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.

Longitudinal Associations of Magnetic Susceptibility with Clinical Severity in Parkinson's Disease.

BACKGROUND: Dementia is common in Parkinson's disease (PD), but there is wide variation in its timing. A critical gap in PD research is the lack of quantifiable markers of progression, and methods to identify early stages of dementia. Atrophy-based magnetic resonance imaging (MRI) has limited sensitivity in detecting or tracking changes relating to PD dementia, but quantitative susceptibility mapping (QSM), sensitive to brain tissue iron, shows potential for these purposes. OBJECTIVE: The objective of the paper is to study, for the first time, the longitudinal relationship between cognition and QSM in PD in detail. METHODS: We present a longitudinal study of clinical severity in PD using QSM, including 59 PD patients (without dementia at study onset), and 22 controls over 3 years. RESULTS: In PD, increased baseline susceptibility in the right temporal cortex, nucleus basalis of Meynert, and putamen was associated with greater cognitive severity after 3 years; and increased baseline susceptibility in basal ganglia, substantia nigra, red nucleus, insular cortex, and dentate nucleus was associated with greater motor severity after 3 years. Increased follow-up susceptibility in these regions was associated with increased follow-up cognitive and motor severity, with further involvement of hippocampus relating to cognitive severity. However, there were no consistent increases in susceptibility over 3 years. CONCLUSIONS: Our study suggests that QSM may predict changes in cognitive severity many months prior to overt cognitive involvement in PD. However, we did not find robust longitudinal changes in QSM over the course of the study. Additional tissue metrics may be required together with QSM for it to monitor progression in clinical practice and therapeutic trials. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Quantitative susceptibility mapping identifies hippocampal and other subcortical grey matter tissue composition changes in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is associated with widespread brain alterations. Using quantitative susceptibility mapping (QSM) alongside transverse relaxation rate ( R 2 * ), we investigated regional brain susceptibility changes in 36 patients with left-sided (LTLE) or right-sided TLE (RTLE) secondary to hippocampal sclerosis, and 27 healthy controls (HC). We compared three susceptibility calculation methods to ensure image quality. Correlations of susceptibility and R 2 * with age of epilepsy onset, frequency of focal-to-bilateral tonic-clonic seizures (FBTCS), and neuropsychological test scores were examined. Weak-harmonic QSM (WH-QSM) successfully reduced noise and removed residual background field artefacts. Significant susceptibility increases were identified in the left putamen in the RTLE group compared to the LTLE group, the right putamen and right thalamus in the RTLE group compared to HC, and a significant susceptibility decrease in the left hippocampus in LTLE versus HC. LTLE patients who underwent epilepsy surgery showed significantly lower left-versus-right hippocampal susceptibility. Significant R 2 * changes were found between TLE and HC groups in the amygdala, putamen, thalamus, and in the hippocampus. Specifically, decreased R2 * was found in the left and right hippocampus in LTLE and RTLE, respectively, compared to HC. Susceptibility and R 2 * were significantly correlated with cognitive test scores in the hippocampus, globus pallidus, and thalamus. FBTCS frequency correlated positively with ipsilateral thalamic and contralateral putamen susceptibility and with R 2 * in bilateral globi pallidi. Age of onset was correlated with susceptibility in the hippocampus and putamen, and with R 2 * in the caudate. Susceptibility and R 2 * changes observed in TLE groups suggest selective loss of low-myelinated neurons alongside iron redistribution in the hippocampi, predominantly ipsilaterally, indicating QSM's sensitivity to local pathology. Increased susceptibility and R 2 * in the thalamus and putamen suggest increased iron content and reflect disease severity.

