Ravinder Reddy

Proteoglycan‐induced changes in T1ρ‐relaxation of articular cartilage at 4T

Proteoglycan (PG) depletion‐induced changes in T1ρ (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, T1ρ 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 T1ρ increases from 110–170 ms. Regression analysis of the data showed a strong correlation (R2 = 0.987) between changes in PG and T1ρ. T1ρ 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, T1ρ‐dispersion changes as a function of PG depletion are described. Magn Reson Med 46:419–423, 2001.

Magnetic resonance imaging of glutamate

Glutamate, a major neurotransmitter in the brain, shows a pH- and concentration-dependent chemical exchange saturation transfer effect (GluCEST) between its amine group and bulk water, with potential for in vivo imaging by nuclear magnetic resonance. GluCEST asymmetry is observed ∼3 p.p.m. downfield from bulk water. Middle cerebral artery occlusion in the rat brain resulted in an ∼100% elevation of GluCEST in the ipsilateral side compared with the contralateral side, predominantly owing to pH changes. 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. GluCEST maps from healthy human brain were also obtained. These results demonstrate the feasibility of using GluCEST for mapping relative changes in glutamate concentration, as well as pH, in vivo. Contributions from other brain metabolites to the GluCEST effect are also discussed.

T1ρ relaxation mapping in human osteoarthritis (OA) cartilage: Comparison of T1ρ with T2

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).

Proteoglycan Depletion–Induced Changes in Transverse Relaxation Maps of Cartilage

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.

Assessment of Human Disc Degeneration and Proteoglycan Content Using T1ρ-weighted Magnetic Resonance Imaging

Study Design. T1&rgr; relaxation was quantified and correlated with intervertebral disc degeneration and proteoglycan content in cadaveric human lumbar spine tissue. Objective. To show the use of T1&rgr;-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. T1&rgr; 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 T1&rgr; in the nucleus pulposus was calculated from quantitative T1&rgr; 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. T1&rgr; 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 T1&rgr; and sulfated-glycosaminoglycan content. T1&rgr; was moderately correlated with water content. Conclusions. Results from this study suggest that T1&rgr; may provide a tool for the diagnosis of early degenerative changes in the disc. T1&rgr;-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.

Quantification of cartilage biomechanical and biochemical properties via T1ρ magnetic resonance imaging

The aim of this study is to develop T1ρ 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 T1ρ relaxation rate in a cytokine‐induced model of degeneration. Bovine cartilage explants were cultured with 30 ng/mL of interleukin‐1β to mimic the cartilage degradation of early osteoarthritis. The average rate of T1ρ relaxation was calculated from T1ρ 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 T1ρ 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 T1ρ MRI can detect changes in proteoglycan content and biomechanical properties of cartilage in a physiologically relevant model of cartilage degeneration. The T1ρ 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. Magn Reson Med, 2005.

In vivo mapping of brain myo-inositol.

Myo-Inositol (MI) is one of the most abundant metabolites in the human brain located mainly in glial cells and functions as an osmolyte. The concentration of MI is altered in many brain disorders including Alzheimers disease and brain tumors. Currently available magnetic resonance spectroscopy (MRS) methods for measuring MI are limited to low spatial resolution. Here, we demonstrate that the hydroxyl protons on MI exhibit chemical exchange with bulk water and saturation of these protons leads to reduction in bulk water signal through a mechanism known as chemical exchange saturation transfer (CEST). The hydroxyl proton exchange rate (k=600 s(-1)) is determined to be in the slow to intermediate exchange regime on the NMR time scale (chemical shift (∆ω)>k), suggesting that the CEST effect of MI (MICEST) can be imaged at high fields such as 7 T (∆ω=1.2×10(3)rad/s) and 9.4 T (∆ω=1.6×10(3) rad/s). Using optimized imaging parameters, concentration dependent broad CEST asymmetry between ~0.2 and 1.5 ppm with a peak at ~0.6 ppm from bulk water was observed. Further, it is demonstrated that MICEST detection is feasible in the human brain at ultra high fields (7 T) without exceeding the allowed limits on radiofrequency specific absorption rate. Results from healthy human volunteers (N=5) showed significantly higher (p=0.03) MICEST effect from white matter (5.2±0.5%) compared to gray matter (4.3±0.5%). The mean coefficient of variations for intra-subject MICEST contrast in WM and GM were 0.49 and 0.58 respectively. Potential overlap of CEST signals from other brain metabolites with the observed MICEST map is discussed. This noninvasive approach potentially opens the way to image MI in vivo and to monitor its alteration in many disease conditions.

Water magnetic relaxation dispersion in biological systems: The contribution of proton exchange and implications for the noninvasive detection of cartilage degradation

Magnetic relaxation has been used extensively to study and characterize biological tissues. In particular, spin-lattice relaxation in the rotating frame (T1ρ) of water in protein solutions has been demonstrated to be sensitive to macromolecular weight and composition. However, the nature of the contribution from low frequency processes to water relaxation remains unclear. We have examined this problem by studying the water T1ρ dispersion in peptide solutions (14N- and 15N-labeled), glycosaminoglycan solutions, and samples of bovine articular cartilage before and after proteoglycan degradation. We find in model systems and tissue that hydrogen exchange from NH and OH groups to water dominates the low frequency water T1ρ dispersion, in the context of the model used to interpret the relaxation data. Further, low frequency dispersion changes are correlated with loss of proteoglycan from the extra-cellular matrix of articular cartilage. This finding has significance for the noninvasive detection of matrix degradation.

Correlation of T1ρ with fixed charge density in cartilage

To establish the specificity of T1ρ with respect to fixed charge density (FCD) as a measure of proteoglycan (PG) content in cartilage during the onset of osteoarthritis (OA).

Reduction of residual dipolar interaction in cartilage by spin-lock technique

The influence of radiofrequency (RF) spin‐lock pulse on the laminar appearance of articular cartilage in MR images was investigated. Spin‐lock MRI experiments were performed on bovine cartilage plugs on a 4.7 Tesla small‐bore MRI scanner, and on human knee cartilage in vivo on a 1.5 Tesla clinical scanner. When the normal to the surface of cartilage was parallel to B0, a typical laminar appearence was exhibited in T2‐weighted images of cartilage plugs, but was absent in T1ρ‐weighted images of the same plugs. At the “magic angle” orientation (when the normal to the surface of cartilage was 54.7° with respect to B0), neither the T2 nor the T1ρ images demonstrated laminae. At the same time, T1ρ values were greater than T2 at both orientations throughout the cartilage. T1ρ dispersion (i.e., the dependence of the relaxation rate on the spin‐lock frequency ω1) was observed, which reached a steady‐state value of close to 2 kHz in both parallel and magic‐angle orientations. These results suggest that residual dipolar interaction from motionally‐restricted water and relaxation processes, such as chemical exchange, contribute to T1ρ dispersion in cartilage. Further, one can reduce the laminar appearance in human articular cartilage by applying spin‐lock RF pulses, which may lead to a more accurate diagnosis of degenerative changes in cartilage. Magn Reson Med 52:1103–1109, 2004.