Prediction of new cerebral ischemic lesion after carotid artery stenting: a high-resolution vessel wall MRI-based radiomics analysis.

OBJECTIVES: Carotid artery stenting (CAS) is an established treatment for local stenosis. The most common complication is new ipsilateral ischemic lesions (NIILs). This study aimed to develop models considering lesion morphological and compositional features, and radiomics to predict NIILs. MATERIALS AND METHODS: One hundred and forty-six patients who underwent brain MRI and high-resolution vessel wall MR imaging (hrVWI) before and after CAS were retrospectively recruited. Lumen and outer wall boundaries were segmented on hrVWI as well as atherosclerotic components. A traditional model was constructed with patient clinical information, and lesion morphological and compositional features. Least absolute shrinkage and selection operator algorithm was performed to determine key radiomics features for reconstructing a radiomics model. The model in predicting NIILs was trained and its performance was tested. RESULTS: Sixty-one patients were NIIL-positive and eighty-five negative. Volume percentage of intraplaque hemorrhage (IPH) and patients' clinical presentation (symptomatic/asymptomatic) were risk factors of NIILs. The traditional model considering these two features achieved an area under the curve (AUC) of 0.778 and 0.777 in the training and test cohorts, respectively. Twenty-two key radiomics features were identified and the model based on these features achieved an AUC of 0.885 and 0.801 in the two cohorts. The AUCs of the combined model considering IPH volume percentage, clinical presentation, and radiomics features were 0.893 and 0.842 in the training and test cohort respectively. CONCLUSIONS: Compared with traditional features (clinical and compositional features), the combination of traditional and radiomics features improved the power in predicting NIILs after CAS. KEY POINTS: • Volume percentage of IPH and symptomatic events were independent risk factors of new ipsilateral ischemic lesions (NIILs). • Radiomics features derived from carotid artery high-resolution vessel wall imaging had great potential in predicting NIILs after CAS. • The combination model with radiomics and traditional features further improved the diagnostic performance than traditional features alone.

Neuroimaging correlates of brain injury in Wilson's disease: a multimodal, whole-brain MRI study.

Wilson's disease is an autosomal-recessive disorder of copper metabolism with neurological and hepatic presentations. Chelation therapy is used to 'de-copper' patients but neurological outcomes remain unpredictable. A range of neuroimaging abnormalities have been described and may provide insights into disease mechanisms, in addition to prognostic and monitoring biomarkers. Previous quantitative MRI analyses have focused on specific sequences or regions of interest, often stratifying chronically treated patients according to persisting symptoms as opposed to initial presentation. In this cross-sectional study, we performed a combination of unbiased, whole-brain analyses on T1-weighted, fluid-attenuated inversion recovery, diffusion-weighted and susceptibility-weighted imaging data from 40 prospectively recruited patients with Wilson's disease (age range 16-68). We compared patients with neurological (n = 23) and hepatic (n = 17) presentations to determine the neuroradiological sequelae of the initial brain injury. We also subcategorized patients according to recent neurological status, classifying those with neurological presentations or deterioration in the preceding 6 months as having 'active' disease. This allowed us to compare patients with active (n = 5) and stable (n = 35) disease and identify imaging correlates for persistent neurological deficits and copper indices in chronically treated, stable patients. Using a combination of voxel-based morphometry and region-of-interest volumetric analyses, we demonstrate that grey matter volumes are lower in the basal ganglia, thalamus, brainstem, cerebellum, anterior insula and orbitofrontal cortex when comparing patients with neurological and hepatic presentations. In chronically treated, stable patients, the severity of neurological deficits correlated with grey matter volumes in similar, predominantly subcortical regions. In contrast, the severity of neurological deficits did not correlate with the volume of white matter hyperintensities, calculated using an automated lesion segmentation algorithm. Using tract-based spatial statistics, increasing neurological severity in chronically treated patients was associated with decreasing axial diffusivity in white matter tracts whereas increasing serum non-caeruloplasmin-bound ('free') copper and active disease were associated with distinct patterns of increasing mean, axial and radial diffusivity. Whole-brain quantitative susceptibility mapping identified increased iron deposition in the putamen, cingulate and medial frontal cortices of patients with neurological presentations relative to those with hepatic presentations and neurological severity was associated with iron deposition in widespread cortical regions in chronically treated patients. Our data indicate that composite measures of subcortical atrophy provide useful prognostic biomarkers, whereas abnormal mean, axial and radial diffusivity are promising monitoring biomarkers. Finally, deposition of brain iron in response to copper accumulation may directly contribute to neurodegeneration in Wilson's disease.

