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PubMed2006

Analysis of the utility of diffusion-weighted MRI and apparent diffusion coefficient values in distinguishing central nervous system toxoplasmosis from lymphoma.

INTRODUCTION: Toxoplasmosis and lymphoma are common lesions of the central nervous system in patients with AIDS. It is often difficult to distinguish between these lesions both clinically and radiographically. Previous research has demonstrated restricted diffusion within cerebral lymphomas and bacterial abscesses. However, little work has been done to evaluate the diffusion characteristics of toxoplasmosis lesions. This study was designed to explore further the utility of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps and values in making the distinction between toxoplasmosis and lymphoma. METHODS: The magnetic resonance imaging (MRI) studies of 36 patients, including 22 with toxoplasmosis (all of whom had AIDS) and 14 with lymphoma (8 of whom had AIDS), at two institutions were reviewed retrospectively. The characteristics of the lesions on DWI were evaluated, and the ADC ratios of the lesions were calculated and compared. RESULTS: There was significant overlap of the ADC ratios of toxoplasma and lymphoma, most notably in the intermediate (1.0-1.6) range. There was variability in ADC ratios even among different lesions in the same patient. In only a minority of the lymphoma patients were the ADC ratios low enough to suggest the correct diagnosis. CONCLUSION: Our study showed that toxoplasmosis exhibits a wide spectrum of diffusion characteristics with ADC ratios which have significant overlap with those of lymphoma. Therefore, in the majority of patients, ADC ratios are not definitive in making the distinction between toxoplasmosis and lymphoma.

AIDS-Related Opportunistic Infections↗
PubMed2003

Deviations from the diffusion tensor model as revealed by contour plot visualization using high angular resolution diffusion-weighted imaging (HARDI).

The standard diffusion tensor model is limited in its ability to provide detailed information about multidirectional fiber architecture in human white matter. Additional directional acquisition of diffusivity properties with high angular resolution diffusion-weighted imaging (HARDI) acquisition schemes may deliver more information on areas with fiber crossings than standard DTI. However, representation of the additional information and the rating and visualization of fiber complexity is challenging. We used projection 2D-plots in combination with a HARDI acquisition scheme of 129 diffusion directions and compared the spherical diffusion variance index (SDI) with the relative anisotropy index (RAI). In normal controls, white matter areas with unidirectional fiber arrangement and areas with more complex fiber composition were identified with this approach. HARDI confirms and can visualize deviations from the tensor-like representation, thereby providing information on fiber structure complexity, which may be of considerable interest for clinical studies.

Anisotropy↗
PubMed1985

Absence of transbilayer diffusion of spin-labeled sphingomyelin on human erythrocytes. Comparison with the diffusion of several spin-labeled glycerophospholipids.

We have measured the transbilayer diffusion at 4 degrees C of spin labeled analogs of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidic acid in the human erythrocyte membrane. Measurements were also carried out in ghosts, released without ATP, and on large unilamellar vesicles made with total lipid extract. As reported previously (Seigneuret, M. and Devaux, P.F. (1984) Proc. Natl. Acad. Sci. USA 81, 3751-3755), the amino phospholipids are rapidly transported from the outer to the inner leaflet on fresh erythrocytes, whereas phosphatidylcholine diffuses slowly. We now show that phosphatidic acid behaves like phosphatidylcholine: approximately 10% is internalized in 5 h at 4 degrees C. Under the same experimental conditions, no inward transport of sphingomyelin can be detected. In ghosts resealed without ATP, all glycerophospholipids tested diffuse slowly from the outer to the inner leaflet (approx. 10% in 5 h) while no transport of sphingomyelin is seen. Finally in lipid vesicles, the inward diffusion of all glycerophospholipids is less than 2% in 5 h and a very small transport of sphingomyelin can be measured. These results confirm the existence of a selective inward aminophospholipid transport of fresh erythrocytes and suggest a slow and passive diffusion of all phospholipids on ghosts, resealed without ATP, as well as on lipid vesicles.

