Functional magnetic resonance imaging (fMRI) has opened new frontiers in neuroscience by instrumentally driving our understanding of brain function and development. Despite its substantial successes, fMRI studies persistently encounter obstacles stemming from inherent, unavoidable physiological confounds. The adverse effects of these confounds are especially noticeable with higher magnetic fields, which have been gaining momentum in fMRI experiments. This review focuses on the four major physiological confounds impacting fMRI studies: low-frequency fluctuations in both breathing depth and rate, low-frequency fluctuations in the heart rate, thoracic movements, and cardiac pulsatility. Over the past three decades, numerous correction techniques have emerged to address these challenges. Correction methods have effectively enhanced the detection of task-activated voxels and minimized the occurrence of false positives and false negatives in functional connectivity studies. While confound correction methods have merit, they also have certain limitations. For instance, model-based approaches require externally recorded physiological data that is often unavailable in fMRI studies. Methods reliant on independent component analysis, on the other hand, need prior knowledge about the number of components. Machine learning techniques, although showing potential, are still in the early stages of development and require additional validation. This article reviews the mechanics of physiological confound correction methods, scrutinizes their performance and limitations, and discusses their impact on fMRI studies.

Quantitative susceptibility mapping (QSM) is a post-processing magnetic resonance imaging (MRI) technique that extracts the distribution of tissue susceptibilities and holds significant promise in the study of neurological diseases. However, the ill-conditioned nature of dipole inversion often results in noise and artifacts during QSM reconstruction from the tissue field. Deep learning methods have shown great potential in addressing these issues; however, most existing approaches rely on basic U-net structures, leading to limited performances and reconstruction artifacts sometimes.

This study aims to develop a novel deep learning-based method, IR2QSM, for improving QSM reconstruction accuracy while mitigating noise and artifacts by leveraging a unique network architecture that enhances latent feature utilization.

IR2QSM, an advanced U-net architecture featuring four iterations of reverse concatenations and middle recurrent modules, was proposed to optimize feature fusion and improve QSM accuracy, and comparative experiments based on both simulated and in vivo datasets were carried out to compare IR2QSM with two traditional iterative methods (iLSQR, MEDI) and four recently proposed deep learning methods (U-net, xQSM, LPCNN, and MoDL-QSM).

In this work, IR2QSM outperformed all other methods in reducing artifacts and noise in QSM images. It achieved on average the lowest XSIM (84.81%) in simulations, showing improvements of 12.80%, 12.68%, 18.66%, 10.49%, 25.57%, and 19.78% over iLSQR, MEDI, U-net, xQSM, LPCNN, and MoDL-QSM, respectively, and yielded results with the least artifacts on the in vivo data and present the most visually appealing results. In the meantime, it successfully alleviated the over-smoothing and susceptibility underestimation in LPCNN results.

Overall, the proposed IR2QSM showed superior QSM results compared to iterative and deep learning-based methods, offering a more accurate QSM solution for clinical applications.

Myelin quantification is essential for understanding a wide range of neurodegenerative pathologies. Voxel-wise multicomponent T2 (mcT2) analysis is the common approach for this purpose, yet no gold standard technique exist that can overcome the ambiguity of fitting several T2 components to a single-voxel signal. This challenge is further exacerbated in preclinical scan settings due to the addition of spurious diffusion encoding, resulting from the use of imaging gradients that are at least an order of magnitude larger than on typical clinical scanners.

Assess the utility of a new data-driven approach for mcT2 analysis, which utilizes information from the entire tissue to analyze the signal from each voxel in healthy and demyelinated tissues. Specifically, this algorithm uses statistical analysis of the entire anatomy to identify tissue-specific multi-T2 signal combinations, and then uses these as basis-functions for voxel-wise mcT2 fitting.

Data-driven mcT2 analysis was performed on N = 7 cuprizone mice and N = 7 healthy mice. Myelin water fraction (MWF) values at six brain regions were evaluated. Correlation with reference immunohistochemical (IHC) staining for myelin basic protein was done in the corpus callosum. To demonstrate the added value of the data-driven approach the analysis was performed twice - with and without the data-driven preprocessing step.

Strong agreement was obtained between data-driven MWF values and histology. Applying the data-driven analysis prior to the voxel-wise fitting improved the mapping accuracy vs. non data-driven analysis, producing statistically significant separation between the two mice groups, good groupwise linear correlation with histology (cuprizone: R² = 0.64, p < 0.05, control: R2 = 0.61, p < 0.05), and addressed the inherent ambiguity, characterizing conventional mcT2 fitting.

The proposed data-driven algorithm provides a reliable tool for mapping myelin content on preclinical scanners, allowing precise classification between healthy and demyelinated tissues in cuprizone mouse model of multiple sclerosis.

Quantitative susceptibility mapping (QSM) is an advanced MRI technique for assessing iron, calcium, and myelin tissue levels based on magnetic susceptibility. QSM consists of multiple processing steps, with various choices for each step. While QSM is increasingly applied in neurodegenerative disease research, its reproducibility and sensitivity in detecting susceptibility changes across groups or over time, which underpin the interpretation of clinical outcomes, have not been thoroughly quantified. This study aimed to evaluate how choices in background field removal (BFR), dipole inversion algorithms, and anatomical referencing impact the detection of changes in deep gray matter susceptibility. We used aging-related changes in brain iron, established in earlier foundational studies, as a surrogate model to test the sensitivity and reproducibility of 378 different QSM pipelines toward the detection of longitudinal susceptibility changes in a clinical setting. We used 10-year follow-up data and scan-rescan data of healthy adults scanned at 3T. Our results demonstrated high variability in the sensitivity of QSM pipelines toward detecting susceptibility changes. While most pipelines detected the same over-time changes, the choice of the BFR algorithm and the referencing strategy influenced reproducibility error and sensitivity substantially. Notably, pipelines using RESHARP with AMP-PE, HEIDI, or LSQR inversion showed the highest overall sensitivity. The findings suggest a strong impact of algorithmic choices in QSM processing on the ability to detect physiological changes in the brain. Careful consideration should be given to the pipeline configuration for reliable clinical outcomes.