Neuroimaging Correlates of Cognitive Deficits in Wilson's Disease.

BACKGROUND: Cognitive impairment is common in neurological presentations of Wilson's disease (WD). Various domains can be affected, and subclinical deficits have been reported in patients with hepatic presentations. Associations with imaging abnormalities have not been systematically tested. OBJECTIVE: The aim was to determine the neuroanatomical basis for cognitive deficits in WD. METHODS: We performed a 16-item neuropsychological test battery and magnetic resonance brain imaging in 40 patients with WD. The scores for each test were compared between patients with neurological and hepatic presentations and with normative data. Associations with Unified Wilson's Disease Rating Scale neurological examination subscores were examined. Quantitative, whole-brain, multimodal imaging analyses were used to identify associations with neuroimaging abnormalities in chronically treated stable patients. RESULTS: Abstract reasoning, executive function, processing speed, calculation, and visuospatial function scores were lower in patients with neurological presentations than in those with hepatic presentations and correlated with neurological examination subscores. Deficits in abstract reasoning and phonemic fluency were associated with lower putamen volumes even after controlling for neurological severity. About half of patients with hepatic presentations had poor performance in memory for faces, cognitive flexibility, or associative learning relative to normative data. These deficits were associated with widespread cortical atrophy and/or white matter diffusion abnormalities. CONCLUSIONS: Subtle cognitive deficits in patients with seemingly hepatic presentations represent a distinct neurological phenotype associated with diffuse cortical and white matter pathology. This may precede the classical neurological phenotype characterized by movement disorders and executive dysfunction and be associated with basal ganglia damage. A binary phenotypic classification for WD may no longer be appropriate. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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

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

Associations of Brain Atrophy and Cerebral Iron Accumulation at MRI with Clinical Severity in Wilson Disease.

Background Abnormal findings at brain MRI in patients with neurologic Wilson disease (WD) are characterized by signal intensity changes and cerebral atrophy. T2 signal hypointensities and atrophy are largely irreversible with treatment; their relationship with permanent disability has not been systematically investigated. Purpose To investigate associations of regional brain atrophy and iron accumulation at MRI with clinical severity in participants with neurologic WD who are undergoing long-term anti-copper treatment. Materials and Methods Participants with WD and controls were compared in a prospective study performed from 2015 to 2019. MRI at 3.0 T included three-dimensional T1-weighted and six-echo multigradient-echo pulse sequences for morphometry and quantitative susceptibility mapping, respectively. Neurologic severity was assessed with the Unified WD Rating Scale (UWDRS). Automated multi-atlas segmentation pipeline with dual contrast (susceptibility and T1) was used for the calculation of volumes and mean susceptibilities in deep gray matter nuclei. Additionally, whole-brain analysis using deformation and surface-based morphometry was performed. Least absolute shrinkage and selection operator regression was used to assess the association of regional volumes and susceptibilities with the UWDRS score. Results Twenty-nine participants with WD (mean age, 47 years ± 9 [standard deviation]; 15 women) and 26 controls (mean age, 45 years ± 12; 14 women) were evaluated. Whole-brain analysis demonstrated atrophy of the deep gray matter nuclei, brainstem, internal capsule, motor cortex and corticospinal pathway, and visual cortex and optic radiation in participants with WD (P < .05 at voxel level, corrected for family-wise error). The UWDRS score was negatively correlated with volumes of putamen (r = -0.63, P < .001), red nucleus (r = -0.58, P = .001), globus pallidus (r = -0.53, P = .003), and substantia nigra (r = -0.50, P = .006) but not with susceptibilities. Only the putaminal volume was identified as a stable factor associated with the UWDRS score (R2 = 0.38, P < .001) using least absolute shrinkage and selection operator regression. Conclusion Individuals with Wilson disease (WD) had widespread brain atrophy most pronounced in the central structures. The putaminal volume was associated with the Unified WD Rating Scale score and can be used as a surrogate imaging marker of clinical severity. © RSNA, 2021 Supplemental material is available for this article. See also the editorial by Du and Bydder in this issue.

