Evaluation of iron overload in nigrosome 1 via quantitative susceptibility mapping as a progression biomarker in prodromal stages of synucleinopathies.

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies, such as Parkinson's disease (PD), which are characterized by the loss of dopaminergic neurons in substantia nigra, associated with abnormal iron load. The assessment of presymptomatic biomarkers predicting the onset of neurodegenerative disorders is critical for monitoring early signs, screening patients for neuroprotective clinical trials and understanding the causal relationship between iron accumulation processes and disease development. Here, we used Quantitative Susceptibility Mapping (QSM) and 7T MRI to quantify iron deposition in Nigrosome 1 (N1) in early PD (ePD) patients, iRBD patients and healthy controls and investigated group differences and correlation with disease progression. We evaluated the radiological appearance of N1 and analyzed its iron content in 35 ePD, 30 iRBD patients and 14 healthy controls via T2*-weighted sequences and susceptibility (χ) maps. N1 regions of interest (ROIs) were manually drawn on control subjects and warped onto a study-specific template to obtain probabilistic N1 ROIs. For each subject the N1 with the highest mean χ was considered for statistical analysis. The appearance of N1 was rated pathological in 45% of iRBD patients. ePD patients showed increased N1 χ compared to iRBD patients and HC but no correlation with disease duration, indicating that iron load remains stable during the early stages of disease progression. Although no difference was reported in iron content between iRBD and HC, N1 χ in the iRBD group increases as the disease evolves. QSM can reveal temporal changes in N1 iron content and its quantification may represent a valuable presymptomatic biomarker to assess neurodegeneration in the prodromal stages of PD.

Iron-sensitive MR imaging of the primary motor cortex to differentiate hereditary spastic paraplegia from other motor neuron diseases.

OBJECTIVES: Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative diseases characterised by upper motor neuron (UMN) impairment of the lower limbs. The differential diagnosis with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) can be challenging. As microglial iron accumulation was reported in the primary motor cortex (PMC) of ALS cases, here we assessed the radiological appearance of the PMC in a cohort of HSP patients using iron-sensitive MR imaging and compared the PMC findings among HSP, PLS, and ALS patients. METHODS: We included 3-T MRI scans of 23 HSP patients, 7 PLS patients with lower limb onset, 8 ALS patients with lower limb and prevalent UMN onset (UMN-ALS), and 84 ALS patients with any other clinical picture. The PMC was visually rated on 3D T2*-weighted images as having normal signal intensity, mild hypointensity, or marked hypointensity, and differences in the frequency distribution of signal intensity among the diseases were investigated. RESULTS: The marked hypointensity in the PMC was visible in 3/22 HSP patients (14%), 7/7 PLS patients (100%), 6/8 UMN-ALS patients (75%), and 35/84 ALS patients (42%). The frequency distribution of normal signal intensity, mild hypointensity, and marked hypointensity in HSP patients was different than that in PLS, UMN-ALS, and ALS patients (p < 0.01 in all cases). CONCLUSIONS: Iron-sensitive imaging of the PMC could provide useful information in the diagnostic work - up of adult patients with a lower limb onset UMN syndrome, as the cortical hypointensity often seen in PLS and ALS cases is apparently rare in HSP patients. KEY POINTS: • The T2* signal intensity of the primary motor cortex was investigated in patients with HSP, PLS with lower limb onset, and ALS with lower limb and prevalent UMN onset (UMN-ALS) using a clinical 3-T MRI sequence. • Most HSP patients had normal signal intensity in the primary motor cortex (86%); on the contrary, all the PLS and the majority of UMN-ALS patients (75%) had marked cortical hypointensity. • The T2*-weighted imaging of the primary motor cortex could provide useful information in the differential diagnosis of sporadic adult-onset UMN syndromes.

Morphometric imaging and quantitative susceptibility mapping as complementary tools in the diagnosis of parkinsonisms.

