Quantitative Susceptibility Mapping Maps Research Articles

Quantitative susceptibility mapping based basal ganglia segmentation via AGSeg: leveraging active gradient guiding mechanism in deep learning.

With better visual contrast and the ability for magnetic susceptibility quantification analysis, quantitative susceptibility mapping (QSM) has emerged as an important magnetic resonance imaging (MRI) method for basal ganglia studies. Precise segmentation of basal ganglia is a prerequisite for quantification analysis of tissue magnetic susceptibility, which is crucial for subsequent disease diagnosis and surgical planning. The conventional method of localizing and segmenting basal ganglia heavily relies on layer-by-layer manual annotation by experts, resulting in a tedious amount of workload. Although several morphology registration and deep learning based methods have been developed to automate segmentation, the voxels around the nuclei boundary remain a challenge to distinguish due to insufficient tissue contrast. This paper proposes AGSeg, an active gradient guidance-based susceptibility and magnitude information complete (MIC) network for real-time and accurate basal ganglia segmentation. Various datasets, including clinical scans and data from healthy volunteers, were collected across multiple centers with different magnetic field strengths (3T/5T/7T), with a total of 210 three-dimensional (3D) susceptibility measurements. Manual segmentations following fixed rules for anatomical borders annotated by experts were used as ground truth labels. The proposed network took QSM maps and Magnitude images as two individual inputs, of which the features are selectively enhanced in the proposed magnitude information complete (MIC) module. AGSeg utilized a dual-branch architecture, with Seg-branch aiming to generate a proper segmentation map and Grad-branch to reconstruct the gradient map of regions of interest (ROIs). With the support of the newly designed active gradient module (AGM) and gradient guiding module (GGM), the Grad-branch provided attention guidance for the Seg-branch, facilitating it to focus on the boundary of target nuclei. Ablation studies were conducted to assess the functionality of the proposed modules. Significant performance decrement was observed after ablating relative modules. AGSeg was evaluated against several existing methods on both healthy and clinical data, achieving an average Dice similarity coefficient (DSC) =0.874 and average 95% Hausdorff distance (HD95) =2.009. Comparison experiments indicated that our model had superior performance on basal ganglia segmentation and better generalization ability over existing methods. The AGSeg outperformed all implemented comparison deep learning algorithms with average DSC enhancement ranging from 0.036 to 0.074. The current work integrates a deep learning-based method into automated basal ganglia segmentation. The high processing speed and segmentation robustness of AGSeg contribute to the feasibility of future surgery planning and intraoperative navigation. Experiments show that leveraging active gradient guidance mechanisms and magnitude information completion can facilitate the segmentation process. Moreover, this approach also offers a portable solution for other multi-modality medical image segmentation tasks.

Phase-sensitive deep reconstruction method for rapid multiparametric MR fingerprinting and quantitative susceptibility mapping in the brain

IntroductionThis study explores the potential of Magnetic Resonance Fingerprinting (MRF) with a novel Phase-Sensitivity Deep Reconstruction Network (PS-DRONE) for simultaneous quantification of T1, T2, Proton Density, B1+, phase and quantitative susceptibility mapping (QSM). MethodsData were acquired at 3 T in vitro and in vivo using an optimized EPI-based MRF sequence. Phantom experiments were conducted using a standardized phantom for T1 and T2 maps and a custom-made agar-based gadolinium phantom for B1 and QSM maps. In vivo experiments included five healthy volunteers and one patient diagnosed with brain metastasis. PSDRONE maps were compared to reference maps obtained through standard imaging sequences. ResultsTotal scan time was 2 min for 32 slices and a resolution of [1 mm, 1 mm, 4.5 mm]. The reconstruction of T1, T2, Proton Density, B1+ and phase maps were reconstructed within 1 s. In the phantoms, PS-DRONE analysis presented accurate and strongly correlated T1 and T2 maps (r = 0.99) compared to the reference maps. B1 maps from PS-DRONE showed slightly higher values, though still correlated (r = 0.6) with the reference. QSM values showed a small bias but were strongly correlated (r = 0.99) with reference data. In the in vivo analysis, PS-DRONE-derived T1 and T2 values for gray and white matter matched reference values in healthy volunteers. PS-DRONE B1 and QSM maps showed strong correlations with reference values. ConclusionThe PS-DRONE network enables concurrent acquisition of T1, T2, PD, B1+, phase and QSM maps, within 2 min of acquisition time and 1 s of reconstruction time.

