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1.
Nature ; 627(8002): 165-173, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38326613

ABSTRACT

The arachnoid barrier delineates the border between the central nervous system and dura mater. Although the arachnoid barrier creates a partition, communication between the central nervous system and the dura mater is crucial for waste clearance and immune surveillance1,2. How the arachnoid barrier balances separation and communication is poorly understood. Here, using transcriptomic data, we developed transgenic mice to examine specific anatomical structures that function as routes across the arachnoid barrier. Bridging veins create discontinuities where they cross the arachnoid barrier, forming structures that we termed arachnoid cuff exit (ACE) points. The openings that ACE points create allow the exchange of fluids and molecules between the subarachnoid space and the dura, enabling the drainage of cerebrospinal fluid and limited entry of molecules from the dura to the subarachnoid space. In healthy human volunteers, magnetic resonance imaging tracers transit along bridging veins in a similar manner to access the subarachnoid space. Notably, in neuroinflammatory conditions such as experimental autoimmune encephalomyelitis, ACE points also enable cellular trafficking, representing a route for immune cells to directly enter the subarachnoid space from the dura mater. Collectively, our results indicate that ACE points are a critical part of the anatomy of neuroimmune communication in both mice and humans that link the central nervous system with the dura and its immunological diversity and waste clearance systems.


Subject(s)
Arachnoid , Brain , Dura Mater , Animals , Humans , Mice , Arachnoid/anatomy & histology , Arachnoid/blood supply , Arachnoid/immunology , Arachnoid/metabolism , Biological Transport , Brain/anatomy & histology , Brain/blood supply , Brain/immunology , Brain/metabolism , Dura Mater/anatomy & histology , Dura Mater/blood supply , Dura Mater/immunology , Dura Mater/metabolism , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Gene Expression Profiling , Magnetic Resonance Imaging , Mice, Transgenic , Subarachnoid Space/anatomy & histology , Subarachnoid Space/blood supply , Subarachnoid Space/immunology , Subarachnoid Space/metabolism , Cerebrospinal Fluid/metabolism , Veins/metabolism
2.
Ann Neurol ; 95(5): 941-950, 2024 May.
Article in English | MEDLINE | ID: mdl-38362961

ABSTRACT

OBJECTIVE: To investigate the relationship between neurocognitive deficits and structural changes on brain magnetic resonance imaging in people living with HIV (PLWH) with good virological control on combination antiretroviral therapy, compared with socioeconomically matched control participants recruited from the same communities. METHODS: Brain magnetic resonance imaging scans, and clinical and neuropsychological data were obtained from virologically controlled PLWH (viral load of <50 c/mL and at least 1 year of combination antiretroviral therapy) and socioeconomically matched control participants. Magnetic resonance imaging was carried out on 3 T scanner with 8-channel head coils and segmented using Classification using Derivative-based Features. Multiple regression analysis was performed to examine the association between brain volume and various clinical and neuropsychiatric parameters adjusting for age, race, and sex. To evaluate longitudinal changes in brain volumes, a random coefficient model was used to evaluate the changes over time (age) adjusting for sex and race. RESULTS: The cross-sectional study included 164 PLWH and 51 controls, and the longitudinal study included 68 PLWH and 20 controls with 2 or more visits (mean 2.2 years, range 0.8-5.1 years). Gray matter (GM) atrophy rate was significantly higher in PLWH compared with control participants, and importantly, the GM and global atrophy was associated with the various neuropsychological domain scores. Higher volume of white matter hyperintensities were associated with increased atherosclerotic cardiovascular disease risk score, and decreased executive functioning and memory domain scores in PLWH. INTERPRETATION: These findings suggest ongoing neurological damage even in virologically controlled participants, with significant implications for clinical management of PLWH. ANN NEUROL 2024;95:941-950.


