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The segregation of the cortical mantle into cytoarchitectonic areas provides a structural basis for the specialization of different brain regions. In vivo neuroimaging experiments can be linked to this postmortem cytoarchitectonic parcellation via Julich-Brain. This atlas embeds probabilistic maps that account for inter-individual variability in the localization of cytoarchitectonic areas in the reference spaces targeted by spatial normalization. We built a framework to improve the alignment of architectural areas across brains using cortical folding landmarks. This framework, initially designed for in vivo imaging, was adapted to postmortem histological data. We applied this to the first 14 brains used to establish the Julich-Brain atlas to infer a refined atlas with more focal probabilistic maps. The improvement achieved is significant in the primary regions and some of the associative areas. This framework also provides a tool for exploring the relationship between cortical folding patterns and cytoarchitectonic areas in different cortical regions to establish new landmarks in the remainder of the cortex.
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Encéfalo , Neuroimagem , Autopsia , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodosRESUMO
BACKGROUND: In CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), clinical severity is not related to the total burden of white matter hyperintensities (WMHs), presumably because of heterogeneous underlying tissue alterations. We aimed to investigate whether WMHs in the corpus callosum (WMHCC) are due to secondary degeneration and related to clinical severity. METHODS: We evaluated data from 228 CADASIL patients included in an ongoing prospective cohort with available 3-dimensional fluid-attenuated inversion recovery magnetic resonance imaging sequences. We analyzed in a blind manner WMHCC and lacunes in presumably connected areas to determine whether WMHCC are related to secondary degeneration. We evaluated the links between WMHCC and the Mattis dementia rating scale and the modified Rankin Scale-widely used measures of global cognitive performances and disability, respectively. Linear regression models were adjusted for age, sex, level of education, brain volume, number of lacunes, and volume of WMH. RESULTS: Among 228 patients, only 105 (46%) had WMHCC while all had WMH in the rest of the white matter. In 74% of cases, WMHCC crossed a presumably connected nearby lacune, which was significantly higher than the expected value if the spatial distributions of WMHCC and nearby lacunes were unrelated (11%; P<0.001). Patients with WMHCC had worse Mattis dementia rating scale (median [P25-P75], 138 [122-142] versus 143 [140-143]; P<0.001) and worse modified Rankin Scale (2 [1-3] versus 1 [0-1]; P<0.001). In adjusted models, Mattis dementia rating scale was significantly associated with WMHCC (estimate, -6.2 [95% CI, -11.8 to -0.1]). CONCLUSIONS: In CADASIL, WMHCC are likely related to secondary degeneration and are independently related to clinical severity, in contrast to the total burden of WMH.
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CADASIL , Substância Branca , Humanos , CADASIL/complicações , Estudos Prospectivos , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imageamento por Ressonância Magnética , Encéfalo/patologiaRESUMO
OBJECTIVE: The majority of patients with a familial cerebral small vessel disease (CSVD) referred for molecular screening do not show pathogenic variants in known genes. In this study, we aimed to identify novel CSVD causal genes. METHODS: We performed a gene-based collapsing test of rare protein-truncating variants identified in exome data of 258 unrelated CSVD patients of an ethnically matched control cohort and of 2 publicly available large-scale databases, gnomAD and TOPMed. Western blotting was used to investigate the functional consequences of variants. Clinical and magnetic resonance imaging features of mutated patients were characterized. RESULTS: We showed that LAMB1 truncating variants escaping nonsense-mediated messenger RNA decay are strongly overrepresented in CSVD patients, reaching genome-wide significance (p < 5 × 10-8 ). Using 2 antibodies recognizing the N- and C-terminal parts of LAMB1, we showed that truncated forms of LAMB1 are expressed in the endogenous fibroblasts of patients and trapped in the cytosol. These variants are associated with a novel phenotype characterized by the association of a hippocampal type episodic memory defect and a diffuse vascular leukoencephalopathy. INTERPRETATION: These findings are important for diagnosis and clinical care, to avoid unnecessary and sometimes invasive investigations, and also from a mechanistic point of view to understand the role of extracellular matrix proteins in neuronal homeostasis. ANN NEUROL 2021;90:962-975.