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 quantitative susceptibility mapping (QSM) for clinical brain research. It is a consensus of the ISMRM 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 give rise to the need in the neuroimaging community for guidelines on implementation. This article describes relevant considerations and provides specific implementation recommendations for all steps in QSM data acquisition, processing, analysis, and presentation in scientific publications. We recommend that data be acquired using a monopolar 3D multi-echo GRE sequence, that phase images be saved and exported in DICOM format and unwrapped using an exact unwrapping approach. Multi-echo images should be combined before background removal, and a brain mask created using a brain extraction tool with the incorporation of phase-quality-based masking. Background fields should be removed within the brain mask 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 whole brain as a region of interest in the analysis, and QSM results should be reported with - as a minimum - the acquisition and processing specifications listed in the last section of the article. These recommendations should facilitate clinical QSM research and lead to increased harmonization in data acquisition, analysis, and reporting.

Incomplete spectrum QSM using support information.

Introduction: Reconstructing a bounded object from incomplete k-space data is a well posed problem, and it was recently shown that this incomplete spectrum approach can be used to reconstruct undersampled MRI images with similar quality to compressed sensing approaches. Here, we apply this incomplete spectrum approach to the field-to-source inverse problem encountered in quantitative magnetic susceptibility mapping (QSM). The field-to-source problem is an ill-posed problem because of conical regions in frequency space where the dipole kernel is zero or very small, which leads to the kernel's inverse being ill-defined. These "ill-posed" regions typically lead to streaking artifacts in QSM reconstructions. In contrast to compressed sensing, our approach relies on knowledge of the image-space support, more commonly referred to as the mask, of our object as well as the region in k-space with ill-defined values. In the QSM case, this mask is usually available, as it is required for most QSM background field removal and reconstruction methods. Methods: We tuned the incomplete spectrum method (mask and band-limit) for QSM on a simulated dataset from the most recent QSM challenge and validated the QSM reconstruction results on brain images acquired in five healthy volunteers, comparing incomplete spectrum QSM to current state-of-the art-methods: FANSI, nonlinear dipole inversion, and conventional thresholded k-space division. Results: Without additional regularization, incomplete spectrum QSM performs slightly better than direct QSM reconstruction methods such as thresholded k-space division (PSNR of 39.9 vs. 39.4 of TKD on a simulated dataset) and provides susceptibility values in key iron-rich regions similar or slightly lower than state-of-the-art algorithms, but did not improve the PSNR in comparison to FANSI or nonlinear dipole inversion. With added (ℓ1-wavelet based) regularization the new approach produces results similar to compressed sensing based reconstructions (at sufficiently high levels of regularization). Discussion: Incomplete spectrum QSM provides a new approach to handle the "ill-posed" regions in the frequency-space data input to QSM.

Brain volume in Tanzanian children with sickle cell anaemia: A neuroimaging study.

Brain injury is a common complication of sickle cell anaemia (SCA). White matter (WM) and cortical and subcortical grey matter (GM), structures may have reduced volume in patients with SCA. This study focuses on whether silent cerebral infarction (SCI), vasculopathy or anaemia affects WM and regional GM volumes in children living in Africa. Children with SCA (n = 144; aged 5-20 years; 74 male) and sibling controls (n = 53; aged 5-17 years; 29 male) underwent magnetic resonance imaging. Effects of SCI (n = 37), vasculopathy (n = 15), and haemoglobin were assessed. Compared with controls, after adjusting for age, sex and intracranial volume, patients with SCA had smaller volumes for WM and cortical, subcortical and total GM, as well as bilateral cerebellar cortex, globus pallidus, amygdala and right thalamus. Left globus pallidus volume was further reduced in patients with vasculopathy. Putamen and hippocampus volumes were larger in patients with SCA without SCI or vasculopathy than in controls. Significant positive effects of haemoglobin on regional GM volumes were confined to the controls. Patients with SCA generally have reduced GM volumes compared with controls, although some subcortical regions may be spared. SCI and vasculopathy may affect the trajectory of change in subcortical GM and WM volume. Brain volume in non-SCA children may be vulnerable to contemporaneous anaemia.

Investigating the effect of oblique image acquisition on the accuracy of QSM and a robust tilt correction method.

