Simulated and experimental phantom data for multi-center quality assurance of quantitative susceptibility maps at 3 T, 7 T and 9.4 T.

PURPOSE: To develop methods for quality assurance of quantitative susceptibility mapping (QSM) using MRI at different magnetic field strengths, and scanners, using different MR-sequence protocols, and post-processing pipelines. METHODS: We built a custom phantom based on iron in two forms: homogeneous susceptibility ('free iron') and with fine-scaled variations in susceptibility ('clustered iron') at different iron concentrations. The phantom was measured at 3.0 T (two scanners), 7.0 T and 9.4 T using multi-echo, gradient echo acquisition sequences. A digital phantom analogue to the iron-phantom, tailored to obtain similar results as in experimentation was developed, with similar geometry and susceptibility values. Morphology enabled dipole inversion was applied to the phase images to obtain QSM for experimental and simulated data using the MEDI + 0 approach for background regularization. RESULTS: Across all scanners, QSM-values showed a linear increase with iron concentrations. The QSM-relaxivity was 0.231 ± 0.047 ppm/mM for free and 0.054 ± 0.013 ppm/mM for clustered iron, with adjusted determination coefficients (DoC) ≥ 0.87. Similarly, the simulations yielded linear increases (DoC ≥ 0.99). In both the experimental and digital phantoms, the estimated molar susceptibility was lower with clustered iron, because clustering led to highly localized field effects. CONCLUSION: Our iron phantom can be used to evaluate the capability of QSM to detect local variations in susceptibility across different field strengths, when using different MR-sequence protocols. The devised simulation method captures the effect of iron clustering in QSM as seen experimentally and could be used in the future to optimize QSM processing pipelines and achieve higher accuracy for local field effects, as also seen in Alzheimer's beta-amyloid plaques.

Phase-based masking for quantitative susceptibility mapping of the human brain at 9.4T.

PURPOSE: To develop improved tissue masks for QSM. METHODS: Masks including voxels at the brain surface were automatically generated from the magnitude alone (MM) or combined with test functions from the first (PG) or second (PB) derivative of the sign of the wrapped phase. Phase images at 3T and 9.4T were simulated at different TEs and used to generate a mask, PItoh , with between-voxel phase differences less than π. MM, PG, and PB were compared with PItoh . QSM were generated from 3D multi-echo gradient-echo data acquired at 9.4T (21 subjects aged: 20-56y), and from the QSM2016 challenge 3T data using different masks, unwrapping, background removal, and dipole inversion algorithms. QSM contrast was quantified using age-based iron concentrations. RESULTS: Close to air cavities, phase wraps became denser with increasing field and echo time, yielding increased values of the test functions. Compared with PItoh , PB had the highest Dice coefficient, while PG had the lowest and MM the highest percentage of voxels outside PItoh. Artifacts observed in QSM at 9.4T with MM were mitigated by stronger background filters but yielded a reduced QSM contrast. With PB, QSM contrast was greater and artifacts diminished. Similar results were obtained with challenge data, evidencing larger effects of mask close to air cavities. CONCLUSION: Automatic, phase-based masking founded on the second derivative of the sign of the wrapped phase, including cortical voxels at the brain surface, was able to mitigate artifacts and restore QSM contrast across cortical and subcortical brain regions.

Ultra-High Field MRI in Alzheimer's Disease: Effective Transverse Relaxation Rate and Quantitative Susceptibility Mapping of Human Brain In Vivo and Ex Vivo compared to Histology.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. So far, diagnosis of AD is only unequivocally defined through postmortem histology. Amyloid plaques are a classical hallmark of AD and amyloid load is currently quantified by Positron Emission tomography (PET) in vivo. Ultra-high field magnetic resonance imaging (UHF-MRI) can potentially provide a non-invasive biomarker for AD by allowing imaging of pathological processes at a very-high spatial resolution. The first aim of this work was to reproduce the characteristic cortical pattern previously observed in vivo in AD patients using weighted-imaging at 7T. We extended these findings using quantitative susceptibility mapping (QSM) and quantification of the effective transverse relaxation rate (R2*) at 9.4T. The second aim was to investigate the origin of the contrast patterns observed in vivo in the cortex of AD patients at 9.4T by comparing quantitative UHF-MRI (9.4T and 14.1T) of postmortem samples with histology. We observed a distinctive cortical pattern in vivo in patients compared to healthy controls (HC), and these findings were confirmed ex vivo. Specifically, we found a close link between the signal changes detected by QSM in the AD sample at 14.1T and the distribution pattern of amyloid plaques in the histological sections of the same specimen. Our findings showed that QSM and R2* maps can distinguish AD from HC at UHF by detecting cortical alterations directly related to amyloid plaques in AD patients. Furthermore, we provided a method to quantify amyloid plaque load in AD patients at UHF non-invasively.

