Susceptibility-weighted Imaging: Technical Essentials and Clinical Neurologic Applications.

Susceptibility-weighted imaging (SWI) evolved from simple two-dimensional T2*-weighted sequences to three-dimensional sequences with improved spatial resolution and enhanced susceptibility contrast. SWI is an MRI sequence sensitive to compounds that distort the local magnetic field (eg, calcium and iron), in which the phase information can differentiate. But the term SWI is colloquially used to denote high-spatial-resolution susceptibility-enhanced sequences across different MRI vendors and sequences even when phase information is not used. The imaging appearance of SWI and related sequences strongly depends on the acquisition technique. Initially, SWI and related sequences were mostly used to improve the depiction of findings already known from standard two-dimensional T2*-weighted neuroimaging: more microbleeds in patients who are aging or with dementia or mild brain trauma; increased conspicuity of superficial siderosis in Alzheimer disease and amyloid angiopathy; and iron deposition in neurodegenerative diseases or abnormal vascular structures, such as capillary telangiectasia. But SWI also helps to identify findings not visible on standard T2*-weighted images: the nigrosome 1 in Parkinson disease and dementia with Lewy bodies, the central vein and peripheral rim signs in multiple sclerosis, the peripheral rim sign in abscesses, arterial signal loss related to thrombus, asymmetrically prominent cortical veins in stroke, and intratumoral susceptibility signals in brain neoplasms.

Distinct pattern of microsusceptibility changes on brain magnetic resonance imaging (MRI) in critically ill patients on mechanical ventilation/oxygenation.

PURPOSE: Over the years, interesting SWI abnormalities in patients from intensive care units (ICU) were observed, not attributable to a specific cause and with uncertain clinical significance. Recently, multiple SWI-hypointense foci were mentioned related to neurological complications of SARS-COV-2 infection. The purpose of the study was to describe the patterns of susceptibility brain changes in critically-ill patients who underwent mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO). METHODS: An institutional board-approved, retrospective study was conducted on 250 ICU patients in whom brain MRI was performed between January 2011 and May 2020. Out of 48 patients who underwent mechanical ventilation/ECMO, in fifteen patients (median age 47.7 years), the presence of SWI abnormalities was observed and described. RESULTS: Microsusceptibilities were located in white-gray matter interface, in subcortical white matter (U-fibers), and surrounding subcortical nuclei in 13/14 (92,8%) patients. In 8/14 (57,1%) patients, SWI foci were seen infratentorially. The corpus callosum was affected in ten (71,4%), internal capsule in five (35,7%), and midbrain/pons in six (42,8%) patients. CONCLUSION: We showed distinct patterns of diffuse brain SWI susceptibilities in critically-ill patients who underwent mechanical ventilation/ECMO. The etiology of these foci remains uncertain, but the association with mechanical ventilation, prolonged respiratory failure, and hypoxemia seems probable explanations.

[Long COVID: long-term symptoms and morphological/radiological correlates]. / Long-COVID: Langzeitsymptome und morphologische/radiologische Korrelate.

BACKGROUND: Neurologic, pulmonary, cardiac and gastrointestinal functional disorders can persist in the post-acute phase and constitute a long COVID syndrome, also known as post-acute sequelae of SARS-CoV­2 infection (PASC). Some patients develop persistent and debilitating symptoms despite a relatively mild illness at onset and they are known as COVID-19 long haulers. OBJECTIVE: Presentation of symptoms, signs and biomarkers present in patients previously affected by COVID-19 and discussion of possible underlying mechanisms and consequences. METHODS: Existing literature and reported cases as well as expert opinions are analyzed and discussed. RESULTS: Long COVID affects survivors of COVID-19 at all levels of disease severity, even in mild to moderate cases and younger adults who did not require respiratory support, hospitalization or intensive care. A challenging aspect is that many long haulers never had laboratory confirmation of COVID-19, raising skepticism that the persistent symptoms have a physiological basis. On the other hand, some symptoms seen in post-acute COVID-19 may occur as a consequence of critical illness or as a side effect of treatment. CONCLUSION: Given that COVID-19 is a new disease, it is not possible to determine how long these effects will last. Long-term monitoring of post-acute COVID-19 symptoms and screening for frequent comorbid conditions are essential.

Leptomeningeal form of Immunoglobulin G4-related hypertrophic meningitis with perivascular spread: a case report and review of the literature.

