Probing rat brain oxygenation with near-infrared spectroscopy (NIRS) and magnetic resonance imaging (MRI).
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Animals↗
Biomedical subjects
Ravinder Reddy
Publications and source records attributed to Ravinder Reddy.
Phosphorus magnetic resonance spectroscopy: its utility in examining the membrane hypothesis of schizophrenia.
A novel approach to understanding the pathophysiology of schizophrenia has been the investigation of membrane composition and functional perturbations, referred to as the "Membrane Hypothesis of Schizophrenia." The evidence in support of this hypothesis has been accumulating in findings in patients with schizophrenia of reductions in phospholipids and essential fatty acids various peripheral tissues. Postmortem studies indicate similar reductions in essential fatty acids in the brain. However, the use of magnetic resonance spectroscopy (MRS) has provided an opportunity to examine aspects of membrane biochemistry in vivo in the living brain. MRS is a powerful, albeit complex, noninvasive quantitative imaging tool that offers several advantages over other methods of in vivo biochemical investigations. It has been used extensively in investigating brain biochemistry in schizophrenia. Phosphorus MRS (31P MRS) can provide important information about neuronal membranes, such as levels of phosphomonoesters that reflect the building blocks of neuronal membranes and phosphodiesters that reflect breakdown products. 31P MRS can also provide information about bioenergetics. Studies in patients with chronic schizophrenia as well as at first episode prior to treatment show a variety of alterations in neuronal membrane biochemistry, supportive of the membrane hypothesis of schizophrenia. Below, we will briefly review the principles underlying 31P MRS and findings to date. Magnetic resonance spectroscopy (MRS) is a powerful, albeit complex, imaging tool that permits investigation of brain biochemistry in vivo. It utilizes the magnetic resonance imaging hardware. It offers several advantages over other methods of in vivo biochemical investigations. MRS is noninvasive, there is no radiation exposure, does not require the use of tracer ligands or contrast media. Because of it is relatively benign, repeated measures are possible. It has been used extensively in investigating brain biochemistry in schizophrenia.
Brain↗
T1rho MR imaging of the human wrist in vivo.
RATIONALE AND OBJECTIVES: The purpose of this study was (a) to demonstrate the feasibility of computing T1rho maps of, and T1rho dispersion in, human wrist cartilage at MR imaging in vivo and (b) to compare T1rho and T2 weighting in terms of magnitude of relaxation times and signal intensity contrast. MATERIALS AND METHODS: T2 and T1rho magnetic resonance images of wrist joints in healthy volunteers (n = 5) were obtained with a spin-echo sequence and a fast spin-echo sequence pre-encoded with a spin-lock pulse cluster. A 1.5-T clinical imager was used (Signa; GE Medical Systems, Milwaukee, Wis) with a 9.5-cm-diameter transmit-receive quadrature birdcage coil tuned to 63.75 MHz. RESULTS: T1rho relaxation times at a spin-lock frequency of 500 Hz vary from 40.5 msec +/- 0.85 to 56.6 msec +/- 4.83, and T2 relaxation times vary from 28.1 msec +/- 1.88 to 34.5 msec +/- 2.63 (mean +/- standard error of the mean, n = 5, P < .016) in various regions of the wrist. T1rho dispersion was observed in the range of spin-lock frequencies studied. T1rho-weighted images not only have higher signal-to-noise ratios but also show better fluid and fat signal suppression than T2-weighted images. CONCLUSION: It was possible to perform T2- and T1rho-weighted MR imaging of human wrist cartilage in vivo with standard clinical imagers. The higher signal-to-noise ratio and improved contrast between cartilage and surrounding fat achieved with T1rho imaging may provide better definition of lesions and accurate quantitation of small changes in cartilage degeneration.
Adult↗
Artifacts in T(1rho)-weighted imaging: correction with a self-compensating spin-locking pulse.
Significant artifacts arise in T(1rho)-weighted imaging when nutation angles suffer small deviations from their expected values. These artifacts vary with spin-locking time and amplitude, severely limiting attempts to perform quantitative imaging or measurement of T(1rho) relaxation times. A theoretical model explaining the origin of these artifacts is presented in the context of a T(1rho)-prepared fast spin-echo imaging sequence. Experimentally obtained artifacts are compared to those predicted by theory and related to B(1) inhomogeneity. Finally, a "self-compensating" spin-locking preparatory pulse cluster is presented, in which the second half of the spin-locking pulse is phase-shifted by 180 degrees. Use of this pulse sequence maintains relatively uniform signal intensity despite large variations in flip angle, greatly reducing artifacts in T(1rho)-weighted imaging.
Artifacts↗
Prolonged untreated illness duration from prodromal onset predicts outcome in first episode psychoses.