PURPOSE: Quantitative susceptibility mapping (QSM) is used increasingly for clinical research where oblique image acquisition is commonplace, but its effects on QSM accuracy are not well understood. THEORY AND METHODS: The QSM processing pipeline involves defining the unit magnetic dipole kernel, which requires knowledge of the direction of the main magnetic field B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ with respect to the acquired image volume axes. The direction of B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ is dependent on the axis and angle of rotation in oblique acquisition. Using both a numerical brain phantom and in vivo acquisitions in 5 healthy volunteers, we analyzed the effects of oblique acquisition on magnetic susceptibility maps. We compared three tilt-correction schemes at each step in the QSM pipeline: phase unwrapping, background field removal and susceptibility calculation, using the RMS error and QSM-tuned structural similarity index. RESULTS: Rotation of wrapped phase images gave severe artifacts. Background field removal with projection onto dipole fields gave the most accurate susceptibilities when the field map was first rotated into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ . Laplacian boundary value and variable-kernel sophisticated harmonic artifact reduction for phase data background field removal methods gave accurate results without tilt correction. For susceptibility calculation, thresholded k-space division, iterative Tikhonov regularization, and weighted linear total variation regularization, all performed most accurately when local field maps were rotated into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ before susceptibility calculation. CONCLUSION: For accurate QSM, oblique acquisition must be taken into account. Rotation of images into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ should be carried out after phase unwrapping and before background-field removal. We provide open-source tilt-correction code to incorporate easily into existing pipelines: https://github.com/o-snow/QSM_TiltCorrection.git.

Quantitative susceptibility mapping (QSM) and R2* of silent cerebral infarcts in sickle cell anemia.

Silent cerebral infarction (SCI) is the most commonly reported radiological abnormality in patients with sickle cell anemia (SCA) and is associated with future clinical stroke risk. To date, there have been few histological and quantitative MRI studies of SCI and multiple radiological definitions exist. As a result, the tissue characteristics and composition of SCI remain elusive. The objective of this work was therefore to investigate the composition of segmented SCI lesions using quantitative MRI for R 2 * and quantitative magnetic susceptibility mapping (QSM). 211 SCI lesions were segmented from 32 participants with SCA and 6 controls. SCI were segmented according to two definitions (FLAIR+/-T1w-based threshold) using a semi-automated pipeline. Magnetic susceptibility (χ) and R 2 * maps were calculated from a multi-echo gradient echo sequence and mean SCI values were compared to an equivalent region of interest in normal appearing white matter (NAWM). SCI χ and R 2 * were investigated as a function of SCI definition, patient demographics, anatomical location, and cognition. Compared to NAWM, SCI were significantly less diamagnetic (χ = -0.0067 ppm vs. -0.0153 ppm, p < 0.001) and had significantly lower R 2 * (16.7 s-1 vs. 19.2 s-1, p < 0.001). SCI definition had a significant effect on the mean SCI χ and R 2 * , with lesions becoming significantly less diamagnetic and having significantly lower R 2 * after the application of a more stringent T1w-based threshold. SCI-NAWM R 2 * decrease was significantly greater in patients with SCA compared with controls (-2.84 s-1 vs. -0.64 s-1, p < 0.0001). No significant association was observed between mean SCI-NAWM χ or R2* differences and subject age, lesion anatomical location, or cognition. The increased χ and decreased R 2 * in SCI relative to NAWM observed in both patients and controls is indicative of lower myelin or increased water content within the segmented lesions. The significant SCI-NAWM R 2 * differences observed between SCI in patients with SCA and controls suggests there may be differences in tissue composition relative to NAWM in SCI in the two populations. Quantitative MRI techniques such as QSM and R 2 * mapping can be used to enhance our understanding of the pathophysiology and composition of SCI in patients with SCA as well as controls.

A Comparison of MRI Quantitative Susceptibility Mapping and TRUST-Based Measures of Brain Venous Oxygen Saturation in Sickle Cell Anaemia.

