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PubMed1994

Site-to-site diffusion in proteins as observed by energy transfer and frequency-domain fluorometry.

We report measurements of the site-to-site diffusion coefficients in proteins and model compounds, which were measured using time-dependent energy transfer and frequency-domain fluorometry. The possibility of measuring these diffusion coefficients were shown from simulations, which demonstrate that donor (D)-to-acceptor (A) diffusion alters the donor frequency response, and that this effect is observable in the presence of a distribution of donor-to-acceptor distances. For decay times typical of tryptophan fluorescence, the simulations indicate that D-A diffusion coefficients can be measured ranging from 10(-7) to 10(-5) cm2/s. This possibility was verified by studies of a methylene-chain linked D-A pair in solutions of varying viscosity. The D-A diffusion was also measured for two labeled peptides and two proteins, melittin and troponin I. In most cases we used global analysis of data sets obtained with varying amounts of collisional quenchers to vary the donor decay time. Unfolding of troponin I results in more rapid D-A diffusion, whereas for melittin more rapid diffusion was observed in the alpha-helical state but over a limited range of distances.

Diffusion↗

PubMed1998

Cation diffusion in calcite: determining closure temperatures and the thermal history for the Allan Hills 84001 meteorite.

The presence of zoned Fe, Mg, Ca, and Mn in the carbonate phases associated with the cracks and inclusions of the Allan Hills (ALH) 84001 meteorite provides evidence for constraining the thermal history of the meteorite. Using self- and tracer-diffusion coefficients obtained from laboratory experiments on natural calcite, cooling rates are calculated for various temperatures and diffusion distances to assist in the evaluation of the compositional zoning associated with the carbonate phases in ALH 84001. The closure temperature model provides the average temperature below which compositional zoning will be preserved for a given cooling rate, that is, the temperature at which diffusion will be ineffective in homogenizing the phase. The validity of various theories for the formation of the carbonate globules may be examined, therefore, in view of the diffusion-limited kinetic constraints. Experiments using a thin film-mineral diffusion couple and ion microprobe for depth profiling analysis were performed for the temperature range of 550-800 degrees C to determine self- and tracer-diffusion coefficients for Ca and Mg and in calcite. The resulting activation energies for Ca (Ea(Ca) = 271 +/- 80 kJ/mol) and for Mg (Ea(Mg) = 284 +/- 74 kJ/mol) were used then to calculate a series of cooling rate, grain size, and closure temperature curves. The data indicate, for example, that by the diffusion of Mg in calcite, a 10 micrometers compositional zone would be completely homogenized at a temperature of 300 degrees C for cooling rates <100 K/Ma. These data provide no constraint on formation models that propose a low-temperature fluid precipitation mechanism; however, they indicate that the carbonate globules were not exposed to a high-temperature environment for long time scales following formation.

Calcium↗

PubMed1995

Role of acid back-diffusion in the formation of mucosal ulceration and its treatment with drugs in diabetic rats.

We have studied the role of acid back-diffusion in the formation of gastric mucosal ulceration and its treatment with several drugs in streptozotocin-induced diabetic rats. After vagotomy, the stomach of 1-8 week-old diabetic rats and age-matched control rats were irrigated with acid solutions of graded concentrations (50-150 mm HCl) for 1 or 3 h. A marked increase in acid back-diffusion and in haemorrhagic ulceration was found in diabetic rats. The extent of acid back-diffusion and the severity of mucosal ulceration were dependent on the concentration and the time of contact of acid solutions with the gastric mucosa. A high correlation (r = 0.9227) between acid back-diffusion and mucosal ulceration was found in 3-h acid-irrigated diabetic rats. In the 2-week diabetic rat, intragastric cimetidine (300 mg kg-1) or NaHCO3 (52 mg kg-1) significantly (P < 0.05) reduced both acid back-diffusion and haemorrhagic ulcer formation, while atropine (1.0 mg kg-1) or bupivacaine (0.5%, 0.4 mL/rat) was ineffective. High blood glucose levels in diabetic rats were not influenced by these agents. Acid back-diffusion and ulceration in the diabetic rat were markedly reduced by daily administration but not single injection of insulin (50 units kg-1, s.c.). Taken together, in the early stage of diabetes development, chronic insulin deficiency rather than nerve degeneration or hyperglycaemia may be responsible for the disruption of mucosal barriers. It is concluded that acid back-diffusion played an important role in the formation of acute haemorrhagic ulceration that can be inhibited by intragastric cimetidine, NaHCO3 or daily injection of insulin.

