Spin-lock MRI Research Articles

Inhomogeneous liver fibrosis distribution revealed by macromolecular proton fraction quantification based on spin-lock MRI.

Inhomogeneous liver fibrosis distribution revealed by macromolecular proton fraction quantification based on spin-lock MRI.

Quantitative kinetic modelling and mapping of cerebral glucose transport and metabolism using glucoCESL MRI

Chemical-exchange spin-lock (CESL) MRI can map regional uptake and utilisation of glucose in the brain at high spatial resolution (i.e sub 0.2 mm3 voxels). We propose two quantitative kinetic models to describe glucose-induced changes in tissue R1ρ and apply them to glucoCESL MRI data acquired in tumour-bearing and healthy rats. When assuming glucose transport is saturable, the maximal transport capacity (Tmax) measured in normal tissue was 3.2 ± 0.6 µmol/min/mL, the half saturation constant (Kt) was 8.8 ± 2.2 mM, the metabolic rate of glucose consumption (MRglc) was 0.21 ± 0.13 µmol/min/mL, and the cerebral blood volume (vb) was 0.006 ± 0.005 mL/mL. Values in tumour were: Tmax = 7.1 ± 2.7 µmol/min/mL, Kt = 14 ± 1.7 mM, MRglc = 0.22 ± 0.09 µmol/min/mL, vb = 0.030 ± 0.035 mL/mL. Tmax and Kt were significantly higher in tumour tissue than normal tissue (p = 0.006 and p = 0.011, respectively). When assuming glucose uptake also occurs via free diffusion, the free diffusion rate (kd) was 0.061 ± 0.017 mL/min/mL in normal tissue and 0.12 ± 0.042 mL/min/mL in tumour. These parameter estimates agree well with literature values obtained using other approaches (e.g. NMR spectroscopy).

Chemical exchange sensitive MRI of glucose uptake using xylose as a contrast agent.

Glucose and its analogs can be detected by CEST and chemical exchange spin-lock (CESL) MRI techniques, but sensitivity is still a bottleneck for human applications. Here, CESL and CEST sensitivity and the effect of injection on baseline physiology were evaluated for a glucose analog, xylose. The CEST and CESL sensitivity were evaluated at 9.4 T in phantoms and by in vivo rat experiments with 0.5 and 1 g/kg xylose injections. Arterial blood glucose level was sampled before and after 1g/kg xylose injection. The effect of injection on baseline neuronal activity was measured by electrophysiology data during injections of saline, xylose, and 2-deoxy-D-glucose. In phantoms, xylose shows similar chemical exchange sensitivity and pH-dependence with that of glucose. In rat experiments with a bolus injection, CESL shows higher sensitivity in the detection of xylose than CEST, and the sensitivity of xylose is much higher than glucose. Injection of xylose does not significantly affect blood glucose level and baseline neural activity for 1-g/kg and 0.6-g/kg doses, respectively. Due to its relatively high sensitivity and safety, xylose is a promising contrast agent for the study of glucose uptake.

Macromolecular proton fraction mapping based on spin-lock magnetic resonance imaging.

In MRI, the macromolecular proton fraction (MPF) is a key parameter of magnetization transfer (MT). It represents the relative amount of immobile protons associated with semi-solid macromolecules involved in MT with free water protons. We aim to quantify MPF based on spin-lock MRI and explore its advantages over the existing MPF-mapping methods. In the proposed method, termed MPF quantification based on spin-lock (MPF-SL), off-resonance spin-lock is used to sensitively measure the MT effect. MPF-SL is designed to measure a relaxation rate (Rmpfsl ) that is specific to the MT effect by removing the R1ρ relaxation due to the mobile water and chemical exchange pools. A theory is derived to quantify MPF from the measured Rmpfsl . No prior knowledge of tissue relaxation parameters, including T1 or T2 , is needed to quantify MPF using MPF-SL. The proposed approach is validated with Bloch-McConnell simulations, phantom, and in vivo liver studies at 3.0T. Both Bloch-McConnell simulations and phantom experiments show that MPF-SL is insensitive to variations of the mobile water pool and the chemical exchange pool. MPF-SL is specific to the MT effect and can measure MPF reliably. In vivo liver studies show that MPF-SL can be used to detect collagen deposition in patients with liver fibrosis. A novel MPF imaging method based on spin-lock MRI is proposed. The confounding factors are removed, and the measurement is specific to the MT effect. It holds promise for MPF-sensitive diagnostic imaging in clinical settings.