BACKGROUND AND PURPOSE: In the quest for in vivo diagnostic biomarkers to discriminate Parkinson's disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA, mainly p phenotype), many advanced magnetic resonance imaging (MRI) techniques have been studied. Morphometric indices, such as the Magnetic Resonance Parkinsonism Index (MRPI), demonstrated high diagnostic value in the comparison between PD and PSP. The potential of quantitative susceptibility mapping (QSM) was hypothesized, as increased magnetic susceptibility (Δχ) was reported in the red nucleus (RN) and medial part of the substantia nigra (SNImed) of PSP patients and in the putamen of MSA patients. However, disease-specific susceptibility values for relevant regions of interest are yet to be identified. The aims of the study were to evaluate the diagnostic potential of a multimodal MRI protocol combining morphometric and QSM imaging in patients with determined parkinsonisms and to explore its value in a population of undetermined cases. METHOD: Patients with suspected degenerative parkinsonism underwent clinical evaluation, 3 T brain MRI and clinical follow-up. The MRPI was manually calculated on T1-weighted images. QSM maps were generated from 3D multi-echo T2*-weighted sequences. RESULTS: In determined cases the morphometric evaluation confirmed optimal diagnostic accuracy in the comparison between PD and PSP but failed to discriminate PD from MSA-p. Significant nigral and extranigral differences were found with QSM. RN Δχ showed excellent diagnostic accuracy in the comparison between PD and PSP and good accuracy in the comparison of PD and MSA-p. Optimal susceptibility cut-off values of RN and SNImed were tested in undetermined cases in addition to MRPI. CONCLUSIONS: A combined use of morphometric imaging and QSM could improve the diagnostic phase of degenerative parkinsonisms.

Three dimensional MRF obtains highly repeatable and reproducible multi-parametric estimations in the healthy human brain at 1.5T and 3T.

Magnetic resonance fingerprinting (MRF) is highly promising as a quantitative MRI technique due to its accuracy, robustness, and efficiency. Previous studies have found high repeatability and reproducibility of 2D MRF acquisitions in the brain. Here, we have extended our investigations to 3D MRF acquisitions covering the whole brain using spiral projection k-space trajectories. Our travelling head study acquired test/retest data from the brains of 12 healthy volunteers and 8 MRI systems (3 systems at 3 T and 5 at 1.5 T, all from a single vendor), using a study design not requiring all subjects to be scanned at all sites. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived PD T1 and T2 maps to an anatomical atlas, coefficients of variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated a high repeatability (CVs 0.7-1.3% for T1, 2.0-7.8% for T2, 1.4-2.5% for normalized PD) and reproducibility (CVs of 2.0-5.8% for T1, 7.4-10.2% for T2, 5.2-9.2% for normalized PD) in gray and white matter. Both repeatability and reproducibility improved when compared to similar experiments using 2D acquisitions. Three-dimensional MRF obtains highly repeatable and reproducible estimations of T1 and T2, supporting the translation of MRF-based fast quantitative imaging into clinical applications.

Retrospective rigid motion correction of three-dimensional magnetic resonance fingerprinting of the human brain.

PURPOSE: To obtain three-dimensional (3D), quantitative and motion-robust imaging with magnetic resonance fingerprinting (MRF). METHODS: Our acquisition is based on a 3D spiral projection k-space scheme. We compared different orderings of trajectory interleaves in terms of rigid motion-correction robustness. In all tested orderings, we considered the whole dataset as a sum of 56 segments of 7-s duration, acquired sequentially with the same flip angle schedule. We performed a separate image reconstruction for each segment, producing whole-brain navigators that were aligned to the first segment using normalized correlation. The estimated rigid motion was used to correct the k-space data, and the aligned data were matched with the dictionary to obtain motion-corrected maps. RESULTS: A significant improvement on the motion-affected maps after motion correction is evident with the suppression of motion artifacts. Correlation with the motionless baseline improved by 20% on average for both T1 and T2 estimations after motion correction. In addition, the average motion-induced quantification bias of 70 ms for T1 and 18 ms for T2 values was reduced to 12 ms and 6 ms, respectively, improving the reliability of quantitative estimations. CONCLUSION: We established a method that allows correcting 3D rigid motion on a 7-s timescale during the reconstruction of MRF data using self-navigators, improving the image quality and the quantification robustness.

