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BACKGROUND AND PURPOSE: Some investigators have proposed that either calculated diffusion trace images or apparent diffusion coefficient (ADC) maps, which require imaging with multiple diffusion sensitivities and/or postacquisition image processing, are essential for the accurate interpretation of diffusion-weighted images in acute stroke because of the possible pitfalls of regional diffusion anisotropy, magnetic susceptibility artifacts, and confounding T2 effects, all of which alter signal on diffusion-weighted MR images. The purpose of our study was to compare the sensitivity, specificity, and accuracy of simple, orthogonal-axis diffusion-weighted imaging for the diagnosis of early cerebral infarction with three other sets of postacquisition-processed images: isotropic diffusion-weighted, diffusion trace-weighted, and diffusion trace images. METHODS: Twenty-six consecutive adult patients with signs and symptoms consistent with a clinical diagnosis of early cortical and/or subcortical cerebral infarction and 17 control subjects were studied with multisection, single-shot, spin-echo echo-planar diffusion-weighted imaging at 1.5 T to generate a set of three orthogonal-axis diffusion-weighted images. Isotropic diffusion-weighted, diffusion trace-weighted, and diffusion trace (mean ADC) images were then generated off-line and all four sets of images were interpreted blindly by two neuroradiologists. RESULTS: The average sensitivity, specificity, and accuracy for the orthogonal-axis diffusion-weighted images were 98.1%, 97.1%, and 97.7%, respectively. The average sensitivity, specificity, and accuracy for isotropic diffusion-weighted images were 88.5%, 100%, and 93% respectively. The average sensitivity, specificity, and accuracy for diffusion trace-weighted images were 82.7%, 73.6%, and 79.1%, respectively. The average sensitivity, specificity, and accuracy for diffusion trace images were 50.0%, 85.3%, and 64.0%, respectively. CONCLUSION: Orthogonal-axis diffusion-weighted images have the highest sensitivity and accuracy and very high specificity for early cerebral infarction. Our data contradict the contention that quantitative diffusion maps, requiring imaging with multiple diffusion sensitivities and/or subsequent image processing, are necessary for clinical stroke imaging.
PURPOSE: To define the principles and technical bases of diffusion weighted MR imaging of the brain and report our experience in the evaluation of selected brain disorders including age-related ischemic white matter changes (leukoaraiosis), neoplastic and infective cysts and wallerian degeneration. MATERIAL AND METHODS: Between May 1999 and June 2000 we examined seventeen patients: 10 patients with leukoaraiosis and deterioration of cognitive and motor function, 5 patients with focal cystic lesions (one anaplastic astrocytoma, one glioblastoma, one metastasis from squamous cell lung carcinoma, one pyogenic abscess and one case with cerebral tubercolosis) and 2 patients with wallerian degeneration (one with post-hemorrhagic degeneration of right corticospinal tract and one with post-traumatic degeneration of left optic tract). All patients underwent a standard cranial MR examination including SE T1-, proton density, T2-weighted, FLAIR and diffusion weighted images. Post-contrast T1-weighted sequences were also obtained in the patients with cystic lesions. Diffusion weighted images were acquired with double shot echoplanar sequences. Diffusion sensitizing gradient along the x, y and z axes and b values ranging 800 to 1200 s/mm2 were used. For each slice a set of three orthogonal diffusion "anisotropic" images, an "isotropic" image and a standard T2-weighted image were reconstructed. Postprocessing included generation of the apparent diffusion coefficient maps and of the "trace" image that reflects pixel by pixel the diffusional properties of water particles only. Values of mean diffusivity within regions of interest were computed in the "trace" image and compared with those obtained in contralateral brain areas. In patients with leukoaraiosis the diffusivity in posterior periventricular white matter was compared with that measured in 10 age-matched control subjects without leukoaraiosis. RESULTS: In patients with leukoaraiosis the areas of increased periventricular signal intensity on T2-weighted images showed a significantly higher (p < 0.001) diffusivity (mean values 124.7 +/- 21.3 x 10(-5) mm2/s) as compared to control subjects (mean values 85 +/- 7 x 10(-5) mm2/s). Diffusion weighted images in 2 patients revealed the presence of a small focal area of increased signal and reduced diffusivity in "trace" images consistent with recent ischemic lesion. In neoplastic cystic lesions the central necrotic/cystic content was always hypointense on diffusion weighted images and showed increased diffusivity on "trace" images. On the other hand the central necrotic content of the pyogenic brain abscess was hyperintense and showed low diffusivity. In patients with wallerian degeneration diffusion weighted images and "trace" images demonstrated loss of anisotropy and increased diffusivity in the affected white matter tract relative to the contralateral. DISCUSSION: The increased diffusivity observed in areas of leukoaraiosis and the identification of subclinical acute ischemic lesions by diffusion weighted images might be more useful than standard MR sequences for monitoring the disease progression. Diffusion weighted images allow differentiation of the different parts of focal cystic lesions (edema, solid and cystic/necrotic portion) and are useful to differentiate pyogenic brain abscess from necrotic tumors. In patients with wallerian degeneration the loss of anisotropy and the increase of diffusivity values in the affected tract are probably related to myelin breakdown and allow better recognition of the affected tract relative to standard MR images. CONCLUSIONS: Diffusion weighted MR imaging can be performed during a standard cranial MR examination and add useful clinical information in several brain disorders besides acute ischemic stroke.