Several, although not all, studies suggest that prolonged duration of untreated illness (DUI) predicts poor outcome in psychotic disorders such as schizophrenia. It is unclear whether this association can be explained by factors such as baseline deficits or poor premorbid adjustment. First episode psychotic patients were evaluated at 1 and 2 years following baseline evaluations. Predictive measures showing significant correlations with outcome were entered in multiple regression analyses with Strauss-Carpenter scale (SC) and Global Assessment of Functioning scale (GAF) outcome scores as dependent variables. Illness duration computed from the onset of the prodrome (DUI-pro), used both as a dichotomous and as a continuous measure, highly significantly predicted both GAF and SC scores at 2 years. On the other hand, baseline functioning significantly predicted the 1-year but not the 2-year outcome. When Premorbid Adjustment Scale (PAS) scores were additionally entered into the analyses in a smaller subset, the relation between DUI-pro and the 2-year outcome scores remained significant. Significant associations were also seen between outcome and baseline neuropsychological deficits involving attention and memory. Further research is needed to examine whether prolonged untreated illness is simply associated with poor outcome or plays a causal role in relation to outcome. The latter, if true, would strongly support therapeutic intervention efforts in the prodromal and early psychotic phases of schizophrenia.
Adolescent↗
In vivo proton MR three-dimensional T1rho mapping of human articular cartilage: initial experience.
The purpose of this study was to demonstrate the feasibility of computing three-dimensional relaxation maps of spin-lattice relaxation time in the rotating frame (T1rho) from in vivo magnetic resonance (MR) images of the human patellofemoral joint. T1rho was measured by applying a three-dimensional gradient-echo pulse sequence in six healthy subjects and one symptomatic subject by using a 1.5-T MR imager and a 15-cm-diameter transmit-receive quadrature birdcage radiofrequency coil. Average T1rho measured in healthy patellar cartilage was 49.7 msec +/- 3.2 (mean +/- SD). Two-dimensional T1rho-weighted images were obtained with a fast spin-echo pulse sequence for comparison. There was good correlation between two-dimensional and three-dimensional T1rho values for the six healthy subjects (R2 = 0.88, slope = 1.16).
Adult↗
Effect of IL-1beta-induced macromolecular depletion on residual quadrupolar interaction in articular cartilage.
PURPOSE: Sodium multiple-quantum filtered (MQF) NMR spectroscopy may potentially be used to measure proteoglycan (PG) depletion in cartilage caused by osteoarthritis (OA). The purpose of this work was to quantify the effect of interleukin-1 (IL-1beta)-induced macromolecule depletion on the residual quadrupolar interaction (RQI) of sodium in bovine cartilage plugs. MATERIALS AND METHODS: Fifteen 8-mm-diameter cartilage plug specimens were cored from the articular surface of fresh bovine patellae. All plugs were kept in culture media and nine of the plugs were subjected to interleukin-1 (IL-1beta)-induced degeneration of cartilage for 4, 6, and 7 days. Sodium NMR spectra were obtained from each sample with a 1-cm-diameter solenoid coil in a 2T whole-body magnet interfaced to a custom-built spectrometer. We employed a previously described theoretical model to analyze triple-quantum filtered (TQF) and double-quantum filtered magic angle (DQFMA) spectra obtained from normal cartilage and cartilage treated with IL-1beta. The model assumes a static Gaussian distribution of the RQI frequency, omega(Q), in the sample. TQF and DQFMA spectra from each sample were fitted with the appropriate signal expressions to determine sigma (the root mean square (RMS) omegaQ), T2f, and T2s. An inversion-recovery sequence was used to determine T1 of each plug. A spectrophotometric assay was used to determine the amount of PG depleted from each plug. Histology was performed to visualize the PG loss in cartilage plugs. We defined sigma as the measure of changes in macroscopic order in the tissue. RESULTS: Simulated spectra from the theoretical model were in excellent agreement with the experimental data. We were able to determine the relaxation times as well as sigma of each specimen from their corresponding fits. T2f ranged between 2.26-3.50 msec, decreasing with increased PG loss. Over the range of PG depletion investigated, T2s increased from 12.3 msec to 14.9 msec, and T1 increased from 16 msec to 21 msec, while sigma decreased from 180 Hz to 120 Hz. The order of macromolecules in the cartilage tissue decreased substantially with PG loss. Histology sections clearly showed qualitative visualization of the PG loss in cartilage following treatment with IL-1beta. CONCLUSION: We demonstrated that IL-beta-induced macromolecule depletion in cartilage not only changes the relaxation characteristics of sodium but also changes RQI of the tissue. Using MQF sodium spectroscopy we quantified the changes in sigma and showed that loss of macromolecules reduces the degree of order in the tissue.
Animals↗
23Na MRI accurately measures fixed charge density in articular cartilage.
