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We believe that osmosis has been overlooked as a possible mechanism for observed low-salinity enhanced-oil-recovery (EOR) effects. Osmosis can occur in an oil/water/rock system when injecting low-salinity water, because the system is full of an excellent semipermeable membrane-the oil itself.In the present work, water transport through oil films was visualized both in 2D micromodels and in sandstone cores imaged in a microcomputed tomography (CT). After treating these model systems with hexamethyldisilazane (HMDS) to render them more oil-wet, water became discontinuous, and it was possible to establish osmotic gradients. Either expansion or contraction of the connate water was observed, depending on the direction of the imposed salinity gradient.Because osmosis could be the underlying mechanism for lowsalinity EOR, two changes in research strategy are proposed: Most importantly, the use of spontaneous-imbibition tests as evidence for wettability alteration in low-salinity water should be critically reinvestigated. This is because observed production could have stemmed from "osmotic expansion" of the connate water rather than wettability change. Second, much research focus should be shifted from sandstone reservoirs to fractured oil-wet carbonates. Osmosis potentially yields larger responses for the latter reservoir type, whereas from a mechanistic perspective the reason behind low-salinity EOR functioning in both sandstones and carbonates deserves further attention.

Purpose:To evaluate manganese (Mn 2ϩ )-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI) as tools for detection of axonal injury and regeneration after intravitreal peripheral nerve graft (PNG) implantation in the rat optic nerve (ON). Materials and Methods:In adult Fischer rats, retinal ganglion cell (RGC) survival was evaluated in Flurogold (FG) back-filled retinal whole mounts after ON crush (ONC), intravitreal PNG, and intravitreal MnCl 2 injection (150 nmol) at 0 and 20 days post lesion (dpl). MEMRI and echoplanar DTI (DTI-EPI) was obtained of noninjured ON one day after intravitreal MnCl 2 injection, and at 1 and 21 dpl after ONC, intravitreal PNG, and intravitreal MnCl 2 injections given at 0 and 20 dpl. GAP-43 immunohistochemistry was performed after the last MRI.Results: ONC reduced RGC density in retina by 94% at 21 dpl compared to noninjured ON without MnCl 2 injections. Both intravitreal PNG and intravitreal MnCl 2 injections improved RGC survival in retina, which was reduced by 90% (ONCϩMnCl 2 ), 82% (ONCϩPNG), and 74% (ONCϩPNGϩMnCl 2 ) compared to noninjured ON. DTIderived parameters (fractional anisotropy [FA], mean diffusivity, axial diffusivity , and radial diffusivity Ќ ) were unaffected by the presence of Mn 2ϩ in the ON. At 1 dpl, CNR MEMRI and were reduced at the injury site, while at 21 dpl they were increased at the injury site compared to values measured at 1 dpl. GAP-43 immunoreactive axons were present in the ON distal to the ONC injury site. Conclusion:MEMRI and DTI enabled detection of functional and structural degradation after rat ON injury, and there was correlation between the MRI-derived and immunohistochemical measures of axon regeneration. UNLIKE AXONS IN THE PERIPHERAL NERVOUS SYS-TEM, those in the central nervous system (CNS) of adult mammals do not regenerate after injury (1,2). Failure to regenerate is attributed to a combination of axon growth arrest by myelin-associated and scar-derived inhibitory molecules (3,4), and to the absence of growth-promoting neurotrophic factors in the adult CNS (5). Several therapeutic interventions have been tested in animal models to try to promote axon regeneration in the adult mammalian CNS, including neutralizing inhibitory molecules by bacterial enzyme chondroitinase ABC (6) and administration of growthpromoting factors released, for example, from olfactory ensheathing cells and stem cells (7,8). One method that has been shown to have an effect in an optic nerve (ON) animal model is the intravitreal implantation of a peripheral nerve graft (PNG) after ON transection. Schwann cells in the PNG produce trophic factors that promote both retinal ganglion cell (RGC) survival and axon growth through the putative inhibitory environment of the injured ON, as documented in several studies (9 -11). Most studies detect regenerating axons in the CNS using traditional axon tracing techniques (e.g.,

