Variable Flip Angle Research Articles

Noncontrast time-resolved pulmonary magnetic resonance angiography with consecutive beam saturation pulse and variable flip angles using three-dimensional fast spin echo: A preliminary study

To develop and validate a novel noncontrast time-resolved magnetic resonance angiography (NC TR-MRA) using consecutive beam pulses with variable flip angles for visualizing hemodynamics in the pulmonary artery, we performed phantom and volunteer studies and applied the novel NC TR-MRA to a 51-year-old woman with pulmonary arteriovenous malformation (PAVM).The novel NC TR-MRA sequence utilized consecutive multiple-beam saturation pulses with variable flip angles considering venous blood T1 relaxation to alter the visualized blood signal length. The flowing blood signal length is suppressed according to the number of beam saturation pulses. NC TR-MRA in each flow phase was assessed by subtracting the images with and without beam saturation pulses. In the flow phantom study, three flow velocities were used to simulate physiological pulmonary arterial blood flow. Signal profiles along the flow direction were evaluated in each flow phase. In the volunteer study, five healthy volunteers were recruited, and NC TR-MRA was applied to evaluate relationships between the flow-saturated time and signal enhancement rates. Four regions of interest (ROIs) were determined on the proximal and distal portions of the right basal artery. A patient with PAVM was included to validate whether a PAVM lesion could be visualized using NC TR-MRA. The visualized flow signal lengths extended proportionally with the number of beam saturation pulses in the steady-flow phantom at all velocities. In the volunteer study, NC TR-MRA images showed signal enhancement from the proximal to distal portions of the right basal artery with increase in the flow-saturated time. Signal enhancement rates in all ROIs were significantly positively correlated with the flow-saturated time (p < 0.001 in all ROIs). Further, the lesion and its hemodynamics could be explicitly visualized in the patient with PAVM. Hence, NC TR-MRA using beam saturation pulse can visualize the hemodynamics of the pulmonary artery and may be useful for diagnosing and following patients with PAVM.

Investigating the impact of RF saturation-pulse parameters on compartment-selective gas-phase depolarization with xenon polarization transfer contrast MRI.

To demonstrate the utility of continuous-wave (CW) saturation pulses in xenon-polarization transfer contrast (XTC) MRI and MRS, to investigate the selectivity of CW pulses applied to dissolved-phase resonances, and to develop a correction method for measurement biases from saturation of the nontargeted dissolved-phase compartment. Studies were performed in six healthy Sprague-Dawley rats over a series of end-exhale breath holds. Discrete saturation schemes included a series of 30 Gaussian pulses (8 ms FWHM), spaced 25 ms apart; CW saturation schemes included single block pulses, with variable flip angle and duration. In XTC imaging, saturation pulses were applied on both dissolved-phase resonance frequencies and off-resonance, to correct for other sources of signal loss and compromised selectivity. In spectroscopy experiments, saturation pulses were applied at a set of 19 frequencies spread out between 185 and 200 ppm to map out modified z-spectra. Both modified z-spectra and imaging results showed that CW RF pulses offer sufficient depolarization and improved selectivity for generating contrast between presaturation and postsaturation acquisitions. A comparison of results obtained using a variety of saturation parameters confirms that saturation pulses applied at higher powers exhibit increased cross-contamination between dissolved-phase resonances. Using CW RF saturation pulses in XTC contrast preparation, with the proposed correction method, offers a potentially more selective alternative to traditional discrete saturation. The suppression of the red blood cell contribution to the gas-phase depolarization opens the door to a novel way of quantifying exchange time between alveolar volume and hemoglobin.

3D variable flip angle T1 mapping for differentiating benign and malignant liver lesions at 3T: comparison with diffusion weighted imaging