In recent years, interest has grown in the potential for magnetic resonance imaging (MRI) measures of venous oxygen saturation (Yv) to improve neurological risk prediction. T2-relaxation-under-spin-tagging (TRUST) is an MRI technique which has revealed changes in Yv in patients with sickle cell anemia (SCA). However, prior studies comparing Yv in patients with SCA relative to healthy controls have reported opposing results depending on whether the calibration model, developed to convert blood T2 to Yv, is based on healthy human hemoglobin (HbA), bovine hemoglobin (HbBV) or sickle hemoglobin (HbS). MRI Quantitative Susceptibility Mapping (QSM) is an alternative technique that may hold promise for estimating Yv in SCA as blood magnetic susceptibility is linearly dependent upon Yv, and no significant difference has been found between the magnetic susceptibility of HbA and HbS. Therefore, the aim of this study was to compare estimates of Yv using QSM and TRUST with five published calibration models in healthy controls and patients with SCA. 17 patients with SCA and 13 healthy controls underwent MRI. Susceptibility maps were calculated from a multi-parametric mapping acquisition and Yv was calculated from the mean susceptibility in a region of interest in the superior sagittal sinus. TRUST estimates of T2, within a similar but much smaller region, were converted to Yv using five different calibration models. Correlation and Bland-Altman analyses were performed to compare estimates of Yv between TRUST and QSM methods. For each method, t-tests were also used to explore group-wise differences between patients with SCA and healthy controls. In healthy controls, significant correlations were observed between QSM and TRUST measures of Yv, while in SCA, there were no such correlations. The magnitude and direction of group-wise differences in Yv varied with method. The TRUST-HbBV and QSM methods suggested decreased Yv in SCA relative to healthy controls, while the TRUST-HbS (p < 0.01) and TRUST-HbA models suggested increased Yv in SCA as in previous studies. Further validation of all MRI measures of Yv, relative to ground truth measures such as O15 PET and jugular vein catheterization, is required in SCA before QSM or TRUST methods can be considered for neurological risk prediction.

Multi-echo quantitative susceptibility mapping: how to combine echoes for accuracy and precision at 3 Tesla.

PURPOSE: To compare different multi-echo combination methods for MRI QSM. Given the current lack of consensus, we aimed to elucidate how to optimally combine multi-echo gradient-recalled echo signal phase information, either before or after applying Laplacian-base methods (LBMs) for phase unwrapping or background field removal. METHODS: Multi-echo gradient-recalled echo data were simulated in a numerical head phantom, and multi-echo gradient-recalled echo images were acquired at 3 Tesla in 10 healthy volunteers. To enable image-based estimation of gradient-recalled echo signal noise, 5 volunteers were scanned twice in the same session without repositioning. Five QSM processing pipelines were designed: 1 applied nonlinear phase fitting over TEs before LBMs; 2 applied LBMs to the TE-dependent phase and then combined multiple TEs via either TE-weighted or SNR-weighted averaging; and 2 calculated TE-dependent susceptibility maps via either multi-step or single-step QSM and then combined multiple TEs via magnitude-weighted averaging. Results from different pipelines were compared using visual inspection; summary statistics of susceptibility in deep gray matter, white matter, and venous regions; phase noise maps (error propagation theory); and, in the healthy volunteers, regional fixed bias analysis (Bland-Altman) and regional differences between the means (nonparametric tests). RESULTS: Nonlinearly fitting the multi-echo phase over TEs before applying LBMs provided the highest regional accuracy of χ $$ \chi $$ and the lowest phase noise propagation compared to averaging the LBM-processed TE-dependent phase. This result was especially pertinent in high-susceptibility venous regions. CONCLUSION: For multi-echo QSM, we recommend combining the signal phase by nonlinear fitting before applying LBMs.

Planning of gamma knife radiosurgery (GKR) for brain arteriovenous malformations using triple magnetic resonance angiography (triple-MRA).