Subject(s)
Gray Matter , HIV Infections , Neurocognitive Disorders , White Matter , Humans , Cross-Sectional Studies , HIV Infections/complications , HIV Infections/diagnostic imaging , HIV Infections/pathology , HIV Infections/therapy , Neurocognitive Disorders/diagnostic imaging , White Matter/diagnostic imaging , White Matter/pathology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Adult , Middle Aged , Male , Female , Cerebrum/diagnostic imaging , Cerebrum/pathology , Longitudinal Studies
3.
Neuroimage ; 296: 120680, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38857819

ABSTRACT

Magnetic Resonance Imaging (MRI) can provide the location and signal characteristics of pathological regions within a postmortem tissue block, thereby improving the efficiency of histopathological studies. However, such postmortem-MRI guided histopathological studies have so far only been performed on fixed samples as imaging tissue frozen at the time of extraction, while preserving its integrity, is significantly more challenging. Here we describe the development of cold-postmortem-MRI, which can preserve tissue integrity and help target techniques such as transcriptomics. As a first step, RNA integrity number (RIN) was used to determine the rate of tissue biomolecular degradation in mouse brains placed at various temperatures between -20 °C and +20 °C for up to 24 h. Then, human tissue frozen at the time of autopsy was immersed in 2-methylbutane, sealed in a bio-safe tissue chamber, and cooled in the MRI using a recirculating chiller to determine MRI signal characteristics. The optimal imaging temperature, which did not show significant RIN deterioration for over 12 h, at the same time giving robust MRI signal and contrast between brain tissue types was deemed to be -7 °C. Finally, MRI was performed on human tissue blocks at this optimal imaging temperatures using a magnetization-prepared rapid gradient echo (MPRAGE, isotropic resolution between 0.3-0.4 mm) revealing good gray-white matter contrast and revealing subpial, subcortical, and deep white matter lesions. RINs measured before and after imaging revealed no significant changes (n = 3, p = 0.18, paired t-test). In addition to improving efficiency of downstream processes, imaging tissue at sub-zero temperatures may also improve our understanding of compartment specificity of MRI signal.


Subject(s)
Autopsy , Brain , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/pathology , Mice , Autopsy/methods , Animals , Freezing , Male , Female , Mice, Inbred C57BL , Neuroimaging/methods
4.
J Fluoresc ; 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37450083

ABSTRACT

Visible and near-infrared (NIR) upconversion luminescence (UCL) emissions originating from the BaY2F8: Yb3+, Tm3+ systems were investigated under a laser excitation at 980 nm. The BaY2F8:20 mol% Yb3+, x mol% Tm3+ and BaY2F8: y mol% Yb3+, 0.5 mol% Tm3+ phosphors showed prominent UCL at 800 and 810 nm. The optimized doping concentrations of Yb3+ and Tm3+ in the BaY2F8 host matrix were evaluated, their spectroscopic properties were determined, and studies on their temperature-dependent behaviour were carried out. The temperature-sensing properties were studied by generating the fluorescence intensity ratio (FIR) of the UCL peaks originating from the thermally-coupled energy levels of the Tm3+ ions. The Stark sublevels of 1G4 level of Tm3+ ions were utilized to estimate the temperature-sensing abilities of the phosphor.