Animals↗

PubMed2005

A least-squares error minimization approach in the determination of ferric ion diffusion coefficient of Fricke-infused dosimeter gels.

A least-squares error minimization approach was adopted to assess ferric ion diffusion coefficient of Fricke-agarose gels. Ferric ion diffusion process was modeled as a Gaussian-shaped degradation kernel operating on an initial concentration distribution. Diffusion coefficient was iteratively determined by minimizing the error function defined as the difference between the theoretically calculated and the experimentally measured dose distributions. A rapid MR image-based differential gel dosimetry technique that time resolves the evolution of the ferric ion diffusion process minimizes smearing of the dose distribution. Our results showed that for a Fricke-agarose gel contained 1 mM ammonium ferrous sulfate, 1% agarose, 1 mM sodium chloride, and 50 mM sulfuric acid, its ferric ion diffusion coefficient is (1.59 +/- 0.28) x 10(-2) cm2 h(-1) at room temperature. This value falls within the 1.00-2.00 x 10(-2) cm2 h(-1) range previously reported under varying gelling ingredients and concentrations. This method allows a quick, nondestructive evaluation of the ferric ion diffusion coefficient that can be used in conjunction with the in situ gel dosimetry experiment to provide a practical diffusion characterization of the dosimeter gel.

Diffusion↗

PubMedDate not supplied

A generalized formulation of diffusion effects in micron resolution nuclear magnetic resonance imaging.

A generalized formulation of the diffusion related nuclear magnetic resonance (NMR) signal is derived from a random walk model. Previous analyses performed in the NMR spectroscopy were the formulations of the diffusion related signal amplitude at a specific time, such as the spin echo formation time. They are, in general, not applicable to continuous time domain analyses. In this paper, we have extended the theory to the two-dimensional imaging case and derived an analytical formula useful for the computation of the diffusion affected signal as a function of continuous time for a time variant gradient. This formulation will be useful in NMR imaging, especially in NMR microscopy where the diffusion associated signal attenuation is serious due to the strong gradient fields (100-1000 G/cm), and at the same time data are acquired continuously for the acquisition period. In addition to the loss of the resolution and signal-to-noise ratio due to the random phase fluctuation by diffusion, the variation of the intensity during the data acquisition period introduces a line broadening whose full width at half-maximum is found to be much larger than the bandwidth-limited resolution or diffusion related intrinsic resolution. This line spreading effect is integrated in a computer simulation and is evaluated as an integral part of the overall diffusion effects in micron resolution NMR imaging or NMR microscopy.

Computer Simulation↗

PubMed1986

Discrepancies between disk diffusion and broth susceptibility studies of the activity of ticarcillin plus clavulanic acid against ticarcillin-resistant Pseudomonas aeruginosa.

