Quantitative Susceptibility Mapping Research Articles

Quantitative susceptibility mapping for detection of kidney stones, hemorrhage differentiation, and cyst classification in ADPKD.

The objective is to demonstrate feasibility of quantitative susceptibility mapping (QSM) in autosomal dominant polycystic kidney disease (ADPKD) patients and to compare imaging findings with traditional T1/T2w magnetic resonance imaging (MRI). Thirty-three consecutive patients (11 male, 22 female) diagnosed with ADPKD were initially selected. QSM images were reconstructed from the multiecho gradient echo data and compared to co-registered T2w, T1w, and CT images. Complex cysts were identified and classified into distinct subclasses based on their imaging features. Prevalence of each subclass was estimated. QSM visualized two renal calcifications measuring 9 and 10mm and three pelvic phleboliths measuring 2mm but missed 24 calcifications measuring 1mm or less and 1 larger calcification at the edge of the field of view. A total of 121 complex T1 hyperintense/T2 hypointense renal cysts were detected. 52 (43%) Cysts appeared hyperintense on QSM consistent with hemorrhage; 60 (49%) cysts were isointense with respect to simple cysts and normal kidney parenchyma, while the remaining 9 (7%) were hypointense. The presentation of the latter two complex cyst subtypes is likely indicative of proteinaceous composition without hemorrhage. Our results indicate that QSM of ADPKD kidneys is possible and uniquely suited to detect large renal calculi without ionizing radiation and able to identify properties of complex cysts unattainable with traditional approaches.

Alterations in subcortical magnetic susceptibility and disease-specific relationship with brain volume in major depressive disorder and schizophrenia

Quantitative susceptibility mapping is a magnetic resonance imaging technique that measures brain tissues’ magnetic susceptibility, including iron deposition and myelination. This study examines the relationship between subcortical volume and magnetic susceptibility and determines specific differences in these measures among patients with major depressive disorder (MDD), patients with schizophrenia, and healthy controls (HCs). This was a cross-sectional study. Sex- and age- matched patients with MDD (n = 49), patients with schizophrenia (n = 24), and HCs (n = 50) were included. Magnetic resonance imaging was conducted using quantitative susceptibility mapping and T1-weighted imaging to measure subcortical susceptibility and volume. The acquired brain measurements were compared among groups using analyses of variance and post hoc comparisons. Finally, a general linear model examined the susceptibility–volume relationship. Significant group-level differences were found in the magnetic susceptibility of the nucleus accumbens and amygdala (p = 0.045). Post-hoc analyses indicated that the magnetic susceptibility of the nucleus accumbens and amygdala for the MDD group was significantly higher than that for the HC group (p = 0.0054, p = 0.0065, respectively). However, no significant differences in subcortical volume were found between the groups. The general linear model indicated a significant interaction between group and volume for the nucleus accumbens in MDD group but not schizophrenia or HC groups. This study showed susceptibility alterations in the nucleus accumbens and amygdala in MDD patients. A significant relationship was observed between subcortical susceptibility and volume in the MDD group’s nucleus accumbens, which indicated abnormalities in myelination and the dopaminergic system related to iron deposition.

Parkinson's disease and Parkinsonism syndromes: Evaluating iron deposition in the putamen using magnetic susceptibility MRI techniques - A systematic review and literature analysis

Magnetic resonance imaging (MRI) techniques, such as quantitative susceptibility mapping (QSM) and susceptibility-weighted imaging (SWI), can detect iron deposition in the brain. Iron accumulation in the putamen (PUT) can contribute to the pathogenesis of Parkinson's disease (PD) and atypical Parkinsonian disorders. This systematic review aimed to synthesize evidence on iron deposition in the PUT assessed by MRI susceptibility techniques in PD and Parkinsonism syndromes. The PubMed and Scopus databases were searched for relevant studies. Thirty-four studies from January 2007 to October 2023 that used QSM, SWI, or other MRI susceptibility methods to measure putaminal iron in PD, progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and healthy controls (HCs) were included. Most studies have found increased putaminal iron levels in PD patients versus HCs based on higher quantitative susceptibility. Putaminal iron accumulation correlates with worse motor scores and cognitive decline in patients with PD. Evidence regarding differences in susceptibility between PD and atypical Parkinsonism is emerging, with several studies showing greater putaminal iron deposition in PSP and MSA than in PD patients. Alterations in putaminal iron levels help to distinguish these disorders from PD. Increased putaminal iron levels appear to be associated with increased disease severity and progression. Thus, magnetic susceptibility MRI techniques can detect abnormal iron accumulation in the PUT of patients with Parkinsonism. Moreover, quantifying putaminal susceptibility may serve as an MRI biomarker to monitor motor and cognitive changes in PD and aid in the differential diagnosis of Parkinsonian disorders.

