T2 of articular cartilage in the presence of Gd-DTPA2-.

T(2) information and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) are both used to characterize articular cartilage. They are currently obtained in separate studies because Gd-DTPA(2-) (which is needed for dGEMRIC) affects the inherent T(2) information. In this study, T(2) was simulated and then measured at 8.45 T in 20 sections from two human osteochondral samples equilibrated with and without Gd-DTPA(2-). Both the simulations and data demonstrated that Gd-DTPA(2-) provides a non-negligible mechanism for relaxation, especially with higher (1 mM) equilibrating Gd-DTPA(2-) concentrations, and in areas of tissue with high T(2) (due to weak inherent T(2) mechanisms) and high tissue Gd-DTPA(2-) (due to a low glycosaminoglycan concentration). Nonetheless, T(2)-weighted images of cartilage equilibrated in 1 mM Gd-DTPA(2-) showed similar T(2) contrast with and without Gd-DTPA(2-), demonstrating that the impact on T(2) was not great enough to affect identification of T(2) lesions. However, T(2) maps of the same samples showed loss of conspicuity of T(2) abnormalities. We back-calculated inherent T(2)'s (T(2,bc)) using a T(2)-relaxivity value from a 20% protein phantom (r(2) = 9.27 +/- 0.09 mM(-1)s(-1)) and the Gd-DTPA(2-) concentration calculated from T(1,Gd). The back-calculation restored the inherent T(2) conspicuity, and a correlation between T(2) and T(2,bc) of r = 0.934 (P < 0.0001) was found for 80 regions of interest (ROIs) in the sections. Back-calculation of T(2) is therefore a viable technique for obtaining T(2) maps at high equilibrating Gd-DTPA(2-) concentrations. With T(2)-weighted images and/or low equilibrating Gd-DTPA(2-) concentrations, it may be feasible to obtain both T(2) and dGEMRIC information in the presence of Gd-DTPA(2-) without such corrections. These conditions can be designed into ex vivo studies of cartilage. They appear to be applicable for clinical T(2) studies, since pilot clinical data at 1.5 T from three volunteers demonstrated that calculated T(2) maps are comparable before and after "double dose" Gd-DTPA(2-) (as utilized in clinical dGEMRIC studies). Therefore, it may be possible to perform a comprehensive clinical examination of dGEMRIC, T(2), and cartilage volume in one scanning session without T(2) data correction.     

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.     

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.     

Spatial assessment of articular cartilage proteoglycans with Gd-DTPA-enhanced T1 imaging.

In Gd-DTPA-enhanced T(1) imaging of articular cartilage, the MRI contrast agent with two negative charges is understood to accumulate in tissue inversely to the negative charge of cartilage glycosaminoglycans (GAGs) of proteoglycans (PGs), and this leads to a decrease in the T(1) relaxation time of tissue relative to the charge in tissue. By assuming a constant relaxivity for Gd-DTPA in cartilage, it has further been hypothesized that the contrast agent concentration in tissue could be estimated from consecutive T(1) measurements in the absence or presence of the contrast agent. The spatial sensitivity of the technique was examined at 9.4 T in normal and PG-depleted bovine patellar cartilage samples. As a reference, spatial PG concentration was assessed with digital densitometry from safranin O-stained cartilage sections. An excellent linear correlation between spatial optical density (OD) of stained GAGs and T(1) with Gd-DTPA was observed in the control and chondroitinase ABC-treated cartilage specimens, and the MR parameter accounted for approximately 80% of the variations in GAG concentration within samples. Further, the MR-resolved Gd-DTPA concentration proved to be an even better estimate for PGs, with an improved correlation. However, the linear relation between MR parameters and PG concentration did not apply in the deep tissue, where MR measurements overestimated the PG content. While the absolute [Gd-DTPA] determination may be prone to error due to uncertainty of relaxivity in cartilage, or to other contributing factors such as variations in tissue permeability, the experimental evidence highlights the sensitivity of this technique to reflect spatial changes in cartilage PG concentration in normal and degenerated tissue.     

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.     

Water spin dynamics during apoptotic cell death in glioma gene therapy probed by T1rho and T2rho.

Longitudinal and transverse relaxations in the rotating frame, with characteristic time constants T1rho and T2rho, respectively, have potential to provide unique MRI contrast in vivo. On-resonance spin-lock T1rho with different spin-lock field strengths and adiabatic T2rho with different radiofrequency-modulation functions were measured in BT4C gliomas treated with Herpes Simplex Virus thymidine kinase (HVS-tk) gene therapy causing apoptotic cell death. These NMR tools were able to discriminate different treatment responses in tumor tissue from day 4 onward. An equilibrium two-site exchange model was used to calculate intrinsic parameters describing changes in water dynamics. Observed changes included increased correlation time of water associated with macromolecules and a decreased fractional population of this pool. These results are consistent with destructive intracellular processes associated with cell death and the increase of extracellular space during the treatment. Furthermore, association between longer exchange correlation time and decreased pH during apoptosis is discussed. In this study, we demonstrated that T1rho and T2rho MR imaging are useful tools to quantify early changes in water dynamics reflecting treatment response during gene therapy.     

