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1.
Science ; 385(6704): eadd8394, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38963856

RESUMO

Transcribed enhancer maps can reveal nuclear interactions underpinning each cell type and connect specific cell types to diseases. Using a 5' single-cell RNA sequencing approach, we defined transcription start sites of enhancer RNAs and other classes of coding and noncoding RNAs in human CD4+ T cells, revealing cellular heterogeneity and differentiation trajectories. Integration of these datasets with single-cell chromatin profiles showed that active enhancers with bidirectional RNA transcription are highly cell type-specific and that disease heritability is strongly enriched in these enhancers. The resulting cell type-resolved multimodal atlas of bidirectionally transcribed enhancers, which we linked with promoters using fine-scale chromatin contact maps, enabled us to systematically interpret genetic variants associated with a range of immune-mediated diseases.


Assuntos
Linfócitos T CD4-Positivos , Elementos Facilitadores Genéticos , Predisposição Genética para Doença , Sítio de Iniciação de Transcrição , Transcrição Gênica , Humanos , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular , Cromatina/metabolismo , Cromatina/genética , Regiões Promotoras Genéticas , Linfócitos T Auxiliares-Indutores/imunologia , Análise da Expressão Gênica de Célula Única , Atlas como Assunto
2.
Hum Brain Mapp ; 45(8): e26718, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38825985

RESUMO

The early stages of human development are increasingly acknowledged as pivotal in laying the groundwork for subsequent behavioral and cognitive development. Spatiotemporal (4D) brain functional atlases are important in elucidating the development of human brain functions. However, the scarcity of such atlases for early life stages stems from two primary challenges: (1) the significant noise in functional magnetic resonance imaging (fMRI) that complicates the generation of high-quality atlases for each age group, and (2) the rapid and complex changes in the early human brain that hinder the maintenance of temporal consistency in 4D atlases. This study tackles these challenges by integrating low-rank tensor learning with spectral embedding, thereby proposing a novel, data-driven 4D functional atlas generation framework based on spectral functional network learning (SFNL). This method utilizes low-rank tensor learning to capture common functional connectivity (FC) patterns across different ages, thus optimizing FCs for each age group to improve the temporal consistency of functional networks. Incorporating spectral embedding aids in mitigating potential noise in FC networks derived from fMRI data by reconstructing networks in the spectral space. Utilizing SFNL-generated functional networks enables the creation of consistent and highly qualified spatiotemporal functional atlases. The framework was applied to the developing Human Connectome Project (dHCP) dataset, generating the first neonatal 4D functional atlases with fine-grained temporal and spatial resolutions. Experimental evaluations focusing on functional homogeneity, reliability, and temporal consistency demonstrated the superiority of our framework compared to existing methods for constructing 4D atlases. Additionally, network analysis experiments, including individual identification, functional systems development, and local efficiency assessments, further corroborate the efficacy and robustness of the generated atlases. The 4D atlases and related codes will be made publicly accessible (https://github.com/zhaoyunxi/neonate-atlases).


Assuntos
Atlas como Assunto , Conectoma , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Recém-Nascido , Conectoma/métodos , Masculino , Feminino , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Encéfalo/crescimento & desenvolvimento , Lactente , Processamento de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Rede Nervosa/crescimento & desenvolvimento
3.
J Vis Exp ; (207)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38884460