Comparison of parameter optimization methods for quantitative susceptibility mapping.

PURPOSE: Quantitative Susceptibility Mapping (QSM) is usually performed by minimizing a functional with data fidelity and regularization terms. A weighting parameter controls the balance between these terms. There is a need for techniques to find the proper balance that avoids artifact propagation and loss of details. Finding the point of maximum curvature in the L-curve is a popular choice, although it is slow, often unreliable when using variational penalties, and has a tendency to yield overregularized results. METHODS: We propose 2 alternative approaches to control the balance between the data fidelity and regularization terms: 1) searching for an inflection point in the log-log domain of the L-curve, and 2) comparing frequency components of QSM reconstructions. We compare these methods against the conventional L-curve and U-curve approaches. RESULTS: Our methods achieve predicted parameters that are better correlated with RMS error, high-frequency error norm, and structural similarity metric-based parameter optimizations than those obtained with traditional methods. The inflection point yields less overregularization and lower errors than traditional alternatives. The frequency analysis yields more visually appealing results, although with larger RMS error. CONCLUSION: Our methods provide a robust parameter optimization framework for variational penalties in QSM reconstruction. The L-curve-based zero-curvature search produced almost optimal results for typical QSM acquisition settings. The frequency analysis method may use a 1.5 to 2.0 correction factor to apply it as a stand-alone method for a wider range of signal-to-noise-ratio settings. This approach may also benefit from fast search algorithms such as the binary search to speed up the process.

Relationship between cortical iron and tau aggregation in Alzheimer's disease.

A growing body of evidence suggests that the dysregulation of neuronal iron may play a critical role in Alzheimer's disease. Recent MRI studies have established a relationship between iron accumulation and amyloid-ß aggregation. The present study provides further insight demonstrating a relationship between iron and tau accumulation using magnetic resonance-based quantitative susceptibility mapping and tau-PET in n = 236 subjects with amyloid-ß pathology (from the Swedish BioFINDER-2 study). Both voxel-wise and regional analyses showed a consistent association between differences in bulk magnetic susceptibility, which can be primarily ascribed to an increase in iron content, and tau-PET signal in regions known to be affected in Alzheimer's disease. Subsequent analyses revealed that quantitative susceptibility specifically mediates the relationship between tau-PET and cortical atrophy measures, thus suggesting a modulatory effect of iron burden on the disease process. We also found evidence suggesting the relationship between quantitative susceptibility and tau-PET is stronger in younger participants (age ≤ 65). Together, these results provide in vivo evidence of an association between iron deposition and both tau aggregation and neurodegeneration, which help advance our understanding of the role of iron dysregulation in the Alzheimer's disease aetiology.

A multi-contrast MRI approach to thalamus segmentation.

Thalamic alterations occur in many neurological disorders including Alzheimer's disease, Parkinson's disease and multiple sclerosis. Routine interventions to improve symptom severity in movement disorders, for example, often consist of surgery or deep brain stimulation to diencephalic nuclei. Therefore, accurate delineation of grey matter thalamic subregions is of the upmost clinical importance. MRI is highly appropriate for structural segmentation as it provides different views of the anatomy from a single scanning session. Though with several contrasts potentially available, it is also of increasing importance to develop new image segmentation techniques that can operate multi-spectrally. We hereby propose a new segmentation method for use with multi-modality data, which we evaluated for automated segmentation of major thalamic subnuclear groups using T1 -weighted, T2* -weighted and quantitative susceptibility mapping (QSM) information. The proposed method consists of four steps: Highly iterative image co-registration, manual segmentation on the average training-data template, supervised learning for pattern recognition, and a final convex optimisation step imposing further spatial constraints to refine the solution. This led to solutions in greater agreement with manual segmentation than the standard Morel atlas based approach. Furthermore, we show that the multi-contrast approach boosts segmentation performances. We then investigated whether prior knowledge using the training-template contours could further improve convex segmentation accuracy and robustness, which led to highly precise multi-contrast segmentations in single subjects. This approach can be extended to most 3D imaging data types and any region of interest discernible in single scans or multi-subject templates.

The 2016 QSM Challenge: Lessons learned and considerations for a future challenge design.