Adenosine Triphosphate↗
PubMed1991

Estimation of diffusion limitation after pneumonectomy from carbon monoxide diffusing capacity.

In three foxhounds, diffusing capacity for carbon monoxide (DLCO) was reduced by 25-30% after left pneumonectomy. Based on previous morphometric data in animals and physiologic data in humans, this reduction should not result in any impairment in gas exchange. However, experimental evidence indicates that diffusion limitation develops during exercise after pneumonectomy. Our objective is to determine whether this diffusion limitation to gas exchange can be predicted from physiologic measurements of DLCO. DLCO measured by the rebreathing technique was translated into diffusing capacity for O2 (DLO2) using an average conversion factor for canids obtained morphometrically (Weibel et al., Respir. Physiol. 54: 173-188, 1983). Arterial O2 saturation (SaO2) at various intensities of steady state exercise was calculated from DLO2 and measured values of O2 consumption, alveolar PO2, hemoglobin and arterial pH, and compared to observed SaO2. After pneumonectomy, SaO2 declined progressively with increasing exercise load. In all dogs, the observed pattern of arterial O2 saturation could be predicted from DLCO measured at similar work loads. The relationship between predicted (Pr) and observed (Ob) SaO2 is: SaO2(Pr) = 22.73 + 0.77SaO2(Ob), r = 0.92. The slope is significantly less than 1.0 (P less than 0.005), indicating that other factors must also contribute to arterial desaturation. We conclude that physiologic measurement of DLCO is a meaningful indicator of diffusion limitation to gas exchange. In the foxhound, a modest reduction in DLCO significantly impairs O2 transport during exercise; but other gas exchange abnormalities, e.g. ventilation perfusion inhomogeneity, must also develop.

Animals↗
PubMed1995

In vivo measurement of diffusion and pseudo-diffusion in skeletal muscle at rest and after exercise.

To investigate whether diffusion-related compartmentalization could be observed in skeletal muscle and whether this compartmentalization was affected by exercising, attenuation curves of signal against diffusion weighting were obtained in skeletal muscle of nine healthy volunteers at rest and after an exercise. Fifteen points were obtained for each diffusion curve with diffusion weightings ranging between approximately 0 and 560 x 10(6) s/m2. Data were fitted a biexponential model using three parameters to yield two apparent diffusion coefficients, a long one, ADCL, and a short one, ADCS, together with the fractional volume, fL, associated with the long one. At rest, values of parameters ADCL, ADCS, and fL were 46 x 10(-9) +/- 37 x 10(-9) m2/s, 1.74 x 10(-9) +/- 0.11 x 10(-9) m2/s, and 3.6 +/- 1.3%, respectively. After exercise, these values were 89 x 10(-9) +/- 37 x 10(-9) m2/s (p < .001 vs. rest), 1.94 x 10(-9) +/- 0.13 x 10(-9) m2/s (p < .001), and 5.2 +/- 1.3% (p < .05), respectively. These variations demonstrate significant changes in attenuation curves between rest and postexercise in skeletal muscle and may support an interpretation of the long and the short components in terms of a microvascular and an extra-microvascular compartments.

Adult↗
PubMed2005

Validation of a diffusion chamber as in vitro system for the analysis of compound diffusibility through cartilage tissue.

The validation of a diffusion chamber comprising a donor and a receptor side separated by a cartilage membrane was undertaken according to the basic principles described by Peng et al. (1998). The study had three targets: first to evaluate the chamber as in vitro system by the examination of the diffusibility of compound through bovine cartilage samples; second the analysis of the affinity of compound (RS-130830) to cartilage; third to test the influence of two pre-incubation periods (one or three nights) of the cartilage samples. The validation of the chamber as in vitro system for the analysis of compound diffusibility and affinity to cartilage was performed using membrane slices of fresh bovine cartilage and a hydroxamic acid derivative (RS-130830) known as matrix metalloproteinase inhibitor (MMPI). The influence of the pre-incubation of cartilage was also examined. Compound concentrations in donor, receptor and membrane were determined by high performance liquid chromatography-mass spectrometry (HPLC-MS). Diffusion could be demonstrated after 6 h and finally 24 h incubation: the compound concentration in the receptor increased from 0 to 35 microM (mean) while it decreased in the donor from 200 to 144 microM (mean). We also found compound in the cartilage membrane (approximately 1.2 nmol (mean)). Pre-incubation of cartilage samples in culture buffer is suitable as a storage procedure, since the results on the donor side only were influenced significantly but not for the receptor and the cartilage affinity. Thus, the system could clearly reflect relevant properties of the tested compound with regard to its diffusibility and affinity to cartilage tissue.