PURPOSE: Immunoglobulin G4 (IgG4)-related disease represents a spectrum of fibro-inflammatory disorders that affects various organ systems, including the central nervous system. METHODS: Here we present the case of lgG4-related hypertrophic meningitis with exclusively leptomeningeal involvement and spread via perivascular spaces. RESULTS: A 58-year-old male patient presented with complex partial seizures. Initial computed tomography examination showed left frontal sulcal hyperdensity. Subsequent magnetic resonance examination revealed FLAIR hyperintensity in the central sulcus, with post-contrast enhancement in the form of "dotted line." Physical examination, routine laboratory, and cerebrospinal fluid analyses were unremarkable. Meningeal biopsy confirmed IgG4-related meningitis. After corticosteroid treatment, a complete resolution of imaging findings was observed. Two months later, the patient presented with relapsing neurological symptoms and radiological findings in postcentral, precentral, and temporal sulci, resembling the form of "dotted line" contrast enhancement. In addition, linear intraparenchymal enhancement that followed perivascular spaces was seen in the left parietal lobe. After repeated steroid therapy, all lesions resolved completely. CONCLUSION: We reported the first case of isolated IgG4-related leptomeningeal involvement with a "dotted line" enhancement and perivascular intraparenchymal spread. Although IgG4-related meningitis represents a rare disease, both clinicians and radiologists should include this condition in the differential diagnosis of unclear leptomeningeal disease.

Differentiation of pyogenic and fungal brain abscesses with susceptibility-weighted MR sequences.

INTRODUCTION: Conventional magnetic resonance imaging (MRI) techniques are insufficient to determine the causative agent of brain abscesses. We investigated: (1) the value of susceptibility-weighted MR sequences (SWMRS) in the differentiation of fungal and pyogenic brain abscesses; and (2) the effect of different SWMRS (susceptibility-weighted imaging (SWI) versus venous blood oxygen level dependent (VenoBOLD)) for the detection of specific imaging characteristics of pyogenic brain abscesses. METHODS: We studied six patients with fungal and ten patients with pyogenic brain abscesses. Imaging characteristics on conventional MRI, diffusion-weighted imaging (DWI) and SWMRS were recorded in all abscesses. All lesions were assessed for the presence of a "dual-rim sign" on SWMRS. RESULTS: Homogenously hyperintense lesions on DWI were present in 60 % of patients with pyogenic abscesses, whereas none of the patients with fungal abscesses showed such lesions. On SWMRS, 90 % of patients with pyogenic abscesses and 60 % of patients with fungal abscesses had only lesions with a low-signal-intensity rim. On SWI, the dual-rim sign was apparent in all pyogenic abscesses. None of the fungal abscesses on SWI (P = 0.005) or any of the pyogenic abscesses on VenoBOLD (P = 0.005) were positive for a dual-rim sign. CONCLUSIONS: In fungal abscesses, the dual-rim sign is not present but a prominent peripheral rim or central susceptibility effects on SWI will be seen. The appearance of pyogenic abscesses on SWMRS depends on the used sequence, with the dual-rim sign a specific feature of pyogenic brain abscesses on SWI.

CNS efficacy parameters of combination antiretroviral therapy in chronic HIV infection: A multi-voxel magnetic resonance spectroscopy study.

This study aimed to determine the correlations of combination antiretroviral therapy (cART) efficacy parameters in the central nervous system (CNS) with a neurometabolic profile on magnetic resonance spectroscopy (MRS) in virally suppressed, neurologically asymptomatic HIV+ individuals. In total, 32 HIV+ individuals on stable cART with an average age of 41.97 ± 10.12 years and with available clinical data, CNS penetration effectiveness (CPE), and monocyte efficacy (ME) scores underwent multi-voxel MRS. The parameters of neuronal number/function (NAA/Cr), membrane turnover (Cho/Cr), and glial proliferation (mI/Cr) were analyzed in supratentorial white and gray matter. Correlations of CPE and ME with neurometabolic ratios were performed using Pearson's correlation test. Statistical significance was set at p < 0.05. A strong positive correlation was observed between Cho/Cr and CPE in the left parietal subcortical white matter (r = 0.577, p = 0.001). A strong positive correlation between NAA/Cr and ME was obtained in the left (r = 0.521, p = 0.003) and the right (r = 0.494, p = 0.005) posterior cingulate. A strong negative correlation between ME and Cho/Cr ratios was observed in the right frontal deep white matter (r = -0.569, p = 0.001). Indices designed to assess cART efficacy in CNS failed to present significant correlations with the neurometabolic profile obtained using MRS. There is a need to define more potent non-invasive tools for neuroinflammation assessment given the prolonged life expectancy in the HIV+ population.

Imaging findings in seven cases of congenital infantile myofibromatosis with cerebral, spinal, or head and neck involvement.

