Initial evaluation of the use of USPIO cell labeling and noninvasive MR monitoring of human tissue-engineered vascular grafts in vivo.

This pilot study examines noninvasive MR monitoring of tissue-engineered vascular grafts (TEVGs) in vivo using cells labeled with iron oxide nanoparticles. Human aortic smooth muscle cells (hASMCs) were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. The labeled hASMCs, along with human aortic endothelial cells, were incorporated into eight TEVGs and were then surgically implanted as aortic interposition grafts in a C.B-17 SCID/bg mouse host. USPIO-labeled hASMCs persisted in the grafts throughout a 3 wk observation period and allowed noninvasive MR imaging of the human TEVGs for real-time, serial monitoring of hASMC retention. This study demonstrates the feasibility of applying noninvasive imaging techniques for evaluation of in vivo TEVG performance.

Significant precision improvement for temperature mapping.

MR temperature measurements are important for applications such as the evaluation of thermal therapies and radiofrequency (RF) coil heating effects. In this work the spherical mean value (SMV) method has been applied to significantly improve the precision of MR temperature mapping in a homogeneous gel phantom. Temperature-increase maps of the phantom were obtained with three-dimensional (3D) MR phase difference mapping after heating with the RF coil. The temperature-increase distribution in most regions in the phantom is a harmonic function with the mean value property. Based on this property, the precision of temperature-increase maps was improved up to sixfold with the SMV method. Comparison of this method with conventional smoothing, further precision improvement, and the in vivo application of the SMV method are discussed.

Proteoglycan-induced changes in T1rho-relaxation of articular cartilage at 4T.

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.

Water distribution patterns inside bovine articular cartilage as visualized by 1H magnetic resonance imaging.

OBJECTIVE: To develop a magnetic resonance imaging (MRI) technique to non-invasively map water volume fraction (WVF) in articular cartilage. Special emphasis was placed on spatial resolution and temporal considerations, aimed at creating a procedure feasible for eventual human studies. DESIGN: Absolute proton density MR images of intact, ex vivo bovine patellae were calculated from fully T(1) relaxed, short echo time images. This was accomplished through compensation for T(2) decay with calculated T(2) maps. Calibration of the signal intensity in the image was accomplished with the use of H2O:D2O phantoms, where the WVF was varied from 0.95 to 0.75. Application of the calibration curve to the entire image yielded images that represent WVF on a pixel by pixel basis. Calculations of water content by weight were performed by considering the density of the solid content. RESULTS: Using four echo time points, experiments comparing MR images from single-echo and multi-echo spin echo sequences yielded similar results. T(2) decreased with depth through the cartilage, with a maximum at the articular surface of approx 100 ms, and a approximately 50 ms minimum at the bone/cartilage interface. The WVF through the depth of the cartilage showed a similar trend, decreasing from 0.9 at the surface, to 0.7 at the bone/cartilage interface. Translation to a weight percent yielded approximately 86% weight at the surface, trending down to approximately 63% at the bone/cartilage interface, with an average of 74.5% for five patellae. These MRI derived values were compared to the measured weight of water in excised cartilage plugs from the same patellae and showed remarkably close agreement. CONCLUSION: We have demonstrated that MRI can non-invasively map WVF in cartilage in a pixel by pixel manner. This was accomplished in a time span that was clinically feasible, allowing the routine use of this method in a clinical setting. Moreover, this procedure employed standard MRI equipment and pulse sequences, avoiding the need for hardware modifications and using simple post processing methods. However, baseline studies need to be performed prior to incorporation into a standard radiological evaluation. Implications in the diagnosis of osteoarthritis (OA) are discussed.

Sensitivity of MRI to proteoglycan depletion in cartilage: comparison of sodium and proton MRI.

OBJECTIVE: The purpose of this work was to evaluate the results from sodium and proton magnetic resonance imaging (MRI) in detecting small changes in proteoglycan (PG) content in bovine articular cartilage specimens. DESIGN: Articular cartilage from 15 specimens of bovine patellae were subjected to partial PG depletion with different concentrations of trypsin for 30 min. Sodium and proton MR images of the intact specimen were obtained on a 4T GE clinical MRI system. Two custom-built 7 cm-diameter solenoid coils tuned to proton and sodium frequencies were employed. Fast gradient echo and spin echo imaging sequences were used to determine sodium density, proton density and proton relaxation times (T(1)and T(2)) of the specimens. Spectrophotometric assay was performed after MRI to determine PG concentrations of the cartilage specimens. RESULTS: The sodium signal change correlated well with the observed PG loss (R(2)=0.85, P< 0.01) whereas the proton signal change was inconsistent (R(2)=0.10, P< 0.8). The change in proton T(1)and T(2)between the two regions did not correlate with PG loss (R(2)=0. 07 and R(2)=0.06, respectively). CONCLUSIONS: Results from these studies demonstrate that sodium MRI is both sensitive and specific in detecting small changes in PG concentration, whereas proton density and relaxation properties are not sensitive to small changes in PG content.

