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Biomedical subjects

Ravinder Reddy

Publications and source records attributed to Ravinder Reddy.

At least 19 recordsLinked to original sources
PubMed2007

Blunted serotonergic responsivity in neuroleptic-naïve patients at first-episode of schizophrenia.

OBJECTIVE: To determine whether serotonergic responsivity, as assessed in platelets, is blunted in treatment-naïve patients with first episode psychosis, similar to observations in chronic schizophrenia. METHODS: Serotonin (5-HT)-amplified platelet aggregation was determined in 26 first-episode treatment-naive patients with psychosis (14 with schizophrenia, 12 with mood disorders with psychosis) and 16 matched healthy comparison subjects. Platelet aggregation was measured in fresh whole blood after stimulation with 5.0 microM adenosine diphosphate (ADP) alone and with the addition of 0.2 microg and 1.0 microg 5-HT. RESULTS: Healthy subjects showed expected robust increases in platelet aggregation (+106% and +146% at 0.2 microg and 1.0 microg 5-HT, respectively). By contrast, patients with schizophrenia showed almost no changes in aggregation (+6% and +3%), while patients with mood disorders showed intermediate increases (+59% and +66%). CONCLUSIONS: Blunted platelet serotonergic responsivity appears to be independent of treatment effects. To determine whether this is trait-related factor will require prospective studies.

Adenosine Diphosphate↗
PubMed2007

Compensation for spin-lock artifacts using an off-resonance rotary echo in T1rhooff-weighted imaging.

The origin of image artifacts in an off-resonance spin-locking experiment is shown to be imperfections in the excitation flip angle. A pulse sequence for off-resonance spin locking is implemented that compensates for imperfections in the excitation flip angle through an off-resonance rotary echo. The off-resonance rotary echo alternates the frequency offset and phase of the RF transmitter during two spin-locking pulses of equal duration. The underlying theory is detailed, and MR images demonstrate the effectiveness of the technique in agarose gel phantoms and in in vivo human brain at 3T.

Algorithms↗
PubMed2006

Assessment of human disc degeneration and proteoglycan content using T1rho-weighted magnetic resonance imaging.

STUDY DESIGN: T1rho relaxation was quantified and correlated with intervertebral disc degeneration and proteoglycan content in cadaveric human lumbar spine tissue. OBJECTIVE: To show the use of T1rho-weighted magnetic resonance imaging (MRI) for the assessment of degeneration and proteoglycan content in the human intervertebral disc. SUMMARY OF BACKGROUND DATA: Loss of proteoglycan in the nucleus pulposus occurs during early degeneration. Conventional MRI techniques cannot detect these early changes in the extracellular matrix content of the disc. T1rho MRI is sensitive to changes in proteoglycan content of articular cartilage and may, therefore, be sensitive to proteoglycan content in the intervertebral disc. METHODS: Intact human cadaveric lumbar spines were imaged on a clinical MR scanner. Average T1rho in the nucleus pulposus was calculated from quantitative T1rho maps. After MRI, the spines were dissected, and proteoglycan content of the nucleus pulposus was measured. Finally, the stage of degeneration was graded using conventional T2 images. RESULTS: T1rho decreased linearly with increasing degeneration (r = -0.76, P < 0.01) and age (r = -0.76, P < 0.01). Biochemical analysis revealed a strong linear correlation between T1rho and sulfated-glycosaminoglycan content. T1rho was moderately correlated with water content. CONCLUSIONS: Results from this study suggest that T1rho may provide a tool for the diagnosis of early degenerative changes in the disc. T1rho-weighted MRI is a noninvasive technique that may provide higher dynamic range than T2 and does not require a high static field or exogenous contrast agents.

Adolescent↗
PubMed2006

In vivo quantification of human lumbar disc degeneration using T(1rho)-weighted magnetic resonance imaging.