Clinical diffusion magnetic resonance (MR) imaging in humans started in the last decade with the demonstration of the capabilities of this technique of depicting the anatomy of the white matter fibre tracts in the brain. Two main approaches in terms of reconstruction and evaluation of the images obtained with application of diffusion sensitising gradients to an echo planar imaging sequence are possible. The first approach consists of reconstruction of images in which the effect of white matter anisotropy is averaged -- known as the isotropic or diffusion weighted images, which are usually evaluated subjectively for possible areas of increased or decreased signal, reflecting restricted and facilitated diffusion, respectively. The second approach implies reconstruction of image maps of the apparent diffusion coefficient (ADC), in which the T2 weighting of the echo planar diffusion sequence is cancelled out, and their objective, i.e. numerical, evaluation with regions of interest or histogram analysis. This second approach enables a quantitative and reproducible assessment of the diffusion changes not only in areas exhibiting signal abnormality in conventional MR images but also in areas of normal signal. A further level of image post-processing requires the acquisition of images after application of sensitising gradients along at least 6 different spatial orientations and consists of computation of the diffusion tensor and reconstruction of maps of the mean diffusivity (D) and of the white matter anisotropic properties, usually in terms of fractional anisotropy (FA). Diffusion-weighted imaging is complementary to conventional MR imaging in the evaluation of the acute ischaemic stroke. The combination of diffusion and perfusion MR imaging has the potential of providing all the information necessary for the diagnosis and management of the individual patient with acute ischaemic stroke. Diffusion-weighted MR, in particular quantitative evaluation based on the diffusion tensor, has a fundamental role in the assessment of brain maturation and of white matter diseases in the fetus, in the neonate and in the child. Diffusion MR imaging enables a better characterisation of the lesions demonstrated by conventional MR imaging, for instance in the hypoxic-ischaemic encephalopathy, in infections and in the inherited metabolic diseases, and is particularly important for the longitudinal evaluation of these conditions. Diffusion-weighted MR imaging has an established role in the differential diagnosis between brain abscess and cystic tumour and between epidermoid tumour and arachnoid cyst. On the other hand, the results obtained with diffusion MR in the characterisation of type and extension of glioma do not yet allow decision making in the individual patient. Diffusion is one of the most relevant MR techniques to have contributed to a better understanding of the pathophysiological mechanisms of multiple sclerosis (MS). In fact, it improves the specificity of MR in characterising the different pathological substrata underlying the rather uniform lesion appearance on the conventional images and enables detection of damage in the normal-appearing white and grey matter. In MS patients the ADC or D values in the normal-appearing white matter are increased as compared to control values, albeit to a lesser degree than in the lesions demonstrated by T2-weighted images. In addition, the D of the normal appearing grey matter is increased in MS patients and this change correlates with the cognitive deficit of these patients. Histogram analysis in MS patients shows that the peak of the brain D is decreased and right-shifted, reflecting an increase of its value, and the two features correlate with the patient's clinical disability. Ageing is associated to a mild but significant increase of the brain ADC or D which is predominantly due to changes in the white matter. Region of interest and histogram studies have demonstrated that D or ADC are increased in either the areas of leukoaraiosis or the normal-appearing white matter in patients with inherited cerebral autosomal dominant arteriopathy with subcortical infarcts and stroke or sporadic ischaemic leukoencephalopathy. Diffusion changes might be a more sensitive marker for progression of the disease than conventional imaging findings. In neurodegenerative diseases of the central nervous system such as Alzheimer's disease, Huntington's disease, hereditary ataxias and motor neuron disease, quantitative diffusion MR demonstrates the cortical and subcortical grey matter damage, which is reflected in a regional increase of D or ADC, but also reveals the concomitant white matter changes that are associated with an increase in D or ADC and decrease in FA. In all these diseases the diffusion changes are correlated to the clinical deficit and are potentially useful for early diagnosis and longitudinal evaluation, especially in the context of pharmacological trials.