Purpose:To assess magnitude and duration of changes in myocardial longitudinal relaxation rate (R 1 ) in humans following infusion of the manganese (Mn) releasing contrast agent MnDPDP (Mn-dipyridoxyl-diphosphate). Materials and Methods:Fifteen healthy volunteers were divided into three groups. After initial myocardial and liver R 1 measurements using an inversion recovery (IR) turbo fast low-angle shot (FLASH) sequence at 1.5 Tesla, the groups were given different doses of intravenous MnDPDP: 5, 10 and 15 mol/kg body weight, respectively, over 30 minutes. R 1 measurements were then repeated at 1, 2, 4, 8, and 24 hours after the infusion ended. Results:The left ventricular wall R 1 prevalue was 0.98 second -1 (Ϯ0.04). R 1 increased on average (all 15 subjects) 0.41 second -1 (Ϯ0.09). The increase was present one hour after the end of the infusion, remained relatively constant the next two hours, and then declined gradually. After 24 hours, there was still a moderate R 1 elevation present, with an average R 1 -value of 1.16 (Ϯ0.05). There were only small differences in myocardial R 1 responses between the three doses investigated, which was contrasted by a marked dose-response in liver tissue. Conclusion:MnDPDP gave a significant and prolonged rise in myocardial R 1 even at a dose of 5 mol/kg. The R 1 -values in the myocardium did not increase linearly with higher doses. THE USE OF manganese-containing contrast agents in magnetic resonance imaging (MRI) for the study of the myocardium has been debated for several years. The background for this interest in manganese is that myocardial cells actively accumulate manganese ions (Mn 2ϩ ) through voltage-dependent slow calcium channels in the cell membrane (1-4). This has raised the question of whether intracellular manganese can be used as a contrast agent for MRI-based myocardial viability diagnosis.Thus far, several research groups have studied myocardial effects of manganese in MRI. Early studies showed that manganese contrast could be used to demarcate infarcted regions in animal hearts, first in excised hearts (5,6), and later on in images obtained with live animals (7-9). The accumulated manganese led to markedly increased longitudinal relaxation rates (R 1 ) in normal myocardium (3,8 -11). Theoretically, the relationship between the concentration of contrast agent in a tissue and the corresponding R 1 should be close to linear. Southon et al (11) demonstrated a steady increase in myocardial R 1 in pigs with intravenous doses of manganese dipyridoxyl diphosphate (MnDPDP) up to 20 mol/kg. Both Bremerich et al (8) and Wendland et al (9) found that R 1 -values increased with increasing doses of MnDPDP in rat myocardium. Both studies used doses of 25, 50, and 100 mol/kg, given over 1.5 and 3 minutes, respectively. Both showed an initial higher rise in R 1 in infarcted myocardium 5-10 minutes after the infusions than in normal myocardium. However, these initial high R 1 -values in infarcted myocardium decreased with time, while normal myocardium had a steady increa...

Purpose: To develop an in vivo MR method for evaluation of myocardial calcium channel activity through quantification of apparent unidirectional manganese influx constants following manganese dipyridoxyl-diphosphate (MnDPDP) infusions. Materials and Methods:A total of 10 healthy volunteers were divided in two groups, and received 5 mol of MnD-PDP per kg of body weight intravenously in a 1.5 Tesla scanner over five or 30 minutes, respectively. A fast inversion recovery gradient echo sequence was used to estimate pre-and postcontrast R 1 values and to measure signal changes following infusions. By assuming equal longitudinal relaxivity (r 1 ) of the contrast in all tissue compartments, signal changes in blood and myocardial tissue yielded temporal input and tissue contrast concentrations respectively. Through a two-tissue compartment model, apparent unidirectional influx constants (K i ) for myocardial manganese accumulation were estimated.Results: Consistent values for K i in left ventricular wall were found, with a mean value of 5.96 mL/100 g/minute (SD ϭ 0.49; N ϭ 10). No statistical significant differences in K i were found between the two infusion groups. Conclusion:Since unidirectional manganese accumulation depends upon intact myocyte membranes with functioning calcium channels, the use of unidirectional manganese influx rates may be a valuable research tool for in vivo studies of myocyte functioning in myocardial disease.