Ticarcillin and clavulanic acid in combination were tested against 40 Pseudomonas aeruginosa isolates resistant to ticarcillin by disk diffusion. A total of 21 isolates (53%) were susceptible to ticarcillin-clavulanate by disk diffusion, under currently recommended criteria for ticarcillin susceptibility. Macro-broth dilution tests (ticarcillin plus clavulanic acid, 2 micrograms/ml) confirmed susceptibility (MIC less than or equal to 64 micrograms/ml) of only 8 (38%) of 21 isolates. Time-kill studies of disk diffusion susceptible isolates indicated 2 log10 or greater killing of most isolates at 6 h in broth containing ticarcillin (64 micrograms/ml) combined with clavulanic acid (1, 2, 5, or 10 micrograms/ml). After 6 h, regrowth was common in all concentrations of clavulanic acid except 10 micrograms/ml. Regrowth populations were resistant to ticarcillin-clavulanate by MIC determination. Poor bactericidal activity of ticarcillin-clavulanate against ticarcillin-resistant P. aeruginosa was confirmed, as most isolates did not undergo 99.9% or greater killing at 24 h in all concentrations of clavulanic acid. Serotype O-11 was our most common serotype and was associated with disk diffusion "pseudosusceptibility." Concomitant disk diffusion testing of ticarcillin-clavulanate and ticarcillin is recommended for testing the susceptibility of P. aeruginosa to ticarcillin-clavulanate by disk diffusion. P. aeruginosa isolates resistant to ticarcillin should as a rule be considered also resistant to ticarcillin-clavulanate, despite apparent susceptibility by disk diffusion.

Clavulanic Acid↗

PubMed1990

Diffusion of beta-lactam antibiotics through liposome membranes reconstituted from purified porins of the outer membrane of Pseudomonas aeruginosa.

Determination of the rates of diffusion of beta-lactam antibiotics through purified Pseudomonas aeruginosa porins C, D2, and E in liposomes yielded the following results. (i) The rates of carbapenem (imipenem and meropenem) diffusion through the protein D2 pore were roughly 2 to 70 times higher than those through other porin pores. It is not clear why the protein D2 pore allowed rapid diffusion of carbapenems. The rates of diffusion of glucosamine and triglycine through the protein D2 pore were about 14 and 4 times higher, respectively, than that of an uncharged test solute with a similar Mr, glucose. (ii) The rates of diffusion of antipseudomonal anionic beta-lactams such as piperacillin, ceftazidime, cefsulodin, and aztreonam through the protein C pore were higher than those through other porin pores. This was probably due to the slightly larger pore size and the slight anion selectivity of protein C, since the apparent exclusion limit of the protein C pore for uncharged saccharides is higher than that of other porins and the rate of diffusion of gluconic acid through the protein C pore is about double that for glucose. (iii) The rates of diffusion of cefoperazone through all three species of porin were relatively high. These results indicate that the antipseudomonal beta-lactams permeate the P. aeruginosa outer membrane via newly identified porins.

Anti-Bacterial Agents↗

PubMed1980

Synovial fluids facilitate small solute diffusivity.

The diffusivity of water, fucose, proline, lysine, glutamic acid, glucose and sucrose was determined in a variety of inflammatory human synovial fluids. In view of the constituents of pathological synovial fluids one would predict impedence to solute movement. In several fluid diffusivity was enhanced relative to translational diffusion in water. In most fluids diffusivity was enhanced relative to diffusion in diluted serum. Diffusivity of the solutes was dependent on size and charge of the solute but independent of fluid characteristics, including glucose, protein, and complement concentrations and cellular constituents. This paper reports aberrant small solute behaviour in synovial fluids. Enhanced diffusivity relative to water was demonstrated in hyaluronate dissolved in diluted serum as well. Hyaluronate domains in the synovial fluids interact with these solutes, facilitating movement. This phenomenon affords a homoestatic mechanism as regards chondrocyte viability in spite of inflammation or a low glucose concentration.

Arthritis↗

PubMed2006

Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment.