5.
Ann Neurol ; 90(4): 612-626, 2021 10.
Article in English | MEDLINE | ID: mdl-34390015

ABSTRACT

OBJECTIVE: To noninvasively assess myelin status in chronic white matter lesions of multiple sclerosis (MS), we developed and evaluated a simple classification scheme based on T1 relaxation time maps derived from 7-tesla postmortem and in vivo MRI. METHODS: Using the MP2RAGE MRI sequence, we classified 36 lesions from 4 postmortem MS brains as "long-T1," "short-T1," and "mixed-T1" by visual comparison to neocortex. Within these groups, we compared T1 times to histologically derived measures of myelin and axons. We performed similar analysis of 235 chronic lesions with known date of onset in 25 MS cases in vivo and in a validation cohort of 222 lesions from 66 MS cases, investigating associations with clinical and radiological outcomes. RESULTS: Postmortem, lesions classified qualitatively as long-T1, short-T1, and mixed-T1 corresponded to fully demyelinated, fully remyelinated, and mixed demyelinated/remyelinated lesions, respectively (p ≤ 0.001). Demyelination (rather than axon loss) dominantly contributed to initial T1 prolongation. We observed lesions with similar characteristics in vivo, allowing manual classification with substantial interrater and excellent intrarater reliability. Short-T1 lesions were most common in the deep white matter, whereas long-T1 and mixed-T1 lesions were prevalent in the juxtacortical and periventricular white matter (p = 0.02) and were much more likely to have paramagnetic rims suggesting chronic inflammation (p < 0.001). Older age at the time of lesion formation portended less remyelination (p = 0.007). INTERPRETATION: 7-tesla T1 mapping with MP2RAGE, a clinically available MRI method, allows qualitative and quantitative classification of chronic MS lesions according to myelin content, rendering straightforward the tracking of lesional myelination changes over time. ANN NEUROL 2021;90:612-626.


Subject(s)
Magnetic Resonance Imaging , Multiple Sclerosis/pathology , Myelin Sheath/pathology , Remyelination/physiology , Aged , Axons/pathology , Cohort Studies , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Multiple Sclerosis/therapy , Radiography/methods , White Matter/pathology
6.
Mult Scler ; 28(12): 1891-1902, 2022 10.
Article in English | MEDLINE | ID: mdl-35674284

ABSTRACT

BACKGROUND: The "central vein sign" (CVS), a linear hypointensity on T2*-weighted imaging corresponding to a central vein/venule, is associated with multiple sclerosis (MS) lesions. The effect of lesion-size exclusion criteria on MS diagnostic accuracy has not been extensively studied. OBJECTIVE: Investigate the optimal lesion-size exclusion criteria for CVS use in MS diagnosis. METHODS: Cross-sectional study of 163 MS and 51 non-MS, and radiological/histopathological correlation of 5 MS and 1 control autopsy cases. The effects of lesion-size exclusion on MS diagnosis using the CVS, and intralesional vein detection on histopathology were evaluated. RESULTS: CVS+ lesions were larger compared to CVS- lesions, with effect modification by MS diagnosis (mean difference +7.7 mm3, p = 0.004). CVS percentage-based criteria with no lesion-size exclusion showed the highest diagnostic accuracy in differentiating MS cases. However, a simple count of three or more CVS+ lesions greater than 3.5 mm is highly accurate and can be rapidly implemented (sensitivity 93%; specificity 88%). On magnetic resonance imaging (MRI)-histopathological correlation, the CVS had high specificity for identifying intralesional veins (0/7 false positives). CONCLUSION: Lesion-size measures add important information when using CVS+ lesion counts for MS diagnosis. The CVS is a specific biomarker corresponding to intralesional veins on histopathology.


Subject(s)
Multiple Sclerosis , Brain/pathology , Cross-Sectional Studies , Humans , Magnetic Resonance Imaging/methods , Multiple Sclerosis/pathology , Veins/diagnostic imaging
7.
Mult Scler ; 28(9): 1351-1363, 2022 08.
Article in English | MEDLINE | ID: mdl-35142571