T1rho-prepared balanced gradient echo for rapid 3D T1rho MRI

PURPOSE: To develop a T1rho-prepared, balanced gradient echo (b-GRE) pulse sequence for rapid three-dimensional (3D) T1rho relaxation mapping within the time constraints of a clinical exam (<10 minutes), examine the effect of acquisition on the measured T1rho relaxation time and optimize 3D T1rho pulse sequences for the knee joint and spine. MATERIALS AND METHODS: A pulse sequence consisting of inversion recovery-prepared, fat saturation, T1rho-preparation, and b-GRE image acquisition was used to obtain 3D volume coverage of the patellofemoral and tibiofemoral cartilage and lower lumbar spine. Multiple T1rho-weighted images at various contrast times (spin-lock pulse duration [TSL]) were used to construct a T1rho relaxation map in both phantoms and in the knee joint and spine in vivo. The transient signal decay during b-GRE image acquisition was corrected using a k-space filter. The T1rho-prepared b-GRE sequence was compared to a standard T1rho-prepared spin echo (SE) sequence and pulse sequence parameters were optimized numerically using the Bloch equations. RESULTS: The b-GRE transient signal decay was found to depend on the initial T1rho-preparation and the corresponding T1rho map was altered by variations in the point spread function with TSL. In a two compartment phantom, the steady state response was found to elevate T1rho from 91.4+/-6.5 to 293.8+/-31 and 66.9+/-3.5 to 661+/-207 with no change in the goodness-of-fit parameter R2. Phase encoding along the longest cartilage dimension and a transient signal decay k-space filter retained T1rho contrast. Measurement of T1rho using the T1rho-prepared b-GRE sequence matches standard T1rho-prepared SE in the medial patellar and lateral patellar cartilage compartments. T1rho-preparedb-GRE T1rho was found to have low interscan variability between four separate scans. Mean patellar cartilage T1rho was elevated compared to femoral and tibial cartilage T1rho. CONCLUSION: The T1rho-prepared b-GRE acquisition rapidly and reliably accelerates T1rho quantification of tissues offset partially by a TSL-dependent point spread function.     

T1rho relaxation mapping in human osteoarthritis (OA) cartilage: comparison of T1rho with T2

PURPOSE: To quantify the spin-lattice relaxation time in the rotating frame (T1rho) in various clinical grades of human osteoarthritis (OA) cartilage specimens obtained from total knee replacement surgery, and to correlate the T1rho with OA disease progression and compare it with the transverse relaxation time (T2). MATERIALS AND METHODS: Human cartilage specimens were obtained from consenting patients (N = 8) who underwent total replacement of the knee joint at the Pennsylvania Hospital, Philadelphia, PA, USA. T2- and T1rho-weighted images were obtained on a 4.0 Tesla whole-body GE Signa scanner (GEMS, Milwaukee, WI, USA). A 7-cm diameter transmit/receive quadrature birdcage coil tuned to 170 MHz was employed. RESULTS: All of the surgical knee replacement OA cartilage specimens showed elevated relaxation times (T2 and T1rho) compared to healthy cartilage tissue. In various grades of OA specimens, the T1rho relaxation times varied from 62 +/- 5 msec to 100 +/- 8 msec (mean +/- SEM) depending on the degree of cartilage degeneration. However, T2 relaxation times varied only from 32 +/- 2 msec to 45 +/- 4 msec (mean +/- SEM) on the same cartilage specimens. The increase in T2 and T1rho in various clinical grades of OA specimens were approximately 5-50% and 30-120%, respectively, compared to healthy specimens. The degenerative status of the cartilage specimens was also confirmed by histological evaluation. CONCLUSION: Preliminary results from a limited number of knee specimens (N = 8) suggest that T1rho relaxation mapping is a sensitive noninvasive marker for quantitatively predicting and monitoring the status of macromolecules in early OA. Furthermore, T1rho has a higher dynamic range (>100%) for detecting early pathology compared to T2. This higher dynamic range can be exploited to measure even small macromolecular changes with greater accuracy compared to T2. Because of these advantages, T1rho relaxation mapping may be useful for evaluating early OA therapy.     

In vivo 3T spiral imaging based multi-slice T(1rho) mapping of knee cartilage in osteoarthritis.