Characterization of quantitative susceptibility mapping in the left ventricular myocardium

Myocardial quantitative susceptibility mapping (QSM) may offer better specificity to iron than conventional T2* imaging in the assessment of cardiac diseases, including intra-myocardial hemorrhage. However, the precision and repeatability of cardiac QSM have not yet been characterized. The aim of this study is to characterize these key metrics in a healthy volunteer cohort and show the feasibility of the method in patients. Free breathing respiratory-navigated multi-echo 3D gradient echo images were acquired, from which QSM maps were reconstructed using the Morphology Enhanced Dipole Inversion toolbox. This technique was first evaluated in a susceptibility phantom containing tubes with known concentrations of gadolinium. In vivo characterization of myocardial QSM was then performed in a cohort of 10 healthy volunteers where each subject was scanned twice. Mean segment susceptibility, precision (standard deviation of voxel magnetic susceptibilities within one segment), and repeatability (absolute difference in segment mean susceptibility between repeats) of QSM were calculated for each American Heart Association (AHA) myocardial segment. Finally, the feasibility of the method was shown in 10 patients, including four with hemorrhagic infarcts. The phantom experiment showed a strong linear relationship between measured and predicted susceptibility shifts (R2 >0.99). For the healthy volunteer cohort, AHA segment analysis showed the mean segment susceptibility was 0.00±0.02ppm, the mean precision was 0.05±0.04ppm, and the mean repeatability was 0.02±0.02ppm. Cardiac QSM was successfully performed in all patients. Focal iron deposits were successfully visualized in the patients with hemorrhagic myocardial infarctions. The precision and repeatability of cardiac QSM were successfully characterized in phantom and in vivo experiments. The feasibility of the technique was also successfully demonstrated in patients. While challenges still remain, further clinical evaluation of the technique is now warranted. This work does not report on a health care intervention.

MRI assessment of different types of chronic demyelinating lesions in patients with multiple sclerosis using quantitative susceptibility mapping (QSM)

Histologically, chronic demyelinating lesions in multiple sclerosis (MS) have been shown to include inactive lesions that do not change over time and active or “smouldering" lesions that tend to enlarge over time and are surrounded by pro-inflammatory activated microglial cells that are loaded with iron. To identify “smouldering" foci of demyelination and assess the “latent” inflammatory process in the brain, MRI sequences sensitive to the detection of substances with paramagnetic properties, including iron, must be used. They include an innovative technique such as quantitative susceptibility mapping (QSM).Objective: to identify, using MRI different types of chronic demyelination foci in MS, based on iron distribution and the degree of damage (myelination) in their structure.Material and methods. The patterns of iron distribution in demyelinating lesions in 90 MS patients were investigated using QSM. In addition, two lesions with different iron distribution patterns were randomly selected on the QSM map for each patient, in which the magnetic transfer ratio (MTR), indirectly reflecting the degree of myelination, was calculated. The identified changes were also compared with visualization of lesions in standard MRI modes (T1 MPRAGE, T2 FLAIR).Results. Despite the predominantly identical visualization in T2 FLAIR mode, chronic foci of demyelination show different patterns on the QSM maps, which is due to the peculiarities of iron distribution: some foci are not detected on QSM, while others are visualized either in the form of a homogeneous or a ring-shaped pattern. When comparing QSM data with MTR, it was found that MTR indicators were highest in non-visualized lesions (demyelination is minimal), while damage was most pronounced in lesions with ring-shaped iron distribution.Conclusion. Different patterns of iron distribution in demyelination foci compared to the degree of myelination in these foci according to MTR were identified using QSM, which is of great importance for the evaluation of latent inflammation and the development of the neurodegenerative process in MS.

Spatiotemporal patterns of brain iron-oxygen metabolism in patients with Parkinson's disease.

