bombyx mori) with a water content of 0.18 g H2O/g dried material. Self-diffusion measurements were conducted by pulsed gradient of magnetic field (stimulated echo) at diffusion times from 10 to 200 mc. The dependence of experimental diffusion coefficients Dexp = f(delta) (observed decrease when delta increased) was determined to be responsible for the restricted diffusion. A model of planar and regularly spaced permeable barriers to diffusion of water molecules was applied to estimate the barrier spacing a and the permeability constant p. The maximal value of Dexp (at short diffusion time) in B. mori silk fibres was about 0.06 of the value of Dexp in bulk free water. The results obtained are compared to literature data on self-diffusion of water in hydrated biopolymer fibers and are discussed in connection with molecular mobility in natural macromolecular systems with low water content.

Diffusion↗

Diffusive boundary layer development above a sediment-water interface.

A model to estimate the entry length to a fully developed diffusive boundary layer above a sediment bed, such as those found in lakes, reservoirs, rivers, and estuaries, is presented. The model is used to determine how the length of a sediment bed in mass-transfer experiments influences the measured vertical diffusive flux at the sediment-water interface. A nondimensional local mass flux is introduced in the form of a Sherwood number (Sh) and expressed as a function of both the distance from the leading edge of the sediment bed (x) and the Schmidt number (Sc). Similarly, a mean Sherwood number (Sh(ave)) for a sediment bed of length (L) is introduced. The diffusive boundary layer grows with distance, and its thickness depends on the Schmidt number (i.e., the diffusive boundary layer gets thicker and develops more quickly as the Schmidt number decreases). For Schmidt numbers greater than or equal to 100, the diffusive boundary layer begins to develop slowly but is fully developed when the nondimensional horizontal coordinate (x+) is approximately 1000. The Sherwood number is largest (i.e., infinity) near the leading edge of the sediment bed (i.e., at x = 0), decreases as the distance from the bed increases, and, finally, approaches a constant value for a fully developed diffusive boundary layer (Sh(infinity)). In this paper, the distance to a fully developed diffusive boundary layer (L99) and the required length of a sediment bed are related explicitly to Sc, sheer velocity (U*), and the relative errors of local or average Sherwood numbers (Sh or Sh(ave), respectively) against the Sherwood number for the fully developed diffusive boundary layer (Sh(infinity)). The lengths L99 and L decrease as the Schmidt number increases and become independent of the Schmidt number when Sc is greater than 1000. A longer sediment bed is needed when the shear velocity or the Schmidt number is small (e.g., L99 and L approximately 1.0 m and 8.0 m, respectively, for Sc = 500, U* = 0.1 cm/s, and a 3% acceptable error). Experimental studies may not be able to meet these requirements and an adjustment of measured mass-transfer rates at a sediment-water interface may be necessary. The magnitude of that adjustment is up to 50%. Its dependence on the Schmidt number, shear velocity, and bed length is given in this paper.

Diffusion↗

MR quantitation of volume and diffusion changes in the developing brain.

BACKGROUND AND PURPOSE: Brain volume and diffusion change during maturation. Quantitation of these changes may be helpful in understanding normal brain development. We used diffusion-weighted imaging to characterize the volumetric and diffusion changes in vivo. METHODS: We recruited 30 pediatric volunteers (aged 1 month-17 years; 14 male, 16 female). Diffusion was measured in three orthogonal directions with a b value of 1000 s/mm2. The diffusion parameters from the entire brain were calculated and fitted to a triple gaussian model. In addition, region-of-interest measurements were made in caudate, thalamus, genu and splenium of the corpus callosum, and periventricular white matter (PVWM). The brain volume was measured by counting pixels and by using the model. RESULTS: Water diffusion of the whole brain, caudate, thalamus, genu and splenium of the corpus callosum, and PVWM decreased during maturation, with the most significant change within the first 2 years. Robust negative correlations were found between age and the measured average diffusion constant (Dav) values in each of the measured locations (P <.005). Volumes of different cerebral compartments and the total intracranial volume (ICV) increased rapidly during the first 2 years of life and then had a slower growth process through adolescence. Age was correlated with the ICV and the volume of each brain compartment (P <.005). CONCLUSION: Brain diffusion decreases and brain volume increases during maturation, with the most significant changes occurring within the first 2 years of life. The brain model used in this study provides a good estimate of the increasing brain volume.

Adolescent↗

Diffusion abnormality of deep gray matter in external capsular hemorrhage.

BACKGROUND AND PURPOSE: To our knowledge, diffusion abnormality of the unaffected deep gray matter during striatocapsular hemorrhage has not been previously described in the literature. We report the presence of the diffusion abnormality separated from hematoma in patients with external capsular (lateral striatocapsular) hemorrhage and suggest the plausible mechanisms of diffusion signal intensity change. METHODS: We retrospectively reviewed MR images in 28 consecutive patients with spontaneous striatocapsular hemorrhage and evaluated signal intensity changes at sites separated from the hemorrhage and the lesions on diffusion-weighted (DW) images. Apparent diffusion coefficients (ADCs) of the lesions were measured, and volume changes in the deep gray matter were assessed at follow-up. RESULTS: On DW images, hyperintensity of deep gray matter was found in nine patients (25%). In all patients with DW imaging abnormality, the hemorrhage was located in the external capsule, and the interval from hemorrhagic ictus to MR imaging study was 8-54 days. Hyperintensity of the deep gray matter was seen in the caudate (n = 8), putamen (n = 7), thalamus (n = 5), and substantia nigra (n = 2). Mean relative ADC ratios of the diffusion abnormality were 0.76 +/- 0.10 in the caudate, 0.79 +/- 0.07 in the putamen, and 0.85 +/- 0.11 in the thalamus. DW imaging abnormality disappeared with mild atrophy in two patients who underwent follow-up imaging. CONCLUSION: External capsular hemorrhage may be uncommonly accompanied by diffusion abnormality in the striatum or thalamus at follow-up, and the lesion should not be misdiagnosed as new-onset infarction. Secondary neuronal degeneration may play an important role in the development of diffusion abnormality.

Adolescent↗