RESUMO
The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Although practiced for many years clinically in nuclear medicine, expansion to other imaging modalities began roughly 25 years ago and has accelerated since. That acceleration derives from the continual appearance of new and highly relevant animal models of human disease, increasingly sensitive imaging devices, high-throughput methods to discover and optimize affinity agents to key cellular targets, new ways to manipulate genetic material, and expanded use of cloud computing. Greater interest by scientists in allied fields, such as chemistry, biomedical engineering, and immunology, as well as increased attention by the pharmaceutical industry, have likewise contributed to the boom in activity in recent years. Whereas researchers and clinicians have applied molecular imaging to a variety of physiologic processes and disease states, here, the authors focus on oncology, arguably where it has made its greatest impact. The main purpose of imaging in oncology is early detection to enable interception if not prevention of full-blown disease, such as the appearance of metastases. Because biochemical changes occur before changes in anatomy, molecular imaging-particularly when combined with liquid biopsy for screening purposes-promises especially early localization of disease for optimum management. Here, the authors introduce the ways and indications in which molecular imaging can be undertaken, the tools used and under development, and near-term challenges and opportunities in oncology.
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Oncologia , Imagem Molecular , Animais , Humanos , Imageamento por Ressonância Magnética , Imagem Molecular/métodos , Tomografia por Emissão de PósitronsRESUMO
Uncovering the genetic architectures of brain morphology offers valuable insights into brain development and disease. Genetic association studies of brain morphological phenotypes have discovered thousands of loci. However, interpretation of these loci presents a significant challenge. One potential solution is exploring the genetic overlap between brain morphology and disorders, which can improve our understanding of their complex relationships, ultimately aiding in clinical applications. In this review, we examine current evidence on the genetic associations between brain morphology and neuropsychiatric traits. We discuss the impact of these associations on the diagnosis, prediction, and treatment of neuropsychiatric diseases, along with suggestions for future research directions.
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Encéfalo , Transtornos Mentais , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Encéfalo/anatomia & histologia , Transtornos Mentais/genética , Transtornos Mentais/patologia , Fenótipo , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Estudos de Associação GenéticaRESUMO
The contents and dynamics of spontaneous thought are important factors for personality traits and mental health. However, assessing spontaneous thoughts is challenging due to their unconstrained nature, and directing participants' attention to report their thoughts may fundamentally alter them. Here, we aimed to decode two key content dimensions of spontaneous thought-self-relevance and valence-directly from brain activity. To train functional MRI-based predictive models, we used individually generated personal stories as stimuli in a story-reading task to mimic narrative-like spontaneous thoughts (n = 49). We then tested these models on multiple test datasets (total n = 199). The default mode, ventral attention, and frontoparietal networks played key roles in the predictions, with the anterior insula and midcingulate cortex contributing to self-relevance prediction and the left temporoparietal junction and dorsomedial prefrontal cortex contributing to valence prediction. Overall, this study presents brain models of internal thoughts and emotions, highlighting the potential for the brain decoding of spontaneous thought.
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Mapeamento Encefálico , Encéfalo , Humanos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Emoções , Córtex Pré-Frontal , Giro do Cíngulo , Imageamento por Ressonância Magnética/métodosRESUMO
Dilated cardiomyopathy (DCM) is defined as dilation and/or reduced function of one or both ventricles and remains a common disease worldwide. An estimated 40% of cases of familial DCM have an identifiable genetic cause. Accordingly, there is a fast-growing interest in the field of molecular genetics as it pertains to DCM. Many gene mutations have been identified that contribute to phenotypically significant cardiomyopathy. DCM genes can affect a variety of cardiomyocyte functions, and particular genes whose function affects the cell-cell junction and cytoskeleton are associated with increased risk of arrhythmias and sudden cardiac death. Through advancements in next-generation sequencing and cardiac imaging, identification of genetic DCM has improved over the past couple decades, and precision medicine is now at the forefront of treatment for these patients and their families. In addition to standard treatment of heart failure and prevention of arrhythmias and sudden cardiac death, patients with genetic cardiomyopathy stand to benefit from gene mechanism-specific therapies.