Iron deposition and mitochondrial dysfunction are closely associated with the genesis and progression of Parkinson's disease (PD). This study aims to extract susceptibility and oxygen extraction fraction (OEF) values of deep grey matter (DGM) to explore spatiotemporal progression patterns of brain iron-oxygen metabolism in PD. Ninety-five PD patients and forty healthy controls (HCs) were included. Quantitative susceptibility mapping (QSM) and OEF maps were computed from MRI multi-echo gradient echo data. Analysis of covariance (ANCOVA) was used to compare mean susceptibility and OEF values in DGM between early-stage PD (ESP), advanced-stage PD (ASP) patients and HCs. Then Granger causality analysis on the pseudo-time-series of MRI data was applied to assess the causal effect of early altered nuclei on iron content and oxygen extraction in other DGM nuclei. The susceptibility values in substantia nigra (SN), red nucleus, and globus pallidus (GP) significantly increased in PD patients compared with HCs, while the iron content in GP did not elevate obviously until the late stage. The mean OEF values for the caudate nucleus, putamen, and dentate nucleus were higher in ESP patients than in ASP patients or/and HCs. We also found that iron accumulation progressively expands from the midbrain to the striatum. These alterations were correlated with clinical features and improved AUC for early PD diagnosis to 0.824. Abnormal cerebral iron deposition and tissue oxygen utilization in PD measured by QSM and OEF maps could reflect pathological alterations in neurodegenerative processes and provide valuable indicators for disease identification and management. Noninvasive assessment of cerebral iron-oxygen metabolism may serve as clinical evidence of pathological changes in PD and improve the validity of diagnosis and disease monitoring. • Quantitative susceptibility mapping and oxygen extraction fraction maps indicated the cerebral pathology of abnormal iron accumulation and oxygen metabolism in Parkinson's disease. • Iron deposition is mainly in the midbrain, while altered oxygen metabolism is concentrated in the striatum and cerebellum. • The susceptibility and oxygen extraction fraction values in subcortical nuclei were associated with clinical severity.

Magnetic susceptibility changes in the brainstem reflect REM sleep without atonia severity in isolated REM sleep behavior disorder

REM sleep without atonia (RWA) is the hallmark of isolated REM sleep behavior disorder (iRBD) and is caused by neurodegeneration of brainstem structures. Previously, quantitative susceptibility mapping (QSM) was shown to detect microstructural tissue changes in neurodegenerative diseases. The goal of the study was to compare brainstem magnetic susceptibility (MS) in iRBD and controls using the voxel-based QSM approach and to examine the association between brainstem MS and severity of RWA in iRBD. Sixty iRBD patients and 41 healthy controls were included in the study. Phasic, tonic, mixed RWA and SINBAR score was quantified. QSM maps were reconstructed with QSMbox software from a multi-gradient-echo sequence acquired at 3T MRI system and normalized using a custom T1 template. Voxel-based analysis with age and gender as covariates was performed using a two-sample t-test model for between-group comparison and using a linear regression model for association with the RWA parameters. Statistical maps were generated using threshold free cluster enhancement with p-value p < 0.05, corrected for family wise error. Compared to controls, the iRBD group had higher MS in bilateral substantia nigra (SN), red nucleus and the ventral tegmental area. MS positively correlated with iRBD duration in the right pedunculotegmental nucleus and white matter of caudal mesencephalic and pontine tegmentum and with phasic RWA in bilateral SN. QSM was able to detect MS abnormalities in several brainstem structures in iRBD. Association of MS levels in the brainstem with the intensity of RWA suggests that increased iron content in SN is related to RWA severity.

Optimal echo times for quantitative susceptibility mapping: A test-retest study on basal ganglia and subcortical brain nuclei

Quantitative Susceptibility Mapping (QSM) is a recent MRI-technique able to quantify the bulk magnetic susceptibility of myelin, iron, and calcium in the brain. Its variability across different acquisition parameters has prompted the need for standardisation across multiple centres and MRI vendors. However, a high level of agreement between repeated imaging acquisitions is equally important. With this study we aimed to assess the inter-scan repeatability of an optimised multi-echo GRE sequence in 28 healthy volunteers. We extracted and compared the susceptibility measures from the scan and rescan acquisitions across 7 bilateral brain regions (i.e., 14 regions of interest (ROIs)) relevant for neurodegeneration. Repeatability was first assessed while reconstructing QSM with a fixed number of echo times (i.e., 8). Excellent inter-scan repeatability was found for putamen, globus pallidus and caudate nucleus, while good performance characterised the remaining structures. An increased variability was instead noted for small ROIs like red nucleus and substantia nigra. Secondly, we assessed the impact exerted on repeatability by the number of echoes used to derive QSM maps. Results were impacted by this parameter, especially in smaller regions. Larger brain structures, on the other hand, showed more consistent performance. Nevertheless, with either 8 or 7 echoes we managed to obtain good inter-scan repeatability on almost all ROIs. These findings indicate that the designed acquisition/reconstruction protocol has wide applicability, particularly in clinical or research settings involving longitudinal acquisitions (e.g. rehabilitation studies).