PURPOSE: Intra-arterial Digital Subtraction Angiography (DSA) is the gold standard technique for radiosurgery target delineation in brain Arterio-Venous Malformations (AVMs). This study aims to evaluate whether a combination of three Magnetic Resonance Angiography sequences (triple-MRA) could be used for delineation of brain AVMs for Gamma Knife Radiosurgery (GKR). METHODS: Fifteen patients undergoing DSA for GKR targeting of brain AVMs also underwent triple-MRA: 4D Arterial Spin Labelling based angiography (ASL-MRA), Contrast-Enhanced Time-Resolved MRA (CE-MRA) and High Definition post-contrast Time-Of-Flight angiography (HD-TOF). The arterial phase of the AVM nidus was delineated on triple-MRA by an interventional neuroradiologist and a consultant neurosurgeon (triple-MRA volume). Triple-MRA volumes were compared to AVM targets delineated by the clinical team for delivery of GKR using the current planning paradigm, i.e., stereotactic DSA and volumetric MRI (DSA volume). Difference in size, degree of inclusion (DI) and concordance index (CcI) between DSA and triple-MRA volumes are reported. RESULTS: AVM target volumes delineated on triple-MRA were on average 9.8% smaller than DSA volumes (95%CI:5.6-13.9%; SD:7.14%; p = .003). DI of DSA volume in triple-MRA volume was on average 73.5% (95%CI:71.2-76; range: 65-80%). The mean percentage of triple-MRA volume not included on DSA volume was 18% (95%CI:14.7-21.3; range: 7-30%). CONCLUSION: The technical feasibility of using triple-MRA for visualisation and delineation of brain AVMs for GKR planning has been demonstrated. Tighter and more precise delineation of AVM target volumes could be achieved by using triple-MRA for radiosurgery targeting. However, further research is required to ascertain the impact this may have in obliteration rates and side effects.

Investigating the effect of flow compensation and quantitative susceptibility mapping method on the accuracy of venous susceptibility measurement.

Quantitative susceptibility mapping (QSM) is a promising non-invasive method for obtaining information relating to oxygen metabolism. However, the optimal acquisition sequence and QSM reconstruction method for reliable venous susceptibility measurements are unknown. Full flow compensation is generally recommended to correct for the influence of venous blood flow, although the effect of flow compensation on the accuracy of venous susceptibility values has not been systematically evaluated. In this study, we investigated the effect of different acquisition sequences, including different flow compensation schemes, and different QSM reconstruction methods on venous susceptibilities. Ten healthy subjects were scanned with five or six distinct QSM sequence designs using monopolar readout gradients and different flow compensation schemes. All data sets were processed using six different QSM pipelines and venous blood susceptibility was evaluated in whole-brain segmentations of the venous vasculature and single veins. The quality of vein segmentations and the accuracy of venous susceptibility values were analyzed and compared between all combinations of sequences and reconstruction methods. The influence of the QSM reconstruction method on average venous susceptibility values was found to be 2.7-11.6 times greater than the influence of the acquisition sequence, including flow compensation. The majority of the investigated QSM reconstruction methods tended to underestimate venous susceptibility values in the vein segmentations that were obtained. In summary, we found that multi-echo gradient-echo acquisition sequences without full flow compensation yielded venous susceptibility values comparable to sequences with full flow compensation. However, the QSM reconstruction method had a great influence on susceptibility values and thus needs to be selected carefully for accurate venous QSM.

Quantitative susceptibility mapping of carotid arterial tissue ex vivo: Assessing sensitivity to vessel microstructural composition.