Plug-and-Play latent feature editing for orientation-adaptive quantitative susceptibility mapping neural networks

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.

Cerebral Tau Deposition in Comorbid Progressive Supranuclear Palsy and Amyotrophic Lateral Sclerosis: An [18F]-Flortaucipir and 7T MRI Study

Introduction: Progressive supranuclear palsy (PSP) is a four-repeat tauopathy characterized by multiple clinicopathologic subtypes. Advanced neuroimaging techniques have shown an early ability to distinguish PSP subtypes noninvasively for improved diagnosis. This study utilized tau PET imaging and MRI techniques at 7T to determine the neuroimaging profile of a participant with comorbid PSP and amyotrophic lateral sclerosis (ALS). Method: [18F]-flortaucipir PET imaging was performed on one participant with PSP-ALS, one participant with typical PSP (Richardson’s syndrome; PSP-RS), and 15 healthy control volunteers. Standardized uptake value ratio (SUVR) in each brain region was compared between PSP participants and controls. Quantitative susceptibility mapping (QSM) and inflow-based vascular-space occupancy MRI at 7T were performed on the two PSP participants and on two age-matched healthy controls to evaluate for differences in regional brain iron content and arteriolar cerebral blood volume (CBVa), respectively. Results: In the participant with PSP-ALS, the precentral gyrus demonstrated the highest [18F]-flortaucipir uptake of all brain regions relative to controls (z-score 1.94). In the participant with PSP-RS, [18F]-flortaucipir uptake relative to controls was highest in subcortical regions, including the pallidum, thalamus, hippocampus, and brainstem (z-scores 1.08, 1.41, 1.49, 1.32, respectively). Susceptibility values as a measure of brain iron content were higher in the globus pallidus and substantia nigra than in the midbrain and pons in each participant, regardless of group. CBVa values tended to be higher in the subcortical gray matter in PSP participants than in controls, although large measurement variability was noted in controls across multiple regions. Conclusion: In vivo tau PET imaging of an individual with PSP-ALS overlap demonstrated increased tau burden in the motor cortex that was not observed in PSP-RS or control participants. Consistent with prior PET studies, tau burden in PSP-RS was mainly observed in subcortical regions, including the brainstem and basal ganglia. QSM data suggest that off-target binding to iron may account for some but not all of the increased [18F]-flortaucipir uptake in the basal ganglia in PSP-RS. These findings support existing evidence that tau PET imaging can distinguish among PSP subtypes by detecting distinct regional patterns of tau deposition in the brain. Larger studies are needed to determine whether CBVa is sensitive to changes in brain microvasculature in PSP.

Reliable differentiation of necrosis and active metabolically contours of glioblastoma multiforme using susceptibility-based imaging

PurposeGadolinium-enhancing necrosis in glioblastoma multiforme (GBM), as an occasionally occurring false positive in contrast enhancement (CE) imaging, leads to trouble for segmentation of GBM and treatment. Therefore, the investigation of complementary detection way to identify the metabolically active volume of the tumor with high reliability is very worth to be addressed. Here, we reported on a case of GBM with gadolinium-enhancing necrosis in an experimental CE imaging study in mice and evaluated the discrimination of the necrosis and metabolically active parts of the GBM using conventional and state-of-the-art susceptibility-based MRI. MethodsIn this study, following 5-aminolevulinic acid (ALA) and iron supplements (FAC, 6 h after ALA, intra-tumoral injection) to animal, T2*-W imaging and quantitative susceptibility mapping (QSM) were performed, and compared with CE imaging. ResultsThe signal intensity (SI) of the active and necrosis areas of the case in the CE image demonstrated no significant difference while the SI on the T2*-W images and susceptibility value in QSM changed 24 and 150%, respectively. ConclusionThe preclinical case report provides valuable insights into the potential of susceptibility-based MRI using ALA + FAC to apply as a robust discriminator between necrotic and viable tumors.

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

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

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

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

Quantifying cerebral microbleeds using quantitative susceptibility mapping from magnetization-prepared rapid gradient-echo.