Epilepsy, a neurological disorder marked by recurrent, unprovoked seizures, is often linked to dysregulated iron metabolism, resulting in iron overload and subsequent cellular dysfunction or death within epileptogenic regions. We proposed a specific, noninvasive technique using paramagnetic susceptibility imaging via magnetic resonance imaging to quantify in vivo brain iron levels, aiming to enhance our understanding of epilepsy pathology and improve diagnostic accuracy. Our imaging and histopathological studies demonstrated that paramagnetic susceptibility is a sensitive biomarker for iron quantification in epilepsy. This method effectively detects iron abnormality from various causes and highlights that iron alters within epileptogenic zones, indicating the presence of potentially salvageable tissue. Furthermore, iron accumulation was observed to disrupt cortical laminar structures in epileptogenic zones and was associated with the proliferation of central nervous system cells, particularly astrocytes. Paramagnetic susceptibility imaging provides previously unknown insights into epilepsy, offering potential applications in diagnostics, monitoring, and personalized treatment strategies.

A recently introduced quantitative susceptibility mapping (QSM) technique, χ-separation, offers the capability to separate paramagnetic (χpara) and diamagnetic (χdia) susceptibility distribution within the brain. In-vivo high-resolution mapping of iron and myelin distribution, estimated by χ-separation, could provide a deeper understanding of brain substructures, assisting the investigation of their functions and alterations. This can be achieved using 7T MRI, which benefits from a high signal-to-noise ratio and susceptibility effects. However, applying χ-separation at 7T presents difficulties due to the requirement of an R2 map, coupled with issues such as high specific absorption rate (SAR), large B1 transmit field inhomogeneities, and prolonged scan time. To address these challenges, we developed a novel deep neural network, R2PRIMEnet7T, designed to convert a 7T R2* map into a 3T R2' map. Building on this development, we present a new pipeline for χ-separation at 7T, enabling us to generate high-resolution χ-separation maps from multi-echo gradient-echo data. The proposed method is compared with alternative pipelines, such as an end-to-end network and linearly-scaled R2', and is validated against χ-separation maps at 3T, demonstrating its accuracy. The 7T χ-separation maps generated by the proposed method exhibit similar contrasts to those from 3T, while 7T high-resolution maps offer enhanced clarity and detail. Quantitative analysis confirms that the proposed method surpasses the alternative pipelines. The proposed method results well delineate the detailed brain structures associated with iron and myelin. This new pipeline holds promise for analyzing iron and myelin concentration changes in various neurodegenerative diseases through precise structural examination.

Magnetic resonance imaging (MRI) is a cornerstone of non-invasive diagnostics and treatment monitoring, particularly for diseases of the central nervous system. Although 1.5- and 3 Tesla (T) field strengths remain the clinical standard, the advent of 7 T MRI represents a transformative step forward, offering superior spatial resolution, contrast, and sensitivity for visualizing neuroanatomy, metabolism, and function. Recent innovations, including parallel transmission and deep learning-based reconstruction, have resolved many prior technical challenges of 7 T MRI, enabling its routine clinical use. This review examines the diagnostic impact, patient value, and practical considerations of 7 T MRI, emphasizing its role in facilitating earlier diagnoses and improving care in conditions, such as amyotrophic lateral sclerosis (ALS), epilepsy, multiple sclerosis (MS), dementia, parkinsonism, tumors, and vascular diseases. Based on insights from over 1200 clinical scans with a second-generation 7 T system, the review highlights disease-specific biomarkers such as the motor band sign in ALS and the new diagnostic markers in MS, the central vein sign, and paramagnetic rim lesions. The unparalleled ability of 7 T MRI to study neurological diseases ex vivo at ultra-high resolution is also explored, offering new opportunities to understand pathophysiology and identify novel treatment targets. Additionally, the review provides a clinical perspective on patient handling and safety considerations, addressing challenges and practicalities associated with clinical 7 T MRI. By bridging research and clinical practice, 7 T MRI has the potential to redefine neuroimaging and advance the understanding and management of complex neurological disorders.

Nigrostriatal dopaminergic degeneration in alpha-synucleinopathies is indirectly reflected by low dopamine transporter (DaT) uptake through [123I]FP-CIT-SPECT. Bulk magnetic susceptibility (χ) in the substantia nigra, from MRI-based quantitative susceptibility mapping (QSM), is a potential biomarker of nigrostriatal degeneration, however, QSM cannot disentangle paramagnetic (e.g. iron) and diamagnetic (e.g. myelin) sources. Using the susceptibility source-separation technique DECOMPOSE, paramagnetic component susceptibility (PCS) and diamagnetic component susceptibility (DCS) were studied in prodromal and overt alpha-synucleinopathies, and their relationships with DaT-SPECT specific binding ratio (SBR) and clinical scores. 78 participants were included (23 controls, 30 prodromal and 25 overt alpha-synucleinopathies). Prodromal patients were subdivided into groups with positive or negative DaT-SPECT (SBR Z-scores below or above -1, respectively). Correlations of putamen and caudate SBR Z-scores with PCS and DCS in the substantia nigra, putamen, and caudate were investigated. Increased PCS was observed in the substantia nigra of prodromal alpha-synucleinopathy patients with positive DaT-SPECT compared to controls and prodromal patients with negative DaT-SPECT. SBR Z-scores in the putamen correlated with increased PCS in the substantia nigra and reduced |DCS| in the putamen, which may reflect dopaminergic degeneration ascribable to iron accumulation and nigrostriatal neuron axonal loss, respectively.

