Multi-echo Gradient Echo Sequence Research Articles

Single vs. multi-slice assessments of in vivo placental T2∗ measurements

IntroductionPlacental health is vital for maternal and fetal well-being, and placental T2∗ has been suggested to identify in vivo placental dysfunction prior to delivery. However, ideal regions of interest to best inform functional assessments of the placenta remain unknown. The aim of this study is to compare global and slice-wise measures of in-vivo placental T2∗ assessments. MethodsThis prospective study recruited pregnant people with singleton pregnancies between December 2017 and February 2022.3D multi-echo RF-spoiled gradient echo sequences were acquired, and placental T2∗ values were derived from global and slice-wise approaches. Statistical analyses included Pearson correlation coefficients, concordance correlation coefficients (CCC), intraclass correlation coefficients (ICC), and Bland-Altman analyses. ResultsOf 115 participants (mean gestational age, 29.25 ± 5.05 weeks), 68 were healthy controls, and 47 were high-risk pregnancies. Global and slice-wise placental T2∗ assessments for the entire cohort showed no significant difference nor for individual subgroups (healthy controls or high-risk). Pearson correlation values ranged between 0.88 and 0.99 for mean global and slice-wise placental T2∗. CCC analyses ranged from 0.88 to 0.99 for mean T2∗, and ICC analyses ranged between 0.88 and 0.99 for mean T2∗, showing a strong agreement between measurements. Bland-Altman analyses depicted T2∗ differences across coverage methods, and groups resided within the 95 % limits of agreement. DiscussionSingle-slice placental assessments offer robust, comparable T2∗ values to global assessments, with the added benefit of reducing post-processing time and SAR exposure. This supports slice-wise approaches as valid alternatives for assessing placental health in various pregnancies.

Simultaneous Increase of Mean Susceptibility and Mean Kurtosis in the Substantia Nigra as an MRI Neuroimaging Biomarker for Early-Stage Parkinson's Disease: A Systematic Review and Meta-Analysis.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Early detection is crucial for treatment and slowing disease progression. Simultaneous alterations in mean susceptibility (MS) from quantitative susceptibility mapping (QSM) and mean kurtosis (MK) from diffusion kurtosis imaging (DKI) can serve as reliable neuroimaging biomarkers for early-stage PD (ESPD) in the basal ganglia nuclei, including the substantia nigra (SN), putamen (PUT), globus pallidus (GP), and caudate nucleus (CN). Systematic review and meta-analysis. One hundred eleven patients diagnosed with ESPD and 81 healthy controls (HCs) were included from four studies that utilized both QSM and DKI in both subject groups. Three-dimensional multi-echo gradient echo sequence for QSM and spin echo planar imaging sequence for DKI at 3 Tesla. A systematic review and meta-analysis using PRISMA guidelines searched PubMed, Web of Science, and Scopus. Random-effects model, standardized mean difference (SMD) to compare MS and MK between ESPD patients and HCs, I2 statistic for heterogeneity, Newcastle-Ottawa Scale (NOS) for risk of bias, and Egger's test for publication bias. A P-value <0.05 was considered significant. MS values were significantly higher in SN (SMD 0.72, 95% CI 0.31 to 1.12), PUT (SMD 0.68, 95% CI 0.29 to 1.07), and GP (SMD 0.53, 95% CI 0.19 to 0.87) in ESPD patients compared to HCs. CN did not show a significant difference in MS values (P = 0.15). MK values were significantly higher only in SN (SMD = 0.72, 95% CI 0.16 to 1.27). MK values were not significantly different in PUT (P = 1.00), GP (P = 0.97), and CN (P = 0.59). Studies had high quality (NOS 7-8) and no publication bias (P = 0.967). Simultaneous use of MS and MK may be useful as an early neuroimaging biomarker for ESPD detection and its differentiation from HCs, with significant differences observed in the SN. 2 TECHNICAL EFFICACY: Stage 2.

Quantification of Cardiac Iron Overload at 3 T MRI in a Rabbit Model Utilizing ME-GRE T2* Sequence.