RESUMO

Cerebral conditions often require precise diagnosis and monitoring, necessitating advanced imaging techniques. Current modalities may not adequately detect early signs of reversible tissue damage, underlining the need for innovative diagnostic tools that can quantify changes in cerebral blood flow (CBF) with high specificity and sensitivity. This study integrates three-dimensional arterial spin labeling (3D-ASL) with structural MRI to develop comprehensive CBF atlases that cover all main functional regions of the brain. This innovative magnetic resonance imaging- arterial spin labeling (MRI-ASL) methodology provides a rapid and noninvasive means of quantifying region-specific CBF, offering a detailed view of CBF levels across different functional regions.The comparison between chronic cerebral ischemia (CCI) patients and healthy subjects revealed significantly diminished CBF across the cerebral functional regions in the constructed CBF atlases for the former. This approach not only allows for the efficient identification of CCI by analyzing concurrent decreases in CBF across critical areas relative to healthy distributions but also enables the tracking of treatment responses and rehabilitation progress through longitudinal CBF atlases.The CBF atlas developed using the MRI-ASL technique represents a novel advancement in the field of cerebral diagnostics and patient care. By comparing regional CBF levels against normative standards, this method enhances diagnostic capabilities, enabling clinicians to provide personalized care to patients with cerebral conditions.


Assuntos
Circulação Cerebrovascular , Imageamento por Ressonância Magnética , Marcadores de Spin , Humanos , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Isquemia Encefálica/diagnóstico por imagem , Atlas como Assunto
5.
Sci Adv ; 10(25): eadj9173, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905344

RESUMO

Sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli to the central nervous system. Single-cell RNA sequencing has provided insights into the diversity of sensory ganglia cell types in rodents, nonhuman primates, and humans, but it remains difficult to compare cell types across studies and species. We thus constructed harmonized atlases of the DRG and TG that describe and facilitate comparison of 18 neuronal and 11 non-neuronal cell types across six species and 31 datasets. We then performed single-cell/nucleus RNA sequencing of DRG from both human and the highly regenerative axolotl and found that the harmonized atlas also improves cell type annotation, particularly of sparse neuronal subtypes. We observed that the transcriptomes of sensory neuron subtypes are broadly similar across vertebrates, but the expression of functionally important neuropeptides and channels can vary notably. The resources presented here can guide future studies in comparative transcriptomics, simplify cell-type nomenclature differences across studies, and help prioritize targets for future analgesic development.


Assuntos
Gânglios Espinais , Transcriptoma , Gânglio Trigeminal , Animais , Humanos , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Gânglio Trigeminal/citologia , Gânglio Trigeminal/metabolismo , Análise de Célula Única/métodos , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/citologia , Especificidade da Espécie , Camundongos , Atlas como Assunto , Perfilação da Expressão Gênica , Ratos
6.
Nature ; 631(8019): 150-163, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38898272

RESUMO

Here, we introduce the Tabulae Paralytica-a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells, a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei, and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord1. The Tabulae Paralytica uncovered new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to upregulate circuit-reorganizing programs after injury; an inverse relationship between neuronal stress responses and the activation of circuit reorganization programs; the necessity of re-establishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI and a failure to form this barrier in old mice. We leveraged the Tabulae Paralytica to develop a rejuvenative gene therapy that re-established this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The Tabulae Paralytica provides a window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.


Assuntos
Núcleo Celular , Epigenômica , Multiômica , Neurônios , Análise de Célula Única , Traumatismos da Medula Espinal , Transcriptoma , Animais , Feminino , Masculino , Camundongos , Atlas como Assunto , Núcleo Celular/metabolismo , Neurônios/patologia , Neurônios/metabolismo , Paralisia/genética , Paralisia/patologia , Paralisia/reabilitação , Paralisia/terapia , Recuperação de Função Fisiológica , Medula Espinal/patologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/terapia , Caminhada , Anatomia Artística , Vias Neurais , Terapia Genética
7.
Leg Med (Tokyo) ; 69: 102473, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38924883