PURPOSE: The 4th International Workshop on MRI Phase Contrast and QSM (2016, Graz, Austria) hosted the first QSM Challenge. A single-orientation gradient recalled echo acquisition was provided, along with COSMOS and the χ33 STI component as ground truths. The submitted solutions differed more than expected depending on the error metric used for optimization and were generally over-regularized. This raised (unanswered) questions about the ground truths and the metrics utilized. METHODS: We investigated the influence of background field remnants by applying additional filters. We also estimated the anisotropic contributions from the STI tensor to the apparent susceptibility to amend the χ33 ground truth and to investigate the impact on the reconstructions. Lastly, we used forward simulations from the COSMOS reconstruction to investigate the impact noise had on the metric scores. RESULTS: Reconstructions compared against the amended STI ground truth returned lower errors. We show that the background field remnants had a minor impact in the errors. In the absence of inconsistencies, all metrics converged to the same regularization weights, whereas structural similarity index metric was more insensitive to such inconsistencies. CONCLUSION: There was a mismatch between the provided data and the ground truths due to the presence of unaccounted anisotropic susceptibility contributions and noise. Given the lack of reliable ground truths when using in vivo acquisitions, simulations are suggested for future QSM Challenges.

Brain iron deposition is linked with cognitive severity in Parkinson's disease.

BACKGROUND: Dementia is common in Parkinson's disease (PD) but measures that track cognitive change in PD are lacking. Brain tissue iron accumulates with age and co-localises with pathological proteins linked to PD dementia such as amyloid. We used quantitative susceptibility mapping (QSM) to detect changes related to cognitive change in PD. METHODS: We assessed 100 patients with early-stage to mid-stage PD, and 37 age-matched controls using the Montreal Cognitive Assessment (MoCA), a validated clinical algorithm for risk of cognitive decline in PD, measures of visuoperceptual function and the Movement Disorders Society Unified Parkinson's Disease Rating Scale part 3 (UPDRS-III). We investigated the association between these measures and QSM, an MRI technique sensitive to brain tissue iron content. RESULTS: We found QSM increases (consistent with higher brain tissue iron content) in PD compared with controls in prefrontal cortex and putamen (p<0.05 corrected for multiple comparisons). Whole brain regression analyses within the PD group identified QSM increases covarying: (1) with lower MoCA scores in the hippocampus and thalamus, (2) with poorer visual function and with higher dementia risk scores in parietal, frontal and medial occipital cortices, (3) with higher UPDRS-III scores in the putamen (all p<0.05 corrected for multiple comparisons). In contrast, atrophy, measured using voxel-based morphometry, showed no differences between groups, or in association with clinical measures. CONCLUSIONS: Brain tissue iron, measured using QSM, can track cognitive involvement in PD. This may be useful to detect signs of early cognitive change to stratify groups for clinical trials and monitor disease progression.

Prominent White Matter Involvement in Multiple System Atrophy of Cerebellar Type.

BACKGROUND: Sporadic degenerative ataxia patients fall into 2 major groups: multiple system atrophy with predominant cerebellar ataxia (MSA-C) and sporadic adult-onset ataxia (SAOA). Both groups have cerebellar volume loss, but little is known about the differential involvement of gray and white matter in MSA-C when compared with SAOA. OBJECTIVES: The objective of this study was to identify structural differences of brain gray and white matter between both patient groups. METHODS: We used magnetic resonance imaging to acquire T1-weighted images and diffusion tensor images from 12 MSA-C patients, 31 SAOA patients, and 55 healthy controls. Magnetic resonance imaging data were analyzed with voxel-based-morphometry, tract-based spatial statistics, and tractography-based regional diffusion tensor images analysis. RESULTS: Whole-brain and cerebellar-focused voxel-based-morphometry analysis showed gray matter volume loss in both patient groups when compared with healthy controls, specifically in the cerebellar areas subserving sensorimotor functions. When compared with controls, the SAOA and MSA-C patients showed white matter loss in the cerebellum, whereas brainstem white matter was reduced only in the MSA-C patients. The tract-based spatial statistics revealed reduced fractional anisotropy within the pons and cerebellum in the MSA-C patients both in comparison with the SAOA patients and healthy controls. In addition, tractography-based regional analysis showed reduced fractional anisotropy along the corticospinal tracts in MSA-C, but not SAOA. CONCLUSION: Although in our cohort extent and distribution of gray and white matter loss were similar between the MSA-C and SAOA patients, magnetic resonance imaging data showed prominent microstructural white matter involvement in the MSA-C patients that was not present in the SAOA patients. Our findings highlight the significance of microstructural white matter changes in the differentiation between both conditions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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

BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration is an autosomal-recessive disorder caused by C19orf12 mutations and characterized by iron deposits in the basal ganglia. OBJECTIVES: 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. METHODS: 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. RESULTS AND CONCLUSION: 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.