T(1rho) describes the spin-lattice relaxation in the rotating frame and has been proposed for detecting damage to the cartilage collagen-proteoglycan matrix in osteoarthritis. In this study, a multi-slice T(1rho) imaging method for knee cartilage was developed using spin-lock techniques and a spiral imaging sequence. The adverse effect of T(1) regrowth during the multi-slice acquisition was eliminated by RF cycling. Agarose phantoms with different concentrations, 10 healthy volunteers, and 9 osteoarthritis patients were scanned at 3T. T(1rho) values decreased as agarose concentration increased. T(1rho) values obtained with imaging methods were compared with those obtained with spectroscopic methods. T(1rho) values obtained during multi-slice acquisition were validated with those obtained in a single slice acquisition. Reproducibility was assessed using the average coefficient of variation of median T(1rho), which was 0.68% in phantoms and 4.8% in healthy volunteers. There was a significant difference (P = 0.002) in the average T(1rho) within patellar and femoral cartilage between controls (45.04 +/- 2.59 ms) and osteoarthritis patients (53.06 +/- 4.60 ms). A significant correlation was found between T(1rho) and T(2); however, the difference of T(2) was not significant between controls and osteoarthritis patients. The results suggest that T(1rho) relaxation times may be a promising clinical tool for osteoarthritis detection and treatment monitoring.     

3D-T1rho quantitation of patellar cartilage at 3.0T

PURPOSE: To demonstrate the feasibility of three-dimensional (3D) T(1rho)-weighted imaging of human knee joint at 3.0T without exceeding the specific absorption rate (SAR) limits and the measurement of the baseline T(1rho) values of patellar cartilage and several muscles at the knee joint. MATERIALS AND METHODS: 3D gradient-echo sequence with a self-compensating spin-lock pulse cluster of 250 Hz power was used to acquire 3D-T(1rho)-weighted images of the knee joint of five healthy subjects. Global and regional analysis of patellar cartilage T(1rho) were performed. Furthermore, T(1rho) of several periarticular muscles were analyzed. RESULTS: The global average T(1rho) value of the patellar cartilage varied from 39 to 43 msec. The regional average T(1rho) values varied from 38 to 42 msec, and from 42 to 44 msec for medial and lateral facets, respectively. In vivo reproducibility of average T(1rho) of patellar cartilage was found to be 5% (coefficient of variation). Similarly, the global average T(1rho) values for biceps femoris, lateral gastrocnemius, medial gastrocnemius, and sartorius varied between 31-46, 29-49, 35-48, and 32-50 msec, respectively. CONCLUSION: We demonstrated the feasibility of 3D-T(1rho)-weighted imaging of the knee joint at 3.0T without exceeding SAR limits.     

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.     

T2* measurement of the knee articular cartilage in osteoarthritis at 3T

Purpose:

To measure reproducibility, longitudinal and cross‐sectional differences in T2* maps at 3 Tesla (T) in the articular cartilage of the knee in subjects with osteoarthritis (OA) and healthy matched controls.

Materials and Methods:

MRI data and standing radiographs were acquired from 33 subjects with OA and 21 healthy controls matched for age and gender. Reproducibility was determined by two sessions in the same day, while longitudinal and cross‐sectional group differences used visits at baseline, 3 and 6 months. Each visit contained symptomological assessments and an MRI session consisting of high resolution three‐dimensional double‐echo‐steady‐state (DESS) and co‐registered T2* maps of the most diseased knee. A blinded reader delineated the articular cartilage on the DESS images and median T2* values were reported.

Results:

T2* values showed an intra‐visit reproducibility of 2.0% over the whole cartilage. No longitudinal effects were measured in either group over 6 months. T2* maps revealed a 5.8% longer T2* in the medial tibial cartilage and 7.6% and 6.5% shorter T2* in the patellar and lateral tibial cartilage, respectively, in OA subjects versus controls (P < 0.02).

Conclusion:

T2* mapping is a repeatable process that showed differences between the OA subject and control groups. J. Magn. Reson. Imaging 2012;35:1422–1429. © 2012 Wiley Periodicals Inc.     

Rotating-frame intermolecular double-quantum spin-lattice relaxation T1rho, DQC-weighted magnetic resonance imaging.

In this study, spin-locking techniques were added as a part of intermolecular multiple-quantum experiments, thereby introducing the concept of rotating-frame intermolecular double-quantum spin-lattice relaxation, T(1rho, DQC). A novel magnetic resonance imaging methodology based on intermolecular multiple-quantum coherences is demonstrated on a 7.05-T microimaging scanner. The results clearly reveal that the intermolecular double-quantum coherence T(1rho, DQC)-weighted imaging technique provides an alternative contrast mechanism to conventional imaging.     

On- and off-resonance T(1rho) MRI in acute cerebral ischemia of the rat.

