Multiple Gradient Echo Sequence Research Articles

Anisotropy of the R1/T2* value dependent on white matter fiber orientation with respect to the B0 field

The R1 (1/T1) map divided by the T2* map (R1/T2* map) draws attention as a high-resolution myelin-related map. However, both R1 and R2* (1/T2*) values demonstrate anisotropy dependent on the white matter (WM) fiber orientation with respect to the static magnetic (B0) field. Therefore, this study primarily aimed to investigate the comprehensive impact of these angular-dependent anisotropies on the R1/T2* value.This study enrolled 10 healthy human volunteers (age = 25 ± 1.3) on the 3.0 T MRI system. For R1/T2* map calculation, whole brain R1 and T2* maps were repeatedly obtained in three head tilt positions by magnetization-prepared two rapid gradient echoes and multiple spoiled gradient echo sequences, respectively. Afterward, all maps were spatially normalized and registered to the Johns Hopkins University WM atlas. R1/T2*, R1, and R2* values were binned for fiber orientation related to the B0 field, which was estimated from diffusion-weighted echo-planar imaging data with 3° intervals, to investigate angular-dependent anisotropies in vivo.A larger change in the R1/T2* value in the global WM region as a function of fiber orientation with respect to the B0 field was observed compared to the R1 and R2* values alone. The minimum R1/T2* value at the near magic-angle range was 18.86% lower than the maximum value at the perpendicular angle range. Furthermore, R1/T2* values in the corpus callosum tract and the right and left cingulum cingulate gyrus tracts changed among the three head tilt positions due to fiber orientation changes. In conclusion, the R1/T2* value demonstrates distinctive and complicated angular-dependent anisotropy indicating the trends of both R1 and R2* values and may provide supplemental information for detecting slight changes in the microstructure of myelin and axons.

Simultaneous T1, T2 and T2⁎ mapping of the liver with multi-shot MI-SAGE

PurposeTo apply multi-shot high-resolution multi inversion spin and gradient echo (MI-SAGE) acquisition for simultaneous liver T1, T2 and T2* mapping. MethodsInversion prepared spin- and gradient-echo EPI was developed with ascending slice order across measurements for efficient acquisition with T1, T2, and T2⁎ weighting. Multi-shot EPI was also implemented to minimize distortion and blurring while enabling high in-plane resolution. A dictionary-matching approach was used to fit the images to quantitative parameter maps, which were compared to T1 measured by modified Look-Locker (MOLLI), T1 measured by variable flip angle (VFA), T2 measured by multiple echo time-based Half Fourier Single-shot Turbo spin-Echo (HASTE), T2 measured by radial turbo-spin-echo (rTSE) and T2⁎ measured by multiple gradient echo (MGRE) sequences. ResultsThe multi-shot variant of the sequence achieved higher in-plane resolution of 1.7 × 1.7 mm2 with good image quality in 28 s. Derived quantitative maps showed comparable values to conventional mapping methods. As measured in phantom and in vivo, MOLLI, MESE and MGRE give closest values to MISAGE. VFA, HASTE and rTSE show obvious overestimation. ConclusionsThe proposed multi-shot inversion prepared spin- and gradient-echo EPI sequence allows for high-resolution quantitative T1, T2 and T2 liver tissue characterization in a single breath-hold scan.

Bone visualization of the cervical spine with deep learning-based synthetic CT compared to conventional CT: A single-center noninferiority study on image quality

PurposeTo investigate whether the image quality of a specific deep learning-based synthetic CT (sCT) of the cervical spine is noninferior to conventional CT. MethodPaired MRI and CT data were collected from 25 consecutive participants (≥ 50 years) with cervical radiculopathy. The MRI exam included a T1-weighted multiple gradient echo sequence for sCT reconstruction. For qualitative image assessment, four structures at two vertebral levels were evaluated on sCT and compared with CT by three assessors using a four-point scale (range 1–4). The noninferiority margin was set at 0.5 point on this scale. Additionally, acceptable image quality was defined as a score of 3–4 in ≥ 80% of the scans. Quantitative assessment included geometrical analysis and voxelwise comparisons. ResultsQualitative image assessment showed that sCT was noninferior to CT for overall bone image quality, artifacts, imaging of intervertebral joints and neural foramina at levels C3-C4 and C6-C7, and cortical delineation at C6-C7. Noninferiority was weak to absent for cortical delineation at level C3-C4 and trabecular bone at both levels. Acceptable image quality was achieved for all structures in sCT and CT, except for trabecular bone in sCT and level C6-C7 in CT.Geometrical analysis of the sCT showed good to excellent agreement with CT. Voxelwise comparisons showed a mean absolute error of 80.05 (±6.12) HU, dice similarity coefficient (cortical bone) of 0.84 (±0.04) and structural similarity index of 0.86 (±0.02). ConclusionsThis deep learning-based sCT was noninferior to conventional CT for the general visualization of bony structures of the cervical spine, artifacts, and most detailed structure assessments.