ABSTRACT

BACKGROUND: Dramatic improvements in visualization of cortical (especially subpial) multiple sclerosis (MS) lesions allow assessment of impact on clinical course. OBJECTIVE: Characterize cortical lesions by 7 tesla (T) T2*-/T1-weighted magnetic resonance imaging (MRI); determine relationship with other MS pathology and contribution to disability. METHODS: Sixty-four adults with MS (45 relapsing-remitting/19 progressive) underwent 3 T brain/spine MRI, 7 T brain MRI, and clinical testing. RESULTS: Cortical lesions were found in 94% (progressive: median 56/range 2-203; relapsing-remitting: 15/0-168; p = 0.004). Lesion distribution across 50 cortical regions was nonuniform (p = 0.006), with highest lesion burden in supplementary motor cortex and highest prevalence in superior frontal gyrus. Leukocortical and white matter lesion volumes were strongly correlated (r = 0.58, p < 0.0001), while subpial and white matter lesion volumes were moderately correlated (r = 0.30, p = 0.002). Leukocortical (p = 0.02) but not subpial lesions (p = 0.40) were correlated with paramagnetic rim lesions; both were correlated with spinal cord lesions (p = 0.01). Cortical lesion volumes (total and subtypes) were correlated with expanded disability status scale, 25-foot timed walk, nine-hole peg test, and symbol digit modality test scores. CONCLUSION: Cortical lesions are highly prevalent and are associated with disability and progressive disease. Subpial lesion burden is not strongly correlated with white matter lesions, suggesting differences in inflammation and repair mechanisms.


Subject(s)
Disabled Persons , Multiple Sclerosis , White Matter , Adult , Brain/pathology , Humans , Magnetic Resonance Imaging/methods , Multiple Sclerosis/pathology , White Matter/pathology
8.
Ann Neurol ; 88(5): 1034-1042, 2020 11.
Article in English | MEDLINE | ID: mdl-32799417

ABSTRACT

In multiple sclerosis (MS), a subset of chronic active white matter lesions are identifiable on magnetic resonance imaging by their paramagnetic rims, and increasing evidence supports their association with severity of clinical disease. We studied their potential role in differential diagnosis, screening an international multicenter clinical research-based sample of 438 individuals affected by different neurological conditions (MS, other inflammatory, infectious, and non-inflammatory conditions). Paramagnetic rim lesions, rare in other neurological conditions (52% of MS vs 7% of non-MS cases), yielded high specificity (93%) in differentiating MS from non-MS. Future prospective multicenter studies should validate their role as a diagnostic biomarker. ANN NEUROL 2020;88:1034-1042.


Subject(s)
Multiple Sclerosis/diagnostic imaging , Adult , Aged , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis/epidemiology , Nervous System Diseases/diagnostic imaging , Neuroimaging , Prevalence , Retrospective Studies , Sensitivity and Specificity , Young Adult
9.
Brain ; 143(7): 2089-2105, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32572488

ABSTRACT

Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P < 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P < 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P < 0.0001), brainstem (r = 0.45, P < 0.0001) and spinal cord (r = 0.57, P < 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.


Subject(s)
Brain/pathology , Multiple Sclerosis/pathology , Pyramidal Tracts/pathology , Adult , Cervical Cord/pathology , Disability Evaluation , Disease Progression , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies
10.
Luminescence ; 36(8): 1847-1850, 2021 Dec.
Article in English | MEDLINE | ID: mdl-32715611

ABSTRACT

A BaY2 F8 :Yb3+ ,Ho3+ phosphor was synthesized using a simple precipitation method. The temperature-sensing properties of BaY2 F8 :Yb3+ ,Ho3+ phosphor were investigated using the fluorescence intensity ratio (FIR) of the thermally coupled energy levels (5 F4 and 5 S2 ) of Ho3+ . Energy transitions 5 F4 →5 I8 and 5 S2 →5 I8 gave rise to emission peaks at 538 nm and 549 nm, respectively. The areas under these two emission peaks were used to calculate the FIR. Temperature-dependent upconversion luminescence was recorded in the temperature range 303-623 K using a 980 nm laser excitation source. The results suggested that the BaY2 F8 :Yb3+ , Ho3+ phosphor has the potential to be used as a non-contact optical temperature sensor.