Echo-time dependency of quantitative susceptibility mapping reproducibility at different magnetic field strengths.

Quantitative Susceptibility Mapping (QSM) provides a way of measuring iron concentration and myelination non-invasively and has the potential of becoming a tool of paramount importance in the study of a host of different pathologies. However, several experimental factors and the physical properties of magnetic susceptibility (χ) can impair the reliability of QSM, and it is therefore essential to assess QSM reproducibility for repeated acquisitions and different field strength. In particular, it has recently been demonstrated that QSM measurements strongly depend on echo time (TE): the same tissue, measured on the same scanner, exhibits different apparent frequency shifts depending on the TE used. This study aims to assess the influence of TE on intra-scanner and inter-scanner reproducibility of QSM, by using MRI systems operating at 3T and 7T. To maximize intra-scanner reproducibility it is necessary to match the TEs of the acquisition protocol, but the application of this rule leads to inconsistent QSM values across scanners operating at different static magnetic field. This study however demonstrates that, provided a careful choice of acquisition parameters, and in particular by using TEs at 3T that are approximately 2.6 times longer than those at 7T, highly reproducible whole-brain χ maps can be achieved also across different scanners, which renders QSM a suitable technique for longitudinal follow-up in clinical settings and in multi-center studies.

Present and Future of Ultra-High Field MRI in Neurodegenerative Disorders.

PURPOSE OF REVIEW: With a high signal-to-noise ratio, unparalleled spatial resolution, and improved contrasts, ultra-high field MR (≥ 7 T) has great potential in depicting the normal radiological anatomy of smaller structures in the brain and can also provide more information about morphological, quantitative, and metabolic changes associated with a wide range of brain disorders. By focusing attention on specific brain regions believed to be associated with early pathological change, or by more closely inspecting recognized foci of brain pathology, ultra-high field MR can improve the accuracy and sensitivity of neuroimaging. This article reviews recent studies at ultra-high field about Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). RECENT FINDINGS: The research on AD has mainly focused on detecting the thinning of hippocampal layers and the susceptibility effect supposed to be related to beta-amyloid deposition. In patients with PD, atypical parkinsonisms and subjects at risk of developing motor symptoms of Parkinson's disease, the main aim was to detect changes in the substantia nigra, probably related to increased iron deposition. In patients with ALS, both brain and spinal cord were investigated, with the aim of finding changes in the primary motor cortex and corticospinal tract which reflect neurodegeneration and neuroinflammation. Ultra-high field MR was shown to be useful for detecting subtle brain changes in patients with AD, and possible new diagnostic biomarkers in patients with PD and ALS were discovered. The ability of 7 T MR to provide prognostic biomarkers in subjects at risk for developing synucleinopathies is currently under evaluation.

Hippocampal subfields at ultra high field MRI: An overview of segmentation and measurement methods.

The hippocampus is one of the most interesting and studied brain regions because of its involvement in memory functions and its vulnerability in pathological conditions, such as neurodegenerative processes. In the recent years, the increasing availability of Magnetic Resonance Imaging (MRI) scanners that operate at ultra-high field (UHF), that is, with static magnetic field strength ≥7T, has opened new research perspectives. Compared to conventional high-field scanners, these systems can provide new contrasts, increased signal-to-noise ratio and higher spatial resolution, thus they may improve the visualization of very small structures of the brain, such as the hippocampal subfields. Studying the morphometry of the hippocampus is crucial in neuroimaging research because changes in volume and thickness of hippocampal subregions may be relevant in the early assessment of pathological cognitive decline and Alzheimer's Disease (AD). The present review provides an overview of the manual, semi-automated and fully automated methods that allow the assessment of hippocampal subfield morphometry at UHF MRI, focusing on the different hippocampal segmentation produced. © 2017 Wiley Periodicals, Inc.