Examining lung microstructure using 19F MR diffusion imaging in COPD patients

To examine the time-dependent diffusion of fluorinated (19 F) gas in human lungs for determination of surface-to-volume ratio in comparison to results from hyperpolarized 129 Xe and lung function testing in healthy volunteers and patients with chronic obstructive pulmonary disease. Diffusion of fluorinated gas in the short-time regime was measured using multiple gradient-echo sequences with a single pair of trapezoidal gradient pulses. Pulmonary surface-to-volume ratio was calculated using a first-order approximation of the time-dependent diffusion in a study with 20 healthy volunteers and 22 patients with chronic obstructive pulmonary disease. The repeatability after 7 days as well as the correlation with hyperpolarized 129 Xe diffusion MRI and lung function testing was analyzed. Using 19 F diffusion MRI, the median surface-to-volume ratio is significantly decreased in chronic obstructive pulmonary disease patients (S/V=126 cm-1 [87-144 cm-1 ]) compared with healthy volunteers (S/V=164 cm-1 [160-84 cm-1 ], p< 0.0001). No significant difference was found between measurements within 7 days for healthy (p= 0.88, median coefficient of variation=4.3%) and diseased subjects (p= 0.58, median coefficient of variation= 6.7%). Linear correlations were found with S/V from 129 Xe diffusion MRI (r= 0.85, p= 0.001) and the forced expiratory volume in 1 second (r= 0.68, p< 0.0001). Examination of lung microstructure using time-dependent diffusion measurement of inhaled 19 F is feasible, repeatable, and correlates with established measurements.

R2* relaxometry analysis for mapping of white matter alteration in Parkinson’s disease with mild cognitive impairment

BackgroundR2* relaxometry analysis combined with quantitative susceptibility mapping (QSM), which has high sensitivity to iron deposition, can distinguish microstructural changes of the white matter (WM) and iron deposition, thereby providing a sensitive and biologically specific measure of the WM owing to the changes in myelin and its surrounding environment. This study aimed to explore the microstructural WM alterations associated with cognitive impairment in patients with Parkinson’s disease (PD) using R2* relaxometry analysis combined with QSM. Materials and methodsWe enrolled 24 patients with PD and mild cognitive impairment (PD-MCI), 22 patients with PD and normal cognition (PD-CN), and 19 age- and sex-matched healthy controls (HC). All participants underwent Montreal Cognitive Assessment (MoCA) and brain magnetic resonance imaging, including structural three-dimensional T1-weighted images and multiple spoiled gradient echo sequence (mGRE). The R2* and susceptibility maps were estimated from the multiple magnitude images of mGRE. The susceptibility maps were used for verifying iron deposition in the WM. The voxel-based R2* of the entire WM and its correlation with cognitive performance were analyzed. ResultsIn the voxel-based group comparisons, the R2* in the PD-MCI group was lower in some WM regions, including the corpus callosum, than R2* in the PD-CN and HC groups. The mean susceptibility values in almost all brain regions were negative and close-to-zero values, indicating no detectable paramagnetic iron deposition in the WM of all subjects. There was a significant positive correlation between R2* and MoCA in some regions of the WM, mainly the corpus callosum and left hemisphere. ConclusionR2* relaxometry analysis for WM microstructural changes provided further biologic insights on demyelination and changes in the surrounding environment, supported by the QSM results demonstrating no iron existence. This analysis highlighted the potential for the early evaluation of cognitive decline in patients with PD.

Fast multi-parametric imaging in abdomen by corrected dual-flip angle sequence with interleaved echo acquisition.