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Cardiomiopatia Dilatada , Insuficiência Cardíaca , Humanos , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/terapia , Arritmias Cardíacas/genética , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Mutação/genéticaRESUMO
Pain perception arises from the integration of prior expectations with sensory information. Although recent work has demonstrated that treatment expectancy effects (e.g., placebo hypoalgesia) can be explained by a Bayesian integration framework incorporating the precision level of expectations and sensory inputs, the key factor modulating this integration in stimulus expectancy-induced pain modulation remains unclear. In a stimulus expectancy paradigm combining emotion regulation in healthy male and female adults, we found that participants' voluntary reduction in anticipatory anxiety and pleasantness monotonically reduced the magnitude of pain modulation by negative and positive expectations, respectively, indicating a role of emotion. For both types of expectations, Bayesian model comparisons confirmed that an integration model using the respective emotion of expectations and sensory inputs explained stimulus expectancy effects on pain better than using their respective precision. For negative expectations, the role of anxiety is further supported by our fMRI findings that (1) functional coupling within anxiety-processing brain regions (amygdala and anterior cingulate) reflected the integration of expectations with sensory inputs and (2) anxiety appeared to impair the updating of expectations via suppressed prediction error signals in the anterior cingulate, thus perpetuating negative expectancy effects. Regarding positive expectations, their integration with sensory inputs relied on the functional coupling within brain structures processing positive emotion and inhibiting threat responding (medial orbitofrontal cortex and hippocampus). In summary, different from treatment expectancy, pain modulation by stimulus expectancy emanates from emotion-modulated integration of beliefs with sensory evidence and inadequate belief updating.
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Antecipação Psicológica , Ansiedade , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Ansiedade/psicologia , Ansiedade/fisiopatologia , Adulto , Antecipação Psicológica/fisiologia , Adulto Jovem , Percepção da Dor/fisiologia , Dor/psicologia , Dor/fisiopatologia , Teorema de Bayes , Emoções/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/fisiologia , Prazer/fisiologia , Mapeamento EncefálicoRESUMO
The suprachiasmatic nucleus (SCN) is the central clock for circadian rhythms. Animal studies have revealed daily rhythms in the neuronal activity in the SCN. However, the circadian activity of the human SCN has remained elusive. In this study, to reveal the diurnal variation of the SCN activity in humans, we localized the SCN by employing an areal boundary mapping technique to resting-state functional images and investigated the SCN activity using perfusion imaging. In the first experiment (n = 27, including both sexes), we scanned each participant four times a day, every 6â h. Higher activity was observed at noon, while lower activity was recorded in the early morning. In the second experiment (n = 20, including both sexes), the SCN activity was measured every 30â min for 6â h from midnight to dawn. The results showed that the SCN activity gradually decreased and was not associated with the electroencephalography. Furthermore, the SCN activity was compatible with the rodent SCN activity after switching off the lights. These results suggest that the diurnal variation of the human SCN follows the zeitgeber cycles of nocturnal and diurnal mammals and is modulated by physical lights rather than the local time.