Cartilage↗
PubMed2006

In vivo isotropic 3D diffusion tensor mapping of the rat brain using diffusion-weighted 3D MP-RAGE MRI.

The purpose of this study was to examine the potential of diffusion-weighted (DW) three-dimensional (3D) MP-RAGE MRI for diffusion-tensor mapping of the rat brain in vivo. A DW-3D-MP-RAGE (3D-DWI) sequence was implemented at 2.0 T using six gradient orientations and a b value of 1000 s/mm2. In this sequence, the preparation sequence with a "90 degrees RF-motion proving gradient (MPG): MPG-180 degrees RF-MPG-90 degrees RF" pulse train (DW driven equilibrium Fourier transform) was used to sensitize the magnetization to diffusion. A centric k-space acquisition order was necessary to minimize saturation effects (T1 contamination) from tissues with short relaxation time. The image matrix was 128x128x128 (interpolated from 64x64x64 acquisitions), which resulted in small isotropic DW image data (voxel size: 0.273x0.273x0.273 mm3). Moreover, 3D-DWI-derived maps of the fractional anisotropy (FA), relative anisotropy (RA) and main-diffusion direction were completely free of susceptibility-induced signal losses and geometric distortions. Two well-known commissural fibers, the corpus callosum and anterior commissure, were indicated and shown to be in agreement with the locations of these known stereotaxic atlases. The experiment took 45 min, and shorter times should be possible in clinical application. The 3D-DWI sequence allows for in vivo 3D diffusion-tensor mapping of the rat brain without motion artifacts and susceptibility to distortion.

Animals↗
PubMed2006

Functional pathway-defined MRI diffusion measures reveal increased transverse diffusivity of water in multiple sclerosis.

The diffusion properties of water are sensitive to microscopic changes in the white matter of multiple sclerosis (MS) patients. Typical MRI measures of disease burden in MS demonstrate modest to poor correlation with disability. Functional MRI and DTI-based fiber tracking were used to define the interhemispheric white matter pathway connecting bilateral supplementary motor areas (SMA) in 16 MS patients sand 16 control subjects. Fractional anisotropy (FA), mean diffusivity (MD), longitudinal (lambda(1)) and transverse diffusivity (lambda(2)) were measured along this pathway in all subjects. Mean FA was 0.587 +/- 0.032 for patients and 0.608 +/- 0.020 for controls (P < 0.02). Mean MD was (0.821 +/- 0.055) x 10(-3) mm(2) s(-1) for patients and (0.770 +/- 0.020) x 10(-3) mm(2) s(-1) for controls (P < 0.004). Mean lambda(1) values were (1.462 +/- 0.099) x 10(-3) mm(2) s(-1) for patients and (1.400 +/- 0.034) x 10(-3) mm(2) s(-1) for controls (P < 0.02). Mean lambda(2) values were (0.500 +/- 0.047) x 10(-3) mm(2) s(-1) for patients and (0.454 +/- 0.027) x 10(-3) mm(2) s(-1) for controls (P < 0.001). In addition, the correlation between the Multiple Sclerosis Functional Composite (MSFC) and transverse diffusivity was -0.341 (P < 0.05). The component test of the MSFC most related to the SMA pathway studied with our MRI method (Nine-hole Peg Test) showed significant correlation with transverse diffusivity (r = 0.392, P < 0.02), indicating that probing functional pathways with MRI measures can lead to a better reflection of disease status.