RESUMO

The objective of this study was to propose categories of morphological classification for the face and its anatomical structures, as well as to propose illustrations to support the development of an atlas that facilitates facial morphological analysis of adult Brazilians. It was a descriptive study based on the analysis of the frequency and distribution of 13 photoanthropometric facial ratios (RFAs) obtained from a representative sample of the Brazilian population. RFAs related to facial height and width, eye width, intercanthal distance, nose length and width, philtrum ridge height and width, mouth thickness and width, upper and lower lip thickness, and chin height were analyzed. The study included a sample of 5.000 individuals aged between 18 and 22 years, evenly distributed between genders. Data normality was assessed using the Shapiro-Wilk test, considering them as parametric when p > 0.05. For the RFAs that showed normal distribution, mean ± 1.5 standard deviations (SD) were used to categorize facial measurements as regular, below average, or above average. Non-parametric RFAs were analyzed based on the median and 10th and 90th percentiles of the data. Based on the established average iris diameter, which is considered the most stable facial measurement, the values of the described RFAs were converted to a numerical scale in centimeters, allowing for the illustration of female and male faces. In this way, it was possible to categorize the facial anatomical structures and, consequently, visualize the facial morphological pattern of the adult Brazilian population.


Assuntos
Face , Humanos , Brasil , Masculino , Feminino , Face/anatomia & histologia , Adulto Jovem , Adolescente , Adulto , Antropologia Forense/métodos , Atlas como Assunto
8.
J Comp Neurol ; 532(6): e25619, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38831653

RESUMO

Zebrafish is a useful model organism in neuroscience; however, its gene expression atlas in the adult brain is not well developed. In the present study, we examined the expression of 38 neuropeptides, comparing with GABAergic and glutamatergic neuron marker genes in the adult zebrafish brain by comprehensive in situ hybridization. The results are summarized as an expression atlas in 19 coronal planes of the forebrain. Furthermore, the scanned data of all brain sections were made publicly available in the Adult Zebrafish Brain Gene Expression Database (https://ssbd.riken.jp/azebex/). Based on these data, we performed detailed comparative neuroanatomical analyses of the hypothalamus and found that several regions previously described as one nucleus in the reference zebrafish brain atlas contain two or more subregions with significantly different neuropeptide/neurotransmitter expression profiles. Subsequently, we compared the expression data in zebrafish telencephalon and hypothalamus obtained in this study with those in mice, by performing a cluster analysis. As a result, several nuclei in zebrafish and mice were clustered in close vicinity. The present expression atlas, database, and anatomical findings will contribute to future neuroscience research using zebrafish.


Assuntos
Neuropeptídeos , Prosencéfalo , Peixe-Zebra , Animais , Peixe-Zebra/anatomia & histologia , Prosencéfalo/metabolismo , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Atlas como Assunto , Expressão Gênica , Bases de Dados Genéticas , Camundongos
9.
Science ; 384(6698): eadh0829, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38781368

RESUMO

Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment for regulatory elements in the developing brain. However, prioritizing risk genes and mechanisms is challenging without a unified regulatory atlas. Across 672 diverse developing human brains, we identified 15,752 genes harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts. Gene expression heritability drops during development, likely reflecting both increasing cellular heterogeneity and the intrinsic properties of neuronal maturation. Isoform-level regulation, particularly in the second trimester, mediated the largest proportion of GWAS heritability. Through colocalization, we prioritized mechanisms for about 60% of GWAS loci across five disorders, exceeding adult brain findings. Finally, we contextualized results within gene and isoform coexpression networks, revealing the comprehensive landscape of transcriptome regulation in development and disease.


Assuntos
Processamento Alternativo , Encéfalo , Regulação da Expressão Gênica no Desenvolvimento , Transtornos Mentais , Humanos , Atlas como Assunto , Transtorno do Espectro Autista/genética , Encéfalo/metabolismo , Encéfalo/crescimento & desenvolvimento , Encéfalo/embriologia , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Locos de Características Quantitativas , Esquizofrenia/genética , Transcriptoma , Transtornos Mentais/genética
10.
Anat Sci Educ ; 17(5): 1055-1070, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38695348

