Quantitative Susceptibility Mapping MRI Research Articles

Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis.

Psychosis is related to neurochemical changes in deep-brain nuclei, particularly suggesting dopamine dysfunctions. We used an magnetic resonance imaging-based technique called quantitative susceptibility mapping (QSM) to study these regions in psychosis. QSM quantifies magnetic susceptibility in the brain, which is associated with iron concentrations. Since iron is a cofactor in dopamine pathways and co-localizes with inhibitory neurons, differences in QSM could reflect changes in these processes. We scanned 83 patients with first-episode psychosis and 64 healthy subjects. We reassessed 22 patients and 21 control subjects after 3 months. Mean susceptibility was measured in 6 deep-brain nuclei. Using linear mixed models, we analyzed the effect of case-control differences, region, age, gender, volume, framewise displacement (FD), treatment duration, dose, laterality, session, and psychotic symptoms on QSM. Patients showed a significant susceptibility reduction in the putamen and globus pallidus externa (GPe). Patients also showed a significant R2* reduction in GPe. Age, gender, FD, session, group, and region are significant predictor variables for QSM. Dose, treatment duration, and volume were not predictor variables of QSM. Reduction in QSM and R2* suggests a decreased iron concentration in the GPe of patients. Susceptibility reduction in putamen cannot be associated with iron changes. Since changes observed in putamen and GPe were not associated with symptoms, dose, and treatment duration, we hypothesize that susceptibility may be a trait marker rather than a state marker, but this must be verified with long-term studies.

Quantitative susceptibility mapping MRI reveals a relationship between iron accumulation, CDR score and cognition across the spectrum from healthy aging to Alzheimer’s disease

AbstractBackgroundThe objective of this study was to determine if there is a relationship between iron accumulation in the various white and gray matter regions of the brain, as assessed by susceptibility changes, measured with Quantitative Susceptibility MRI (QSM‐MRI), Clinical Dementia Rating (CDR) Score and a Cognitive Measure of Delayed Recall. Iron is an essential element for normal neuronal functioning. The accumulation of brain iron may signal a reduction in neuronal metabolism and/or trigger a neuroinflammatory response with microglia transporting iron to regions where pathology is taking place. This has led to the hypothesis that disruption of brain iron homeostasis contributes to Alzheimer’s disease symptoms.MethodThis study used a cross‐sectional design. MRI scans (T1 MPRAGE, QSM‐MRI with multi‐echo acquisition) were acquired on 57 participants from the Boston University Alzheimer’s Disease Center. Freesurfer 6.0 was used to generate regional brain volumes. The T1 maps from Freesurfer were co‐registered with the QSM scans to get regional brain QSM intensity values for each of the Desikan‐Killiany gray matter regions and Salat white matter regions. Values from the two hemispheres were combined. Associations between QSM values and clinical outcomes were assessed using stepwise ordinal logistic regression (CDR) or multiple regression (Neuropsychological Assessment Battery list learning long delay) in JMP 15 with age, sex and whole brain volume forced into the analyses as control variables.ResultThe ordinal logistic analysis produced a significant model (R Squared = 0.76). Following FDR correction, the volume of the hippocampus combined with susceptibility regions from subcortical gray matter and parietal white matter regions were important contributors to the logistic model. The multiple regression also produced a significant model (R Squared = 0.73). Following FDR correction, susceptibility values from medial temporal gray matter and parietal white matter regions were selected as important contributors to the regression model. Little overlap was found amongst the predictors chosen in these models.ConclusionThese findings support to the notion that a disruption of brain iron homeostasis is related to clinical status and memory function. As such, it may help us to better understand the clinical syndrome of Alzheimer’s disease.

Quantitative susceptibility mapping in β-Amyloid PET-stratified patients with dementia and healthy controls – A hybrid PET/MRI study

