Biomedical subjects

Andrew J Wheaton

Publications and source records attributed to Andrew J Wheaton.

At least 19 recordsLinked to original sources

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

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↗

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

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↗

PubMed2004

Method for reduced SAR T1rho-weighted MRI.

A reduced specific absorption rate (SAR) version of the T(1rho)-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 T(1rho)-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 T(1rho) 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 T(1rho) differed by only 2%. The reduced SAR sequence enables T(1rho)-weighted MRI in a clinical setting, even at high field strengths.

Animals↗

PubMed2004

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 appearance was exhibited in T2-weighted images of cartilage plugs, but was absent in T1rho-weighted images of the same plugs. At the "magic angle" orientation (when the normal to the surface of cartilage was 54.7 degrees with respect to B0), neither the T2 nor the T1rho images demonstrated laminae. At the same time, T1rho values were greater than T2 at both orientations throughout the cartilage. T1rho dispersion (i.e., the dependence of the relaxation rate on the spin-lock frequency omega1) 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 T1rho 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.

Animals↗

PubMed2004

In vivo quantification of T1rho 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 T1rho contrast with an additional factor of intrinsic T2rho weighting, which hinders direct measurement of T1rho. A method is presented to compensate the MS-SL-generated data with regard to T2rho in an effort to accurately calculate multislice T1rho maps in a feasible experimental time. The T2rho-compensated multislice T1rho maps produced errors in the measurement of T1rho in healthy patellar cartilage of approximately 5% compared to the gold standard measurement of T1rho acquired with single-slice spin-lock pulse sequence. The MS-SL sequence has potential as an important clinical tool for the acquisition of multislice T1rho-weighted images and/or quantitative multislice T1rho maps.

Adult↗

PubMed2004

T2rho-weighted contrast in MR images of the human brain.

In this work, the feasibility of using T2rho weighting as an MR contrast mechanism is evaluated. Axial images of a human brain were acquired using a single-slice spin-lock T2rho-weighted pulse sequence and compared to analogous T2-weighted images of the same slice. The contrast between white matter and gray matter in T2rho-weighted images was approximately 40% greater than that from T2-weighted data. These preliminary data suggest that the novel contrast mechanism of T2rho can be used to yield high-contrast T2-like images.

Adult↗

PubMed2004

3D-T1rho-relaxation mapping of articular cartilage: in vivo assessment of early degenerative changes in symptomatic osteoarthritic subjects.

RATIONALE AND OBJECTIVES: To determine the in vivo feasibility of quantifying early degenerative changes in patellofemoral joint of symptomatic human knee using spin-lattice relaxation time in the rotating frame (T(1rho)) magnetic resonance imaging (MRI). MATERIALS AND METHODS: All the MRI experiments were performed on a 1.5 T whole-body GE Signa clinical scanner using a custom built 15-cm diameter transmit-receive quadrature birdcage radiofrequency coil. The T(1rho)-prepared magnetization was imaged with a three-dimensional gradient-echo pulse sequence pre-encoded with a three-pulse cluster consisting of two hard 90 degrees pulses and a low power spin-lock pulse. Quantitative T(1rho) relaxation maps of asymptomatic (n = 8 males), and six symptomatic human volunteers (four men, two women) were computed using a appropriate signal expression. RESULTS: All six symptomatic volunteers showed elevation in T(1rho) relaxation times when compared with asymptomatic subjects. In symptomatic population, the T(1rho) relaxation times varied from 63 +/- 4 ms to 95 +/- 12 ms (mean +/- standard deviation) depending on the degree of cartilage degeneration. The increase in T(1rho) of symptomatic population was statistically significant (n = 6, P <.002) when compared with corresponding asymptomatic population. However, in asymptomatic population the relaxation times varied only from approximately 45 to 55 ms (n = 8, age range 22-45 years). CONCLUSION: Preliminary results demonstrated the in vivo feasibility of quantifying early biochemical changes in symptomatic osteoarthritis subjects employing T(1rho)-weighted MRI on a 1.5 T clinical scanner. This study on limited number of symptomatic population shows that T(1rho)-weighted MRI provides a noninvasive marker for quantitation of early degenerative changes of cartilage in vivo. However, further studies are needed to correlate early osteoarthritis determined from arthroscopy with T(1rho) in a large symptomatic population.

Adult↗

PubMed2004

Cartilage volume quantification via Live Wire segmentation.