RESUMO

Previous research suggests that underrepresentation in medical curricula perpetuates inequities in healthcare. This study aimed to quantify the prevalence of human phenotypic diversity (e.g., skin tone, sex, body size, and age) across 11 commonly used anatomy atlases and textbooks in pre-clerkship medical education, published from 2015 to 2020. A systematic visual content analysis was conducted on 5001 images in which at least one phenotypic attribute was quantifiable. Anatomy images most prevalently portrayed light skin tones, males, persons with intermediate body sizes, and young to middle-aged adults. Of the 3883 images in which there was a codable skin tone, 81.2% (n = 3154) depicted light, 14.3% (n = 554) depicted intermediate, and 4.5% (n = 175) depicted dark skin tones. Of the 2384 images that could be categorized into a sex binary, 38.4% (n = 915) depicted females and 61.6% (n = 1469) depicted males. A male bias persisted across all whole-body and regional-body images, including those showing sex organs or those showing characteristics commonly associated with a specific sex (e.g. for males, facial hair and/or muscle hypertrophy). Within sex-specific contexts, darker skin was underrepresented, but male depictions displayed greater overall skin tone variation. Although most images could not be assigned to a body size or age category, when codable, these images overwhelmingly depicted adults (85.0%; 482 of 567) with smaller (34.7%; 93 of 268) or intermediate (64.6%; 173 of 268) body sizes. Ultimately, these outcomes provide reference metrics for monitoring ongoing and future efforts to address representation inequalities portrayed in anatomical imagery.


Assuntos
Anatomia , Livros de Texto como Assunto , Humanos , Masculino , Anatomia/educação , Feminino , Adulto , Adulto Jovem , Atlas como Assunto , Pessoa de Meia-Idade , Pigmentação da Pele , Currículo , Adolescente , Anatomia Artística
11.
BMC Med Educ ; 24(1): 500, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711070

RESUMO

BACKGROUND: According to the German Physiotherapy Education and Qualification Regulations, teaching of anatomical structures is one of the fundamental subjects of physiotherapy education. Besides exhibits and models, anatomy atlases are usually used as teaching and learning tools. These are available in both analog form such as printed books or in digital form as a mobile application. Furthermore, the use of digital teaching and learning tools is steadily increasing within the education of health professionals. AIM: To assess the efficacy of a digital educational tool in contrast to an analog anatomical atlas in acquiring knowledge about anatomical structures. MATERIAL AND METHOD: The data collection took place in the context of an anatomy tutorial for students of the bachelor's degree program in physiotherapy. In a cross-over design, the students completed two learning assignments, each, with different learning materials provided, either with an anatomy app on a tablet or with an anatomy atlas as a book. The tests to assess the newly acquired knowledge immediately after the task, consisted of questions about the anatomical structures of the knee as well as the shoulder. In addition, the students' satisfaction with the learning materials provided was surveyed using a questionnaire. The survey assessed their satisfaction, their assessment of learning success, and their affinity to digital learning materials. This was done using a 5-point Likert scale and a free-text field. The data was analyzed descriptively, and group differences were calculated using a t-tests. RESULTS: Thirty students participated. The group comparison showed a significantly better outcome for the group that prepared with the analog anatomy atlas for the questions on the knee than the comparison group that used the anatomy app (t(28) = 2.6; p = 0.007). For the questions concerning the shoulder, there was no significant difference between the digital and analog groups (t(28) = 1.14; p = 0.26). The questionnaire revealed that satisfaction with the analog anatomy atlas was significantly higher than with the anatomy app. A total of 93.34% rated their experience with the analog learning tool at least "somewhat satisfied". In contrast, 72.67% of students partially or fully agreed that they "enjoyed learning with digital learning tools". DISCUSSION: Learning anatomical structures with the Human Anatomy Atlas 2023 + app did not show a clear advantage when compared to an anatomy book in these two cohorts of physiotherapy students. The results of the questionnaire also showed greater satisfaction with the analog anatomy atlas than with the anatomy app, whereas most students stated that they frequently use digital learning tools, including some for anatomical structures. Satisfaction with the learning tool seems to play a central role in their effectiveness. In addition, sufficient time must be provided for users to familiarize themselves with the user interface of digital applications to use them effectively. REGISTRATION: Diese klinische Studie wurde nicht in einem Studienregister registriert.