Magnetic susceptibility source separation (χ-separation), an advanced quantitative susceptibility mapping (QSM) method, enables the separate estimation of paramagnetic and diamagnetic susceptibility source distributions in the brain. Similar to QSM, it requires solving the ill-conditioned problem of dipole inversion, suffering from so-called streaking artifacts. Additionally, the method utilizes reversible transverse relaxation (R 2 ' = R 2 * - R 2 $$ {R}_2^{\prime }={R}_2^{\ast }-{R}_2 $$ ) to complement frequency shift information for estimating susceptibility source concentrations, requiring time-consuming data acquisition forR 2 $$ {R}_2 $$ (e.g., multi-echo spin-echo) in addition to multi-echo GRE data forR 2 * $$ {R}_2^{\ast } $$ . To address these challenges, we develop a new deep learning network, χ-sepnet, and propose two deep learning-based susceptibility source separation pipelines, χ-sepnet-R 2 ' $$ {R}_2^{\prime } $$ for inputs with multi-echo GRE and multi-echo spin-echo (or turbo spin-echo) and χ-sepnet-R 2 * $$ {R}_2^{\ast } $$ for input with multi-echo GRE only. The neural network is trained using multiple head orientation data that provide streaking artifact-free labels, generating high-quality χ-separation maps. The evaluation of the pipelines encompasses both qualitative and quantitative assessments in healthy subjects, and visual inspection of lesion characteristics in multiple sclerosis patients. The susceptibility source-separated maps of the proposed pipelines delineate detailed brain structures with substantially reduced artifacts compared to those from the conventional regularization-based reconstruction methods. In quantitative analysis, χ-sepnet-R 2 ' $$ {R}_2^{\prime } $$ achieves the best outcomes followed by χ-sepnet-R 2 * $$ {R}_2^{\ast } $$ , outperforming the conventional methods. When the lesions of multiple sclerosis patients are classified into subtypes, most lesions are identified as the same subtype in the maps from χ-sepnet-R 2 ' $$ {R}_2^{\prime } $$ and χ-sepnet-R 2 * $$ {R}_2^{\ast } $$ (paramagnetic susceptibility: 99.6% and diamagnetic susceptibility: 98.4%; both out of 250 lesions). The χ-sepnet-R 2 * $$ {R}_2^{\ast } $$ pipeline, which only requires multi-echo GRE data, has demonstrated its potential to offer broad clinical and scientific applications, although further evaluations for various diseases and pathological conditions are necessary.

The structural similarity index measure (SSIM) has become a popular quality metric to evaluate QSM in a way that is closer to human perception than RMS error (RMSE). However, SSIM may overpenalize errors in diamagnetic tissues and underpenalize them in paramagnetic tissues, resulting in biasing. In addition, extreme artifacts may compress the dynamic range, resulting in unrealistically high SSIM scores (hacking). To overcome biasing and hacking, we propose XSIM: SSIM implemented in the native QSM range, and with internal parameters optimized for QSM.

We used forward simulations from a COSMOS ground-truth brain susceptibility map included in the 2016 QSM Reconstruction Challenge to investigate the effect of QSM reconstruction errors on the SSIM, XSIM, and RMSE metrics. We also used these metrics to optimize QSM reconstructions of the in vivo challenge data set. We repeated this experiment with the QSM abdominal phantom. To validate the use of XSIM instead of SSIM for QSM quality assessment across a range of different reconstruction techniques/algorithms, we analyzed the reconstructions submitted to the 2019 QSM Reconstruction Challenge 2.0.

Our experiments confirmed the biasing and hacking effects on the SSIM metric applied to QSM. The XSIM metric was robust to those effects, penalizing the presence of streaking artifacts and reconstruction errors. Using XSIM to optimize QSM reconstruction regularization weights returned less overregularization than SSIM and RMSE.

XSIM is recommended over traditional SSIM to evaluate QSM reconstructions against a known ground truth, as it avoids biasing and hacking effects and provides a larger dynamic range of scores.

Quantitative Susceptibility Mapping (QSM) is a technique that derives tissue magnetic susceptibility distributions from phase measurements obtained through Magnetic Resonance (MR) imaging. This involves solving an ill-posed dipole inversion problem, however, and thus time-consuming and cumbersome data acquisition from several distinct head orientations becomes necessary to obtain an accurate solution. Most recent (supervised) deep learning methods for single-phase QSM require training data obtained via multiple orientations. In this work, we present an alternative unsupervised learning approach that can efficiently train on single-orientation measurement data alone, named ProxiMO (Proximal Multi-Operator), combining Learned Proximal Convolutional Neural Networks (LP-CNN) with multi-operator imaging (MOI). This integration enables LP-CNN training for QSM on single-phase data without ground truth reconstructions. We further introduce a semi-supervised variant, which further boosts the reconstruction performance, compared to the traditional supervised fashions. Extensive experiments on multicenter datasets illustrate the advantage of unsupervised training and the superiority of the proposed approach for QSM reconstruction. Code is available at https://github.com/shmuelor/ProxiMO.

Currently, two major magnetic resonance (MR) vendors provide commercial 7‑T scanners that are approved by the Food and Drug Administration (FDA) for clinical application. There is growing interest in ultrahigh-field MRI because of the improved clinical results in terms of morphological detail, as well as functional and metabolic imaging capabilities.

The 7‑T systems benefit from a higher signal-to-noise ratio, which scales supralinearly with field strength, a supralinear increase in the blood oxygenation level dependent (BOLD) contrast for functional MRI and susceptibility weighted imaging (SWI), and the chemical shift increases linearly with field strength with consequently higher spectral resolution.

In multiple sclerosis (MS), 7‑T imaging enables visualization of cortical lesions, the central vein sign, and paramagnetic rim lesions, which may be beneficial for the differential diagnosis between MS and other neuroinflammatory diseases in challenging and inconclusive clinical presentations and are seen as promising biomarkers for prognosis and treatment monitoring. The recent development of high-resolution proton MR spectroscopic imaging in clinically reasonable scan times has provided new insights into tumor metabolism and tumor grading as well as into early metabolic changes that may precede inflammatory processes in MS. This technique also improves the detection of epileptogenic foci in the brain. Multi-nuclear clinical applications, such as sodium imaging, have shown great potential for the evaluation of repair tissue quality after cartilage transplantation and in the monitoring of newly developed cartilage regenerative drugs for osteoarthritis.

For special clinical applications, such as SWI in MS, MR spectroscopic imaging in tumors, MS and epilepsy, and sodium imaging in cartilage repair, 7T may become a new standard.

Currently, there is still a lack of valuable neuroimaging markers to assess the clinical severity of stroke patients with small artery occlusion (SAO). Quantitative susceptibility mapping (QSM) is a quantitative processing method for neuroradiological diagnostics. Gray matter (GM) volume changes in stroke patients are also proved to be associated with neurological deficits. This study aims to explore the predictive value of QSM and GM volume in neurological deficits of patients with SAO.

As neurological deficits, the National Institutes of Health Stroke Scale (NIHSS) was used. Sixty-six SAO participants within 24 h of first onset were enrolled and divided into mild and moderate groups based on NIHSS. QSM values of infarct area and GM volume were calculated from magnetic resonance imaging (MRI) data. Two-sample t-tests were used to compare differences in QSM value and GM volume between the two groups, and the diagnostic efficacy of the combination of QSM value and GM volume was evaluated.

The results revealed both the QSM value and GM volume within the infarct area of the moderate group were lower compared to the mild group. Moderate group exhibited lower GM volume in some specific gyrus compared with mild group in the case of voxel-wise GM volume on whole-brain voxel level. The support vector machine (SVM) classifier's analysis showed a high power for the combination of QSM value, GM volume within the infarct area, and voxel-wise GM volume.