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Doenças de Pequenos Vasos Cerebrais/genética , Hipocampo/diagnóstico por imagem , Laminina/genética , Leucoencefalopatias/genética , Transtornos da Memória/genética , Adulto , Idoso , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Exoma , Feminino , Humanos , Leucoencefalopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/diagnóstico por imagem , Pessoa de Meia-Idade , Fenótipo , Sistema de RegistrosRESUMO
In the human brain, the appearance of cortical sulci is a complex process that takes place mostly during the second half of pregnancy, with a relatively stable temporal sequence across individuals. Since deviant gyrification patterns have been observed in many neurodevelopmental disorders, mapping cortical development in vivo from the early stages on is an essential step to uncover new markers for diagnosis or prognosis. Recently this has been made possible by MRI combined with post-processing tools, but the reported results are still fragmented. Here we aimed to characterize the typical folding progression ex utero from the pre- to the post-term period, by considering 58 healthy preterm and full-term newborns and infants imaged between 27 and 62 weeks of post-menstrual age. Using a method of spectral analysis of gyrification (SPANGY), we detailed the spatial-frequency structure of cortical patterns in a quantitative way. The modeling of developmental trajectories revealed three successive waves that might correspond to primary, secondary and tertiary folding. Some deviations were further detected in 10 premature infants without apparent neurological impairment and imaged at term equivalent age, suggesting that our approach is sensitive enough to highlight the subtle impact of preterm birth and extra-uterine life on folding.
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Córtex Cerebral/embriologia , Córtex Cerebral/crescimento & desenvolvimento , Neuroimagem/métodos , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Recém-Nascido , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética , MasculinoRESUMO
BACKGROUND: Segmentation of white matter hyperintensities (WMH) in CADASIL, one of the most severe cerebral small vessel disease of genetic origin, is challenging. METHOD: We adapted and validated an automatic method based on a convolutional neural network (CNN) algorithm and using a large dataset of 2D and/or 3D FLAIR and T1-weighted images acquired in 132 patients, to measure the progression of WMH in this condition. RESULTS: The volume of WMH measured using this method correlated strongly with reference data validated by experts. WMH segmentation was also clearly improved compared to the BIANCA segmentation method. Combining two successive learning models was found to be of particular interest, reducing the number of false-positive voxels and the extent of under-segmentation detected after a single-stage process. With the two-stage approach, WMH progression correlated with measures derived from the reference masks for lesions increasing with age, and with the variable WMH progression trajectories at individual level. We also confirmed the expected effect of the initial load of WMH and the influence of the type of MRI acquisition on measures of this progression. CONCLUSION: Altogether, our findings suggest that WMH progression in CADASIL can be measured automatically with adequate confidence by a CNN segmentation algorithm.
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A major hurdle to therapeutic development in cerebral small vessel diseases is the lack of in-vivo method that can be used repeatedly for evaluating directly cerebral microvessels. We hypothesised that Adaptive Optics (AO), which allows resolution images up to 1-2 µm/pixel at retinal level, could provide a biomarker for monitoring vascular changes in CADASIL, a genetic form of such condition. In 98 patients and 35 healthy individuals, the wall to lumen ratio (WLR), outer and inner diameter, wall thickness and wall cross-sectional area were measured in a parapapillary and/or paramacular retinal artery. The ratio of vessel diameters before and after light flicker stimulations was also calculated to measure vasoreactivity (VR). Multivariate mixed-model analysis showed that WLR was increased and associated with a larger wall thickness and smaller internal diameter of retinal arteries in patients. The difference was maximal at the youngest age and gradually reduced with aging. Average VR in patients was less than half of that of controls since the youngest age. Any robust association was found with clinical or imaging manifestations of the disease. Thus, AO enables the detection of early functional or structural vascular alterations in CADASIL but with no obvious link to the clinical or imaging severity.