Assuntos
Anatomia , Estudos Cross-Over , Humanos , Anatomia/educação , Masculino , Instrução por Computador/métodos , Avaliação Educacional , Especialidade de Fisioterapia/educação , Alemanha , Feminino , Atlas como Assunto , Adulto , Inquéritos e Questionários , Adulto Jovem , Aprendizagem , Ombro/anatomia & histologia , Joelho/anatomia & histologia
12.
Hum Brain Mapp ; 45(7): e26695, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38727010

RESUMO

Human infancy is marked by fastest postnatal brain structural changes. It also coincides with the onset of many neurodevelopmental disorders. Atlas-based automated structure labeling has been widely used for analyzing various neuroimaging data. However, the relatively large and nonlinear neuroanatomical differences between infant and adult brains can lead to significant offsets of the labeled structures in infant brains when adult brain atlas is used. Age-specific 1- and 2-year-old brain atlases covering all major gray and white matter (GM and WM) structures with diffusion tensor imaging (DTI) and structural MRI are critical for precision medicine for infant population yet have not been established. In this study, high-quality DTI and structural MRI data were obtained from 50 healthy children to build up three-dimensional age-specific 1- and 2-year-old brain templates and atlases. Age-specific templates include a single-subject template as well as two population-averaged templates from linear and nonlinear transformation, respectively. Each age-specific atlas consists of 124 comprehensively labeled major GM and WM structures, including 52 cerebral cortical, 10 deep GM, 40 WM, and 22 brainstem and cerebellar structures. When combined with appropriate registration methods, the established atlases can be used for highly accurate automatic labeling of any given infant brain MRI. We demonstrated that one can automatically and effectively delineate deep WM microstructural development from 3 to 38 months by using these age-specific atlases. These established 1- and 2-year-old infant brain DTI atlases can advance our understanding of typical brain development and serve as clinical anatomical references for brain disorders during infancy.


Assuntos
Atlas como Assunto , Encéfalo , Imagem de Tensor de Difusão , Substância Cinzenta , Substância Branca , Humanos , Lactente , Pré-Escolar , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/anatomia & histologia , Substância Branca/crescimento & desenvolvimento , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/crescimento & desenvolvimento , Substância Cinzenta/anatomia & histologia , Imagem de Tensor de Difusão/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Encéfalo/anatomia & histologia , Processamento de Imagem Assistida por Computador/métodos
13.
Science ; 384(6695): eadj4088, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38696552

RESUMO

The developmental decision made by malaria parasites to become sexual underlies all malaria transmission. Here, we describe a rich atlas of short- and long-read single-cell transcriptomes of over 37,000 Plasmodium falciparum cells across intraerythrocytic asexual and sexual development. We used the atlas to explore transcriptional modules and exon usage along sexual development and expanded it to include malaria parasites collected from four Malian individuals naturally infected with multiple P. falciparum strains. We investigated genotypic and transcriptional heterogeneity within and among these wild strains at the single-cell level, finding differential expression between different strains even within the same host. These data are a key addition to the Malaria Cell Atlas interactive data resource, enabling a deeper understanding of the biology and diversity of transmission stages.


Assuntos
Eritrócitos , Malária Falciparum , Plasmodium falciparum , Desenvolvimento Sexual , Humanos , Eritrócitos/parasitologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Plasmodium falciparum/genética , Plasmodium falciparum/crescimento & desenvolvimento , Desenvolvimento Sexual/genética , Análise de Célula Única , Transcriptoma , Atlas como Assunto
14.
J Neuroinflammation ; 21(1): 112, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684986