Disruption of neurite morphology parallels MS progression.

OBJECTIVES: To apply advanced diffusion MRI methods to the study of normal-appearing brain tissue in MS and examine their correlation with measures of clinical disability. METHODS: A multi-compartment model of diffusion MRI called neurite orientation dispersion and density imaging (NODDI) was used to study 20 patients with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS), and 20 healthy controls. Maps of NODDI were analyzed voxel-wise to assess the presence of abnormalities within the normal-appearing brain tissue and the association with disease severity. Standard diffusion tensor imaging (DTI) parameters were also computed for comparing the 2 techniques. RESULTS: Patients with MS showed reduced neurite density index (NDI) and increased orientation dispersion index (ODI) compared with controls in several brain areas (p < 0.05), with patients with SPMS having more widespread abnormalities. DTI indices were also sensitive to some changes. In addition, patients with SPMS showed reduced ODI in the thalamus and caudate nucleus. These abnormalities were associated with scores of disease severity (p < 0.05). The association with the MS functional composite score was higher in patients with SPMS compared with patients with RRMS. CONCLUSIONS: NODDI and DTI findings are largely overlapping. Nevertheless, NODDI helps interpret previous findings of increased anisotropy in the thalamus of patients with MS and are consistent with the degeneration of selective axon populations.

Damage to the Frontal Aslant Tract Accounts for Visuo-Constructive Deficits in Alzheimer's Disease.

The frontal aslant tract (FAT) has been described as a bundle connecting the Broca's area to the supplementary motor area (SMA) and the pre-SMA in both hemispheres. The functional properties of this tract and its role in degenerative dementia, such as Alzheimer's disease (AD), still need to be fully clarified. The aim of this study was to explore the microstructural integrity of the FAT in patients with AD and its potential relationship with cognitive functioning. Twenty-three patients with AD and 25 healthy subjects (HS) were enrolled. All subjects underwent cognitive and MRI examination. MRI, including diffusion sequences, was used for probabilistic tractography analysis. We reconstructed individual FATs bilaterally and assessed their microstructural integrity using fractional anisotropy (FA), computed as both mean tract value and voxel-wise using SPM-8. Mean FA values were then used to test for correlations with cognitive measures. Mean tract FA and voxel-wise analyses revealed that patients with AD, compared to HS, had decreased FA in the FAT bilaterally. In addition, positive associations were found between FA in the FATs and patients' performance at tests for constructional praxis and visuospatial logical reasoning. The present results reveal a bilateral damage of FAT in AD patients. The association between FATs' microscopic abnormalities and constructive abilities fits well with the knowledge of a functional involvement of SMA and pre-SMA in movement sequences when executing constructive praxis tasks. The FAT is an associative bundle critically involved in the network sub-serving constructional praxis in patients with AD.

Strategic lesions in the anterior thalamic radiation and apathy in early Alzheimer's disease.

BACKGROUND: Behavioural disorders and psychological symptoms of Dementia (BPSD) are commonly observed in Alzheimer's disease (AD), and strongly contribute to increasing patients' disability. Using voxel-lesion-symptom mapping (VLSM), we investigated the impact of white matter lesions (WMLs) on the severity of BPSD in patients with amnestic mild cognitive impairment (a-MCI). METHODS: Thirty-one a-MCI patients (with a conversion rate to AD of 32% at 2 year follow-up) and 26 healthy controls underwent magnetic resonance imaging (MRI) examination at 3T, including T2-weighted and fluid-attenuated-inversion-recovery images, and T1-weighted volumes. In the patient group, BPSD was assessed using the Neuropsychiatric Inventory-12. After quantitative definition of WMLs, their distribution was investigated, without an a priori anatomical hypothesis, against patients' behavioural symptoms. Unbiased regional grey matter volumetrics was also used to assess the contribution of grey matter atrophy to BPSD. RESULTS: Apathy, irritability, depression/dysphoria, anxiety and agitation were shown to be the most common symptoms in the patient sample. Despite a more widespread anatomical distribution, a-MCI patients did not differ from controls in WML volumes. VLSM revealed a strict association between the presence of lesions in the anterior thalamic radiations (ATRs) and the severity of apathy. Regional grey matter atrophy did not account for any BPSD. CONCLUSIONS: This study indicates that damage to the ATRs is strategic for the occurrence of apathy in patients with a-MCI. Disconnection between the prefrontal cortex and the mediodorsal and anterior thalamic nuclei might represent the pathophysiological substrate for apathy, which is one of the most common psychopathological symptoms observed in dementia.