Our research first reported the combination of QSM value, GM volume within the infarct area, and voxel-wise GM volume could be used to predict neurological impairment of patients with SAO, which provides new insights for further understanding the SAO stroke.

Simultaneous positron emission tomography (PET)/magnetic resonance imaging provides concurrent information about anatomic, functional, and molecular changes in disease. We are developing a second generation MR-compatible RF-penetrable TOF-PET insert. The insert has a smaller scintillation crystal size and ring diameter compared to clinical whole-body PET scanners, resulting in higher spatial resolution and sensitivity. This paper reports the initial system performance of this full-ring PET insert. The global photopeak energy resolution and global coincidence time resolution, 11.74 ± 0.03 % FWHM and 238.1 ± 0.5 ps FWHM, respectively, are preserved as we scaled up the system to a full ring comprising 12, 288 LYSO-SiPM channels (crystal size: 3.2 × 3.2 × 20 mm3). Throughout a ten-hour experiment, the system performance remained stable, exhibiting a less than 1% change in all measured parameters. In a resolution phantom study, the system successfully resolved all 2.8 mm diameter rods, achieving an average VPR of 0.28 ± 0.08 without TOF and 0.24 ± 0.07 with TOF applied. Moreover, the implementation of TOF in the Hoffman phantom study also enhanced image quality. Initial MR compatibility studies of the full PET ring were performed with it unpowered as a milestone to focus on looking for material and geometry-related artifacts. During all MR studies, the MR body coil functioned as both the transmit and receive coil, and no observable artifacts were detected. As expected, using the body coil also as the RF receiver, MR image signal-to-noise ratio exhibited degradation (∼30%), so we are developing a high quality receive-only coil that resides inside the PET ring.

Deep grey matter pathology is a key driver of disability worsening in people with multiple sclerosis. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique which quantifies local magnetic susceptibility from variations in phase produced by changes in the local magnetic field. In the deep grey matter, susceptibility has previously been validated against tissue iron concentration. However, it currently remains unknown whether susceptibility is abnormal in older progressive MS cohorts, and whether it correlates with disability.

To investigate differences in mean regional susceptibility in deep grey matter between people with secondary progressive multiple sclerosis (SPMS) and healthy controls; to examine in patients the relationships between deep grey matter susceptibility and clinical and imaging measures of disease severity.

Baseline data from a subgroup of the MS-STAT2 trial (simvastatin vs. placebo in SPMS, NCT03387670) were included. The subgroup underwent clinical assessments and an advanced MRI protocol at 3T. A cohort of age-matched healthy controls underwent the same MRI protocol. Susceptibility maps were reconstructed using a robust QSM pipeline from multi-echo 3D gradient-echo sequence. Regions of interest (ROIs) in the thalamus, globus pallidus and putamen were segmented from 3D T1-weighted images, and lesions segmented from 3D fluid-attenuated inversion recovery images. Linear regression was used to compare susceptibility from ROIs between patients and controls, adjusting for age and sex. Where significant differences were found, we further examined the associations between ROI susceptibility and clinical and imaging measures of MS severity.

149 SPMS (77% female; mean age: 53 yrs; median Expanded Disability Status Scale (EDSS): 6.0 [interquartile range 4.5-6.0]) and 33 controls (52% female, mean age: 57) were included.Thalamic susceptibility was significantly lower in SPMS compared to controls: mean (SD) 28.6 (12.8) parts per billion (ppb) in SPMS vs. 39.2 (12.7) ppb in controls; regression coefficient: -12.0 [95% confidence interval: -17.0 to -7.1], p < 0.001. In contrast, globus pallidus and putamen susceptibility were similar between both groups.In SPMS, a 10 ppb lower thalamic susceptibility was associated with a +0.13 [+0.01 to +0.24] point higher EDSS (p < 0.05), a -2.4 [-3.8 to -1.0] point lower symbol digit modality test (SDMT, p = 0.001), and a -2.4 [-3.7 to -1.1] point lower Sloan low contrast acuity, 2.5% (p < 0.01).Lower thalamic susceptibility was also strongly associated with a higher T2 lesion volume (T2LV, p < 0.001) and lower normalised whole brain, deep grey matter and thalamic volumes (all p < 0.001).

The reduced thalamic susceptibility found in SPMS compared to controls suggests that thalamic iron concentrations are lower at this advanced stage of the disease. The observed relationships between lower thalamic susceptibility and more severe physical, cognitive and visual disability suggests that reductions in thalamic iron may correlate with important mechanisms of clinical disease progression. Such mechanisms appear to intimately link reductions in thalamic iron with higher T2LV and the development of thalamic atrophy, encouraging further research into QSM-derived thalamic susceptibility as a biomarker of disease severity in SPMS.

Susceptibility source separation, or χ-separation, estimates diamagnetic (χdia) and paramagnetic susceptibility (χpara) signals in the brain using local field and R2' (= R2* - R2) maps. Recently proposed R2*-based χ-separation methods allow for χ-separation using only multi-echo gradient echo (ME-GRE) data, eliminating the need for additional data acquisition for R2 mapping. Although this approach reduces scan time and enhances clinical utility, the impact of missing R2 information remains a subject of exploration. In this study, we evaluate the viability of two previously proposed R2*-based χ-separation methods as alternatives to their R2'-based counterparts: model-based R2*-χ-separation versus χ-separation and deep learning-based χ-sepnet-R2* versus χ-sepnet-R2'. Their performances are assessed in individuals with multiple sclerosis (MS), comparing them with their corresponding R2'-based counterparts (i.e., R2*-χ-separation vs. χ-separation and χ-sepnet-R2* vs. χ-sepnet-R2'). The evaluations encompass qualitative visual assessments by experienced neuroradiologists and quantitative analyses, including region of interest analyses and linear regression analyses. Qualitatively, R2*-χ-separation tends to report higher χpara and χdia values compared with χ-separation, leading to less distinct lesion contrasts, while χ-sepnet-R2* closely aligns with χ-sepnet-R2'. Quantitative analysis reveals a robust correlation between both R2*-based methods and their R2'-based counterparts (r ≥ 0.88). Specifically, in the whole-brain voxels, χ-sepnet-R2* exhibits higher correlation and better linearity than R2*-χ-separation (χdia/χpara from R2*-χ-separation: r = 0.88/0.90, slope = 0.79/0.86; χdia/χpara from χ-sepnet-R2*: r = 0.90/0.92, slope = 0.99/0.97). In MS lesions, both R2*-based methods display comparable correlation and linearity (χdia/χpara from R2*-χ-separation: r = 0.90/0.91, slope = 0.98/0.91; χdia/χpara from χ-sepnet-R2*: r = 0.88/0.88, slope = 0.91/0.95). Notably, χ-sepnet-R2* demonstrates negligible offsets, whereas R2*-χ-separation exhibits relatively large offsets (0.02 ppm in the whole brain and 0.01 ppm in the MS lesions), potentially indicating the false presence of myelin or iron in MS lesions. Overall, both R2*-based χ-separation methods demonstrated their viability as alternatives to their R2'-based counterparts. χ-sepnet-R2* showed better alignment with its R2'-based counterpart with minimal susceptibility offsets, compared with R2*-χ-separation that reported higher χpara and χdia values compared with R2'-based χ-separation.