Diagnostic methods and biomarkers of early disc degeneration are needed as emerging treatment technologies develop (e.g., nucleus replacement, total disc arthroplasty, cell therapy, growth factor therapy) to serve as an alternative to lumbar spine fusion in treatment of low back pain. We have recently demonstrated in cadaveric human discs an MR imaging and analysis technique, spin-lock T(1rho)-weighted MRI, which may provide a quantitative, objective, and non-invasive assessment of disc degeneration. The goal of the present study was to assess the feasibility of using T(1rho) MRI in vivo to detect intervertebral disc degeneration. We evaluated ten asymptomatic 40-60-year-old subjects. Each subject was imaged on a 1.5 T whole-body clinical MR scanner. Mean T(1rho) values from a circular region of interest in the center of the nucleus pulposus were calculated from maps generated from a series of T(1rho)-weighted images. The degenerative grade of each lumbar disc was assessed from conventional T(2)-weighted images according to the Pfirmann classification system. The T(1rho) relaxation correlated significantly with disc degeneration (r=-0.51, P<0.01) and the values were consistent with our previous cadaveric study, in which we demonstrated correlation between T(1rho) and proteoglycan content. The technique allows for spatial measurements on a continuous rather than an integer-based scale, minimizes the potential for observer bias, has a greater dynamic range than T(2)-weighted imaging, and can be implemented on a 1.5 T clinical scanner without significant hardware modifications. Thus, there is a strong potential to use T(1rho) in vivo as a non-invasive biomarker of proteoglycan loss and early disc degeneration.

Adult↗
PubMed2006

T1rho relaxation mapping in human osteoarthritis (OA) cartilage: comparison of T1rho with T2.

PURPOSE: To quantify the spin-lattice relaxation time in the rotating frame (T1rho) in various clinical grades of human osteoarthritis (OA) cartilage specimens obtained from total knee replacement surgery, and to correlate the T1rho with OA disease progression and compare it with the transverse relaxation time (T2). MATERIALS AND METHODS: Human cartilage specimens were obtained from consenting patients (N = 8) who underwent total replacement of the knee joint at the Pennsylvania Hospital, Philadelphia, PA, USA. T2- and T1rho-weighted images were obtained on a 4.0 Tesla whole-body GE Signa scanner (GEMS, Milwaukee, WI, USA). A 7-cm diameter transmit/receive quadrature birdcage coil tuned to 170 MHz was employed. RESULTS: All of the surgical knee replacement OA cartilage specimens showed elevated relaxation times (T2 and T1rho) compared to healthy cartilage tissue. In various grades of OA specimens, the T1rho relaxation times varied from 62 +/- 5 msec to 100 +/- 8 msec (mean +/- SEM) depending on the degree of cartilage degeneration. However, T2 relaxation times varied only from 32 +/- 2 msec to 45 +/- 4 msec (mean +/- SEM) on the same cartilage specimens. The increase in T2 and T1rho in various clinical grades of OA specimens were approximately 5-50% and 30-120%, respectively, compared to healthy specimens. The degenerative status of the cartilage specimens was also confirmed by histological evaluation. CONCLUSION: Preliminary results from a limited number of knee specimens (N = 8) suggest that T1rho relaxation mapping is a sensitive noninvasive marker for quantitatively predicting and monitoring the status of macromolecules in early OA. Furthermore, T1rho has a higher dynamic range (>100%) for detecting early pathology compared to T2. This higher dynamic range can be exploited to measure even small macromolecular changes with greater accuracy compared to T2. Because of these advantages, T1rho relaxation mapping may be useful for evaluating early OA therapy.

Arthroplasty, Replacement, Knee↗
PubMed2006

A pulse sequence for rapid in vivo spin-locked MRI.

PURPOSE: To develop a novel pulse sequence called spin-locked echo planar imaging (EPI), or (SLEPI), to perform rapid T1rho-weighted MRI. MATERIALS AND METHODS: SLEPI images were used to calculate T1rho maps in two healthy volunteers imaged on a 1.5-T Sonata Siemens MRI scanner. The head and extremity coils were used for imaging the brain and blood in the popliteal artery, respectively. RESULTS: SLEPI-measured T1rho was 83 msec and 103 msec in white (WM) and gray matter (GM), respectively, 584 msec in cerebrospinal fluid (CSF), and was similar to values obtained with the less time-efficient sequence based on a turbo spin-echo readout. T1rho was 183 msec in arterial blood at a spin-lock (SL) amplitude of 500 Hz. CONCLUSION: We demonstrate the feasibility of the SLEPI pulse sequence to perform rapid T1rho MRI. The sequence produced images of higher quality than a gradient-echo EPI sequence for the same contrast evolution times. We also discuss applications and limitations of the pulse sequence.

Brain Mapping↗
PubMed2006

In vivo measurement of plaque burden in a mouse model of Alzheimer's disease.