PurposePost-mortem and in-vivo MRI data suggest an accumulation of iron in the brain of Alzheimer’s disease (AD) patients. The majority of studies in clinically diagnosed AD patients found an increase of iron-sensitive MRI signals in the putamen. As the clinical diagnosis shows only a moderate sensitivity, Aβ-PET was used to further stratify patients with the clinical diagnosis of AD. Aim of this exploratory study was to examine whether Aβ-positive (AD) and Aβ-negative (non-AD) patients differ in their regional magnetic susceptibility compared to healthy controls (HCs) and whether regional susceptibility values correlate with mini mental state examination (MMSE) scores or global Aβ-load. MethodsWe retrospectively analyzed [11C]PiB PET/MRI data of 11 HCs, 16 AD and 10 non-AD patients. We used quantitative susceptibility mapping (QSM) as iron-sensitive MRI signal measured at the 3 T PET/MR scanner. Global cerebral Aβ-load was determined by composite [11C]PiB SUV ratios. ResultsCompared to HCs, AD patients showed higher QSM values in putamen (0.049 ± 0.033 vs. 0.002 ± 0.031; p = 0.006), while non-AD patients showed lower QSM values in caudate nucleus (0.003 ± 0.027 vs. 0.051 ± 0.039; p = 0.006). There was a trend towards a significant correlation between putaminal QSM and MMSE values (ρ=-0.340, p = 0.053). In AD patients, global Aβ-load and putaminal QSM values were significantly correlated (ρ=-0.574, p = 0.020). ConclusionsThese data indicate that AD and non-AD patients may show different cerebral iron pathologies which might be detectable by QSM MRI, and might be linked to neurodegeneration. Overall, the data encourage further investigations in well-defined patient cohorts to clarify the value of QSM/magnetic susceptibility in the course of neurodegenerative diseases and its potential as diagnostic biomarker.

Motoric impairment versus iron deposition gradient in the subthalamic nucleus in Parkinson's disease.

The objective of this study was to investigate the correlation between the quantitative susceptibility mapping (QSM) signal gradient of the subthalamic nucleus (STN) and motor impairment in patients with Parkinson's disease (PD). All PD patients who had undergone QSM MRI for presurgical deep brain stimulation (DBS) planning were eligible for inclusion in this study. The entire STN and its three functional subdivisions, as well as the adjacent white matter (WM), were segmented and measured. The QSM value difference between the entire STN and adjacent WM (STN-WM), between the limbic and associative regions of the STN (L-A), and between the associative and motor regions of the STN (A-M) were obtained as measures of gradient and were input into an unsupervised k-means clustering algorithm to automatically categorize the overall boundary distinctness between the STN and adjacent WM and between STN subdivisions (gradient blur [GB] and gradient sharp [GS] groups). Statistical tests were performed to compare clinical and image measurements for discrimination between GB and GS groups. Of the 39 study patients, 19 were categorized into the GB group and 20 into the GS group, based on quantitative cluster analysis. The GB group had a significantly higher presurgical off-medication Unified Parkinson's Disease Rating Scale Part III score (51.289 ± 20.741) than the GS group (38.5 ± 16.028; p = 0.037). The GB group had significantly higher QSM values for the STN and its three subdivisions and adjacent WM than those for the GS group (p < 0.01). The GB group also demonstrated a significantly higher STN-WM gradient in the right STN (p = 0.01). The GB group demonstrated a significantly lower L-A gradient in both the left and the right STN (p < 0.02). Advancing PD with more severe motor impairment leads to more iron deposition in the STN and adjacent WM, as shown in the QSM signal. Loss of the STN inner QSM signal gradient should be considered as an image marker for more severe motor impairment in PD patients.

Quantitative Susceptibility Mapping MRI to Assess the Relationship Between Iron Accumulation and Hippocampal Atrophy as a Measure of the N Aspect of the A/T/N Alzheimer’s Disease Definition (1899)

Quantitative Susceptibility Mapping MRI to Assess the Relationship Between Iron Accumulation and Hippocampal Atrophy as a Measure of the N Aspect of the A/T/N Alzheimer’s Disease Definition (1899)

Brain iron and metabolic abnormalities in C19orf12 mutation carriers: A 7.0 tesla MRI study in mitochondrial membrane protein-associated neurodegeneration.

Mitochondrial membrane protein-associated neurodegeneration is an autosomal-recessive disorder caused by C19orf12 mutations and characterized by iron deposits in the basal ganglia. The aim of this study was to quantify iron concentrations in deep gray matter structures using quantitative susceptibility mapping MRI and to characterize metabolic abnormalities in the pyramidal pathway using 1 H MR spectroscopy in clinically manifesting membrane protein-associated neurodegeneration patients and asymptomatic C19orf12 gene mutation heterozygous carriers. We present data of 4 clinically affected membrane protein-associated neurodegeneration patients (mean age: 21.0 ± 2.9 years) and 9 heterozygous gene mutation carriers (mean age: 50.4 ± 9.8 years), compared to age-matched healthy controls. MRI assessments were performed on a 7.0 Tesla whole-body system, consisting of whole-brain gradient-echo scans and short echo time, single-volume MR spectroscopy in the white matter of the precentral/postcentral gyrus. Quantitative susceptibility mapping, a surrogate marker for iron concentration, was performed using a state-of-the-art multiscale dipole inversion approach with focus on the globus pallidus, thalamus, putamen, caudate nucleus, and SN. In membrane protein-associated neurodegeneration patients, magnetic susceptibilities were 2 to 3 times higher in the globus pallidus (P = 0.02) and SN (P = 0.02) compared to controls. In addition, significantly higher magnetic susceptibility was observed in the caudate nucleus (P = 0.02). Non-manifesting heterozygous mutation carriers exhibited significantly increased magnetic susceptibility (relative to controls) in the putamen (P = 0.003) and caudate nucleus (P = 0.001), which may be an endophenotypic marker of genetic heterozygosity. MR spectroscopy revealed significantly increased levels of glutamate, taurine, and the combined concentration of glutamate and glutamine in membrane protein-associated neurodegeneration, which may be a correlate of corticospinal pathway dysfunction frequently observed in membrane protein-associated neurodegeneration patients. © 2019 International Parkinson and Movement Disorder Society.