Quantitative Susceptibility Mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique to quantify the magnetic susceptibility of the tissue under investigation. Deep learning methods have shown promising results in deconvolving the susceptibility distribution from the measured local field obtained from the MR phase. Although existing deep learning based QSM methods can produce high-quality reconstruction, they are highly biased toward training data distribution with less scope for generalizability. This work proposes a hybrid two-step reconstruction approach to improve deep learning based QSM reconstruction. The susceptibility map prediction obtained from the deep learning methods has been refined in the framework developed in this work to ensure consistency with the measured local field. The developed method was validated on existing deep learning and model-based deep learning methods for susceptibility mapping of the brain. The developed method resulted in improved reconstruction for MRI volumes obtained with different acquisition settings, including deep learning models trained on constrained (limited) data settings.

Functional neuroimaging studies demonstrate disinhibition of the cortico-striatal-thalamo-cortical circuit. However, structural imaging studies revealed conflicting results, some suggesting smaller volumes of the caudate nucleus (CN) in children with Gilles de la Tourette syndrome (TS). Here we wanted to find out whether transcranial sonography (TCS) detects alterations of raphe nuclei, substantia nigra, lenticular nucleus (LN), or CN in children with Tic disorder or TS (TIC/TS).The study included 25 treatment-naive children (age: 12.2 ± 2.5 years) with a DSM-V based diagnosis of Tic disorder or TS (10 subjects), without other psychiatric or neurologic diagnosis, and 25 healthy controls (age: 12.17 ± 2.57 years), matched for age and sex. Parental rating of behavioral, emotional abnormalities, somatic complaints and social competencies of the participants were assessed using the Child Behavior Check List (CBCL/4-18R). TCS of deep brain structures was conducted through the preauricular acoustic bone windows using a 2.5-MHz phased-array ultrasound system. Fisher's exact test and Mann-Whitney-U test were used for comparisons between TIC/TS patients and healthy volunteers. The number of participants with hyperechogenic area of left CN in the TIC/TS sample was increased, compared to the healthy control group. TIC/TS patients with hyperechogenic CN showed an increased occurrence of thought- and obsessive-compulsive problems. This TCS study revealed pathologic structural changes in CN, its higher occurrence in TIC/TS compared to healthy controls and the relation to comorbidity of thought problems. Further research should focus on the molecular cause of these alterations, probably the disturbed iron metabolism.

Quantitative susceptibility mapping (QSM) is an MRI-based technique that estimates the underlying tissue magnetic susceptibility based on phase signal. Deep learning (DL)-based methods have shown promise in handling the challenging ill-posed inverse problem for QSM reconstruction. However, they require extensive paired training data that are typically unavailable and suffer from generalization problems. Recent model-incorporated DL approaches also overlook the non-local effect of the tissue phase in applying the source-to-field forward model due to patch-based training constraint, resulting in a discrepancy between the prediction and measurement and subsequently suboptimal QSM reconstruction. This study proposes an unsupervised and subject-specific DL method for QSM reconstruction based on implicit neural representation (INR), referred to as INR-QSM. INR has emerged as a powerful framework for learning a high-quality continuous representation of the signal (image) by exploiting its internal information without training labels. In INR-QSM, the desired susceptibility map is represented as a continuous function of the spatial coordinates, parameterized by a fully-connected neural network. The weights are learned by minimizing a loss function that includes a data fidelity term incorporated by the physical model and regularization terms. Additionally, a novel phase compensation strategy is proposed for the first time to account for the non-local effect of tissue phase in data consistency calculation to make the physical model more accurate. Our experiments show that INR-QSM outperforms traditional established QSM reconstruction methods and the compared unsupervised DL method both qualitatively and quantitatively, and is competitive against supervised DL methods under data perturbations.

Field-to-susceptibility inversion in quantitative susceptibility mapping (QSM) is ill-posed and needs numerical stabilization through either regularization or oversampling by acquiring data at three or more object orientations. Calculation Of Susceptibility through Multiple Orientations Sampling (COSMOS) is an established oversampling approach and regarded as QSM gold standard. It achieves a well-conditioned inverse problem, requiring rotations by 0°, 60° and 120° in the yz-plane. However, this is impractical in vivo, where head rotations are typically restricted to a range of ±25°. Non-ideal sampling degrades the conditioning with residual streaking artifacts whose mitigation needs further regularization. Moreover, susceptibility anisotropy in white matter is not considered in the COSMOS model, which may introduce additional bias. The current work presents a thorough investigation of these effects in primate brain.

Gradient-recalled echo (GRE) data of an entire fixed chimpanzee brain were acquired at 7 T (350 μm resolution, 10 orientations) including ideal COSMOS sampling and realistic rotations in vivo. Comparisons of the results included ideal COSMOS, in-vivo feasible acquisitions with 3-8 orientations and single-orientation iLSQR QSM.

In-vivo feasible and optimal COSMOS yielded high-quality susceptibility maps with increased SNR resulting from averaging multiple acquisitions. COSMOS reconstructions from non-ideal rotations about a single axis required additional L2-regularization to mitigate residual streaking artifacts.

In view of unconsidered anisotropy effects, added complexity of the reconstruction, and the general challenge of multi-orientation acquisitions, advantages of sub-optimal COSMOS schemes over regularized single-orientation QSM appear limited in in-vivo settings.