Abstract WMP23: Dynamic Imaging Of Blood Coagulation Within The Hematoma Of Patients With Acute Intracerebral Hemorrhage

Objective: To serially quantify the blood coagulation within hematoma of patients with hyper-acute intracerebral hemorrhagic (ICH) stroke using non-invasive quantitative susceptibility mapping (QSM) MRI. Introduction: A blood clot is a combination of aggregated red blood cells, fibrin, platelets, hemosiderin, and other cell debris. An accurate evaluation of clot formation within hematoma could advance the clinical management of hematoma expansion, blood pressure management, and reversal of anticoagulants. Post-ICH hemolysis changes the heme iron oxidation state from oxy to deoxyhemoglobin (deoxy-Hb) resulting in unpaired iron electrons on aggregated RBC’s deoxy-Hb inducing magnetic susceptibility (χ). Therefore, a region with a higher number of aggregated RBC deoxy-Hb molecules, the dominant component of clots, will exhibit a higher positive χ susceptibility. We hypothesized that coagulated blood within hematoma will exhibit a higher positive χ in comparison to the non-clotted which can be quantified using quantitative susceptibility mapping (QSM), which is an advanced MRI image-processing algorithm. Methods: For proof of concept, we measured susceptibilities of 5 human blood phantoms with various percentages of the clot. Twenty-four patients with acute spontaneous ICH were enrolled and serially imaged 3 times within 12-24 (T1), 36-48 (T2), and 60-72(T3) hours of last known well (LNW). A 3D anatomical and multi-echo gradient echo images were obtained using a 3T MRI system. Hematoma and edema volumes were segmented and used as a region of interest (ROI). The rate of coagulation was assessed by measuring the change in susceptibilities within the hematoma. Results: The blood phantom exhibited a linear relationship between the percent coagulation and χ (R 2 =0.91). The QSM maps showed a significant increased in hematoma susceptibility over time (T1=0.29 ± 0.04, T2=0.36 ± 0.04, T3= 0.45 ± 0.04 ppm, p&lt;0.0001). The overall average rate of coagulation was 0.00290 ± 0.0029 ppm per hour. No significant change in hematoma volume (18.9 ±3.1 cc) over time. A significant edema growth over time (T1=25.3 ± 3.6, T2= 28.1 ± 3, T3= 32.37 cc, p&lt;0.05). Conclusion: In conclusion, we present novel surrogate imaging markers of coagulation within the hematoma of ICH.

Comparison of quantitative susceptibility mapping methods for iron-sensitive susceptibility imaging at 7T: An evaluation in healthy subjects and patients with Huntington's disease

Quantitative susceptibility mapping (QSM) is a promising tool for investigating iron dysregulation in neurodegenerative diseases, including Huntington's disease (HD). Many diverse methods have been proposed to generate accurate and robust QSM images. In this study, we evaluated the performance of different dipole inversion algorithms for iron-sensitive susceptibility imaging at 7T on healthy subjects of a large age range and patients with HD. We compared an iterative least-squares-based method (iLSQR), iterative methods that use regularization, single-step approaches, and deep learning-based techniques. Their performance was evaluated by comparing: (1) deviations from a multiple-orientation QSM reference; (2) visual appearance of QSM maps and the presence of artifacts; (3) susceptibility in subcortical brain regions with age; (4) regional brain susceptibility with published postmortem brain iron quantification; and (5) susceptibility in HD-affected basal ganglia regions between HD subjects and healthy controls. We found that single-step QSM methods with either total variation or total generalized variation constraints (SSTV/SSTGV) and the single-step deep learning method iQSM generally provided the best performance in terms of correlation with iron deposition and were better at differentiating between healthy controls and premanifest HD individuals, while deep learning QSM methods trained with multiple-orientation susceptibility data created QSM maps that were most similar to the multiple orientation reference and with the best visual scores.

Test-retest analysis of cerebral oxygen extraction estimates in healthy volunteers: comparison of methods based on quantitative susceptibility mapping and dynamic susceptibility contrast magnetic resonance imaging

BackgroundEstimation of the oxygen extraction fraction (OEF) by quantitative susceptibility mapping (QSM) magnetic resonance imaging (MRI) is promising but requires systematic evaluation. Extraction of OEF-related information from the tissue residue function in dynamic susceptibility contrast MRI (DSC-MRI) has also been proposed. In this study, whole-brain OEF repeatability was investigated, as well as the relationships between QSM-based OEF and DSC-MRI-based parameters, i.e., mean transit time (MTT) and an oxygen extraction index, referred to as apparent OEF (AOEF). MethodTest-retest data were obtained from 20 healthy volunteers at 3 T. QSM maps were reconstructed from 3D gradient-echo MRI phase data, using morphology-enabled dipole inversion. DSC-MRI was accomplished using gradient-echo MRI at a temporal resolution of 1.24 s. ResultsThe whole-brain QSM-based OEF was (40.4±4.8) % and, in combination with a previously published cerebral blood flow (CBF) estimate, this corresponds to a cerebral metabolic rate of oxygen level of CMRO2 = 3.36 ml O2/min/100 g. The intra-class correlation coefficient [ICC(2,1)] for OEF test-retest data was 0.73. The MTT-versus-OEF and AOEF-versus-OEF relationships showed correlation coefficients of 0.61 (p = 0.004) and 0.52 (p = 0.019), respectively. DiscussionQSM-based OEF showed a convincing absolute level and good test-retest results in terms of the ICC. Moderate to good correlations between QSM-based OEF and DSC-MRI-based parameters were observed. The present results constitute an indicator of the level of robustness that can be achieved without applying extraordinary resources in terms of MRI equipment, imaging protocol, QSM reconstruction, and OEF analysis.