Chemical-shift encoding-based water-fat separation with multifrequency fat spectrum modeling in spin-lock MRI.

Chemical exchange saturation transfer is used commonly to generate MRI contrast based on the chemical exchange effect. The spin-lock techniques can also be used to probe the chemical exchange and other molecular motion processes in tissues. The presence of fat can cause errors in spin-lock MRI. Signals from fat are typically suppressed based on spectral selectivity or T1 nulling approaches in spin-lock imaging. However, these methods cannot be used to suppress fat signals from multiple fat peaks. To address this problem, we report chemical-shift encoding-based water-fat separation approaches with multifrequency fat spectrum modeling. Both the conventional spin-lock and the adiabatic continuous-wave constant-amplitude spin lock (ACCSL) with multi-echo acquisitions are investigated for chemical-shift encoding-based water-fat separation in spin-lock imaging. A comparison is made of reconstructions based on 3 models: a single-peak fat spectrum model, a standard precalibrated proton density 6-peak fat spectrum model, and the self-calibrated relaxation-dependent 3-peak fat spectrum model. Comparisons were performed using Bloch simulations, phantom, and in vivo experiments at 3 T. Conventional spin-lock acquisitions cannot be used for reliable water-fat separation with a multipeak fat spectrum model. Water-fat separation based on ACCSL acquisitions achieves superior performance compared with the use of conventional spin-lock acquisitions. The best result is achieved from ACCSL acquisition with self-calibrated relaxation-dependent multipeak fat spectrum modeling. The ACCSL acquisition can be used for chemical-shift encoding-based water-fat separation with multipeak fat spectrum modeling. This approach has the potential to improve quantitative analysis using spin-lock MRI for assessing the biochemical properties of tissues.

On-resonance and off-resonance continuous wave constant amplitude spin-lock and T1ρ quantification in the presence of B1 and B0 inhomogeneities.

Spin-lock MRI is a valuable diagnostic imaging technology, as it can be used to probe the macromolecule environment of tissues. Quantitative T1ρ imaging is one application of spin-lock MRI that is reported to be promising for a number of clinical applications. Spin-lock is often performed with a continuous RF wave at a constant RF amplitude either on resonance or off resonance. However, both on- and off-resonance spin-lock approaches are susceptible to B1 and B0 inhomogeneities, which results in image artifacts and quantification errors. In this work, we report a continuous wave constant amplitude spin-lock approach that can achieve negligible image artifacts in the presence of B1 and B0 inhomogeneities for both on- and off-resonance spin-lock. Under the adiabatic condition, by setting the maximum B1 amplitude of the adiabatic pulses equal to the B1 amplitude of spin-lock RF pulse, the spins are ensured to align along the effective field throughout the spin-lock process. We show that this results in simultaneous compensation of B1 and B0 inhomogeneities for both on- and off-resonance spin-lock. The relaxation effect during the entire adiabatic half passage (AHP) and reverse AHP, and the stationary solution of the Bloch-McConnell equation present at off-resonance frequency offset, are considered in the revised relaxation model. We demonstrate that these factors create a direct current component to the conventional relaxation model. In contrast to the previously reported dual-acquisition method, the revised relaxation model just requires one acquisition to perform quantification. The simulation, phantom, and in vivo experiments demonstrate that the proposed approach achieves superior image quality compared with the existing methods, and the revised relaxation model can perform T1ρ quantification with one acquisition instead of two.

Chemical exchange-sensitive spin-lock (CESL) MRI of glucose and analogs in brain tumors.