BackgroundDifferent methods have been used to improve the imaging diagnosis of focal liver lesions (FLL). Among them, magnetic resonance imaging (MRI) has received more attention since it provides significant amount of information without radiation exposure. However, atypical imaging characteristics of FLL on MRI may complicate the differential diagnosis between benign and malignant FLL. This study aimed to compare the diagnostic value of T1 mapping and diffusion-weighted imaging (DWI) for differentiating of benign and malignant FLLs.MethodsThis retrospective study enrolled 294 FLLs, including 150 benign and 144 malignant lesions. Whole liver T1 mapping sequences were obtained before and 2 min after the administration of Gd-DTPA to acquire native T1 and enhanced T1 and ΔT1%. Additionally, DWI sequence was conducted to generate apparent diffusion coefficient (ADC) maps. These quantitative parameters were compared using one-way analysis of variance, and the diagnostic accuracy of T1 mapping and ADC for FLLs was calculated by area under the curve (AUC).ResultsSignificant differences were observed regarding the native T1, enhanced T1, ΔT1%, and ADC between benign and malignant FLLs. Furthermore, the sensitivity and specificity of the parameters are as follows: native T1 0.797/0.702 (cut off value 1635.5 ms); enhanced T1, 0.911/0.976 (cutoff value 339.2 ms); ΔT1%, 0.901/0.905 (cutoff value 70.8%); and ADC, 0.975/0.952 (cutoff value 1.21 × 10−3 mm2/s). The ideal cutoff values for native T1 and ADC in identifying cyst and haemangioma were 2422.9 ms (AUC 0.990, P < 0.01) and 2.077 × 10–3 mm2/s (AUC 0.949, P < 0.01), respectively, with a sensitivity and specificity of 0.963/1 and 0.852/0.892, respectively. ADC was significantly positively correlated with T1 and ΔT1%, and significantly negatively correlated with enhanced T1.ConclusionThe 3D Variable flip angle T1 mapping technique with Gd-DTPA has a high clinical potential for identifying benign and malignant FLLs. The enhanced T1 and ΔT1% values have similar diagnostic accuracy compared with DWI in evaluating FLLs. Native T1 shows better performance than DWI in distinguishing benign liver lesions, specifically, cysts, and haemangioma.

Mapping pH using stimulated echoes formed via chemical exchange

PurposeRACETE (refocused acquisition of chemical exchange transferred excitations) is a recently developed approach to imaging solute exchange with water. However, it lacks biophysical specificity, as it is sensitive to exchange rates, relaxation rates, solute concentration, and macromolecular content. We modified this sequence and developed a protocol and corresponding metric with specific sensitivity to the solute exchange rate and hence a means for mapping pH. Theory and methodsRACETE splits the two gradients traditionally used in a stimulated-echo sequence into one applied after exciting solutes and one applied after exciting water, hence requiring exchange for echo formation. In this work, we leverage the dependence of the stimulated-echo signal on the exchange process. By preserving the total irradiation power and using a ratio metric, the other signal dependencies cancel, leaving a specific measure of exchange rate. Additionally, artifacts due to off-resonance excitation of water are addressed using a phase cancelling approach; and a gradient-echo imaging sequence with a variable flip angle excitation is tailored for a fast read-out of RECETE prepared signals. This method is validated using numerical simulations and salicylic acid phantom experiments at 9.4 T. ResultsNumerical simulations and phantom experiments demonstrate that the ratio-metric is a single-variable function of exchange rate with extremely low dependence on confounding factors. Additionally, artifacts due to direct water excitation are removed and robustness to B0 and B1 inhomogeneities is demonstrated. ConclusionThe proposed method can be used for fast pH mapping with robustness against the confounding effects that widely exist in other methods.

Rapid variable flip angle positive susceptibility contrast imaging for clinical metal seeds

Positive susceptibility contrast imaging (PSCI) based on susceptibility mapping exhibits excellent efficacy for visualizing magnetic resonance (MR)-compatible metallic devices because of their high magnetic susceptibility compared to that of human tissues. However, the long-acquisition time required by the two-dimensional fast spin echo (2D FSE)-based PSCI approach, impedes its practical applications in 3D imaging. In this study, a three-dimensional (3D) susceptibility-based variable flip angle (vFA) FSE sequence was proposed to accelerate data acquisition in the clinical radiotherapy applications of ex vivo and in vivo rapid 3D PSCI for the imaging of metal seeds. Here, the proposed scheme applied a 3D modulated vFA technique for refocused imaging with an extended echo-train sequence for sampling data. The scheme integrated the projection-onto-dipole fields (PDF) to remove the background field and accelerate PSCI by using a compressive sensing framework with a variable-densitysampling mask. The experiments involved some gelatin phantoms, porcine tissues and patients with scapular tumors and brachytherapy seeds. All of the experimental results showed that the proposed scheme could accelerate data acquisition of 3D PSCI at the reduction factors of 2 ∼ 5 while accurately localizing the actual positions of the brachytherapy seeds in the ex vivo and in vivo applications. The results were compared with those of the existing methods, including susceptibility gradient mapping using the original resolution (SUMO) and gradient echo acquisition for superparamagnetic particle (GRASP).

Synthetic MRI for Radiotherapy Planning for Brain and Prostate Cancers: Phantom Validation and Patient Evaluation.

