Andrew J. Wheaton

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.

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.

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

To demonstrate an MRI method for directly visualizing amyloid‐β (Aβ) plaques in the APP/PS1 transgenic (tg) mouse brain in vivo, and show that T1ρ relaxation rate increases progressively with Alzheimers disease (AD)‐related pathology in the tg mouse brain.

In vivo measurement of T1ρ dispersion in the human brain at 1.5 tesla

To measure T1ρ relaxation times and T1ρ dispersion in the human brain in vivo.

Sodium magnetic resonance imaging of proteoglycan depletion in an in vivo model of osteoarthritis1

RATIONALE AND OBJECTIVES The aim of the study was to investigate the feasibility of using sodium magnetic resonance imaging (MRI) as a noninvasive quantitative technique for measuring proteoglycan (PG) content in an in vivo porcine model of osteoarthritis (OA). MATERIALS AND METHODS Biochemical conditions similar to those of OA were created by an intra-articular injection of recombinant porcine interleukin-1beta (IL-1beta) into the knee joint of pigs (n = 6) before performing MRI. The contralateral knee joint was given a saline injection to serve as an internal control. Sodium MRI data were acquired on a 4-T clinical MR scanner and used to compute quantitative sodium and fixed charge density (FCD) maps based on a previously established methodology. In vivo FCD maps were compared with FCD maps obtained using ex vivo patellae harvested from the specimens. The tissue and joint fluid were subjected to histologic and immunohistochemical analyses as independent measurements of IL-1beta activity and PG loss. RESULTS The average FCD of IL-1beta-treated patellae was measured to be 49% lower than that of saline-treated patellae, indicating a loss of PG content. These results were supported by histologic and immunochemical findings, most notably a reduction in staining for PG and an increase in matrix metalloproteinases in the synovial fluid. CONCLUSION Sodium MRI can serve as a quantitative method to measure in vivo changes in PG content in an animal model of OA. The use of a noninvasive quantitative in vivo PG measurement technique such as sodium MRI on an animal model would aid greatly in efforts to monitor the efficacy of treatments for OA. Furthermore, these results indicate that early degenerative events could be detected noninvasively in vivo in humans with PG-depleting diseases such as OA.

In vivo quantification of T1ρ using a multislice spin‐lock pulse sequence

A multislice spin‐lock (MS‐SL) pulse sequence is implemented on a clinical scanner to acquire multiple images with spin‐lock‐generated contrast of the knee joints of six healthy human subjects. The MS‐SL sequence produces images with T1ρ contrast with an additional factor of intrinsic T2ρ weighting, which hinders direct measurement of T1ρ. A method is presented to compensate the MS‐SL‐generated data with regard to T2ρ in an effort to accurately calculate multislice T1ρ maps in a feasible experimental time. The T2ρ‐compensated multislice T1ρ maps produced errors in the measurement of T1ρ in healthy patellar cartilage of ∼5% compared to the gold standard measurement of T1ρ acquired with single‐slice spin‐lock pulse sequence. The MS‐SL sequence has potential as an important clinical tool for the acquisition of multislice T1ρ‐weighted images and/or quantitative multislice T1ρ maps. Magn Reson Med 52:1453–1458, 2004.

T1ρ-relaxation mapping of human femoral-tibial cartilage in vivo

To demonstrate the in vivo feasibility of measuring spin‐lattice relaxation time in the rotating frame (T1ρ); and T1ρ‐dispersion in human femoral cartilage. Furthermore, we aimed to compute the baseline T1ρ‐relaxation times and spin‐lock contrast (SLC) maps on healthy volunteers, and compare relaxation times and signal‐to‐noise ratio (SNR) with corresponding T2‐weighted images.

Method for reduced SAR T1ρ-weighted MRI

A reduced specific absorption rate (SAR) version of the T1ρ‐weighted MR pulse sequence was designed and implemented. The reduced SAR method employs a partial k‐space acquisition approach in which a full power spin‐lock pulse is applied to only the central phase‐encode lines of k‐space, while the remainder of k‐space receives a low‐power spin‐lock pulse. Acquisition of high‐ and low‐power phase‐encode lines are interspersed chronologically to minimize average power deposition. In this way, the majority of signal energy in the central portion of k‐space receives full T1ρ‐weighting, while the average SAR of the overall acquisition can be reduced, thereby lowering the minimum safely allowable TR. The pulse sequence was used to create T1ρ maps of a phantom, an in vivo mouse brain, and the brain of a human volunteer. In the images of the human brain, SAR was reduced by 40% while the measurements of T1ρ differed by only 2%. The reduced SAR sequence enables T1ρ‐weighted MRI in a clinical setting, even at high field strengths. Magn Reson Med 51:1096–1102, 2004.