Subject(s)
Thermometry , Ytterbium , Bays , Luminescence , Temperature
11.
Neuroimage ; 223: 117285, 2020 12.
Article in English | MEDLINE | ID: mdl-32828923

ABSTRACT

PURPOSE: To perform magnetic resonance microscopy (MRM) on human cortex and a cortical lesion as well as the adjacent normal appearing white matter. To shed light on the origins of MRI contrast by comparison with histochemical and immunostaining. METHODS: 3D MRM at a nominal isotropic resolution of 15 and 18 µm was performed on 2 blocks of tissue from the brain of a 77-year-old man who had MS for 47 years. One block contained normal appearing cortical gray matter (CN block) and adjacent normal appearing white matter (NAWM), and the other also included a cortical lesion (CL block). Postmortem ex-vivo MRI was performed at 11.7T using a custom solenoid coil and T2*-weighted 3D GRE sequence. Histochemical and immunostaining were done after paraffin embedding for iron, myelin, oligodendrocytes, neurons, blood vessels, macrophages and microglia, and astrocytes. RESULTS: MRM could identify individual iron-laden oligodendrocytes with high sensitivity (70% decrease in signal compared to surrounding) in CN and CL blocks, as well as some iron-laden activated macrophages and microglia. Iron-deficient oligodendrocytes seemed to cause relative increase in MRI signal within the cortical lesion. High concentration of myelin in the white matter was primarily responsible for its hypointense appearance relative to the cortex, however, signal variations within NAWM could be attributed to changes in density of iron-laden oligodendrocytes. CONCLUSION: Changes in iron accumulation within cells gave rise to imaging contrast seen between cortical lesions and normal cortex, as well as the patchy signal in NAWM. Densely packed myelin and collagen deposition also contributed to MRM signal changes. Even though we studied only one block each from normal appearing and cortical lesions, such studies can help better understand the origins of histopathological and microstructural correlates of MRI signal changes in multiple sclerosis and contextualize the interpretation of lower-resolution in vivo MRI scans.


Subject(s)
Brain/diagnostic imaging , Brain/pathology , Histocytological Preparation Techniques/methods , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/pathology , Neurons/pathology , Aged , Brain Chemistry , Gray Matter/diagnostic imaging , Gray Matter/pathology , Humans , Iron , Magnetic Resonance Imaging , Male , Microscopy/methods , White Matter/diagnostic imaging , White Matter/pathology
12.
Ann Neurol ; 85(6): 934-942, 2019 06.
Article in English | MEDLINE | ID: mdl-30847935

ABSTRACT

Accumulating evidence corroborates the role of the "central vein sign" in the radiological diagnosis of multiple sclerosis (MS). Here, we report human magnetic resonance imaging (MRI) and corresponding pathological data that inflammation-dependent intracerebral remodeling of the vessel wall is directly associated with the prominence of intralesional veins on susceptibility-based MRI. In adult marmosets with experimental autoimmune encephalomyelitis, vessel-wall fibrosis was detected early in the demyelinating process, even in lesions <2 weeks old, though fibrosis was more evident after 6 weeks. Vascular remodeling consisted of both luminal enlargement and eccentric thickening of the perivascular space (fibrillar collagen type I deposition) and affected almost exclusively white matter, but not subpial cortical, lesions. The long-term effect of vessel remodeling in MS lesions is currently unknown, but it might potentially affect tissue repair. ANN NEUROL 2019;85:934-942.


Subject(s)
Cerebral Veins/chemistry , Cerebral Veins/diagnostic imaging , Demyelinating Diseases/diagnostic imaging , Fibrillar Collagens/analysis , Fibrillar Collagens/physiology , Adult , Aged , Aged, 80 and over , Animals , Callithrix , Cerebral Veins/metabolism , Demyelinating Diseases/metabolism , Female , Humans , Male , Middle Aged
13.
Ann Neurol ; 86(6): 878-884, 2019 12.
Article in English | MEDLINE | ID: mdl-31600832

