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Four-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R tauopathies are progressive supranuclear palsy (PSP) and corticobasal degeneration characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction, and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces remote neuronal dysfunction in functionally connected cortical regions to test a pathophysiological model that mechanistically links subcortical tau accumulation to cortical neuronal dysfunction in 4R tauopathies. We included 51 Aß-negative patients with clinically diagnosed PSP variants (n = 26) or corticobasal syndrome (n = 25) who underwent structural MRI and 18F-PI-2620 tau-PET. 18F-PI-2620 tau-PET was recorded using a dynamic one-stop-shop acquisition protocol to determine an early 0.5-2.5 min post tracer-injection perfusion window for assessing cortical neuronal dysfunction, as well as a 20-40 min post tracer-injection window to determine 4R-tau load. Perfusion-PET (i.e. early window) was assessed in 200 cortical regions, and tau-PET was assessed in 32 subcortical regions of established functional brain atlases. We determined tau epicentres as subcortical regions with the highest 18F-PI-2620 tau-PET signal and assessed the connectivity of tau epicentres to cortical regions of interest using a resting-state functional MRI-based functional connectivity template derived from 69 healthy elderly controls from the ADNI cohort. Using linear regression, we assessed whether: (i) higher subcortical tau-PET was associated with reduced cortical perfusion; and (ii) cortical perfusion reductions were observed preferentially in regions closely connected to subcortical tau epicentres. As hypothesized, higher subcortical tau-PET was associated with overall lower cortical perfusion, which remained consistent when controlling for cortical tau-PET. Using group-average and subject-level PET data, we found that the seed-based connectivity pattern of subcortical tau epicentres aligned with cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicentre showed lower perfusion. Together, subcortical tau-accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions in 4R-tauopathies. This suggests that subcortical tau pathology may induce cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity.
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Corteza Cerebral , Tomografía de Emisión de Positrones , Parálisis Supranuclear Progresiva , Tauopatías , Proteínas tau , Humanos , Masculino , Femenino , Tomografía de Emisión de Positrones/métodos , Anciano , Tauopatías/diagnóstico por imagen , Tauopatías/metabolismo , Tauopatías/patología , Proteínas tau/metabolismo , Persona de Mediana Edad , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Parálisis Supranuclear Progresiva/diagnóstico por imagen , Parálisis Supranuclear Progresiva/metabolismo , Parálisis Supranuclear Progresiva/patología , Parálisis Supranuclear Progresiva/fisiopatología , Imagen por Resonancia Magnética/métodosRESUMEN
OBJECTIVE: Intracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus, ICV serves as a surrogate marker for brain growth integrity. To assess the potential impact of adult-onset multiple sclerosis (MS) and its preceding prodromal subclinical changes on ICV in a large cohort of monozygotic twins clinically discordant for MS. METHODS: FSL software was used to derive ICV estimates from 3D-T1-weighted-3 T-MRI images by using an atlas scaling factor method. ICV were compared between clinically affected and healthy co-twins. All twins were compared to a large healthy reference cohort using standardized ICV z-scores. Mixed models assessed the impact of age at MS diagnosis on ICV. RESULTS: 54 twin-pairs (108 individuals/80female/42.45 ± 11.98 years), 731 individuals (375 non-twins, 109/69 monozygotic/dizygotic twin-pairs; 398female/29.18 ± 0.13 years) and 35 healthy local individuals (20male/31.34 ± 1.53 years). In 45/54 (83 %) twin-pairs, both clinically affected and healthy co-twins showed negative ICV z-scores, i.e., ICVs lower than the average of the healthy reference cohort (M = -1.53 ± 0.11, P<10-5). Younger age at MS diagnosis was strongly associated with lower ICVs (t = 3.76, P = 0.0003). Stratification of twin-pairs by age at MS diagnosis of the affected co-twin (≤30 versus > 30 years) yielded lower ICVs in those twin pairs with younger age at diagnosis (P = 0.01). Comparison within individual twin-pairs identified lower ICVs in the MS-affected co-twins with younger age at diagnosis compared to their corresponding healthy co-twins (P = 0.003). CONCLUSION: We offer for the first-time evidence for strong associations between adult-onset MS and lower ICV, which is more pronounced with younger age at diagnosis. This suggests pre-clinical alterations in early neurodevelopment associated with susceptibility to MS both in individuals with and without clinical manifestation of the disease.