Myocardial iron overload can lead to myocardial dysfunction, muscle cell injury, and end-stage heart failure. The enhanced signal-to-noise ratio and technical advancements have made 3 T magnetic resonance imaging (MRI) more accessible in clinical settings. However, 3 T assessments for early diagnosis of myocardial iron overload are scarce. To evaluate the feasibility of myocardial iron quantification using 3 T MRI in a rabbit model of iron overload. Animal model. Overall, 40 male New Zealand white rabbits were categorized into control (N = 8; no treatment) and experimental (N = 32; weekly 200 mg/kg iron dextran injections) groups. 3 T MRI with multi-echo gradient echo (ME-GRE) T2* sequence. Each week, two experimental rabbits were randomly selected for blood collection to determine serum iron (SI) levels; their tissue was harvested to assess myocardial and hepatic iron deposition. Spearman's rank correlation tests were used to evaluate the correlations among R2*, cardiac iron concentration (CIC), liver iron concentration (LIC), total amount of iron injected, and SI levels. P ≤ 0.05 was considered statistically significant. The myocardial T2* value in the experimental group was significantly lower than that of the control group. An excellent correlation was observed between R2* values and CIC (r = 0.854). CIC moderately correlated with LIC (r = 0.712) and the total amount of iron injected (r = 0.698). A strong correlation was observed between the total amount of iron injected and LIC (r = 0.866). SI levels poorly correlated with the total amount of iron injected (r = 0.205, P = 0.277) and LIC (r = 0.170, P = 0.370) but fairly correlated with CIC (r = 0.415, P = 0.022). A 3 T MRI with an ME-GRE sequence may serve as a noninvasive method for evaluating cardiac iron content. N/A TECHNICAL EFFICACY: Stage 1.

Parameter optimization for proton density fat fraction quantification in skeletal muscle tissue at 7T.

To establish an image acquisition and post-processing workflow for the determination of the proton density fat fraction (PDFF) in calf muscle tissue at 7T. Echo times (TEs) of the applied vendor-provided multi-echo gradient echo sequence were optimized based on simulations of the effective number of signal averages (NSA*). The resulting parameters were validated by measurements in phantom and in healthy calf muscle tissue (n = 12). Additionally, methods to reduce phase errors arising at 7T were evaluated. Finally, PDFF values measured at 7T in calf muscle tissue of healthy subjects (n = 9) and patients with fatty replacement of muscle tissue (n = 3) were compared to 3T results. Simulations, phantom and in vivo measurements showed the importance of using optimized TEs for the fat-water separation at 7T. Fat-water swaps could be mitigated using a phase demodulation with an additional B0 map, or by shifting the TEs to longer values. Muscular PDFF values measured at 7T were comparable to measurements at 3T in both healthy subjects and patients with increased fatty replacement. PDFF determination in calf muscle tissue is feasible at 7T using a chemical shift-based approach with optimized acquisition and post-processing parameters.

Prospective longitudinal cohort study of quantitative muscle magnetic resonance imaging in a healthy control population.

Quantitative muscle magnetic resonance imaging (qMRI) is a valuable methodology for assessing muscular injuries and neuromuscular disorders. Notably, muscle diffusion tensor imaging (DTI) gives insights into muscle microstructural and macrostructural characteristics. However, the long-term reproducibility and robustness of these measurements remain relatively unexplored. The purpose of this prospective longitudinal cohort study was to assess the long-term robustness and range of variation of qMRI parameters, especially DTI metrics, in the lower extremity muscles of healthy controls under real-life conditions. Twelve volunteers (seven females, age 44.1 ± 12.1 years, body mass index 23.3 ± 2.0 kg/m2) underwent five leg muscle MRI sessions every 20 ± 4 weeks over a total period of 1.5 years. A multiecho gradient-echo Dixon-based sequence, a multiecho spin-echo T2-mapping sequence, and a spin-echo echo planar imaging diffusion-weighted sequence were acquired bilaterally with a Philips 3-T Achieva MR System using a 16-channel torso coil. Fifteen leg muscles were segmented in both lower extremities. qMRI parameters, including fat fraction (FF), water T2 relaxation time, and the diffusion metrics fractional anisotropy (FA) and mean diffusivity (MD), were evaluated. Coefficients of variance (wsCV) and intraclass correlation coefficients (ICCs) were calculated to assess the reproducibility of qMRI parameters. The standard error of measurement (SEM) and the minimal detectable change (MDC) were calculated to determine the range of variation. All tests were applied to all muscles and, subsequently, to each muscle separately. wsCV showed good reproducibility (≤ 10%) for all qMRI parameters in all muscles. The ICCs revealed excellent agreement between time points (FF = 0.980, water T2 = 0.941, FA = 0.952, MD = 0.948). Random measurement errors assessed by SEM and the MDC were low (< 12%). In conclusion, in this study, we showed that qMRI parameters in healthy volunteers living normal lives are stable over 18 months, thereby defining a benchmark for the expected range of variation over time.

Silicone implant and fibrous capsule assessment based on water-fat-silicone chemical shift encoding-based species separation in breast MRI.