BACKGROUND: Magnetic resonance diffusion tensor imaging (DTI) shows promise in the early detection of microstructural pathophysiological changes in the brain. OBJECTIVES: To measure microstructural differences in the brains of participants with amnestic mild cognitive impairment (MCI) compared with an age-matched control group using an optimised DTI technique with fully automated image analysis tools and to investigate the correlation between diffusivity measurements and neuropsychological performance scores across groups. METHODS: 34 participants (17 participants with MCI, 17 healthy elderly adults) underwent magnetic resonance imaging (MRI)-based DTI. To control for the effects of anatomical variation, diffusion images of all participants were registered to standard anatomical space. Significant statistical differences in diffusivity measurements between the two groups were determined on a pixel-by-pixel basis using gaussian random field theory. RESULTS: Significantly raised mean diffusivity measurements (p<0.001) were observed in the left and right entorhinal cortices (BA28), posterior occipital-parietal cortex (BA18 and BA19), right parietal supramarginal gyrus (BA40) and right frontal precentral gyri (BA4 and BA6) in participants with MCI. With respect to fractional anisotropy, participants with MCI had significantly reduced measurements (p<0.001) in the limbic parahippocampal subgyral white matter, right thalamus and left posterior cingulate. Pearson's correlation coefficients calculated across all participants showed significant correlations between neuropsychological assessment scores and regional measurements of mean diffusivity and fractional anisotropy. CONCLUSIONS: DTI-based diffusivity measures may offer a sensitive method of detecting subtle microstructural brain changes associated with preclinical Alzheimer's disease.

Aged↗

PubMed2006

Diffusion tensor magnetic resonance imaging at 3.0 tesla shows subtle cerebral grey matter abnormalities in patients with migraine.

BACKGROUND AND OBJECTIVE: Diffusion tensor (DT) magnetic resonance imaging (MRI) has the potential to disclose subtle abnormalities in the brain of migraine patients. This ability may be increased by the use of high field magnets. A DT MRI on a 3.0 tesla scanner was used to measure the extent of tissue damage of the brain normal appearing white (NAWM) and grey matter in migraine patients with T2 visible abnormalities. METHODS: Dual echo, T1 weighted and DT MRI with diffusion gradients applied in 32 non-collinear directions were acquired from 16 patients with migraine and 15 sex and age matched controls. Lesion load on T2 weighted images was measured using a local thresholding segmentation technique, and brain atrophy assessed on T1 weighted images using SIENAx. Mean diffusivity and fractional anisotropy histograms of the NAWM and mean diffusivity histograms of the grey matter were also derived. RESULTS: Brain atrophy did not differ between controls and patients. Compared with healthy subjects, migraine patients had significantly reduced mean diffusivity histogram peak height of the grey matter (p=0.04). No diffusion changes were detected in patients' NAWM. In migraine patients, no correlation was found between T2 weighted lesion load and brain DT histogram derived metrics, whereas age was significantly correlated with grey matter mean diffusivity histogram peak height (p=0.05, r=-0.52). CONCLUSIONS: DT MRI at high field strength discloses subtle grey matter damage in migraine patients, which might be associated with cognitive changes in these patients.

Adult↗

PubMed1987

Lateral diffusion of proteins in membranes.

Membrane protein lateral diffusion can be constrained in several ways: Diffusion can be slower than that predicted for a simple, fluid lipid bilayer; diffusion can be confined to certain regions within the total membrane; and diffusion may not be equally probable in all directions, i.e. it may be anisotropic. We know that protein diffusion is reduced by increasing concentrations of membrane proteins and by interactions of the diffusant with structure(s) peripheral to the membrane. The molecular nature of such peripheral constraints has been difficult to pinpoint, but attention is now being directed to the extracellular matrix in addition to the membrane-associated cytoskeleton. There are many proteins that are confined to lateral domains in differentiated, isolated cells and in cells organized into tissue. The mechanisms that maintain such inhomogeneous distributions should be elucidated in the next few years. Whether lateral diffusion of membrane proteins over distances of a few micrometers is usually isotropic or anisotropic will be ascertained in the near future using imaging methods combined with photobleaching.

Diffusion↗

PubMed2004

Normal and transplanted rat kidneys: diffusion MR imaging at 7 T.