PURPOSE: To demonstrate an MRI method for directly visualizing amyloid-beta (Abeta) plaques in the APP/PS1 transgenic (tg) mouse brain in vivo, and show that T1rho relaxation rate increases progressively with Alzheimer's disease (AD)-related pathology in the tg mouse brain. MATERIALS AND METHODS: We obtained in vivo MR images of a mouse model of AD (APP/PS1) that overexpresses human amyloid precursor protein, and measured T1rho via quantitative relaxometric maps. RESULTS: A significant decrease in T1rho was observed in the cortex and hippocampus of 12- and 18-month-old animals compared to their age-matched controls. There was also a correlation between changes in T1rho and the age of the animals. CONCLUSION: T1rho relaxometry may be a sensitive method for noninvasively determining AD-related pathology in APP/PS1 mice.

Alzheimer Disease↗
PubMed2006

Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage.

In this article, both sodium magnetic resonance (MR) and T1rho relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T1rho, a brief description of (i) principles of measuring T1rho relaxation, (ii) pulse sequences for computing T1rho relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T1rho in biological tissues and (v) effects of exchange and dipolar interaction on T1rho dispersion are discussed. Correlation of T1rho relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokine-induced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T1rho data from osteoarthritic specimens, animal models, healthy human subjects and as well from osteoarthritic patients are provided. The current status of T1rho relaxation mapping of cartilage and future directions is also discussed.

Animals↗
PubMed2006

Altered glutathione redox state in schizophrenia.

Altered antioxidant status has been reported in schizophrenia. The glutathione (GSH) redox system is important for reducing oxidative stress. GSH, a radical scavenger, is converted to oxidized glutathione (GSSG) through glutathione peroxidase (GPx), and converted back to GSH by glutathione reductase (GR). Measurements of GSH, GSSG and its related enzymatic reactions are thus important for evaluating the redox and antioxidant status. In the present study, levels of GSH, GSSG, GPx and GR were assessed in the caudate region of postmortem brains from schizophrenic patients and control subjects (with and without other psychiatric disorders). Significantly lower levels of GSH, GPx, and GR were found in schizophrenic group than in control groups without any psychiatric disorders. Concomitantly, a decreased GSH:GSSG ratio was also found in schizophrenic group. Moreover, both GSSG and GR levels were significantly and inversely correlated to age of schizophrenic patients, but not control subjects. No significant differences were found in any GSH redox measures between control subjects and individuals with other types of psychiatric disorders. There were, however, positive correlations between GSH and GPx, GSH and GR, as well as GPx and GR levels in control subjects without psychiatric disorders. These positive correlations suggest a dynamic state is kept in check during the redox coupling under normal conditions. By contrast, lack of such correlations in schizophrenia point to a disturbance of redox coupling mechanisms in the antioxidant defense system, possibly resulting from a decreased level of GSH as well as age-related decreases of GSSG and GR activities.

Age Factors↗
PubMed2006

Arrhythmogenic right ventricular dysplasia: initial presentation in a middle-aged woman.

Arrhythmogenic right ventricular dysplasia is a rare disorder that is familial in 30% to 50% of cases. It is characterized by structural and functional abnormalities of the right ventricle and a propensity for ventricular arrhythmias and sudden death. We report the case of a 59-year-old woman who had idiopathic, severe, right-sided heart failure and nonsustained ventricular tachycardia. She was diagnosed with arrhythmogenic right ventricular dysplasia by means of cardiac magnetic resonance imaging. We discuss the clinical features, diagnostic criteria, and role of cardiac magnetic resonance imaging in the diagnosis of arrhythmogenic right ventricular dysplasia.

Arrhythmogenic Right Ventricular Dysplasia↗
PubMed2005

Depth-dependent proton magnetization transfer in articular cartilage.