Choroid Plexus Calcification Associations with Brain Morphology and Family History of Alzheimer's Disease

AbstractBackgroundThe choroid plexus (CP) is the primary source of cerebrospinal fluid (CSF) production and forms the blood‐CSF barrier which regulates nutrients and hormones to the brain. Changes in CSF production are associated with aging and Alzheimer’s disease (Saade 2019, Hubert 2019). CP calcification (CPcal) has been associated with metabolic disorders, cerebrovascular diseases, and tumors (Wu, 2009). Here, we used MRI‐derived quantitative susceptibility mapping (QSM) from the UK Biobank(Miller, 2016) to investigate whether CPcal is associated with morphological brain alterations and family history of Alzheimer's disease or related dementias (ADRD).MethodWe analyzed susceptibility weighted images (SWI) from 32,426 participants (aged 45‐83 years, F = 54%) from the UK Biobank, and 1716 follow‐up scans (aged 50‐83 years, F = 53%) Table 1. CPcal volumes were extracted from processed QSM maps (Figure 1) within FreeSurfer‐defined brain ventricles: total, lateral (LV), third (3rdV), and fourth ventricle (4thV). 34 regional cortical thickness and surface area measures, and 11 subcortical volumes were extracted using FreeSurfer. Linear regressions were used to assess the relationship between log‐transformed CPcal volumes and cross‐sectional and longitudinal change in FreeSurfer brain metrics (tp2‐tp1/tp1) adjusting for age, sex, LV and intracranial volumes. The false discovery rate (FDR, q=0.05) was applied to adjust for multiple comparisons across brain regions. Linear regression was used to investigate whether CPcal volumes were associated with family history of AD or dementia.ResultGreater CPcal volumes were associated with regional brain morphometry, cross sectionally, and longitudinally (Figure 2). Total CPcal were associated with family history of AD; specifically maternal history of AD showed a stronger association with total CPcal while paternal history showed no association (Table 2).ConclusionUsing QSM, we show that CP calcification impacts structural brain measures and is associated with family history of ADRD. This suggests that CPcal may be an important biomarker for tracking age related changes and AD, and may be an important biomarker for imaging genetic studies.

The Effects of Wearing a 3-Ply or KN95 Face Mask on Cerebral Blood Flow and Oxygenation.

BackgroundThe SARS‐CoV‐2 virus has impacted life in many ways, one change being the use of face masks. Their effect on MRI‐based measurements of cerebral oxygen levels with quantitative susceptibility mapping (QSM) and cerebral blood flow (CBF) is not known.PurposeThis study investigated whether wearing a face mask leads to changes in CBF and cerebral venous oxygen saturation measured with MRI.Study TypeRepeated‐measures cohort study.PopulationA total of 16 healthy volunteers (eight male, eight female; 22–36 years) were recruited for the 3‐ply study. Ten of the 16 participants (five male, five female; 23–36 years) took part in the KN95 study.Field Strength/SequenceA 3 T, single‐delay 3D gradient‐and spin‐echo pseudo‐continuous arterial spin labeling (pCASL) scan for CBF quantification, and gradient‐echo for QSM and oxygenation quantification.AssessmentGray matter CBF and magnetic susceptibility were assessed by masking the pCASL CBF map and the QSM map to the T1‐weighted gray matter tissue segmentation. Venous oxygenation was determined from venous segmentation of QSM maximum intensity projections.Statistical TestsPaired Student's t‐tests and Cohen's d effect sizes were used to compare the face mask and no face mask scans for gray matter CBF, gray matter magnetic susceptibility, and cerebral venous oxygen saturation. Standard t‐tests were used to assess whether the order of scanning with and without a mask had any impact. A statistical cut off of P < 0.05 was used.ResultsThe 3‐ply masks increased gray matter CBF from an average of 43.99 mL/(100 g*min) to 46.81 mL/(100 g*min). There were no significant changes in gray matter magnetic susceptibility (P = 0.07), or cerebral venous oxygen saturation (P = 0.36) for the 3‐ply data set. The KN95 masks data set showed no statistically significant changes in gray matter CBF (P = 0.52) and magnetic susceptibility (P = 0.97), or cerebral venous oxygen saturation (P = 0.93).Data ConclusionThe changes in blood flow and oxygenation due to face masks are small. Only CBF increased significantly due to wearing a 3‐ply mask.Evidence Level2Technical EfficacyStage 3