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Encéfalo , Imagen por Resonancia Magnética , Esclerosis Múltiple , Gemelos Monocigóticos , Humanos , Adulto , Femenino , Masculino , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Persona de Mediana Edad , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Adulto Joven , Edad de Inicio , Tamaño de los ÓrganosRESUMEN
Cognitive deficits are a core symptom of schizophrenia, but research on their neural underpinnings has been challenged by the heterogeneity in deficits' severity among patients. Here, we address this issue by combining logistic regression and random forest to classify two neuropsychological profiles of patients with high (HighCog) and low (LowCog) cognitive performance in two independent samples. We based our analysis on the cortical features grey matter volume (VOL), cortical thickness (CT), and mean curvature (MC) of N = 57 patients (discovery sample) and validated the classification in an independent sample (N = 52). We investigated which cortical feature would yield the best classification results and expected that the 10 most important features would include frontal and temporal brain regions. The model based on MC had the best performance with area under the curve (AUC) values of 76% and 73%, and identified fronto-temporal and occipital brain regions as the most important features for the classification. Moreover, subsequent comparison analyses could reveal significant differences in MC of single brain regions between the two cognitive profiles. The present study suggests MC as a promising neuroanatomical parameter for characterizing schizophrenia cognitive subtypes.
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Esquizofrenia , Humanos , Esquizofrenia/complicaciones , Esquizofrenia/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Encéfalo , Sustancia Gris/diagnóstico por imagen , CogniciónRESUMEN
Purpose: To analyze the performance of deep learning (DL) models for segmentation of the neonatal lung in MRI and investigate the use of automated MRI-based features for assessment of neonatal lung disease. Materials and Methods: Quiet-breathing MRI was prospectively performed in two independent cohorts of preterm infants (median gestational age, 26.57 weeks; IQR, 25.3-28.6 weeks; 55 female and 48 male infants) with (n = 86) and without (n = 21) chronic lung disease (bronchopulmonary dysplasia [BPD]). Convolutional neural networks were developed for lung segmentation, and a three-dimensional reconstruction was used to calculate MRI features for lung volume, shape, pixel intensity, and surface. These features were explored as indicators of BPD and disease-associated lung structural remodeling through correlation with lung injury scores and multinomial models for BPD severity stratification. Results: The lung segmentation model reached a volumetric Dice coefficient of 0.908 in cross-validation and 0.880 on the independent test dataset, matching expert-level performance across disease grades. MRI lung features demonstrated significant correlations with lung injury scores and added structural information for the separation of neonates with BPD (BPD vs no BPD: average area under the receiver operating characteristic curve [AUC], 0.92 ± 0.02 [SD]; no or mild BPD vs moderate or severe BPD: average AUC, 0.84 ± 0.03). Conclusion: This study demonstrated high performance of DL models for MRI neonatal lung segmentation and showed the potential of automated MRI features for diagnostic assessment of neonatal lung disease while avoiding radiation exposure.Keywords: Bronchopulmonary Dysplasia, Chronic Lung Disease, Preterm Infant, Lung Segmentation, Lung MRI, BPD Severity Assessment, Deep Learning, Lung Imaging Biomarkers, Lung Topology Supplemental material is available for this article. Published under a CC BY 4.0 license.See also the commentary by Parraga and Sharma in this issue.
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BACKGROUND: To date, studies on positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) in progressive supranuclear palsy (PSP) usually included PSP cohorts overrepresenting patients with Richardson's syndrome (PSP-RS). OBJECTIVES: To evaluate FDG-PET in a patient sample representing the broad phenotypic PSP spectrum typically encountered in routine clinical practice. METHODS: This retrospective, multicenter study included 41 PSP patients, 21 (51%) with RS and 20 (49%) with non-RS variants of PSP (vPSP), and 46 age-matched healthy controls. Two state-of-the art methods for the interpretation of FDG-PET were compared: visual analysis supported by voxel-based statistical testing (five readers) and automatic covariance pattern analysis using a predefined PSP-related pattern. RESULTS: Sensitivity and specificity of the majority visual read for the detection of PSP in the whole cohort were 74% and 72%, respectively. The percentage of false-negative cases was 10% in the PSP-RS subsample and 43% in the vPSP subsample. Automatic covariance pattern analysis provided sensitivity and specificity of 93% and 83% in the whole cohort. The percentage of false-negative cases was 0% in the PSP-RS subsample and 15% in the vPSP subsample. CONCLUSIONS: Visual interpretation of FDG-PET supported by voxel-based testing provides good accuracy for the detection of PSP-RS, but only fair sensitivity for vPSP. Automatic covariance pattern analysis outperforms visual interpretation in the detection of PSP-RS, provides clinically useful sensitivity for vPSP, and reduces the rate of false-positive findings. Thus, pattern expression analysis is clinically useful to complement visual reading and voxel-based testing of FDG-PET in suspected PSP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Trastornos del Movimiento , Parálisis Supranuclear Progresiva , Humanos , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Parálisis Supranuclear Progresiva/diagnósticoRESUMEN
