Biomedical subjects

Rohit Sood

Publications and source records attributed to Rohit Sood.

9 recordsLinked to original sources

PubMed2007

Quantitative evaluation of the effect of propylene glycol on BBB permeability.

PURPOSE: To establish the blood-brain barrier (BBB) blocking property of propylene glycol (PG) using the (14)C sucrose technique, quantitatively evaluate the effect of PG on BBB permeability using an MRI technique based on graphical analysis, and demonstrate the sensitivity of MRI for testing newer investigational drugs. MATERIALS AND METHODS: Brain uptake of sucrose was measured in treated (PG+) and untreated (PG-) rats using a (14)C sucrose technique in rat brains (N = 10) that had undergone two hours of middle cerebral artery occlusion (MCAO) and three hours of reperfusion. Another group of PG+ and PG- rats (N = 8) underwent MRI. T2-weighted (T2W) and diffusion-weighted (DW) images were acquired on a 4.7T MR system. A rapid T1 mapping protocol was implemented to acquire a baseline data set followed by postinjection data sets at regular intervals. The data were postprocessed pixelwise to generate permeability coefficient color maps. RESULTS: A significant (P < 0.05) reduction in (14)C sucrose space was observed on the ischemic side of PG+ rats only. Permeability coefficient estimates obtained by MRI from the ipsilateral hemisphere in PG+ rats were significantly lower than those in PG- rats (P < 0.05). There was no significant change on the contralateral side in PG+ rats. The results show that PG protects the BBB in ischemic stroke, and MRI measurements are sufficiently sensitive to noninvasively detect small drug effects. CONCLUSION: MRI is useful for evaluating the BBB blocking effect of PG in an ischemic stroke model of rat brain. The results from the MR experiment agree well with findings from the (14)C sucrose technique.

Analysis of Variance↗

PubMed2006

Kalman filtering for reliable estimation of BBB permeability.

INTRODUCTION: The blood-brain barrier (BBB) plays an important role in the pathophysiology of a number of central nervous system disorders. In the past, a number of laboratory techniques have been proposed to quantify permeability coefficient ki, an important index of barrier function. Recently, magnetic resonance imaging (MRI) has been used to estimate ki based on graphical plot technique. The MR technique was found to be in good agreement with the gold standard, quantitative autoradiography (QAR). However, a reduced image signal-to-noise ratio, among other factors such as partial volume effects, did not allow reliable estimation of permeability coefficients. This proof-of-principle study proposes the use of Kalman filter as a filtering technique for a reliable estimation of permeability coefficients. The results are compared to those obtained using the Wiener filter technique. MATERIALS AND METHODS: MRI experiments were performed in Wistar rats (N=2) using a 4.7-T Bruker Biospec MR system (Bruker Biospin, Billerica, MA). After acquiring localizer images, T2-weighted diffusion-weighted imaging images were acquired. Finally, a rapid T1 mapping protocol was implemented to acquire one pre-gadolinium diethylenetriamine pentaacetic acid baseline data set followed by postinjection data sets at 3-min intervals for 45 min. Data were postprocessed with and without the application of Kalman and Wiener filters to obtain an estimate of ki. RESULTS AND DISCUSSION: Comparing T1 maps, Patlak plots and permeability maps with and without the Kalman filtering presented several interesting observations. Kalman-filtered Patlak plots, compared to nonfiltered plots, showed that discrete data points on the plot were closer to the line fit. The number of time points used for the construction of the graphical plot had no effect on permeability coefficient estimates when the Kalman filter was used. A box-and-whiskers plot showed longer Y-error bars for nonfiltered and Wiener data compared to Kalman-filtered data. These observations suggest that it may be possible to obtain reliable permeability coefficient estimates in a short study time by applying the Kalman filter to the data. Future work involves investigating the application of this filter on a large-sample-size animal study and evaluating the role of partial volume effects on BBB permeability estimation.