PURPOSE: To investigate the feasibility of obtaining reproducible apparent diffusion coefficient (ADC) maps of normal rat kidneys by using respiratory-triggered spin-echo diffusion-weighted magnetic resonance (MR) imaging, to investigate the sensitivity of ADC maps in the evaluation of renal blood flow, and to use this technique to monitor acute graft rejection in transplanted rat kidneys. MATERIALS AND METHODS: Spin-echo diffusion-weighted MR imaging measurements were performed in 20 normal rats and nine rats that had undergone transplantation (six rats had received allografts; three had received isografts) at 7 T. To evaluate the effect of alteration in blood flow and water transport function, angiotensin II was infused in six normal rats and a series of spin-echo diffusion-weighted MR images was obtained at five time points. Transplanted kidneys were monitored by obtaining spin-echo diffusion-weighted MR images and gradient-echo MR images every 2 hours for 8 hours on postoperative day 4. Statistical analysis was performed with repeated-measures multivariate analysis of variance and the paired t test. RESULTS: No significant differences in ADC values were observed between right and left kidneys in all three orthogonal directions; however, a small difference was observed between the cortex and medulla. ADC values in the cephalocaudal and mediolateral directions were higher than those in the anteroposterior direction (P <.01 for all). ADC values in the cortex and medulla decreased significantly (by >35%, P <.01) during angiotensin II-induced reduction in renal blood flow. No significant signal intensity change was observed between native and transplanted kidneys on gradient-echo MR images. Allografts exhibited decreased ADC values (P <.01) and isografts exhibited similar ADC values compared with native kidneys. CONCLUSION: These findings suggest that reproducible renal ADC maps can be obtained in rats by using spin-echo diffusion-weighted MR imaging at 7 T. Spin-echo diffusion-weighted MR imaging may have potential as a noninvasive tool for monitoring early graft rejection after kidney transplantation.

Angiotensin II↗

PubMed2005

Diffusion-weighted MR imaging sequence in the detection of postoperative recurrent cholesteatoma.

PURPOSE: To prospectively evaluate a fast spin-echo (SE) diffusion-weighted sequence for magnetic resonance (MR) imaging of recurrent cholesteatoma in patients who have undergone middle ear surgery. MATERIALS AND METHODS: The study was approved by the institutional review board, and informed consent was obtained from all patients. Twenty-four patients (10 female and 14 male patients; mean age, 44 years) who had undergone resection of cholesteatoma were referred for MR imaging. MR imaging was performed with a 1.5-T unit by using unenhanced diffusion-weighted fast SE imaging at b factors of 0 and 800 sec/mm(2), unenhanced T2-weighted fast SE imaging, unenhanced T1-weighted SE imaging, and delayed contrast material-enhanced T1-weighted imaging. Two radiologists evaluated the diffusion-weighted fast SE images for the presence of a high-signal-intensity cholesteatoma. Results from MR imaging were compared with reports from second- or third-look surgery. Interobserver agreement was assessed with the kappa statistic. RESULTS: A recurrent cholesteatoma was correctly identified in 13 of 14 patients with diffusion-weighted fast SE images obtained with a b factor of 800 sec/mm(2), for a positive predictive value of 93%. In patients without recurrent cholesteatoma, all diffusion-weighted fast SE MR images obtained with a b factor of 800 sec/mm(2) were correctly interpreted as showing no high signal intensity. Thus, the negative predictive value was 100%. Sensitivity and specificity were 100% (13 of 13 patients) and 91% (10 of 11 patients), respectively. Interobserver agreement was excellent (kappa = 0.92). The smallest recurrent cholesteatoma was 5 mm in diameter, and this was correctly detected with the diffusion-weighted fast SE sequence. CONCLUSION: Diffusion-weighted fast SE imaging enables the depiction of recurrent cholesteatoma in patients who have undergone middle ear surgery.

Adolescent↗

PubMed1992

Calculation of oxygen diffusion across the surface of isolated perfused hearts.