Reproducibility of quantitative susceptibility mapping in lumbar vertebra.

To evaluate the reliability and reproducibility of quantitative susceptibility mapping (QSM) in the lumbar vertebra. From May 2017 to September 2017, 61 subjects who underwent QSM MRI and quantitative computed tomography (QCT) were consecutively enrolled in this prospective study. QSM examination was performed two times with an interval of less than 1 week for each subject. For each data set, the QSM and QCT values on L1-L4 vertebral bodies were measured independently by two radiologists. The correlation coefficient between QSM and QCT values was calculated on L1-L4 vertebral bodies. The intraclass correlation coefficient (ICC) and Bland-Altman plots were used to evaluate the inter-observer reliability and the inter-scan reproducibility on QSM. A total of 61 subjects (mean age, 55.5±13.7 years) with 244 vertebral bodies were analyzed. Overall, QSM and QCT showed good correlation in the L1-L4 vertebral body, especially in the L3 (R=-0.75). QSM value showed excellent inter-observer reliability (ICC, 0.992, 95% CI: 0.985-0.996) with a mean difference of 0.35 and 95% limits of agreements of within -22.74 to 23.45 ppb, and very good inter-scan reproducibility (ICC, 0.932, 95% CI: 0.886-0.959) with a mean difference of -7.60 ppb and 95% limits of agreements of within of -92.85 to 77.62 ppb. QSM in the lumbar vertebra is a reliable and reproducible technique for evaluating bone mineral density.

Elevated brain oxygen extraction fraction measured by MRI susceptibility relates to perfusion status in acute ischemic stroke

Recent clinical trials of new revascularization therapies in acute ischemic stroke have highlighted the importance of physiological imaging to identify optimal treatments for patients. Oxygen extraction fraction (OEF) is a hallmark of at-risk tissue in stroke, and can be quantified from the susceptibility effect of deoxyhemoglobin molecules in venous blood on MRI phase scans. We measured OEF within cerebral veins using advanced quantitative susceptibility mapping (QSM) MRI reconstructions in 20 acute stroke patients. Absolute OEF was elevated in the affected (29.3 ± 3.4%) versus the contralateral hemisphere (25.5 ± 3.1%) of patients with large diffusion–perfusion lesion mismatch (P = 0.032). In these patients, OEF negatively correlated with relative CBF measured by dynamic susceptibility contrast MRI (P = 0.004), suggesting compensation for reduced flow. Patients with perfusion–diffusion match or no hypo-perfusion showed less OEF difference between hemispheres. Nine patients received longitudinal assessment and showed OEF ratio (affected to contralateral) of 1.2 ± 0.1 at baseline that normalized (decreased) to 1.0 ± 0.1 at follow-up three days later (P = 0.03). Our feasibility study demonstrates that QSM MRI can non-invasively quantify OEF in stroke patients, relates to perfusion status, and is sensitive to OEF changes over time. Clinical trial registration: Longitudinal MRI examinations of patients with brain ischemia and blood brain barrier permeability; clinicaltrials.org: NCT02077582

Imaging beta amyloid aggregation and iron accumulation in Alzheimer's disease using quantitative susceptibility mapping MRI