One of the initiating steps of osteoarthritis is the loss of proteoglycan (PG) molecules from the cartilage matrix. One method for assessing cartilage integrity, therefore, is to measure the PG content or fixed charge density (FCD) of cartilage. This report shows the feasibility of calculating FCD by (23)Na MRI and introduces MRI protocols for human studies, in vivo. (23)Na MRI was used to measure the sodium concentration inside bovine patellar cartilage. The sodium concentration was then converted to FCD (mM) by considering ideal Donnan equilibrium. These FCD measurements were compared to FCD measurements obtained through standard dimethylmethylene blue PG assays. There was a high correlation (slope = 0.89, r(2) = 0.81) between the FCD measurements obtained by (23)Na MRI and those obtained by the PG assays. These methods were then employed in quantifying the FCD of articular cartilage of human volunteers in vivo. Two imaging protocols were compared: one using a birdcage coil, the other using a transmit/receive surface coil. Both methodologies gave similar results, with the average sodium concentration of normal human patellar cartilage ranging from approximately 240 to 260 mM. This corresponds to FCDs of -158 mM to -182 mM.
Animals↗
Fast MRI of RF heating via phase difference mapping.
A method is presented for the rapid acquisition of temperature maps derived from phase difference maps. The temperature-dependent chemical shift coefficients (TDCSCs) of various concentrations of aqueous cobalt and dysprosium-based compounds were measured. The largest TDCSC calculated was for 100 mM DyEDTA, which had a TDCSC of -0.09 PPM/K; 160 mM CoCl2 had a TDCSC of -0.04 PPM/K. These temperature-dependent chemical shifts (TDCSs) result in phase changes in the MR signal with changing temperature. Agarose phantoms were constructed with each paramagnetic metal. A fast gradient-echo (FGRE) MR image was acquired to serve as the baseline image. A "test" MRI procedure was then performed on the phantom. Immediately afterwards, a second FGRE MR image was acquired, serving as the probing image. Proper image processing as a phase difference map between the probing image and the baseline image resulted in an image which quantitatively described the temperature increase of the phantom in response to a particular "test" imaging experiment. Applications of this technique in assessing the safety of pulse sequences and MR coils are discussed.
Biophysical Phenomena↗
Proteoglycan depletion-induced changes in transverse relaxation maps of cartilage: comparison of T2 and T1rho.
RATIONALE AND OBJECTIVES: The authors performed this study to (a) measure changes in T2 relaxation rates, signal-to-noise ratio (SNR), and contrast with sequential depletion of proteoglycan in cartilage; (b) determine whether there is a relationship between the T2 relaxation rate and proteoglycan in cartilage; and (c) compare the T2 mapping method with the spin-lattice relaxation time in the rotating frame (T1rho) mapping method in the quantification of proteoglycan-induced changes. MATERIALS AND METHODS: T2- and T1rho-weighted magnetic resonance (MR) images were obtained in five bovine patellae. All images were obtained with a 4-T whole-body MR unit and a 10-cm-diameter transmit-receive quadrature birdcage coil tuned to 170 MHz. T2 and T1rho maps were computed. RESULTS: The SNR and contrast on the T2-weighted images were, on average, about 43% lower than those on the corresponding T1rho-weighted images. The T2 relaxation rates varied randomly without any particular trend, which yielded a poor correlation with sequential depletion of proteoglycan (R2 = 0.008, P < .70). There was excellent linear correlation between the percentage of proteoglycan in the tissue and the T1rho relaxation rate (R2 = 0.85, P < .0001). CONCLUSION: T2-weighted imaging neither yields quantitative information about the changes in proteoglycan distribution in cartilage nor can be used for longitudinal studies to quantify proteoglycan-induced changes. T1rho-weighted imaging, however, is sensitive to sequential depletion of proteoglycan in bovine cartilage and can be used to quantify proteoglycan-induced changes.
Animals↗
Quantifying sodium in the human wrist in vivo by using MR imaging.
The authors quantified sodium content in the wrist joints of six healthy volunteers with no known history of arthritis or pain. Average sodium concentrations ranged from 115 to 150 mmol/L in noncartilaginous regions and from 200 to 210 mmol/L in cartilaginous regions. The feasibility of quantifying sodium in vivo was demonstrated. This method has potential applications in monitoring the integrity of cartilaginous tissue in vivo.
Adult↗
Persistence of serum antibodies to Sarcocystis neurona in horses moved from North America to India.
BACKGROUND: The study reported here was undertaken to assess the presence of antibodies to Sarcocystis neurona in the serum of horses of North American origin that had been relocated for 1 year or more to India (ie, outside of the known endemic areas for S. neurona). HYPOTHESIS: The presence or absence of such antibodies should provide information concerning the persistence of such antibodies, or support the presence of chronic infection, or both. ANIMALS: A total of 228 Thoroughbred horses were sampled in India, of which 86 were of North American origin that had been in India between 1 and 13 years, 124 were Indian-born horses that had never been out of India, 8 were of Irish origin, 8 were of English origin, and 2 were originally from France. METHODS: Sera were tested using established western blot analysis. RESULTS: Of the Indian-born horses, 0.8% were test positive, and of the North American horses, 42% were test positive. All of the English and Irish horses were test negative, and the 2 French horses were test positive. CONCLUSIONS AND CLINICAL IMPORTANCE: These data indicate that antibodies against S. neurona can be detected for many years after horses have been removed from an endemic area and that this may be attributable to long half-life of the antibodies or to chronic infection and ongoing antibody production, or both.
Animals↗