Morphometric imaging and quantitative susceptibility mapping as complementary tools in the diagnosis of parkinsonisms

Background and purposeIn the quest for in vivo diagnostic biomarkers to discriminate Parkinson's disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA, mainly p phenotype), many advanced magnetic resonance imaging (MRI) techniques have been studied. Morphometric indices, such as the Magnetic Resonance Parkinsonism Index (MRPI), demonstrated high diagnostic value in the comparison between PD and PSP. The potential of quantitative susceptibility mapping (QSM) was hypothesized, as increased magnetic susceptibility (Δχ) was reported in the red nucleus (RN) and medial part of the substantia nigra (SNImed) of PSP patients and in the putamen of MSA patients. However, disease‐specific susceptibility values for relevant regions of interest are yet to be identified. The aims of the study were to evaluate the diagnostic potential of a multimodal MRI protocol combining morphometric and QSM imaging in patients with determined parkinsonisms and to explore its value in a population of undetermined cases.MethodPatients with suspected degenerative parkinsonism underwent clinical evaluation, 3 T brain MRI and clinical follow‐up. The MRPI was manually calculated on T1‐weighted images. QSM maps were generated from 3D multi‐echo T2*‐weighted sequences.ResultsIn determined cases the morphometric evaluation confirmed optimal diagnostic accuracy in the comparison between PD and PSP but failed to discriminate PD from MSA‐p. Significant nigral and extranigral differences were found with QSM. RN Δχ showed excellent diagnostic accuracy in the comparison between PD and PSP and good accuracy in the comparison of PD and MSA‐p. Optimal susceptibility cut‐off values of RN and SNImed were tested in undetermined cases in addition to MRPI.ConclusionsA combined use of morphometric imaging and QSM could improve the diagnostic phase of degenerative parkinsonisms.

Quantitative susceptibility mapping reveals brain iron deficiency in children with attention-deficit/hyperactivity disorder: a whole-brain analysis.

To quantitatively measure and compare the whole-brain iron deposition between attention-deficit/hyperactivity disorder (ADHD) patients and typically developing (TD) children using the quantitative susceptibility mapping (QSM) technique. This study was approved by the institutional review board of our institution (No. [2019]328). Fifty-one patients between 6 and 14years with clinical diagnosis of ADHD and 51 age- and gender-paired TD children were enrolled. For each participant, the 3D T1 and multi-echo GRE sequence were performed to acquire the whole-brain data with 3.0-T MRI. The QSM maps were calculated using STISuite toolbox. After normalizing the QSM images to MNI space, the voxel-based analysis was used to compare the iron content between the two groups. Pearson's correlation test was used to assess the associations between the iron content and the score of the tablet-PC-based cancellation test, which was done to evaluate the attention concentration level. Iron deficiency was observed in several brain regions in children with ADHD, including bilateral striatums, anterior cingulum, olfactory gyrus, and right lingual gyri. In further correlation analysis, the left anterior cingulum was found to show positive correlation with the symptom severity (r = 0.326, p < 0.05). Our study demonstrated that the iron deficiency in several brain regions might be related with ADHD, which might be valuable for further studies. And QSM might have the potential efficacy in the auxiliary diagnosis of ADHD. • Iron deficiency was observed in several brain regions in children with ADHD, which include bilateral striatums, the critical regions in the dopaminergic transmitter system. • The iron content in the left ACG may have association with the symptom severity of ADHD. • QSM might have the potential efficacy in the auxiliary diagnosis of ADHD.