The impact of white matter fiber orientation in single-acquisition quantitative susceptibility mapping.

The aim of this work was to assess the impact of tissue structural orientation on quantitative susceptibility mapping (QSM) reliability, and to provide a criterion to identify voxels in which measures of magnetic susceptibility (χ) are most affected by spatial orientation effects. Four healthy volunteers underwent 7-T magnetic resonance imaging (MRI). Multi-echo, gradient-echo sequences were used to obtain quantitative maps of frequency shift (FS) and χ. Information from diffusion tensor imaging (DTI) was used to investigate the relationship between tissue orientation and FS measures and QSM. After sorting voxels on the basis of their fractional anisotropy (FA), the variations in FS and χ values over tissue orientation were measured. Using a K-means clustering algorithm, voxels were separated into two groups depending on the variability of measures within each FA interval. The consistency of FS and QSM values, observed at low FA, was disrupted for FA > 0.6. The standard deviation of χ measured at high FA (0.0103 ppm) was nearly five times that at low FA (0.0022 ppm). This result was consistent through data across different head positions and for different brain regions considered separately, which confirmed that such behavior does not depend on structures with different bulk susceptibility oriented along particular angles. The reliability of single-orientation QSM anticorrelates with local FA. QSM provides replicable values with little variability in brain regions with FA < 0.6, but QSM should be interpreted cautiously in major and coherent fiber bundles, which are strongly affected by structural anisotropy and magnetic susceptibility anisotropy.

Assessment of Silent T1-weighted head imaging at 7 T.

OBJECTIVES: This study aimed to assess the performance of a "Silent" zero time of echo (ZTE) sequence for T1-weighted brain imaging using a 7 T MRI system. METHODS: The Silent sequence was evaluated qualitatively by two neuroradiologists, as well as quantitatively in terms of tissue contrast, homogeneity, signal-to-noise ratio (SNR) and acoustic noise. It was compared to conventional T1-weighted imaging (FSPGR). Adequacy for automated segmentation was evaluated in comparison with FSPGR acquired at 7 T and 1.5 T. Specific absorption rate (SAR) was also measured. RESULTS: Tissue contrast and homogeneity in Silent were remarkable in deep brain structures and in the occipital and temporal lobes. Mean tissue contrast was significantly (p < 0.002) higher in Silent (0.25) than in FSPGR (0.11), which favoured automated tissue segmentation. On the other hand, Silent images had lower SNR with respect to conventional imaging: average SNR of FSPGR was 2.66 times that of Silent. Silent images were affected by artefacts related to projection reconstruction, which nevertheless did not compromise the depiction of brain tissues. Silent acquisition was 35 dB(A) quieter than FSPGR and less than 2.5 dB(A) louder than ambient noise. Six-minute average SAR was <2 W/kg. CONCLUSIONS: The ZTE Silent sequence provides high-contrast T1-weighted imaging with low acoustic noise at 7 T. KEY POINTS: • "Silent" is an MRI technique allowing zero time of echo acquisition • Its feasibility and performance were assessed on a 7 T MRI system • Image quality in several regions was higher than in conventional techniques • Imaging acoustic noise was dramatically reduced compared with conventional imaging • "Silent" is suitable for T1-weighted head imaging at 7 T.

Time-of-flight MRA of intracranial vessels at 7 T.