T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) is commonly included in brain studies for structural imaging using magnitude images; however, its phase images can provide an opportunity to assess microbleed burden using quantitative susceptibility mapping (QSM). This potential application for MPRAGE-based QSM was evaluated using in vivo and simulated measurements. Possible factors affecting image quality were also explored. Detection sensitivity was evaluated against standard multiecho gradient echo (MEGE) QSM using 3-T in vivo data of 15 subjects with a combined total of 108 confirmed microbleeds. The two methods were compared based on the microbleed size and susceptibility measurements. In addition, simulations explored the detection sensitivity of MPRAGE-QSM at different representative magnetic field strengths and echo times using microbleeds of different size, susceptibility, and location. Results showed that in vivo microbleeds appeared to be smaller (× 0.54) and of higher mean susceptibility (× 1.9) on MPRAGE-QSM than on MEGE-QSM, but total susceptibility estimates were in closer agreement (slope: 0.97, r2: 0.94), and detection sensitivity was comparable. In simulations, QSM at 1.5 T had a low contrast-to-noise ratio that obscured the detection of many microbleeds. Signal-to-noise ratio (SNR) levels at 3 T and above resulted in better contrast and increased detection. The detection rates for microbleeds of minimum one-voxel diameter and 0.4-ppm susceptibility were 0.55, 0.80, and 0.88 at SNR levels of 1.5, 3, and 7 T, respectively. Size and total susceptibility estimates were more consistent than mean susceptibility estimates, which showed size-dependent underestimation. MPRAGE-QSM provides an opportunity to detect and quantify the size and susceptibility of microbleeds of at least one-voxel diameter at B0of 3 T or higher with no additional time cost, when standard T2*-weighted images are not available or have inadequate spatial resolution. The total susceptibility measure is more robust against sequence variations and might allow combining data from different protocols.

Incorporating a-priori information in deep learning models for quantitative susceptibility mapping via adaptive convolution.

Quantitative susceptibility mapping (QSM) has attracted considerable interest for tissue characterization (e.g., iron and calcium accumulation, myelination, venous vasculature) in the human brain and relies on extensive data processing of gradient-echo MRI phase images. While deep learning-based field-to-susceptibility inversion has shown great potential, the acquisition parameters applied in clinical settings such as image resolution or image orientation with respect to the magnetic field have not been fully accounted for. Furthermore, the lack of comprehensive training data covering a wide range of acquisition parameters further limits the current QSM deep learning approaches. Here, we propose the integration of a priori information of imaging parameters into convolutional neural networks with our approach, adaptive convolution, that learns the mapping between the additional presented information (acquisition parameters) and the changes in the phase images associated with these varying acquisition parameters. By associating a-priori information with the network parameters itself, the optimal set of convolution weights is selected based on data-specific attributes, leading to generalizability towards changes in acquisition parameters. Moreover, we demonstrate the feasibility of pre-training on synthetic data and transfer learning to clinical brain data to achieve substantial improvements in the computation of susceptibility maps. The adaptive convolution 3D U-Net demonstrated generalizability in acquisition parameters on synthetic and in-vivo data and outperformed models lacking adaptive convolution or transfer learning. Further experiments demonstrate the impact of the side information on the adaptive model and assessed susceptibility map computation on simulated pathologic data sets and measured phase data.

Visualizing the Habenula Using 3T High-Resolution MP2RAGE and QSM: A Preliminary Study.

The habenula is a key node in the regulation of emotion-related behavior. Accurate visualization of the habenula and its reliable quantitative analysis is vital for the assessment of psychiatric disorders. To obtain high-contrast habenula images and allow them to be compatible with clinical applications, this preliminary study compared 3T MP2RAGE and quantitative susceptibility mapping with MPRAGE by evaluating the habenula segmentation performance. Ten healthy volunteers were scanned twice with 3T MPRAGE and MP2RAGE and once with quantitative susceptibility mapping. Image quality and visibility of habenula anatomic features were analyzed by 3 radiologists using a 5-point scale. Contrast assessments of the habenula and thalamus were also performed. The reproducibility of the habenula volume from MPRAGE and MP2RAGE was evaluated by manual segmentation and the Multiple Automatically Generated Template brain segmentation algorithm (MAGeTbrain). T1 values and susceptibility were measured in the whole habenula and habenula geometric subregion using MP2RAGE T1-mapping and quantitative susceptibility mapping. The 3T MP2RAGE and quantitative susceptibility mapping demonstrated clear boundaries and anatomic features of the habenula compared with MPRAGE, with a higher SNR and contrast-to-noise ratio (all P < .05). Additionally, 3T MP2RAGE provided reliable habenula manual and MAGeTbrain segmentation volume estimates with greater reproducibility. T1-mapping derived from MP2RAGE was highly reliable, and susceptibility contrast was highly nonuniform within the habenula. We identified an optimized sequence combination (3T MP2RAGE combined with quantitative susceptibility mapping) that may be useful for enhancing habenula visualization and yielding more reliable quantitative data.

