Rotary excitation of non-sinusoidal pulsed magnetic fields: Towards non-invasive direct detection of cardiac conduction.

PURPOSE: There is a need for high resolution non-invasive imaging methods of physiologic magnetic fields. The purpose of this work is to develop a MRI detection approach for non-sinusoidal magnetic fields based on the rotary excitation (REX) mechanism which was previously successfully applied for the detection of oscillating magnetic fields in the sub-nT range. METHODS: The new detection concept was examined by means of Bloch simulations, evaluating the interaction effect of spin-locked magnetization and low-frequency pulsed magnetic fields. The REX detection approach was validated under controlled conditions in phantom experiments at 3 T. Gaussian and sinc-shaped stimuli were investigated. In addition, the detection of artificial fields resembling a cardiac QRS complex, which is the most prominent peak visible on a magnetocardiogram, was tested. RESULTS: Bloch simulations demonstrated that the REX method has a high sensitivity to pulsed fields in the resonance case, which is met when the spin-lock frequency coincides with a non-zero Fourier component of the stimulus field. In the experiments, we found that magnetic stimuli of different durations and waveforms can be distinguished by their characteristic REX response spectrum. The detected REX amplitude was proportional to the stimulus peak amplitude (R2 > 0.98) and the lowest field detection was 1 nT. Furthermore, the detection of QRS-like fields with varying QRS durations yielded significant results in a phantom setup (p < 0.001). CONCLUSION: REX detection can be transferred to non-sinusoidal pulsed magnetic fields and could provide a non-invasive, quantitative tool for spatially resolved assessment of cardiac biomagnetism. Potential applications include the direct detection and characterization of cardiac conduction.

Novel spin-lock time sampling strategies for improved reproducibility in quantitative T1ρ mapping.

This study aimed to optimize the sampling of spin-lock times (TSLs) in quantitative T1ρ mapping for improved reproducibility. Two new TSL sampling schemes were proposed: (i) reproducibility-guided random sampling (RRS) and (ii) reproducibility-guided optimal sampling (ROS). They were compared to the existing linear sampling (LS) and precision-guided sampling (PS) schemes for T1ρ reproducibility through numerical simulations, phantom experiments, and volunteer studies. Each study evaluated the four sampling schemes with three commonly used T1ρ preparations based on composite and balanced spin-locking. Additionally, the phantom and volunteer studies investigated the impact of B0 and B1 field inhomogeneities on T1ρ reproducibility, respectively. The reproducibility was assessed using the coefficient of variation (CoV) by repeating the T1ρ measurements eight times for phantom experiments and five times for volunteer studies. Numerical simulations resulted in lower mean CoVs for the proposed RRS (1.74%) and ROS (0.68%) compared to LS (2.93%) and PS (3.68%). In the phantom study, the mean CoVs were also lower for RRS (2.7%) and ROS (2.6%) compared to LS (4.1%) and PS (3.1%). Furthermore, the mean CoVs of the proposed RRS and ROS were statistically lower (P < 0.001) compared to existing LS and PS schemes at a B1 offset of 20%. In the volunteer study, consistently lower mean CoVs were observed in bilateral thigh muscles for RRS (9.3%) and ROS (9.2%) compared to LS (10.9%) and PS (10.2%), and the difference was more prominent at B0 offsets higher than 50 Hz. The proposed sampling schemes improve the reproducibility of quantitative T1ρ mapping by optimizing the selection of TSLs. This improvement is especially beneficial for longitudinal studies that track and monitor disease progression and treatment response.

Quantification of the rotating frame relaxation time T2ρ: Comparison of balanced spin-lock and continuous-wave Malcolm-Levitt preparations.

For the quantification of rotating frame relaxation times, the T2ρ relaxation pathway plays an essential role. Nevertheless, T2ρ imaging has been studied only to a small extent compared with T1ρ, and preparation techniques for T2ρ have so far been adapted from T1ρ methods. In this work, two different preparation concepts are compared specifically for the use of T2ρ mapping. The first approach involves transferring the balanced spin-locking (B-SL) concept of T1ρ imaging. The second and newly proposed approach is a continuous-wave Malcolm-Levitt (CW-MLEV) pulse train with zero echo times and was motivated from T2 preparation strategies. The modules are tested in Bloch simulations for their intrinsic sensitivity to field inhomogeneities and validated in phantom experiments. In addition, myocardial T2ρ mapping was performed in mice as an exemplary application. Our results demonstrate that the CW-MLEV approach provides superior robustness and thus suggest that established methods of T1ρ imaging are not best suited for T2ρ experiments. In the presence of field inhomogeneities, the simulations indicated an increased banding compensation by a factor of 4.1 compared with B-SL. Quantification of left ventricular T2ρ time in mice yielded more consistent results, and values in the range of 59.2-61.1 ms (R2 = 0.986-0.992) were observed at 7 T.