In MRI, researchers have long endeavored to effectively visualize myelin distribution in the brain, a pursuit with significant implications for both scientific research and clinical applications. Over time, various methods such as myelin water imaging, magnetization transfer imaging, and relaxometric imaging have been developed, each carrying distinct advantages and limitations. Recently, an innovative technique named as magnetic susceptibility source separation has emerged, introducing a novel surrogate biomarker for myelin in the form of a diamagnetic susceptibility map. This paper comprehensively reviews this cutting-edge method, providing the fundamental concepts of magnetic susceptibility, susceptibility imaging, and the validation of the diamagnetic susceptibility map as a myelin biomarker that indirectly measures myelin content. Additionally, the paper explores essential aspects of data acquisition and processing, offering practical insights for readers. A comparison with established myelin imaging methods is also presented, and both current and prospective clinical and scientific applications are discussed to provide a holistic understanding of the technique. This work aims to serve as a foundational resource for newcomers entering this dynamic and rapidly expanding field.

Quantitative MRI (qMRI) has been shown to be clinically useful for numerous applications in the brain and body. The development of rapid, accurate, and reproducible qMRI techniques offers access to new multiparametric data, which can provide a comprehensive view of tissue pathology. This work introduces a multiparametric qMRI protocol along with full postprocessing pipelines, optimized for brain imaging at 3 Tesla and using state-of-the-art qMRI tools. The total scan time is under 50 minutes and includes eight pulse-sequences, which produce range of quantitative maps including T1, T2, and T2* relaxation times, magnetic susceptibility, water and macromolecular tissue fractions, mean diffusivity and fractional anisotropy, magnetization transfer ratio (MTR), and inhomogeneous MTR. Practical tips and limitations of using the protocol are also provided and discussed. Application of the protocol is presented on a cohort of 28 healthy volunteers and 12 brain regions-of-interest (ROIs). Quantitative values agreed with previously reported values. Statistical analysis revealed low variability of qMRI parameters across subjects, which, compared to intra-ROI variability, was x4.1 ± 0.9 times higher on average. Significant and positive linear relationship was found between right and left hemispheres' values for all parameters and ROIs with Pearson correlation coefficients of r>0.89 (P<0.001), and mean slope of 0.95 ± 0.04. Finally, scan-rescan stability demonstrated high reproducibility of the measured parameters across ROIs and volunteers, with close-to-zero mean difference and without correlation between the mean and difference values (across map types, mean P value was 0.48 ± 0.27). The entire quantitative data and postprocessing scripts described in the manuscript are publicly available under dedicated GitHub and Figshare repositories. The quantitative maps produced by the presented protocol can promote longitudinal and multi-center studies, and improve the biological interpretability of qMRI by integrating multiple metrics that can reveal information, which is not apparent when examined using only a single contrast mechanism.

To investigate potential correlations between the susceptibility values of certain brain regions and the severity of disease or neurodevelopmental status in children with autism spectrum disorder (ASD), 18 ASD children and 15 healthy controls (HCs) were recruited. The neurodevelopmental status was assessed by the Gesell Developmental Schedules (GDS) and the severity of the disease was evaluated by the Autism Behavior Checklist (ABC). Eleven brain regions were selected as regions of interest and the susceptibility values were measured by quantitative susceptibility mapping. To evaluate the diagnostic capacity of susceptibility values in distinguishing ASD and HC, the receiver operating characteristic (ROC) curve was computed. Pearson and Spearman partial correlation analysis were used to depict the correlations between the susceptibility values, the ABC scores, and the GDS scores in the ASD group. ROC curves showed that the susceptibility values of the left and right frontal white matter had a larger area under the curve in the ASD group. The susceptibility value of the right globus pallidus was positively correlated with the GDS-fine motor scale score. These findings indicated that the susceptibility value of the right globus pallidus might be a viable imaging biomarker for evaluating the neurodevelopmental status of ASD children.

Quantitative susceptibility mapping (QSM) is a post-processing technique for deriving tissue magnetic susceptibility distribution from MRI phase measurements. Deep learning (DL) algorithms hold great potential for solving the ill-posed QSM reconstruction problem. However, a significant challenge facing current DL-QSM approaches is their limited adaptability to magnetic dipole field orientation variations during training and testing. In this work, we propose a novel Orientation-Adaptive Latent Feature Editing (OA-LFE) module to learn the encoding of acquisition orientation vectors and seamlessly integrate them into the latent features of deep networks. Importantly, it can be directly Plug-and-Play (PnP) into various existing DL-QSM architectures, enabling reconstructions of QSM from arbitrary magnetic dipole orientations. Its effectiveness is demonstrated by combining the OA-LFE module into our previously proposed phase-to-susceptibility single-step instant QSM (iQSM) network, which was initially tailored for pure-axial acquisitions. The proposed OA-LFE-empowered iQSM, which we refer to as iQSM+, is trained in a simulated-supervised manner on a specially-designed simulation brain dataset. Comprehensive experiments are conducted on simulated and in vivo human brain datasets, encompassing subjects ranging from healthy individuals to those with pathological conditions. These experiments involve various MRI platforms (3T and 7T) and aim to compare our proposed iQSM+ against several established QSM reconstruction frameworks, including the original iQSM. The iQSM+ yields QSM images with significantly improved accuracies and mitigates artifacts, surpassing other state-of-the-art DL-QSM algorithms. The PnP OA-LFE module's versatility was further demonstrated by its successful application to xQSM, a distinct DL-QSM network for dipole inversion. In conclusion, this work introduces a new DL paradigm, allowing researchers to develop innovative QSM methods without requiring a complete overhaul of their existing architectures.

The data-driven approach of supervised learning methods has limited applicability in solving dipole inversion in Quantitative Susceptibility Mapping (QSM) with varying scan parameters across different objects. To address this generalization issue in supervised QSM methods, we propose a novel training-free model-based unsupervised method called MoDIP (Model-based Deep Image Prior). MoDIP comprises a small, untrained network and a Data Fidelity Optimization (DFO) module. The network converges to an interim state, acting as an implicit prior for image regularization, while the optimization process enforces the physical model of QSM dipole inversion. Experimental results demonstrate MoDIP's excellent generalizability in solving QSM dipole inversion across different scan parameters. It exhibits robustness against pathological brain QSM, achieving over 32 % accuracy improvement than supervised deep learning methods. It is also 33 % more computationally efficient and runs 4 times faster than conventional DIP-based approaches, enabling 3D high-resolution image reconstruction in under 4.5 min.