BACKGROUND: Three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) is a largely adopted non-invasive technique for assessing cerebrovascular diseases. We aimed to optimize the 7-T TOF-MRA acquisition protocol, confirm that it outperforms conventional 3-T TOF-MRA, and compare 7-T TOF-MRA with digital subtraction angiography (DSA) in patients with different vascular pathologies. METHODS: Seven-tesla TOF-MRA sequences with different spatial resolutions acquired in four healthy subjects were compared with 3-T TOF-MRA for signal-to-noise and contrast-to-noise ratios as well as using a qualitative scale for vessel visibility and the quantitative Canny algorithm. Four patients with cerebrovascular disease (primary arteritis of the central nervous system, saccular aneurism, arteriovenous malformation, and dural arteriovenous fistula) underwent optimized 7-T TOF-MRA and DSA as reference. Images were compared visually and using the complex-wavelet structural similarity index. RESULTS: Contrast-to-noise ratio was higher at 7 T (4.5 ± 0.8 (mean ± standard deviation)) than at 3 T (2.7 ± 0.9). The mean quality score for all intracranial vessels was higher at 7 T (2.89) than at 3 T (2.28). Angiogram quality demonstrated a better vessel border detection at 7 T than at 3 T (44,166 versus 28,720 pixels). Of 32 parameters used for diagnosing cerebrovascular diseases on DSA, 27 (84%) were detected on 7-T TOF-MRA; the similarity index ranged from 0.52 (dural arteriovenous fistula) to 0.90 (saccular aneurysm). CONCLUSIONS: Seven-tesla TOF-MRA outperformed conventional 3-T TOF-MRA in evaluating intracranial vessels and exhibited an excellent image quality when compared to DSA. Seven-tesla TOF-MRA might improve the non-invasive diagnostic approach to several cerebrovascular diseases. RELEVANCE STATEMENT: An optimized TOF-MRA sequence at 7 T outperforms 3-T TOF-MRA, opening perspectives to its clinical use for noninvasive diagnosis of paradigmatic pathologies of intracranial vessels. KEY POINTS: • An optimized 7-T TOF-MRA protocol was selected for comparison with clinical 3-T TOF-MRA for assessing intracranial vessels. • Seven-tesla TOF-MRA outperformed 3-T TOF-MRA in both quantitative and qualitative evaluation. • Seven-tesla TOF-MRA is comparable to DSA for the diagnosis and characterization of intracranial vascular pathologies.

Detection of pathological contrast enhancement with synthetic brain imaging from quantitative multiparametric MRI.

BACKGROUND AND PURPOSE: We aimed to test whether synthetic T1-weighted imaging derived from a post-contrast Quantitative Transient-state Imaging (QTI) acquisition enabled revealing pathological contrast enhancement in intracranial lesions. METHODS: The analysis included 141 patients who underwent a 3 Tesla-MRI brain exam with intravenous contrast media administration, with the post-contrast acquisition protocol comprising a three-dimensional fast spoiled gradient echo (FSPGR) sequence and a QTI acquisition. Synthetic T1-weighted images were generated from QTI-derived quantitative maps of relaxation times and proton density. Two neuroradiologists assessed synthetic and conventional post-contrast T1-weighted images for the presence and pattern of pathological contrast enhancement in intracranial lesions. Enhancement volumes were quantitatively compared. RESULTS: Using conventional imaging as a reference, synthetic T1-weighted imaging was 93% sensitive in revealing the presence of contrast enhancing lesions. The agreement for the presence/absence of contrast enhancement was almost perfect both between readers (k = 1 for both conventional and synthetic imaging) and between sequences (k = 0.98 for both readers). In 91% of lesions, synthetic T1-weighted imaging showed the same pattern of contrast enhancement visible in conventional imaging. Differences in enhancement pattern in the remaining lesions can be due to the lower spatial resolution and the longer acquisition delay from contrast media administration of QTI compared to FSPGR. Overall, enhancement volumes appeared larger in synthetic imaging. CONCLUSIONS: QTI-derived post-contrast synthetic T1-weighted imaging captures pathological contrast enhancement in most intracranial enhancing lesions. Further comparative studies employing quantitative imaging with higher spatial resolution is needed to support our data and explore possible future applications in clinical trials.

Case report: Exploring chemoradiotherapy-induced leukoencephalopathy with 7T imaging and quantitative susceptibility mapping.