Although exact mathematical descriptions of oxygen diffusion into unperfused isolated organs are known, no analytic solution is available for perfused organs. Here, we derive an equation for oxygen diffusion across the epicardial surface of perfused hearts. Our oxygen transport model incorporates oxygen delivery from the capillary perfusate, oxygen consumption, diffusion among adjacent capillary exchange regions, and diffusion across the epicardial surface. The wall of the heart is modeled by a slab of tissue. The derived equation fits experimental data on the diffusive oxygen flux across the surface of isolated saline-perfused guinea pig hearts, obtained by measuring oxygen uptake from the perfusate at various oxygen tensions in the surroundings of the isolated heart. The model predicts that in isolated arrested guinea pig hearts suspended in air, 25% of the oxygen taken up from the saline perfusate (PO2 approximately 680 mmHg) diffuses out of the heart across the surface. In beating isolated guinea pig hearts, 5% of the oxygen taken up from the perfusate diffuses across the surface.

Animals↗

PubMed1997

In vivo diffusion of immunoglobulin G in muscle: effects of binding, solute exclusion, and lymphatic removal.

Previously, we demonstrated that immunoglobulin G (IgG), dissolved in an isotonic solution in the peritoneal cavity, transported rapidly into the abdominal wall when the intraperitoneal (ip) pressure was > 2 cmH2O. We hypothesized that this was chiefly caused by convection and that diffusion of IgG was negligible. To investigate the role of diffusion, we dialyzed rats with no pressure gradient across the abdominal wall muscle for 2 or 6 h with an ip isotonic solution containing 125I-labeled IgG. At the end of the experiment, the animal was euthanized and frozen and abdominal wall tissue was processed to produce cross-sectional autoradiograms. Quantitative densitometric analysis resulted in IgG concentration profiles with far lower magnitude than profiles from experiments in which convection dominated. In other in vivo experiments, we determined the lymph flow rate to be 0.8 x 10(-4) ml.min-1.g-1 and the fraction of extravascular tissue (theta s) available to the IgG to be 0.041 +/- 0.001. An in vitro binding assay was used to determine the time-dependent, nonsaturable binding constant: 0.0065 min-1 x duration of exposure. A non-steady-state diffusion model that included effects of theta s, time-dependent binding, and lymph flow was fitted to the diffusion profile data, and the IgG diffusivity within the tissue void was estimated to be 2 x 10(-7) cm2/s, a value much higher than that published by other groups. We also demonstrate from our previous data that convection of IgG through tissue dominates over diffusion at ip pressures > 2 cmH2O, but diffusion may not be negligible. Furthermore, nonsaturable binding must be accounted for in the interpretation of tissue protein concentration profiles.

Abdominal Muscles↗

PubMed1985

Characteristics of water diffusion in the rabbit proximal convoluted tubule.

Water diffusion in the in vitro microperfused rabbit proximal convoluted tubule was measured to assess the transepithelial pathway for water movement and the physical characteristics of the water permeation pathway. The measured diffusive water permeability (PDW(MEASURED] was high, 5 X 10(-3) cm/s, suggesting a transcellular transport route. Simultaneously measured n-butanol permeability (PDNB(MEASURED], an index of the cytoplasmic resistance to water diffusion, was 3.6 X 10(-3) cm/s. PDW(MEASURED], PDNB(MEASURED) and the free solution diffusion coefficients for water and n-butanol were used to derive a minimum membrane PDW (PDW(MEMBRANE] of 12.5 X 10(-3) cm/s. These data suggest that at least 60% of the transepithelial resistance to water diffusion resides in the cell cytoplasm. Measurement of the temperature dependence of PDW(MEASURED) and PDNB(MEASURED) gave an apparent activation energy of PDW(MEMBRANE) that was constant between 20 and 40 degrees C at about 4.3 kcal/mol. The organic mercurial sulfhydryl reagent p-chloromercuribenzene sulfonate, which has been shown to reduce diffusive water permeability in the red cell membrane by 50%, reduced PDW(MEMBRANE) by 54% without affecting PDNB(MEASURED). These last two independent lines of evidence are consistent with water diffusion through small, aqueous, protein-bounded channels.