Glucose uptake and metabolism can be measured by chemical exchange-sensitive spin-lock (CESL) MRI with an administration of glucose or its analogs. This study investigates the sensitivity, the spatiotemporal characteristics, and the signal source of glucoCESL with a 9L rat brain tumor model. Dynamic CESL MRI with intravenous injection of D-glucose, 2-deoxy-D-glucose (2DG), and L-glucose were measured and compared with gadolinium-based dynamic contrast-enhanced (DCE) MRI. The CESL signals with an injection of glucose or analogs have faster and larger changes in tumors than normal brain tissue. In tumors, the CESL signal with 2DG injection has larger and slower peak response than that with D-glucose due to the accumulation of 2DG and 2DG-6-phosphate in the intracellular compartment, whereas L-glucose, which cannot be transported intracellularly by glucose transporters, only induces a small change. The initial glucoCESL maps (< 4 minutes) are qualitatively similar to DCE maps, whereas later maps (> 4 minutes) show more widespread responses. The rise times of D-glucose-CESL and 2DG-CESL signals in the tumor are slower than that of DCE. Our data suggest that the initial CESL contrast primarily reflects a passive increase of glucose content in the extracellular space of tumors due to a higher vascular permeability, whereas the later period may have a significant contribution from the uptake/metabolism of glucose in the intracellular compartment. Our results demonstrate that glucoCESL MRI has both extracellular and intracellular contributions, and can be a useful tool for measurements of both vascular permeability and glucose uptake in tumors.

Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-d-glucose in normal and ischemic brain

Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-d-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-d-glucose showed comparable chemical exchange properties with d-glucose and 2-deoxy-d-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-d-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (ΔR1ρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/kg 3-O-methyl-d-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-d-glucose were linearly correlated with ΔR1ρ. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-d-glucose injection at 1 h after stroke onset showed reduced ΔR1ρ in the ischemic core but higher ΔR1ρ in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-d-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.

Glucose metabolism-weighted imaging with chemical exchange-sensitive MRI of 2-deoxyglucose (2DG) in brain: Sensitivity and biological sources

Recent proof-of-principle studies have demonstrated the feasibility of measuring the uptake and metabolism of non-labeled 2-deoxy-D-glucose (2DG) by a chemical exchange-sensitive spin-lock (CESL) MRI approach. In order to gain better understanding of this new approach, we performed dynamic in vivo CESL MRI on healthy rat brains with an intravenous injection of 2DG under various conditions at 9.4T. For three 2DG doses of 0.25, 0.5 and 1g/kg, we found that 2DG-CESL signals increased linearly with injection dose at the initial (<20min) but not the later period (>40min) suggesting time-dependent differential weightings of 2DG transport and metabolism. Remaining 2DG-CESL studies were performed with 0.25g/kg 2DG. Since a higher isoflurane level reduces glucose metabolism and increases blood flow, 2DG-CESL was measured under 0.5%, 1.5% and 2.2% isoflurane. The 2DG-CESL signal was reduced at higher isoflurane levels correlating well with the 2DG phosphorylation in the intracellular space. To detect regional heterogeneities of glucose metabolism, 2DG-CESL with 0.33×0.33×1.50mm3 resolution was obtained, which indeed showed a higher response in the cortex compared to the corpus callosum. Lastly, unlike CESL MRI with the injection of non-transportable mannitol, the 2DG-CESL response decreased with an increased spin-lock pulse power confirming that 2DG-CESL is dominated by chemical exchange processes in the extravascular space. Taken together, our results showed that 2DG-CESL MRI signals mainly indicate glucose transport and metabolism and may be a useful biomarker for metabolic studies of normal and diseased brains.

Effects of spin-lock field direction on the quantitative measurement of spin-lattice relaxation time constant in the rotating frame (T1ρ) in a clinical MRI system.