Water dehydration experiments on rhyolitic glasses have been carried out at 400-550 degrees C under a N2 atmosphere. Concentration profiles of both H2O molecules and OH groups were measured by Fourier transform infrared spectroscopy. As found in previous studies of water diffusion in rhyolitic melts, the measured total water concentration profiles do not match expectations based on a single constant diffusion coefficient for total water. The diffusion of total water is described by considering the diffusion of both H2O molecules and OH groups and the reaction between them. The concentration relationship between the two species has been obtained from direct infrared measurement on quenched experimental charges. The quench is inferred to be rapid enough to preserve concentrations of both species at experimental temperature based on experimental results designed to examine reaction kinetics. The measured species concentrations along diffusion profiles show that local equilibrium between H2O and OH is approximately reached at high temperatures and high water contents. However, at lower water content or lower temperature, local equilibrium is not reached. In treating the diffusion problem, this disequilibrium effect is partially compensated by using empirical relationships between H2O and OH concentrations based on measurements, instead of using an equilibrium relationship. It is thus possible to obtain diffusion coefficients for both species from their concentration profiles. The diffusion coefficient of OH is found to be negligible compared to that of H2O at 403-530 degrees C (DOH < 0.02 DH2O and could be much smaller); i.e., H2O is the dominant diffusing species even at total water concentration as low as 0.2 wt%. The variation of OH concentration along the diffusion profile is inferred to be due to the local interconversion between OH groups and H2O molecules; the reaction also provides the diffusing H2O species. DH20 values are found to vary by less than a factor of 2 over a total water concentration range of 0.2 to 1.7 wt%. This simple model, coupled with the assumption of local equilibrium between H2O and OH, yields a very good fit to the data from diffusion-couple experiments of LAPHAM et al. (1984) at 850 degrees C. When our data are combined with DH2O obtained from that fit, DH2O (in m2/s) is given by: ln DH2O = (-14.59 +/- 1.59) - (103000 +/- 5000) / RT; 673 K < or = T < or = 1123 K, where T is temperature in K and R is the gas constant in J K-1 mol-1. This equation also approximates well DH2O values calculated from previous measurements of concentration-dependent bulk water diffusion coefficients of KARSTEN et al. (1982). The diffusion of H2O is also compared to the diffusion of the noble gas elements. The activation energy for diffusion in rhyolitic glasses is well correlated with neutral species radii of He, Ne, H2O, and Ar. This supports the contention that the diffusing species for "water" is neutral molecular H2O. The role of speciation may also be important in understanding the diffusion of many other multi-species components, and the effect can be treated in a similar fashion as that during water diffusion.
OBJECTIVE: Our objective was to evaluate a new scanning method, MR line scan diffusion imaging, and assess the apparent diffusion coefficient in the brains of healthy subjects and stroke patients. SUBJECTS AND METHODS: Line scan diffusion imaging without cardiac gating or head restraints was implemented on low- (0.5 T) and medium- (1.5 T) field-strength scanners with conventional hardware. Diffusion-weighted images were obtained in six healthy subjects and eight stroke patients. Unidirectional diffusion encoding was used for fast localization of stroke lesions. For further characterization, orthogonal diffusion encoding was applied, and the trace of the apparent diffusion coefficient was calculated. Single-shot diffusion-weighted echoplanar imaging served as the reference standard. For healthy subjects, imaging was repeated four times on each scanner. Mean and relative precision of the apparent diffusion coefficient trace values were calculated for each pixel. In stroke lesions and adjacent normal tissue, apparent diffusion coefficient trace values were determined. RESULTS: In the 108 scans obtained, line scan diffusion imaging proved to be robust, virtually free of artifact (independent of slice location and orientation), reproducible, and rapid for localization of a stroke. Scan time for 14 slices at 7-mm thickness was 8 min at 0.5 T and 7 min at 1.5 T. Image qualities with line scan diffusion imaging and single-shot diffusion-weighted echoplanar imaging were comparable. At 1.5 T, precision was essentially the same for line scan diffusion imaging (4.3%) and echoplanar imaging (4.7%). With line scan diffusion imaging at 0.5 T and 1.5 T, normal paraventricular apparent diffusion coefficient trace values averaged 0.71 microm2/msec, and with echoplanar imaging these values averaged 0.69 microm2/msec. In acute lesions apparent diffusion coefficient trace values were low, and in chronic lesions these values were high. CONCLUSION: Line scan diffusion imaging on low- and medium-field-strength MR scanners equipped with conventional hardware was reliable and practical for measuring brain apparent diffusion values, which can be applied to the early diagnosis, and hence timely management, of stroke.