Severity of polycystic kidney disease revealed by multiparametric MRI.

PURPOSE: We aimed to compare multiple MRI parameters, including relaxation rates ( R 1 $$ {R}_1 $$ , R 2 $$ {R}_2 $$ , and R 1 ρ $$ {R}_{1\rho } $$ ), ADC from diffusion weighted imaging, pool size ratio (PSR) from quantitative magnetization transfer, and measures of exchange from spin-lock imaging ( S ρ $$ {S}_{\rho } $$ ), for assessing and predicting the severity of polycystic kidney disease (PKD) over time. METHODS: Pcy/Pcy mice with CD1 strain, a mouse model of autosomal dominant PKD, were imaged at 5, 9, and 26 wk of age using a 7T MRI system. Twelve-week normal CD1 mice were used as controls. Post-mortem paraffin tissue sections were stained using hematoxylin and eosin and picrosirius red to identify histological changes. RESULTS: Histology detected segmental cyst formation in the early stage (week 5) and progression of PKD over time in Pcy kidneys. In T 2 $$ {T}_2 $$ -weighted images, small cysts appeared locally in cystic kidneys in week 5 and gradually extended to the whole cortex and outer stripe of outer medulla region from week 5 to week 26. Regional PSR, R 1 $$ {R}_1 $$ , R 2 $$ {R}_2 $$ , and R 1 ρ $$ {R}_{1\rho } $$ decreased consistently over time compared to normal kidneys, with significant changes detected in week 5. Among all the MRI measures, R 2 $$ {R}_2 $$ and R 1 ρ $$ {R}_{1\rho } $$ allow highest detectability to PKD, while PSR and R 1 $$ {R}_1 $$ have highest correlation with pathological indices of PKD. Using optimum MRI parameters as regressors, multiple linear regression provides reliable prediction of PKD progression. CONCLUSION: R 2 $$ {R}_2 $$ , R 1 $$ {R}_1 $$ , and PSR are sensitive indicators of the presence of PKD. Multiparametric MRI allows a comprehensive analysis of renal changes caused by cyst formation and expansion.

Robust cardiac T 1 ρ $$ {\mathrm{T}}_{1_{\boldsymbol{\rho}}} $$ mapping at 3T using adiabatic spin-lock preparations.

PURPOSE: The aim of this study is to develop and optimize an adiabatic T 1 ρ $$ {\mathrm{T}}_{1\uprho} $$ ( T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ ) mapping method for robust quantification of spin-lock (SL) relaxation in the myocardium at 3T. METHODS: Adiabatic SL (aSL) preparations were optimized for resilience against B 0 $$ {\mathrm{B}}_0 $$ and B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities using Bloch simulations. Optimized B 0 $$ {\mathrm{B}}_0 $$ -aSL, Bal-aSL and B 1 $$ {\mathrm{B}}_1 $$ -aSL modules, each compensating for different inhomogeneities, were first validated in phantom and human calf. Myocardial T 1 ρ $$ {\mathrm{T}}_{1\uprho} $$ mapping was performed using a single breath-hold cardiac-triggered bSSFP-based sequence. Then, optimized T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ preparations were compared to each other and to conventional SL-prepared T 1 ρ $$ {\mathrm{T}}_{1\uprho} $$ maps (RefSL) in phantoms to assess repeatability, and in 13 healthy subjects to investigate image quality, precision, reproducibility and intersubject variability. Finally, aSL and RefSL sequences were tested on six patients with known or suspected cardiovascular disease and compared with LGE, T 1 $$ {\mathrm{T}}_1 $$ , and ECV mapping. RESULTS: The highest T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ preparation efficiency was obtained in simulations for modules comprising 2 HS pulses of 30 ms each. In vivo T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ maps yielded significantly higher quality than RefSL maps. Average myocardial T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ values were 183.28 ± $$ \pm $$ 25.53 ms, compared with 38.21 ± $$ \pm $$ 14.37 ms RefSL-prepared T 1 ρ $$ {\mathrm{T}}_{1\uprho} $$ . T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ maps showed a significant improvement in precision (avg. 14.47 ± $$ \pm $$ 3.71% aSL, 37.61 ± $$ \pm $$ 19.42% RefSL, p < 0.01) and reproducibility (avg. 4.64 ± $$ \pm $$ 2.18% aSL, 47.39 ± $$ \pm $$ 12.06% RefSL, p < 0.0001), with decreased inter-subject variability (avg. 8.76 ± $$ \pm $$ 3.65% aSL, 51.90 ± $$ \pm $$ 15.27% RefSL, p < 0.0001). Among aSL preparations, B 0 $$ {\mathrm{B}}_0 $$ -aSL achieved the better inter-subject variability. In patients, B 1 $$ {\mathrm{B}}_1 $$ -aSL preparations showed the best artifact resilience among the adiabatic preparations. T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ times show focal alteration colocalized with areas of hyper-enhancement in the LGE images. CONCLUSION: Adiabatic preparations enable robust in vivo quantification of myocardial SL relaxation times at 3T.