With rising breast augmentations worldwide, there is an increasing clinical need for an early and accurate detection of implant complications. To compare the quality of chemical shift encoding-based (CSE) water-fat-silicone separation compared to double inversion recovery (DIR) silicone-only imaging in breast magnetic resonance imaging (MRI). This retrospective, single-center study included women with silicone implants subjected to 3-T MRI between January 2021 and March 2022. MRI included (i) two-dimensional silicone-only T2-weighted turbo spin echo DIR acquisition and (ii) three-dimensional CSE imaging based on multi-echo gradient-echo sequence enabling water-, fat-, and silicone-image separation. Images were evaluated and compared by three independent radiologists using a clinically established rating including differentiability of the silicone implant, visibility and contouring of the adjacent fibrous capsule, and accuracy of intralesional folds in a ranking of 1-5. The apparent contrast-to-noise (aCNR) was calculated. In 71 women, the average quality of water-fat-silicone images from CSE imaging was assessed as "good" (assessment 4 ± 0.9). In 68 (96%) patients, CSE imaging achieved a concise delineation of the silicone implant and precise visualization of the fibrous capsule that was not distinguishable in DIR imaging. Implant ruptures were more easily detected in CSE imaging. The aCNR was higher in CSE compared to DIR imaging (18.43 ± 9.8 vs. 14.73 ± 2.5; P = 0.002). Intrinsically co-registered water-fat-silicone-separated CSE-based images enable a reliable assessment of silicone implants. The simultaneously improved differentiability of the implant and fibrous capsule may provide clinicians with a valuable tool for an accurate evaluation of implant integrity and early detection of potential complications.

Feasibility of omega-3 fatty acid fraction mapping using chemical shift encoding-based imaging at 3 T.

The aim of this work is to develop an ω-3 fatty acid fraction mapping method at 3 T based on a chemical shift encoding model, to assess its performance in a phantom and in vitro study, and to further demonstrate its feasibility in vivo. A signal model was heuristically derived based on spectral appearance and theoretical considerations of the corresponding molecular structures to differentiate between ω-3 and non-ω-3 fatty acid substituents in triacylglycerols in addition to the number of double bonds (ndb), the number of methylene-interrupted double bonds (nmidb), and the mean fatty acid chain length (CL). First, the signal model was validated using single-voxel spectroscopy and a time-interleaved multi-echo gradient-echo (TIMGRE) sequence in gas chromatography-mass spectrometry (GC-MS)-calibrated oil phantoms. Second, the TIMGRE-based method was validated in vitro in 21 adipose tissue samples with corresponding GC-MS measurements. Third, an in vivo feasibility study was performed for the TIMGRE-based method in the gluteal region of two healthy volunteers. Phantom and in vitro data was analyzed using a Bland-Altman analysis. Compared with GC-MS, MRS showed in the phantom study significant correlations in estimating the ω-3 fraction (p < 0.001), ndb (p < 0.001), nmidb (p < 0.001), and CL (p = 0.001); MRI showed in the phantom study significant correlations (all p < 0.001) for the ω-3 fraction, ndb, and nmidb, but no correlation for CL. Also in the in vitro study, significant correlations (all p < 0.001) between MRI and GC-MS were observed for the ω-3 fraction, ndb, and nmidb, but not for CL. An exemplary ROI measurement in vivo in the gluteal subcutaneous adipose tissue yielded (mean ± standard deviation) 0.8% ± 1.9% ω-3 fraction. The present study demonstrated strong correlations between gradient-echo imaging-based ω-3 fatty acid fraction mapping and GC-MS in the phantom and in vitro study. Furthermore, feasibility was demonstrated for characterizing adipose tissue in vivo.

Quantitative susceptibility mapping of multiple system atrophy and Parkinson's disease correlates with neurotransmitter reference maps

BackgroundMultiple system atrophy (MSA) and Parkinson's disease (PD) are neurodegenerative disorders characterized by α-synuclein pathology, disrupted iron homeostasis and impaired neurochemical transmission. Considering the critical role of iron in neurotransmitter synthesis and transport, our study aims to identify distinct patterns of whole-brain iron accumulation in MSA and PD, and to elucidate the corresponding neurochemical substrates. MethodsA total of 122 PD patients, 58 MSA patients and 78 age-, sex-matched health controls underwent multi-echo gradient echo sequences and neurological evaluations. We conducted voxel-wise and regional analyses using quantitative susceptibility mapping to explore MSA or PD-specific alterations in cortical and subcortical iron concentrations. Spatial correlation approaches were employed to examine the topographical alignment of cortical iron accumulation patterns with normative atlases of neurotransmitter receptor and transporter densities. Furthermore, we assessed the associations between the colocalization strength of neurochemical systems and disease severity. ResultsMSA patients exhibited increased susceptibility in the striatal, midbrain, cerebellar nuclei, as well as the frontal, temporal, occipital lobes, and anterior cingulate gyrus. In contrast, PD patients displayed elevated iron levels in the left inferior occipital gyrus, precentral gyrus, and substantia nigra. The excessive iron accumulation in MSA or PD correlated with the spatial distribution of cholinergic, noradrenaline, glutamate, serotonin, cannabinoids, and opioid neurotransmitters, and the degree of this alignment was related to motor deficits. ConclusionsOur findings provide evidence of the interaction between iron accumulation and non-dopamine neurotransmitters in the pathogenesis of MSA and PD, which inspires research on potential targets for pharmacotherapy.