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CADASIL , Artéria Retiniana , Humanos , CADASIL/fisiopatologia , CADASIL/diagnóstico por imagem , CADASIL/patologia , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Artéria Retiniana/diagnóstico por imagem , Artéria Retiniana/fisiopatologia , Artéria Retiniana/patologia , Idoso , Luz , Vasodilatação/fisiologia , Remodelação Vascular/fisiologiaRESUMO
Background: Lacunes represent key imaging markers of cerebral small vessel diseases (cSVDs). During their progression, incident lacunes are related to stroke manifestations and contribute to progressive cognitive and/or motor decline. Assessing new lesions has become crucial but remains time-consuming and error-prone, even for an expert. We, thus, sought to develop and validate an automatic segmentation method of incident lacunes in CADASIL caused by cysteine mutation in the EGFr domains of the NOTCH3 gene, a severe and progressive monogenic form of cSVD. Methods: Incident lacunes were identified based on difference maps of 3D T1-weighted MRIs obtained at the baseline and 2 years later. These maps were thresholded using clustering analysis and compared with results obtained by expert visual analysis, which is considered the gold standard approach. Results: The median number of lacunes at the baseline in 30 randomly selected patients was 7 (IQR = [2, 11]). The median number of incident lacunes was 2 (IQR = [0, 3]) using the automatic method (mean time-processing: 25 s/patient) and 0.5 (IQR = [0, 2]) using the standard visual approach (mean time-processing: 8 min/patient). The complementary analysis of segmentation results is enabled to quickly remove false positives detected in specific locations and to identify true incident lesions not previously detected by the standard analysis (2 min/case). A combined approach based on automatic segmentation of incident lacunes followed by quick corrections of false positives allowed to reach high individual sensitivity (median at 0.66, IQR = [0.21, 1.00]) and global specificity scores (0.80). Conclusion: The automatic segmentation of incident lacunes followed by quick corrections of false positives appears promising for properly and rapidly quantifying incident lacunes in large cohorts of cSVDs.
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Background and objective: Retinal vascular density (VD) measured using optical coherence tomography with angiography (OCTA) has been suggested as a potential marker of intracerebral vascular changes in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). We aimed to determine whether VD is related to the clinical and imaging manifestations of the disease. Methods: OCTA was performed in 104 CADASIL patients (parallel to their clinical and imaging assessment) and in 83 healthy individuals. Results: A significant reduction of VD related to age was detected in patients and controls in the superficial and deep vascular plexus of the whole foveal or parafoveal retinal area (p<0.0001). After adjustment for age, these parameters were found significantly lower in patients than in controls (p<0.03). Multivariable analysis did not show any association between retinal VD and history of stroke, modified Rankin Scale or Mini-Mental Status Examination scores. No significant association was found with MRI lesions either. Conclusion: In CADASIL, retinal VD is decreased early and progresses with ageing but does not appear related to the severity of clinical or imaging manifestations.
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BACKGROUND AND OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent genetic cerebrovascular disease. The clinical aspects of the disease in relation to the various types of lesions on MRI vary widely not only within families but also between different cohorts reported worldwide. Many limitations prevent comparison of imaging data obtained with different scanners and sequences in different patient cohorts. We aimed to develop and validate a simple tool to inventory quickly the key MRI features in CADASIL to compare imaging data across different populations. METHODS: The Inventory Tool (CADA-MRIT) was designed by consensus after repeated expert meetings. It consists of 11 imaging items to assess periventricular, deep, and superficial white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMB), centrum semiovale and basal ganglia dilated perivascular spaces (dPVS), superficial and deep atrophy, large infarcts, and macrobleeds. The reliability, clinical relevance, and time-effectiveness of CADA-MRIT were assessed using data from 3 independent patient cohorts. RESULTS: Imaging data from 671 patients with CADASIL (440 from France, 119 from Germany, and 112 from Taiwan) were analyzed. Their mean age was 53.4 ± 12.2 years, 54.5% were women, 56.2% had stroke, and 31.1% had migraine with aura. Any lacune was present in at least 70% of individuals, whereas CMB occurred in 83% of patients from the Asian cohort and in only 35% of European patients. CADA-MRIT scores obtained for WMH, CMB, and dPVS were comparable regardless of the scanner or sequence used (weighted κ > 0.60). Intrarater and interrater agreements were from good to very good (weighted κ > 0.60). Global WMH and atrophy scores correlated strongly with accurate volumetric quantification of WMH or brain parenchymal fraction (Pearson r > 0.60). Different imaging scores were significantly associated with the main clinical manifestations of the disease. The time for evaluating 1 patient was approximately 2-3 minutes. DISCUSSION: The CADA-MRIT is an easy-to-use tool for analyzing and comparing the most frequent MRI lesions of CADASIL across different populations. This instrument is reliable. It can be used with different imaging sequences or scanners. It also provides clinically relevant scores in a very short time for completion.