A robust adiabatic constant amplitude spin-lock preparation module for myocardial T1ρ quantification at 3 T.

T1ρ quantification has the potential to assess myocardial fibrosis without contrast agent. However, its preparation spin-lock pulse is sensitive to B1 and B0 inhomogeneities, resulting in severe banding artifacts in the heart region, especially at high magnetic field such as 3 T. We aimed to design a robust spin-lock (SL) preparation module that can be used in myocardial T1ρ quantification at 3 T. We used the tan/tanh pulse to tip up and tip down the magnetization in the spin-lock preparation module (tan/tanh-SL). Bloch simulation was used to optimize pulse shape parameters of the tan/tanh with a pulse duration (Tp ) of 8, 4, and 2 ms, respectively. The designed tan/tanh-SL modules were implemented on a 3-T MR scanner. They were evaluated in phantom studies under three different cases of B0 and B1 inhomogeneities, and tested in cardiac T1ρ quantification of healthy volunteers. The performance of the tan/tanh-SL was compared with the composite SL preparation pulses and the commonly used hyperbolic secant pulse for spin-lock (HS-SL). Feasible pulse shape parameters were obtained using Bloch simulation. Compared with HS-SL, the quantification error of tan/tanh-SL was reduced by 27.7% for Tp = 8 ms (mean ∆Q = 126.15 vs. 174.42) and 75.6% for Tp = 4 ms (mean ∆Q = 136.65 vs. 559.53). In the phantom study, tan/tanh-SL was less sensitive to B1 and B0 inhomogeneity compared with composite SL pulses and HS-SL. In cardiac T1ρ quantification, the T1ρ maps using tan/tanh-SL showed fewer banding artifacts than using composite SL pulses and HS-SL. The proposed tan/tanh-SL preparation module greatly improves the robustness to B0 and B1 field inhomogeneities and can be used in cardiac T1ρ quantification at 3 T.

Correction of errors in estimates of T1ρ at low spin-lock amplitudes in the presence of B0 and B1 inhomogeneities.

Relaxation rates R1ρ in the rotating frame measured by spin-lock methods at very low locking amplitudes (≤ 100 Hz) are sensitive to the effects of water diffusion in intrinsic gradients and may provide information on tissue microvasculature, but accurate estimates are challenging in the presence of B0 and B1 inhomogeneities. Although composite pulse preparations have been developed to compensate for nonuniform fields, the transverse magnetization comprises different components and the spin-lock signals measured do not decay exponentially as a function of locking interval at low locking amplitudes. For example, during a typical preparation sequence, some of the magnetization in the transverse plane is nutated to the Z-axis and later tipped back, and so does not experience R1ρ relaxation. As a result, if the spin-lock signals are fit to a monoexponential decay with locking interval, there are residual errors in quantitative estimates of relaxation rates R1ρ and their dispersion with weak locking fields. We developed an approximate theoretical analysis to model the behaviors of the different components of the magnetization, which provides a means to correct these errors. The performance of this correction approach was evaluated both through numerical simulations and on human brain images at 3 T, and compared with a previous correction method using matrix multiplication. Our correction approach has better performance than the previous method at low locking amplitudes. Through careful shimming, the correction approach can be applied in studies using low spin-lock amplitudes to assess the contribution of diffusion to R1ρ dispersion and to derive estimates of microvascular sizes and spacings. The results of imaging eight healthy subjects suggest that R1ρ dispersion in human brain at low locking fields arises from diffusion among inhomogeneities that generate intrinsic gradients on a scale of capillaries (~7.4 ± 0.5 µm).

Detecting Early-Stage Liver Fibrosis Using Macromolecular Proton Fraction Mapping Based on Spin-Lock MRI: Preliminary Observations.