MR imaging of the magnetic fields induced by injected currents can guide improvements of individualized head volume conductor models

Abstract Volume conductor models of the human head are routinely used to estimate the induced electric fields in transcranial brain stimulation (TBS) and for source localization in electro- and magnetoencephalography (EEG and MEG). Magnetic resonance current density imaging (MRCDI) has the potential to act as a non-invasive method for dose control and model validation but requires very sensitive MRI acquisition approaches. A double-echo echo-planar imaging (EPI) method is here introduced. It combines fast and sensitive imaging of the magnetic fields generated by the current flow of transcranial electric stimulation with increased robustness to physiological noise. For validation, noise floor measurements without injected currents were obtained in five subjects for an established multi-echo gradient-echo (MGRE) sequence and the new EPI method. In addition, data with current injection were acquired in each subject with a right-left (RL) and anterior-posterior (AP) electrode montage with both sequences to assess the accuracy of subject-specific detailed head models. In line with previous findings, the noise floor measurements showed that the MGRE results suffered from spatial low-frequency noise patterns, which were mostly absent in the EPI data. A recently published approach optimizes the ohmic conductivities of subject-specific head models by minimizing the difference between simulated and measured current-induced magnetic fields. Here, simulations demonstrated that the MGRE noise patterns have a larger negative impact on the optimization results than the EPI noise. For the current injection measurements, a larger discrepancy was found for the RL electrode montage compared with the AP electrode montage consistently for all subjects. This discrepancy that remained in part also after optimization of the ohmic conductivities, was similar for the data of the two sequences and larger than the measurement noise, and thus demonstrates systematic biases in the volume conductor models. We have shown that EPI-based MRCDI is superior to established techniques by mitigating the effects of previously reported spatial low-frequency noise in MRCDI if limited spatial resolution is acceptable. Additionally, the consistent inter-subject results indicate that MRCDI is capable of picking up inaccuracies in computational head models and will be useful to guide systematic improvements.

Practical Application of Multivendor MRI-Based R2* Mapping for Liver Iron Quantification at 1.5 T and 3.0 T.

Recent multicenter, multivendor MRI-based R2* vs. liver iron concentration (LIC) calibrations (i.e., MCMV calibrations) may facilitate broad clinical dissemination of R2*-based LIC quantification. However, these calibrations are based on a centralized offline R2* reconstruction, and their applicability with vendor-provided R2* maps is unclear. To determine R2* ranges of agreement between the centralized and three MRI vendors' R2* reconstructions. Prospective. Two hundred and seven subjects (mean age 37.6 ± 19.6 years; 117 male) with known or suspected iron overload from four academic medical centers. Standardized multiecho spoiled gradient echo sequence at 1.5 T and 3.0 T for R2* mapping and a multiple spin-echo sequence at 1.5 T for LIC quantification. MRI vendors: GE Healthcare, Philips Healthcare, and Siemens Healthineers. R2* maps were generated using both the centralized and vendor reconstructions, and ranges of agreement were determined. R2*-LIC linear calibrations were determined for each site, field strength, and reconstruction and compared with the MCMV calibrations. Bland-Altman analysis to determine ranges of agreement. Linear regression, analysis of covariance F tests, and Tukey's multiple comparison testing to assess reproducibility of calibrations across sites and vendors. A P value <0.05 was considered significant. The upper limits of R2* ranges of agreement were approximately 500, 375, and 330 s-1 for GE, Philips, and Siemens reconstructions, respectively, at 1.5 T and approximately 700 and 800 s-1 for GE and Philips, respectively, at 3.0 T. Within the R2* ranges of agreement, vendor R2*-LIC calibrations demonstrated high reproducibility (no significant differences between slopes or intercepts; P ≥ 0.06) and agreed with the MCMV calibrations (overlapping 95% confidence intervals). Based on the determined upper limits, R2* measurements obtained from vendor-provided R2* maps may be reliably and practically used to quantify LIC less than approximately 8-13 mg/g using the MCMV calibrations and similar acquisition parameters as this study. 1 TECHNICAL EFFICACY: Stage 3.