BACKGROUND: Brain magnetic resonance imaging (MRI) is used to support the diagnosis of progressive supranuclear palsy (PSP). However, the value of visual descriptive, manual planimetric, automatic volumetric MRI markers and fully automatic categorization is unclear, particularly regarding PSP predominance types other than Richardson's syndrome (RS). OBJECTIVES: To compare different visual reading strategies and automatic classification of T1-weighted MRI for detection of PSP in a typical clinical cohort including PSP-RS and (non-RS) variant PSP (vPSP) patients. METHODS: Forty-one patients (21 RS, 20 vPSP) and 46 healthy controls were included. Three readers using three strategies performed MRI analysis: exclusively visual reading using descriptive signs (hummingbird, morning-glory, Mickey-Mouse), visual reading supported by manual planimetry measures, and visual reading supported by automatic volumetry. Fully automatic classification was performed using a pre-trained support vector machine (SVM) on the results of atlas-based volumetry. RESULTS: All tested methods achieved higher specificity than sensitivity. Limited sensitivity was driven to large extent by false negative vPSP cases. Support by automatic volumetry resulted in the highest accuracy (75.1% ± 3.5%) among the visual strategies, but performed not better than the midbrain area (75.9%), the best single planimetric measure. Automatic classification by SVM clearly outperformed all other methods (accuracy, 87.4%), representing the only method to provide clinically useful sensitivity also in vPSP (70.0%). CONCLUSIONS: Fully automatic classification of volumetric MRI measures using machine learning methods outperforms visual MRI analysis without and with planimetry or volumetry support, particularly regarding diagnosis of vPSP, suggesting the use in settings with a broad phenotypic PSP spectrum. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Encéfalo , Parálisis Supranuclear Progresiva , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Mesencéfalo/patología , Parálisis Supranuclear Progresiva/patologíaRESUMEN
INTRODUCTION: Persistent postural-perceptual dizziness (PPPD) (ICD-11) and anxiety disorders (ANX) share behavioural symptoms like anxiety, avoidance, social withdrawal, hyperarousal, or palpitation as well as neurological symptoms like vertigo, stance and gait disorders. Furthermore, previous studies have shown a bidirectional link between vestibulo-spatial and anxiety neural networks. So far, there have been no neuroimaging-studies comparing these groups. OBJECTIVES: The aim of this explorative study was to investigate differences and similarities of neural correlates between these two patient groups and to compare their findings with a healthy control group. METHODS: 63 participants, divided in two patient groups (ANX = 20 and PPPD = 14) and two sex and age matched healthy control groups (HC-A = 16, HC-P = 13) were included. Anxiety and dizziness related pictures were shown during fMRI-measurements in a block-design in order to induce emotional responses. All subjects filled in questionnaires regarding vertigo (VSS, VHQ), anxiety (STAI), depression (BDI-II), alexithymia (TAS), and illness-perception (IPQ). After modelling the BOLD response with a standard canonical HRF, voxel-wise t-tests between conditions (emotional-negative vs neutral stimuli) were used to generate statistical contrast maps and identify relevant brain areas (pFDR < 0.05, cluster size >30 voxels). ROI-analyses were performed for amygdala, cingulate gyrus, hippocampus, inferior frontal gyrus, insula, supramarginal gyrus and thalamus (p ≤ 0.05). RESULTS: Patient groups differed from both HC groups regarding anxiety, dizziness, depression and alexithymia scores; ratings of the PPPD group and the ANX group did differ significantly only in the VSS subscale 'vertigo and related symptoms' (VSS-VER). The PPPD group showed increased neural responses in the vestibulo-spatial network, especially in the supramarginal gyrus (SMG), and superior temporal gyrus (STG), compared to ANX and HC-P group. The PPPD group showed increased neural responses compared to the HC-P group in the anxiety network including amygdala, insula, lentiform gyrus, hippocampus, inferior frontal gyrus (IFG) and brainstem. Neuronal responses were enhanced in visual structures, e.g. fusiform gyrus, middle occipital gyrus, and in the medial orbitofrontal cortex (mOFC) in healthy controls compared to patients with ANX and PPPD, and in the ANX group compared to the PPPD group. CONCLUSIONS: These findings indicate that neuronal responses to emotional information in the PPPD and the ANX group are comparable in anxiety networks but not in vestibulo-spatial networks. Patients with PPPD revealed a stronger neuronal response especially in SMG and STG compared to the ANX and the HC group. These results might suggest higher sensitivity and poorer adaptation processes in the PPPD group to anxiety and dizziness related pictures. Stronger activation in visual processing areas in HC subjects might be due to less emotional and more visual processing strategies.