PurposeWe aimed to evaluate the accuracy of T1 and T2 mappings derived from a multispectral pulse sequence (magnetic resonance image compilation, MAGiC®) on 1.5-T MRI and with conventional sequences [gradient echo with variable flip angle (GRE-VFA) and multi-echo spin echo (ME-SE)] compared to the reference values for the purpose of radiotherapy treatment planning.MethodsThe accuracy of T1 and T2 measurements was evaluated with 2 coils [head and neck unit (HNU) and BODY coils] on phantoms using descriptive statistics and Bland–Altman analysis. The reproducibility and repeatability of T1 and T2 measurements were performed on 15 sessions with the HNU coil. The T1 and T2 synthetic sequences obtained by both methods were evaluated according to quality assurance (QA) requirements for radiotherapy. T1 and T2 in vivo measurements of the brain or prostate tissues of two groups of five subjects were also compared.ResultsThe phantom results showed good agreement (mean bias, 8.4%) between the two measurement methods for T1 values between 490 and 2,385 ms and T2 values between 25 and 400 ms. MAGiC® gave discordant results for T1 values below 220 ms (bias with the reference values, from 38% to 1,620%). T2 measurements were accurately estimated below 400 ms (mean bias, 8.5%) by both methods. The QA assessments are in agreement with the recommendations of imaging for contouring purposes for radiotherapy planning. On patient data of the brain and prostate, the measurements of T1 and T2 by the two quantitative MRI (qMRI) methods were comparable (max difference, <7%).ConclusionThis study shows that the accuracy, reproducibility, and repeatability of the multispectral pulse sequence (MAGiC®) were compatible with its use for radiotherapy treatment planning in a range of values corresponding to soft tissues. Even validated for brain imaging, MAGiC® could potentially be used for prostate qMRI.

From Dose Reduction to Contrast Maximization: Can Deep Learning Amplify the Impact of Contrast Media on Brain Magnetic Resonance Image Quality? A Reader Study.

The aim of this study was to evaluate a deep learning method designed to increase the contrast-to-noise ratio in contrast-enhanced gradient echo T1-weighted brain magnetic resonance imaging (MRI) acquisitions. The processed images are quantitatively evaluated in terms of lesion detection performance. A total of 250 multiparametric brain MRIs, acquired between November 2019 and March 2021 at Gustave Roussy Cancer Campus (Villejuif, France), were considered for inclusion in this retrospective monocentric study. Independent training (107 cases; age, 55 ± 14 years; 58 women) and test (79 cases; age, 59 ± 14 years; 41 women) samples were defined. Patients had glioma, brain metastasis, meningioma, or no enhancing lesion. Gradient echo and turbo spin echo with variable flip angles postcontrast T1 sequences were acquired in all cases. For the cases that formed the training sample, "low-dose" postcontrast gradient echo T1 images using 0.025 mmol/kg injections of contrast agent were also acquired. A deep neural network was trained to synthetically enhance the low-dose T1 acquisitions, taking standard-dose T1 MRI as reference. Once trained, the contrast enhancement network was used to process the test gradient echo T1 images. A read was then performed by 2 experienced neuroradiologists to evaluate the original and processed T1 MRI sequences in terms of contrast enhancement and lesion detection performance, taking the turbo spin echo sequences as reference. The processed images were superior to the original gradient echo and reference turbo spin echo T1 sequences in terms of contrast-to-noise ratio (44.5 vs 9.1 and 16.8; P < 0.001), lesion-to-brain ratio (1.66 vs 1.31 and 1.44; P < 0.001), and contrast enhancement percentage (112.4% vs 85.6% and 92.2%; P < 0.001) for cases with enhancing lesions. The overall image quality of processed T1 was preferred by both readers (graded 3.4/4 on average vs 2.7/4; P < 0.001). Finally, the proposed processing improved the average sensitivity of gradient echo T1 MRI from 88% to 96% for lesions larger than 10 mm ( P = 0.008), whereas no difference was found in terms of the false detection rate (0.02 per case in both cases; P > 0.99). The same effect was observed when considering all lesions larger than 5 mm: sensitivity increased from 70% to 85% ( P < 0.001), whereas false detection rates remained similar (0.04 vs 0.06 per case; P = 0.48). With all lesions included regardless of their size, sensitivities were 59% and 75% for original and processed T1 images, respectively ( P < 0.001), and the corresponding false detection rates were 0.05 and 0.14 per case, respectively ( P = 0.06). The proposed deep learning method successfully amplified the beneficial effects of contrast agent injection on gradient echo T1 image quality, contrast level, and lesion detection performance. In particular, the sensitivity of the MRI sequence was improved by up to 16%, whereas the false detection rate remained similar.

Single shot spiral TSE with annulated segmentation.