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CADASIL , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , CADASIL/complicações , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Atrofia/patologiaRESUMO
The recent discovery that the prevalence of cysteine mutations in the NOTCH3 gene responsible for CADASIL was more than 100 times higher in the general population than that estimated in patients highlighted that the mutation location in EGFr-like-domains of the NOTCH3 receptor could have a major effect on the phenotype of the disease. The exact impact of such mutations locations on the multiple facets of the disease has not been fully evaluated. We aimed to describe the phenotypic spectrum of a large population of CADASIL patients and to investigate how this mutation location influenced various clinical and imaging features of the disease. Both a supervised and a non-supervised approach were used for analysis. The results confirmed that the mutation location is strongly related to clinical severity and showed that this effect is mainly driven by a different development of the most damaging ischemic tissue lesions at cerebral level. These effects were detected in addition to those of aging, male sex, hypertension and hypercholesterolemia. The exact mechanisms relating the location of mutations along the NOTCH3 receptor, the amount or properties of the resulting NOTCH3 products accumulating in the vessel wall, and their final consequences at cerebral level remain to be determined.
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CADASIL , Receptor Notch3 , Humanos , Masculino , Mutação , Receptor Notch3/genética , Fatores de Risco , CADASIL/genéticaRESUMO
Cerebral small vessel disease (SVD) is common during ageing and can present as stroke, cognitive decline, neurobehavioural symptoms, or functional impairment. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive and other symptoms and affect activities of daily living. Standards for Reporting Vascular Changes on Neuroimaging 1 (STRIVE-1) categorised and standardised the diverse features of SVD that are visible on structural MRI. Since then, new information on these established SVD markers and novel MRI sequences and imaging features have emerged. As the effect of combined SVD imaging features becomes clearer, a key role for quantitative imaging biomarkers to determine sub-visible tissue damage, subtle abnormalities visible at high-field strength MRI, and lesion-symptom patterns, is also apparent. Together with rapidly emerging machine learning methods, these metrics can more comprehensively capture the effect of SVD on the brain than the structural MRI features alone and serve as intermediary outcomes in clinical trials and future routine practice. Using a similar approach to that adopted in STRIVE-1, we updated the guidance on neuroimaging of vascular changes in studies of ageing and neurodegeneration to create STRIVE-2.
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Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Doenças Neurodegenerativas , Humanos , Atividades Cotidianas , Neuroimagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagemRESUMO
BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most devastating cerebral small vessel diseases. However, despite its progression with aging, some patients remain neurologically intact (Nint) even when they get older. Their main characteristics are poorly known. We aimed to delineate their clinical, imaging, and molecular features. METHODS: Individuals aged over 65 years were selected from a cohort of 472 CADASIL patients. Subjects who had no focal deficit, cognitive impairment, or disability were considered Nint. Their demographic, genetic, clinical, and imaging features were compared to those with permanent neurological symptoms (Nps). RESULTS: Among 129 patients, 23 (17.8%) individuals were considered Nint. The frequency of vascular risk factors and NOTCH3 cysteine mutations in epidermal growth factor-like repeat (EGFr) domains 7-34 did not differ between Nint and Nps patients but Nint patients had less stroke events and were more likely to have migraine with aura. The number of lacunes and microbleeds and degree of brain atrophy were lower in the Nint group, but the volume of white matter hyperintensities did not differ between the two groups. CONCLUSIONS: Nearly one in five CADASIL patients can remain Nint after the age of 65 years. Their clinical and imaging profile differed from that of other age-matched CADASIL patients. The location of NOTCH3 mutation inside or outside EGFr domains 1-6 cannot fully explain this discrepancy. The factors involved in their relative preservation of brain tissue from severe damage despite aging remain to be determined.
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Brain mapping studies often need to identify brain structures or functional circuits into a set of individual brains. To this end, multiple atlases have been published to represent such structures based on different modalities, subject sets, and techniques. The mainstream approach to exploit these atlases consists in spatially deforming each individual data onto a given atlas using dense deformation fields, which supposes the existence of a continuous mapping between atlases and individuals. However, this continuity is not always verified, and this "iconic" approach has limits. We present in this study an alternative, complementary, "structural" approach, which consists in extracting structures from the individual data, and comparing them without deformation. A "structural atlas" is thus a collection of annotated individual data with a common structure nomenclature. It may be used to characterize structure shape variability across individuals or species, or to train machine learning systems. This study exhibits Anatomist, a powerful structural 3D visualization software dedicated to building, exploring, and editing structural atlases involving a large number of subjects. It has been developed primarily to decipher the cortical folding variability; cortical sulci vary enormously in both size and shape, and some may be missing or have various topologies, which makes iconic approaches inefficient to study them. We, therefore, had to build structural atlases for cortical sulci, and use them to train sulci identification algorithms. Anatomist can display multiple subject data in multiple views, supports all kinds of neuroimaging data, including compound structural object graphs, handles arbitrary coordinate transformation chains between data, and has multiple display features. It is designed as a programming library in both C++ and Python languages, and may be extended or used to build dedicated custom applications. Its generic design makes all the display and structural aspects used to explore the variability of the cortical folding pattern work in other applications, for instance, to browse axonal fiber bundles, deep nuclei, functional activations, or other kinds of cortical parcellations. Multimodal, multi-individual, or inter-species display is supported, and adaptations to large scale screen walls have been developed. These very original features make it a unique viewer for structural atlas browsing.