Adult↗
PubMed1985

Diffusion of molecules on biological membranes of nonplanar form. II. Diffusion anisotropy.

Molecules diffusing on nonplanar membranes, which have different amounts of corrugation in different directions, may experience dissimilar diffusion coefficients in each direction. Smith et al. (1979, Proc. Natl. Acad. Sci. USA, 76:5641-5644) measured diffusion anisotropy on fibroblast cell membranes in which the ratio of the diffusion coefficients, in different directions, was 0.27. In the present work we calculate the effect of anisotropic corrugation on the rate of diffusion of molecules on membranes. We find that part of the anisotropy reported by Smith et al. (1979, Proc. Natl. Acad. Sci. USA, 76:5641-5644) can be explained by the membrane nonplanarity, and we present the way of calculating this geometric factor.

Diffusion↗
PubMed1985

Orientation constraints in diffusion-limited macromolecular association. The role of surface diffusion as a rate-enhancing mechanism.

Ligand association to a reactive site on a macromolecular surface could be very slow if the site is small. The effective capture radius of the reactive site can be significantly increased if the ligand can bind weakly to the nonspecific surface around the site and then slide in a two-dimensional diffusion along the surface. In this model, the diffusion along the surface has to be properly coupled with the free diffusion in solution and the effective bimolecular association rate constant to the reactive site can be calculated as a function of the nonspecific affinity. This is carried out both for a plane and spherical surface, modeling the association to a membrane receptor or to the catalytic site on an enzyme. The result of these calculations can be used to assign reasonable values to the parameters in the quasichemical approximation of K. Solc and W. H. Stockmayer (1973, Int. J. Chem. Kinet., 5:733-752). In this way a simple analytical expression can be derived for the diffusion-limited association rate constant of two asymmetrically reactive molecules, with or without surface diffusion contributing.

Binding Sites↗
PubMed1995

Effect of hydrodynamic interactions on the diffusion of integral membrane proteins: tracer diffusion in organelle and reconstituted membranes.

A persistent discrepancy exists between theoretical predictions and experimental observations for the diffusion coefficients of integral membrane proteins in lipid bilayers free of immobilized proteins. Current thermodynamic theories overestimate tracer diffusion coefficients at high area fractions. We explore the hypothesis that the combined effect of hydrodynamic and thermodynamic interactions reconciles theory with experiment. We have determined previously the short- and long-time tracer diffusivities, Ds and Dl, respectively, of integral membrane proteins in lipid bilayers as a function of their area fraction, phi. The results are based on two-particle hydrodynamic and thermodynamic interactions and are precise to O(phi). Here we extend the results for Dl to high phi by combining the hydrodynamic results for Ds into theories for Dl based on many-particle thermodynamic interactions. The results compare favorably with the experimental measurements of Dl as a function of protein area fraction for bacteriorhodopsin in reconstituted membranes and for complex III of the mitochondrial inner membrane. The agreement suggests that both hydrodynamic and thermodynamic interactions are important determinants of diffusion coefficients of proteins in lipid bilayers. Additional experiments are required to verify the role of hydrodynamic interactions in protein diffusion in reconstituted systems.

Bacteriorhodopsins↗
PubMed2003

Epidermoid of the lateral ventricle: evaluation with diffusion-weighted and diffusion tensor imaging.

We report of a large epidermoid tumor of the lateral ventricle in a 67-year-old man. Conventional imaging (CT, T1/T2, MRI) could not differentiate the tumor from the surrounding cerebral spinal fluid (CSF). On diffusion-weighted and diffusion anisotropy images the tumor was clearly seen as a hyperintense mass surrounded by hypointense CSF, highly suspected for epidermoid. Diffusion-tensor imaging (DTI) accentuated its lobulated structure and clearly demonstrated its relationship to neighboring white matter tracts. We suggest that in case of the suspicion of a space-occupying lesion in CSF containing areas, not distinguishable from CSF by conventional MR imaging, diffusion-weighted and diffusion-tensor MR imaging should be added.