INTRODUCTION: Congenital infantile myofibromatosis (IM) is a rare mesenchymal disease, presenting with tumors in the skin, muscle, viscera, bone, and subcutaneous tissue. It can present as (a) a solitary form with subcutaneous, erythematous nodules, (b) a multicentric form with subcutaneous, muscle, and/or bony lesions, and (c) a multicentric form with visceral involvement. Cerebral or spinal involvement in myofibromatosis has been reported rarely. METHODS: We report seven cases of histology-proven infantile myofibromatosis with brain, spine, and/or head and neck involvement. RESULTS: In three patients with multiple subcutaneous nodules, a multicentric form of IM with visceral involvement was diagnosed. In three patients, a multicentric form without visceral involvement was found. Two patients had brain involvement, and four patients had vertebral body involvement. CONCLUSION: In a newborn presenting with intraparenchymal brain lesions, epidural spinal masses, and/or vertebra plana or lytic lesions of the calvarium and spine, infantile myofibromatosis should be considered as a possible differential diagnosis. The presence of subcutaneous or muscular nodules facilitates the diagnosis.

Gradient Patterns of Age-Related Diffusivity Changes in Cerebral White Matter.

The current concept of brain aging proposes three gradient patterns of changes in white matter that occur during healthy brain aging: antero-posterior, supero-inferior, and the myelodegeneration-retrogenesis (or the "last-in-first-out") concept. The aim of this study was to correlate white matter diffusivity measures (fractional anisotropy-FA, mean diffusivity-MD, radial diffusivity-RD, and axial diffusivity-AD) in healthy volunteers with chronological age and education level, in order to potentially incorporate the findings with proposed patterns of physiological brain aging. The study was performed on 75 healthy participants of both sexes, with an average age of 37.32 ± 11.91 years underwent brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). DTI was performed using tract-based spatial statistics (TBSS), with the analysis of four parameters: FA, MD, RD, and AD. Skeletonized measures were averaged in 29 regions of interest in white matter. Correlations between age and DTI measures and between education-level and DTI measures were performed using Pearson's correlation test. To correct for multiple comparisons, we applied a Bonferroni correction to the p-values. Significance was set at p ≤ 0.001. A significant negative correlation of FA with age was observed in posterior thalamic radiation (PTR) (p< 0.001). A significant positive correlation between age and MD was observed in sagittal stratum (SS) (p< 0.001), between age and RD in PTR, SS, and retrolenticular internal capsule (p< 0.001), and between age and AD in the body of the corpus callosum (p< 0.001). There were no significant correlations of DTI parameters with educational level. According to our study, RD showed the richest correlations with age, out of all DTI metrics. FA, MD, and RD showed significant changes in the diffusivity of projection fibers, while AD presented diffusivity changes in the commissural fibers. The observed heterogeneity in diffusivity changes across the brain cannot be explained by a single aging gradient pattern, since it seems that different patterns of degradation are true for different fiber tracts that no currently available theory can globally explain age-related changes in the brain. Additional factors, such as the effect of somatosensory decline, should be included as one of the important covariables to the existing patterns.

Diffusion tensor MR imaging (DTI) metrics in the cervical spinal cord in asymptomatic HIV-positive patients.

INTRODUCTION: This study was conducted to compare diffusion tensor MR imaging (DTI) metrics of the cervical spinal cord in asymptomatic human immunodeficiency virus (HIV)-positive patients with those measured in healthy volunteers, and to assess whether DTI is a valuable diagnostic tool in the early detection of HIV-associated myelopathy (HIVM). METHODS: MR imaging of the cervical spinal cord was performed in 20 asymptomatic HIV-positive patients and in 20 healthy volunteers on a 3-T MR scanner. Average fractional anisotropy (FA), mean diffusivity (MD), and major (E1) and minor (E2, E3) eigenvalues were calculated within regions of interest (ROIs) at the C2/3 level (central and bilateral anterior, lateral and posterior white matter). RESULTS: Statistical analysis showed significant differences with regard to mean E3 values between patients and controls (p = 0.045; mixed-model analysis of variance (ANOVA) test). Mean FA was lower, and mean MD, mean E1, and mean E2 were higher in each measured ROI in patients compared to controls, but these differences were not statistically significant. CONCLUSION: Asymptomatic HIV-positive patients demonstrate only subtle changes in DTI metrics measured in the cervical spinal cord compared to healthy volunteers that currently do not support using DTI as a diagnostic tool for the early detection of HIVM.

Magnetic resonance imaging spectrum of medulloblastoma.