PURPOSE: To characterize microstructural contributions to the magnetic susceptibility of carotid arteries. METHOD: Arterial vessels were scanned using high-resolution quantitative susceptibility mapping (QSM) at 7 Tesla. Models of vessel degradation were generated using ex vivo porcine carotid arteries that were subjected to several different enzymatic digestion treatments that selectively removed microstructural components (smooth muscle cells, collagen, and elastin). Magnetic susceptibilities measured in these tissue models were compared to those in untreated (native) porcine arteries. Magnetic susceptibility measured in native porcine carotid arteries was further compared to the susceptibility of cadaveric human carotid arteries to investigate their similarity. RESULTS: The magnetic susceptibility of native porcine vessels was diamagnetic (χnative = -0.1820 ppm), with higher susceptibilities in all models of vessel degradation (χelastin-degraded = -0.0163 ppm; χcollagen-degraded = -0.1158 ppm; χdecellularized = -0.1379 ppm; χfixed native = -0.2199 ppm). Magnetic susceptibility was significantly higher in collagen-degraded compared to native porcine vessels (Tukey-Kramer, P < .01) and between elastin-degraded and all other models (including native, Tukey-Kramer, P < .001). The susceptibility of fixed healthy human arterial tissue was diamagnetic, and no significant difference was found between fixed human and fixed porcine arterial tissue susceptibilities (analysis of variance, P > .05). CONCLUSIONS: Magnetic susceptibility measured using QSM is sensitive to the microstructural composition of arterial vessels-most notably to collagen. The similarity of human and porcine arterial tissue susceptibility values provides a solid basis for translational studies. Because vessel microstructure becomes disrupted during the onset and progression of carotid atherosclerosis, QSM has the potential to provide a sensitive and specific marker of vessel disease.

Quantitative MRI susceptibility mapping reveals cortical signatures of changes in iron, calcium and zinc in malformations of cortical development in children with drug-resistant epilepsy.

OBJECTIVE: Malformations of cortical development (MCD), including focal cortical dysplasia (FCD), are the most common cause of drug-resistant focal epilepsy in children. Histopathological lesion characterisation demonstrates abnormal cell types and lamination, alterations in myelin (typically co-localised with iron), and sometimes calcification. Quantitative susceptibility mapping (QSM) is an emerging MRI technique that measures tissue magnetic susceptibility (χ) reflecting it's mineral composition. We used QSM to investigate abnormal tissue composition in a group of children with focal epilepsy with comparison to effective transverse relaxation rate (R2*) and Synchrotron radiation X-ray fluorescence (SRXRF) elemental maps. Our primary hypothesis was that reductions in χ would be found in FCD lesions, resulting from alterations in their iron and calcium content. We also evaluated deep grey matter nuclei for changes in χ with age. METHODS: QSM and R2* maps were calculated for 40 paediatric patients with suspected MCD (18 histologically confirmed) and 17 age-matched controls. Patients' sub-groups were defined based on concordant electro-clinical or histopathology data. Quantitative investigation of QSM and R2* was performed within lesions, using a surface-based approach with comparison to homologous regions, and within deep brain regions using a voxel-based approach with regional values modelled with age and epilepsy as covariates. Synchrotron radiation X-ray fluorescence (SRXRF) was performed on brain tissue resected from 4 patients to map changes in iron, calcium and zinc and relate them to MRI parameters. RESULTS: Compared to fluid-attenuated inversion recovery (FLAIR) or T1-weighted imaging, QSM improved lesion conspicuity in 5% of patients. In patients with well-localised lesions, quantitative profiling demonstrated decreased χ, but not R2*, across cortical depth with respect to the homologous regions. Contra-lateral homologous regions additionally exhibited increased χ at 2-3 mm cortical depth that was absent in lesions. The iron decrease measured by the SRXRF in FCDIIb lesions was in agreement with myelin reduction observed by Luxol Fast Blue histochemical staining. SRXRF analysis in two FCDIIb tissue samples showed increased zinc and calcium in one patient, and decreased iron in the brain region exhibiting low χ and high R2* in both patients. QSM revealed expected age-related changes in the striatum nuclei, substantia nigra, sub-thalamic and red nucleus. CONCLUSION: QSM non-invasively revealed cortical/sub-cortical tissue alterations in MCD lesions and in particular that χ changes in FCDIIb lesions were consistent with reduced iron, co-localised with low myelin and increased calcium and zinc content. These findings suggest that measurements of cortical χ could be used to characterise tissue properties non-invasively in epilepsy lesions.

Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson's disease.