RESUMO

BACKGROUND: Dimethyl fumarate (DMF) is a fumaric acid ester that exhibits immunoregulatory and anti-inflammatory properties. However, the function of DMF in autoimmune uveitis (AU) is incompletely understood, and studies comprehensively exploring the impact of DMF on immune cells are still lacking. METHODS: To explore the function of DMF in uveitis and its underlying mechanisms, we conducted single-cell RNA sequencing (scRNA-seq) on the cervical draining lymph node (CDLN) cells of normal, experimental autoimmune uveitis (EAU), and DMF-treated EAU mice. Additionally, we integrated scRNA-seq data of the retina and CDLNs to identify the potential impact of DMF on ocular immune cell infiltration. Flow cytometry was conducted to verify the potential target molecules of DMF. RESULTS: Our study showed that DMF treatment effectively ameliorated EAU symptoms. The proportional and transcriptional alterations in each immune cell type during EAU were reversed by DMF treatment. Bioinformatics analysis in our study indicated that the enhanced expression of Pim1 and Cxcr4 in EAU was reversed by DMF treatment. Further experiments demonstrated that DMF restored the balance between effector T (Teff) /regulatory T (Treg) cells through inhibiting the pathway of PIM1-protein kinase B (AKT)-Forkhead box O1 (FOXO1). By incorporating the scRNA-seq data of the retina from EAU mice into analysis, our study identified that T cells highly expressing Pim1 and Cxcr4 were enriched in the retina. DMF repressed the ocular infiltration of Teff cells, and this effect might depend on its inhibition of PIM1 and CXCR4 expression. Additionally, our study indicated that DMF might reduce the proportion of plasma cells by inhibiting PIM1 expression in B cells. CONCLUSIONS: DMF effectively attenuated EAU symptoms. During EAU, DMF reversed the Teff/Treg cell imbalance and suppressed the ocular infiltration of Teff cells by inhibiting PIM1 and CXCR4 expression. Thus, DMF may act as a new drug option for the treatment of AU.


Assuntos
Anti-Inflamatórios não Esteroides , Doenças Autoimunes , Fumarato de Dimetilo , Imunossupressores , Retina , Uveíte , Fumarato de Dimetilo/administração & dosagem , Fumarato de Dimetilo/farmacologia , Uveíte/genética , Uveíte/imunologia , Uveíte/terapia , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Análise da Expressão Gênica de Célula Única , Modelos Animais de Doenças , Animais , Camundongos , Feminino , Camundongos Endogâmicos C57BL , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/genética , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Transcrição Gênica , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Atlas como Assunto , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Retina/efeitos dos fármacos , Retina/imunologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia
15.
J Med Imaging Radiat Sci ; 55(2): 281-288, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38609834

RESUMO

PURPOSE/OBJECTIVE: To determine the impact of a MR-based contouring atlas for male pelvis radiotherapy delineation on inter-observer variation to support radiographer led real-time magnetic resonance image guided adaptive radiotherapy (MRgART). MATERIAL/METHODS: Eight RTTs contoured 25 MR images in the Monaco treatment planning system (Monaco 5.40.01), from 5 patients. The prostate, seminal vesicles, bladder, and rectum were delineated before and after the introduction of an atlas developed through multi-disciplinary consensus. Inter-observer contour variations (volume), time to contour and observer contouring confidence were determined at both time-points using a 5-point Likert scale. Descriptive statistics were used to analyse both continuous and categorical variables. Dice similarity coefficient (DSC), Dice-Jaccard coefficient (DJC) and Hausdorff distance were used to calculate similarity between observers. RESULTS: Although variation in volume definition decreased for all structures among all observers post intervention, the change was not statistically significant. DSC and DJC measurements remained consistent following the introduction of the atlas for all observers. The highest similarity was found in the bladder and prostate whilst the lowest was the seminal vesicles. The mean contouring time for all observers was reduced by 50% following the introduction of the atlas (53 to 27 minutes, p=0.01). For all structures across all observers, the mean contouring confidence increased significantly from 2.3 to 3.5 out of 5 (p=0.02). CONCLUSION: Although no significant improvements were observed in contour variation amongst observers, the introduction of the consensus-based contouring atlas improved contouring confidence and speed; key factors for a real-time RTT-led MRgART.