BACKGROUND: Liver fibrosis is characterized by macromolecule depositions. Recently, a novel technology termed macromolecular proton fraction quantification based on spin-lock magnetic resonance imaging (MPF-SL) is reported to measure macromolecule levels. HYPOTHESIS: MPF-SL can detect early-stage liver fibrosis by measuring macromolecule levels in the liver. STUDY TYPE: Retrospective. SUBJECTS: Fifty-five participants, including 22 with no fibrosis (F0) and 33 with early-stage fibrosis (F1-2), were recruited. FIELD STRENGTH/SEQUENCE: 3 T; two-dimensional (2D) MPF-SL turbo spin-echo sequence, 2D spin-lock T1rho turbo spin-echo sequence, and multi-slice 2D gradient echo sequence. ASSESSMENT: Macromolecular proton fraction (MPF), T1rho, liver iron concentration (LIC), and fat fraction (FF) biomarkers were quantified within regions of interest. STATISTICAL TESTS: Group comparison of the biomarkers using Mann-Whitney U tests; correlation between the biomarkers assessed using Spearman's rank correlation coefficient and linear regression with goodness-of-fit; fibrosis stage differentiation using receiver operating characteristic curve (ROC) analysis. P-value < 0.05 was considered statistically significant. RESULTS: Average T1rho was 41.76 ± 2.94 msec for F0 and 41.15 ± 3.73 msec for F1-2 (P = 0.60). T1rho showed nonsignificant correlation with either liver fibrosis (ρ = -0.07; P = 0.61) or FF (ρ = -0.14; P = 0.35) but indicated a negative correlation with LIC (ρ = -0.66). MPF was 4.73 ± 0.45% and 5.65 ± 0.81% for F0 and F1-2 participants, respectively. MPF showed a positive correlation with liver fibrosis (ρ = 0.59), and no significant correlations with LIC (ρ = 0.02; P = 0.89) or FF (ρ = 0.05; P = 0.72). The area under the ROC curve was 0.85 (95% confidence interval [CI] 0.75-0.95) and 0.55 (95% CI 0.39-0.71; P = 0.55) for MPF and T1rho to discriminate between F0 and F1-2 fibrosis, respectively. DATA CONCLUSION: MPF-SL has the potential to diagnose early-stage liver fibrosis and does not appear to be confounded by either LIC or FF. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Normal Values of Magnetic Resonance T1ρ Relaxation Times in the Adult Heart at 1.5 T MRI.

BACKGROUND: T1ρ mapping is a new quantitative MRI technique in recent years. In order to use T1ρ mapping as a noncontrast method to assess myocardial fibrosis, it is necessary to establish a range of normal values. PURPOSE: To establish a potential normal range of cardiac T1ρ values in healthy adults and to explore the influence of slice location and gender on T1ρ values. STUDY TYPE: Prospective. POPULATION: A total of 57 healthy volunteers without cardiovascular risk factors (age 26.7 ± 11.8 years; 29 males). FIELD STRENGTH/SEQUENCE: 1.5 T; modified Look-Locker inversion recovery (MOLLI) (T1 mapping), multiecho gradient-spin-echo (GraSE) (T2 mapping) and T1ρ -prepared steady-state free precession (T1ρ mapping) sequences. ASSESSMENT: Basal, mid, and apical short-axis left ventricular T1 , T2 , and T1ρ maps were acquired. T1ρ maps at spin-locking frequencies of 5 and 400 Hz were subtracted to create myocardial fibrosis index (mFI) maps. Slice-average and global average T1 , T2 , T1ρ , and mFI values were determined. STATISTICAL TESTS: Shapiro-Wilk test, Independent t-test, ANOVA test, Pearson correlation coefficient (r). SIGNIFICANCE: P value < 0.05. RESULTS: The global average values of T1 , T2 , T1ρ, and mFI were 1053 ± 34 msec, 51.9 ± 2.3 msec, 47.9 ± 2.8 msec, and 4.4 ± 1.6 msec. T1ρ values showed a significant gradual increase from the basal slice to the apical slice of the heart (basal 46.5 ± 2.7 msec, mid 48.0 ± 2.9 msec, apical 49.2 ± 3.3 msec). The T1ρ and mFI values of females (49.7 ± 2.4 msec and 5.1 ± 1.2 msec, respectively) were significantly higher than those of males (46.2 ± 1.9 msec and 3.7 ± 1.7 msec, respectively). In addition, there was a moderate positive correlation between global T1ρ values and global T1 values (r = 0.44, P < 0.05) and a moderate positive correlation between global T1ρ values and global T2 values (r = 0.42, P < 0.05). DATA CONCLUSION: In this study, the global T1ρ values of healthy adults' hearts were 47.9 ± 2.8 msec. This study found that gender and slice location of myocardium can affect the T1ρ values. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

Accelerated 3D free-breathing high-resolution myocardial T1ρ mapping at 3 Tesla.