ABSTRACT

OBJECTIVE: JC virus (JCV) infection is a lytic infection of oligodendrocytes in progressive multifocal leukoencephalopathy; less common forms of central nervous system manifestations associated with JCV infection include granule cell neuronopathy, encephalopathy, and meningitis. Presented is the first case of fatal JCV encephalopathy after immunosuppressive therapy that included ruxolitinib. METHODS: Postmortem analysis included next generation sequencing, Sanger sequencing, tissue immunohistochemistry, and formalin-fixed hemisphere 7T magnetic resonance imaging. RESULTS: JCV DNA isolated from postmortem tissue samples identified a novel 12bp insertion that altered the transcription site binding pattern in an otherwise "wild-type virus," which has long been thought to be the nonpathogenic form of JCV. Anti-VP1 staining demonstrated infection in cortical neurons, hippocampal neurons, and glial and endothelial cells. INTERPRETATION: This expands the spectrum of identified JCV diseases associated with broad-spectrum immunosuppression, including JAK-STAT inhibitors, and sheds light on an additional neurotropic virus strain of the archetype variety. ANN NEUROL 2019;86:878-884.


Subject(s)
Brain Diseases/drug therapy , Brain Diseases/genetics , JC Virus/genetics , Janus Kinases/genetics , Pyrazoles/therapeutic use , Adolescent , Base Sequence , Brain Diseases/diagnostic imaging , Fatal Outcome , Female , Humans , JC Virus/isolation & purification , Nitriles , Pyrimidines
14.
Brain ; 142(11): 3550-3564, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31608359

ABSTRACT

Traumatic microbleeds are small foci of hypointensity seen on T2*-weighted MRI in patients following head trauma that have previously been considered a marker of axonal injury. The linear appearance and location of some traumatic microbleeds suggests a vascular origin. The aims of this study were to: (i) identify and characterize traumatic microbleeds in patients with acute traumatic brain injury; (ii) determine whether appearance of traumatic microbleeds predict clinical outcome; and (iii) describe the pathology underlying traumatic microbleeds in an index patient. Patients presenting to the emergency department following acute head trauma who received a head CT were enrolled within 48 h of injury and received a research MRI. Disability was defined using Glasgow Outcome Scale-Extended ≤6 at follow-up. All magnetic resonance images were interpreted prospectively and were used for subsequent analysis of traumatic microbleeds. Lesions on T2* MRI were stratified based on 'linear' streak-like or 'punctate' petechial-appearing traumatic microbleeds. The brain of an enrolled subject imaged acutely was procured following death for evaluation of traumatic microbleeds using MRI targeted pathology methods. Of the 439 patients enrolled over 78 months, 31% (134/439) had evidence of punctate and/or linear traumatic microbleeds on MRI. Severity of injury, mechanism of injury, and CT findings were associated with traumatic microbleeds on MRI. The presence of traumatic microbleeds was an independent predictor of disability (P < 0.05; odds ratio = 2.5). No differences were found between patients with punctate versus linear appearing microbleeds. Post-mortem imaging and histology revealed traumatic microbleed co-localization with iron-laden macrophages, predominately seen in perivascular space. Evidence of axonal injury was not observed in co-localized histopathological sections. Traumatic microbleeds were prevalent in the population studied and predictive of worse outcome. The source of traumatic microbleed signal on MRI appeared to be iron-laden macrophages in the perivascular space tracking a network of injured vessels. While axonal injury in association with traumatic microbleeds cannot be excluded, recognizing traumatic microbleeds as a form of traumatic vascular injury may aid in identifying patients who could benefit from new therapies targeting the injured vasculature and secondary injury to parenchyma.


Subject(s)
Brain Injuries, Traumatic/diagnostic imaging , Disability Evaluation , Intracranial Hemorrhages/diagnostic imaging , Vascular System Injuries/diagnostic imaging , Vascular System Injuries/pathology , Adolescent , Adult , Autopsy , Axons/pathology , Brain Injuries, Traumatic/pathology , Female , Glasgow Outcome Scale , Humans , Intracranial Hemorrhages/pathology , Iron/blood , Macrophages/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Tomography, X-Ray Computed , Treatment Outcome
15.
Brain ; 142(3): 633-646, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30715195

ABSTRACT

Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T2- and T2*-weighted axial and sagittal MRI scans acquired at 3 or 7 T. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P < 0.001), which was further confirmed by absolute and normalized lesion volumes (P < 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P < 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P < 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P < 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups.