Assuntos
Imageamento por Ressonância Magnética , Variações Dependentes do Observador , Neoplasias da Próstata , Radioterapia Guiada por Imagem , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/diagnóstico por imagem , Radioterapia Guiada por Imagem/métodos , Pelve/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Atlas como Assunto , Próstata/diagnóstico por imagem
16.
Neuroimage ; 292: 120603, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38588833

RESUMO

Fetal brain development is a complex process involving different stages of growth and organization which are crucial for the development of brain circuits and neural connections. Fetal atlases and labeled datasets are promising tools to investigate prenatal brain development. They support the identification of atypical brain patterns, providing insights into potential early signs of clinical conditions. In a nutshell, prenatal brain imaging and post-processing via modern tools are a cutting-edge field that will significantly contribute to the advancement of our understanding of fetal development. In this work, we first provide terminological clarification for specific terms (i.e., "brain template" and "brain atlas"), highlighting potentially misleading interpretations related to inconsistent use of terms in the literature. We discuss the major structures and neurodevelopmental milestones characterizing fetal brain ontogenesis. Our main contribution is the systematic review of 18 prenatal brain atlases and 3 datasets. We also tangentially focus on clinical, research, and ethical implications of prenatal neuroimaging.


Assuntos
Atlas como Assunto , Encéfalo , Imageamento por Ressonância Magnética , Neuroimagem , Feminino , Humanos , Gravidez , Encéfalo/diagnóstico por imagem , Encéfalo/embriologia , Conjuntos de Dados como Assunto , Desenvolvimento Fetal/fisiologia , Feto/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos
17.
Cereb Cortex ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38647221

RESUMO

A comprehensive three-dimensional digital brain atlas of cortical and subcortical regions based on MRI and histology has a broad array of applications in anatomical, functional, and clinical studies. We first generated a Subcortical Atlas of the Marmoset, called the "SAM," from 251 delineated subcortical regions (e.g. thalamic subregions, etc.) derived from high-resolution Mean Apparent Propagator-MRI, T2W, and magnetization transfer ratio images ex vivo. We then confirmed the location and borders of these segmented regions in the MRI data using matched histological sections with multiple stains obtained from the same specimen. Finally, we estimated and confirmed the atlas-based areal boundaries of subcortical regions by registering this ex vivo atlas template to in vivo T1- or T2W MRI datasets of different age groups (single vs. multisubject population-based marmoset control adults) using a novel pipeline developed within Analysis of Functional NeuroImages software. Tracing and validating these important deep brain structures in 3D will improve neurosurgical planning, anatomical tract tracer injections, navigation of deep brain stimulation probes, functional MRI and brain connectivity studies, and our understanding of brain structure-function relationships. This new ex vivo template and atlas are available as volumes in standard NIFTI and GIFTI file formats and are intended for use as a reference standard for marmoset brain research.


Assuntos
Atlas como Assunto , Encéfalo , Callithrix , Imageamento por Ressonância Magnética , Callithrix/anatomia & histologia , Animais , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/anatomia & histologia , Masculino , Feminino , Imageamento Tridimensional/métodos , Processamento de Imagem Assistida por Computador/métodos
18.
Nat Commun ; 15(1): 3530, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664422

RESUMO

This paper explicates a solution to building correspondences between molecular-scale transcriptomics and tissue-scale atlases. This problem arises in atlas construction and cross-specimen/technology alignment where specimens per emerging technology remain sparse and conventional image representations cannot efficiently model the high dimensions from subcellular detection of thousands of genes. We address these challenges by representing spatial transcriptomics data as generalized functions encoding position and high-dimensional feature (gene, cell type) identity. We map onto low-dimensional atlas ontologies by modeling regions as homogeneous random fields with unknown transcriptomic feature distribution. We solve simultaneously for the minimizing geodesic diffeomorphism of coordinates through LDDMM and for these latent feature densities. We map tissue-scale mouse brain atlases to gene-based and cell-based transcriptomics data from MERFISH and BARseq technologies and to histopathology and cross-species atlases to illustrate integration of diverse molecular and cellular datasets into a single coordinate system as a means of comparison and further atlas construction.