To investigate whether the direction of spin-lock field, either parallel or antiparallel to the rotating magnetization, has any effect on the spin-lock MRI signal and further on the quantitative measurement of T1ρ, in a clinical 3 T MRI system. The effects of inverted spin-lock field direction were investigated by acquiring a series of spin-lock MRI signals for an American College of Radiology MRI phantom, while the spin-lock field direction was switched between the parallel and antiparallel directions. The acquisition was performed for different spin-locking methods (i.e., for the single- and dual-field spin-locking methods) and for different levels of clinically feasible spin-lock field strength, ranging from 100 to 500 Hz, while the spin-lock duration was varied in the range from 0 to 100 ms. When the spin-lock field was inverted into the antiparallel direction, the rate of MRI signal decay was altered and the T1ρ value, when compared to the value for the parallel field, was clearly different. Different degrees of such direction-dependency were observed for different spin-lock field strengths. In addition, the dependency was much smaller when the parallel and the antiparallel fields are mixed together in the dual-field method. The spin-lock field direction could impact the MRI signal and further the T1ρ measurement in a clinical MRI system.

The influence of static and RF field heterogeneity on T1rho cardiovascular MRI

Background Spin lock or T1rho MRI methods may be very useful for assessing myocardial disease. Recently, we reported that there is significant low field relaxation dispersion in myocardial and fibrotic scar tissue during in vivo T1rho MRI, contributing to contrast enhancement compared to spin echo (T2) MRI. However, we also observed that differences in magnetic field susceptibility between the heart and lung organs and poor RF penetration and field homogeneity in large patients and at 3 T contribute to T1rho quantification errors. Our goal was to determine the influence of static (B0 )a nd RF (B1) heterogeneity on in vivo myocardial T1rho quantification. Methods We performed simulations and experiments to explore how B0 and B1 field heterogeneity influences T1rho MRI. Tilted rotating frame (TRF) Bloch simulations were performed for a rotary-echo spin lock, varying field heterogeneity and spin lock duration (TSL = 2-50 ms, B1 = 60-140% nominal spin lock, and ΔB0 = -2-2 ppm at 1.5 T) with random Gaussian noise (s =1 -20% of initial magnetization). Phantom experiments were performed using a homogeneous H2O cylinder (MnCl2 = 0.016%). In vivo experiments were performed in Yorkshire swine (n = 5). Simulated phantom and in vivo images were derived from B0 and B1 maps using the TRF Bloch simulations and were correlated with experimental images at the same spin lock duration. Results We investigated the effect of field heterogeneity on measured T1rho relaxation times in simulations, phantom experiments and in vivo. T1rho artifacts were characterized by banding artifacts resulting from incomplete longitudinal restoration of the T1rho-prepared magnetization, leading to RF field heterogeneity and rotation about the effective field during the spin lock pulse. These artifacts were most prominent at the LV posterolateral wall where significant static field heterogeneity (± 200 Hz) could result in nutation about an effective field oriented away from the idealized spin lock axis. In vivo results correlated well with simulations and phantoms experiments. Measured T1rho relaxation times in the three identical compartments were constant in the homogeneous B0 field and in the 50 mT/m field gradient in which the B0 field was less than 50 Hz off-resonance. Noticeable variations were observed at 100 Hz off-resonance (100 mT/m gradient). The B0 field in vivo is much less homogeneous than that for the phantom; therefore the T1rho images show much more complex patterns (Figure 1C). Mean B0 and B1 field over the left ventricle in the short axis view of the pig heart in vivo are in ranged -85.14 to 34.7 Hz and 244.30 to 361.87 Hz respectively with 95% confidence interval. Conclusions Spin lock artifacts were the result of static field heterogeneity predominantly confined to the left ventricular posterolateral wall. Static field heterogeneity should be reduced to less than 10% of the spin lock field amplitude to minimize T1rho quantification errors.

Characterization of non-hemodynamic functional signal measured by spin-lock fMRI

Current functional MRI techniques measure hemodynamic changes induced by neural activity. Alternative measurement of signals originated from tissue is desirable and may be achieved using T1ρ, the spin-lattice relaxation time in the rotating-frame, which is measured by spin-lock MRI. Functional T1ρ changes in the brain can have contributions from vascular dilation, tissue acidosis, and potentially other contributions. When the blood contributions were suppressed with a contrast agent at 9.4 T, a small tissue-originated T1ρ change was consistently observed at the middle cortical layers of cat visual cortex during visual stimulation, which had different dynamic characteristics compared to hemodynamic fMRI such as a faster response and no post-stimulus undershoot. Functional tissue T1ρ is highly dependent on the magnetic field strength and experimental parameters such as the power of the spin-locking pulse. With a 500Hz spin-locking pulse, the tissue T1ρ without the blood contribution increased during visual stimulation, but decreased during acidosis-inducing hypercapnia and global ischemia, indicating different signal origins. Phantom studies suggest that it may have contribution from concentration decrease in metabolites. Even though the sensitivity is much weaker than BOLD and its exact interpretation needs further investigation, our results show that non-hemodynamic functional signal can be consistently observed by spin-lock fMRI.

