Arijitt Borthakur

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.

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.

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.

Noninvasive Quantification of Human Nucleus Pulposus Pressure with Use of T1ρ-Weighted Magnetic Resonance Imaging

BACKGROUND Early diagnosis is a challenge in the treatment of degenerative disc disease. A noninvasive biomarker detecting functional mechanics of the disc is needed. T1rho-weighted imaging, a spin-lock magnetic resonance imaging technique, has shown promise for meeting this need in in vivo studies demonstrating the clinical feasibility of evaluating both intervertebral discs and articular cartilage. The objectives of the present study were (1) to quantitatively determine the relationship between T1rho relaxation time and measures of nucleus pulposus mechanics, and (2) to evaluate whether the quantitative relationship of T1rho relaxation time with the degenerative grade and glycosaminoglycan content extend to more severe degeneration. It was hypothesized that the isometric swelling pressure and compressive modulus would be directly correlated with the T1rho relaxation time and the apparent permeability would be inversely correlated with the T1rho relaxation time. METHODS Eight cadaver human lumbar spines were imaged to measure T1rho relaxation times. The nucleus pulposus tissue from the L1 disc through the S1 disc was tested in confined compression to determine the swelling pressure, compressive modulus, and permeability. The glycosaminoglycan and water contents were measured in adjacent tissue. Linear regression analyses were performed to examine the correlation between the T1rho relaxation time and the other measured variables. Mechanical properties and biochemical content were evaluated for differences associated with degeneration. RESULTS A positive linear correlation was observed between the T1rho relaxation time on the images of the nucleus pulposus and the swelling pressure (r = 0.59), glycosaminoglycan content per dry weight (r = 0.69), glycosaminoglycan per wet weight (r = 0.49), and water content (r = 0.53). No significant correlations were observed between the T1rho relaxation time and the modulus or permeability. Similarly, the T1rho relaxation time, swelling pressure, glycosaminoglycan content per dry weight, and water content were significantly altered with degeneration, whereas the modulus and permeability were not. CONCLUSIONS T1rho-weighted magnetic resonance imaging has a strong potential as a quantitative biomarker of the mechanical function of the nucleus pulposus and of disc degeneration.

Knee Articular Cartilage Damage in Osteoarthritis: Analysis of MR Image Biomarker Reproducibility in ACRIN-PA 4001 Multicenter Trial

PURPOSE To prospectively determine the reproducibility of quantitative magnetic resonance (MR) imaging biomarkers of the morphology and composition (spin lattice relaxation time in rotating frame [T1-ρ], T2) of knee cartilage in a multicenter multivendor trial involving patients with osteoarthritis (OA) and asymptomatic control subjects. MATERIALS AND METHODS This study was HIPAA compliant and approved by the institutional review committees of the participating sites, with written informed consent obtained from all participants. Fifty subjects from five sites who were deemed to have normal knee joints (n = 18), mild OA (n = 16), or moderate OA (n = 16) on the basis of Kellgren-Lawrence scores were enrolled. Each participant underwent four sequential 3-T knee MR imaging examinations with use of the same imager and with 2-63 days (median, 18 days) separating the first and last examinations. Water-excited three-dimensional T1-weighted gradient-echo imaging, T1-ρ imaging, and T2 mapping of cartilage in the axial and coronal planes were performed. Biomarker reproducibility was determined by using intraclass correlation coefficients (ICCs) and root-mean-square coefficients of variation (RMS CVs, expressed as percentages). RESULTS Morphometric biomarkers had high reproducibility, with ICCs of 0.989 or greater and RMS CVs lower than 4%. The largest differences between the healthy subjects and the patients with radiographically detected knee OA were those in T1-ρ values, but precision errors were relatively large. Reproducibility of T1-ρ values was higher in the thicker patellar cartilage (ICC range, 0.86-0.93; RMS CV range, 14%-18%) than in the femorotibial joints (ICC range, 0.20-0.84; RMS CV range, 7%-19%). Good to high reproducibility of T2 was observed, with ICCs ranging from 0.61 to 0.98 and RMS CVs ranging from 4% to 14%. CONCLUSION MR imaging measurements of cartilage morphology, T2, and patellar T1-ρ demonstrated moderate to excellent reproducibility in a clinical trial network.

Biomarkers for Early Detection of Alzheimer Pathology

The increasing prevalence of Alzheimer’s disease and the devastating consequences of late-life dementia motivates the drive to develop diagnostic biomarkers to reliably identify the pathology associated with this disorder. Strategies to accomplish this include the detection of altered levels of tau and amyloid in cerebrospinal fluid, the use of structural MRI to identify disease-specific patterns of regional atrophy and MRI T1ρ to detect disease-related macromolecular protein aggregation, and the direct imaging of amyloid deposits using positron emission tomography and single photon emission computerized tomography. Success will facilitate the ability to reliably diagnose Alzheimer’s disease while the symptoms of brain failure are mild and may provide objective measures of disease-modifying treatment efficacy.

Sodium MR Imaging Detection of Mild Alzheimer Disease: Preliminary Study

BACKGROUND AND PURPOSE: There is significant interest in the development of novel noninvasive techniques for the diagnosis of Alzheimer disease (AD) and tracking its progression. Because MR imaging has detected alterations in sodium levels that correlate with cell death in stroke, we hypothesized that there would be alterations of sodium levels in the brains of patients with AD, related to AD cell death. MATERIALS AND METHODS: A total of 10 volunteers (5 with mild AD and 5 healthy control subjects) were scanned with a 20-minute sodium (23Na) MR imaging protocol on a 3T clinical scanner. RESULTS: After normalizing the signal intensity from the medial temporal lobes corresponding to the hippocampus with the ventricular signal intensity, we were able to detect a 7.5% signal intensity increase in the brains of patients with AD (AD group, 68.25% ± 3.4% vs control group, 60.75% ± 2.9%; P < .01). This signal intensity enhancement inversely correlated with hippocampal volume (AD group, 3.22 ± 0.50 cm3 vs control group, 3.91 ± 0.45 cm3; r2 = 0.50). CONCLUSIONS: This finding suggests that sodium imaging may be a clinically useful tool to detect the neuropathologic changes associated with AD.

Proton spin‐lock ratio imaging for quantitation of glycosaminoglycans in articular cartilage

To quantify glycosaminoglycans (GAG) in intact bovine patellar cartilage using the proton spin‐lock ratio imaging method. This approach exploits spin‐lattice relaxation time in the rotating frame (T1ρ) imaging and T1ρ relaxivity (R1ρ).