PURPOSE: To measure the proton magnetization transfer ratio (MTR) maps in control and collagen-depleted bovine patellar cartilage specimens as a function of cartilage depth during mechanical compression. MATERIALS AND METHODS: One-dimensional proton projection MR images employing a spin-echo imaging sequence were obtained on a custom-built NMR spectrometer interfaced to an Oxford magnet operating at 2T. The mechanical compressions were performed with a custom-built MR-compatible pressure cell and evaluated dynamically via one-dimensional projection. High-spatial-resolution two-dimensional MT images were obtained using a fast spin-echo (FSE) sequence on a 4T whole-body GE Signa scanner (GEMS, Milwaukee, WI, USA) to quantify the MTR maps of normal and collagen-depleted bovine patellae. RESULTS: All of the cartilage plugs from the bovine patellae showed that the MTR value increases continuously as a function of cartilage depth. Although the overall MTR trend as a function of depth is the same in both control and collagen-depleted cartilage, the magnitude of the MTR value differs between the two. The MTR value is decreased with collagen depletion and increased with mechanical compression. The increase in MTR value during compression may be due to a decrease in free water content and volume, resulting in an increase in collagen concentration. CONCLUSION: We demonstrated that the MTR in bovine patellar cartilage is depth-dependent and is relatively higher in the radial zone compared to the superficial zone. The high MTR in the radial zone not only depends on collagen content, it may also reflect a number of other parameters, such as the arrangement of macromolecules, high solid content, bound water fraction attached to macromolecules, radial orientation, etc.

Animals↗
PubMed2005

Quantification of cartilage biomechanical and biochemical properties via T1rho magnetic resonance imaging.

The aim of this study is to develop T1rho as an MR marker of the compositional and functional condition of cartilage. Specifically, we investigate the correlation of changes in cartilage biomechanical and biochemical properties with T1rho relaxation rate in a cytokine-induced model of degeneration. Bovine cartilage explants were cultured with 30 ng/mL of interleukin-1beta to mimic the cartilage degradation of early osteoarthritis. The average rate of T1rho relaxation was calculated from T(1rho) maps acquired on a 4.7 T research scanner. Stress-relaxation biomechanical tests were conducted with a confined compression apparatus to measure uniaxial aggregate modulus (HA) and hydraulic permeability (k0) using linear biphasic theory. Proteoglycan, collagen, and water content were measured via biochemical assays. Average T(1rho) relaxation rate was strongly correlated with proteoglycan content (R2 = 0.926), HA (R2 = 0.828), and log10 k0 (R2 = 0.862). Results of this study demonstrate that T1rho MRI can detect changes in proteoglycan content and biomechanical properties of cartilage in a physiologically relevant model of cartilage degeneration. The T1rho technique can potentially be used to noninvasively and quantitatively assess the biochemical and biomechanical characteristics of articular cartilage in humans during the progression of osteoarthritis.

Animals↗
PubMed2005

T1rho contrast in functional magnetic resonance imaging.

The application of T1 in the rotating frame (T1rho) to functional MRI in humans was studied at 3 T. Increases in neural activity increased parenchymal T1rho. Modeling suggested that cerebral blood volume mediated this increase. A pulse sequence named spin-locked echo planar imaging (SLEPI) that produces both T1rho and T2* contrast was developed and used in a visual functional MRI (fMRI)experiment. Spin-locked contrast significantly augments the T2* blood oxygen level-dependent (BOLD) contrast in this sequence. The total functional contrast generated by the SLEPI sequence (1.31%) was 54% larger than the contrast (0.85%) obtained from a conventional gradient-echo EPI sequence using echo times of 30 ms. Analysis of image SNR revealed that the spin-locked preparation period of the sequence produced negligible signal loss from static dephasing effects. The SLEPI sequence appears to be an attractive alternative to conventional BOLD fMRI, particularly when long echo times are undesirable, such as when studying prefrontal cortex or ventral regions, where static susceptibility gradients often degrade T2*-weighted images.

Algorithms↗
PubMed2005

Detection of changes in articular cartilage proteoglycan by T(1rho) magnetic resonance imaging.