Spin-lock MRI with amplitude- and phase-modulated adiabatic waveforms: an MR simulation study

Image contrast between tissue types can be generated based on their T1/T2 ratio using spin-lock MRI techniques. An interesting application of such a concept would be to generate contrast in tissue with tissue relaxation times modified using exogenous contrast agents. An amplitude-modulated adiabatic waveform has been shown in the past to perform spin-lock MRI. However, implementation of this waveform may not prove to be efficient and practical in research or a clinical setup due to high radiofrequency power deposition. Recent advancement in software and hardware MR technology allows implementation of amplitude- and phase-modulated adiabatic waveforms on MR systems. The aim of this work was to explore role of adiabatic waveforms in performing rho imaging and demonstrate that amplitude- and phase-modulated waveforms [e.g., hyperbolic secant, B1 independent rotation-4 (BIR-4) waveforms] can be used to distinguish materials that differ in T1/T2 ratio. MR simulation was performed using computer routines implemented in MATLAB environment (Mathworks, Natick, MA). Modified Bloch equations with trapezoidal, hyperbolic secant and BIR-4 waveforms were used to perform MR simulation. Trapezoidal waveforms were only used for comparison to other waveforms. Gadolinium DTPA (Gad-DTPA) (T1/T2 approximately 1) and manganese chloride (MnCl(2)) (T1/T2 approximately 10) were used as examples of contrast agents due to their routine use in clinical and research setups and more importantly because they provide good examples of materials differing in T1/T2 ratios. Results of spin locking using trapezoidal waveform agree very well with the previously published results, thereby validating the computer routines used in this MR simulation. Plots of M(rho) (magnetization vector in rho domain) vs. offset frequency show distinct curves for these materials differing in T1/T2 for the three waveforms. BIR-4 waveform demonstrated a 40% difference in M(rho) ( approximately 150 Hz) for the materials. Rate of spin lock with hyperbolic secant waveform was rapid compared to other waveforms. MR simulation using contrast agents Gad-DTPA and MnCl(2) provided a useful way to demonstrate that amplitude- and phase-modulated adiabatic waveforms can be used to perform spin-lock imaging. Future work involves implementation of these waveforms on MR scanners and performing in vivo imaging to generate tissue contrast based on relaxation times ratio.

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.

Contrast-to-noise ratio of multiple slice spin lock technique: prospects for liver imaging.

Spin lock (SL) MRI technique has been demonstrated to provide similar lesion/liver contrast to conventional MR technique. Multiple slice SL technique allows a large number of slices to be collected within a given repetition time due to the short echo time. In addition, the short echo time reduces movement and susceptibility artefacts. In the present study, the potential of the multiple slice SL technique in liver imaging was evaluated by using tissue nuclear magnetic resonance (NMR) information and tissue NMR parameters obtained at 0.1 T. 10 healthy volunteers were imaged at 0.1 T for the measurement of tissue T1rho, T1, and T2 relaxation times. Tissue radiofrequency-attenuation information was obtained from the literature, and included in the contrast-to-noise ratio (CNR) calculations. Our results demonstrated that by increasing the number of slices the acquired liver-to-spleen CNR decreases with all locking field durations (locking time, TL). However, with small TLs, the difference is small which is important for liver MRI where a wide coverage, i.e. large number of slices, is important. Long locking pulse durations are more favourable than short TLs if large flip angles are used. With an optimal combination of a moderate amount of slices, reasonably large flip angle, and TL of the order of 20 ms, high CNR is achieved in SL MRI.