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Ravinder Reddy

Bio: Ravinder Reddy is an academic researcher from University of Pennsylvania. The author has contributed to research in topics: Cartilage & Magnetic resonance imaging. The author has an hindex of 57, co-authored 249 publications receiving 11091 citations. Previous affiliations of Ravinder Reddy include Osmania Medical College & National Institutes of Health.


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Journal ArticleDOI
TL;DR: In a rat brain tumor model with blood-brain barrier disruption, intravenous glutamate injection resulted in a clear elevation of GluCEST and a similar increase in the proton magnetic resonance spectroscopy signal of glutamate, demonstrating the feasibility of using GLUCEST for mapping relative changes in glutamate concentration, as well as pH, in vivo.
Abstract: Glutamate (Glu) exhibits a pH and concentration dependent chemical exchange saturation transfer effect (CEST) between its -amine group and bulk water, here termed GluCEST. GluCEST asymmetry is observed at ~3 parts per million downfield from bulk water. Following middle cerebral artery occlusion in the rat brain, an approximately 100% elevation of GluCEST in the ipsilateral side compared to the contralateral side was observed, and is predominantly due to pH changes. In a rat brain tumor model with blood brain barrier disruption, intravenous Glu injection resulted in a clear elevation of GluCEST and a comparable increase in the proton magnetic resonance spectroscopy signal of Glu. GluCEST maps from healthy human brain at 7T were also obtained. These results demonstrate the feasibility and potential of GluCEST for mapping relative changes in Glu concentration as well as pH in vivo. Potential contributions from other brain metabolites to the GluCEST effect are also discussed.

533 citations

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TL;DR: Proteoglycan depletion‐induced changes in T1ρ (spin‐lattice relaxation in rotating frame) relaxation and dispersion in articular cartilage were studied at 4T and showed a strong correlation between changes in PG and T1RH.
Abstract: Proteoglycan (PG) depletion-induced changes in T1rho (spin-lattice relaxation in rotating frame) relaxation and dispersion in articular cartilage were studied at 4T. Using a spin-lock cluster pre-encoded fast spin echo sequence, T1rho maps of healthy bovine specimens and specimens that were subjected to PG depletion were computed at varying spin-lock frequencies. Sequential PG depletion was induced by trypsinization of cartilage for varying amounts of time. Results demonstrated that over 50% depletion of PG from bovine articular cartilage resulted in average T1rho increases from 110-170 ms. Regression analysis of the data showed a strong correlation (R2 = 0.987) between changes in PG and T1rho. T1rho values were highest at the superficial zone and decreased gradually in the middle zone and again showed an increasing trend in the region near the subchondral bone. The potentials of this method in detecting early degenerative changes of cartilage are discussed. Also, T(1rho)-dispersion changes as a function of PG depletion are described.

356 citations

Journal ArticleDOI
TL;DR: The results suggest that T1ρ measurements are selectively sensitive to proteoglycan content, and the potential of this method in distinguishing the early degenerative changes in cartilage associated with osteoarthritis is discussed.
Abstract: Spin-lattice relaxation in the rotating frame (T1rho) dispersion spectroscopy and imaging were used to study normal and enzymatically degraded bovine articular cartilage. Normal specimens demonstrate significant T1rho "dispersion" (approximately 60 to approximately 130 ms) in the 100 Hz to 9 kHz frequency range. Proteoglycan-degraded specimens have 33% greater T1rho values than collagen-degraded or normal samples. T1rho-weighted images reveal structure not found in conventional T1- or T2-weighted images. Our results suggest that T1rho measurements are selectively sensitive to proteoglycan content. The potential of this method in distinguishing the early degenerative changes in cartilage associated with osteoarthritis is discussed.

289 citations

Journal ArticleDOI
TL;DR: To quantify the spin‐lattice relaxation time in the rotating frame (T1ρ) in various clinical grades of human osteoarthritis cartilage specimens obtained from total knee replacement surgery, and to correlate the T1ρ with OA disease progression and compare it with the transverse relaxation time (T2).
Abstract: Purpose To quantify the spin-lattice relaxation time in the rotating frame (T1ρ) in various clinical grades of human osteoarthritis (OA) cartilage specimens obtained from total knee replacement surgery, and to correlate the T1ρ 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 T1ρ-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 T1ρ) compared to healthy cartilage tissue. In various grades of OA specimens, the T1ρ 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 T1ρ in various clinical grades of OA specimens were ∼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 T1ρ relaxation mapping is a sensitive noninvasive marker for quantitatively predicting and monitoring the status of macromolecules in early OA. Furthermore, T1ρ 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, T1ρ relaxation mapping may be useful for evaluating early OA therapy. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

286 citations

Journal ArticleDOI
TL;DR: The feasibility of calculating FCD by 23Na MRI is shown and MRI protocols for human studies, in vivo, are introduced and employed in quantifying the FCD of articular cartilage of human volunteers in vivo.
Abstract: 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.

260 citations


Cited by
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TL;DR: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors.
Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

6,968 citations

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TL;DR: The unique and complex structure of articular cartilage makes treatment and repair or restoration of the defects challenging for the patient, the surgeon, and the physical therapist.
Abstract: Articular cartilage is the highly specialized connective tissue of diarthrodial joints. Its principal function is to provide a smooth, lubricated surface for articulation and to facilitate the transmission of loads with a low frictional coefficient (Figure 1). Articular cartilage is devoid of blood vessels, lymphatics, and nerves and is subject to a harsh biomechanical environment. Most important, articular cartilage has a limited capacity for intrinsic healing and repair. In this regard, the preservation and health of articular cartilage are paramount to joint health. Figure 1. Gross photograph of healthy articular cartilage in an adult human knee. Injury to articular cartilage is recognized as a cause of significant musculoskeletal morbidity. The unique and complex structure of articular cartilage makes treatment and repair or restoration of the defects challenging for the patient, the surgeon, and the physical therapist. The preservation of articular cartilage is highly dependent on maintaining its organized architecture.

1,835 citations

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TL;DR: In the coming years, a better definition of osteoarthritis is expected by delineating different phenotypes of the disease, and treatment targeted more specifically at these phenotypes might lead to improved outcomes.

1,743 citations

Journal ArticleDOI
TL;DR: There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.
Abstract: Context Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. Objectives To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. Data Sources The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. Study Selection Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. Data Extraction Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. Data Synthesis Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. Conclusions There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.

1,377 citations

Journal ArticleDOI
TL;DR: Results from these studies reveal considerable support for longitudinal associations between cognition and community outcome in schizophrenia and demonstrate that cognitive assessment predict later functional outcome and provide a rationale for psychopharmacological interventions for cognitive deficits in schizophrenia.

1,355 citations