Subject(s)
Cervical Cord/pathology , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/pathology , Adult , Brain/pathology , Cervical Cord/diagnostic imaging , Cervical Cord/metabolism , Disability Evaluation , Disease Progression , Female , Gray Matter/pathology , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/pathology , Multiple Sclerosis, Relapsing-Remitting/pathology , Spatial Analysis , Spinal Cord/pathology , Spinal Cord Diseases , White Matter/pathology
16.
Neuroimage ; 184: 901-915, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30300751

ABSTRACT

The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in MS. Automating this operation eliminates inter-rater variability and increases the efficiency of large-throughput analysis pipelines. Robust and reliable segmentation across multi-site spinal cord data is challenging because of the large variability related to acquisition parameters and image artifacts. In particular, a precise delineation of lesions is hindered by a broad heterogeneity of lesion contrast, size, location, and shape. The goal of this study was to develop a fully-automatic framework - robust to variability in both image parameters and clinical condition - for segmentation of the spinal cord and intramedullary MS lesions from conventional MRI data of MS and non-MS cases. Scans of 1042 subjects (459 healthy controls, 471 MS patients, and 112 with other spinal pathologies) were included in this multi-site study (n = 30). Data spanned three contrasts (T1-, T2-, and T2∗-weighted) for a total of 1943 vol and featured large heterogeneity in terms of resolution, orientation, coverage, and clinical conditions. The proposed cord and lesion automatic segmentation approach is based on a sequence of two Convolutional Neural Networks (CNNs). To deal with the very small proportion of spinal cord and/or lesion voxels compared to the rest of the volume, a first CNN with 2D dilated convolutions detects the spinal cord centerline, followed by a second CNN with 3D convolutions that segments the spinal cord and/or lesions. CNNs were trained independently with the Dice loss. When compared against manual segmentation, our CNN-based approach showed a median Dice of 95% vs. 88% for PropSeg (p ≤ 0.05), a state-of-the-art spinal cord segmentation method. Regarding lesion segmentation on MS data, our framework provided a Dice of 60%, a relative volume difference of -15%, and a lesion-wise detection sensitivity and precision of 83% and 77%, respectively. In this study, we introduce a robust method to segment the spinal cord and intramedullary MS lesions on a variety of MRI contrasts. The proposed framework is open-source and readily available in the Spinal Cord Toolbox.


Subject(s)
Image Processing, Computer-Assisted/methods , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/pathology , Neural Networks, Computer , Spinal Cord/pathology , Humans , Magnetic Resonance Imaging/methods , Observer Variation , Pattern Recognition, Automated , Reproducibility of Results , Sensitivity and Specificity
18.
J Magn Reson Imaging ; 50(3): 878-888, 2019 09.
Article in English | MEDLINE | ID: mdl-30652391

