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.

Midbrain MRI assessments in progressive supranuclear palsy subtypes.

OBJECTIVES: To explore the role of the available midbrain-based MRI morphometric assessments in (1) differentiating among progressive supranuclear palsy (PSP) subtypes (PSP Richardson's syndrome (PSP-RS), PSP with predominant parkinsonism (PSP-P) and the other variant syndromes of PSP (vPSP)), and (2) supporting the diagnosis of PSP subtypes compared with Parkinson's disease (PD) and healthy controls (HC). METHODS: Seventy-eight patients with PSP (38 PSP-RS, 21 PSP-P and 19 vPSP), 35 PD and 38 HC were included in the present analysis. Available midbrain-based MRI morphometric assessments were calculated for all participants. RESULTS: Current MRI midbrain-based assessments do not display an adequate sensitivity and specificity profile in differentiating PSP subtypes. On the other hand, we confirmed MR Parkinsonism Index (MRPI) and pons area to midbrain area ratio (P/M) have adequate diagnostic value to support PSP-RS clinical diagnosis compared with both PD and HC, but low sensitivity and specificity profile in differentiating PSP-P from PD as well as from HC. The same measures show acceptable sensitivity and specificity profile in supporting clinical diagnosis of vPSP versus HC but not versus PD. Similar findings were detected for the newer MRPI and P/M versions. CONCLUSIONS: Further studies are warranted to identify neuroimaging biomarkers supporting the clinical phenotypic categorisation of patients with PSP. MRPI and P/M have diagnostic value in supporting the clinical diagnosis of PSP-RS. CLASSIFICATION OF EVIDENCE: This study provides class III evidence that available MRI midbrain-based assessments do not have diagnostic value in differentiating the Movement Disorder Society PSP subtypes.

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.

Multi-site repeatability and reproducibility of MR fingerprinting of the healthy brain at 1.5 and 3.0 T.

Fully-quantitative MR imaging methods are useful for longitudinal characterization of disease and assessment of treatment efficacy. However, current quantitative MRI protocols have not been widely adopted in the clinic, mostly due to lengthy scan times. Magnetic Resonance Fingerprinting (MRF) is a new technique that can reconstruct multiple parametric maps from a single fast acquisition in the transient state of the MR signal. Due to the relative novelty of this technique, the repeatability and reproducibility of quantitative measurements obtained using MRF has not been extensively studied. Our study acquired test/retest data from the brains of nine healthy volunteers, each scanned on five MRI systems (two at 3.0 T and three at 1.5 T, all from a single vendor) located at two different centers. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived M0, 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 an excellent repeatability (CVs of 2-3% for T1, 5-8% for T2, 3% for normalized-M0) and a good reproducibility (CVs of 3-8% for T1, 8-14% for T2, 5% for normalized-M0) in grey and white matter.

Potentials of Ultrahigh-Field MRI for the Study of Somatosensory Reorganization in Congenital Hemiplegia.

Reorganization of somatosensory function influences the clinical recovery of subjects with congenital unilateral brain lesions. Ultrahigh-field (UHF) functional MRI (fMRI) with the use of a 7 T magnet has the potential to contribute fundamentally to the current knowledge of such plasticity mechanisms. The purpose of this study was to obtain preliminary information on the possible advantages of the study of somatosensory reorganization at UHF fMRI. We enrolled 6 young adults (mean age 25 ± 6 years) with congenital unilateral brain lesions (4 in the left hemisphere and 2 in the right hemisphere; 4 with perilesional motor reorganization and 2 with contralesional motor reorganization) and 7 healthy age-matched controls. Nondominant hand sensory assessment included stereognosis and 2-point discrimination. Task-dependent fMRI was performed to elicit a somatosensory activation by using a safe and quantitative device developed ad hoc to deliver a reproducible gentle tactile stimulus to the distal phalanx of thumb and index fingers. Group analysis was performed in the control group. Individual analyses in the native space were performed with data of hemiplegic subjects. The gentle tactile stimulus showed great accuracy in determining somatosensory cortex activation. Single-subject gentle tactile stimulus showed an S1 activation in the postcentral gyrus and an S2 activation in the inferior parietal insular cortex. A correlation emerged between an index of S1 reorganization (distance between expected and reorganized S1) and sensory deficit (p < 0.05) in subjects with hemiplegia, with higher distance related to a more severe sensory deficit. Increase in spatial resolution at 7 T allows a better localization of reorganized tactile function validated by its correlation with clinical measures. Our results support the S1 early-determination hypothesis and support the central role of topography of reorganized S1 compared to a less relevant S1-M1 integration.

