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.     

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.     

Exchange-mediated contrast agents for spin-lock imaging

Measurements of relaxation rates in the rotating frame with spin-locking techniques are sensitive to substances with exchanging protons with appropriate chemical shifts. The authors develop a novel approach to exchange-rate selective imaging based on measured T(1ρ) dispersion with applied locking field strength, and demonstrate the method on samples containing the X-ray contrast agent Iohexol with and without cross-linked bovine serum albumin. T(1ρ) dispersion of water in the phantoms was measured with a Varian 9.4-T magnet by an on-resonance spin-locking pulse with fast spin-echo readout, and the results used to estimate exchange rates. The Iohexol phantom alone gave a fitted exchange rate of ~1 kHz, bovine serum albumin alone was ~11 kHz, and in combination gave rates in between. By using these estimated rates, we demonstrate how a novel spin-locking imaging method may be used to enhance contrast due to the presence of a contrast agent whose protons have specific exchange rates.     

MR angiography using spin-lock flow tagging.

A method for MR angiography using an RF labeling technique is suggested. The method utilizes a slice-selective spin-lock pulse sequence for tagging the spins of inflowing blood. The pulse sequence begins with a spatially selective 90 degrees (x) RF pulse, followed by a nonselective composite locking pulse of 135 degrees (y) - n[360 degrees (y)]-135 degrees (y) and by a 90 degrees (-x) pulse. A spoiler gradient is then applied. A rapid imaging stage, which yields a T(1)rho-weighted signal from the tagged spins, completes the sequence. Untagged spins are thoroughly dephased and consequently suppressed in the image. Thus, contrast is obtained without an injection of a contrast material or image subtraction. Furthermore, the flow of the tagged bolus can be visualized. The sequence was implemented on phantoms and on human volunteers using a 1.5T scanner. The results indicate the feasibility of the suggested sequence.     

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.     

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.     

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.     

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

PURPOSE: 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 (T(1rho)) imaging and T(1rho) relaxivity (R(1rho)). MATERIALS AND METHODS: All the magnetic resonance imaging (MRI) experiments were performed on a 4-T whole-body GE Signa scanner (GEMS, Milwaukee, WI), and spectroscopy experiments of chondroitin sulfate (CS) phantoms were done on a 2-T custom-built spectrometer. A custom-built 11-cm-diameter transmit-receive birdcage coil, which was tuned to a proton frequency of 170 MHz, was employed for the imaging experiments. T(1rho) measurements were made using a fast spin echo (FSE) sequence pre-encoded with a three-pulse cluster consisting of two 90 degrees hard pulses separated by a low-power rectangle pulse for spin-locking. RESULTS: The methodology is first validated on CS phantoms and then used to quantify GAG content in intact bovine cartilage (N = 5). There is a good agreement between the GAG map calculated from the T(1rho) ratio imaging method (71 +/- 4%) and GAG measured from spectrophotometric assay (75 +/- 5%) in intact bovine tissue. CONCLUSION: We have demonstrated a proton spin-lock ratio imaging method to quantify absolute GAG distribution in the cartilage in a noninvasive and nondestructive manner.     

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.     

In vivo T(1rho) mapping in cartilage using 3D magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (3D MAPSS)

For T(1rho) quantification, a three-dimensional (3D) acquisition is desired to obtain high-resolution images. Current 3D methods that use steady-state spoiled gradient-echo (SPGR) imaging suffer from high SAR, low signal-to-noise ratio (SNR), and the need for retrospective correction of contaminating T(1) effects. In this study, a novel 3D acquisition scheme-magnetization-prepared angle-modulated partitioned-k-space SPGR snapshots (3D MAPSS)-was developed and used to obtain in vivo T(1rho) maps. Transient signal evolving towards the steady-state were acquired in an interleaved segmented elliptical centric phase encoding order immediately after a T(1rho) magnetization preparation sequence. RF cycling was applied to eliminate the adverse impact of longitudinal relaxation on quantitative accuracy. A variable flip angle train was designed to provide a flat signal response to eliminate the filtering effect in k-space caused by transient signal evolution. Experiments in phantoms agreed well with results from simulation. The T(1rho) values were 42.4 +/- 5.2 ms in overall cartilage of healthy volunteers. The average coefficient-of-variation (CV) of mean T(1rho) values (N = 4) for overall cartilage was 1.6%, with regional CV ranging from 1.7% to 8.7%. The fitting errors using MAPSS were significantly lower (P < 0.05) than those using sequences without RF cycling and variable flip angles.     

Application of the keyhole technique to T1rho relaxation mapping

PURPOSE: To demonstrate the feasibility of using the keyhole technique to minimize error in a least squares regression estimation of T(1rho) from magnetic resonance (MR) image data. MATERIALS AND METHODS: The keyhole method of partial k-space acquisition was simulated using data from a virtual phantom and MR images of ex vivo bovine and in vivo human cartilage. T(1rho) maps were reconstructed from partial k-space (keyhole) image data using linear regression, and error was measured with relation to T(1rho) maps created from the full k-space images. An error model was created based on statistical theory and fitted to the error measurements. RESULTS: T(1rho) maps created from keyhole images of a human knee produced levels of error on the order of 1% while reducing standard image acquisition time approximately by half. The resultant errors were strongly correlated with expectations derived from statistical theory. CONCLUSION: The error model can be used to analytically optimize the keyhole method in order to minimize the overall error in the estimation of the relaxation parameter of interest. The keyhole method can be generalized to significantly expedite all forms of relaxation mapping.     