To develop, optimize, and implement a single shot spiral turbo spin echo (TSE) sequence at 3T and to demonstrate its feasibility to acquire artifact free images of the central nervous system with 1 mm spatial resolution in <200 ms. Spiral TSE sequences with annulated spiral segmentation have been implemented with different acquisition modes. In fixed mode, the duration of each spiral segment is fixed to fill the available acquisition time tacq . In tangential mode, the beginning of each spiral segment is reached via a straight tangential trajectory. Tangential mode allows faster transition and thus longer tacq for a given echo spacing (ESP), but less data points can be acquired per acquisition interval. Alternating between spiral-in and spiral-out readout in alternating echoes leads to a somewhat different point spread function for off-resonant spins. Images of the brain with 1 mm spatial resolution acquired with a variable density spiral with ∼40% undersampling can be acquired in a single shot. All acquisition modes produce comparable image quality. Only mild artifacts in regions of strong susceptibility effects can be observed for ESP of 10 ms and below. The use of variable flip angle schemes allows seamless acquisition of consecutive slices and/or dynamic scans without waiting time between consecutive acquisitions. Comparison with images acquired at 1.5T shows reduced susceptibility artifacts within the brain and facial structures. Single shot spiral TSE has been demonstrated to enable highly efficient acquisition of high-resolution images of the brain in <200 ms per slice.

Quantitative analysis of liver function: 3D variable-flip-angle versus Look-Locker T1 relaxometry in hepatocyte-specific contrast-enhanced liver MRI.

Gd-EOB-DTPA, a liver specific contrast agent with T1- shortening effects, is routinely used in clinical magnetic resonance imaging (MRI) for detection and characterization of focal liver lesions. Gd-EOB-DTPA-enhanced T1 relaxometry has recently received increasing attention as a tool for the quantitative analyses of liver function. However, this T1 relaxometry technique is limited due to various artifacts caused by B1 inhomogeneities and motion artifacts. This study aims to compare two different T1 relaxometry techniques for evaluating liver function as determined using a 13C-methacetin-based breath test (13C-MBT). Ninety-six patients underwent gadoxetic acid-enhanced MRI of the liver at 3T and a 13C-MBT. Two different prototype sequences for T1 relaxometry were used, a 3D VIBE sequence using Dixon water-fat separation and variable-flip-angles (VFA), as well as a 2D Look-Locker sequence (LL). Images were acquired before (T1 pre) and 20 minutes after (T1 post) administration of liver-specific contrast agent to evaluate the reduction rates of T1 relaxation time (rrT1) in accordance with the 13C-MBT outcome. To analyze both MR sequences' performance, the intraclass correlation coefficient (ICC) between four ROI measurements within the same liver and the coefficient of repeatability (CR) were calculated. T1 relaxometry measurements based on MR sequences, VFA, and LL show a constant change in line with impaired liver function progression. Simple regression models showed a log-linear correlation of 13C-MBT values with all evaluated T1 relaxometry measurements (VFA T1post, VFA rrT1, LL T1post, LL rrT1, P<0.001). Both ICC (VFA T1post, LL T1post; 0.75, 0.95) and CR (VFA T1 post, LL T1 post; 179, 101) showed a better agreement between ROI measurements using the LL sequence. Both T1 relaxometry sequences are suitable for the evaluation of liver function based on 13C-MBT. However, the Look-Locker sequence is less susceptible to artifacts and might be more advantageous, especially in patients with impaired liver function.

Evaluation of Dynamic Contrast-Enhanced MRI Measures of Lung Congestion and Endothelial Permeability in Heart Failure: A Prospective Method Validation Study.

BackgroundMethods for accurate quantification of lung fluid in heart failure (HF) are needed. Dynamic contrast‐enhanced (DCE)‐MRI may be an appropriate modality.PurposeDCE‐MRI evaluation of fraction of fluid volume in the interstitial lung space (v e ) and vascular permeability (K trans).Study TypeProspective, single‐center method validation.PopulationSeventeen evaluable healthy volunteers (HVs), 12 participants with HF, and 3 with acute decompensated HF (ADHF).Field Strength/Sequence T 1 mapping (spoiled gradient echo variable flip angle acquisition) followed by dynamic series (three‐dimensional spoiled gradient‐recalled echo acquisitions [constant echo time, repetition time, and flip angle at 1.5 T]).AssessmentThree whole‐chest scans were acquired: baseline (Session 1), 1‐week later (Session 2), following exercise (Session 3). Extended Tofts model quantified v e and K trans (voxel‐wise basis); total lung median measures were extracted and fitted via repeat measure analysis of variance (ANOVA) model. Patient tolerability of the scanning protocol was assessed.Statistical TestsThis was constructed as an experimental medicine study. Primary endpoints: K trans and v e at baseline (HV vs. HF), change in K trans and v e following exercise, and following lung congestion resolution (ADHF). K trans and v e were fitted separately using ANOVA. Secondary endpoint: repeatability, that is, within‐participant variability in v e and K trans between sessions (coefficient of variation estimated via mixed effects model).ResultsThere was no significant difference in mean K trans between HF and HV (P ≤ 0.17): 0.2216 minutes−1 and 0.2353 minutes−1 (Session 1), 0.2044 minutes−1 and 0.2567 minutes−1 (Session 2), 0.1841 minutes−1 and 0.2108 minutes−1 (Session 3), respectively. v e was greater in the HF group (all scans, P ≤ 0.02). Results were repeatable between Sessions 1 and 2; mean values for HF and HV were 0.4946 and 0.3346 (Session 1), 0.4353 and 0.3205 (Session 2), respectively. There was minimal difference in K trans or v e between scans for participants with ADHF (small population precluded significance testing). Scanning was well tolerated.Data ConclusionWhile no differences were detected in K trans, v e was greater in chronic HF patients vs. HV, augmented beyond plasma and intracellular volume. DCE‐MRI is a valuable diagnostic and physiologic tool to evaluate changes in fluid volume in the interstitial lung space associated with symptomatic HF.Level of Evidence2Technical Efficacy Stage2