The burden of microstructural damage modulates cortical activation in elderly subjects with MCI and leuko-araiosis. A DTI and fMRI study.

The term leuko-araiosis (LA) describes a common chronic affection of the cerebral white matter (WM) in the elderly due to small vessel disease with variable clinical correlates. To explore whether severity of LA entails some adaptive reorganization in the cerebral cortex we evaluated with functional MRI (fMRI) the cortical activation pattern during a simple motor task in 60 subjects with mild cognitive impairment and moderate or severe (moderate-to-severe LA group, n = 46) and mild (mild LA group, n = 14) LA extension on visual rating. The microstructural damage associated with LA was measured on diffusion tensor data by computation of the mean diffusivity (MD) of the cerebral WM and by applying tract based spatial statistics (TBSS). Subjects were examined with fMRI during continuous tapping of the right dominant hand with task performance measurement. Moderate-to-severe LA group showed hyperactivation of left primary sensorimotor cortex (SM1) and right cerebellum. Regression analyses using the individual median of WM MD as explanatory variable revealed a posterior shift of activation within the left SM1 and hyperactivation of the left SMA and paracentral lobule and of the bilateral cerebellar crus. These data indicate that brain activation is modulated by increasing severity of LA with a local remapping within the SM1 and increased activity in ipsilateral nonprimary sensorimotor cortex and bilateral cerebellum. These potentially adaptive changes as well lack of contralateral cerebral hemisphere hyperactivation are in line with sparing of the U fibers and brainstem and cerebellar WM tracts and the emerging microstructual damage of the corpus callosum revealed by TBSS with increasing severity of LA.

Abnormal response to photic stimulation in juvenile myoclonic epilepsy: an EEG-fMRI study.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is a young-onset electroclinical syndrome, characterized by myoclonic, generalized tonic-clonic, and possibly typical absence seizures. Interictal electroencephalography (EEG) displays 3-6 Hz spike/polyspike and wave pattern. Photosensitivity is common. Our aim was to explore the blood oxygen level-dependent (BOLD) response evoked by a highly provocative photic stimulus in a cohort of people with JME compared to a group of nonphotosensitive healthy controls, and to investigate the hemodynamic phenomena seen in patients with photosensitive JME. METHODS: We studied 13 JME patients and 18 healthy controls using EEG-functional magnetic resonance imaging (fMRI) performed during low luminance intermittent photic stimulation (IPS). The BOLD response to IPS was investigated both in JME and control groups. In photosensitive JME subjects, we also performed a dynamic evaluation of BOLD signal changes evoked by the photoparoxysmal response (PPR) in a time frame ranging from 10 s before the onset of the EEG paroxysm up until 10 s afterward. RESULTS: The IPS evoked a positive BOLD response in striate and extrastriate visual areas, which was less in JME patients than in controls. Moreover, people with JME had a reduced positive BOLD response in the frontoparietal areas and putamen but a stronger negative BOLD response in the primary sensorimotor cortex (SM1) and in cortical regions belonging to the default mode network (DMN). In JME, the dynamic evaluation of BOLD signal changes related to PPR revealed an early positive response in the putamen and SM1, followed by BOLD signal decrements in the putamen, caudate nuclei, thalami, and SM1. SIGNIFICANCE: Our results confirm the hypothesis that people with JME might have an altered interaction between the motor circuit and other neuronal networks, with prominent involvement of basal ganglia circuitry. The PPR could be a final expression of pathogenic phenomena occurring in the striato-thalamocortical system, possibly a core feature of system epilepsy JME.

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.

Pleomorphic xanthoastrocytoma: long-term results of surgical treatment and analysis of prognostic factors.