Chemotherapy and radiotherapy are widely used in the treatment of central nervous system tumors and acute lymphocytic leukemia even in the pediatric population. However, such treatments run the risk of a broad spectrum of cognitive and neurological deficits. Even though the correlation with cognitive decline is still not clear, neuroradiological defects linked to white matter injury and vasculopathies may be identified. Thanks to the use of 7T MRI it is possible to better define the vascular pattern of the brain lesions with the added advantage of identifying their characteristics and anatomical localization, which, however, are not evident with a conventional brain scan. Moreover, the use of Quantitative Susceptibility Mapping (QSM) makes it possible to discriminate between calcium deposits on vessels (chemo-radiation-induced) and hemoglobin deposition in radio-induced cavernomas, speculating, as a result, about the pathophysiology of iatrogenic brain damage. We describe the case of a 9 year-old boy with a T-type acute lymphoid leukemia who had previously been treated with polychemotherapy and high-dose RT. To better define the child's neuroradiological pattern, 7T MRI and QSM were performed in addition to conventional imaging examinations. Our case report suggests the potential usefulness of a QSM study to distinguish radio-induced vascular malformations from mineralizing microangiopathy.

Generating Synthetic Radiological Images with PySynthMRI: An Open-Source Cross-Platform Tool.

Synthetic MR Imaging allows for the reconstruction of different image contrasts from a single acquisition, reducing scan times. Commercial products that implement synthetic MRI are used in research. They rely on vendor-specific acquisitions and do not include the possibility of using custom multiparametric imaging techniques. We introduce PySynthMRI, an open-source tool with a user-friendly interface that uses a set of input images to generate synthetic images with diverse radiological contrasts by varying representative parameters of the desired target sequence, including the echo time, repetition time and inversion time(s). PySynthMRI is written in Python 3.6, and it can be executed under Linux, Windows, or MacOS as a python script or an executable. The tool is free and open source and is developed while taking into consideration the possibility of software customization by the end user. PySynthMRI generates synthetic images by calculating the pixelwise signal intensity as a function of a set of input images (e.g., T1 and T2 maps) and simulated scanner parameters chosen by the user via a graphical interface. The distribution provides a set of default synthetic contrasts, including T1w gradient echo, T2w spin echo, FLAIR and Double Inversion Recovery. The synthetic images can be exported in DICOM or NiFTI format. PySynthMRI allows for the fast synthetization of differently weighted MR images based on quantitative maps. Specialists can use the provided signal models to retrospectively generate contrasts and add custom ones. The modular architecture of the tool can be exploited to add new features without impacting the codebase.

Brainstem anatomy with 7-T MRI: in vivo assessment and ex vivo comparison.

BACKGROUND: The brainstem contains grey matter nuclei and white matter tracts to be identified in clinical practice. The small size and the low contrast among them make their in vivo visualisation challenging using conventional magnetic resonance imaging (MRI) sequences at high magnetic field strengths. Combining higher spatial resolution, signal- and contrast-to-noise ratio and sensitivity to magnetic susceptibility (χ), susceptibility-weighted 7-T imaging could improve the assessment of brainstem anatomy. METHODS: We acquired high-resolution 7-T MRI of the brainstem in a 46-year-old female healthy volunteer (using a three-dimensional multi-echo gradient-recalled-echo sequence; spatial resolution 0.3 × 0.3 × 1.2 mm3) and in a brainstem sample from a 48-year-old female body donor that was sectioned and stained. Images were visually assessed; nuclei and tracts were labelled and named according to the official nomenclature. RESULTS: This in vivo imaging revealed structures usually evaluated through light microscopy, such as the accessory olivary nuclei, oculomotor nucleus and the medial longitudinal fasciculus. Some fibre tracts, such as the medial lemniscus, were visible for most of their course. Overall, in in vivo acquisitions, χ and frequency maps performed better than T2*-weighted imaging and allowed for the evaluation of a greater number of anatomical structures. All the structures identified in vivo were confirmed by the ex vivo imaging and histology. CONCLUSIONS: The use of multi-echo GRE sequences at 7 T allowed the visualisation of brainstem structures that are not visible in detail at conventional magnetic field and opens new perspectives in the diagnostic and therapeutical approach to brain disorders. RELEVANCE STATEMENT: In vivo MR imaging at UHF provides detailed anatomy of CNS substructures comparable to that obtained with histology. Anatomical details are fundamentals for diagnostic purposes but also to plan a direct targeting for a minimally invasive brain stimulation or ablation. KEY POINTS: • The in vivo brainstem anatomy was explored with ultrahigh field MRI (7 T). • In vivo T2*-weighted magnitude, χ, and frequency images revealed many brainstem structures. • Ex vivo imaging and histology confirmed all the structures identified in vivo. • χ and frequency imaging revealed more brainstem structures than magnitude imaging.