Assuntos
Ritmo Circadiano , Núcleo Supraquiasmático , Masculino , Animais , Feminino , Humanos , Ritmo Circadiano/fisiologia , Núcleo Supraquiasmático/fisiologia , Roedores , Mamíferos , NeurôniosRESUMO
BACKGROUND: Current cardiovascular magnetic resonance sequences cannot discriminate between different myocardial extracellular space (ECSs), including collagen, noncollagen, and inflammation. We sought to investigate whether cardiovascular magnetic resonance radiomics analysis can distinguish between noncollagen and inflammation from collagen in dilated cardiomyopathy. METHODS: We identified data from 132 patients with dilated cardiomyopathy scheduled for an invasive septal biopsy who underwent cardiovascular magnetic resonance at 3 T. Cardiovascular magnetic resonance imaging protocol included native and postcontrast T1 mapping and late gadolinium enhancement (LGE). Radiomic features were computed from the midseptal myocardium, near the biopsy region, on native T1, extracellular volume (ECV) map, and LGE images. Principal component analysis was used to reduce the number of radiomic features to 5 principal radiomics. Moreover, a correlation analysis was conducted to identify radiomic features exhibiting a strong correlation (r>0.9) with the 5 principal radiomics. Biopsy samples were used to quantify ECS, myocardial fibrosis, and inflammation. RESULTS: Four histopathological phenotypes were identified: low collagen (n=20), noncollagenous ECS expansion (n=49), mild to moderate collagenous ECS expansion (n=42), and severe collagenous ECS expansion (n=21). Noncollagenous expansion was associated with the highest risk of myocardial inflammation (65%). Although native T1 and ECV provided high diagnostic performance in differentiating severe fibrosis (C statistic, 0.90 and 0.90, respectively), their performance in differentiating between noncollagen and mild to moderate collagenous expansion decreased (C statistic: 0.59 and 0.55, respectively). Integration of ECV principal radiomics provided better discrimination and reclassification between noncollagen and mild to moderate collagen (C statistic, 0.79; net reclassification index, 0.83 [95% CI, 0.45-1.22]; P<0.001). There was a similar trend in the addition of native T1 principal radiomics (C statistic, 0.75; net reclassification index, 0.93 [95% CI, 0.56-1.29]; P<0.001) and LGE principal radiomics (C statistic, 0.74; net reclassification index, 0.59 [95% CI, 0.19-0.98]; P=0.004). Five radiomic features per sequence were identified with correlation analysis. They showed a similar improvement in performance for differentiating between noncollagen and mild to moderate collagen (native T1, ECV, LGE C statistic, 0.75, 0.77, and 0.71, respectively). These improvements remained significant when confined to a single radiomic feature (native T1, ECV, LGE C statistic, 0.71, 0.70, and 0.64, respectively). CONCLUSIONS: Radiomic features extracted from native T1, ECV, and LGE provide incremental information that improves our capability to discriminate noncollagenous expansion from mild to moderate collagen and could be useful for detecting subtle chronic inflammation in patients with dilated cardiomyopathy.
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Cardiomiopatia Dilatada , Matriz Extracelular , Humanos , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/patologia , Matriz Extracelular/patologia , Matriz Extracelular/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Colágeno/metabolismo , Miocárdio/patologia , Idoso , Fibrose , Imageamento por Ressonância Magnética/métodos , Biópsia , Análise de Componente Principal , RadiômicaRESUMO
Multiple applications for machine learning and artificial intelligence (AI) in cardiovascular imaging are being proposed and developed. However, the processes involved in implementing AI in cardiovascular imaging are highly diverse, varying by imaging modality, patient subtype, features to be extracted and analyzed, and clinical application. This article establishes a framework that defines value from an organizational perspective, followed by value chain analysis to identify the activities in which AI might produce the greatest incremental value creation. The various perspectives that should be considered are highlighted, including clinicians, imagers, hospitals, patients, and payers. Integrating the perspectives of all health care stakeholders is critical for creating value and ensuring the successful deployment of AI tools in a real-world setting. Different AI tools are summarized, along with the unique aspects of AI applications to various cardiac imaging modalities, including cardiac computed tomography, magnetic resonance imaging, and positron emission tomography. AI is applicable and has the potential to add value to cardiovascular imaging at every step along the patient journey, from selecting the more appropriate test to optimizing image acquisition and analysis, interpreting the results for classification and diagnosis, and predicting the risk for major adverse cardiac events.