UNLABELLED: There is no consensus on the pathogenesis and incidence of diffusion disorder in chronic liver diseases. It is supposed that the pathogenic mechanisms responsible for the reduction of diffusion capacity in liver diseases are multifactorial, including: ventilation-perfusion mismatching, diffuse interstitial pulmonary diseases and reduced transitory time in hyperperfused lung areas [1]. The increase of diffusion of oxygen molecules within dilated blood vessels during the inspiration of 100% O2 in patients with liver cirrhosis is called "diffusion-perfusion defect" or "alveolar-capillary oxygen disequilibrium" [3]. AIM OF THE STUDY: The aim of the study was to determine how the inadequate pulmonary perfusion and intrapulmonary vascular dilatation affect the diffusion disorder in liver cirrhosis. One of the aims was to establish the correlative relations between diffusion disorder and cirrhosis grade according to Child classification. METHOD: The study was performed over the period 1997-2000, including 50 patients with liver cirrhosis. They were diagnosed and treated at the Department of Hepatology and Gastroenterology, Clinical Centre of Serbia, Belgrade. Functional and morphological studies were based on the laboratory tests of liver function and histopathologic findings. The grade of liver insufficiency (A, B or C) was determined according to Child-Pugh score. The alveolar-arterial gradient was calculated from the gas analysis in the arterial blood, in supine and sitting position, in conditions of room air breathing and 100% oxygen. Diffusion parameters were measured by method of single inspiration of carbon monoxide. Spirometry and body pletismography were used for determination of ventilatory disorders. RESULTS: The reduced transfer factor (TLco) was recorded in 27 (54%) patients, while reduced transfer coefficient (Kco) was found in 33 (66%) patients. The mean TLco value was 7.27 (73%) in Child group A (n = 16); 6.98 (73%) in Child B group (n = 20); 6.65 (71%) in Child C group (n = 14). The comparison of these values in Child A, B and C groups by t-test showed no statistically significant difference (p > 0.05). The mean value of TLco was 7.24 (73%) in patients with spider naevi (n = 19), and 6.86 (72%) in patients without spiders (n = 31), without statistically significant difference among these mean values (t-test, p = 0.52). The restrictive ventilation disorders were present in 14 (28%) patients, while the reduced transfer factor was found in 27 (54%) patients. The incidences of restrictive ventilatory disorders and reduced transfer factor were compared (x2-test). The incidence of TLco, decrease was more significant than the incidence of restrictive disorders (p = 0.0082). The elevated alveolar-arterial gradient was present in 29 (58%) patients. No significant difference was found between alveolar-arterial gradient and diffusion disorders (x2-test, p = 0.62). DISCUSSION: There is no consensus on the incidence of diffusion disorder in chronic liver diseases. Robin et al. 1982 reported that only 20% of patients with liver cirrhosis had pathological diffusion, presuming that it was induced by reduction of transit time in hyperperfused lung regions [8]. Hourani et al. 1991 reported that the most frequent functional disorder was TLco decrease (52%) in the group of 116 patients planned for liver transplantation [1]. Krowka et al. 1992 found the lowest values of diffusion capacity in patients with Child C grade of liver cirrhosis [11]. Our results confirm the high incidence (54%) of diffusion disorder in liver cirrhosis, but the grade of liver insufficiency (Child score) does not correlate with the reduction of diffusion capacity. Several studies have reported various degrees of restrictive ventilatory disorders, with disproportionately higher reduction of TLco [1, 14, 15]. Our results confirm the higher incidence of diffusion disorder compared to restrictive disorders. Recent studies report that the isolated reduction of TLco is caused mainly by the intrapulmonary vascular dilatation, but the other factors also play the role (diffuse interstitial lung diseases without restrictive disorders in early stages, the passage through nonventilated alveoli, i.e. ventilatory perfusion mismatching and/or the other pulmonary vascular diseases) [16]. CONCLUSION: The impairment of diffusion capacity is a very common functional disorder in patients with liver cirrhosis and portal hypertension. Disproportionately, higher reduction of the transfer factor compared to restrictive ventilatory disorder, suggests that diffusion disorder is primarily induced by inadequate pulmonary perfusion. The isolated reduction of the transfer factor cannot be only explained in each case by intrapulmonary vascular dilatation.
Diffusion is a measure of motion freedom and is a sensitive parameter to characterize the tissue at the microscopic level. The methods of measuring in vivo diffusion by magnetic resonance imaging (MRI) have been based mainly on the addition of two motion-probing gradients (MPG) to the spin echo sequence to produce signal attenuation for the spins moving at random. The resultant MR images reflect the intravoxel incoherent motions (IVIM), which contain both water molecule diffusion and perfusion in the capillary network, and can be quantified by an apparent diffusion coefficient (ADC). Diffusion weighted MRI, acquired from IVIM MR imaging by the addition of the very strong MPG predicate water diffusion and anisotropy. High signal or reduced ADC can be observed in case of the slower diffusion. The anisotropy depends upon the orientation of the subjects and the gradients. Greater signal attenuation (faster diffusion) can be observed when the relative orientation of white matter tracts to the MPG is parallel as compared to that obtained with a perpendicular alignment. This anisotropy may preclude the detection or delineation of an ischemic lesion. Diffusion tensor trace has been designated to eliminate this anisotropy effect. In ischemic animal models, low signal (fast diffusion) and high signal (slow diffusion) have been noted in the vasogenic edema and cytotoxic edema, respectively. High signal appears only in case of cerebral blood flow below 15-20 ml/100 g per minute, a value identical to the threshold of tissue at high energetic metabolism and ion homeostasis. ADC value decreases following the cerebral vessel occlusion, or remains unchanged when collateral circulation develops. It has been speculated that reduction in ADC reflects the water shift from extracellular space to intracellular space due to the membrane permeability and/or intracellular osmolality increase. These results suggest that diffusion weighted MRI correlates well with the cell metabolism, and cytotoxic edema plays an important role in the acute cerebral stroke. In clinical setting of acute cerebral ischemia, diffusion weighted MRI may detect superacute infarction by showing high signal (slower ADC) over the 6 hours following the insult, whereas conventional MRI generally fails to do so. In chronic liquefied cerebral infarction, increased ADC, or attenuated signal are the most frequent findings, suggestive of an elevated diffusion. Therefore, diffusion weighted MRI improves early diagnosis of stroke and help differentiate acute from chronic stroke. One disadvantage of diffusion weighted MRI is motion artifact, which may be reduced by the introduction of a navigator echo to correct for the phase shift caused by the first imaging echo, or by the utility of ultrafast imaging technique, such as echo planar. Another shortcomings is the susceptibility artifact incorporating the diffusion weighted MRI. The eddy current may also result from the strong gradients, producing shiftlike artifact. Such artifacts can be compensated for by appropriate shaping of the current pulses sent into the gradient coils, or by use of shielded gradients. As with rapid progresses in perfusion imaging of ischemia penumbra, misery perfusion and luxury perfusion, new insight into the diffusion weighted MRI will be significant.