PURPOSE: To develop a fast free-breathing whole-heart high-resolution myocardial T1ρ mapping technique with robust spin-lock preparation that can be performed at 3 Tesla. METHODS: An adiabatically excited continuous-wave spin-lock module, insensitive to field inhomogeneities, was implemented with an electrocardiogram-triggered low-flip angle spoiled gradient echo sequence with variable-density 3D Cartesian undersampling at a 3 Tesla whole-body scanner. A saturation pulse was performed at the beginning of each cardiac cycle to null the magnetization before T1ρ preparation. Multiple T1ρ -weighted images were acquired with T1ρ preparations with different spin-lock times in an interleaved fashion. Respiratory self-gating approach was adopted along with localized autofocus to enable 3D translational motion correction of the data acquired in each heartbeat. After motion correction, multi-contrast locally low-rank reconstruction was performed to reduce undersampling artifacts. The accuracy and feasibility of the 3D T1ρ mapping technique was investigated in phantoms and in vivo in 10 healthy subjects compared with the 2D T1ρ mapping. RESULTS: The 3D T1ρ mapping technique provided similar phantom T1ρ measurements in the range of 25-120 ms to the 2D T1ρ mapping reference over a wide range of simulated heart rates. With the robust adiabatically excited continuous-wave spin-lock preparation, good quality 2D and 3D in vivo T1ρ -weighted images and T1ρ maps were obtained. Myocardial T1ρ values with the 3D T1ρ mapping were slightly longer than 2D breath-hold measurements (septal T1ρ : 52.7 ± 1.4 ms vs. 50.2 ± 1.8 ms, P < 0.01). CONCLUSION: A fast 3D free-breathing whole-heart T1ρ mapping technique was proposed for T1ρ quantification at 3 T with isotropic spatial resolution (2 mm3 ) and short scan time of ∼4.5 min.

Characterization and correction of the effects of hepatic iron on T1ρ relaxation in the liver at 3.0T.

PURPOSE: Quantitative T1ρ imaging is an emerging technique to assess the biochemical properties of tissues. In this paper, we report our observation that liver iron content (LIC) affects T1ρ quantification of the liver at 3.0T field strength and develop a method to correct the effect of LIC. THEORY AND METHODS: On-resonance R1ρ (1/T1ρ ) is mainly affected by the intrinsic R2 (1/T2 ), which is influenced by LIC. As on-resonance R1ρ is closely related to the Carr-Purcell-Meiboom-Gill (CPMG) R2 , and because the calibration between CPMG R2 and LIC has been reported at 1.5T, a correction method was proposed to correct the R2 contribution to the R1ρ . The correction coefficient was obtained from the calibration results and related transformed factors. To compensate for the difference between CPMG R2 and R1ρ , a scaling factor was determined using the values of CPMG R2 and R1ρ , obtained simultaneously from a single breath-hold from volunteers. The livers of 110 subjects were scanned to validate the correction method. RESULTS: LIC was significantly correlated with R1ρ in the liver. However, when the proposed correction method was applied to R1ρ , LIC and the iron-corrected R1ρ were not significantly correlated. CONCLUSION: LIC can affect T1ρ in the liver. We developed an iron-correction method for the quantification of T1ρ in the liver at 3.0T.

Optimization of spin-lock times in T1ρ mapping of knee cartilage: Cramér-Rao bounds versus matched sampling-fitting.

PURPOSE: To compare different optimization approaches for choosing the spin-lock times (TSLs), in spin-lattice relaxation time in the rotating frame (T1ρ ) mapping. METHODS: Optimization criteria for TSLs based on Cramér-Rao lower bounds (CRLB) are compared with matched sampling-fitting (MSF) approaches for T1ρ mapping on synthetic data, model phantoms, and knee cartilage. The MSF approaches are optimized using robust methods for noisy cost functions. The MSF approaches assume that optimal TSLs depend on the chosen fitting method. An iterative non-linear least squares (NLS) and artificial neural networks (ANN) are tested as two possible T1ρ fitting methods for MSF approaches. RESULTS: All optimized criteria were better than non-optimized ones. However, we observe that a modified CRLB and an MSF based on the mean of the normalized absolute error (MNAE) were more robust optimization approaches, performing well in all tested cases. The optimized TSLs obtained the best performance with synthetic data (3.5-8.0% error), model phantoms (1.5-2.8% error), and healthy volunteers (7.7-21.1% error), showing stable and improved quality results, comparing to non-optimized approaches (4.2-13.3% error on synthetic data, 2.1-6.2% error on model phantoms, 9.8-27.8% error on healthy volunteers). CONCLUSION: A modified CRLB and the MSF based on MNAE are robust optimization approaches for choosing TSLs in T1ρ mapping. All optimized criteria allowed good results even using rapid scans with two TSLs when a complex-valued fitting is done with iterative NLS or ANN.