The mechanisms responsible for the selective vulnerability of specific neuronal populations in Parkinson's disease are poorly understood. Oxidative stress secondary to brain iron accumulation is one postulated mechanism. We measured iron deposition in 180 cortical regions of 96 patients with Parkinson's disease and 35 control subjects using quantitative susceptibility mapping. We estimated the expression of 15 745 genes in the same regions using transcriptomic data from the Allen Human Brain Atlas. Using partial least squares regression, we then identified the profile of gene transcription in the healthy brain that underlies increased cortical iron in patients with Parkinson's disease relative to controls. Applying gene ontological tools, we investigated the biological processes and cell types associated with this transcriptomic profile and identified the sets of genes with spatial expression profiles in control brains that correlated significantly with the spatial pattern of cortical iron deposition in Parkinson's disease. Gene ontological analyses revealed that these genes were enriched for biological processes relating to heavy metal detoxification, synaptic function and nervous system development and were predominantly expressed in astrocytes and glutamatergic neurons. Furthermore, we demonstrated that the genes differentially expressed in Parkinson's disease are associated with the pattern of cortical expression identified in this study. Our findings provide mechanistic insights into regional selective vulnerabilities in Parkinson's disease, particularly the processes involving iron accumulation.

Phase unwrapping with a rapid opensource minimum spanning tree algorithm (ROMEO).

PURPOSE: To develop a rapid and accurate MRI phase-unwrapping technique for challenging phase topographies encountered at high magnetic fields, around metal implants, or postoperative cavities, which is sufficiently fast to be applied to large-group studies including Quantitative Susceptibility Mapping and functional MRI (with phase-based distortion correction). METHODS: The proposed path-following phase-unwrapping algorithm, ROMEO, estimates the coherence of the signal both in space-using MRI magnitude and phase information-and over time, assuming approximately linear temporal phase evolution. This information is combined to form a quality map that guides the unwrapping along a 3D path through the object using a computationally efficient minimum spanning tree algorithm. ROMEO was tested against the two most commonly used exact phase-unwrapping methods, PRELUDE and BEST PATH, in simulated topographies and at several field strengths: in 3T and 7T in vivo human head images and 9.4T ex vivo rat head images. RESULTS: ROMEO was more reliable than PRELUDE and BEST PATH, yielding unwrapping results with excellent temporal stability for multi-echo or multi-time-point data. It does not require image masking and delivers results within seconds, even in large, highly wrapped multi-echo data sets (eg, 9 seconds for a 7T head data set with 31 echoes and a 208 × 208 × 96 matrix size). CONCLUSION: Overall, ROMEO was both faster and more accurate than PRELUDE and BEST PATH, delivering exact results within seconds, which is well below typical image acquisition times, enabling potential on-console application.

Quantitative susceptibility mapping of the rat brain after traumatic brain injury.

The primary lesion arising from the initial insult after traumatic brain injury (TBI) triggers a cascade of secondary tissue damage, which may also progress to connected brain areas in the chronic phase. The aim of this study was, therefore, to investigate variations in the susceptibility distribution related to these secondary tissue changes in a rat model after severe lateral fluid percussion injury. We compared quantitative susceptibility mapping (QSM) and R2 * measurements with histological analyses in white and grey matter areas outside the primary lesion but connected to the lesion site. We demonstrate that susceptibility variations in white and grey matter areas could be attributed to reduction in myelin, accumulation of iron and calcium, and gliosis. QSM showed quantitative changes attributed to secondary damage in areas located rostral to the lesion site that appeared normal in R2 * maps. However, combination of QSM and R2 * was informative in disentangling the underlying tissue changes such as iron accumulation, demyelination, or calcifications. Therefore, combining QSM with R2 * measurement can provide a more detailed assessment of tissue changes and may pave the way for improved diagnosis of TBI, and several other complex neurodegenerative diseases.

An optimized and highly repeatable MRI acquisition and processing pipeline for quantitative susceptibility mapping in the head-and-neck region.