Aged↗
PubMed2003

Diffusion-weighted magnetic resonance imaging for monitoring diffusion changes in rectal carcinoma during combined, preoperative chemoradiation: preliminary results of a prospective study.

PURPOSE: To evaluate the clinical value of diffusion-weighted magnetic resonance imaging (DW-MRI) to monitor response of primary carcinoma of the rectum to preoperative chemoradiation by measuring tumor apparent diffusion coefficient (ADC). MATERIALS AND METHODS: Diffusion data of nine patients undergoing preoperative combined chemoradiation for clinical staged T3, N(0-2), M(0) carcinoma of the rectum were analyzed. Diffusion-weighted echo-planar MR images were obtained prior to and at specified intervals during chemoradiation and ADCs calculated from acquired tumor images. RESULTS: Comparison of mean ADC and cumulative radiation dose showed a significant decrease of mean ADC at the 2nd (P = 0.028), 3rd (P = 0.012), and 4th (P = 0.008) weeks of treatment. Cytotoxic edema and fibrosis were considered as reasons for ADC decrease. CONCLUSION: This study demonstrated tumor ADC changes via detection of therapy-induced alterations in tumor water mobility. Our results indicate that diffusion-weighted imaging may be a valuable clinical tool to diagnose the early stage of radiation-induced fibrosis.

Adenocarcinoma↗
PubMed2002

Brain diffusion during hyperventilation: diffusion-weighted MR-monitoring in patients with temporal lobe epilepsy and in healthy volunteers.

Hyperventilation (HV) can be used to provoke epileptiform activity and occasionally seizures in generalised and in focal epilepsies. Based on the hypothesis that HV might alter brain diffusion in the epileptogenic areas of patients with temporal lobe epilepsy (TLE), we examined these alterations using quantitative diffusion MR imaging (DI) in four patients with TLE and unilateral hippocampal sclerosis (TLE-HS) and six patients with TLE without hippocampal sclerosis (TLE-pure), and in 10 healthy volunteers. Brain diffusion was measured at baseline and immediately after 4 min of HV. In all patients with TLE HV was repeated two times, 4 min each, followed by subsequent DI. The apparent diffusion coefficient (ADC) was quantified in predefined regions of interest. In controls, the ADC did not differ between baseline and HV and between right and left side. Compared to controls TLE-HS patients showed significantly higher ADC at baseline in the hippocampus of the ictogenic side (111+/-13 vs. 87.5+/-4.26 x 10(-5) mm(2)/s, P=0.029). During HV ADC decreased significantly in the ictogenic hippocampus compared to controls (-17.3+/-7.1 vs. -3.34+/-8.7, P=0.004). In TLE-pure patients ADC of the ictogenic hippocampus was higher than in normals (99.3+/-14.2 vs. 87.5+/-4.26 x 10(-5) mm(2)/s, P=0.031) but there was no significant decrease during HV. Serial HV did not further enhance this decrease. No significant HV-induced changes were seen in other brain areas. In conclusion, our results show that HV can induce dynamic changes of brain diffusion in patients with sclerotic hippocampi but not in non-sclerotic hippocampi. These findings may be utilized for lateralisation of the epileptogenic hippocampus during presurgical evaluation of TLE.

Adult↗
PubMed1999

Drug release from diffusion pellets coated with the aqueous ethyl cellulose dispersion Aquacoat ECD-30 and 20% dibutyl sebacate as plasticizer: partition mechanism and pore diffusion.