Purpose: To assess the effects of Rician bias and physiological noise on parameter estimation for non-Gaussian diffusion models. Materials and Methods:At high b-values, there are deviations from monoexponential signal decay known as nonGaussian diffusion. Magnitude images have a Rician distribution, which introduces a bias that appears as non-Gaussian diffusion. A second factor that complicates parameter estimation is physiological noise. It has an intensity that depends on the b-value in a complicated manner. Hence, the signal distribution is unknown a priori. By measuring a large number of averages, however, the variance at each b-value can be estimated. Using Monte Carlo simulations, we compared uncorrected estimation to a corrected scheme that involves fitting to the mean value of the Rician distribution. We also evaluated effects of weighting with the inverse of the estimated variance in least-squares fitting. A human brain experiment illustrates parameter estimation effects and identifies brain regions affected by physiological noise. Results:The simulations show that the corrected estimator is very accurate. The uncorrected estimator is heavily biased. In the human brain experiment, the magnitude of the relative bias ranges from 6%-31%, depending on the diffusion model. Weighting has negligible effects on accuracy, but improves precision in the presence of physiological noise. At low b-values, physiological noise is prominent in cerebrospinal fluid. At high b-values there is physiological noise in white matter structures near the ventricles.Conclusion: Bias correction is essential and weighting may be beneficial. Physiological noise has significant effects.

In human brain diffusion measurements, there are deviations from monoexponential signal decay at high values of the diffusion-weighting factor b. This is known as non-Gaussian diffusion and can provide novel kinds of image contrast. We evaluated quantitatively the goodness-of-fit of five popular diffusion models. Because of the Rician signal distribution and physiological noise, the measurement errors are unknown. This precludes standard x 2 testing. By repeating the measurement 25 times, the errors were estimated. Hypothesis testing based on the residual after least squares curve fitting was then carried out. Systematic errors originating from the Rician signal bias were eliminated in the fitting procedure. We performed diffusion measurements on four healthy volunteers with b-values ranging from 0 to 5000 s/mm 2 . The data were analyzed voxelwise. The null hypothesis of a given model being adequate was rejected, if the residual after fitting exceeded a limit that corresponds to a significance level of 1%. In human brain diffusion-weighted imaging, the signal may deviate from monoexponential decay, in particular, at high values of the diffusion-weighting factor, b. This phenomenon is termed non-Gaussian diffusion. The term multiexponential diffusion is also used, although this is a less general concept. Non-Gaussian diffusion constitutes a new kind of MRI contrast that has shown diagnostic potential (1-3). The most important physical mechanisms behind non-Gaussian diffusion are compartmentalization and microscopic restrictions experienced by the diffusing water molecules. At low b-values, also there may be a contribution from intravoxel incoherent motion (4). Many models have been proposed to describe non-Gaussian diffusion (5-13). Recently, a theoretical comparison of such models was provided in Ref. (14). Five models are discussed in the next section.A crucial question in mathematical modeling is the following: Does the model fit the observations? This is the subject of the present article. If the measurement uncertainties are known, the goodness-of-fit can be quantified by using the residual after least squares fitting to perform a x 2 test. This gives a rigorous and quantitative measure of the quality of the mathematical model. It also allows testing of the null-hypothesis of the model being correct. In human brain diffusion measurements, however, this procedure cannot be applied without modifications.It is common to use magnitude-reconstructed images. This implies that the signal has a Rician (15) distribution with a noise level that is not uniform. The effect of the Rician distribution on the measured signal intensities has been discussed in Refs. 16-20 and the context of diffusion coefficient and relaxation rate estimation in Refs. 21-24. Another factor that complicates the estimation of the measurement uncertainties is nonthermal noise (25). The most prominent source is physiological noise. This includes breathing and cardiac-induced pulsatile motions that appear as quasi-periodic oscillations (26) as we...

Purpose: 1) To evaluate a novel theoretical model for in vivo axonal Mn 2þ transport with MRI data from the rat optic nerve (ON); and 2) to compare predictions from the new model with previously reported experimental data. Materials and Methods:Time-resolved in vivo T 1 -weighted magnetic resonance imaging (MRI) of adult female Sprague-Dawley rat (n ¼ 9) ON was obtained at different timepoints after intravitreal MnCl 2 injection. A concentration-dependent and a rate-dependent function for the Mn 2þ retinal ganglion cell (RGC) axon entrance was convolved with three different transport functions and each model system was optimized to fit the ON data.Results: The rate-limited input function gave a better fit to the data than the concentration-limited input. Simulations showed that the rate-limited input leads to a semilogarithmic relationship between injected dose and Mn 2þ concentration in the ON, which is in agreement with previously reported in vivo experiments. A random walk transport model and an anterograde predominant slow model gave a similar fit to the data, both better than an anterograde predominant fast model. Conclusion:The results indicate that Mn 2þ input into RGC axons is limited by a maximum entrance rate into the axons. Also, a wide range of apparent Mn 2þ transport rates seems to be involved, different from synaptic vesicle transport rates, meaning that manganese does not depict synaptic vesicle transport rates directly.