Associations of quantitative susceptibility mapping with cortical atrophy and brain connectome in Alzheimer's disease: A multi-parametric study

Aberrant susceptibility due to iron level abnormality and brain network disconnections are observed in Alzheimer's disease (AD), with disrupted iron homeostasis hypothesized to be linked to AD pathology and neuronal loss. However, whether associations exist between abnormal quantitative susceptibility mapping (QSM), brain atrophy, and altered brain connectome in AD remains unclear. Based on multi-parametric brain imaging data from 30 AD patients and 26 healthy controls enrolled at the China-Japan Friendship Hospital, we investigated the abnormality of the QSM signal and volumetric measure across 246 brain regions in AD patients. The structural and functional connectomes were constructed based on diffusion MRI tractography and functional connectivity, respectively. The network topology was quantified using graph theory analyses. We identified seven brain regions with both reduced cortical thickness and abnormal QSM (p < 0.05) in AD, including the right superior frontal gyrus, left superior temporal gyrus, right fusiform gyrus, left superior parietal lobule, right superior parietal lobule, left inferior parietal lobule, and left precuneus. Correlations between cortical thickness and network topology computed across patients in the AD group resulted in statistically significant correlations in five of these regions, with higher correlations in functional compared to structural topology. We computed the correlation between network topological metrics, QSM value and cortical thickness across regions at both individual and group-averaged levels, resulting in a measure we call spatial correlations. We found a decrease in the spatial correlation of QSM and the global efficiency of the structural network in AD patients at the individual level. These findings may provide insights into the complex relationships among QSM, brain atrophy, and brain connectome in AD.

A rapid multi-parametric quantitative MR imaging method to assess Parkinson’s disease: a feasibility study

BackgroundMULTIPLEX is a single-scan three-dimensional multi-parametric MRI technique that provides 1 mm isotropic T1-, T2*-, proton density- and susceptibility-weighted images and the corresponding quantitative maps. This study aimed to investigate its feasibility of clinical application in Parkinson’s disease (PD).Methods27 PD patients and 23 healthy control (HC) were recruited and underwent a MULTIPLEX scanning. All image reconstruction and processing were automatically performed with in-house C + + programs on the Automatic Differentiation using Expression Template platform. According to the HybraPD atlas consisting of 12 human brain subcortical nuclei, the region-of-interest (ROI) based analysis was conducted to extract quantitative parameters, then identify PD-related abnormalities from the T1, T2* and proton density maps and quantitative susceptibility mapping (QSM), by comparing patients and HCs.ResultsThe ROI-based analysis revealed significantly decreased mean T1 values in substantia nigra pars compacta and habenular nuclei, mean T2* value in subthalamic nucleus and increased mean QSM value in subthalamic nucleus in PD patients, compared to HCs (all p values < 0.05 after FDR correction). The receiver operating characteristic analysis showed all these four quantitative parameters significantly contributed to PD diagnosis (all p values < 0.01 after FDR correction). Furthermore, the two quantitative parameters in subthalamic nucleus showed hemicerebral differences in regard to the clinically dominant side among PD patients.ConclusionsMULTIPLEX might be feasible for clinical application to assist in PD diagnosis and provide possible pathological information of PD patients’ subcortical nucleus and dopaminergic midbrain regions.