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American Heart Association , Inteligência Artificial , Humanos , Aprendizado de Máquina , Coração , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Randomized trials in obstructive coronary artery disease (CAD) have largely shown no prognostic benefit from coronary revascularization. Although there are several potential reasons for the lack of benefit, an underexplored possible reason is the presence of coincidental nonischemic cardiomyopathy (NICM). We investigated the prevalence and prognostic significance of NICM in patients with CAD (CAD-NICM). METHODS: We conducted a registry study of consecutive patients with obstructive CAD on coronary angiography who underwent contrast-enhanced cardiovascular magnetic resonance imaging for the assessment of ventricular function and scar at 4 hospitals from 2004 to 2020. We identified the presence and cause of cardiomyopathy using cardiovascular magnetic resonance imaging and coronary angiography data, blinded to clinical outcomes. The primary outcome was a composite of all-cause death or heart failure hospitalization, and secondary outcomes were all-cause death, heart failure hospitalization, and cardiovascular death. RESULTS: Among 3023 patients (median age, 66 years; 76% men), 18.2% had no cardiomyopathy, 64.8% had ischemic cardiomyopathy (CAD+ICM), 9.3% had CAD+NICM, and 7.7% had dual cardiomyopathy (CAD+dualCM), defined as both ICM and NICM. Thus, 16.9% had CAD+NICM or dualCM. During a median follow-up of 4.8 years (interquartile range, 2.9, 7.6), 1116 patients experienced the primary outcome. In Cox multivariable analysis, CAD+NICM or dualCM was independently associated with a higher risk of the primary outcome compared with CAD+ICM (adjusted hazard ratio, 1.23 [95% CI, 1.06-1.43]; P=0.007) after adjustment for potential confounders. The risks of the secondary outcomes of all-cause death and heart failure hospitalization were also higher with CAD+NICM or dualCM (hazard ratio, 1.21 [95% CI, 1.02-1.43]; P=0.032; and hazard ratio, 1.37 [95% CI, 1.11-1.69]; P=0.003, respectively), whereas the risk of cardiovascular death did not differ from that of CAD+ICM (hazard ratio, 1.15 [95% CI, 0.89-1.48]; P=0.28). CONCLUSIONS: In patients with CAD referred for clinical cardiovascular magnetic resonance imaging, NICM or dualCM was identified in 1 of every 6 patients and was associated with worse long-term outcomes compared with ICM. In patients with obstructive CAD, coincidental NICM or dualCM may contribute to the lack of prognostic benefit from coronary revascularization.
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Cardiomiopatias , Doença da Artéria Coronariana , Insuficiência Cardíaca , Isquemia Miocárdica , Masculino , Humanos , Idoso , Feminino , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/epidemiologia , Cardiomiopatias/complicações , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/complicações , PrognósticoRESUMO
AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.
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American Heart Association , Cardiologia , Cardiomiopatia Hipertrófica , Humanos , Cardiologia/normas , Cardiomiopatia Hipertrófica/terapia , Cardiomiopatia Hipertrófica/diagnóstico , Gerenciamento Clínico , Estados UnidosRESUMO
The spleen plays a key role in iron homeostasis. It is the largest filter of the blood and performs iron reuptake from old or damaged erythrocytes. Despite this role, spleen iron concentration has not been measured in a large, population-based cohort. In this study, we quantify spleen iron in 41,764 participants of the UK Biobank by using magnetic resonance imaging and provide a reference range for spleen iron in an unselected population. Through genome-wide association study, we identify associations between spleen iron and regulatory variation at two hereditary spherocytosis genes, ANK1 and SPTA1. Spherocytosis-causing coding mutations in these genes are associated with lower reticulocyte volume and increased reticulocyte percentage, while these common alleles are associated with increased expression of ANK1 and SPTA1 in blood and with larger reticulocyte volume and reduced reticulocyte percentage. As genetic modifiers, these common alleles may explain mild spherocytosis phenotypes that have been observed clinically. Our genetic study also identifies a signal that co-localizes with a splicing quantitative trait locus for MS4A7, and we show this gene is abundantly expressed in the spleen and in macrophages. The combination of deep learning and efficient image processing enables non-invasive measurement of spleen iron and, in turn, characterization of genetic factors related to the lytic phase of the erythrocyte life cycle and iron reuptake in the spleen.