Assuntos
Atlas como Assunto , Encéfalo , Transcriptoma , Animais , Encéfalo/metabolismo , Camundongos , Transcriptoma/genética , Processamento de Imagem Assistida por Computador/métodos , Perfilação da Expressão Gênica/métodos , Humanos
19.
IEEE J Biomed Health Inform ; 28(5): 3029-3041, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38427553

RESUMO

The roles of brain region activities and genotypic functions in the pathogenesis of Alzheimer's disease (AD) remain unclear. Meanwhile, current imaging genetics methods are difficult to identify potential pathogenetic markers by correlation analysis between brain network and genetic variation. To discover disease-related brain connectome from the specific brain structure and the fine-grained level, based on the Automated Anatomical Labeling (AAL) and human Brainnetome atlases, the functional brain network is first constructed for each subject. Specifically, the upper triangle elements of the functional connectivity matrix are extracted as connectivity features. The clustering coefficient and the average weighted node degree are developed to assess the significance of every brain area. Since the constructed brain network and genetic data are characterized by non-linearity, high-dimensionality, and few subjects, the deep subspace clustering algorithm is proposed to reconstruct the original data. Our multilayer neural network helps capture the non-linear manifolds, and subspace clustering learns pairwise affinities between samples. Moreover, most approaches in neuroimaging genetics are unsupervised learning, neglecting the diagnostic information related to diseases. We presented a label constraint with diagnostic status to instruct the imaging genetics correlation analysis. To this end, a diagnosis-guided deep subspace clustering association (DDSCA) method is developed to discover brain connectome and risk genetic factors by integrating genotypes with functional network phenotypes. Extensive experiments prove that DDSCA achieves superior performance to most association methods and effectively selects disease-relevant genetic markers and brain connectome at the coarse-grained and fine-grained levels.


Assuntos
Doença de Alzheimer , Encéfalo , Imageamento por Ressonância Magnética , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/diagnóstico por imagem , Análise por Conglomerados , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Conectoma/métodos , Algoritmos , Idoso , Biomarcadores , Feminino , Masculino , Atlas como Assunto , Neuroimagem/métodos
20.
Nat Neurosci ; 27(5): 1000-1013, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38532024

RESUMO

Although the general location of functional neural networks is similar across individuals, there is vast person-to-person topographic variability. To capture this, we implemented precision brain mapping functional magnetic resonance imaging methods to establish an open-source, method-flexible set of precision functional network atlases-the Masonic Institute for the Developing Brain (MIDB) Precision Brain Atlas. This atlas is an evolving resource comprising 53,273 individual-specific network maps, from more than 9,900 individuals, across ages and cohorts, including the Adolescent Brain Cognitive Development study, the Developmental Human Connectome Project and others. We also generated probabilistic network maps across multiple ages and integration zones (using a new overlapping mapping technique, Overlapping MultiNetwork Imaging). Using regions of high network invariance improved the reproducibility of executive function statistical maps in brain-wide associations compared to group average-based parcellations. Finally, we provide a potential use case for probabilistic maps for targeted neuromodulation. The atlas is expandable to alternative datasets with an online interface encouraging the scientific community to explore and contribute to understanding the human brain function more precisely.


Assuntos
Encéfalo , Conectoma , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Adolescente , Masculino , Feminino , Adulto , Adulto Jovem , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem , Mapeamento Encefálico/métodos , Atlas como Assunto , Criança , Probabilidade , Vias Neurais/fisiologia
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