Ironsmith: An automated pipeline for QSM-based data analyses

Quantitative susceptibility mapping (QSM) is an MRI-based, computational method for anatomically localizing and measuring concentrations of specific biomarkers in tissue such as iron. Growing research suggests QSM is a viable method for evaluating the impact of iron overload in neurological disorders and on cognitive performance in aging. Several software toolboxes are currently available to reconstruct QSM maps from 3D GRE MR Images. However, few if any software packages currently exist that offer fully automated pipelines for QSM-based data analyses: from DICOM images to region-of-interest (ROI) based QSM values. Even less QSM-based software exist that offer quality control measures for evaluating the QSM output. Here, we address these gaps in the field by introducing and demonstrating the reliability and external validity of Ironsmith; an open-source, fully automated pipeline for creating and processing QSM maps, extracting QSM values from subcortical and cortical brain regions (89 ROIs) and evaluating the quality of QSM data using SNR measures and assessment of outlier regions on phase images. Ironsmith also features automatic filtering of QSM outlier values and precise CSF-only QSM reference masks that minimize partial volume effects. Testing of Ironsmith revealed excellent intra- and inter-rater reliability. Finally, external validity of Ironsmith was demonstrated via an anatomically selective relationship between motor performance and Ironsmith-derived QSM values in motor cortex. In sum, Ironsmith provides a freely-available, reliable, turn-key pipeline for QSM-based data analyses to support research on the impact of brain iron in aging and neurodegenerative disease.

Multiecho complex total field inversion method (mcTFI) for improved signal modeling in quantitative susceptibility mapping.

Typical quantitative susceptibility mapping (QSM) reconstruction steps consist of first estimating the magnetization field from the gradient-echo images, and then reconstructing the susceptibility map from the estimated field. The errors from the field-estimation steps may propagate into the final QSM map, and the noise in the estimated field map may no longer be zero-mean Gaussian noise, thus, causing streaking artifacts in the resulting QSM. A multiecho complex total field inversion (mcTFI) method was developed to compute the susceptibility map directly from the multiecho gradient echo images using an improved signal model that retains the Gaussian noise property in the complex domain. It showed improvements in QSM reconstruction over the conventional field-to-source inversion. The proposed mcTFI method was compared with the nonlinear total field inversion (nTFI) method in a numerical brain with hemorrhage and calcification, the numerical brains provided by the QSM Challenge 2.0, 18 brains with intracerebral hemorrhage scanned at 3T, and 6 healthy brains scanned at 7T. Compared with nTFI, the proposed mcTFI showed more accurate QSM reconstruction around the lesions in the numerical simulations. The mcTFI reconstructed QSM also showed the best image quality with the least artifacts in the brains with intracerebral hemorrhage scanned at 3T and healthy brains scanned at 7T. The proposed multiecho complex total field inversion improved QSM reconstruction over traditional field-to-source inversion through better signal modeling.

Iterative Restoration of the Fringe Phase (REFRASE) for QSM.

In quantitative susceptibility mapping (QSM), reconstructed results can be critically biased by misinterpreted or missing phase data near the edges of the brain support originating from the non-local relationship between field and susceptibility. These data either have to be excluded or corrected before further processing can take place. To address this, our iterative restoration of the fringe phase (REFRASE) approach simultaneously enhances the accuracy of multi-echo phase data QSM maps and the extent of the area available for evaluation. Data loss caused by strong local phase gradients near the surface of the brain support is recovered within the original phase data using harmonic and dipole-based fields extrapolated from a robust support region toward an extended brain mask. Over several iterations, phase data are rectified prior to the application of further QSM processing steps. The concept is successfully validated on numerical phantoms and brain scans from a cohort of volunteers. The increased extent of the mask and improved numerical stability within the segmented globus pallidus confirm the efficacy of the presented method in comparison to traditional evaluation.

QSMART: Quantitative susceptibility mapping artifact reduction technique

Purpose: Quantitative susceptibility mapping (QSM) is a novel MR technique that allows mapping of tissue susceptibility values from MR phase images. QSM is an ill-conditioned inverse problem, and although several methods have been proposed in the field, in the presence of a wide range of susceptibility sources, streaking artifacts appear around high susceptibility regions and contaminate the whole QSM map. QSMART is a post-processing pipeline that uses two-stage parallel inversion to reduce the streaking artifacts and remove banding artifact at the cortical surface and around the vasculature. Method: Tissue and vein susceptibility values were separately estimated by generating a mask of vasculature driven from the magnitude data using a Frangi filter. Spatially dependent filtering was used for the background field removal step and the two susceptibility estimates were combined in the final QSM map. QSMART was compared to RESHARP/iLSQR and V-SHARP/iLSQR inversion in a numerical phantom, 7T in vivo single and multiple-orientation scans, 9.4T ex vivo mouse data, and 4.7T in vivo rat brain with induced focal ischemia. Results: Spatially dependent filtering showed better suppression of phase artifacts near cortex compared to RESHARP and V-SHARP, while preserving voxels located within regions of interest without brain edge erosion. QSMART showed successful reduction of streaking artifacts as well as improved contrast between different brain tissues compared to the QSM maps obtained by RESHARP/iLSQR and V-SHARP/iLSQR. Conclusion: QSMART can reduce QSM artifacts to enable more robust estimation of susceptibility values in vivo and ex vivo.