Assuntos
Hemólise , Esferocitose Hereditária , Bancos de Espécimes Biológicos , Proteínas do Citoesqueleto/genética , Estudo de Associação Genômica Ampla , Homeostase/genética , Humanos , Ferro , Imageamento por Ressonância Magnética , Mutação , Esferocitose Hereditária/genética , Baço , Reino UnidoRESUMO
Infection with SARS-CoV-2, the virus that causes COVID, is associated with numerous potential secondary complications. Global efforts have been dedicated to understanding the myriad potential cardiovascular sequelae which may occur during acute infection, convalescence, or recovery. Because patients often present with nonspecific symptoms and laboratory findings, cardiac imaging has emerged as an important tool for the discrimination of pulmonary and cardiovascular complications of this disease. The clinician investigating a potential COVID-related complication must account not only for the relative utility of various cardiac imaging modalities but also for the risk of infectious exposure to staff and other patients. Extraordinary clinical and scholarly efforts have brought the international medical community closer to a consensus on the appropriate indications for diagnostic cardiac imaging during this protracted pandemic. In this review, we summarize the existing literature and reference major societal guidelines to provide an overview of the indications and utility of echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging for the diagnosis of cardiovascular complications of COVID.
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COVID-19 , Cardiopatias , Humanos , SARS-CoV-2 , COVID-19/diagnóstico por imagem , COVID-19/complicações , Coração , Cardiopatias/etiologia , Imagem Multimodal/métodos , Imageamento por Ressonância MagnéticaRESUMO
Early life experiences can exert a significant influence on cortical and cognitive development. Very preterm birth exposes infants to several adverse environmental factors during hospital admission, which affect cortical architecture. However, the subsequent consequence of very preterm birth on cortical growth from infancy to adolescence has never been defined; despite knowledge of critical periods during childhood for establishment of cortical networks. Our aims were to: chart typical longitudinal cortical development and sex differences in cortical development from birth to adolescence in healthy term-born children; estimate differences in cortical development between children born at term and very preterm; and estimate differences in cortical development between children with normal and impaired cognition in adolescence. This longitudinal cohort study included children born at term (≥37 weeks' gestation) and very preterm (<30 weeks' gestation) with MRI scans at ages 0, 7 and 13 years (n = 66 term-born participants comprising 34 with one scan, 18 with two scans and 14 with three scans; n = 201 very preterm participants comprising 56 with one scan, 88 with two scans and 57 with three scans). Cognitive assessments were performed at age 13 years. Cortical surface reconstruction and parcellation were performed with state-of-the-art, equivalent MRI analysis pipelines for all time points, resulting in longitudinal cortical volume, surface area and thickness measurements for 62 cortical regions. Developmental trajectories for each region were modelled in term-born children, contrasted between children born at term and very preterm, and contrasted between all children with normal and impaired cognition. In typically developing term-born children, we documented anticipated patterns of rapidly increasing cortical volume, area and thickness in early childhood, followed by more subtle changes in later childhood, with smaller cortical size in females than males. In contrast, children born very preterm exhibited increasingly reduced cortical volumes, relative to term-born children, particularly during ages 0-7 years in temporal cortical regions. This reduction in cortical volume in children born very preterm was largely driven by increasingly reduced cortical thickness rather than area. This resulted in amplified cortical volume and thickness reductions by age 13 years in individuals born very preterm. Alterations in cortical thickness development were found in children with impaired language and memory. This study shows that the neurobiological impact of very preterm birth on cortical growth is amplified from infancy to adolescence. These data further inform the long-lasting impact on cortical development from very preterm birth, providing broader insights into neurodevelopmental consequences of early life experiences.