The changes of oxygen extraction fraction in different types of lesions in relapsing-remitting multiple sclerosis: A cross-sectional and longitudinal study.

To explore the oxygen metabolism level of different types of lesions in relapsing-remitting multiple sclerosis (RRMS) patients by oxygen extraction fraction (OEF) both cross-sectionally and longitudinally. Forty-six RRMS patients and forty-one healthy controls (HC) went MRI examination. The quantitative susceptibility mapping (QSM) and OEF map were reconstructed from a 3D multi-echo gradient echo sequence. MS lesions in white matter were classified as contrast-enhancing lesions (CELs) on post-gadolinium T1-weighted sequence, paramagnetic rim lesions (PRLs), hyperintense lesions and non-hyperintense lesions on QSM, respectively. The susceptibility and OEF of different types of lesions were compared. The susceptibility and OEF values were measured and compared among different types of lesions. Among these RRMS patients, seventeen had follow-up MRI and 232 lesions, and baseline to follow-up longitudinal changes in susceptibility and OEF were measured. PRLs had higher susceptibility and lower OEF than CELs, hyperintense lesions, and non-hyperintense lesions. The hyperintense lesions had higher susceptibility and lower OEF than non-hyperintense lesions. In longitudinal changes, PRLs had susceptibility increased (P < 0.001) and OEF decreased (P < 0.001). The hyperintense lesions showed significant decreases in susceptibility (P = 0.020), and non-hyperintense lesions showed significant increases in OEF during follow-up (P = 0.005). Notably, hyperintense lesions may convert to PRLs or non-hyperintense lesions as time progresses, accompanied by changes of OEF and susceptibility in the lesions. This study revealed tissue damage and oxygen metabolism level in different types of MS lesions. The OEF may contribute to further understanding the evolution of MS lesions.

Application of the magnetic resonance 3D multiecho Dixon sequence for quantifying hepatic iron overload and steatosis in patients with thalassemia

ObjectiveTo investigate the feasibility and diagnostic efficacy of a 3D multiecho Dixon (qDixon) research application for simultaneously quantifying the liver iron concentration (LIC) and steatosis in thalassemia patients. Materials and methodsThis prospective study enrolled participants with thalassemia who underwent 3 T MRI of the liver for the evaluation of hepatic iron overload. The imaging protocol including qDixon and conventional T2* mapping based on 2D multiecho gradient echo (ME GRE) sequences respectively. Regions of interest (ROIs) were drawn in the liver on the qDixon maps to obtain R2* and proton density fat fraction (PDFF). The reference R2* value was measured and calculated on conventional T2* mapping using the CMRtools software. Correlation analysis, Linear regression analysis, and Bland–Altman analysis were performed. Results84 patients were finally included in this study. The median R2*-ME-GRE was 366.97 (1/s), range [206.68 (1/s), 522.20 (1/s)]. 8 patients had normal hepatic iron deposition, 16 had Insignificant, 42 had mild, 18 had moderate. The median of R2*-qDixon was 376.88 (1/s) [219.33 (1/s), 491.75 (1/s)]. A strong correlation was found between the liver R2*-qDixon and the R2*-ME-GRE (r = 0.959, P < 0.001). The median value of PDFF was 1.76% (1.10%, 2.95%). 8 patients had mild fatty liver, and 1 had severe fatty liver. ConclusionMR qDixon research sequence can rapidly and accurately quantify liver iron overload, that highly consistent with the measured via conventional GRE sequence, and it can also simultaneously detect hepatic steatosis, this has great potential for clinical evaluation of thalassemia patients.

Recommended implementation of quantitative susceptibility mapping for clinical research in the brain: A consensus of the ISMRM electro-magnetic tissue properties study group.