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Infant brain development incorporates several intermingled mechanisms leading to intense and asynchronous maturation across cerebral networks and functional modalities. Combining electroencephalography (EEG) and diffusion magnetic resonance imaging (MRI), previous studies in the visual modality showed that the functional maturation of the event-related potentials (ERP) during the first postnatal semester relates to structural changes in the corresponding white matter pathways. Here investigated similar issues in the auditory modality. We measured ERPs to syllables in 1- to 6-month-old infants and related them to the maturational properties of underlying neural substrates measured with diffusion tensor imaging (DTI). We first observed a decrease in the latency of the auditory P2, and in the diffusivities in the auditory tracts and perisylvian regions with age. Secondly, we highlighted some of the early functional and structural substrates of lateralization. Contralateral responses to monoaural syllables were stronger and faster than ipsilateral responses, particularly in the left hemisphere. Besides, the acoustic radiations, arcuate fasciculus, middle temporal and angular gyri showed DTI asymmetries with a more complex and advanced microstructure in the left hemisphere, whereas the reverse was observed for the inferior frontal and superior temporal gyri. Finally, after accounting for the age-related variance, we correlated the inter-individual variability in P2 responses and in the microstructural properties of callosal fibers and inferior frontal regions. This study combining dedicated EEG and MRI approaches in infants highlights the complex relation between the functional responses to auditory stimuli and the maturational properties of the corresponding neural network.
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Vias Auditivas/anatomia & histologia , Encéfalo/anatomia & histologia , Eletroencefalografia/métodos , Imageamento por Ressonância Magnética/métodos , Feminino , Humanos , Lactente , MasculinoRESUMO
Accurate and robust segmentation of subcortical gray matter (SGM) nuclei is required in many neuroimaging applications. FMRIB's Integrated Registration and Segmentation Tool (FIRST) is one of the most popular software tools for automated subcortical segmentation based on T1-weighted (T1w) images. In this work, we demonstrate that FIRST tends to produce inaccurate SGM segmentation results in the case of abnormal brain anatomy, such as present in atrophied brains, due to a poor spatial match of the subcortical structures with the training data in the MNI space as well as due to insufficient contrast of SGM structures on T1w images. Consequently, such deviations from the average brain anatomy may introduce analysis bias in clinical studies, which may not always be obvious and potentially remain unidentified. To improve the segmentation of subcortical nuclei, we propose to use FIRST in combination with a special Hybrid image Contrast (HC) and Non-Linear (nl) registration module (HC-nlFIRST), where the hybrid image contrast is derived from T1w images and magnetic susceptibility maps to create subcortical contrast that is similar to that in the Montreal Neurological Institute (MNI) template. In our approach, a nonlinear registration replaces FIRST's default linear registration, yielding a more accurate alignment of the input data to the MNI template. We evaluated our method on 82 subjects with particularly abnormal brain anatomy, selected from a database of >2000 clinical cases. Qualitative and quantitative analyses revealed that HC-nlFIRST provides improved segmentation compared to the default FIRST method.
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Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Atrofia/patologia , Encéfalo/patologia , Feminino , Substância Cinzenta/anatomia & histologia , Voluntários Saudáveis , Humanos , Masculino , Imagem Multimodal , Neuroimagem , Imagens de Fantasmas , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Software , Adulto JovemRESUMO
This work aimed at combining different segmentation approaches to produce a robust and accurate segmentation result. Three to five segmentation results of the left ventricle were combined using the STAPLE algorithm and the reliability of the resulting segmentation was evaluated in comparison with the result of each individual segmentation method. This comparison was performed using a supervised approach based on a reference method. Then, we used an unsupervised statistical evaluation, the extended Regression Without Truth (eRWT) that ranks different methods according to their accuracy in estimating a specific biomarker in a population. The segmentation accuracy was evaluated by estimating six cardiac function parameters resulting from the left ventricle contour delineation using a public cardiac cine MRI database. Eight different segmentation methods, including three expert delineations and five automated methods, were considered, and sixteen combinations of the automated methods using STAPLE were investigated. The supervised and unsupervised evaluations demonstrated that in most cases, STAPLE results provided better estimates than individual automated segmentation methods. Overall, combining different automated segmentation methods improved the reliability of the segmentation result compared to that obtained using an individual method and could achieve the accuracy of an expert.