Water diffusion in brain tissue is affected by the presence of barriers to translational motion such as cell membranes and myelin fibers. The measured water apparent diffusion coefficient (ADC) value is therefore frequently anisotropic and varies depending upon the orientation of restricting barriers (such as white matter tracts) relative to the diffusion-sensitive-gradient direction. Anisotropic water diffusion can be specified using indices of diffusion anisotropy [e.g. standard deviation of the individual ADC values, fractional anisotropy (FA), lattice index (LI)], which are derived from measurements of the full diffusion tensor. The rotationally invariant nature of particular diffusion anisotropy indices (e.g. FA, LI) allows orientation-independent comparisons of these parameters between different subjects. Pathophysiological processes (such as cerebral ischemia) that modify the integrity of the tissue microstructure result in significant alterations in tissue anisotropy and make this metric a useful endpoint for characterizing the temporal evolution of the disease. Diffusion-tensor imaging (DTI) studies of both experimental and human stroke suggest that DTI may provide additional information about the evolution of the disease that is not available from diffusion-weighted MRI (DWI) alone. Acute reductions in the average diffusivity [ = (lambda(1) + lambda(2) + lambda(3))/3 where lambda(1), lambda(2), and lambda(3) are the eigenvalues of the diffusion tensor] following the onset of cerebral ischemia are often accompanied by increases in diffusion anisotropy. In the transition from acute to sub-acute and chronic stroke, renormalizes and subsequently increases whereas diffusion anisotropy measures (e.g. FA) decline and remained reduced in chronic infarcts. Overall isotropic ADC changes during infarct evolution have been observed to be greater in white matter (WM) than in gray matter (GM) lesions (although there have been conflicting reports on this issue) and GM lesions tend to renormalize prior to WM lesions as the infarct evolves. Ischemic WM exhibits a significant decrease in diffusion anisotropy (relative to normal WM) during ischemic evolution whereas that of ischemic GM remains statistically unchanged. Furthermore, the percentage decrease in ischemic WM is largely determined by reductions in lambda(1), the eigenvalue that coincides with the long axis of the WM fiber tract. Variations in unidirectional ADC or over the ischemic time course limit the usefulness of this parameter alone as a predictor of ischemic injury. Consequently, ADC information has been combined with that of other MR parameters (including DTI) to unambiguously stage and predict ischemic brain injury over its entire temporal evolution. Combined and diffusion anisotropy measurements have identified three phases of diffusion abnormality: (1) reduced and elevated anisotropy; (2) reduced and reduced anisotropy; and (3) elevated and reduced anisotropy. However, variations in the differential patterns of and diffusion anisotropy evolution have been observed by a number of investigators and more work is needed to clarify the role of these measurements in characterizing the severity of the ischemic insult as well as the potential outcome in response to the initial ischemic injury. The use of DTI, in combination with more sophisticated analysis methods for performing multiparametric segmentation, such as multispectral analysis, may enhance the use of MRI for accurate diagnosis and prognosis of stroke. Furthermore, these techniques may also play an important role in the clinical evaluation of new stroke treatments.