To achieve simultaneous T1, w /proton density fat fraction (PDFF)/ mapping in abdomen within a single breadth-hold, and validate the accuracy using state-of-art measurement. An optimized multiple echo gradient echo (GRE) sequence with dual flip-angle acquisition was used to realize simultaneous water T1 (T1, w )/PDFF/ quantification. A new method, referred to as "solving the fat-water ambiguity based on their T1 difference" (SORT), was proposed to address the fat-water separation problem. This method was based on the finding that compared to the true solution, the wrong (or aliased) solution to fat-water separation problem showed extra dependency on the applied flip angle due to the T1 difference between fat and water. The measurement sequence was applied to correct the inhomogeneity for T1, w relaxometry. The 2D parallel imaging was incorporated to enable the acquisition within a single breath-hold in abdomen. The multi-parametric quantification results of the proposed method were consistent with the results of reference methods in phantom experiments (PDFF quantification: R2 =0.993, mean error 0.73%; T1, w quantification: R2 =0.999, mean error 4.3%; quantification: R2 =0.949, mean error 4.07s-1 ). For volunteer studies, robust fat-water separation was achieved without evident fat-water swaps. Based on the accurate fat-water separation, simultaneous T1, w /PDFF/ quantification was realized for whole liver within a single breath-hold. The proposed method accurately quantified T1, w /PDFF/ for the whole liver within a single breath-hold. This technique serves as a quantitative tool for disease management in patients with hepatic steatosis.

Characteristics of diffusion-weighted and blood oxygen level-dependent magnetic resonance imaging in Tubulointerstitial nephritis: an initial experience

BackgroundDiffusion-weighted (DW) and blood oxygen level-dependent (BOLD) magnetic resonance imaging are classical sequences of functional MR, but the exploration in non-transplanted kidney disease is limited. Objects: To analyze the characteristics of apparent diffusion coefficient (ADC) and R2* value using DW and BOLD imaging in tubulointerstitial nephritis (TIN).MethodsFour acute TIN, thirteen chronic TIN patients, and four controls were enrolled. We used multiple gradient-echo sequences to acquire 12 T2*-weighted images to calculate the R2* map. DW imaging acquired ADC values by combining a single-shot spin-echo echo-planar imaging pulse sequence and the additional motion probing gradient pulses along the x,y, z-axes with two b values:0 and 200, as well as 0 and 800 s/mm2. ATIN patients performed DW and BOLD magnetic resonance at renal biopsy(T0) and the third month(T3). We assessed the pathological changes semiquantitatively, and conducted correlation analyses within functional MR, pathological and clinical indexes.ResultsIn ATIN, ADCs were significantly lower(b was 0,200 s/mm2, 2.86 ± 0.19 vs. 3.39 ± 0.11, b was 0,800 s/mm2, 1.76 ± 0.12 vs. 2.16 ± 0.08, P < 0.05) than controls, showing an obvious remission at T3. Cortical and medullary R2* values (CR2*,MR2*) were decreased, significant difference was only observed in MR2*(T0 24.3 ± 2.1vs.T3 33.1 ± 4.1,P < 0.05). No relationship was found between functional MR and histopathological indexes.MR2* had a close relationship with eGFR (R = 0.682,P = 0.001) and serum creatinine(R = -0.502,P = 0.012). Patients with lower ADC when b was 0,200 s/mm2 showed more increase of ADC(R = -0.956,P = 0.044) and MR2*(R = -0.949,P = 0.05) after therapy. In CTIN group, lowered MR2* and MR2*/CR2* provided evidence of intrarenal ischemia. CTIN with advanced CKD (eGFR< 45) had significantly lower ADCb200 value.ConclusionsWe observed the reduction and remission of ADC and R2* values in ATIN case series. ATIN patients had concurrently decreased ADCb800 and MR2*. The pseudo normalization of CR2* with persistently low MR2* in CTIN suggested intrarenal hypoxia.

Optimal sequences and sequence parameters for GBCA-enhanced MRI of the glymphatic system: a systematic literature review