Animals↗

PubMed2006

Interaction of the antimicrobial peptide pheromone Plantaricin A with model membranes: implications for a novel mechanism of action.

Plantaricin A (plA) is a 26-residue bacteria-produced peptide pheromone with membrane-permeabilizing antimicrobial activity. In this study the interaction of plA with membranes is shown to be highly dependent on the membrane lipid composition. PlA bound readily to zwitterionic 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) monolayers and liposomes, yet without significantly penetrating into these membranes. The presence of cholesterol attenuated the intercalation of plA into SOPC monolayers. The association of plA to phosphatidylcholine was, however, sufficient to induce membrane permeabilization, with nanomolar concentrations of the peptide triggering dye leakage from SOPC liposomes. The addition of the negatively charged phospholipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol POPG (SOPC/POPG; molar ratio 8:2) enhanced the membrane penetration of the peptide, as revealed by (i) peptide-induced increment in the surface pressure of lipid monolayers, (ii) increase in diphenylhexatriene (DPH) emission anisotropy measured for bilayers, and (iii) fluorescence characteristics of the two Trps of plA in the presence of liposomes, measured as such as well as in the presence of different quenchers. Despite deeper intercalation of plA into the SOPC/POPG lipid bilayer, much less peptide-induced dye leakage was observed for these liposomes than for the SOPC liposomes. Further changes in the mode of interaction of plA with lipids were evident when also the zwitterionic phospholipid, 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphoethanolaminne (POPE) was present (SOPC/POPG/POPE, molar ratio 3:2:5), thus suggesting increase in membrane spontaneous negative curvature to affect the mode of association of this peptide with lipid bilayer. PlA induced more efficient aggregation of the SOPC/POPG and SOPC/POPG/POPE liposomes than of the SOPC liposomes, which could explain the attenuated peptide-induced dye leakage from the former liposomes. At micromolar concentrations, plA killed human leukemic T-cells by both necrosis and apoptosis. Interestingly, plA formed supramolecular protein-lipid amyloid-like fibers upon binding to negatively charged phospholipid-containing membranes, suggesting a possible mechanistic connection between fibril formation and the cytotoxicity of plA.

Acrylamide↗

PubMed2006

Longitudinal brain magnetic resonance imaging study of the alcohol-preferring rat. Part I: adult brain growth.

BACKGROUND: The alcohol-preferring (P) rat, a Wistar strain selectively bred to consume large amounts of alcohol voluntarily, has been used as an animal model of human alcoholism for 3 decades. Heretofore, knowledge about brain morphology has been confined to postmortem examination. Quantitative neuroimaging procedures make it feasible to examine the potential longitudinal effects of alcohol exposure in vivo, while controlling modifying factors, such as age, nutrition, and exercise. To date, few imaging studies have considered what morphological changes occur with age in the rodent brain, and none has systematically applied quantitative neuroimaging approaches to measure volume changes in regional brain structures over extended periods in the adult rat. METHODS: We used structural magnetic resonance imaging (MRI) in a longitudinal design to examine 2 cohorts of adult P rats, never exposed to alcohol: Cohort A included 8 rats, 7 of which survived the entire study (578 days) and 4 MRI sessions; Cohort B included 9 rats, all of which survived the study (452 days) and 5 MRI sessions. RESULTS: Growth in whole-brain volume reached maximal levels by about 450 days of age, whereas body weight continued its gain without asymptote. Growth was not uniform across the brain structures measured. Over the initial 12 months of the study, the corpus callosum area expanded 36%, cerebellum 17%, and hippocampus 10%, whereas ventricle size was unchanged. Factors affecting growth rate estimates included litter effects, MR image signal-to-noise ratio, and measurement error. CONCLUSION: Unlike longitudinal human reports of regional volume declines in aging brain tissue, several brain structures in adult rats continued growing, and some growth patterns were litter-dependent. Determining normal regional growth patterns of brain and of the substantial variance exerted by litter differences, even in selectively bred rats, is essential for establishing baselines against which normal and aberrant dynamic changes can be detected in animal models of aging and disease.