Sensitivity schemes for dynamic glucose-enhanced magnetic resonance imaging to detect glucose uptake and clearance in mouse brain at 3 T.

We investigated three dynamic glucose-enhanced (DGE) MRI methods for sensitively monitoring glucose uptake and clearance in both brain parenchyma and cerebrospinal fluid (CSF) at clinical field strength (3 T). By comparing three sequences, namely, Carr-Purcell-Meiboom-Gill (CPMG), on-resonance variable delay multipulse (onVDMP), and on-resonance spin-lock (onSL), a high-sensitivity DGE MRI scheme with truncated multilinear singular value decomposition (MLSVD) denoising was proposed. The CPMG method showed the highest sensitivity in detecting the parenchymal DGE signal among the three methods, while both onVDMP and onSL were more robust for CSF DGE imaging. Here, onVDMP was applied for CSF imaging, as it displayed the best stability of the DGE results in this study. The truncated MLSVD denoising method was incorporated to further improve the sensitivity. The proposed DGE MRI scheme was examined in mouse brain with 50%/25%/12.5% w/w D-glucose injections. The results showed that this combination could detect DGE signal changes from the brain parenchyma and CSF with as low as a 12.5% w/w D-glucose injection. The proposed DGE MRI schemes could sensitively detect the glucose signal change from brain parenchyma and CSF after D-glucose injection at a clinically relevant concentration, demonstrating high potential for clinical translation.

Quantification correction for free-breathing myocardial T1ρ mapping in mice using a recursively derived description of a T1ρ* relaxation pathway.

BACKGROUND: Fast and accurate T1ρ mapping in myocardium is still a major challenge, particularly in small animal models. The complex sequence design owing to electrocardiogram and respiratory gating leads to quantification errors in in vivo experiments, due to variations of the T1ρ relaxation pathway. In this study, we present an improved quantification method for T1ρ using a newly derived formalism of a T1ρ* relaxation pathway. METHODS: The new signal equation was derived by solving a recursion problem for spin-lock prepared fast gradient echo readouts. Based on Bloch simulations, we compared quantification errors using the common monoexponential model and our corrected model. The method was validated in phantom experiments and tested in vivo for myocardial T1ρ mapping in mice. Here, the impact of the breath dependent spin recovery time Trec on the quantification results was examined in detail. RESULTS: Simulations indicate that a correction is necessary, since systematically underestimated values are measured under in vivo conditions. In the phantom study, the mean quantification error could be reduced from - 7.4% to - 0.97%. In vivo, a correlation of uncorrected T1ρ with the respiratory cycle was observed. Using the newly derived correction method, this correlation was significantly reduced from r = 0.708 (p < 0.001) to r = 0.204 and the standard deviation of left ventricular T1ρ values in different animals was reduced by at least 39%. CONCLUSION: The suggested quantification formalism enables fast and precise myocardial T1ρ quantification for small animals during free breathing and can improve the comparability of study results. Our new technique offers a reasonable tool for assessing myocardial diseases, since pathologies that cause a change in heart or breathing rates do not lead to systematic misinterpretations. Besides, the derived signal equation can be used for sequence optimization or for subsequent correction of prior study results.

Fast myocardial T1ρ mapping in mice using k-space weighted image contrast and a Bloch simulation-optimized radial sampling pattern.