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.     

Rapid 3D-T1rho mapping of the knee joint at 3.0T with parallel imaging.

Three-dimensional spin-lattice relaxation time in the rotating frame (3D-T1rho) with parallel imaging at 3.0T was implemented on a whole-body clinical scanner. A 3D gradient-echo sequence with a self-compensating spin-lock pulse cluster was combined with generalized autocalibrating partially parallel acquisitions (GRAPPA) to acquire T1rho-weighted images. 3D-T1rho maps of an agarose phantom and three healthy subjects were constructed using an eight-channel phased-array coil without parallel imaging and with parallel imaging acceleration factors of 2 and 3, in order to assess the reproducibility of the method. The coefficient of variation (CV) of the median T1rho of the agarose phantom was 0.44%, which shows excellent reproducibility. The reproducibility of in vivo 3D-T1rho maps was also investigated in three healthy subjects. The CV of the median T1rho of the patellar cartilage varied between approximately 1.1% and 4.3%. Similarly, the CV varied between approximately 2.1-5.8%, approximately 1.4-8.7%, and approximately 1.5-4.1% for the biceps femoris and lateral and medial gastrocnemius muscles, respectively. The preliminary results demonstrate that 3D-T1rho maps can be constructed with good reproducibility using parallel imaging. 3D-T1rho with parallel imaging capability is an important clinical tool for reducing both the total acquisition time and RF energy deposition at 3T.     

Optimized T1-weighted contrast for single-slab 3D turbo spin-echo imaging with long echo trains: application to whole-brain imaging.

T(1)-weighted contrast is conventionally obtained using multislice two-dimensional (2D) spin-echo (SE) imaging. Achieving isotropic, high spatial resolution is problematic with conventional methods due to a long acquisition time, imperfect slice profiles, or high-energy deposition. Single-slab 3D SE imaging was recently developed employing long echo trains with variable low flip angles to address these problems. However, long echo trains may yield suboptimal T(1)-weighted contrast, since T(2) weighting of the signals tends to develop along the echo train. Image blurring may also occur if high spatial frequency signals are acquired with low signal intensity. The purpose of this work was to develop an optimized T(1)-weighted version of single-slab 3D SE imaging with long echo trains. Refocusing flip angles were calculated based on a tissue-specific prescribed signal evolution. Spatially nonselective excitation was used, followed by half-Fourier acquisition in the in-plane phase encoding (PE) direction. Restore radio frequency (RF) pulses were applied at the end of the echo train to optimize T(1)-weighted contrast. Imaging parameters were optimized by using Bloch equation simulation, and imaging studies of healthy subjects were performed to investigate the feasibility of whole-brain imaging with isotropic, high spatial resolution. The proposed technique permitted highly-efficient T(1)-weighted 3D SE imaging of the brain.     

A technique for rapid single‐echo spin‐echo T2 mapping

A rapid technique for mapping of T₂ relaxation times is presented. The method is based on the conventional single‐echo spin echo approach but uses a much shorter pulse repetition time to accelerate data acquisition. The premise of the new method is the use of a constant difference between the echo time and pulse repetition time, which removes the conventional and restrictive requirement of pulse repetition time ? T₁. Theoretical and simulation investigations were performed to evaluate the criteria for accurate T₂ measurements. Measured T₂s were shown to be within 1% error as long as the key criterion of pulse repetition time/T₂ ≥3 is met. Strictly, a second condition of echo time/T₁ ? 1 is also required. However, violations of this condition were found to have minimal impact in most clinical scenarios. Validation was conducted in phantoms and in vivo T₂ mapping of healthy cartilage and brain. The proposed method offers all the advantages of single‐echo spin echo imaging (e.g., immunity to stimulated echo effects, robustness to static field inhomogeneity, flexibility in the number and choice of echo times) in a considerably reduced amount of time and is readily implemented on any clinical scanner. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

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.     

B0 dependence of the on-resonance longitudinal relaxation time in the rotating frame (T1rho) in protein phantoms and rat brain in vivo.

On-resonance longitudinal relaxation time in the rotating frame (T1rho) has been shown to provide unique information during the early minutes of acute stroke. In the present study, the contributions of the different relaxation mechanisms to on-resonance T1rho relaxation were assessed by determining relaxation rates (R1rho) in both protein phantoms and in rat brain at 2.35, 4.7, and 9.4 T. Similar to transverse relaxation rate (R2), R1rho increased substantially with increasing magnetic field strength (B0). The B0 dependence was more pronounced at weak spin-lock fields. In contrast to R1rho, longitudinal relaxation rate (R1) decreased as a function of increasing B0 field. The present data argue that dipole-dipole interaction forms only one pathway for T1rho relaxation and the contributions from other physicochemical factors need to be considered.