Aging↗

PubMed2006

Longitudinal brain magnetic resonance imaging study of the alcohol-preferring rat. Part II: effects of voluntary chronic alcohol consumption.

BACKGROUND: Tracking the dynamic course of human alcoholism brain pathology can be accomplished only through naturalistic study and without opportunity for experimental manipulation. Development of an animal model of alcohol-induced brain damage, in which animals consume large amounts of alcohol following cycles of alcohol access and deprivation and are examined regularly with neuroimaging methods, would enable hypothesis testing focused on the degree, nature, and factors resulting in alcohol-induced brain damage and the prospects for recovery or relapse. METHODS: We report the results of longitudinal magnetic resonance imaging (MRI) studies of the effects of free-choice chronic alcohol intake on the brains of 2 cohorts of selectively bred alcohol-preferring (P) rats. In the companion paper, we described the MRI acquisition and analysis methods, delineation of brain regions, and growth patterns in total brain and selective structures of the control rats in the present study. Both cohorts were studied as adults for about 1 year and consumed high doses of alcohol for most of the study duration. The paradigm involved a 3-bottle choice with 0, 15 (or 20%), and 30% (or 40%) alcohol available in several different exposure schemes: continuous exposure, cycles of 2 weeks on followed by 2 weeks off alcohol, and binge drinking in the dark. RESULTS: Brain structures of the adult P rats in both the alcohol-exposed and the water control conditions showed significant growth, which was attenuated in a few measures in the alcohol-exposed groups. The region with the greatest demonstrable effect was the corpus callosum, measured on midsagittal images. CONCLUSION: The P rats showed an age-alcohol interaction different from humans, in that normal growth in selective brain regions that continues in adult rats was retarded.

Animals↗

PubMed2005

Spin-lock MRI with amplitude- and phase-modulated adiabatic waveforms: an MR simulation study.

INTRODUCTION: Image contrast between tissue types can be generated based on their T1/T2 ratio using spin-lock MRI techniques. An interesting application of such a concept would be to generate contrast in tissue with tissue relaxation times modified using exogenous contrast agents. An amplitude-modulated adiabatic waveform has been shown in the past to perform spin-lock MRI. However, implementation of this waveform may not prove to be efficient and practical in research or a clinical setup due to high radiofrequency power deposition. Recent advancement in software and hardware MR technology allows implementation of amplitude- and phase-modulated adiabatic waveforms on MR systems. The aim of this work was to explore role of adiabatic waveforms in performing rho imaging and demonstrate that amplitude- and phase-modulated waveforms [e.g., hyperbolic secant, B1 independent rotation-4 (BIR-4) waveforms] can be used to distinguish materials that differ in T1/T2 ratio. METHODS AND RESULTS: MR simulation was performed using computer routines implemented in MATLAB environment (Mathworks, Natick, MA). Modified Bloch equations with trapezoidal, hyperbolic secant and BIR-4 waveforms were used to perform MR simulation. Trapezoidal waveforms were only used for comparison to other waveforms. Gadolinium DTPA (Gad-DTPA) (T1/T2 approximately 1) and manganese chloride (MnCl(2)) (T1/T2 approximately 10) were used as examples of contrast agents due to their routine use in clinical and research setups and more importantly because they provide good examples of materials differing in T1/T2 ratios. Results of spin locking using trapezoidal waveform agree very well with the previously published results, thereby validating the computer routines used in this MR simulation. Plots of M(rho) (magnetization vector in rho domain) vs. offset frequency show distinct curves for these materials differing in T1/T2 for the three waveforms. BIR-4 waveform demonstrated a 40% difference in M(rho) ( approximately 150 Hz) for the materials. Rate of spin lock with hyperbolic secant waveform was rapid compared to other waveforms. DISCUSSION: MR simulation using contrast agents Gad-DTPA and MnCl(2) provided a useful way to demonstrate that amplitude- and phase-modulated adiabatic waveforms can be used to perform spin-lock imaging. Future work involves implementation of these waveforms on MR scanners and performing in vivo imaging to generate tissue contrast based on relaxation times ratio.