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.

To develop a method for unwrapping temporally undersampled and nonlinear gradient recalled echo (GRE) phase.

Temporal unwrapping is performed as a sequential one step prediction of the echo phase, followed by a correction to the nearest integer wrap-count. A spatio-temporal extension of the 1D predictor corrector unwrapping (PCU) algorithm improves the prediction accuracy, and thereby maintains spatial continuity. The proposed method is evaluated using numerical phantom, physical phantom, and in vivo brain data at both 3 T and 9.4 T. The unwrapping performance is compared with the state-of-the-art temporal and spatial unwrapping algorithms, and the spatio-temporal iterative virtual-echo based Nyquist sampled (iVENyS) algorithm.

Simulation results showed significant reduction in unwrapping errors at higher echoes compared with the state-of-the-art algorithms. Similar to the iVENyS algorithm, the PCU algorithm was able to generate spatially smooth phase images for in vivo data acquired at 3 T and 9.4 T, bypassing the use of additional spatial unwrapping step. A key advantage over iVENyS algorithm is the superior performance of PCU algorithm at higher echoes.

PCU algorithm serves as a robust phase unwrapping method for temporally undersampled and nonlinear GRE phase, particularly in the presence of high field gradients.

Parkinson's disease (PD) is a common neurodegenerative disease, and apart from a few rare genetic causes, its pathogenesis remains largely unclear. Recent scientific interest has been captured by the involvement of iron biochemistry and the disruption of iron homeostasis, particularly within the brain regions specifically affected in PD. The advent of Quantitative Susceptibility Mapping (QSM) has enabled non-invasive quantification of brain iron in vivo by MRI, which has contributed to the understanding of iron-associated pathogenesis and has the potential for the development of iron-based biomarkers in PD. This review elucidates the biochemical underpinnings of brain iron accumulation, details advancements in iron-sensitive MRI technologies, and discusses the role of QSM as a biomarker of iron deposition in PD. Despite considerable progress, several challenges impede its clinical application after a decade of QSM studies. The initiation of multi-site research is warranted for developing robust, interpretable, and disease-specific biomarkers for monitoring PD disease progression.

Quantitative susceptibility mapping (QSM) utilizes the relationship between the measured local field and the unknown susceptibility map to perform dipole deconvolution. The aim of this work is to introduce and systematically evaluate the model resolution-based deconvolution for improved estimation of the susceptibility map obtained using the thresholded k-space division (TKD). A two-step approach has been proposed, wherein the first step involves the TKD susceptibility map computation and the second step involves the correction of this susceptibility map using the model-resolution matrix. The TKD-estimated susceptibility map can be expressed as the weighted average of the true susceptibility map, where the weights are determined by the rows of the model-resolution matrix, and hence a deconvolution of the TKD susceptibility map using the model-resolution matrix yields a better approximation to the true susceptibility map. The model resolution-based deconvolution is realized using closed-form, iterative, and sparsity-regularized implementations. The proposed approach was compared with L2 regularization, TKD, rescaled TKD in superfast dipole inversion, the modulated closed-form method, and iterative dipole inversion, as well as sparsity-regularized dipole inversion. It was observed that the proposed approach showed a substantial reduction in the streaking artifacts across 94 test volumes considered in this study. The proposed approach also showed better error reduction and edge preservation compared with other approaches. The proposed model resolution-based deconvolution compensates for the truncation of zero coefficients in the dipole kernel at the magic angle and hence provides a closer approximation to the true susceptibility map compared with other direct methods.

Intracranial hemorrhage (ICH) volume assessment is an important part of patient management and is routinely obtained by non-contrast head CT (NCHCT) using the validated ABC/2 measurement method. Because conventional MRI imaging sequences demonstrate variability in ICH appearance, volumetric analyses for MRI bleed volume in a standardized manner using ABC/2 is not possible. The recently introduced multiecho-complex total field inversion quantitative susceptibility mapping (mcTFI QSM) MRI technique, which maps brain tissue susceptibility to both depict brain tissue structures and quantify tissue susceptibility, may provide a viable alternative. In this study we evaluated mcTFI QSM ABC/2 ICH volume assessment relative to NCHCT.

Patients with ICH who had undergone NCHCT and MRI brain scans within 48 h were recruited for this retrospective study. The ABC/2 method was applied to estimate the bleed volume for both NCHCT and MRI by a CAQ-certified neuroradiologist with 10 years of experience and a trained laboratory assistant. Results were analyzed via Bland-Altman (B-A) and linear regression.

54 patients (27 females) who had undergone NCHCT and MRI within 48 h (<24 h., n = 31, 24-48 h, n = 10) were enrolled. mcTFI QSM ICH volume measurement method showed a positive correlation (99.5%) compared to NCHCT. B-A plot comparing ABC/2 ICH volume on NCHCT and mcTFI MRI done for patients within 24 h demonstrates a bias of -0.09%.

ICH volume calculation using ABC/2 on mcTFI QSM showed a high correlation with NCHCT measurement. These results suggest mcTFI QSM is a promising MRI method for ABC/2 for bleed volume measurement.

To increase the number of images that can be acquired in MR examinations using quantitative parameters, we developed a method for obtaining arterial and venous images with mapping of proton density (PD), RF inhomogeneity (B1), longitudinal relaxation time (T1), apparent transverse relaxation time (T2*), and magnetic susceptibility through calculation, all with the same spatial resolution.

The proposed method uses partially RF-spoiled gradient echo sequences to obtain 3D images of a subject with multiple scan parameters. The PD, B1, T1, T2*, and magnetic susceptibility maps are estimated using the quantification method we previously developed. Arterial images are obtained by adding images using optimized weights to emphasize the arteries. A morphology filter is used to obtain venous images from the magnetic susceptibility maps. For evaluation, images obtained from four out of five healthy volunteers were used to optimize the weights used in the arterial-image calculation, and the optimized weights were applied to the images from the fifth volunteer to obtain an arterial image. Arterial images of the five volunteers were calculated using the leave-one-out method, and the contrast between the arterial and background regions defined using the reference time-of-flight (TOF) method was evaluated using the area under the receiver operation characteristic curve (AUC). The contrast between venous and background regions defined by a reference quantitative susceptibility mapping (QSM) method was also evaluated for the venous image.

The AUC to discriminate blood vessels and background using the proposed method was 0.905 for the arterial image and 0.920 for the venous image.