Liver T1 relaxation time of the 'normal liver' in healthy Asians: measurement with MOLLI and B1-corrected VFA methods at 3T.

Liver T1 is a potential magnetic resonance imaging biomarker for liver diseases. This study aimed to determine the T1 relaxation time of the normal liver (PDFF<5%) in healthy Asian volunteers using modified look-locker inversion recovery (MOLLI) and B1 inhomogeneity-corrected variable flip angle (B1-corrected VFA). 60 healthy Asian volunteers without focal or diffuse liver disease underwent a liver scan at 3T magnetic resonance. Proton density fat fraction (PDFF) and liver stiffness measurements were applied for the quantification of liver fat and fibrosis. T1 mapping was performed with MOLLI and B1-corrected VFA sequences. Bland-Altman, linear regression, Student t-test, and one-way analysis of variance were used for statistical analysis. The mean T1 relaxation times of the whole liver were 901 ± 34 ms by MOLLI, and 948 ± 29 ms by B1-corrected VFA in healthy volunteers. There was a strong correlation (r = 0.86, p < 0.0001) for liver T1 between two T1 mapping methods. There were significant differences between the right and left lobes in liver T1 relaxation times using both methods (p < 0.05). Gender and Asian ethnic disparities had no impact on liver T1 relaxation times. T1 relaxation times of the normal liver (PDFF<5%) in healthy volunteers were established by MOLLI and B1-corrected VFA T1 mapping methods at 3T. It may provide suitable and robust baseline values for the assessment of liver diseases. Gender and Asian ethnic disparities do not impact liver T1 relaxation time measurements.

Correcting inter-scan motion artifacts in quantitative R1 mapping at 7T.

PurposeInter‐scan motion is a substantial source of error in R1 estimation methods based on multiple volumes, for example, variable flip angle (VFA), and can be expected to increase at 7T where B1 fields are more inhomogeneous. The established correction scheme does not translate to 7T since it requires a body coil reference. Here we introduce two alternatives that outperform the established method. Since they compute relative sensitivities they do not require body coil images.TheoryThe proposed methods use coil‐combined magnitude images to obtain the relative coil sensitivities. The first method efficiently computes the relative sensitivities via a simple ratio; the second by fitting a more sophisticated generative model.Methods R1 maps were computed using the VFA approach. Multiple datasets were acquired at 3T and 7T, with and without motion between the acquisition of the VFA volumes. R1 maps were constructed without correction, with the proposed corrections, and (at 3T) with the previously established correction scheme. The effect of the greater inhomogeneity in the transmit field at 7T was also explored by acquiring B1+ maps at each position.ResultsAt 3T, the proposed methods outperform the baseline method. Inter‐scan motion artifacts were also reduced at 7T. However, at 7T reproducibility only converged on that of the no motion condition if position‐specific transmit field effects were also incorporated.ConclusionThe proposed methods simplify inter‐scan motion correction of R1 maps and are applicable at both 3T and 7T, where a body coil is typically not available. The open‐source code for all methods is made publicly available.

Assessment of dynamic hepatic and renal imaging changes in COVID-19 survivors using T1 mapping and IVIM-DWI.