Multiparametric Quantitative Brain MRI in Neurological and Hepatic Forms of Wilson's Disease.

BACKGROUND: In Wilson's disease (WD), demyelination, rarefaction, gliosis, and iron accumulation in the deep gray matter cause opposing effects on T2 -weighted MR signal. However, the degree and interplay of these changes in chronically treated WD patients has not been quantitatively studied. PURPOSE: To compare differences in brain multiparametric mapping between controls and chronically treated WD patients with neurological (neuro-WD) and hepatic (hep-WD) forms to infer the nature of residual WD neuropathology. STUDY TYPE: Cross-sectional. POPULATION/SUBJECTS: Thirty-eight WD patients (28 neuro-WD, 10 hep-WD); 26 healthy controls. FIELD STRENGTH/SEQUENCE: 3.0T: susceptibility, T2 *, T2 , T1 relaxometry; 1.5T: T2 , T1 relaxometry. ASSESSMENT: The following 3D regions of interest (ROIs) were manually segmented: globus pallidus, putamen, caudate nucleus, and thalamus. Mean bulk magnetic susceptibility, T2 *, T2 , and T1 relaxation times were calculated for each ROI. STATISTICAL TESTS: The effect of group (neuro-WD, hep-WD, controls) and age was assessed using a generalized least squares model with different variance for each ROI and quantitative parameter. A general linear hypothesis test with Tukey adjustment was used for post-hoc between-group analysis; P < 0.05 was considered significant. RESULTS: Susceptibility values were higher in all ROIs in neuro-WD compared to controls and hep-WD (P < 0.001). In basal ganglia, lower T2 and T2 * were found in neuro-WD compared to controls (P < 0.01) and hep-WD (P < 0.05) at 3.0T. Much smaller intergroup differences for T2 in basal ganglia were observed at 1.5T compared to 3.0T. In the thalamus, increased susceptibility in neuro-WD was accompanied by increased T1 at both field strengths (P < 0.001 to both groups), and an increased T2 at 1.5T only (P < 0.001 to both groups). DATA CONCLUSION: We observed significant residual brain MRI abnormalities in neuro-WD but not in hep-WD patients on chronic anticopper treatment. Patterns of changes were suggestive of iron accumulation in the basal ganglia and demyelination in the thalamus; 3.0T was more sensitive for detection of the former and 1.5T of the latter abnormality. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1829-1835.

Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases.

Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer's disease, atypical neurodegenerative dementias and Parkinson's disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.

Diffusion Tensor MRI to Distinguish Progressive Supranuclear Palsy from α-Synucleinopathies.

Background The differential diagnosis of progressive supranuclear palsy (PSP) and Lewy body disorders, which include Parkinson disease and dementia with Lewy bodies, is often challenging due to the overlapping symptoms. Purpose To develop a diagnostic tool based on diffusion tensor imaging (DTI) to distinguish between PSP and Lewy body disorders at the individual-subject level. Materials and Methods In this retrospective study, skeletonized DTI metrics were extracted from two independent data sets: the discovery cohort from the Swedish BioFINDER study and the validation cohort from the Penn Frontotemporal Degeneration Center (data collected between 2010 and 2018). Based on previous neuroimaging studies and neuropathologic evidence, a combination of regions hypothesized to be sensitive to pathologic features of PSP were identified (ie, the superior cerebellar peduncle and frontal white matter) and fractional anisotropy (FA) was used to compute an FA score for each individual. Classification performances were assessed by using logistic regression and receiver operating characteristic analysis. Results In the discovery cohort, 16 patients with PSP (mean age ± standard deviation, 73 years ± 5; eight women, eight men), 34 patients with Lewy body disorders (mean age, 71 years ± 6; 14 women, 20 men), and 44 healthy control participants (mean age, 66 years ± 8; 26 women, 18 men) were evaluated. The FA score distinguished between clinical PSP and Lewy body disorders with an area under the curve of 0.97 ± 0.04, a specificity of 91% (31 of 34), and a sensitivity of 94% (15 of 16). In the validation cohort, 34 patients with PSP (69 years ± 7; 22 women, 12 men), 25 patients with Lewy body disorders (70 years ± 7; nine women, 16 men), and 32 healthy control participants (64 years ± 7; 22 women, 10 men) were evaluated. The accuracy of the FA score was confirmed (area under the curve, 0.96 ± 0.04; specificity, 96% [24 of 25]; and sensitivity, 85% [29 of 34]). Conclusion These cross-validated findings lay the foundation for a clinical test to distinguish progressive supranuclear palsy from Lewy body disorders. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Shah in this issue.