ABSTRACT

BACKGROUND: MRI is the imaging modality of choice for diagnosis and intervention assessment in neurological disease. Its full potential has not been realized due in part to challenges in harmonizing advanced techniques across multiple sites. PURPOSE: To develop a method for the assessment of reliability and repeatability of advanced multisite-multisession neuroimaging studies and specifically to assess the reliability of an advanced MRI protocol, including multiband fMRI and diffusion tensor MRI, in a multisite setting. STUDY TYPE: Prospective. POPULATION: Twice repeated measurement of a single subject with stable relapsing-remitting multiple sclerosis (MS) at seven institutions. FIELD STRENGTH/SEQUENCE: A 3 T MRI protocol included higher spatial resolution anatomical scans, a variable flip-angle longitudinal relaxation rate constant (R1 ≡ 1/T1 ) measurement, quantitative magnetization transfer imaging, diffusion tensor imaging, and a resting-state fMRI (rsFMRI) series. ASSESSMENT: Multiple methods of assessing intrasite repeatability and intersite reliability were evaluated for imaging metrics derived from each sequence. STATISTICAL TESTS: Student's t-test, Pearson's r, and intraclass correlation coefficient (ICC) (2,1) were employed to assess repeatability and reliability. Two new statistical metrics are introduced that frame reliability and repeatability in the respective units of the measurements themselves. RESULTS: Intrasite repeatability was excellent for quantitative R1 , magnetization transfer ratio (MTR), and diffusion-weighted imaging (DWI) based metrics (r > 0.95). rsFMRI metrics were less repeatable (r = 0.8). Intersite reliability was excellent for R1 , MTR, and DWI (ICC >0.9), and moderate for rsFMRI metrics (ICC∼0.4). DATA CONCLUSION: From most reliable to least, using a new reliability metric introduced here, MTR > R1 > DWI > rsFMRI; for repeatability, MTR > DWI > R1 > rsFMRI. A graphical method for at-a-glance assessment of reliability and repeatability, effect sizes, and outlier identification in multisite-multisession neuroimaging studies is introduced. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:878-888.


Subject(s)
Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Brain/pathology , Clinical Protocols , Diffusion Tensor Imaging/methods , Humans , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/pathology , Prospective Studies , Reproducibility of Results
19.
Luminescence ; 34(3): 382-386, 2019 May.
Article in English | MEDLINE | ID: mdl-30784183

ABSTRACT

An energy transfer process from Ce3+ to Tb3+ ions was successfully achieved in a Li2 SO4 -Al2 (SO4 )3 mixed-sulphate system. A wet-chemical synthesis was employed to prepare the Li2 SO4 -Al2 (SO4 )3 system by doping Ce3+ and Tb3+ ions individually as well as collectively. The phases were identified using X-ray diffraction studies. The as-prepared samples were characterized by FT-IR and photoluminescence measurements. Green-light emission was exhibited by Ce3+ , Tb3+ co-doped Li2 SO4 -Al2 (SO4 )3 system, thus, indicating its potential as a material for display devices or in the lamp industry.


Subject(s)
Alum Compounds/chemistry , Cerium/chemistry , Lithium Compounds/chemistry , Sulfates/chemistry , Terbium/chemistry , Energy Transfer , Light , Luminescence , Spectroscopy, Fourier Transform Infrared
20.
Luminescence ; 34(8): 804-811, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31273930

ABSTRACT

Dy3+ -doped CaAl12 O19 phosphors were synthesized utilizing a combustion method. Crystal structure and morphological examinations were performed respectively using X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques to identify the phase and morphology of the synthesized samples. Fourier transform infrared spectroscopy (FTIR) estimations were carried out using the KBr method. Photoluminescence properties (excitation and emission) were recorded at room temperature. CaAl12 O19 :Dy3+ phosphor showed two emission peaks respectively under a 350-nm excitation wavelength, centered at 477 nm and 573 nm. Dipole-dipole interaction via nonradiative energy shifting has been considered as the major cause of concentration quenching when Dy3+ concentration was more than 3 mol%. The CIE chromaticity coordinates positioned at (0.3185, 0.3580) for the CaAl12 O19 :0.03Dy3+ phosphor had a correlated color temperature (CCT) of 6057 K, which is situated in the cool white area. Existing results point out that the CaAl12 O19 :0.03Dy3+ phosphor could be a favorable candidate for use in white light-emitting diodes (WLEDs).


Subject(s)
Aluminum/chemistry , Calcium/chemistry , Dysprosium/chemistry , Light , Luminescence , Luminescent Agents/chemistry , Oxygen/chemistry , Particle Size , Spectrometry, Fluorescence
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