INTRODUCTION: Two medulloblastoma variants were recently added to the WHO classification of CNS tumours. We retrospectively analysed the imaging findings of 37 classic and 27 cases of variant medulloblastomas to identify imaging characteristics that might suggest a particular MB subtype. METHODS: Sixty-four patients from three institutions were included. Location, tumour margins, signal intensities on conventional MRI, enhancement pattern, the presence of haemorrhage, calcifications and hydrocephalus were recorded and analysed. Signal characteristics on diffusion-weighted MR images and MR spectra were evaluated when available. RESULTS: Thirty-seven classic type of MB (CMB), twelve cases of desmoplastic/nodular medulloblastoma (DMB), nine medulloblastomas with extensive nodularity (MB-EN), five cases of anaplastic and one of large-cell medulloblastoma were included. Fifty of 64 tumours were located in the 4th ventricle region. On T2WI, CMB were all hyperintense, whereas DMB and MB-EN showed isointensity in up to 66%. One third of the classic MB showed only subtle marginal or linear enhancement. All medulloblastoma variants showed marked enhancement. CONCLUSION: The results of our study suggest: (a) an age-dependent distribution of MB variants, with DMB and MB-EN more common in younger children; (b) a female predominance in DMB; (c) a more common off-midline location in DMB (50%) and MB-EN (33%) variants.

Congenital tumors of the central nervous system.

Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into "definitely congenital" (present or producing symptoms at birth), "probably congenital" (present or producing symptoms within the first week of life), and "possibly congenital" (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors, where aggressive surgical treatment leads to disease-free survival.

Neuroimaging evaluation of non-accidental head trauma with correlation to clinical outcomes: a review of 57 cases.

OBJECTIVE: To review the clinical presentation and neuroimaging findings in patients with high clinical suspicion for non-accidental trauma (NAT) of the head, to investigate associations between imaging findings and long-term neurologic outcome in abused children. STUDY DESIGN: A retrospective review of 57 cases of NAT of the head from a single institution was performed. Neuroimaging studies (computed tomography [CT] and magnetic resonance imaging [MRI]) were reviewed by a senior neuroradiologist, a neuroradiology fellow, and a radiology resident. Clinical history and physical findings, including retinal examination, imaging, and follow-up assessment, were reviewed. RESULTS: The mean time between the patient's arrival at the hospital and CT and MRI imaging was 2.9 hours and 40.6 hours, respectively. The most common clinical presentation was mental status changes, seen in 47% of patients. The most common neuroimaging finding was subdural hematoma, seen in 86% of patients. In the 47 patients who underwent both MRI and CT, 1 case of suspected NAT was missed on head CT. CT detected signs of global ischemia in all 11 patients who died (mean time after arrival at the hospital until undergoing CT, 1.1 hours). MRI detected additional signs of injury in patients who developed mild to moderate developmental delay. CONCLUSION: CT was able to detect evidence of NAT of the head in 56 of 57 abused children included in our cohort and predicted severe neurologic injury and mortality. MRI was useful in detecting additional evidence of trauma, which can be helpful in risk stratification for neurologic outcomes as well in providing confirming evidence of repeated injury.

Neurometabolic Remodeling in Chronic Hiv Infection: a Five-Year Follow-up Multi-Voxel Mrs Study.

There is a lack of data about the long-term follow-up changes in neurometabolic profile and neuropsychological performance of HIV-positive subjects under continuous antiretroviral therapy (cART). The aim of the study was to assess changes in neurometabolic profile in chronically-infected, HIV-positive subjects during a five-year follow-up period, using multi-voxel proton magnetic resonance spectroscopy (1H-MRS). Nineteen neurologically asymptomatic, aviremic, HIV-positive subjects, underwent multi-voxel 2D MRS on a 3 T MR unit and synchronous neurocognitive assessment in a five-year follow-up period. Twelve voxels were placed in prefrontal cortices, anterior and posterior cingulate gyrus, intraparietal sulci, and frontal centrum semiovale white matter, to identify peaks of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myoinositol (mI). Ratios of NAA/Cr, NAA/Cho, NAA/mI, mI/Cr, and Cho/Cr were analyzed. Longitudinal differences in ratios and neurocognitive scores were tested with the Wilcoxon signed-rank-test. Statistical significance was set at p ≤ 0.004 significant, and 0.05 > p > 0.004 trending toward significance. A significant longitudinal increase in NAA/Cr ratio was observed in 5/12 voxels, while there was a trend toward significance in an additional three. The increase in Cho/Cr reached statistical significance in one voxel. Changes in the mI/Cr ratio demonstrated a significant increase in 4/12 voxels. A progressive increase in NAA/Cr, followed by better neurocognitive performance, may be an indicator of brain plasticity in the setting of chronic HIV-related neuronal injury. A progressive mI/Cr increase could be partly explained by glial proliferation due to functional compartment remodeling and partly attributable to insufficient control of persistent neuroinflammation by cART.