PurposeTo explore the imaging changes of the liver and kidneys in COVID-19 survivors using variable flip angle (VFA) T1 mapping and intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI).MethodsThis prospective study included 37 discharged COVID-19 participants and 24 age-matched non-COVID-19 volunteers who underwent abdominal MRI with VFA T1 mapping and IVIM-DWI sequencing as a COVID-19 group and control group, respectively. Among those discharged COVID-19 participants, 23 patients underwent two follow-up MRI scans, and were enrolled as the 3-month follow-up group and 1-year follow-up group, respectively. The demographics, clinical characteristics, and laboratory tests were collected. Imaging parameters of the liver and kidneys were measured. All collected values were compared among different groups.ResultsThe 3-month follow-up group had the lowest hepatic T1 value, which was significantly lower than the value in the control group (P < 0.001). Additionally, the 3-month follow-up group had the highest hepatic ADC and D values, cortical ADC and f values, which were significantly higher than those in the control group (for all, P < 0.05). The hepatic D value in the 1-year follow-up group decreased significantly in comparison with that in the 3-month follow-up group (P = 0.001). Compared to non-severe patients, severe cases had significantly higher hepatic D* and f*D* values (P = 0.031, P = 0.015, respectively).ConclusionThe dynamic alterations of hepatic and renal imaging parameters detected with T1 mapping and IVIM-DWI suggested that COVID-19 survivors might develop mild, non-symptomatic liver and kidney impairments, of which liver impairment could probably relieve over time and kidney impairment might be long-existing.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s00261-022-03471-y.

Bias, Repeatability and Reproducibility of Liver T1 Mapping With Variable Flip Angles.

BackgroundThree‐dimensional variable flip angle (VFA) methods are commonly used for T1 mapping of the liver, but there is no data on the accuracy, repeatability, and reproducibility of this technique in this organ in a multivendor setting.PurposeTo measure bias, repeatability, and reproducibility of VFA T1 mapping in the liver.Study TypeProspective observational.PopulationEight healthy volunteers, four women, with no known liver disease.Field Strength/Sequence1.5‐T and 3.0‐T; three‐dimensional steady‐state spoiled gradient echo with VFAs; Look‐Locker.AssessmentTraveling volunteers were scanned twice each (30 minutes to 3 months apart) on six MRI scanners from three vendors (GE Healthcare, Philips Medical Systems, and Siemens Healthineers) at two field strengths. The maximum period between the first and last scans among all volunteers was 9 months. Volunteers were instructed to abstain from alcohol intake for at least 72 hours prior to each scan and avoid high cholesterol foods on the day of the scan.Statistical TestsRepeated measures ANOVA, Student t‐test, Levene's test of variances, and 95% significance level. The percent error relative to literature liver T1 in healthy volunteers was used to assess bias. The relative error (RE) due to intrascanner and interscanner variation in T1 measurements was used to assess repeatability and reproducibility.ResultsThe 95% confidence interval (CI) on the mean bias and mean repeatability RE of VFA T1 in the healthy liver was 34 ± 6% and 10 ± 3%, respectively. The 95% CI on the mean reproducibility RE at 1.5 T and 3.0 T was 29 ± 7% and 25 ± 4%, respectively.Data ConclusionBias, repeatability, and reproducibility of VFA T1 mapping in the liver in a multivendor setting are similar to those reported for breast, prostate, and brain.Level of Evidence1Technical Efficacy Stage1

Water Specific MRI T1 Mapping for Evaluating Liver Inflammation Activity Grades in Rats With Methionine-Choline-Deficient Diet-Induced Nonalcoholic Fatty Liver Disease.

Early detection and grading of liver inflammation are important for the management of nonalcoholic fatty liver disease (NAFLD) patients. There is still lack of a noninvasive way for the inflammation characterization in NAFLD. To assess liver inflammation grades by water specific T1 (wT1) in a rat model. Prospective. A total of 65 male rats with methionine-choline-deficient diet-induced NAFLD and 15 male normal rats as control. A 3 T; multiecho variable flip angle gradient echo sequence. The wT1 and proton density fat fraction were quantified. Inflammation and fibrosis were assessed histologically with H&E and Sirius red stained slices according to the nonalcoholic steatohepatitis scoring system. Inflammation grade was scored with G0/G1/G2/G3 as none/mild/moderate/severe inflammation in NALFD rats. G0 + G1 and G2 + G3 were combined as none-to-mild grade (GL) and moderate-to-severe grade (GH) inflammation groups. Analysis of variance (ANOVA), Mann-Whitney U test, Spearman's correlation, and receiver operating characteristic (ROC) analysis were performed. The areas under ROC (AUROC) was used for the diagnostic performance of wT1 in discriminating GH and GL. A P value < 0.01 was considered statistically significant. Seventy-six rats were included in the analysis. The numbers in G0-G3 groups were 5, 16, 13, and 27. wT1 of G0-G3 was 568.55 ± 63.93 msec, 582.53 ± 62.98 msec, 521.21 ± 67.31 msec, and 508.79 ± 60.53 msec. A moderate but significant negative correlation between wT1 and histopathological inflammation grades was observed (rs =-0.42). The wT1 of GH (512.80 ± 62.22 msec) was significantly lower than GL (579.20 ± 61.89 msec). The AUROC of wT1 was 0.79, and the optimal cut-off of wT1 was 562.64 msec (sensitivity: 90%, specificity: 76%), for the discrimination of GL and GH. wT1 could differentiate none-to-mild inflammation from moderate-to-severe inflammation in the early stage of the NAFLD rat model. 1 TECHNICAL EFFICACY: Stage 1.