Development of associational fiber tracts in fetal human brain: a cadaveric laboratory investigation.

The advent of diffusion tensor imaging (DTI) in addition to cadaveric brain dissection allowed a comprehensive description of an adult human brain. Nonetheless, the knowledge of the development of the internal architecture of the brain is mostly incomplete. Our study aimed to provide a description of the anatomical variations of the major associational bundles, among fetal and early post-natal periods. Seventeen formalin-fixed fetal human brains were enrolled for sulci analysis, and 13 specimens were dissected under the operating microscope, using Klingler's technique. Although fronto-temporal connections could be observed in all stages of development, a distinction between the uncinate fascicle, and the inferior fronto-occipital fascicle was clear starting from the early preterm period (25-35 post-conceptional week). Similarly, we were consistently able to isolate the periatrial white matter that forms the sagittal stratum (SS), with no clear distinction among SS layers. Arcuate fascicle and superior longitudinal fascicle were isolated only at the late stage of development without a reliable description of their entire course. The results of our study demonstrated that, although white matter is mostly unmyelinated among fetal human brains, cadaveric dissection can be performed with consistent results. Furthermore, the stepwise development of the associational fiber tracts strengthens the hypothesis that anatomy and function run in parallel, and higher is the cognitive functions subserved by an anatomical structure, later the development of the fascicle. Further histological-anatomical-DWI investigations are required to appraise and explore this topic.

Quantitative T1 mapping detects blood-brain barrier breakdown in apparently non-enhancing multiple sclerosis lesions.

OBJECTIVES: The disruption of the blood-brain barrier (BBB) is a key and early feature in the pathogenesis of demyelinating multiple sclerosis (MS) lesions and has been neuropathologically demonstrated in both active and chronic plaques. The local overt BBB disruption in acute demyelinating lesions is captured as signal hyperintensity in post-contrast T1-weighted images because of the contrast-related shortening of the T1 relaxation time. On the contrary, the subtle BBB disruption in chronic lesions is not visible at conventional radiological evaluation but it might be of clinical relevance. Indeed, persistent, subtle BBB leakage might be linked to low-grade inflammation and plaque evolution. Here we hypothesised that 3D Quantitative Transient-state Imaging (QTI) was able to reveal and measure T1 shortening (ΔT1) reflecting small amounts of contrast media leakage in apparently non-enhancing lesions (ANELs). MATERIALS AND METHODS: Thirty-four patients with relapsing remitting MS were included in the study. All patients underwent a 3 T MRI exam of the brain including conventional sequences and QTI acquisitions (1.1 mm isotropic voxel) performed both before and after contrast media administration. For each patient, a ΔT1 map was obtained via voxel-wise subtraction of pre- and post- contrast QTI-derived T1 maps. ΔT1 values measured in ANELs were compared with those recorded in enhancing lesions and in the normal appearing white matter. A reference distribution of ΔT1 in the white matter was obtained from datasets acquired in 10 non-MS patients with unrevealing MR imaging. RESULTS: Mean ΔT1 in ANELs (57.45 ± 48.27 ms) was significantly lower than in enhancing lesions (297.71 ± 177.52 ms; p < 0. 0001) and higher than in the normal appearing white matter (36.57 ± 10.53 ms; p < 0.005). Fifty-two percent of ANELs exhibited ΔT1 higher than those observed in the white matter of non-MS patients. CONCLUSIONS: QTI-derived quantitative ΔT1 mapping enabled to measure contrast-related T1 shortening in ANELs. ANELs exhibiting ΔT1 values that deviate from the reference distribution in non-MS patients may indicate persistent, subtle, BBB disruption. Access to this information may be proved useful to better characterise pathology and objectively monitor disease activity and response to therapy.