PURPOSE: T1ρ dispersion quantification can potentially be used as a cardiac magnetic resonance index for sensitive detection of myocardial fibrosis without the need of contrast agents. However, dispersion quantification is still a major challenge, because T1ρ mapping for different spin lock amplitudes is a very time consuming process. This study aims to develop a fast and accurate T1ρ mapping sequence, which paves the way to cardiac T1ρ dispersion quantification within the limited measurement time of an in vivo study in small animals. METHODS: A radial spin lock sequence was developed using a Bloch simulation-optimized sampling pattern and a view-sharing method for image reconstruction. For validation, phantom measurements with a conventional sampling pattern and a gold standard sequence were compared to examine T1ρ quantification accuracy. The in vivo validation of T1ρ mapping was performed in N = 10 mice and in a reproduction study in a single animal, in which ten maps were acquired in direct succession. Finally, the feasibility of myocardial dispersion quantification was tested in one animal. RESULTS: The Bloch simulation-based sampling shows considerably higher image quality as well as improved T1ρ quantification accuracy (+ 56%) and precision (+ 49%) compared to conventional sampling. Compared to the gold standard sequence, a mean deviation of - 0.46 ± 1.84% was observed. The in vivo measurements proved high reproducibility of myocardial T1ρ mapping. The mean T1ρ in the left ventricle was 39.5 ± 1.2 ms for different animals and the maximum deviation was 2.1% in the successive measurements. The myocardial T1ρ dispersion slope, which was measured for the first time in one animal, could be determined to be 4.76 ± 0.23 ms/kHz. CONCLUSION: This new and fast T1ρ quantification technique enables high-resolution myocardial T1ρ mapping and even dispersion quantification within the limited time of an in vivo study and could, therefore, be a reliable tool for improved tissue characterization.

Renal tubular dilation and fibrosis after unilateral ureter obstruction revealed by relaxometry and spin-lock exchange MRI.

We evaluated the use of quantitative MRI relaxometry, including the dispersion of spin-lock relaxation with different locking fields, for detecting and assessing tubular dilation and fibrosis in a mouse model of unilateral ureter obstruction (UUO). C57BL/6 J and BALB/c mice that exhibit different levels of tubular dilation and renal fibrosis after UUO were subjected to MR imaging at 7 T. Mice were imaged before UUO surgery, and at 5, 10 and 15 days after surgery. We acquired maps of relaxation rates and fit the dispersion of spin-lock relaxation rates R1ρ at different locking fields (frequencies) to a model of exchanging water pools, and assessed the sensitivity of the derived quantities for detecting tubular dilation and fibrosis in kidney. Histological scores for tubular dilation and fibrosis, based on luminal space and positive fibrotic areas in sections, were obtained for comparison. Histology detected extensive tubular dilation and mild to moderate fibrosis in the UUO kidneys, in which enlargement of luminal space, deposition of collagen, and reductions in capillary density were observed in the cortex and outer stripe of the outer medulla. Relaxation rates R1 , R2 and R1ρ clearly decreased in these regions of UUO kidneys longitudinally. While R1 showed the highest detectability to tubular dilation and overall changes in UUO kidneys, Sρ , a parameter derived from R1ρ dispersion data, showed the highest correlation with renal fibrosis in UUO. While relaxation parameters are sensitive to tubular dilation in UUO kidneys, Sρ depends primarily on the average exchange rate between water and other chemically shifted resonances such as hydroxyls and amides, and provides additional specific information for evaluating fibrosis in kidney disease.

An efficient R1ρ dispersion imaging method for human knee cartilage using constant magnetization prepared turbo-FLASH.

This work aimed to develop an efficient R1ρ dispersion imaging method for clinical studies of human knee cartilage at 3 T. Eight constant magnetizations (Mprep ) were prepared by tailoring both the duration and amplitude (ω1 ) of a fully refocused spin-lock preparation pulse. The limited Mprep dynamic range was expanded by the measure, equivalent to that with ω1 = ∞, from the magic angle location in the deep femoral cartilage. The developed protocol with Mprep = 60% was demonstrated on one subject's bilateral and two subjects' unilateral asymptomatic knees. The repeatability of the proposed protocol was estimated by two repeated scans with a three-month gap for the last two subjects. The synthetic R1ρ and R2 derived from R1ρ dispersions were compared with the published references using state-of-the-art R1ρ and R2 mapping (MAPSS). The proposed protocol demonstrated good (<5%) repeatability quantified by the intra- and intersubject coefficients of variation in the femoral and tibial cartilage. The synthetic R1ρ (1/s) and the references were comparable in the femoral (23.0 ± 5.3 versus 24.1 ± 3.8, P = 0.67) and the tibial (29.1 ± 8.8 versus 27.1 ± 5.1, P = 0.62), but not the patellar (16.5 ± 4.9 versus 22.7 ± 1.6, P < 0.01) cartilage. The same trends were also observed for the current and the previous R2 . In conclusion, the developed R1ρ dispersion imaging scheme has been revealed to be not only efficient but also robust for clinical studies of human knee cartilage at 3 T.

Whole Brain Adiabatic T1rho and Relaxation Along a Fictitious Field Imaging in Healthy Volunteers and Patients With Multiple Sclerosis: Initial Findings.