The glymphatic system (GS) is a recently discovered waste clearance system in the brain. To evaluate the most promising magnetic resonance imaging (MRI) sequence(s) and the most optimal sequence parameters for glymphatic MRI (gMRI) 4-24 h after administration of gadolinium-based contrast agent (GBCA). Multiple literature databases were systematically searched for articles regarding gMRI or MRI of the perilymph in the inner ear until 11 May 2020. All relevant MRI sequence parameters were tabulated for qualitative analysis. Their potential was assessed based on detection of low dose GBCA, primarily measured as signal intensity (SI) ratio. Thirty articles were included in the analysis. Three-dimensional fluid attenuated inversion recovery (3D-FLAIR), 3D Real Inversion Recovery (3D-Real IR), and multiple 3D T1-weighted gradient echo sequences were used. In perilymph, 3D-FLAIR with a TE of at least 400 ms yielded the highest SIRs. In the qualitative analysis of inner ear studies using 3D-FLAIR, TR was in the range of 4400-10,000 ms, TI 1500-2600 ms, refocusing flip angle (rFA) (range 120°-180°), and echo train length (ETL) 23-173. In the gMRI studies, quantitative analysis was not possible. In the qualitative analysis, 3D-FLAIR was used in the majority (8/12) of the studies, usually with TR 4800-9000 ms, TI 1650-2500 ms, TE 311-561 ms, rFA 90°-120°, and ETL 167-278. Long TE 3D-FLAIR is the most promising sequence for detection of low-dose GBCA in the GS. Clinical and/or phantom studies on other MRI parameters are needed for further optimization of gMRI.

Development of a method for the Bloch image simulation of biological tissues

PurposeThe purpose of this study is to develop a method for the Bloch image simulation of biological tissues including various chemical components and T2* distribution. MethodsThe nuclear spins in the object material were modeled as a spectral intensity function Sr→ω defined by superposition of Lorentz functions with various central precession frequencies and the half width of 1/(πT2′), where 1/T2′ is a relaxation rate attributable to microscopic field inhomogeneity in a voxel. Four-dimensional numerical phantoms were created to simulate Sr→ω and used for MRI simulations of the phantoms containing water and fat protons. Single slice multiple (16) gradient-echo sequences (ΔTE = 2.2 and 1.384 ms) were used for experiments at 1.5 T and 3 T and MRI simulations to evaluate the validity of the approach. ResultsExperimentally measured image intensities of the multiple gradient-echo imaging sequences were well reproduced by the MRI simulations. The correlation coefficients between the experimentally measured image intensities and those numerically simulated were 0.9895 to 0.9992 for the 4-component phantom at 1.5 T and 0.9580 to 0.9996 for the 7-component phantom at 3 T. ConclusionT2* and chemical shift effects were successfully implemented in the MRI simulator (BlochSolver). Because this approach can be applied to other MRI simulators, the method developed in this study is useful for MRI simulation of biological tissues containing water and fat protons.

Simultaneous voxel-based magnetic susceptibility and morphometry analysis using magnetization-prepared spoiled turbo multiple gradient echo.

This study aimed to develop and test a simultaneous acquisition and analysis pipeline for voxel-based magnetic susceptibility and morphometry (VBMSM) on a single dataset using young volunteers, elderly healthy volunteers, and an Alzheimer's disease (AD) group. 3D T1 -weighted and multi-echo phase images for VBM and quantitative susceptibility mapping (QSM) were simultaneously acquired using a magnetization-prepared spoiled turbo multiple gradient echo sequence with inversion pulse for QSM (MP-QSM). The magnitude image was split into gray matter (GM) and white matter (WM) and was spatially normalized. The susceptibility map was reconstructed from the phase images. The segmented image and susceptibility map were compared with those obtained from conventional multiple spoiled gradient echo (mGRE) and MP-spoiled gradient echo (MP-GRE) in healthy volunteers to validate the availability of MP-QSM by numerical measurements. To assess the feasibility of the VBMSM analysis pipeline, voxel-based comparisons of susceptibility and morphometry in MP-QSM were conducted in volunteers with a bimodal age distribution, and in elderly volunteers and the AD group, using spatially normalized GM and WM volume images and a susceptibility map. GM/WM contrasts in MP-QSM, MP-GRE, and mGRE were 0.14 ± 0.011, 0.17 ± 0.015, and 0.045 ± 0.010, respectively. Segmented GM and WM volumes in the MP-QSM closely coincided with those in the MP-GRE. Region of interest analyses indicated that the mean susceptibility values in MP-QSM were completely in agreement with those in mGRE. In an evaluation of the aging effect, a significant increase and decrease in susceptibility and volume were found by VBMSM in deep GM and WM, respectively. Between the elderly volunteers and the AD group, the characteristic susceptibility and volume changes in GM and WM were observed. The proposed MP-QSM sequence makes it possible to acquire acceptable-quality images for simultaneous analysis and determine brain atrophy and susceptibility distribution without image registration by using voxel-based analyses.