RATIONALE AND OBJECTIVES: A reduction in cartilage volume is characteristic of osteoarthritis and hence there exists a need for an accurate and reproducible method to measure in vivo cartilage volume. Quantification of cartilage volume from magnetic resonance (MR) images requires a segmentation technique such as the user-driven "Live Wire" strategy that can reliably delineate object volumes in a time-efficient manner. In the present work, the accuracy and reproducibility of the Live Wire method for the quantification of cartilage volume in MR images is evaluated. MATERIALS AND METHODS: The accuracy of the Live Wire method was assessed by comparing the MR-based volume measurement of a patellar cartilage-shaped phantom versus data calculated via water displacement. The inter- and intra-operator reproducibility of the technique was evaluated from Live Wire segmentation of the patellar cartilage volume from fat-suppressed 3-dimensional spoiled-gradient-echo images of five healthy human volunteers performed by three operators. To provide data for analysis of inter-scan reproducibility, the human scans were repeated five times with the aid of a leg-restraining jig to minimize repositioning error. RESULTS: The volume of the patellar cartilage-shaped phantom measured via Live Wire segmentation of MR images was within 97.8% of its true volume. The average inter- and intra-operator coefficients of variation of three operators were 3.0% and 0.4%, respectively. The average inter-scan coefficient of variation of five repeated scans of each volunteer was 2.7%. CONCLUSION: The data suggest that the Live Wire strategy is an accurate, reproducible, and efficient technique to measure cartilage volume in vivo in a feasible amount of operator time.

Adult↗

PubMed2004

Sodium magnetic resonance imaging of proteoglycan depletion in an in vivo model of osteoarthritis.

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.

Animals↗

PubMed2004

Proteoglycan loss in human knee cartilage: quantitation with sodium MR imaging--feasibility study.

The feasibility of using sodium magnetic resonance (MR) imaging to detect proteoglycan loss in early-stage osteoarthritis is evaluated. Fixed charge density (FCD) maps were calculated from sodium MR imaging data collected in nine healthy volunteers and three individuals with symptoms of early-stage osteoarthritis by using a 4.0-T clinical MR imaging unit. Data from the healthy individuals revealed a mean FCD of -182 mmol/L +/- 9. Data from the symptomatic subjects revealed focal regions of decreased FCD, with mean values ranging from -108 to -144 mmol/L, indicating proteoglycan loss from the cartilage matrix. The data suggest that sodium MR imaging has potential for use as a quantitative diagnostic tool to measure changes in proteoglycan content in early-stage osteoarthritis.

Adult↗

PubMed2003

T 1 rho-relaxation mapping of human femoral-tibial cartilage in vivo.

PURPOSE: To demonstrate the in vivo feasibility of measuring spin-lattice relaxation time in the rotating frame (T(1rho)); and T(1rho)-dispersion in human femoral cartilage. Furthermore, we aimed to compute the baseline T(1rho)-relaxation times and spin-lock contrast (SLC) maps on healthy volunteers, and compare relaxation times and signal-to-noise ratio (SNR) with corresponding T(2)-weighted images. MATERIALS AND METHODS: All MR imaging experiments were performed on a 1.5 T GE Signa scanner (GEMS, Milwaukee, WI) using a custom built 15-cm transmit-receive quadrature birdcage radio-frequency (RF) coil. The T(1rho)-prepared magnetization was imaged with a single-slice two-dimensional fast spin-echo (FSE) pulse sequence preencoded with a three-pulse cluster consisting of two hard 90 degrees pulses and a low power spin-lock pulse. T(1rho)-dispersion imaging was performed by varying the spin-lock frequency from 100 to 500 Hz in five steps in addition to varying the length of the spin-lock pulse. RESULTS: The average T(1rho)-relaxation times in the weight-bearing (WB) and nonweight-bearing (NWB) regions of the femoral condyle were 42.2 +/- 3.6 msec and 55.7 +/- 2.3 msec (mean +/- SD, N = 5, P < 0.0001), respectively. In the same regions, the corresponding T(2)-relaxation times were 31.8 +/- 1.5 msec and 37.6 +/- 3.6 msec (mean +/- SD, N = 5, P < 0.0099). T(1rho)-weighted images have approximately 20%-30% higher SNR than the corresponding T(2)-weighted images for similar echo time. The average SLC in the WB region of femoral cartilage was 30 +/-4.0%. Furthermore, SLC maps provide better contrast between fluid and articular surface of femoral-tibial joint than T(1rho)-maps. The T(1rho)-relaxation times varied from 32 msec to 42 msec ( approximately 31%) in the WB and 37 msec to 56 msec ( approximately 51%) in NWB regions of femoral condyle, respectively, in the frequency range 0-500 Hz (T(1rho)-dispersion). CONCLUSION: The feasibility of performing in vivo T(1rho) relaxation mapping in femoral cartilage at 1.5T clinical scanner without exceeding Food and Drug Administration (FDA) limits on specific absorption rate (SAR) of RF energy was demonstrated.

Adult↗