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Mareo , Vértigo , Humanos , Mareo/diagnóstico por imagen , Vértigo/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Trastornos de Ansiedad/diagnóstico por imagen , Corteza Cerebral , Ansiedad/diagnóstico por imagenRESUMEN
Alzheimer's disease (AD) is associated with alterations in functional connectivity (FC) of the brain. The FC underpinnings of CR, that is, lifelong experiences, are largely unknown. Resting-state FC and structural MRI were performed in 76 CSF amyloid-ß (Aß) negative healthy controls and 152 Aß positive individuals as an AD spectrum cohort (ADS; 55 with subjective cognitive decline, SCD; 52 with mild cognitive impairment; 45 with AD dementia). Following a region-of-interest (ROI) FC analysis, intrinsic network connectivity within the default-mode network (INC-DMN) and anti-correlation in INC between the DMN and dorsal attention network (DMN:DAN) were obtained as composite scores. CR was estimated by education and Lifetime Experiences Questionnaire (LEQ). The association between INC-DMN and MEM was attenuated by higher LEQ scores in the entire ADS group, particularly in SCD. In ROI analyses, higher LEQ scores were associated with higher FC within the DMN in ADS group. INC-DMN remains relatively intact despite memory decline in individuals with higher lifetime activity estimates, supporting a role for functional networks in maintaining cognitive function in AD.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Reserva Cognitiva , Humanos , Mapeo Encefálico , Cognición , Encéfalo/diagnóstico por imagen , Péptidos beta-Amiloides , Imagen por Resonancia MagnéticaRESUMEN
PURPOSE: Early after [18F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [18F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [18F]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs. METHODS: Seventy-eight patients with 4RTs (71 ± 7 years, 39 female), 79 patients with other neurodegenerative diseases (67 ± 12 years, 35 female) and twelve age-matched controls (69 ± 8 years, 8 female) underwent dynamic (0-60 min) [18F]PI-2620 PET imaging. Regional perfusion (0.5-2.5 min p.i.) and tau load (20-40 min p.i.) were measured in 246 predefined brain regions [standardized-uptake-value ratios (SUVr), cerebellar reference]. Regional SUVr were compared between 4RTs and controls by an ANOVA including false-discovery-rate (FDR, p < 0.01) correction. Hypoperfusion in resulting 4RT target regions was evaluated at the patient level in all patients (mean value - 2SD threshold). Additionally, perfusion and tau pattern expression levels were explored regarding their potential discriminatory value of 4RTs against other neurodegenerative disorders, including validation in an independent external dataset (n = 37), and correlated with clinical severity in 4RTs (PSP rating scale, MoCA, activities of daily living). RESULTS: Patients with 4RTs had significant hypoperfusion in 21/246 brain regions, most dominant in thalamus, caudate nucleus, and anterior cingulate cortex, fitting to the topology of the 4RT disease spectrum. However, single region hypoperfusion was not specific regarding the discrimination of patients with 4RTs against patients with other neurodegenerative diseases. In contrast, perfusion pattern expression showed promise for discrimination of patients with 4RTs from other neurodegenerative diseases (AUC: 0.850). Discrimination by the combined perfusion-tau pattern expression (AUC: 0.903) exceeded that of the sole tau pattern expression (AUC: 0.864) and the discriminatory power of the combined perfusion-tau pattern expression was replicated in the external dataset (AUC: 0.917). Perfusion but not tau pattern expression was associated with PSP rating scale (R = 0.402; p = 0.0012) and activities of daily living (R = - 0.431; p = 0.0005). CONCLUSION: [18F]PI-2620 perfusion imaging mirrors known topology of regional hypoperfusion in 4RTs. Single region hypoperfusion is not specific for 4RTs, but perfusion pattern expression may provide an additive value for the discrimination of 4RTs from other neurodegenerative diseases and correlates closer with clinical severity than tau pattern expression.