Effects of T2 * on accuracy and precision of dynamic T1 measurements using the single reference variable flip angle method: a simulation study.

To study in simulation and in theory the accuracy and precision of dynamic T1 measurements obtained using the previously published single-reference variable flip angle (SR-VFA) technique, with a focus on the effects of dynamic changes in T2 * on the calculation. Monte Carlo simulations were performed over 1000 noisy iterations for the VFA method, the SR-VFA method, and a proposed method, SR-VFA with a T2 * correction (SR-VFA-T2 *). Dynamic T1 estimates were calculated analytically for each method, with signals modeled by the steady-state spoiled gradient echo equation. The mean and standard deviation of these estimates were calculated and compared to truth, while varying repetition time (TR), baseline and dynamic T1 , echo time (TE), baseline and dynamic T2 *, flip angles, and the number of averages on baseline scans. Additionally, the variance of T1 in the SR-VFA and SR-VFA-T2 * methods was derived analytically based on the theory of propagation of errors. This equation was used to produce an inverse-variance weighted linear combination to improve T1 mapping precision in the SR-VFA-T2 * method. Flip angle sensitivity of dynamic T1 precision in the SR-VFA and SR-VFA-T2 * methods was also performed. Substantial bias can be produced by the SR-VFA method when the ratio of the T2 * decay of the dynamic signal versus that of the baseline signals deviates from 1, with a 0.01 deviation leading to approximately a 1% bias in cases of high SNR and TR ≫ T1 . This bias can be corrected by estimating the baseline and dynamic T2 * values in this ratio via multiecho measurements. The bias and precision of the SR-VFA-T2 * method, when normalized to scan time, is found to rival and sometimes improve upon the two flip angle VFA method when an inverse variance weighted linear combination is applied across its multiecho T1 maps. The analytic variance equation presented is found to be accurate within 1% relative to the Monte Carlo simulations over a broad parameter space. Flip angle ranges that maximize SR-VFA and SR-VFA-T2 *T1 precision over a broad parameter space are given, and each is defined relative to TR and T1 . Multiecho SR-VFA-T2 * T1 mapping is found in simulation and theory to be a promising alternative to the VFA method that maintains speed of the SR-VFA method with accuracy and precision similar to the VFA method.

Individualized arterial spin labeling background suppression by rapid T1 mapping during acquisition

ObjectiveArterial spin labeling blood perfusion signal relies on the difference between a label and a control image. Background suppression pulses are commonly used to improve the contrast, yet these are based on estimates of tissue relaxation times. The aim of this study is to improve the perfusion contrast by individualizing the timing of these background suppression pulses by means of T1 mapping.MethodsThe optimized timing of the background suppression pulses is obtained by rapid T1 mapping employing the variable flip angle technique. Ten healthy volunteers were included in this study. To compare the results, visual grading and the Wilcoxon signed-rank test was used comparing three categories of image quality.ResultsThe readers confirmed that the images of the proposed method generally show a higher signal-to-background ratio and cortical structures are better visible. Noise was mostly comparable to the standard method. Relative blood flow was statistically significant higher in the modified method.ConclusionThe individually optimized background suppression pulses improve the image appearance and allow for a better visualization of cortical structures. The proposed technique however prolongs scan time, which can be seen as negative result, yet needs to be further evaluated.Key Points• Background suppression timing in ASL can vary.• Both the label and control condition can be modified for T1 mapping.• Adapting the pulse timing improves the signal-to-background ratio.