The Analysis of relation to brain iron deposition of Parkinson’s Disease using Quantitative Susceptibility Mapping

Objectives: This study aimed to investigate the levels of brain iron deposition in Parkinson's disease (PD) patients using Quantitative Susceptibility Mapping (QSM) and to determine whether distinctions compared to the general population exist. Furthermore, we examined potential variations in iron deposition among different PD subtypes.Methods: Structural brain imaging was conducted on 75 participants at Gangdong Kyung Hee University Hospital between August 2017 and May 2020. PD patients were categorized into Tremor Dominant (TD) and Postural Instability and Gait Difficulty (PIGD) subtypes. Voxel-based morphometry and QSM were employed to compare voxel-wise magnetic susceptibility across the entire brain between Normal Controls (NC) and PD groups. Subsequently, QSM values were compared between TD and PIGD groups.Results: QSM values were compared among 46 PD patients and 23 normal controls, as well as between TD (n=22) and PIGD (n=24) groups. Voxel-based QSM analysis revealed no significant differences between groups. Similarly, ROI-based QSM analysis showed no significant distinctions.Conclusions: No significant variations were observed between the PD patient group, NC group, or PD subtypes. This study systematically compared QSM values across a broad range of brain regions potentially linked to PD pathology. Additionally, the subdivision of the PD group into TD and PIGD subtypes for QSM-based iron deposition analysis represents a meaningful and innovative approach.

Iron Deposition and Distribution Across the Hippocampus Is Associated with Pattern Separation and Pattern Completion in Older Adults at Risk for Alzheimer's Disease.

Elevated iron deposition in the brain has been observed in older adult humans and persons with Alzheimer's disease (AD), and has been associated with lower cognitive performance. We investigated the impact of iron deposition, and its topographical distribution across hippocampal subfields and segments (anterior, posterior) measured along its longitudinal axis, on episodic memory in a sample of cognitively unimpaired older adults at elevated familial risk for AD (N = 172, 120 females, 52 males; mean age = 68.8 ± 5.4 years). MRI-based quantitative susceptibility maps were acquired to derive estimates of hippocampal iron deposition. The Mnemonic Similarity Task was used to measure pattern separation and pattern completion, two hippocampally mediated episodic memory processes. Greater hippocampal iron load was associated with lower pattern separation and higher pattern completion scores, both indicators of poorer episodic memory. Examination of iron levels within hippocampal subfields across its long axis revealed topographic specificity. Among the subfields and segments investigated here, iron deposition in the posterior hippocampal CA1 was the most robustly and negatively associated with the fidelity memory representations. This association remained after controlling for hippocampal volume and was observed in the context of normal performance on standard neuropsychological memory measures. These findings reveal that the impact of iron load on episodic memory performance is not uniform across the hippocampus. Both iron deposition levels as well as its spatial distribution, must be taken into account when examining the relationship between hippocampal iron and episodic memory in older adults at elevated risk for AD.

Neuroimaging of Parkinson's disease by quantitative susceptibility mapping

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.

Paramagnetic rim lesions predict greater long-term relapse rates and clinical progression over 10 years

Background: Paramagnetic rim lesions (PRLs) have been linked to higher clinical disease severity and relapse frequency. However, it remains unclear whether PRLs predict future, long-term disease progression. Objectives: The study aimed to assess whether baseline PRLs were associated with subsequent long-term (10 years) Expanded Disability Status Scale (EDSS) increase and relapse frequency and, if so, whether PRL-associated EDSS increase was mediated by relapse. Methods: This retrospective analysis included 172 people with multiple sclerosis (pwMS) with 1868 yearly clinical visits over a mean follow-up time of 10.2 years. 3T magnetic resonance imaging (MRI) was acquired at baseline and PRLs were assessed on quantitative susceptibility mapping (QSM) images. The associations between PRLs, relapse, and rate of EDSS change were assessed using linear models. Results: PRL+ pwMS had greater overall annual relapse rate (β = 0.068; p = 0.010), three times greater overall odds of relapse (exp(β) = 3.472; p = 0.009), and greater rate of yearly EDSS change (β = 0.045; p = 0.010) than PRL− pwMS. Greater PRL number was associated with greater odds of at least one progression independent of relapse activity (PIRA) episode over follow-up (exp(β) = 1.171, p = 0.009). Mediation analysis showed that the association between PRL presence (yes/no) and EDSS increase was 96.7% independent of relapse number. Conclusion: PRLs are a marker of aggressive ongoing disease inflammatory activity, including more frequent future clinical relapses and greater long-term, relapse-independent disability progression.