Water-fat separation and parameter mapping in cardiac MRI via deep learning with a convolutional neural network.

Water-fat separation is a postprocessing technique most commonly applied to multiple-gradient-echo magnetic resonance (MR) images to identify fat, provide images with fat suppression, and to measure fat tissue concentration. Recently, Numerous advancements have been reported. In contrast to early methods, the process of water-fat separation has become complicated due to multiparametric analytic models, optimization methods, and the absence of a unified framework for diverse source data. To determine the feasibility and performance of MRI water-fat separation and parametric mapping via deep learning (DL) with a range of inputs. Retrospective data usage. Ninety cardiac MR examinations from normal control, acute, subacute, and chronic myocardial infarction subjects were obtained, providing 1200 multiple gradient-echo acquisitions. 1.5 T/2D multiple gradient-echo pulse sequence ASSESSMENT: Ground-truth training and validation water-fat separation were obtained using a graph cut method with R2 *, off-resonance correction, and a multipeak fat spectrum. U-Net DL training with single and multiecho, complex, and magnitude inputs were compared using quantitative and three-observer subjective analysis. DL methods' image structural similarity, and quantitative proton density fat fraction (PDFF), R2 *, and off-resonance quantitative values were statistically compared with the GraphCut reference standard using Student's t-test and Pearson's correlation. Myocardial fat deposition in chronic myocardial infarction and intramyocardial hemorrhage in acute myocardial infarction were well visualized in the DL results. Predicted values for R2 *, off-resonance, water, and fat signal intensities were well correlated with a conventional model-based water fat separation (R2 ≥ 0.97, P < 0.001) with appropriate inputs. DL parameter maps had a 14% higher signal-to-noise ratio (P < 0.001) when compared with a conventional method. DL water-fat separation is feasible with a wide range of inputs, while R2 * and off-resonance mapping requires multiple echoes and complex images. With appropriate inputs, DL provides quantitative and subjective results comparable to conventional model-based methods. 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:655-665.

Non-invasive T1ρ mapping of the human cartilage response to loading and unloading.

To define the physiological response to sequential loading and unloading in histologically intact human articular cartilage using serial T1ρ mapping, as T1ρ is considered to indicate the tissue's macromolecular content. 18 macroscopically intact cartilage-bone samples were obtained from the central lateral femoral condyles of 18 patients undergoing total knee replacement. Serial T1ρ mapping was performed on a clinical 3.0-T MRI system using a modified prostate coil. Spin-lock multiple gradient-echo sequences prior to, during and after standardized indentation loading (displacement controlled, strain 20%) were used to obtain seven serial T1ρ maps: unloaded (δ0), quasi-statically loaded (indentation1-indentation3) and under subsequent relaxation (relaxation1-relaxation3). After manual segmentation, zonal and regional regions-of-interest were defined. ROI-specific relative changes were calculated and statistically assessed using paired t-tests. Histological (Mankin classification) and biomechanical (unconfined compression) evaluations served as references. All samples were histologically and biomechanically grossly intact (Mankin sum: 1.8±1.2; Young's Modulus: 0.7±0.4MPa). Upon loading, T1ρ consistently increased throughout the entire sample thickness, primarily subpistonally (indentation1 [M±SD]: 9.5±7.8% [sub-pistonal area, SPA] vs 4.2±5.8% [peri-pistonal area, PPA]; P<0.001). T1ρ further increased with ongoing loading (indentation3: 14.1±8.1 [SPA] vs 7.7±5.9% [PPA]; P<0.001). Even upon unloading (i.e., relaxation), T1ρ persistently increased in time. Serial T1ρ-mapping reveals distinct and complex zonal and regional changes in articular cartilage as a function of loading and unloading. Thereby, longitudinal adaptive processes in hyaline cartilage become evident, which may be used for the tissue's non-invasive functional characterization by T1ρ.