Quantitative Susceptibility Mapping of the Hippocampal Fimbria in Alzheimer's Disease.

The fimbria is a small white matter bundle that connects the hippocampus to the rest of the brain. Damage to the hippocampal gray matter is established in Alzheimer's disease (AD), but the hippocampal fimbrial status in the pathogenesis of AD is unclear. AD-related demyelination and iron deposition alter the diamagnetic and paramagnetic composition of tissues, which can be measured by quantitative susceptibility mapping (QSM). AD is associated with microstructural changes in the fimbria that might be detected by QSM. Retrospective cross-sectional study. In all, 53 adults comprised of controls (n =30), subjects with early stage AD (n =13), and late stage AD (n =10) who were classified according to their amyloid and tau status and presence of hippocampal atrophy. 3T; 3D fast-field echo sequence for QSM analysis and 3D T1 -weighted MP-RAGE sequence for anatomical analysis. Segmentation of the left hippocampal fimbria subfield was performed on T1 -weighted images and was applied to the coregistered QSM map for extraction of the mean, median, minimum, and maximum values of QSM. Group comparison of QSM values using analysis of variance (ANOVA) with post-hoc Tukey's test, accuracy of binary differentiation using receiver operating characteristic (ROC), and individual classification using discriminant analysis. QSMmean and QSMmedian values were significantly different among the three groups (P < 0.05) and showed a shifting from negative in the control group to positive in the AD group. The control and early AD subjects, who have normal hippocampal volumes, were differentiated by the QSMmean value (area under the curve [AUC] 0.744, P < 0.05) and the QSMmedian value (AUC 0.782, P < 0.05). Up to 76% of subjects (inclusive of 26 controls and six with early AD) were correctly classified using a model incorporating clinical and radiologic data. The fimbria showed higher magnetic susceptibility in AD compared with controls. 2 TECHNICAL EFFICACY STAGE: 3.

Increased Brain Iron Deposition in the Putamen in Patients with Type 2 Diabetes Mellitus Detected by Quantitative Susceptibility Mapping.

Background The underlying brain structural changes in type 2 diabetes mellitus (T2DM) patients have attracted increasing attention. The insulin-resistant state causes iron overload in neurons and leads to lesions in the central nervous system. Quantitative susceptibility mapping (QSM) can provide a noninvasive quantitative analysis of brain iron deposition. We aimed to compare the difference of brain iron deposition in the gray matter nucleus between T2DM patients and healthy elderly individuals using QSM. Methods Thirty-two T2DM patients and thirty-two age- and gender-matched healthy controls (HCs) were enrolled in this research. Twenty-three patients and twenty-six HCs underwent cognitive assessments. Brain QSM maps were computed from multiecho GRE data using morphology-enabled dipole inversion with automatic uniform cerebrospinal fluid zero reference algorithm (MEDI+0). ITK-SNAP was used to measure the susceptibility values reflecting the content of iron in the regions of interest (ROIs). Results The study included thirty-two T2DM patients (20 males and 12 females; mean age of 61.09 ± 9.99 years) and 32 HCs (14 males and 18 females; mean age of 59.09 ± 9.77 years). These participants had no significant difference in age or gender (P > 0.05). Twenty-three patients with T2DM (11 males and 12 females; mean age, 64.65 ± 8.44 years) and twenty-six HCs (14 males and 12 females; mean age, 62.30 ± 6.13 years) received an assessment of cognitive function. T2DM patients exhibited an obviously (t = 3.237, P = 0.003) lower Montreal Cognitive Assessment (MoCA) score (26.78 ± 2.35; HCs, 28.42 ± 0.64; normal standard ≥26) and a higher Stroop color-word test (SCWT)-C score [87(65,110); HC, 63(60,76.75), Z = −2.232, P = 0.003] than HCs. The mean susceptibility values in the putamen appeared obviously higher in T2DM patients than in HCs (t = −3.994, P < 0.001). The susceptibility values and cognitive assessment scores showed no obvious association (P > 0.05). However, an obvious correlation was observed between the changes in the susceptibility values in the putamen and the thalamus/dentate nucleus (r = 0.404, P < 0.001; r = 0.423, P < 0.001). Conclusion T2DM patients showed increased susceptibility values in the putamen and had declines in executive functions, but the linear association between them was not statistically significant. Changes in susceptibility values in the putamen indicated increased iron deposition and might be used as a quantitative imaging marker of central nervous system injury in T2DM patients. QSM might be able to help probe micro neuronal damage in gray matter and provide information on diabetic encephalopathy.