The release of the hydrophilic etofylline and the lipophilic propyphenazone (octanol/water partition coefficient PC = 0.35 and 119, respectively) from diffusion pellets coated with the aqueous ethyl cellulose dispersion Aquacoat ECD-30 and 20% dibutyl sebacate (DBS) as plasticizer is investigated as a function of pH. The relatively slow release is not constant, due to the broad distribution of different release rates within the pellet population and the non-linearity of the release of each diffusion pellet itself. The release proceeds according to a partition mechanism at a pH < 6. The partition mechanism is not influenced by the osmotic pressure difference between the release medium and the saturated solution within the diffusion pellets. The diffusion coefficients of different drugs in the plasticized coating are in the range 1 to 5 x 10(-8) cm2/s. At a of pH > 6 an additional hydrophilic pathway without partition exists if the diffusion pellets did not have any contact with an acidic medium. This is due to the strongly increased water uptake of more than 20% by the coatings as a consequence of the dissociation of carboxyl groups in the ethyl cellulose.

Cellulose↗
PubMed2003

Imaging of brain tumors with diffusion-weighted and diffusion tensor MR imaging.

The advent of diffusion-weighted MR imaging and diffusion tensor MR imaging has had little impact on brain tumor detection. Diffusion-weighted imaging has been effective in characterizing specific types of masses, particularly in distinguishing epidermoids from arachnoid cysts, and cystic tumors from intracerebral abscesses. Presurgical planning using tractography with diffusion tensor MR imaging, and perhaps the evaluation of tumor response to chemotherapy and radiation therapy with diffusion-weighted imaging, may become important applications in the near future.

Brain↗
PubMed1997

Measurement of biomolecular diffusion coefficients in blood plasma using two-dimensional 1H-1H diffusion-edited total-correlation NMR spectroscopy.

The use of two-dimensional diffusion-edited total-correlation NMR spectroscopy (DETOCSY) to measure diffusion coefficients of molecules in biofluids is demonstrated. The method takes advantage of the increased peak dispersion in a two-dimensional spectrum and allows the measurement of diffusion coefficients of individual molecules in complex biofluid samples in a condition close to their natural state. The NMR spectra can be edited on the basis of diffusion coefficient, and hence, approximate molecular size and this provides a qualitative means of simplifying the spectra for assignment purposes. The use of two-dimensional DETOCSY NMR spectra increases the probability that the individual cross-peaks arise from single components and hence allows single-exponential fitting of the magnetic field gradient dependence of cross-peak volumes. Interpretation of the derived diffusion coefficients improves the NMR resonance assignment process in complex biofluid mixtures by giving additional information on the molecular size. The DETOCSY approach also provides information on small molecule-macromolecule interactions such as the binding of drugs or endogenous species to serum proteins such as albumin.

Diffusion↗
PubMed1997

Diffusion coefficients of polymer chains in the diffusion layer adjacent to a swollen hydrophilic matrix.

A semiempirical formula was developed for the diffusion coefficient, Dp, of polymer within the diffusion layer adjacent to a matrix undergoing swelling and dissolution. This formula of Dp was a key element in a comprehensive mathematical model that described the swelling and dissolution of polymer and the release of drug. For hydroxypropyl methylcellulose (HPMC), Dp can be related to molecular weight (M) and concentration (Cp) of HPMC as Dp approximately 7.24 x 10(-5) M-0.6 [1+ 700(M/ 96000)0.7Cp/8]-2. Consistent with literature results, this formula yields Dp infinity M-0.64 under a dilute condition and Dp infinity Cp-7/4M-2 under a semidilute condition. Accordingly, the average Dp within the diffusion layer, was determined as infinity M-0.53, suggesting that the average mobility of HPMC within the diffusion layer decreases with M. This scaling law, combined with the relationship of Cp.dis infinity M-0.8, led to an important scaling law for matrix dissolution flux, Jp infinity M-1.15. The parameter Cp.dis, defined as the polymer disentanglement concentration or the polymer concentration at the tablet-diffusion layer interface, was a key parameter in that mathematical-model. The scaling law of Jp infinity M-1.15 indicates that the matrix dissolution rate decrease sharply with M at low M and gradually approaches a plateau as M becomes large. The plateau characteristics of Jp with M is consistent with the limiting drug release rate observed for HPMC-containing matrices, suggesting the critical role matrix dissolution plays in drug release.

Diffusion↗