Comparison of ferumoxytol‐based cerebral blood volume estimates using quantitative R1 and relaxometry

Cerebral perfusion is commonly assessed clinically with dynamic susceptibility contrast MRI using a bolus injection of gadolinium-based contrast agents, resulting in semi-quantitative values of cerebral blood volume (CBV). Steady-state imaging with ferumoxytol allows estimation of CBV with the potential for higher precision and accuracy. Prior CBV studies have focused on the signal disrupting T2* effects, but ferumoxytol also has high signal-enhancing T1 relaxivity. The purpose of this study was to investigate and compare CBV estimation using T1 and T2*, with the goal of understanding the contrast mechanisms and quantitative differences. Changes in R1 (1/T1 ) and R2* (1/ T2*) were measured after the administration of ferumoxytol using high-resolution quantitative approaches. Images were acquired at 3.0T and R1 was estimated from an ultrashort echo time variable flip angle approach, while R2* was estimated from a multiple gradient echo sequence. Twenty healthy volunteers were imaged at two doses. CBV was derived and compared from relaxometry in gray and white matter using different approaches. R1 measurements showed a linear dependence of blood R1 with respect to dose in large vessels, in contrast to the nonlinear dose-dependence of blood R2* estimates. In the brain parenchyma, R2* showed linear dose-dependency whereas R1 showed nonlinearity. CBV calculations based on R2* changes in tissue and ferumoxytol blood concentration estimates based on R1 relaxivity showed the lowest variability in our cohort. CBV measurements were successfully derived using a combined approach of R1 and R2* relaxometry. Magn Reson Med 79:3072-3081, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Functional MR Imaging Mapping of Human Articular Cartilage Response to Loading.

Purpose To determine if multiparametric magnetic resonance (MR) imaging mapping can be used to quantify the response to loading of histologically intact human knee cartilage. Materials and Methods Institutional review board approval and written informed consent were obtained. Twenty macroscopically intact cartilage-bone samples were obtained from the central lateral femoral condyles in 11 patients undergoing total knee replacement. A clinical 3.0-T MR imaging system was used to generate T1, T1ρ, T2, and T2* maps with inversion recovery, spin-lock multiple gradient-echo, multiple spin-echo, and multiple gradient-echo sequences. Serial mapping was performed at three defined strain levels (strain 0 [δ0], 0%; strain 1 [δ1/2], 19.8% ± 4.6 [standard deviation]; strain 2 [δ1], 39.5% ± 9.3) by using displacement-controlled static indentation loading. The entire sample and specific cartilage zones (superficial zone [SZ], transitional zone [TZ], and deep zone [DZ]) and regions (subpistonal area [SPA] and peripistonal area [PPA]) were defined as regions of interest. Upon log transformation, repeated measures analysis of variance was used to detect groupwise regional and zonal differences. Load-induced relative changes were determined and analyzed by using paired Student t test and Spearman correlation. Biomechanical testing (unconfined compression) and histologic assessment (Mankin score) served as the reference standard. Results All samples were histologically intact. Strain-related decreases were found at the SZ and TZ for T1 and T2*; for T1ρ, increases were seen in all zones; and for T2, increases were seen at the SZ and PPA only. Significant parameter changes in the entire sample depth of SPA versus PPA were found for δ1/2 (T1ρ, 14% ± 12 vs 6% ± 9) and δ1 (T1, -4% ± 5 vs -1% ± 3; T1ρ, 13% ± 12 vs 7% ± 7; T2*, -9% ± 12 vs -2% ± 8). SPA versus PPA changes were significant at the SZ and TZ (T1), TZ and DZ (T1ρ), and SZ (T2*). No significant correlations were found between relative changes and biomechanical or histologic parameters. Conclusion Serial multiparametric MR imaging mapping can be used to evaluate cartilage beyond mere static analysis and may provide the basis for more refined graduation strategies of cartilage degeneration. © RSNA, 2016 Online supplemental material is available for this article.

Repeatability and sensitivity of T2* measurements in patients with head and neck squamous cell carcinoma at 3T.