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Enfermedad de Alzheimer , Degeneración Corticobasal , Parálisis Supranuclear Progresiva , Anciano , Femenino , Humanos , Persona de Mediana Edad , Actividades Cotidianas , Enfermedad de Alzheimer/complicaciones , Degeneración Corticobasal/diagnóstico por imagen , Enfermedades Neurodegenerativas/diagnóstico por imagen , Tomografía de Emisión de Positrones , Parálisis Supranuclear Progresiva/diagnóstico por imagenRESUMEN
Knowledge of the physiological endolymphatic space (ELS) is necessary to estimate endolymphatic hydrops (ELH) in patients with vestibulocochlear syndromes. Therefore, the current study investigated age-dependent changes in the ELS of participants with normal vestibulocochlear testing. Sixty-four ears of 32 participants with normal vestibulocochlear testing aged between 21 and 75 years (45.8 ± 17.2 years, 20 females, 30 right-handed, two left-handed) were examined by intravenous delayed gadolinium-enhanced magnetic resonance imaging of the inner ear (iMRI). Clinical diagnostics included neuro-otological assessment, video-oculography during caloric stimulation, and head-impulse test. iMRI data analysis provided semi-quantitative visual grading and automatic algorithmic quantitative segmentation of ELS volume (3D, mm3) using a deep learning-based segmentation of the inner ear's total fluid space (TFS) and volumetric local thresholding, as described earlier. As a result, following a 4-point ordinal scale, a mild ELH (grade 1) was found in 21/64 (32.8%) ears uni- or bilaterally in either cochlear, vestibulum, or both. Age and ELS were found to be positively correlated for the inner ear (r(64) = 0.33, p < 0.01), and vestibulum (r(64) = 0.25, p < 0.05). For the cochlea, the values correlated positively without reaching significance (r(64) = 0.21). In conclusion, age-dependent increases of the ELS should be considered when evaluating potential ELH in single subjects and statistical group comparisons.
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Oído Interno , Hidropesía Endolinfática , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Imagenología Tridimensional , Imagen por Resonancia Magnética/métodos , SíndromeRESUMEN
PURPOSE: Glioma patients, especially recurrent glioma, suffer from a poor prognosis. While advances to classify glioma on a molecular level improved prognostication at initial diagnosis, markers to prognosticate survival in the recurrent situation are still needed. As 18 kDa translocator protein (TSPO) was previously reported to be associated with aggressive histopathological glioma features, we correlated the TSPO positron emission tomography (PET) signal using [18F]GE180 in a large cohort of recurrent glioma patients with their clinical outcome. METHODS: In patients with [18F]GE180 PET at glioma recurrence, [18F]GE180 PET parameters (e.g., SUVmax) as well as other imaging features (e.g., MRI volume, [18F]FET PET parameters when available) were evaluated together with patient characteristics (age, sex, Karnofsky-Performance score) and neuropathological features (e.g. WHO 2021 grade, IDH-mutation status). Uni- and multivariate Cox regression and Kaplan-Meier survival analyses were performed to identify prognostic factors for post-recurrence survival (PRS) and time to treatment failure (TTF). RESULTS: Eighty-eight consecutive patients were evaluated. TSPO tracer uptake correlated with tumor grade at recurrence (p < 0.05), with no significant differences in IDH-wild-type versus IDH-mutant tumors. Within the subgroup of IDH-mutant glioma (n = 46), patients with low SUVmax (median split, ≤ 1.60) had a significantly longer PRS (median 41.6 vs. 25.3 months, p = 0.031) and TTF (32.2 vs 8.7 months, p = 0.001). Also among IDH-wild-type glioblastoma (n = 42), patients with low SUVmax (≤ 1.89) had a significantly longer PRS (median not reached vs 8.2 months, p = 0.002). SUVmax remained an independent prognostic factor for PRS in the multivariate analysis including CNS WHO 2021 grade, IDH status, and age. Tumor volume defined by [18F]FET PET or contrast-enhanced MRI correlated weakly with TSPO tracer uptake. Treatment regimen did not differ among the median split subgroups. CONCLUSION: Our data suggest that TSPO PET using [18F]GE180 can help to prognosticate recurrent glioma patients even among homogeneous molecular subgroups and may therefore serve as valuable non-invasive biomarker for individualized patient management.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Recurrencia Local de Neoplasia/diagnóstico por imagen , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/terapia , Tomografía de Emisión de Positrones/métodos , Tirosina , Receptores de GABA/genética , Receptores de GABA/metabolismoRESUMEN
Neonatal chronic lung disease lacks standardized assessment of lung structural changes. We addressed this clinical need by the development of a novel scoring system [UNSEAL BPD (UNiforme Scoring of the disEAsed Lung in BPD)] using T2-weighted single-shot fast-spin-echo sequences from 3 T MRI in very premature infants with and without bronchopulmonary dysplasia (BPD). Quantification of interstitial and airway remodeling, emphysematous changes, and ventilation inhomogeneity was achieved by consensus scoring on a five-point Likert scale. We successfully identified moderate and severe disease by logistic regression [area under the curve (AUC), 0.89] complemented by classification tree analysis revealing gestational age-specific structural changes. We demonstrated substantial interreader reproducibility (weighted Cohen's κ 0.69) and disease specificity (AUC = 0.91). Our novel MRI score enables the standardized assessment of disease-characteristic structural changes in the preterm lung exhibiting significant potential as a quantifiable endpoint in early intervention clinical trials and long-term disease monitoring.