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Interpretação de Imagem Assistida por Computador/métodos , Imagem Cinética por Ressonância Magnética/métodos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Algoritmos , Humanos , Aumento da Imagem/métodos , Reconhecimento Automatizado de Padrão/métodos , Reprodutibilidade dos TestesRESUMO
A statistical methodology is proposed to rank several estimation methods of a relevant clinical parameter when no gold standard is available. Based on a regression without truth method, the proposed approach was applied to rank eight methods without using any a priori information regarding the reliability of each method and its degree of automation. It was only based on a prior concerning the statistical distribution of the parameter of interest in the database. The ranking of the methods relies on figures of merit derived from the regression and computed using a bootstrap process. The methodology was applied to the estimation of the left ventricular ejection fraction derived from cardiac magnetic resonance images segmented using eight approaches with different degrees of automation: three segmentations were entirely manually performed and the others were variously automated. The ranking of methods was consistent with the expected performance of the estimation methods: the most accurate estimates of the ejection fraction were obtained using manual segmentations. The robustness of the ranking was demonstrated when at least three methods were compared. These results suggest that the proposed statistical approach might be helpful to assess the performance of estimation methods on clinical data for which no gold standard is available.
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Processamento de Imagem Assistida por Computador/métodos , Imagem Cinética por Ressonância Magnética/métodos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Análise por Conglomerados , Coração/anatomia & histologia , Coração/fisiologia , Humanos , Análise de RegressãoRESUMO
A statistical method is proposed to compare several estimates of a relevant clinical parameter when no gold standard is available. The method is illustrated by considering the left ventricle ejection fraction derived from cardiac magnetic resonance images and computed using seven approaches with different degrees of automation. The proposed method did not use any a priori regarding with the reliability of each method and its degree of automation. The results showed that the most accurate estimates of the ejection fraction were obtained using manual segmentations, followed by the semiautomatic methods, while the methods with the least user input yielded the least accurate ejection fraction estimates. These results were consistent with the expected performance of the estimation methods, suggesting that the proposed statistical approach might be helpful to assess the performance of estimation methods on clinical data for which no gold standard is available.
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Coração/fisiologia , Imageamento por Ressonância Magnética/métodos , Função Ventricular Esquerda , Humanos , Análise de RegressãoRESUMO
Brain glucose uptake was examined in transgenic mice relevant to Alzheimer's disease (APP/PS1) and their control littermates (PS1). Glucose distribution in the brain of the resting animals was measured using 3D-reconstructed autoradiography and analysed by a voxel-wise approach using SPMMouse combined to an MRI-based 3D digital atlas. Prompt and direct indexation of metabolic changes between the two groups was achieved, showing both hypo- and hypermetabolism of glucose in the brain of APP/PS1 mice. We confirm and extend previous study, since we identified brain structures affected in this pathological model and demonstrate glucose uptake changes in structures like the olfactory bulb. Our results pave the way to complete and accurate examination of functional data from cerebral structures involved in models of neurodegenerative diseases.
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Doença de Alzheimer/metabolismo , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Software , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Automação , Encéfalo/metabolismo , Encéfalo/patologia , Camundongos , Camundongos Transgênicos , Tamanho do Órgão , Presenilina-1/metabolismoRESUMO
The work reported in this paper aimed at developing and testing an automated method to calculate the biodistribution of a specific PET tracer in mouse brain PET/CT images using an MRI-based 3D digital atlas. Surface-based registration strategy and affine transformation estimation were considered. Such an approach allowed overcoming the lack of anatomical information in the inner regions of PET/CT brain scans. Promising results were obtained in one mouse (on two scans) and will be extended to a neuroinflammation mouse model to characterize the pathology and its evolution. Major improvements are expected regarding automation, time computation, robustness and reproducibility of mouse brain segmentation. Due to its generic implementation, this method could be successfully applied to PET/CT brain scans of other species (rat, primate) for which 3D digital atlases are available.