Computer Simulation↗

PubMed2004

Favorable interactions of amine- and ester-terminated PAMAM with cationic surfactants: photophysical and transport studies.

Conductivity (kappa), turbidity (tau), and fluorescence (I1/I3) studies of hexadecyltrimethylammonium bromide (HTAB), hexadecylpyridinium bromide (HPyBr), and hexadecylpyridinium chloride (HPyCl) in aqueous poly(amido amine) (PAMAM) dendrimers of generations 0 to 2.5 G have been carried out. The complexation of surfactant monomers with the PAMAM surface groups is demonstrated by the critical aggregation concentration (cac), which is two to three orders of magnitude less than the micellization of cationic surfactants in aqueous PAMAM and denoted by critical micelle concentration (cmc*). In the presence of aqueous amine-terminated PAMAM, the cmc* value for each surfactant was much lower than the cmc in pure water, while they remain close to each other in the presence of aqueous ester-terminated PAMAM for each surfactant. The fluorescence studies demonstrated that both amine- and ester-terminated PAMAM interact with the cationic surfactants, though the mode of interaction varied due to the different nature of surface groups.

Journal Article↗

PubMed2004

Mixed micelles of benzyldimethyltetradecylammonium chloride with tetradecyltrimethylammonium and tetradecyltriphenylphosphonium bromides: a head group contribution.

Mixed micelle formation by tetradecyltrimethylammonium (TTAB) and tetradecyltriphenylphosphonium bromides (TTPB) with benzyldimethyltetradecylammonium chloride (BTDACl) was studied with the help of conductivity and Kraft point measurements. The BTDACl + TTAB mixtures showed synergistic interactions whereas those of BTDACl + TTPB indicated weak antagonistic behavior. From Kraft temperature measurements, the enthalpy of fusion (H(1)(0)) from solid hydrated BTDACl to the liquid state in the presence of TTAB or TTPB was computed. It was found that DeltaH(1)(0) was much more positive for BTDACl + TTPB than for BTDACl + TTAB mixtures.

Journal Article↗

PubMed2004

Off-resonance binomial preparatory pulse technique for high sensitivity MRI of H2O17.

H2O17 is a freely diffusible tracer and naturally occurring isotope of O16 detectable by MRI and has been shown to be useful for assessing cerebral perfusion in animal studies using direct and indirect MR detection techniques. However, earlier MR techniques are either not sensitive to changes in small concentrations of tissue H2O17 or are not practical for use on clinical scanners. In this work, a novel method for detecting H2O17 with high sensitivity has been proposed that uses a short, intense, binomial preparatory spin lock pulse with resonance offsets for high sensitive rapid, multislice imaging of tissue H2O17. Two sets of phantom experiments were performed on the 1.5 T and repeated on 3.0 T to assess the feasibility of the proposed technique. The phantom was constructed using ovalbumin and doped with 0.4 atom% and 1.0 atom% H2O17. After obtaining initial parameters, the proposed technique was validated in an anesthetized primate model that was injected with 1.8 cc of 40 atom% H2O17. Phantom experiments showed that the proposed technique was able to detect H2O17 with relatively high sensitivity and high B1 amplitude (and small offsets) preparatory pulses produced similar results as low B1 amplitude (and larger offsets). Primate brain study showed a 42.97% difference in mean signal intensity between pre- and post-H2O17 injection. The proposed technique was successfully implemented on a clinical scanner and was able to detect H2O17 with relatively high sensitivity. Primate study has shown that such a technique can be successfully used for human imaging applications to investigate and assess cerebral perfusion.

Animals↗