FID-calibrated simultaneous multi-slice fast spin echo with long trains of hard pulses

Objective. To develop a novel, free-induction-decay (FID)-calibrated single-shot simultaneous multi-slice fast spin echo (SMS-FSE) with very long hard pulse trains for high encoding efficiency and low energy deposition. Approach. The proposed single-shot SMS-FSE employs a mixed pulse configuration in which a long excitation pulse that is spatially multi-band (MB) selective is used in conjunction with short spatially nonselective refocusing pulses. To alleviate energy deposition to tissues while reducing signal modulation along the echo train, variable low flip angles with signal prescription are utilized in the refocusing pulse train. A time-efficient FID calibration and correction method is introduced before aliased voxels in the slice direction are resolved. Simulations and experiments are performed to demonstrate the feasibility of the proposed method as an alternative to conventional HASTE for generating T 2-weighted images. Main results. Compared with conventional HASTE, the proposed method enhances imaging speed effectively by an MB factor up to 5 without apparent loss of image contrast while successfully eliminating FID artifacts. Significance. We successfully demonstrated the feasibility of the proposed method as an encoding- and energy-efficient alternative to conventional HASTE for generation of T 2-weighted contrast.

T1 mapping as a surrogate marker of chemotherapy response evaluation in patients with osteosarcoma

ObjectivesTo characterize baseline T1 values of tumors, measure changes after the course of chemotherapy, and evaluate its potential as a marker of response assessment in patients with osteosarcoma. Materials and MethodsA total of 35 patients (male:female = 27:8; age = 17.9 ± 6 years; metastatic:localized = 11:24) with biopsy-proven osteosarcoma were analyzed prospectively. All patients underwent magnetic resonance imaging before neoadjuvant chemotherapy (NACT) (baseline) and after NACT completion (follow-up), followed by surgery and histopathological evaluation. Histopathological necrosis served as the gold standard for assessing chemotherapy response (responder: ≥50% necrosis and non-responder: <50% necrosis). Three-dimensional spoiled gradient recalled echo images were acquired with varying flip angles (50, 100, 200, and 300) using a 1.5 Tesla scanner. T1 values were estimated in healthy muscle tissue and tumors at baseline and follow-up, and the relative percentage changes after NACT (ΔT1) were evaluated, and histogram analysis was performed to characterize the T1 value of the tumor and predict the NACT response using the Pearson correlation coefficient (r) and receiver operating characteristic curve analysis. ResultsAt baseline, a significantly higher T1-mean (830.96 ± 193.88 msec versus 683.29 ± 210.00 msec; p = 0.003) and lower T1-skewness (0.86 ± 1.66 versus 1.60 ± 1.55; p = 0.02) were observed in osteosarcoma than healthy tissue. Responder:non-responder ratio was 13:22. At baseline, a significantly higher T1-mean (936.14 ± 193.17 msec versus 768.82 ± 169.25 msec; p = 0.018) and lower T1-skewness (-0.17 ± 0.85 versus 1.47 ± 1.73; p = 0.003) were observed among responders, than non-responders. After NACT, ΔT1 in tumor was significantly higher among responders than non-responders (-27.22 ± 12.17% versus −15.70 ± 18.99%; p = 0.034). ΔT1-mean and ΔT1-skewness after NACT were moderately correlated (r = − 0.4, p = 0.030; r = 0.4, p = 0.011) with histopathological necrosis. For predicting NACT response, T1-mean and T1-skewness jointly produced an area under the curve (AUC) = 0.80 at baseline, and ΔT1-mean and ΔT1-skewness jointly produced AUC = 0.76 after NACT. ConclusionThe mean and skewness of T1 values in osteosarcoma are potential non-invasive imaging markers for chemotherapy response assessment.

Rapid analytical CEST spectroscopy of competitive host–guest interactions using spatial parallelization with a combined approach of variable flip angle, keyhole and averaging (CAVKA)

A serious limitation of high resolution 129Xe chemical exchange saturation transfer (CEST) NMR spectroscopy for comparing competitive host-guest interactions from different samples is the long acquisition time due to step-wise encoding of the chemical shift dimension. A method of optimized use of 129Xe spin magnetization to enable the accelerated and simultaneous acquisition of CEST spectra from multiple samples or regions in a setup is described. The method is applied to investigate the host-guest system of commercially available cucurbit[7]uril (CB7) and xenon with competing guests: cis-1,4-bis(aminomethyl)cyclohexane, cadaverine, and putrescine. Interactions with the different guests prove that the observed CEST signal is from a CB6 impurity and that CB7 itself does not produce a CEST signal. Instead, rapid interactions between xenon and CB7 manifest in the spectrum as a broad saturation response that could be suppressed by cis-1,4-bis(aminomethyl)cyclohexane. This guest prevents interactions at the CB7 portals. The suggested method represents a type of spectroscopic imaging that is capable of capturing the exchange kinetics information of systems that otherwise suffer from shortened T2 times and yields multiple spectra for comparing exchange conditions with a reduction of >95% in acquisition time. The spectral quality is sufficient to perform quantitative analysis and quantifications relative to a CB6 standard as well as relative to a known blocker concentration (putrescine) that both reveal an unexpectedly high CB6 impurity of ca. 8%.