This article provides recommendations for implementing QSM for clinical brain research. It is a consensus of the International Society of Magnetic Resonance in Medicine, Electro-Magnetic Tissue Properties Study Group. While QSM technical development continues to advance rapidly, the current QSM methods have been demonstrated to be repeatable and reproducible for generating quantitative tissue magnetic susceptibility maps in the brain. However, the many QSM approaches available have generated a need in the neuroimaging community for guidelines on implementation. This article outlines considerations and implementation recommendations for QSM data acquisition, processing, analysis, and publication. We recommend that data be acquired using a monopolar 3D multi-echo gradient echo (GRE) sequence and that phase images be saved and exported in Digital Imaging and Communications in Medicine (DICOM) format and unwrapped using an exact unwrapping approach. Multi-echo images should be combined before background field removal, and a brain mask created using a brain extraction tool with the incorporation of phase-quality-based masking. Background fields within the brain mask should be removed using a technique based on SHARP or PDF, and the optimization approach to dipole inversion should be employed with a sparsity-based regularization. Susceptibility values should be measured relative to a specified reference, including the common reference region of the whole brain as a region of interest in the analysis. The minimum acquisition and processing details required when reporting QSM results are also provided. These recommendations should facilitate clinical QSM research and promote harmonized data acquisition, analysis, and reporting.

Assessing brain integrity in patients with long-term and well-functioning metal-based hip implants.

Production of metal debris from implant wear and corrosion processes is now a well understood occurrence following hip arthroplasty. Evidence has shown that metal ions can enter the bloodstream and travel to distant organs including the brain, and in extreme cases, can induce sensorial and neurological diseases. Our objective was tosimultaneously analyze brain anatomy and physiology in patients with long-term and well-functioning implants. Included were subjects who had received total hip or hip resurfacing arthroplastywith an implantation time of a minimum of 7 years (n = 28) and age- and sex-matched controls (n = 32). Blood samples were obtained to measure ion concentrations of cobalt and chromium, and the Montreal Cognitive Assessment was performed. 3T MRI brain scans were completed with an MPRAGE sequence for ROI segmentation and multiecho gradient echo sequences to generate QSM and R2* maps. Mean QSM and R2* values were recorded for five deep brain and four middle and cortical brain structures on both hemispheres: pallidum, putamen, caudate, amygdala, hippocampus, anterior cingulate, inferior temporal, and cerebellum. No differences in QSM or R2* or cognition scores were found between both groups (p > 0.6654). No correlation was found between susceptibility and blood ion levels for cobalt or chromium in any region of the brain. No correlation was found between blood ion levels and cognition scores.Clinical significance: Results suggest that metal ions released by long-term and well-functioning implants do not affect brain integrity.

Combination of high resolution MRI with 3D-printed needle guides for ex vivo myocardial biopsies

Magnetic resonance imaging (MRI) provides a multitude of techniques to detect and characterize myocardial infarction. To correlate MRI findings with histology, in most cases terminal animal studies are performed; however, precise extraction and spatial correlation of myocardial tissue samples to MRI image data is difficult. In this proof of concept study, we present a 3D-printing technique to facilitate the extraction of tissue samples from myocardial regions. Initially, seven pig hearts embedded in formaldehyde were imaged on a clinical 3 T system to define biopsy targets on high resolution ex vivo images. Magnitude images and R2*-maps acquired with a 3D multi-echo gradient echo sequence and 0.58 mm isotropic resolution were used to create digital models of the cardiac anatomy. Biopsy guides were 3D-printed to steer the extraction of myocardial samples. In total, 61 tissue samples were extracted with an average offset of the tissue sample location from the target location of 0.59 ± 0.36 mm. This offset was not dependent on the distance of the target point to the epicardial surface. Myocardial tissue could be extracted from all samples. The presented method enables extraction of myocardial tissue samples that are selected by ex vivo MRI with submillimeter precision.

Segmental quantification of hepatic lipid content based on volumetric MRI data in patients with suspected iron overload.

To investigate the segmental distribution of hepatic fat fraction, determined with MRI (MR proton density fat fraction, short MR-PDFF) in patients suspected of having liver iron overload. The liver of 44 patients examined with MRI using a 3D multi-echo gradient-echo sequence was segmented semiautomatically and subdivided into nine segments (segment 4 divided in 4a and 4b). Segmental fat content was determined on MR-PDFF maps. Whole-liver steatosis grades were compared to those found in individual segments. Segmental MR-PDFF differences were tested for statistical significance. The most common diseases were thalassemia, various forms of anemia, and hereditary hemochromatosis. No patients suffered from fat metabolism disease. Iron overload was present in 37/44 (84 %) patients. For the whole liver, 22patients showed a steatosis grade of 0, 21 patients were graded S1, and one patient had a steatosis grade of 2. The grade of steatosis was underestimated in 5 of 21 patients (24 %) in segment 8 and in 8 of 21 patients (38 %) in segment 7. Highly significant segmental MR-PDFF differences were detected with p < 0.00 001, e. g., comparing segment 2 to 5. Segments 1 to 3 had the highest fat content, segments 7 and 8 had the lowest. Our results suggest that the storage of fat in the liver is inhomogeneous, so that segment-wise differing fat concentrations were found. Fat distribution in patients with suspected hepatic iron overload was similar to living liver donors. However, it showed significant differences compared with the values published for NAFLD patients, which were less pronounced in the group with high average hepatic MR-PDFF values than in the group with normal lipid content. In patients suspected of having iron overload, segment 8, which is mainly targeted for biopsy, and segment 7 may underestimate steatosis grade. · A volumetric analysis of 3D MRI data of patients with suspected hepatic iron overload yielded a markedly elevated MR proton density fat fraction (MR-PDFF) in hepatic segments 1 to 3.. · This hepatic fat distribution, observed for the whole patient cohort, is similar to healthy living liver donors.. · The subgroup of patients with a high average MR-PDFF ≥ 6.5 % shows this effect with lower segmental deviations.. · In patients without fat metabolic disorders, the steatosis grade may be underestimated when taking biopsies in segment 8 or 7..