Motor cortical patterns of upper motor neuron pathology in amyotrophic lateral sclerosis: A 3 T MRI study with iron-sensitive sequences.

BACKGROUND: Patterns of initiation and propagation of disease in Amyotrophic Lateral Sclerosis (ALS) are still partly unknown. Single or multiple foci of neurodegeneration followed by disease diffusion to contiguous or connected regions have been proposed as mechanisms underlying symptom occurrence. Here, we investigated cortical patterns of upper motor neuron (UMN) pathology in ALS using iron-sensitive MR imaging. METHODS: Signal intensity and magnetic susceptibility of the primary motor cortex (M1), which are associated with clinical UMN burden and neuroinflammation, were assessed in 78 ALS patients using respectively T2*-weighted images and Quantitative Susceptibility Maps. The signal intensity of the whole M1 and each of its functional regions was rated as normal or reduced, and the magnetic susceptibility of each M1 region was measured. RESULTS: The highest frequencies of T2* hypointensity were found in M1 regions associated with the body sites of symptom onset. Homologous M1 regions were both hypointense in 80-93 % of patients with cortical abnormalities, and magnetic susceptibility values measured in homologous M1 regions were strongly correlated with each other (ρ = 0.88; p < 0.0001). In some cases, the T2* hypointensity was detectable in two non-contiguous M1 regions but spared the cortex in between. CONCLUSIONS: M1 regions associated with the body site of onset are frequently affected at imaging. The simultaneous involvement of both homologous M1 regions is frequent, followed by that of adjacent regions; the affection of non-contiguous regions, instead, seems rare. This type of cortical involvement suggests the interhemispheric connections as one of the preferential paths for the UMN pathology diffusion in ALS.

Abducens nerve palsy in a congenital anomalous neurovascular development of the sixth cranial nerve and anterior inferior cerebellar artery: A case report.

Abducens nerve palsy is a common ocular motor paralysis with a broad set of etiopathogenetic causes. Magnetic resonance imaging is a key diagnostic technique to investigate organic causes of sixth nerve palsy, as it allows a detailed representation of the course of the nerve, particularly in its intracisternal tract. Anatomical variants of the sixth cranial nerve comprise duplications and fenestrations in various traits. Anatomical variants of cerebellar arteries have also been described. We report the case of a patient with abducens nerve palsy presumably related to a neurovascular conflict due to a peculiar anatomical variant, which consists in a cerebellar artery passing through the intracisternal duplication of the abducens nerve.

Distribution Indices of Magnetic Susceptibility Values in the Primary Motor Cortex Enable to Classify Patients with Amyotrophic Lateral Sclerosis.

Quantitative Susceptibility Mapping (QSM) can measure iron concentration increase in the primary motor cortex (M1) of patients with Amyotrophic Lateral Sclerosis (ALS). However, such alteration is confined to only specific regions interested by upper motor neuron pathology; therefore, mean QSM values in the entire M1 have limited diagnostic accuracy in discriminating between ALS patients and control subjects. This study investigates the diagnostic accuracy of a broader set of M1 QSM distribution indices in classifying ALS patients and controls. Mean, standard deviation, skewness and kurtosis of M1 QSM values were used either individually or as combined predictors in support vector machines. The classification performance was compared to that obtained by the radiological assessment of T2* signal hypo-intensity of M1 in susceptibility-weighted MRI. The least informative index for the classification of ALS patients and controls was the subject's mean QSM value in M1. The highest diagnostic performance was obtained when all the distribution indices of positive QSM values in M1 were considered, which yielded a diagnostic accuracy of 0.90, with sensitivity = 0.89 and specificity = 1. The radiological assessment of M1 yielded a diagnostic accuracy of 0.79, with sensitivity = 0.76 and specificity = 0.90. The joint evaluation of QSM distribution indices could support the clinical examination in ALS diagnosis and patient monitoring.