BACKGROUND: In preclinical models of multiple sclerosis (MS), both adiabatic T1rho (T1ρadiab ) and relaxation along a fictitious field (RAFF) imaging have demonstrated potential to noninvasively characterize MS. PURPOSE: To evaluate the feasibility of whole brain T1ρadiab and RAFF imaging in healthy volunteers and patients with MS. STUDY TYPE: Single institutional clinical trial. SUBJECTS: 38 healthy volunteers (24-69 years) and 21 patients (26-59 years) with MS. Five healthy volunteers underwent a second MR examination performed within 8 days. Clinical disease severity (The Expanded Disability Status Scale [EDSS] and The Multiple Sclerosis Severity Score [MSSS]) was evaluated at baseline and 1-year follow-up (FU). FIELD STRENGTH/SEQUENCE: RAFF in second rotating frame of reference (RAFF2) was performed at 3 T using 3D-fast-field echo with magnetization preparation, RF amplitude of 11.74 µT while the corresponding value for T1ρadiab was 13.50 µT. T1 -, T2 -, and FLAIR-weighted images were acquired with reconstruction voxel size 1.0 × 1.0 × 1.0 mm3 . ASSESSMENT: The parametric maps of T1ρadiab and RAFF2 (TRAFF2 ) were calculated using a monoexponential model. Semi-automatic segmentation of MS lesions, white matter (WM), and gray matter (GM), and WM tracks was performed using T1 -, T2 -, and FLAIR-weighted images. STATISTICAL TESTS: Regression analysis was used to evaluate correlation of T1ρadiab and TRAFF2 with age and disease severity while a Friedman test followed by Wilcoxon Signed Rank test for differences between tissue types. Short-term repeatability was evaluated on voxel level. RESULTS: Both T1ρadiab and TRAFF2 demonstrated good short-term repeatability with relative differences on voxel level in the range of 6.1%-11.9%. Differences in T1ρadiab and TRAFF2 between the tissue types in MS patients were significant (P < 0.05). T1ρadiab and TRAFF2 correlated (P < 0.001) with baseline EDSS/MSSM and disease progression at FU (P < 0.001). DATA CONCLUSION: Whole brain T1ρadiab and TRAFF2 at 3 T was feasible with significant differences in T1ρadiab and TRAFF2 values between tissues types and correlation with disease severity. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Homonuclear J-Coupling Spectroscopy at Low Magnetic Fields using Spin-Lock Induced Crossing*.

Nuclear magnetic resonance (NMR) spectroscopy usually requires high magnetic fields to create spectral resolution among different proton species. Although proton signals can also be detected at low fields the spectrum exhibits a single line if J-coupling is stronger than chemical shift dispersion. In this work, we demonstrate that the spectra can nevertheless be acquired in this strong-coupling regime using a novel pulse sequence called spin-lock induced crossing (SLIC). This techniques probes energy level crossings induced by a weak spin-locking pulse and produces a unique J-coupling spectrum for most organic molecules. Unlike other forms of low-field J-coupling spectroscopy, our technique does not require the presence of heteronuclei and can be used for most compounds in their native state. We performed SLIC spectroscopy on a number of small molecules at 276 kHz and 20.8 MHZ and show that the simulated SLIC spectra agree well with measurements.

Efficient affinity ranking of fluorinated ligands by 19F NMR: CSAR and FastCSAR.

Fluorine NMR has recently gained high popularity in drug discovery as it allows efficient and sensitive screening of large numbers of ligands. However, the positive hits found in screening must subsequently be ranked according to their affinity in order to prioritize them for follow-up chemistry. Unfortunately, the primary read-out from the screening experiments, namely the increased relaxation rate upon binding, is not proportional to the affinity of the ligand, as it is polluted by effects such as exchange broadening. Here we present the method CSAR (Chemical Shift-anisotropy-based Affinity Ranking) for reliable ranking of fluorinated ligands by NMR, without the need of isotope labeled protein, titrations or setting up a reporter format. Our strategy is to produce relaxation data that is directly proportional to the binding affinity. This is achieved by removing all other contributions to relaxation as follows: (i) exchange effects are efficiently suppressed by using high power spin lock pulses, (ii) dipolar relaxation effects are approximately subtracted by measuring at two different magnetic fields and (iii) differences in chemical shift anisotropy are normalized using calculated values. A similar ranking can be obtained with the simplified approach FastCSAR that relies on a measurement of a single relaxation experiment at high field (preferably > 600 MHz). An affinity ranking obtained in this simple way will enable prioritizing ligands and thus improve the efficiency of fragment-based drug design.