PurposeTo determine whether quantitation of T2* is sufficiently repeatable and sensitive to detect clinically relevant oxygenation levels in head and neck squamous cell carcinoma (HNSCC) at 3T.Materials and MethodsTen patients with newly diagnosed locally advanced HNSCC underwent two magnetic resonance imaging (MRI) scans between 24 and 168 hours apart prior to chemoradiotherapy treatment. A multiple gradient echo sequence was used to calculate T2* maps. A quadratic function was used to model the blood transverse relaxation rate as a function of blood oxygenation. A set of published coefficients measured at 3T were incorporated to account for tissue hematocrit levels and used to plot the dependence of fractional blood oxygenation (Y) on T2* values, together with the corresponding repeatability range. Repeatability of T2* using Bland–Altman analysis, and calculation of limits of agreement (LoA), was used to assess the sensitivity, defined as the minimum difference in fractional blood oxygenation that can be confidently detected.Results T2* LoA for 22 outlined tumor volumes were 13%. The T2* dependence of fractional blood oxygenation increases monotonically, resulting in increasing sensitivity of the method with increasing blood oxygenation. For fractional blood oxygenation values above 0.11, changes in T2* were sufficient to detect differences in blood oxygenation greater than 10% (Δ T2* > LoA for ΔY > 0.1).ConclusionQuantitation of T2* at 3T can detect clinically relevant changes in tumor oxygenation within a wide range of blood volumes and oxygen tensions, including levels reported in HNSCC. J. Magn. Reson. Imaging 2016;44:72–80.

Longitudinal change in magnetic susceptibility of new enhanced multiple sclerosis (MS) lesions measured on serial quantitative susceptibility mapping (QSM).

To measure the longitudinal change in multiple sclerosis (MS) lesion susceptibility using quantitative susceptibility mapping (QSM). The study was approved by our Institutional Review Board. Longitudinal changes in quantitative susceptibility values of new enhanced-with-Gd MS lesions were measured at baseline magnetic resonance imaging (MRI) and on a follow-up MRI in 29 patients within 2 years using a 3D multiple echo gradient echo sequence on a 3T scanner. Paired t-test and the generalized estimating equations (GEE) model was used to analyze the longitudinal change. Lesion susceptibility values relative to normal-appearing white matter (NAWM) changed from 3.61 ± 6.11 ppb when enhanced-with-Gd at the baseline MRI to 20.42 ± 10.23 ppb when not-enhanced-with-Gd at the follow-up MRI (P < 0.001). MS lesion susceptibility value increases significantly as the lesion evolves from enhanced-with-Gd to not-enhanced-with-Gd, serving as a disease biomarker. J. Magn. Reson. Imaging 2016;44:426-432.

In vivo Tracking of Dendritic Cell using MRI Reporter Gene, Ferritin.

The noninvasive imaging of dendritic cells (DCs) migrated into lymph nodes (LNs) can provide helpful information on designing DCs-based immunotherapeutic strategies. This study is to investigate the influence of transduction of human ferritin heavy chain (FTH) and green fluorescence protein (GFP) genes on inherent properties of DCs, and the feasibility of FTH as a magnetic resonance imaging (MRI) reporter gene to track DCs migration into LNs. FTH-DCs were established by the introduction of FTH and GFP genes into the DC cell line (DC2.4) using lentivirus. The changes in the rate of MRI signal decay (R2*) resulting from FTH transduction were analyzed in cell phantoms as well as popliteal LN of mice after subcutaneous injection of those cells into hind limb foot pad by using a multiple gradient echo sequence on a 9.4 T MR scanner. The transduction of FTH and GFP did not influence the proliferation and migration abilities of DCs. The expression of co-stimulatory molecules (CD40, CD80 and CD86) in FTH-DCs was similar to that of DCs. FTH-DCs exhibited increased iron storage capacity, and displayed a significantly higher transverse relaxation rate (R2*) as compared to DCs in phantom. LNs with FTH-DCs exhibited negative contrast, leading to a high R2* in both in vivo and ex vivo T2*-weighted images compared to DCs. On histological analysis FTH-DCs migrated to the subcapsular sinus and the T cell zone of LN, where they highly expressed CD25 to bind and stimulate T cells. Our study addresses the feasibility of FTH as an MRI reporter gene to track DCs migration into LNs without alteration of their inherent properties. This study suggests that FTH-based MRI could be a useful technique to longitudinally monitor DCs and evaluate the therapeutic efficacy of DC-based vaccines.

Combined gadoxetic acid and gadofosveset enhanced liver MRI: A feasibility and parameter optimization study.