The ability of water and solutes to move through the cartilage matrix is important to the normal function of cartilage and is presumed to be altered in degenerative diseases of cartilage such as osteoarthritis and rheumatoid arthritis. Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) techniques were used to measure a self diffusion coefficient (D) for small solutes in samples of explanted cartilage for diffusion times ranging from 13 ms to 2 s. With a diffusion time of 13 ms, the intratissue diffusivity of several small solutes (water, Na+, Li+, and CF3CO2-) was found consistently to be about 60% of the diffusivity of the same species in free solution. Equilibration of the samples at low pH (which titrates the charge groups so that the net matrix charge of -300 mM at pH 8 becomes approximately -50 mM at pH 2) did not affect the diffusivity of water or Na+. These data, and the similarity between the D in cartilage relative to free solution for water, anions, and cations, are consistent with the view that charge is not an important determinant of the intratissue diffusivity of small solutes in cartilage. With 35% compression, the diffusivity of water and Li+ dropped by 19 and 39%, respectively. In contrast, the diffusivity of water increased by 20% after treatment with trypsin (to remove the proteoglycans and noncollagenous proteins). These data and the lack of an effect of charge on diffusivity are consistent with D being dependent on the composition and density of the solid tissue matrix. A series of diffusion-weighted proton images demonstrated that D could be measured on a localized basis and that changes in D associated with an enzymatically depleted matrix could be clearly observed. Finally, evidence of restriction to diffusion within the tissue was found with studies in which D was measured as a function of diffusion time. The measured D for water in cartilage decreased with diffusion times ranging from 25 ms to 2 s, at which point the measured D was roughly 40% of the diffusivity in free solution. Although changes in matrix density by compression or digestion with trypsin led to a decrease or increase, respectively, in the measured D, the functional change in measured diffusivity with diffusion time remained essentially unchanged. In a different type of study, in which bulk transport could be observed over long periods of time, cartilage was submerged in 99% D2O and MRI studies were performed to demonstrate the bulk movement of water out of the cartilage matrix.(ABSTRACT TRUNCATED AT 400 WORDS)
The diffusion tensor is currently the accepted model of diffusion in biological tissues. The measured diffusion behavior may be more complex when two or more distinct tissues with different diffusion tensors occupy the same voxel. In this study, a partial volume model of MRI signal behavior for two diffusion-tensor compartments is presented. Simulations using this model demonstrate that the conventional single diffusion tensor model could lead to highly variable and inaccurate measurements of diffusion behavior. The differences between the single and two-tensor models depend on the orientations, fractions, and exchange between the two diffusion tensor compartments, as well as the diffusion-tensor encoding technique and diffusion-weighting that is used in the measurements. The current single compartment model's inaccuracies could cause diffusion-based characterization of cerebral ischemia and white matter connectivity to be incorrect. A diffusion-tensor MRI imaging experiment on a normal human brain revealed significant partial volume effects between oblique white matter regions when using very large voxels and large diffusion-weighting (b approximately 2.69 x 10(3) sec/mm(2)). However, the apparent partial volume effects in white matter decreased significantly when smaller voxel dimensions were used. For diffusion tensor studies obtained using typical diffusion-weighting values (b approximately 1 x 10(3) sec/mm(2)) partial volume effects are much more difficult to detect and resolve. More accurate measurements of multiple diffusion compartments may lead to improved confidence in diffusion measurements for clinical applications.
Diffusion measurements were performed on water and N-acetyl aspartate (NAA) molecules in excised brain tissue using a wide range of b-values (up to 28.3 x 10(6) and 35.8 x 10(6) s cm-2 for water and NAA, respectively). The attenuation of the signals of water and NAA due to diffusion was measured at fixed diffusion times (tD). These measurements, in which the echo time (TE) was set to 70 ms, were repeated for several diffusion times ranging from 35 to 305 ms. Signal attenuations were fitted to mono-, bi-, and triexponential functions to obtain the apparent diffusion coefficients (ADCs) of these molecules at each diffusion time. From these experiments the following observations and conclusions were made: (1) Signal attenuation of water and NAA due to diffusion over the entire range of b values examined is not monoexponential and the extracted ADCs depend on the diffusion time; (2) In the case of water the experimental data are best fitted by a triexponential function, while for b values up to 1 x 10(6) s cm-2, a biexponential function seems to reproduce the experimental data as well as the triexponential function; (3) If only the low range of b values are fitted (up to 0.5 x 10(6) s cm-2) signal attenuation of water is monoexponential and insensitive to tD; (4) Water ADCs decreased with the increase in tD but the relative population of the fast diffusing component increases such that at a tD of 305 ms there is nearly a single population; (5) The major fast diffusion component of the water shows only very limited restriction; (6) NAA signal attenuation is biexponential and analysis of the low b-value range gives only monoexponential decay, but the obtained ADC is sensitive to the diffusion time; (7) The ADCs obtained from fitting the data with a biexponential function decrease as diffusion time increases; (8) The relative population of the slow-diffusing component decreases with increasing tD; (9) Both the fast and the slow diffusing components of NAA show a considerable restriction by what seems to be a nonpermeable barrier from which two compartments, one of 7-8 micron and one of approximately 1 micron, were calculated using the Einstein equation. It is suggested that the two compartments represent the NAA in cell bodies and in the intra-axonal space. The effect of the range of the b value used in the diffusion experiments on the results is discussed and used to reconcile some of the apparent discrepancies obtained in different experiments concerning water diffusion in brain tissue. The potential of NAA diffusion experiments to probe cellular structure is discussed.