Beta amyloid is a protein fragment snipped from the amyloid precursor protein (APP). Aggregation of these peptides into amyloid plaques is one of the hallmarks of Alzheimer's disease. MR imaging of beta amyloid plaques has been attempted using various techniques, notably with T2* contrast. The non-invasive detectability of beta amyloid plaques in MR images has so far been largely attributed to focal iron deposition accompanying the plaques. It is believed that the T2* shortening effects of paramagnetic iron are the primary source of contrast between plaques and surrounding tissue. Amyloid plaque itself has been reported to induce no magnetic susceptibility effect. We hypothesized that aggregations of beta amyloid would increase electron density and induce notable changes in local susceptibility value, large enough to generate contrast relative to surrounding normal tissues that can be visualized by quantitative susceptibility mapping (QSM) MR imaging. To test this hypothesis, we first demonstrated in a phantom that beta amyloid is diamagnetic and can generate strong contrast on susceptibility maps. We then conducted experiments on a transgenic mouse model of Alzheimer's disease that is known to mimic the formation of human beta amyloid but without neurofibrillary tangles or neuronal death. Over a period of 18 months, we showed that QSM can be used to longitudinally monitor beta amyloid accumulation and accompanied iron deposition in vivo. Individual beta amyloid plaque can also be visualized ex vivo in high resolution susceptibility maps. Moreover, the measured negative susceptibility map and positive susceptibility map could provide histology-like image contrast for identifying deposition of beta amyloid plaques and iron. Finally, we demonstrated that the diamagnetic susceptibility of beta amyloid can also be observed in brain specimens of AD patients. The ability to assess beta amyloid aggregation non-invasively with QSM MR imaging may aid the diagnosis of Alzheimer's disease.

Diffusion kurtosis and quantitative susceptibility mapping MRI are sensitive to structural abnormalities in amyotrophic lateral sclerosis.

ObjectiveTo construct a clinical diagnostic biomarker using state-of-the-art microstructural MRI in the motor cortex of people with amyotrophic lateral sclerosis (ALS).MethodsClinical and MRI data were obtained from 21 ALS patients (aged 54 ± 14 years, 33% female) and 63 age- and gender-matched controls (aged 48 ± 18 years, 43% female). MRI was acquired at 3T and included T1-weighted scan (for volumetrics), arterial spin labelling (for cerebral blood flow), susceptibility-weighted angiography (for iron deposition) and multiband diffusion kurtosis imaging (for tissue microstructure). Group differences in imaging measures in the motor cortex were tested by general linear model and relationships to clinical variables by linear regression.ResultsThe ALS group had mild-to-moderate impairment (disease duration: 1.8 ± 0.8 years; ALS functional rating scale 40.2 ± 6.0; forced vital capacity 83% ± 22%). No age or gender differences were present between groups. We found significant group differences in diffusion kurtosis metrics (apparent, mean, radial and axial kurtosis: p < .01) and iron deposition in the motor cortex (p = .03). Within the ALS group, we found significant relationships between motor cortex volume, apparent diffusion and disease duration (adjusted R2 = 0.27, p = .011); and between the apparent and radial kurtosis metrics and ALS functional rating scale (adjusted R2 = 0.25, p = .033). A composite imaging biomarker comprising kurtosis and iron deposition measures yielded a maximal diagnostic accuracy of 83% (81% sensitivity, 85% specificity) and an area-under-the-curve of 0.86.ConclusionDiffusion kurtosis is sensitive to early changes present in the motor region in ALS. We propose a composite imaging biomarker reflecting tissue microstructural changes in early ALS that may provide clinically valuable diagnostic information.

7-Tesla Magnetic Resonance Imaging for Brain Iron Quantification in Homozygous and Heterozygous PANK2 Mutation Carriers.

Pantothenate-kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder characterized by iron deposits in basal ganglia. The aim of this study was to quantify iron concentrations of deep gray matter structures in heterozygous PANK2 mutation carriers and in PKAN patients using quantitative susceptibility mapping MRI. By determining iron concentration, we intended to find mutation-specific brain parenchymal stigmata in heterozygous PANK2 mutation carriers in comparison to age-matched healthy volunteers. We studied 11 heterozygous PANK2 gene mutation carriers (mean age: 43.4 years; standard deviation [SD]: 10.5), who were found to be clinically asymptomatic by neurological examination. These carriers were compared to 2 clinically affected PKAN patients 21 and 32years of age and to 13 age-matched, healthy controls (mean age: 39.7; SD, 13.6). Scanning was performed on a 7.0-Tesla whole-body scanner applying three-dimensional susceptibility-weighted gradient echo acquisitions. Susceptibility maps were calculated by threshold-based k-space division with single-orientation acquisition. Magnetic susceptibility values, relative to the occipital white matter, were determined for the following regions of interest (ROI): globus pallidus (GP), thalamus, putamen, internal capsule (IC), caudate nucleus, substantia nigra (SN), and red nucleus. Heterozygous PANK2 mutation carriers did not show increased brain iron concentrations, compared to healthy controls (P>0.05), in any of the examined ROIs. In PKAN patients, more than 3 times higher concentrations of iron were found in the GP, SN, and IC. Our results suggest that heterozygous mutations in PANK2 gene do not cause brain iron accumulation nor do they cause movement disorders.