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Displasia Broncopulmonar , Recien Nacido Prematuro , Lactante , Humanos , Recién Nacido , Displasia Broncopulmonar/diagnóstico por imagen , Displasia Broncopulmonar/patología , Reproducibilidad de los Resultados , Pulmón/diagnóstico por imagen , Pulmón/patología , Edad Gestacional , Imagen por Resonancia MagnéticaRESUMEN
INTRODUCTION: Individual real-time functional magnetic resonance imaging neurofeedback (rtfMRI NF) might be a promising adjuvant in treating depressive symptoms. Further studies showed functional variations and connectivity-related changes in the dorsolateral prefrontal cortex (dlPFC) and the insular cortex. OBJECTIVES: The aim of this pilot study was to investigate whether individualized connectivity-based rtfMRI NF training can improve symptoms in depressed patients as an adjunct to a psychotherapeutic programme. The novel strategy chosen for this was to increase connectivity between individualized regions of interest, namely the insula and the dlPFC. METHODS: Sixteen patients diagnosed with major depressive disorder (MDD, ICD-10) and 19 matched healthy controls (HC) participated in a rtfMRI NF training consisting of two sessions with three runs each, within an interval of one week. RtfMRI NF was applied during a sequence of negative emotional pictures to modulate the connectivity between the dlPFC and the insula. The MDD REAL group was divided into a Responder and a Non-Responder group. Patients with an increased connectivity during the second NF session or during both the first and the second NF session were identified as "MDD REAL Responder" (N = 6). Patients that did not show any increase in connectivity and/or a decreased connectivity were identified as "MDD REAL Non-Responder" (N = 7). RESULTS: Before the rtfMRI sessions, patients with MDD showed higher neural activation levels in ventromedial PFC and the insula than HC; by contrast, HC revealed increased hemodynamic activity in visual processing areas (primary visual cortex and visual association cortex) compared to patients with MDD. The comparison of hemodynamic responses during the first compared to during the last NF session demonstrated significantly increased BOLD-activation in the medial orbitofrontal cortex (mOFC) in patients and HC, and additionally in the lateral OFC in patients with MDD. These findings were particularly due to the MDD Responder group, as the MDD Non-Responder group showed no increase in this region during the last NF run. There was a decrease of neural activation in emotional processing brain regions in both groups in the last NF run compared to the first: HC showed differences in the insula, parahippocampal gyrus, basal ganglia, and cingulate gyrus. Patients with MDD demonstrated deceased responses in the parahippocampal gyrus. There was no significant reduction of BDI scores after NF training in patients. CONCLUSIONS: Increased neural activation in the insula and vmPFC in MDD suggests an increased emotional reaction in patients with MDD. The activation of the mOFC could be associated with improved control-strategies and association-learning processes. The increased lOFC activation could indicate a stronger sensitivity to failed NF attempts in MDD. A stronger involvement of visual processing areas in HC may indicate better adaptation to negative emotional stimuli after repeated presentation. Overall, the rtfMRI NF had an impact on neurobiological mechanisms, but not on psychometric measures in patients with MDD.
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Negative symptoms and cognitive deficits are common in individuals with schizophrenia, greatly affect their outcome, and have been associated with alterations in cerebral gray and white matter volume (GMV, WMV). In the last decade, aerobic endurance training has emerged as a promising intervention to alleviate these symptoms and improved aerobic fitness has been suggested as a key moderator variable. In the present study, we investigated, whether aerobic fitness is associated with fewer cognitive deficits and negative symptoms and with GMVs and WMVs in individuals with schizophrenia in a cross-sectional design. In the largest study to date on the implications of fitness in individuals with schizophrenia, 111 participants at two centers underwent assessments of negative symptoms, cognitive functioning, and aerobic fitness and 69 underwent additional structural magnetic resonance imaging. Multilevel Bayesian partial correlations were computed to quantify relationships between the variables of interest. The main finding was a positive association of aerobic fitness with right hippocampal GMV and WMVs in parahippocampal and several cerebellar regions. We found limited evidence for an association of aerobic fitness with cognitive functioning and negative symptoms. In summary, our results strengthen the notion that aerobic fitness and hippocampal plasticity are interrelated which holds implications for the design of exercise interventions in individuals with schizophrenia.