Iron content affects age group differences in associative learning-related fMRI activity

Brain regions accumulate different amounts of iron with age, with older adults having higher iron in the basal ganglia (globus pallidus, putamen, caudate) relative to the hippocampus. This has important implications for functional magnetic resonance imaging (fMRI) studies in aging as the presence of iron may influence both neuronal functioning as well as the measured fMRI (BOLD) signal, and these effects will vary across age groups and brain regions. To test this hypothesis, the current study examined the effect of iron on age group differences in task-related activity within each basal nuclei and the hippocampus. Twenty-eight younger and 22 older adults completed an associative learning task during fMRI acquisition. Iron content (QSM, R2*) was estimated from a multi-echo gradient echo sequence. As previously reported, older adults learned significantly less than younger adults and age group differences in iron content were largest in the basal ganglia (putamen, caudate). In the hippocampus (early task stage) and globus pallidus (late task stage), older adults had significantly higher learning-related activity than younger adults both before and after controlling for iron. In the putamen (late task stage), however, younger adults had significantly higher learning-related activity than older adults that was only seen after controlling for iron. These findings support the notion that age-related differences in iron influence both neuronal functioning and the measured fMRI signal in select basal nuclei. Moreover, previous fMRI studies in aging populations may have under-reported age group differences in task-related activity by not accounting for iron within these regions.

Myelin water imaging at 0.55 T using a multigradient-echo sequence.

To investigate the prospects of a multigradient-echo (mGRE) acquisition for in vivo myelin water imaging at 0.55 T. Scans were performed on the brain of four healthy volunteers at 0.55 and 3 T, using a 3D mGRE sequence. The myelin water fraction (MWF) was calculated for both field strengths using a nonnegative least squares (NNLS) algorithm, implemented in the qMRLab suite. The quality of these maps as well as single-voxel fits were compared visually for 0.55 and 3 T. The obtained MWF values at 0.55 T are consistent with previously reported ones at higher field strengths. The MWF maps are a considerable improvement over the ones at 3 T. Example fits show that 0.55 T data is better described by an exponential model than 3 T data, making the assumed multi-exponential model of the NNLS algorithm more accurate. This first assessment shows that mGRE myelin water imaging at 0.55 T is feasible and has the potential to yield better results than at higher fields.

Cerebral Oxygen Metabolism Improves Following Hematopoietic Cell Transplantation in Children with Sickle Cell Disease