The results indicate that the arterial images and venous images have high signal intensity at the same region as determined from the reference TOF and QSM methods, demonstrating the possibility of acquiring vasculature images with quantitative parameter mapping through calculation in an integrated manner.

Quantitative Susceptibility Mapping has the potential to provide additional insights into neurological diseases but is typically based on a quite long (5-10 min) 3D gradient-echo scan which is highly sensitive to motion. We propose an ultra-fast acquisition based on three orthogonal (sagittal, coronal and axial) 2D simultaneous multi-slice EPI scans with 1 mm in-plane resolution and 3 mm thick slices. Images in each orientation are corrected for susceptibility-related distortions and co-registered with an iterative non-linear Minimum Deformation Averaging (Volgenmodel) approach to generate a high SNR, super-resolution data set with an isotropic resolution of close to 1 mm. The net acquisition time is 3 times the volume acquisition time of EPI or about 12 s, but the three volumes could also replace "dummy scans" in fMRI, making it feasible to acquire QSM in little or No Additional Time for Imaging (NATIve). NATIve QSM values agreed well with reference 3D GRE QSM in the basal ganglia in healthy subjects. In patients with multiple sclerosis, there was also a good agreement between the susceptibility values within lesions and control ROIs and all lesions which could be seen on 3D GRE QSMs could also be visualized on NATIve QSMs. The approach is faster than conventional 3D GRE by a factor of 25-50 and faster than 3D EPI by a factor of 3-5. As a 2D technique, NATIve QSM was shown to be much more robust to motion than the 3D GRE and 3D EPI, opening up the possibility of studying neurological diseases involving iron accumulation and demyelination in patients who find it difficult to lie still for long enough to acquire QSM data with conventional methods.

Accurate preoperative identification of isocitrate dehydrogenase (IDH) genotypes and tumor subtypes is highly important for proper treatment planning and prognosis evaluation in patients with glioma. This study aimed to differentiate IDH genotypes and tumor subtypes of adult-type diffuse gliomas using histogram features of quantitative susceptibility mapping (QSM) and apparent diffusion coefficient (ADC).

This prospective study enrolled patients with suspected gliomas between March 2019 and January 2022 in a random series. Histogram features of QSM and ADC were extracted from the tumor parenchyma. The Mann-Whitney U test was used to compare the difference in histogram features between different IDH genotypes and among tumor subtypes. Receiver operating characteristic (ROC) curves were constructed to assess the corresponding diagnostic performance.

This study included 47 patients with histopathologically confirmed adult-type diffuse gliomas. Totals of seven QSM features including 10th percentile (P10), 90th percentile (P90), interquartile range (IQR), maximum, mean absolute deviation (MAD), root mean squared (RMS), and variance, and five ADC features including P10, mean, median, RMS, and skewness exhibited significant differences between different IDH genotypes (P<0.05 for all), with the IQR of QSM demonstrating the highest area under curve (AUC) of 0.774 [95% confidence interval (CI): 0.635-0.913]. For separating tumor subtypes, the IQR of QSM also showed the highest AUC of 0.745 (95% CI: 0.566-0.924) for glioblastoma (GBM) versus astrocytoma and 0.848 (95% CI: 0.706-0.989) for GBM versus oligodendroglioma, but none of the features could discriminate astrocytoma from oligodendroglioma. The combination of the IQR of QSM, P10 of ADC, and age achieved the highest AUC of 0.910 (95% CI: 0.826-0.994) for IDH genotypes, and 0.939 (95% CI: 0.859-1.000) and 0.967 (95% CI: 0.904-1.000) for GBM versus astrocytoma and GBM versus oligodendroglioma, respectively.

QSM and ADC histogram features may serve as potential imaging markers for noninvasively assessing IDH genotypes and tumor subtypes of adult-type diffuse gliomas. Combining significant features may enhance the diagnostic performance substantially.

Susceptibility maps reconstructed from thin slabs may suffer underestimation due to background-field removal imperfections near slab boundaries and the increased difficulty of solving a 3D-inversion problem with reduced support, particularly in the direction of the main magnetic field. Reliable QSM reconstruction from thin slabs would enable focal acquisitions in a much-reduced scan time.

This work proposes using additional rapid low-resolution data of extended spatial coverage to improve background-field estimation and regularize the inversion-to-susceptibility process for high resolution, thin slab data. The new method was tested using simulated and in-vivo brain data of high resolution (0.33 × 0.33 × 0.33 mm3 and 0.54 × 0.54 × 0.65 mm3 , respectively) at 3T, and compared to the standard large volume approach.

Using the proposed method, in-vivo high-resolution QSM at 3T was obtained from slabs of width as small as 10.4 mm, aided by a lower-resolution dataset of 24 times coarser voxels. Simulations showed that the proposed method produced more consistent measurements from slabs of at least eight slices. Reducing the mean ROI error to 5% required the low-resolution data to cover ˜60 mm in the direction of the main field, have at least 2-mm isotropic resolution that is not coarser than the high-resolution data by more than four-fold in any direction.

Applying the proposed method enabled focal QSM acquisitions at sub-millimeter resolution within reasonable acquisition time.

Uncovering brain-tissue microstructure including axonal characteristics is a major neuroimaging research focus. Within this scope, anisotropic properties of magnetic susceptibility in white matter have been successfully employed to estimate primary axonal trajectories using mono-tensorial models. However, anisotropic susceptibility has not yet been considered for modeling more complex fiber structures within a voxel, such as intersecting bundles, or an estimation of orientation distribution functions (ODFs). This information is routinely obtained by high angular resolution diffusion imaging (HARDI) techniques. In applications to fixed tissue, however, diffusion-weighted imaging suffers from an inherently low signal-to-noise ratio and limited spatial resolution, leading to high demands on the performance of the gradient system in order to mitigate these limitations. In the current work, high angular resolution susceptibility imaging (HARSI) is proposed as a novel, phase-based methodology to estimate ODFs. A multiple gradient-echo dataset was acquired in an entire fixed chimpanzee brain at 61 orientations by reorienting the specimen in the magnetic field. The constant solid angle method was adapted for estimating phase-based ODFs. HARDI data were also acquired for comparison. HARSI yielded information on whole-brain fiber architecture, including identification of peaks of multiple bundles that resembled features of the HARDI results. Distinct differences between both methods suggest that susceptibility properties may offer complementary microstructural information. These proof-of-concept results indicate a potential to study the axonal organization in post-mortem primate and human brain at high resolution.