An important but poorly understood factor that affects diffusion rates is the role of speciation during diffusion of a multi-species component. The diffusion of such a component is complicated by the different diffusion coefficient of each species and the interconversion reactions among the species. These complexities can be treated by a diffusion equation that incorporates the diffusive fluxes of all species contributing to the concentration of the component. The effects of speciation on the diffusion of the component can be investigated experimentally in some simple cases by measuring concentration profiles of all species developed during diffusion experiments or by studying some of their other consequences. Experimental data on water diffusion in rhyolitic glasses indicate that although dissolved water is present as two species, H2O molecules and OH groups, molecular H2O is the dominant diffusing species at very low to high water concentrations. This explains the apparently complex behavior of water diffusion. Experimental data on oxygen diffusion in some silicates using 18O tracers in the form of H2(18O) are consistent with the idea that 18O transport is dominated by diffusion of H2O molecules even at lower water contents (ppm or less). This explains why oxygen transport depends on the presence of water and generally depends on water fugacity linearly. For this mode of oxygen transport, there is a simple theoretical relationship between the effective total oxygen diffusion coefficient and the total water diffusion coefficient that is a function of only the water concentration of the silicate at low water content. This relationship appears to describe quantitatively the existing data over a wide range in water contents and diffusion coefficients in several phases.
Lateral diffusion of membrane components makes possible any in-plane membrane reaction and has a key role in signaling in cell membranes. In this report the equilibrium lateral diffusion of intrinsic molecules in an equimolar DMPC/DSPC mixture is simulated using a thoroughly tested two-state model of two-component phospholipid bilayers. The model has been successful in calculating the excess heat capacity function, the most frequent center-to-center distances between DSPC clusters, and the fractal dimensions of gel clusters (Sugar, I. P., Thompson, T. E., Biltonen, R. L. Biophys. J. 1999, 76, 2099-2110). In the gel/fluid mixed phase region, a diffusing intrinsic molecule may change its state from fluid to gel (or from gel to fluid) at any time. A common characterization of the diffusion of intrinsic molecules is given by the simulated average first-passage time curves. We find that these curves can be described as power functions containing two parameters, alpha and beta, except near the percolation threshold of gel/fluid or compositional clusters. We find also that the intrinsic molecules are involved in approximately normal diffusion, i.e., beta approximately 2 in the extreme gel and fluid phase regions, while in the gel/fluid and gel/gel mixed phase regions the diffusion is anomalous, i.e., beta not equal 2. In the mixed phase regions, when the initial local state of the diffusing molecule is not specified, each component is involved in sub-diffusion (beta > 2). In the gel/fluid mixed phase region molecules situated initially inside a fluid cluster are involved in sub-diffusion, but DMPC molecules situated initially inside a gel cluster are involved in super-diffusion (beta < 2). The possibility of anomalous diffusion in membranes apparently arises because the diffusing molecule visits a variety of different environments characterized by its relative proximity to various membrane components. The diffusion is actually anomalous when the components of the bilayer are nonrandomly distributed. The deviation from random distribution is strongly correlated with beta. Similar to the results of the NMR experiments, the calculated relative diffusion coefficient continuously decreases in the gel/fluid mixed phase region with decreasing temperature. In apparent contradiction, diffusion measured by fluorescence recovery after photobleaching (FRAP) demonstrates the existence of a threshold temperature, below which long-range diffusion of FRAP probe molecules is essentially blocked. This threshold temperature is highly correlated with the percolation temperature of gel clusters.
PURPOSE: To quantify age-related changes of the average diffusion coefficient value in normal adult brain using orientation-independent diffusion tensor trace mapping and to address the methodological influences on diffusion quantification. MATERIAL AND METHODS: Fifty-four normal subjects (aged 20-79 years) were studied on a 1.5-T whole-body MR medical unit using a diffusion-weighted single-shot echo-planar imaging technique. Orientation-independent diffusion tensor trace maps were constructed for each subject using diffusion-weighted MR measurements in four different directions using a tetrahedral gradient combination pattern. The global average (including cerebral spinal fluid) and the tissue average of diffusion coefficients in adult brains were determined by analyzing the diffusion coefficient distribution histogram for the entire brain. Methodological influences on the measured diffusion coefficient were also investigated by comparing the results obtained using different experimental settings. RESULTS: Both global and tissue averages of the diffusion coefficient are significantly correlated with age (p<0.03). The global average of the diffusion coefficient increases 3% per decade after the age of 40, whereas the increase in the tissue average of diffusion coefficient is about 1% per decade. Experimental settings for self-diffusion measurements, such as data acquisition methods and number of b-values, can slightly influence the statistical distribution histogram of the diffusion tensor trace and its average value. CONCLUSION: Increased average diffusion coefficient in adult brains with aging are consistent with findings regarding structural changes in the brain that have been associated with aging. The study also demonstrates that it is desirable to use the same experimental parameters for diffusion coefficient quantification when comparing between different subjects and groups of interest.