A spatially adaptive regularization based three-dimensional reconstruction network for quantitative susceptibility mapping

Objective. Quantitative susceptibility mapping (QSM) is a new imaging technique for non-invasive characterization of the composition and microstructure of in vivo tissues, and it can be reconstructed from local field measurements by solving an ill-posed inverse problem. Even for deep learning networks, it is not an easy task to establish an accurate quantitative mapping between two physical quantities of different units, i.e. field shift in Hz and susceptibility value in ppm for QSM. Approach. In this paper, we propose a spatially adaptive regularization based three-dimensional reconstruction network SAQSM. A spatially adaptive module is specially designed and a set of them at different resolutions are inserted into the network decoder, playing a role of cross-modality based regularization constraint. Therefore, the exact information of both field and magnitude data is exploited to adjust the scale and shift of feature maps, and thus any information loss or deviation occurred in previous layers could be effectively corrected. The network encoding has a dynamic perceptual initialization, which enables the network to overcome receptive field intervals and also strengthens its ability to detect features of various sizes. Main results. Experimental results on the brain data of healthy volunteers, clinical hemorrhage and simulated phantom with calcification demonstrate that SAQSM can achieve more accurate reconstruction with less susceptibility artifacts, while perform well on the stability and generalization even for severe lesion areas. Significance. This proposed framework may provide a valuable paradigm to quantitative mapping or multimodal reconstruction.

Iron/ROS/Itga3 mediated accelerated depletion of hippocampal neural stem cell pool contributes to cognitive impairment after hemorrhagic stroke

Hemorrhagic stroke, specifically intracerebral hemorrhage (ICH), has been implicated in the development of persistent cognitive impairment, significantly compromising the quality of life for affected individuals. Nevertheless, the precise underlying mechanism remains elusive. Here, we report for the first time that the accumulation of iron within the hippocampus, distal to the site of ICH in the striatum, is causally linked to the observed cognitive impairment with both clinical patient data and animal model. Both susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) demonstrated significant iron accumulation in the hippocampus of ICH patients, which is far from the actual hematoma. Logistical regression analysis and multiple linear regression analysis identified iron level as an independent risk factor with a negative correlation with post-ICH cognitive impairment. Using a mouse model of ICH, we demonstrated that iron accumulation triggers an excessive activation of neural stem cells (NSCs). This overactivation subsequently leads to the depletion of the NSC pool, diminished neurogenesis, and the onset of progressive cognitive dysfunction. Mechanistically, iron accumulation elevated the levels of reactive oxygen species (ROS), which downregulated the expression of Itga3. Notably, pharmacological chelation of iron accumulation or scavenger of aberrant ROS levels, as well as conditionally overexpressed Itga3 in NSCs, remarkably attenuated the exhaustion of NSC pool, abnormal neurogenesis and cognitive decline in the mouse model of ICH. Together, these results provide molecular insights into ICH-induced cognitive impairment, shedding light on the value of maintaining NSC pool in preventing cognitive dysfunction in patients with hemorrhagic stroke or related conditions.

Characteristics, Prevalence, and Clinical Relevance of Juxtacortical Paramagnetic Rims in Patients With Multiple Sclerosis.

A subgroup of patients with multiple sclerosis (MS) presents focal paramagnetic rims at the border between cortex and white matter (juxtacortical paramagnetic rims [JPRs]). We investigated the presence of this finding in our in vivo MS cohort and explored its potential clinical relevance. Moreover, we exploited postmortem MRI of fixed whole MS brains to (1) detect those rims and (2) investigate their histologic correlation. Quantitative susceptibility mapping (QSM) and magnetization-prepared 2 rapid acquisition gradient-echo (MP2RAGE) images at 3T-MRI of 165 patients with MS from the in vivo cohort were screened for JPRs and the presence of cortical lesions. Five postmortem brains from patients with MS were imaged with 3T-MRI to obtain QSM and MP2RAGE sequences. Tissue blocks containing JPRs were excised and paraffin-embedded slices stained by immunohistochemistry for myelin basic protein (for myelin) and anti-CR3/43 (for major histocompatibility complex II-positive microglia/macrophages). DAB-Turnbull stain was performed to detect iron. JPRs are present in approximately 10% of in vivo patients and are associated with increased cortical lesion load. One of the 5 postmortem brains showed JPRs. Histologically, JPRs correspond to an accumulation of activated iron-laden phagocytes and are associated with demyelination of the whole overlying cortical ribbon. JPRs are a novel potential MRI biomarker of focal cortical demyelination, which seems related to global cortical pathology and might be useful for diagnostic and stratification purposes in a clinical setting.