4-Chloromercuribenzenesulfonate↗

PubMed2004

The evaluation of Wallerian degeneration in chronic paediatric middle cerebral artery infarction using diffusion tensor MR imaging.

BACKGROUND: The long-term neuromotor outcome in paediatric strokes ranges from normal to varying degrees of hemiplegia. We evaluated the indices of diffusion tensor magnetic resonance imaging (DTI), fractional anisotropy and mean diffusivity to determine if these indices can identify and quantify the presence of Wallerian degeneration in paediatric patients with chronic middle cerebral artery infarction, and to determine if these quantitative parameters correlate with the neuromotor outcome. METHODS: Eleven children (mean age 8.1 years) with evidence of unilateral middle cerebral artery stroke on magnetic resonance imaging and 10 control subjects (mean age 8.7 years) were studied. Neuromotor outcome was based on functions of the affected hand: mild (n = 3), moderate (n = 6), and severe (n = 2) hemiparesis. Fractional anisotropy and mean diffusivity of the ipsilateral corticospinal tract were compared with matched contralateral regions using the Mann-Whitney U test. Spearman's test was performed to study the relationship between neuromotor outcome and the following: ipsilateral-to-contralateral ratio of fractional anisotropy, mean diffusivity and cerebral peduncle area, and the largest infarction size. RESULTS: For control subjects, there were no significant differences in fractional anisotropy and mean diffusivity of the corticospinal tract between the right and left side. For patients, fractional anisotropy decreased by 18% and mean diffusivity increased by 8% in the ipsilateral compared to the contralateral corticospinal tract. Neuromotor outcome correlated with the ipsilateral-to-contralateral ratio of fractional anisotropy (r = -0.638, p = 0.035) but not with the mean diffusivity ratio, cerebral peduncle area ratio and largest infarction size. CONCLUSION: DTI can be used to detect and quantify Wallerian degeneration in chronic paediatric middle cerebral artery infarction. Our preliminary data show that loss of anisotropy in the corticospinal tract correlates with neuromotor outcome.

Adolescent↗

PubMed1995

Alteration of intracellular metabolite diffusion in rat brain in vivo during ischemia and reperfusion.

BACKGROUND AND PURPOSE: Diffusion-weighted MRI can demonstrate decreases of the apparent diffusion coefficient (ADC) of brain tissue water shortly after the onset of ischemia. To further elucidate underlying mechanisms, this study extended diffusion assessment to intracellular metabolites in rat brain in vivo before, during, and after ischemia. METHODS: Changes in molecular mobility were studied in a rat model of global forebrain ischemia (n = 8, 20-minute occlusion, 120-minute reperfusion) with the use of diffusion-weighted localized proton MR spectroscopy. During ischemia and early reperfusion the time course of ADC changes was monitored by strongly diffusion-weighted spectra. ADC values of N-acetylaspartate, creatines, cholines, and myo-inositol were evaluated from series of differently diffusion-weighted spectra before ischemia, 90 minutes after reperfusion, and 60 minutes postmortem. RESULTS: Parallel to a rise in diffusion-weighted water signal (133 +/- 20%), pertinent intensities of all brain metabolites increased during ischemia. Changes were most pronounced for myo-inositol (46 +/- 9%) and smallest for N-acetylaspartate (12 +/- 4%). During reperfusion water ADC values returned to basal values, whereas metabolite ADC values were decreased by 22% (after 40 minutes). Postmortem ADC values (after 60 minutes) were reduced by 46% for water and 38% for metabolites. CONCLUSIONS: The present findings indicate that water ADC changes during ischemic stroke are accompanied by significant alterations in intracellular mobility in both neuronal and glial cell populations as reflected by N-acetylaspartate and myo-inositol, respectively. Altered metabolite ADC values during reperfusion are consistent with irreversible tissue damage in this model and offer new means to assess circulatory and metabolic compromise.

Animals↗