Robust 3D Bloch-Siegert based B1+ mapping using multi-echo general linear modeling.

PURPOSE: Quantitative MRI applications, such as mapping the T1 time of tissue, puts high demands on the accuracy and precision of transmit field ( B1+ ) estimation. A candidate approach to satisfy these requirements exploits the difference in phase induced by the Bloch-Siegert frequency shift (BSS) of 2 acquisitions with opposite off-resonance frequency radiofrequency pulses. Interleaving these radiofrequency pulses ensures robustness to motion and scanner drifts; however, here we demonstrate that doing so also introduces a bias in the B1+ estimates. THEORY AND METHODS: It is shown here by means of simulation and experiments that the amplitude of the error depends on MR pulse sequence parameters, such as repetition time and radiofrequency spoiling increment, but more problematically, on the intrinsic properties, T1 and T2 , of the investigated tissue. To solve these problems, a new approach to BSS-based B1+ estimation that uses a multi-echo acquisition and a general linear model to estimate the correct BSS-induced phase is presented. RESULTS: In line with simulations, phantom and in vivo experiments confirmed that the general linear model-based method removed the dependency on tissue properties and pulse sequence settings. CONCLUSION: The general linear model-based method is recommended as a more accurate approach to BSS-based B1+ mapping.

Prospective motion correction improves high-resolution quantitative susceptibility mapping at 7T.

PURPOSE: Recent literature has shown the potential of high-resolution quantitative susceptibility mapping (QSM) with ultra-high field MRI for imaging the anatomy, the vasculature, and investigating their magnetostatic properties. Higher spatial resolutions, however, translate to longer scans resulting, therefore, in higher vulnerability to, and likelihood of, subject movement. We propose a gradient-recalled echo sequence with prospective motion correction (PMC) to address such limitation. METHODS: Data from 4 subjects were acquired at 7T. The effect of small and large motion on QSM with and without PMC was assessed qualitatively and quantitatively. Full brain QSM and QSM-based venograms with up to 0.33 mm isotropic voxel size were reconstructed. RESULTS: With PMC, motion artifacts in QSM and QSM-based venograms were largely eliminated, enabling-in both large- and small-amplitude motion regimes-accurate depiction of the cortex, vasculature, and other small anatomical structures that are often blurred as a result of head movement or indiscernible at lower image resolutions. Quantitative analyses demonstrated that uncorrected motion could bias regional susceptibility distributions, a trend that was greatly reduced with PMC. CONCLUSION: Qualitatively, PMC prevented image degradation because of motion artifacts, providing highly detailed QSM images and venograms. Quantitatively, PMC increased the reproducibility of susceptibility measures.

Establishing intra- and inter-vendor reproducibility of T1 relaxation time measurements with 3T MRI.