PURPOSE: Quantitative Susceptibility Mapping (QSM) is an emerging technique sensitive to disease-related changes including oxygenation. It is extensively used in brain studies and has increasing clinical applications outside the brain. Here we present the first MRI acquisition protocol and QSM pipeline optimized for the head-and-neck region together with a repeatability analysis performed in healthy volunteers. METHODS: We investigated both the intrasession and the intersession repeatability of the optimized method in 10 subjects. We also implemented two, Tikhonov-regularisation-based susceptibility calculation techniques that were found to have higher contrast-to-noise than existing methods in the head-and-neck region. Repeatability was evaluated by calculating the distributions of susceptibility differences between repeated scans and the corresponding minimum detectable effect sizes (MDEs). RESULTS: Deep brain regions had higher QSM repeatability than neck regions. As expected, intrasession repeatability was generally better than intersession repeatability. Susceptibility maps calculated using projection onto dipole fields for background field removal were more repeatable than using the Laplacian boundary value method in the head-and-neck region. Small (short-axis diameter <5 mm) lymph nodes had the lowest repeatability (MDE = 0.27 ppm) as imperfect segmentation included some of the surrounding paramagnetic fatty fascia, highlighting the importance of accurate region delineation. MDEs in the larger lymph nodes (0.16 ppm), submandibular glands (0.10 ppm), and especially the parotid glands (0.06 ppm) were much lower, comparable to those of the brain regions. CONCLUSIONS: The high repeatability of the acquisition and pipeline optimized for QSM will facilitate clinical studies in the head-and-neck region.

Investigating the accuracy and precision of TE-dependent versus multi-echo QSM using Laplacian-based methods at 3 T.

PURPOSE: Multi-echo gradient-recalled echo acquisitions for QSM enable optimizing the SNR for several tissue types through multi-echo (TE) combination or investigating temporal variations in the susceptibility (potentially reflecting tissue microstructure) by calculating one QSM image at each TE (TE-dependent QSM). In contrast with multi-echo QSM, applying Laplacian-based methods (LBMs) for phase unwrapping and background field removal to single TEs could introduce nonlinear temporal variations (independent of tissue microstructure) into the measured susceptibility. Here, we aimed to compare the effect of LBMs on the QSM susceptibilities in TE-dependent versus multi-echo QSM. METHODS: TE-dependent recalled echo data simulated in a numerical head phantom and gradient-recalled echo images acquired at 3 T in 10 healthy volunteers. Several QSM pipelines were tested, including four distinct LBMs: sophisticated harmonic artifact reduction for phase data (SHARP), variable-radius sophisticated harmonic artifact reduction for phase data (V-SHARP), Laplacian boundary value background field removal (LBV), and one-step total generalized variation (TGV). Results from distinct pipelines were compared using visual inspection, summary statistics of susceptibility in deep gray matter/white matter/venous regions of interest, and, in the healthy volunteers, regional susceptibility bias analysis and nonparametric tests. RESULTS: Multi-echo versus TE-dependent QSM had higher regional accuracy, especially in high-susceptibility regions and at shorter TEs. Everywhere except in the veins, a processing pipeline incorporating TGV provided the most temporally stable TE-dependent QSM results with an accuracy similar to multi-echo QSM. CONCLUSIONS: For TE-dependent QSM, carefully choosing LBMs can minimize the introduction of LBM-related nonlinear temporal susceptibility variations.

PET/MRI attenuation estimation in the lung: A review of past, present, and potential techniques.

Positron emission tomography/magnetic resonance imaging (PET/MRI) potentially offers several advantages over positron emission tomography/computed tomography (PET/CT), for example, no CT radiation dose and soft tissue images from MR acquired at the same time as the PET. However, obtaining accurate linear attenuation correction (LAC) factors for the lung remains difficult in PET/MRI. LACs depend on electron density and in the lung, these vary significantly both within an individual and from person to person. Current commercial practice is to use a single-valued population-based lung LAC, and better estimation is needed to improve quantification. Given the under-appreciation of lung attenuation estimation as an issue, the inaccuracy of PET quantification due to the use of single-valued lung LACs, the unique challenges of lung estimation, and the emerging status of PET/MRI scanners in lung disease, a review is timely. This paper highlights past and present methods, categorizing them into segmentation, atlas/mapping, and emission-based schemes. Potential strategies for future developments are also presented.