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Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/terapia , Quimioradioterapia , Glioma/diagnóstico por imagen , Glioma/terapia , Humanos , Isocitrato Deshidrogenasa/genética , Mutación , Tomografía de Emisión de Positrones , Receptores de GABARESUMEN
Corticobasal syndrome (CBS) is a rare neurodegenerative condition characterized by four-repeat tau aggregation in the cortical and subcortical brain regions and accompanied by severe atrophy. The aim of this study was to evaluate partial volume effect correction (PVEC) in patients with CBS compared to a control cohort imaged with the 18-kDa translocator protein (TSPO) positron emission tomography (PET) tracer [18F]GE-180. Eighteen patients with CBS and 12 age- and sex-matched healthy controls underwent [18F]GE-180 PET. The cortical and subcortical regions were delineated by deep nuclei parcellation (DNP) of a 3D-T1 MRI. Region-specific subcortical volumes and standardized uptake values and ratios (SUV and SUVr) were extracted before and after region-based voxel-wise PVEC. Regional volumes were compared between patients with CBS and controls. The % group differences and effect sizes (CBS vs. controls) of uncorrected and PVE-corrected SUVr data were compared. Single-region positivity in patients with CBS was assessed by a >2 SD threshold vs. controls and compared between uncorrected and PVE-corrected data. Smaller regional volumes were detected in patients with CBS compared to controls in the right ventral striatum (p = 0.041), the left putamen (p = 0.005), the right putamen (p = 0.038) and the left pallidum (p = 0.015). After applying PVEC, the % group differences were distinctly higher, but the effect sizes of TSPO uptake were only slightly stronger due to the higher variance after PVEC. The single-region positivity of TSPO PET increased in patients with CBS after PVEC (100 vs. 83 regions). PVEC in the cortical and subcortical regions is valuable for TSPO imaging of patients with CBS, leading to the improved detection of elevated [18F]GE-180 uptake, although the effect sizes in the comparison against the controls did not improve strongly.
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BACKGROUND: Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the relationship of these abnormalities with functional outcome remains unclear. METHODS: In two independent cohorts (C1, C2), patients with SZ were divided into two subgroups: patients with higher cognitive performance (SZ-HCP-C1, n = 25; SZ-HCP-C2, n = 24) and patients with lower cognitive performance (SZ-LCP-C1, n = 25; SZ-LCP-C2, n = 24). Healthy controls (HC) were included in both cohorts (HC-C1, n = 52; HC-C2, n = 27). We compared fractional anisotropy (FA) of the whole-brain WM skeleton between the three groups (SZ-LCP, SZ-HCP, HC) by a whole-brain exploratory approach and an atlas-defined WM regions-of-interest approach via tract-based spatial statistics. In addition, we explored whether FA values were associated with Global Assessment of Functioning (GAF) scores in the SZ groups. RESULTS: In both cohorts, mean FA values of whole-brain WM skeleton were significantly lower in the SCZ-LCP group than in the SCZ-HCP group. Whereas in C1 the FA of the frontal part of the left inferior fronto-occipital fasciculus (IFOF) was positively correlated with GAF score, in C2 the FA of the temporal part of the left IFOF was positively correlated with GAF score. CONCLUSIONS: We provide robust evidence for WM microstructural abnormalities in SZ. These abnormalities are more prominent in patients with low cognitive performance and are associated with the level of functioning.
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Esquizofrenia , Sustancia Blanca , Anisotropía , Encéfalo/diagnóstico por imagen , Cognición , Imagen de Difusión Tensora , Humanos , Esquizofrenia/complicaciones , Esquizofrenia/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
Multiple genetic and non-heritable factors have been linked to the risk of multiple sclerosis (MS). These factors seem to contribute to disease pathogenesis before the onset of clinical symptoms, as suggested by incidental MRI evidence of subclinical MS neuropathology in individuals without clinical symptoms. Individuals with high familial risk for MS, such as first-degree relatives of patients with MS, can be studied by MRI to characterize the neuropathology during a subclinical period of MS. 16 studies published in English, which performed brain MRI on healthy individuals with high familial risk of MS were included in this scoping review. Studies suggest either no conclusive (5), or inconclusive yet considerable (4), or conclusive evidence (7) for the incidence of subclinical neuropathology, including focal and diffuse tissue damage. Across all studies, white matter lesions fulfilling MS criteria were observed in 86 of 613 individuals (14%). Future research is needed to evaluate the longitudinal dynamics and clinical relevance of preclinical imaging abnormalities in MS.