Neuroimaging in the brain in HIV-1-infected patients.

The brain may be affected by a variety of abnormalities in association with HIV infection. Knowledge of these abnormalities and their characteristic imaging features is important to neuroradiologists for the detection, diagnosis, and initiation of appropriate treatment. This review attempts to describe the imaging findings associated with brain disorders in HIV-seropositive patients and the rationales for integrating neuroradiologic techniques.

Imaging of slow viruses.

The symptoms associated with slow viral or prion diseases of the central nervous system tend to have multiple neurologic symptoms, and different patients may present with different symptoms. This review discusses the most common slow virus infections and their imaging findings.

Apparent diffusion coefficient reproducibility in brain tumors measured on 1.5 and 3 T clinical scanners: A pilot study.

BACKGROUND: Gradient and coil systems, pulse sequence design, and imaging parameters, as well as different scanners, can influence apparent diffusion coefficient (ADC) values. The aim of this study was to evaluate the effect of two different field strengths on the reproducibility of mean absolute ADC measurements in various primary and secondary brain tumors. METHODS: Fifty patients with histologically proven brain tumors were prospectively examined on two MR scanners from the same vendor, with different field strengths-1.5T and 3T-on the same day. Absolute ADC values were compared using the Wilcoxon matched-pairs signed-rank test. Inter-scanner agreement between two different fields in the same tumor was examined using correlation coefficients, and the discrepancy between the highest and the lowest mean absolute ADC values between scanners was tested using a one-way analysis of variance. Statistical significance was set at p < 0.05. RESULTS: There was no statistically significant difference between mean absolute ADC values obtained on 1.5T and 3T scanners for all patients and all brain tumor types. The intratumoral difference in ADC values, averaged from two scanners in the same tumor type, ranged from 1.58 to 4.5% for 1.5T, and from 1.18 to 4.37% for 3T.Inter-scanner agreement was high, and the kappa coefficient ranged from 0.88 to 0.99, with no significant difference between obtained values on different field strengths. CONCLUSION: Based on the results obtained in our study, there is no significant difference between mean absolute ADC values measured in various primary and secondary brain tumors at different field strengths (1.5 and 3.0T MR systems), in the same patient, and in the same tumor, measured on the same day.

Early Introduction of cART Reverses Brain Aging Pattern in Well-Controlled HIV Infection: A Comparative MR Spectroscopy Study.

Introduction: The aim of this study was to compare age-related changes in chronically infected, asymptomatic HIV-positive patients under combination antiretroviral therapy (cART), with age-, gender-, and educational-level-matched healthy subjects, using multi-voxel magnetic-resonance spectroscopy (MRS). Methods: There were 66 chronically infected HIV-positive subjects and 65 age-, gender-, and educational-level-matched control subjects, divided into four groups according to the age: group 1 (20-29 years old), group 2 (30-39), group 3 (40-49) and group 4 (50-59). MRS was performed and ratios of N-acetyl-aspartate (NAA)/creatine (Cr) were analyzed in ten locations of the supracallosal gray matter. For the comparison of NAA/Cr ratios in healthy and HIV-positive subjects, ANCOVA with age and education as covariates was performed. Correlations of NAA/Cr ratios with duration of cART were performed using Pearson's correlation test. Statistical significance was set at p < 0.05. Results: The NAA/Cr ratios were decreased in the 20-29-year-old HIV-positive subjects in 8/10 locations (p < 0.005) compared to the healthy controls, while in the 50-59-year-old groups they were significiantly lower only in one location (p = 0.004). There were significant positive correlations of NAA/Cr levels with the duration of cART in the oldest group of HIV-positive subjects, while in the youngest group there were no significant correlations. Conclusion: The aging pattern in chronic HIV infection under cART is accentuated rather than accelerated. There is an initial HIV-related neuronal damage with a significant decline in NAA/Cr ratios; after the initiation of cART, however, NAA/Cr ratios increase continuously to become similar to healthy aging individuals, probably due to beneficial effect of long-standing cART. Summary: Brain aging in chronic HIV infection under cART is accentuated, with an initial HIV-related neuronal damage followed by a subtle NAA/Cr increase after the initiation of cART. Under cART, in advanced age, NAA/Cr ratios become similar to healthy aging individuals.