Demonstration of feasibility and protocol optimization for the combined use of gadofosveset trisodium with gadoxetic acid for delayed T1-weighted liver MRI. Eleven healthy volunteers underwent hepatobiliary phase imaging at 3 Tesla (T) using gadoxetic acid. Multiple breathheld T1-weighted three-dimensional spoiled gradient echo sequences were performed at varying flip angles before and after injection of gadofosveset. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured to determine optimal T1-weighting. Examples of three patients with focal liver lesions were acquired. The addition of gadofosveset to the hepatobiliary phase of gadoxetic acid renders vessels isointense to liver tissue at low flip angles due to increased vessel SNR (P < 0.001). The lowest CNR of liver relative to portal vein (CNR = 15; 95% confidence interval [CI]: -14-44) was observed at a 10º flip angle. The highest CNR of liver relative to muscle (CNR = 214; 95% CI: 191-237) was observed at a 20º flip angle. The combined enhancement leads to homogenously enhanced liver tissue and liver vasculature. Cysts were detected in three volunteers and metastases were detected in two patients. In these anecdotal cases the cysts and metastases stood out as conspicuous focal hypointensities on combined gadoxetic acid and gadofosveset enhanced images. Combined gadoxetic acid and gadofosveset enhanced liver MRI is feasible, with low flip angles minimizing contrast between vessels and liver. Further clinical studies are needed to confirm that low flip angles provide an optimal combination of sensitivity and specificity for lesion detection in patients.

In vivo visualization and ex vivo quantification of murine breast cancer cells in the mouse brain using MRI cell tracking and electron paramagnetic resonance

Cell tracking could be useful to elucidate fundamental processes of cancer biology such as metastasis. The aim of this study was to visualize, using MRI, and to quantify, using electron paramagnetic resonance (EPR), the entrapment of murine breast cancer cells labeled with superparamagnetic iron oxide particles (SPIOs) in the mouse brain after intracardiac injection. For this purpose, luciferase-expressing murine 4 T1-luc breast cancer cells were labeled with fluorescent Molday ION Rhodamine B SPIOs. Following intracardiac injection, SPIO-labeled 4 T1-luc cells were imaged using multiple gradient-echo sequences. Ex vivo iron oxide quantification in the mouse brain was performed using EPR (9 GHz). The long-term fate of 4 T1-luc cells after injection was characterized using bioluminescence imaging (BLI), brain MRI and immunofluorescence. We observed hypointense spots due to SPIO-labeled cells in the mouse brain 4 h after injection on T2 *-weighted images. Histology studies showed that SPIO-labeled cancer cells were localized within blood vessels shortly after delivery. Ex vivo quantification of SPIOs showed that less than 1% of the injected cells were taken up by the mouse brain after injection. MRI experiments did not reveal the development of macrometastases in the mouse brain several days after injection, but immunofluorescence studies demonstrated that these cells found in the brain established micrometastases. Concerning the metastatic patterns of 4 T1-luc cells, an EPR biodistribution study demonstrated that SPIO-labeled 4 T1-luc cells were also entrapped in the lungs of mice after intracardiac injection. BLI performed 6 days after injection of 4 T1-luc cells showed that this cell line formed macrometastases in the lungs and in the bones. Conclusively, EPR and MRI were found to be complementary for cell tracking applications. MRI cell tracking at 11.7 T allowed sensitive detection of isolated SPIO-labeled cells in the mouse brain, whereas EPR allowed the assessment of the number of SPIO-labeled cells in organs shortly after injection.

Longitudinal midbrain changes in early Parkinson's disease: iron content estimated from R2*/MRI.

To determine whether, in patients with early Parkinson's disease (PD), longitudinal changes in midbrain iron content are associated with declining motor function over a period of three years. Nineteen untreated subjects with early PD and 13 age- and sex-matched controls were followed clinically for 36 months. MRI with a 3 T magnet was performed at baseline, 18 months and 36 months with a multiple gradient echo sequence designed for rapid single-scan mapping of the proton transverse relaxation rate R2*. R2* was calculated for midbrain and forebrain basal ganglia regions. A difference in R2* between patients and controls was observed at baseline (p = 0.035) but not at 18 or 36 months in the lateral substantia nigra pars compacta (SNc). Linear regression indicated significant correlations between the change in R2* in the lateral SNc and the change score in UPDRS III (p = 0.008) and the PDQ-39 -mobility sub-score (p = 0.03) from baseline to 36 months. R2* tended to increase in those with more advanced disease and to decrease in those with milder disease. High field MRI demonstrates lateral SNc abnormalities that progress over 3 years in early PD consistent with increased iron content in those with more advanced disease, corresponding to the known distribution of neuronal loss occurring in this disorder, and correlating with motor symptomatology. Larger and longer investigations with more precise mapping of iron-containing midbrain structures are needed to fully evaluate the potential of R2* as a biomarker of disease progression in PD.