PURPOSE: Parametric imaging methods (e.g., T1 relaxation time mapping) have been shown to be more reproducible across time and vendors than weighted (e.g., T1 -weighted) images. The purpose of this work was to more extensively evaluate the validity of this assertion. METHODS: Seven volunteers underwent twice-repeated acquisitions of variable flip-angle T1 mapping, including B1+ calibration, on a 3T Philips Achieva and 3T Siemens Trio scanner. Intra-scanner and inter-vendor T1 variability were calculated. To determine T1 reproducibility levels in longitudinal settings, or after changing hardware or software, four additional data sets were acquired from two of the participants; one participant was scanned on a different 3T Siemens Trio scanner and another on the same 3T Philips Achieva scanner but after a software upgrade. RESULTS: Intra-scanner variability of voxel-wise T1 values was consistent between the two vendors, averaging 0.7/0.7/1.3/1.4% in white matter/cortical gray matter/subcortical gray matter/cerebellum, respectively. We observed, however, a systematic bias between the two vendors of https://doi.org/10.0/7.8/8.6/10.0%, respectively. The T1 bias across two scanners of the same model was greater than intra-scanner variability, although still only at 1.4/1.0/1.9/2.3%, respectively. A greater bias was identified for data sets acquired before/after software upgrade in white matter/cortical gray matter (3.6/2.7%) whereas variability in subcortical gray matter/cerebellum was comparable (1.7/1.9%). CONCLUSION: We established intra- and inter-vendor reproducibility levels for a widely used T1 mapping protocol. We anticipate that these results will guide the design of multi-center studies, particularly those encompassing multiple vendors. Furthermore, this baseline level of reproducibility should be established or surpassed during the piloting phase of such studies.

Weak-harmonic regularization for quantitative susceptibility mapping.

PURPOSE: Background-field removal is a crucial preprocessing step for quantitative susceptibility mapping (QSM). Remnants from this step often contaminate the estimated local field, which in turn leads to erroneous tissue-susceptibility reconstructions. The present work aimed to mitigate this undesirable behavior with the development of a new approach that simultaneously decouples background contributions and local susceptibility sources on QSM inversion. METHODS: Input phase data for QSM can be seen as a composite scalar field of local effects and residual background components. We developed a new weak-harmonic regularizer to constrain the latter and to separate the 2 components. The resulting optimization problem was solved with the alternating directions of multipliers method framework to achieve fast convergence. In addition, for convenience, a new alternating directions of multipliers method-based preconditioned nonlinear projection onto dipole fields solver was developed to enable initializations with wrapped-phase distributions. Weak-harmonic QSM, with and without nonlinear projection onto dipole fields preconditioning, was compared with the original (alternating directions of multipliers method-based) total variation QSM algorithm in phantom and in vivo experiments. RESULTS: Weak-harmonic QSM returned improved reconstructions regardless of the method used for background-field removal, although the proposed nonlinear projection onto dipole fields method often obtained better results. Streaking and shadowing artifacts were substantially suppressed, and residual background components were effectively removed. CONCLUSION: Weak-harmonic QSM with field preconditioning is a robust dipole inversion technique and has the potential to be extended as a single-step formulation for initialization with uncombined multi-echo data.

The choice of embedding media affects image quality, tissue R2* , and susceptibility behaviors in post-mortem brain MR microscopy at 7.0T.

PURPOSE: The quality and precision of post-mortem MRI microscopy may vary depending on the embedding medium used. To investigate this, our study evaluated the impact of 5 widely used media on: (1) image quality, (2) contrast of high spatial resolution gradient-echo (T1 and T2* -weighted) MR images, (3) effective transverse relaxation rate (R2* ), and (4) quantitative susceptibility measurements (QSM) of post-mortem brain specimens. METHODS: Five formaldehyde-fixed brain slices were scanned using 7.0T MRI in: (1) formaldehyde solution (formalin), (2) phosphate-buffered saline (PBS), (3) deuterium oxide (D2 O), (4) perfluoropolyether (Galden), and (5) agarose gel. SNR and contrast-to-noise ratii (SNR/CNR) were calculated for cortex/white matter (WM) and basal ganglia/WM regions. In addition, median R2* and QSM values were extracted from caudate nucleus, putamen, globus pallidus, WM, and cortical regions. RESULTS: PBS, Galden, and agarose returned higher SNR/CNR compared to formalin and D2 O. Formalin fixation, and its use as embedding medium for scanning, increased tissue R2* . Imaging with agarose, D2 O, and Galden returned lower R2* values than PBS (and formalin). No major QSM offsets were observed, although spatial variance was increased (with respect to R2* behaviors) for formalin and agarose. CONCLUSIONS: Embedding media affect gradient-echo image quality, R2* , and QSM in differing ways. In this study, PBS embedding was identified as the most stable experimental setup, although by a small margin. Agarose and Galden were preferred to formalin or D2 O embedding. Formalin significantly increased R2* causing noisier data and increased QSM variance.