MR imaging of RF heating using a paramagnetic doped agarose phantom.

In this paper, we present the first description of a technique to visualize and quantitate radiofrequency (RF) heating of a tissue phantom during a magnetic resonance imaging (MRI) procedure. We evaluated the heating patterns of four 10 cm diameter transmit/receive surface coils with differing degrees of distributed capacitance. The tissue phantom was a 6% agarose gel doped with 40 mM Na(4)HTm[DOTP], and possesses a conductivity intermediate to human muscle and fat. Heating was discerned via phase difference mapping using the large temperature dependent chemical shift coefficient for 23Na in Na(4)HTm[DOTP]. This coefficient is -0.5 ppm/ degrees C. Heating was highest where the phantom was closest to the surface coils, dropping off towards the center of the coil. No significant difference was observed in the heating patterns between the different surface coils. For the experimental setups used in this study, electric field 'hot spots' at the areas corresponding to the placement of the capacitor gaps were not observed.

Temperature-dependent chemical shift and relaxation times of (23)Na in Na(4)HTm[DOTP].

We describe the characterization of a (23)Na temperature-dependent chemical shift and relaxation rates in the complex, Na(4)HTm[DOTP]. This is the first characterization of a (23)Na temperature-dependent chemical shift in a nonmetallic sample. The (23)Na temperature-dependent chemical shift coefficient is approximately -0. 5 PPM/ degrees C for both an aqueous solution and a 6% agarose gel of this compound. This is 50 times the magnitude of the temperature-dependent chemical shift coefficient of water protons. The relaxation times, T(1), T(2f), and T(2s) increased by 0.1, 0.01, and 0.05 ms/ degrees C, respectively. Applications of these unique properties for designing an MRI technique for monitoring heat deposition in tissue and tissue phantoms are discussed.

Sodium visibility and quantitation in intact bovine articular cartilage using high field (23)Na MRI and MRS.

Noninvasive methods of detecting cartilage degeneration can have an impact on identifying the early stages of osteoarthritis. Accurate measurement of sodium concentrations within the cartilage matrix provides a means for analyzing tissue integrity. Here a method is described for quantitating sodium concentration and visibility in cartilage, with general applications to all tissue types. The sodium concentration in bovine patellar cartilage plugs was determined by three different methods: NMR spectroscopy of whole cartilage plugs, NMR spectroscopy of liquefied cartilage in concentrated HCl, and inductively coupled plasma emission spectroscopy. Whole bovine patellae were imaged with relaxation normalized calibration phantoms to ascertain sodium concentrations inside the articular cartilage. Sodium concentrations in intact articular cartilage were found to range from approximately 200 mM on the edges to approximately 390 mM in the center, with an average of approximately 320 mM in five separate bovine patellae studied. In essence, we have created sodium distribution maps of the cartilage, showing for the first time, spatial variations of sodium concentration in intact cartilage. This average concentration measurement correlates very well with the values obtained from the spectroscopic methods. Furthermore, sodium was found to be 100% NMR visible in cartilage plugs. Applications of this method in diagnosing and monitoring treatment of osteoarthritis are discussed.

In vivo triple quantum filtered twisted projection sodium MRI of human articular cartilage.

In this work, we present the first triple quantum filtered (TQF) sodium MR images of the human knee joint in vivo. A 3D TQF data set of 16 slices was obtained in 20 min using a TQF pulse sequence preencoded to a twisted projection imaging readout. Images clearly demarcate patellar cartilage and also demonstrate fluid signal suppressed by the triple quantum filter. Biexponential transverse relaxation times were calculated by fitting the TQF free induction decay to a theoretical signal expression. The average values from three healthy volunteers were T(2fall)(*) = 9.59 +/- 0.35 ms and T(2rise)(*) = 0.84 +/- 0.06 ms. Application of TQF imaging in biological tissues is discussed.