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Esclerosis Múltiple , Enfermedades del Sistema Nervioso , Encéfalo/diagnóstico por imagen , Predisposición Genética a la Enfermedad , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/genéticaRESUMEN
BACKGROUND: Mapping of T1 and T2 relaxation times in cardiac MRI is an invaluable tool for the diagnosis and risk stratification of a wide spectrum of cardiac diseases. PURPOSE: To investigate the global and regional reproducibility of native T1 and T2 mapping and to analyze the influence of demographic factors, physiological parameters, slice position, and myocardial regions on reproducibility. STUDY TYPE: Prospective single-center cohort-study. POPULATION: Fifty healthy volunteers (29 female, 21 male) with a mean age of 39.4 ± 13.7 years. FIELD STRENGTH/SEQUENCE: Each volunteer was investigated twice at 1.5 T using a modified look-locker inversion-recovery (MOLLI) sequence (T1 mapping) and a T2-prepared steady-state free precession (SSFP) sequence (T2 mapping). ASSESSMENT: Global T1 and T2 values were quantified for the entire left ventricle in three short-axis slices. Regional T1 and T2 values were measured for each myocardial segment and for myocardial segments grouped by slice position and anatomical region. STATISTICAL TESTS: Test-retest reproducibility was assessed using intraclass correlation coefficient (ICC) and Bland-Altman statistics. A P value < 0.05 was considered statistically significant. RESULTS: Reproducibility was good for global T1 values (ICC 0.88) and excellent for global T2 values (ICC 0.91). Reproducibility of T1 values was excellent (ICC 0.91) for midventricular slice and good for apical (ICC 0.86) and basal slice (ICC 0.81). Reproducibility of T1 mapping values was highest in the septum (ICC 0.90) compared to the anterior (0.81), lateral (0.86), and inferior (0.86) wall. For T2 mapping, reproducibility was good for all slice positions (ICC 0.86 for midventricular, 0.83 for basal, and 0.80 for apical slice). Reproducibility of T2 mapping was significantly lower for the inferior wall (ICC 0.58) than for septum (0.89), anterior (0.85), and lateral (0.87) wall. DATA CONCLUSION: Native T1 and T2 mapping has good to excellent reproducibility with significant regional differences. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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Corazón , Imagen por Resonancia Magnética , Adulto , Femenino , Corazón/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Miocardio , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: This is a cross-sectional study to evaluate whether ß-amyloid-(Aß)-PET positivity and cortical superficial siderosis (cSS) in patients with cerebral amyloid angiopathy (CAA) are regionally colocalized. METHODS: Ten patients with probable or possible CAA (73.3 ± 10.9 years, 40% women) underwent MRI examination with a gradient-echo-T2*-weighted-imaging sequence to detect cSS and 18F-florbetaben PET examination to detect fibrillar Aß. In all cortical regions of the Hammers Atlas, cSS positivity (MRI: ITK-SNAP segmentation) and Aß-PET positivity (PET: ≥ mean value + 2 standard deviations of 14 healthy controls) were defined. Regional agreement of cSS- and Aß-PET positivity was evaluated. Aß-PET quantification was compared between cSS-positive and corresponding contralateral cSS-negative atlas regions. Furthermore, the Aß-PET quantification of cSS-positive regions was evaluated in voxels close to cSS and in direct cSS voxels. RESULTS: cSS- and Aß-PET positivity did not indicate similarity of their regional patterns, despite a minor association between the frequency of Aß-positive patients and the frequency of cSS-positive patients within individual regions (r s = 0.277, p = 0.032). However, this association was driven by temporal regions lacking cSS- and Aß-PET positivity. When analyzing all composite brain regions, Aß-PET values in regions close to cSS were significantly higher than in regions directly affected with cSS (p < 0.0001). However, Aß-PET values in regions close to cSS were not different when compared to corresponding contralateral cSS-negative regions (p = 0.603). CONCLUSION: In this cross-sectional study, cSS and Aß-PET positivity did not show regional association in patients with CAA and deserve further exploitation in longitudinal designs. In clinical routine, a specific cross-sectional evaluation of Aß-PET in cSS-positive regions is probably not useful for visual reading of Aß-PETs in patients with CAA.