BACKGROUND: Pleomorphic Xanthoastrocytoma (PXA) is a rare brain tumour, most commonly affecting children and young adults. To date, only few data regarding the long-term follow-up of these patients after surgery are available. The aim of this study is to describe our single-institution experience in the surgical management of this particular glioma over a period of over 18 years. METHODS: We performed a retrospective review of all cases of PXA (40 patients) operated upon at the Department of Neurosurgery of Verona, Italy, between 1990 and 2008. The impact of clinical, radiological, surgical and histological factors on overall survival (OS) and progression-free survival (PFS) was analysed by means of univariate and multivariate models. FINDINGS: We achieved a gross total resection (GTR) in 65% of patients. Histological diagnosis was of grade II in 80%; anaplastic features were present in the remaining 20%. Adjuvant treatment, radiotherapy or chemo-radiotherapy, was administered in 40% of the cases. Median follow-up was 74 months. OS at 5- and 10 years was 76.32% and 68.24%, respectively. PFS at 5- and 10 years was 71% and 58%, respectively. In the multivariate model, histological grade, extent of resection and age at diagnosis (≤ 30 years vs > 30 years) were the only independent prognostic factors for both OS and PFS. CONCLUSIONS: Our retrospective long-term study confirms the relatively favourable prognosis associated with PXA. Young patients with a low-grade tumour (WHO grade II) who underwent GTR carry the longest OS and PFS.

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.

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.

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.

Neurodegeneration in friedreich's ataxia is associated with a mixed activation pattern of the brain. A fMRI study.

Friedreich's ataxia (FRDA) is associated with a distributed pattern of neurodegeneration in the spinal cord and the brain secondary to selective neuronal loss. We used functional MR Imaging (fMRI) to explore brain activation in FRDA patients during two motor-sensory tasks of different complexity, i.e. continuous hand tapping and writing of "8" figure, with the right dominant hand and without visual feedback. Seventeen FRDA patients and two groups of age-matched healthy controls were recruited. Task execution was monitored and recorded using MR-compatible devices. Hand tapping was correctly performed by 11 (65%) patients and writing of the "8" by 7 (41%) patients. After correction for behavioral variables, FRDA patients showed in both tasks areas of significantly lower activation in the left primary sensory-motor cortex and right cerebellum. Also left thalamus and right dorsolateral prefrontal cortex showed hypo-activation during hand tapping. During writing of the "8" task FRDA patients showed areas of higher activation in the right parietal and precentral cortex, globus pallidus, and putamen. Activation of right parietal cortex, anterior cingulum, globus pallidus, and putamen during writing of the "8" increased with severity of the neurological deficit. In conclusion fMRI demonstrates in FRDA a mixed pattern constituted by areas of decreased activation and areas of increased activation. The decreased activation in the primary motor cortex and cerebellum presumably reflects a regional neuronal damage, the decreased activation of the left thalamus and primary sensory cortex could be secondary to deafferentation phenomena, and the increased activation of right parietal cortex and striatum might have a possible compensatory significance.

Hypoactivation of the primary sensorimotor cortex in de novo Parkinson's disease : a motor fMRI study under controlled conditions.

INTRODUCTION: Nuclear medicine studies in Parkinson's disease (PD) indicate that nigrostriatal damage causes a widespread cortical hypoactivity assumed to be due to reduced excitatory thalamic outflow. However, so far, functional MRI (fMRI) studies have provided controversial data about this "functional deafferentation" phenomenon. To further clarify this issue, we assessed, with fMRI, de novo drug-naive PD patients using a relatively complex motor task under strictly controlled conditions. METHODS: Nineteen de novo PD patients with right-predominant or bilateral symptoms and 13 age-matched healthy volunteers performed continuous writing of "8" figures with the right-dominant hand using a MR-compatible device that enables identification of incorrectly performed tasks and measures the size and the frequency of the "8"s. The data were analyzed with FSL software and correlated with the clinical severity rated according to the Hoehn and Yahr (HY) staging system. RESULTS: Fifteen (89%) of 19 PD patients and 12 (92%) of 13 controls correctly executed the task. PD patients showed significant hypoactivation of the left primary sensorimotor cortex (SM1) and cerebellum and no hyperactive areas as compared to controls. However, activation in SM1 and supplementary motor area bilaterally, in left supramarginal, parietal inferior, parietal superior and frontal superior gyri as well as in right parietal superior and angular gyri paralleled increasing disease severity as assessed with the HY stage. CONCLUSIONS: In line with the "deafferentation hypothesis", fMRI demonstrates hypoactivation of the SM1 in the early clinical stage of PD.

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.