A novel method was developed for studying the diffusion of proteins through poly(D,L-lactide-co-glycolide) (PLG), using a diffusion cell. To develop improved formulations for the controlled release of encapsulated drugs it is important to understand the underlying release mechanisms. When using low-molecular-weight PLG as the release-controlling polymer, diffusion through the pores is often proposed as the main release mechanism. The experimental set-up and method of determining the diffusion coefficient were thoroughly evaluated with regard to the reliability and the influence of the stirring rate. A procedure for spraying thin films of PLG onto a filter, which could be placed in the diffusion cell, was optimized. The method was then applied to the determination of the diffusion coefficient of human growth hormone (hGH) through a PLG film. The results show that the method enables measurements of the diffusion coefficient through the polymer film. Neither the stirring rate nor the concentration of hGH influenced the diffusion coefficient. The diffusion coefficient of hGH through degraded PLG films was 5.0 x 10(-13) m2/s, which is in the range that could be expected, i.e., several orders of magnitude smaller than its the diffusivity in pure water. The reproducibility was good, considering the dynamic properties of PLG, i.e., the difference in diffusion coefficients, at, for example, different stages of degradation and for different compositions of PLG, is expected to be much higher. The variation is probably also present in PLG films used for controlled-release formulations. Although the PLG film contains a large amount of water, a considerable time elapsed before pores of sufficient size formed and diffusion through the film started. In two-component diffusion experiments, the difference in diffusion rate did not correspond to the difference in molecular weight of the solutes, indicating a size exclusion effect. This method can be used to study the effect of changes in the formulation specification. By studying the change in the diffusion coefficient through the degradation process of PLG, or similar polymers, a better understanding of diffusion and, thus, also release mechanisms can be obtained.
PURPOSE: To determine the nature of hyaline membranes in different manifestations of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory distress syndrome], and idiopathic [acute interstitial pneumonia]. MATERIALS AND METHODS: Pulmonary specimens were obtained from 17 patients with acute respiratory distress syndrome and 9 patients with acute interstitial pneumonia. They were separated into 3 different groups: (a) pulmonary diffuse alveolar damage (pDAD) (n = 8), consisting only of pneumonia cases; (b) extrapulmonary diffuse alveolar damage (expDAI) (n = 9), consisting of sepsis and septic shock cases; and (c) idiopathic diffuse alveolar damage (iDAD) (n = 9), consisting of idiopathic cases (acute interstitial pneumonia). Hyaline membranes, the hallmark of the diffuse alveolar damage histological pattern, were examined using various kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP-A), cytokeratin 7 (CK7), cytokeratin 8 (CK8), alpha smooth muscle actin (alpha-SMA), cytokeratin AE1/AE3 (AE1/AE3), and factor VIII-related antigen (factor VIII). RESULTS: Pulmonary diffuse alveolar damage showed the largest quantity of hyaline membranes (12.65% +/- 3.24%), while extrapulmonary diffuse alveolar damage (9.52% +/- 3.64%) and idiopathic diffuse alveolar damage (7.34% +/- 2.11%) showed intermediate and lower amounts, respectively, with the difference being statistically significant between pulmonary and idiopathic diffuse alveolar damage (P < 0.05). No significant difference was found for hyaline membranes Sp-A immunostaining among pulmonary (15.36% +/- 3.12%), extrapulmonary (16.12% +/- 4.58%), and idiopathic (13.74 +/- 4.20%) diffuse alveolar damage groups. Regarding factor VIII, we found that idiopathic diffuse alveolar damage presented larger amounts of immunostained hyaline membranes (14.12% +/- 6.25%) than extrapulmonary diffuse alveolar damage (3.93% +/- 2.86%), with this difference being statistically significant (P < 0.001). Equally significant was the difference for progressive decrease of cytokeratin AE1/AE3 immunostaining in hyaline membranes present in the extrapulmonary diffuse alveolar damage (5.42% +/- 2.80%) and idiopathic diffuse alveolar damage (0.47% +/- 0.81%) groups (P < 0.001). None of the groups stained for cytokeratin CK-7, CK-8, vimentin, or a anti-smooth muscle actin. CONCLUSIONS: This study showed that only the epithelial/endothelial components (SP-A, factor VIII, and AE1/AE3) of the alveolar/capillary barrier are present in hyaline membranes formation in the 3 groups of patients with diffuse alveolar damage. The significant difference in the expression of factor VIII-related antigen and cytokeratin AE1/AE3 in the expDA versus iDAD groups as well as the significant difference in the amount of hyaline membranes present in the pDAD versus iDAD groups are suggestive of a local and specific lesion with different pathways (direct, indirect, or idiopathic), depending on the type of diffuse alveolar damage.