The purpose of this work is to demonstrate the feasibility of T(1rho)-weighted magnetic resonance imaging (MRI) to quantitatively measure changes in proteoglycan content in cartilage. The T(1rho) MRI technique was implemented in an in vivo porcine animal model with rapidly induced cytokine-mediated cartilage degeneration. Six pigs were given an intra-articular injection of recombinant porcine interleukin-1beta (IL-1beta) into the knee joint before imaging to induce changes in cartilage via matrix metalloproteinase (MMP) induction. The induction of MMPs by IL-1 was used since it has been extensively studied in many systems and is known to create conditions that mimic in part characteristics similar to those of osteoarthritis. The contralateral knee joint was given a saline injection to serve as an internal control. T(1rho)-weighted MRI was performed on a 4 T whole-body clinical scanner employing a 2D fast spin-echo-based T(1rho) imaging sequence. T(1rho) relaxation parameter maps were computed from the T(1rho)-weighted image series. The average T(1rho) relaxation rate, R(1rho) (1/T(1rho)) of the IL-1beta-treated patellae was measured to be on average 25% lower than that of saline-injected patellae indicating a loss of proteoglycan. There was an average reduction of 49% in fixed charge density, measured via sodium MRI, of the IL-1beta-treated patellae relative to control corroborating the loss of proteoglycan. The effects of IL-1beta, primarily loss of PG, were confirmed by histological and immunochemical findings. The results from this study demonstrate that R(1rho) is able to track proteoglycan content in vivo.

Animals↗
PubMed2004

In vivo measurement of T1rho dispersion in the human brain at 1.5 tesla.

PURPOSE: To measure T1rho relaxation times and T1rho dispersion in the human brain in vivo. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) was performed on a 1.5-T GE Signa clinical scanner using the standard GE head coil. A fast spin-echo (FSE)-based T1rho-weighted MR pulse sequence was employed to obtain images from five healthy male volunteers. Optimal imaging parameters were determined while considering both the objective of the study and the guarantee that radio-frequency (RF) power deposition during MR did not exceed Food and Drug Administration (FDA)-mandated safety levels. RESULTS: T1rho-weighted MR images showed excellent contrast between different brain tissues. These images were less blurred than corresponding T2-weighted images obtained with similar contrast, especially in regions between brain parenchyma and cerebrospinal fluid (CSF). Average T1rho values for white matter (WM), gray matter (GM), and CSF were 85 +/- 3, 99 +/- 1, and 637 +/- 78 msec, respectively, at a spin-locking field of 500 Hz. T1rho is 30% higher in the parenchyma and 78% higher in CSF compared to the corresponding T2 values. T1rho dispersion was observed between spin-locking frequencies 0 and 500 Hz. CONCLUSION: T1rho-weighted MRI provides images of the brain with superb contrast and detail. T1rho values measured in the different brain tissues will serve as useful baseline values for analysis of T1rho changes associated with pathology.

Adult↗
PubMed2004

Correlation of T1rho with fixed charge density in cartilage.

PURPOSE: To establish the specificity of T1rho with respect to fixed charge density (FCD) as a measure of proteoglycan (PG) content in cartilage during the onset of osteoarthritis (OA). MATERIALS AND METHODS: T1rho-weighted and sodium MRI were performed on cartilage samples of enzymatically degraded bovine explants and natural osteoarthritic human samples representing controlled and physiological models of OA, respectively. Spatial maps of T1rho and FCD (measured using the previously validated method of sodium MRI) were calculated from image data. Data were extracted from the maps and subjected to linear regression to compare changes in T1rho with changes in FCD in each model. Tissue samples were subjected to histological staining for a reduction in PG content. RESULTS: Plots of normalized T1rho rate vs. FCD were found to be strongly correlated (R2 > 0.75 and 0.85) in both models with nearly the same slope of approximately 1/2 (P > 0.51). Loss of PG in bovine and human tissue was confirmed by histology. CONCLUSION: The strong correlation of the FCD and T1rho data in both the controlled and physiological models demonstrates that changes in T1rho are due predominantly to changes in PG content. This work is a first step in establishing T1rho as a method of quantifying PG changes in early-stage OA.

Animals↗
PubMed2004

Pulse sequence for multislice T1rho-weighted MRI.

A 2D multislice spin-lock (MS-SL) MR pulse sequence is presented for rapid volumetric T1rho-weighted imaging. Image quality is compared with T1rho-weighted data collected using a single-slice (SS) SL sequence and T2-weighted data from a standard MS spin-echo (SE) sequence. Saturation of longitudinal magnetization by the application of nonselective SL pulses is experimentally measured and theoretically modeled as T2rho decay. The saturation data is used to correct the image data as a function of the SL pulse duration to make quantitative measurements of T1rho. Measurements of T1rho using the saturation-corrected MS-SL data are nearly identical to those measured using an SS-SL sequence. The MS-SL sequence produces quantitative T1rho maps of an entire sample volume with the high-SNR advantages conferred by SE-based sequences.

Animals↗