Introduction: Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for patients with sickle cell disease (SCD). It is often recommended for patients with severe SCD, including those at risk of, or with a history of stroke. There has been limited investigation into the direct impact of HCT on cerebral hemodynamics. Quantitative biomarkers of cerebral hemodynamics, including oxygen extraction fraction (OEF) and cerebral blood flow (CBF), can provide an objective assessment of therapeutic efficacy of HCT as well as other emerging therapies. We have previously shown that CBF improves after HCT in patients with SCD (Sharma A, et al. Suppl 1, Blood 2021). Here, we performed a prospective evaluation using magnetic resonance imaging (MRI) to measure the OEF of the whole brain and the superior sagittal sinus (SSS), to compare cerebral oxygen metabolism in SCD patients before and after HCT. Methods: We performed anatomical and hemodynamic MRI of the brain prior to, and at 6 months after HCT in children with SCD undergoing a reduced intensity conditioning based HCT on a clinical trial (NCT04362293). Patients were receiving either hydroxyurea (HU) or chronic transfusion therapy (CTT) before HCT. MRI brain scanning was performed for all patients in a 3 Tesla MRI imaging system (Siemens MAGNETOM Prisma, Erlangen, Germany) with a 16-channel phased-array coil. Quantitative susceptibility map (QSM) imaging was performed through a 3D multi-echo gradient echo sequence with flow compensation and reconstructed with the morphology-enabled dipole inversion (MEDI) method (Liu T, et al. MRM 2013). The oxygen extraction fraction was calculated utilizing the established formula incorporating clinically measured hematocrit, tissue susceptibility, and hemoglobin susceptibility values quantified through quantitative susceptibility mapping (QSM), as previously delineated (Fan A, et al. JCBFM 2020) for the segmented vessels from the whole brain and the SSS. Results: The median age at HCT was 15.6 years (N=11). Hematocrit as well as global and regional (SSS) OEF of the patients were quantified and compared between baseline and at 6 months after HCT (Fig 1). All patients experienced a decrease in OEF after HCT. We then stratified the patients into those who were receiving HU or CTT prior to HCT. In patients receiving HU prior to HCT (n=7), there was a small decrease in OEF for the whole brain (42.4% vs. 39.9%, P = 0.40) and SSS (33.1% vs. 31.3%, P =0.12) at 6 months after HCT compared to baseline. However, in patients receiving CTT prior to HCT (n=4) both the global OEF (50.0% vs. 34.4 %, P &amp;lt; 0.01) and regional OEF (31.8% vs. 26.7 %, P &amp;lt; 0.05) decreased significantly at 6 months after HCT. All patients exhibited an increased hematocrit following HCT (Fig 2). Specifically, the HU cohort improved from a mean of 27.4% to 37.5% ( P&amp;lt;0.01), while the CTT cohort increased from 26.2% to 39.6% ( P&amp;lt;0.01) after HCT. Conclusions: Our results demonstrate the feasibility of global and regional OEF quantification using MRI in patients undergoing HCT for SCD. We observed that the OEF of the whole brain and SSS exhibited a similar downward trend after HCT in patients receiving either HU or CTT. This indicates an overall improvement in oxygen delivery after HCT. OEF decrease was marked after HCT in the CTT group, suggesting that HCT provided better cerebral hemodynamic outcomes than at baseline for this group. In contrast, the cohort of patients receiving HU showed a subtle decrease in OEF after HCT, perhaps implying that these patients had milder cerebral hemodynamic compromise than the CTT group. Both pretreatment groups demonstrated significantly higher hemoglobin concentrations after HCT compared to before treatment which may have contributed to the improvement in OEF. Our study presents objective physiologic comparisons of different clinical therapies on cerebral hemodynamics, providing early data on the effects of cerebral oxygen delivery in pediatric patients with SCD. Further studies with larger patient numbers are warranted to confirm the trends observed in oxygen metabolism and understand the mechanisms underlying differential responses to HCT and other disease-modifying therapies. These imaging biomarkers may also help assess different genetic therapies currently in development.

In Vivo Measurement of Rat Brain Water Content at 9.4 T MR Using Super-Resolution Reconstruction: Validation With Ex Vivo Experiments.

Given that changes in brain water content are often correlated with disease, investigating water content non-invasively and in vivo could lead to a better understanding of the pathogenesis of several neurologic diseases. To adapt a super-resolution-based technique, previously developed for humans, to the rat brain and report in vivo high-resolution (HR) water content maps in comparison with ex vivo wet/dry methods. Prospective. Eight healthy male Wistar rats. 9.4-T, multi-echo gradient-echo (mGRE) sequence. Using super-resolution reconstruction (SRR), a HR mGRE image (200 μm isotropic) was reconstructed from three low-resolution (LR) orthogonal whole-brain images in each animal, which was followed by water content mapping in vivo. The animals were subsequently sacrificed, the brains excised and divided into five regions (front left, front right, middle left, middle right, and cerebellum-brainstem regions), and the water content was measured ex vivo using wet/dry measurements as the reference standard. The water content values of the in vivo and ex vivo methods were then compared for the whole brain and also for the different regions separately. Friedman's non-parametric test was used to test difference between the five regions, and Pearson's correlation coefficient was used for correlation between in vivo and ex vivo measurements. A P-value <0.05 was considered statistically significant. Water content values derived from in vivo MR measurements showed strong correlations with water content measured ex vivo at a regional level (r = 0.902). Different brain regions showed significantly different water content values. Water content values were highest in the frontal brain, followed by the midbrain, and lowest in the cerebellum and brainstem regions. An in vivo technique to achieve HR isotropic water content maps in the rat brain using SRR was adopted in this study. The MRI-derived water content values obtained using the technique showed strong correlations with water content values obtained using ex vivo wet/dry methods. 1 TECHNICAL EFFICACY: Stage 1.