The ability of on-resonance T(1rho) (T(1rho)) and off-resonance T(1rho) (T(1rho)(off)) measurements to indicate acute cerebral ischemia in a rat model of transient middle cerebral artery (MCA) occlusion was investigated at 4.7 T. T(1rho) was determined with B(1) fields of 0.4, 0.8, and 1.6 G, and T(1rho)(off) with five offset frequencies ((Delta)omega) ranging from 0-7.5 kHz at B(1) of 0.4 G, yielding effective B(1) (B(eff)) from 0.4 to 1.8 G. Diffusion, T(1), and T(2) were also quantified. Both T(1rho) and T(1rho)(off) acquired with (Delta)(o)< 2.5 kHz showed positive contrast during the first hours of MCA occlusion in the ischemic tissue delineated by low diffusion. Interestingly, T(1rho)(off) contrast acquired with (Delta)omega > 2.5 kHz was clearly less sensitive to ischemic alterations, and developed with a delayed time course. This discrepancy is thought to be a consequence of the frequency dependency of cross-relaxation during irradiation with spin-lock pulses.     

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.     

3 T MRI关节软骨生化成分成像的研究进展

近年来,3 T MRI技术发展十分迅速,已广泛应用于软骨病变的诊断和疗效评价。各种软骨成像序列不断被开发和应用,目前已从传统的二维、三维形态成像向生化成分成像转变,以期能够对关节软骨形态学改变之前的软骨生化改变进行显示,为早期软骨损伤诊断和监测提供临床参考依据。目前,关节软骨生化成分成像技术包括T2mapping、T2＊mapping及T1ρ成像等。就3 T MR关节软骨生化成分成像的临床应用及研究进展予以综述。     

Three-dimensional T1rho-weighted MRI at 1.5 Tesla

PURPOSE: To design and implement a magnetic resonance imaging (MRI) pulse sequence capable of performing three-dimensional T(1rho)-weighted MRI on a 1.5-T clinical scanner, and determine the optimal sequence parameters, both theoretically and experimentally, so that the energy deposition by the radiofrequency pulses in the sequence, measured as the specific absorption rate (SAR), does not exceed safety guidelines for imaging human subjects. MATERIALS AND METHODS: A three-pulse cluster was pre-encoded to a three-dimensional gradient-echo imaging sequence to create a three-dimensional, T(1rho)-weighted MRI pulse sequence. Imaging experiments were performed on a GE clinical scanner with a custom-built knee-coil. We validated the performance of this sequence by imaging articular cartilage of a bovine patella and comparing T(1rho) values measured by this sequence to those obtained with a previously tested two-dimensional imaging sequence. Using a previously developed model for SAR calculation, the imaging parameters were adjusted such that the energy deposition by the radiofrequency pulses in the sequence did not exceed safety guidelines for imaging human subjects. The actual temperature increase due to the sequence was measured in a phantom by a MRI-based temperature mapping technique. Following these experiments, the performance of this sequence was demonstrated in vivo by obtaining T(1rho)-weighted images of the knee joint of a healthy individual. RESULTS: Calculated T(1rho) of articular cartilage in the specimen was similar for both and three-dimensional and two-dimensional methods (84 +/- 2 msec and 80 +/- 3 msec, respectively). The temperature increase in the phantom resulting from the sequence was 0.015 degrees C, which is well below the established safety guidelines. Images of the human knee joint in vivo demonstrate a clear delineation of cartilage from surrounding tissues. CONCLUSION: We developed and implemented a three-dimensional T(1rho)-weighted pulse sequence on a 1.5-T clinical scanner.     

Investigation of apparent diffusion constant as an indicator of early degenerative disease in articular cartilage

PURPOSE: To investigate the apparent diffusion constant (ADC) as a prospective magnetic resonance imaging (MRI) marker of early degeneration in articular cartilage. MATERIALS AND METHODS: Early degenerative changes were studied using in vitro MRI on cartilage-bone specimens excised from human femoral condyles. The loss of proteoglycans developed in vivo due to a degenerative process was compared with a gadolinium diethylenetriamine pentaacetate anion (Gd-DTPA(2-)) enhanced decrease of T(1) relaxation times, and with an increase of ADCs and T(2) relaxation times. RESULTS: Contrast enhanced T(1) values decreased and the diffusion constants increased in cartilage regions with depleted proteoglycans. The relative changes in diffusion constants were smaller than those of Gd-DTPA(2-) enhanced T(1), and in some proteoglycan-depleted regions no changes in the diffusion constants were detected. T(2) relaxation times showed considerable spatial variability that did not correlate with proteoglycan concentration. CONCLUSION: In contrast to Gd-DTPA(2-) enhanced T(1), which reflects changes in chemical composition, diffusion constants may reflect structural degradation of the cartilage matrix.