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Nascimento Prematuro , Lactente , Criança , Recém-Nascido , Humanos , Masculino , Pré-Escolar , Feminino , Adolescente , Estudos Longitudinais , Cognição , Idade Gestacional , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagemRESUMO
Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5-17â years of age with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation and infusion were completed by 48 h post-injury. A Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between two doses. Primary end points were quantitative brain volumes using MRI and microstructural integrity of the corpus callosum (diffusivity and oedema measurements) at 6â months and 12â months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days and therapeutic intensity measures were compared between groups. Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring days and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1â year in the BMMNC group was significantly preserved compared to placebo [decrease of 19 891 versus 40 491, respectively; mean difference of -20 600, 95% confidence interval (CI): -35 868 to -5332; P = 0.01], and the number of corpus callosum streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved corpus callosum connectivity in the treated groups (-431 streamlines placebo versus -37 streamlines BMMNC; mean difference of -394, 95% CI: -803 to 15; P = 0.055), but this did not reach statistical significance due to high variability. We conclude that autologous BMMNC infusion in children within 48 h after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to: (i) shorter intensive care duration and decreased ICU intensity; (ii) white matter structural preservation; and (iii) enhanced corpus callosum connectivity and improved microstructural metrics.
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Transplante de Medula Óssea , Lesões Encefálicas Traumáticas , Transplante Autólogo , Humanos , Criança , Lesões Encefálicas Traumáticas/terapia , Masculino , Feminino , Adolescente , Método Duplo-Cego , Pré-Escolar , Transplante de Medula Óssea/métodos , Transplante Autólogo/métodos , Imageamento por Ressonância Magnética , Resultado do Tratamento , Leucócitos Mononucleares/transplante , Teorema de BayesRESUMO
It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum, traditionally termed non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analysed speech, language and disease severity features in a comprehensive cohort of patients with progressive motor speech impairment and/or agrammatism to ascertain evidence of naturally occurring, clinically meaningful non-overlapping syndromic entities (e.g. PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with aetiologic/prognostic value could be identified. We included 98 participants, 43 of whom had an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating Sum of Boxes (CDR-SB). We investigated the data's clustering tendency and cluster stability to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated using linear mixed-effects models. Of the participants included in this study, 93 conformed to previously reported clinical profiles (75 with AOS and agrammatism, 12 PPAOS and six PAA). The remaining five participants were characterized by non-fluent speech, executive dysfunction and dysarthria without apraxia of speech or frank agrammatism. No baseline clinical features differentiated between frontotemporal lobar degeneration neuropathological subgroups. The Hopkins statistic demonstrated a low cluster tendency in the entire sample (0.45 with values near 0.5 indicating random data). Cluster stability analyses showed that only two robust subgroups (differing in agrammatism, executive dysfunction and overall disease severity) could be identified. Three data-driven components accounted for 71% of the variance [(i) severity-agrammatism; (ii) prominent AOS; and (iii) prominent dysarthria]. None of these data-driven LCDs allowed an accurate prediction of neuropathology. The severity-agrammatism component was an independent predictor of a faster CDR-SB increase in all the participants. Higher dysarthria severity, reduced words per minute and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression. Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum. In our cohort, splitting the nfvPPA spectrum into separate clinical phenotypes did not improve clinical-pathological correlations, stressing the need for new biological markers and consensus regarding updated terminology and clinical classification.
Assuntos
Afasia Primária Progressiva , Apraxias , Afasia Primária Progressiva não Fluente , Humanos , Afasia de Broca/patologia , Disartria , Apraxias/patologia , Idioma , FalaRESUMO
Depression in bipolar disorder (BD-II) is frequently misdiagnosed as unipolar depression (UD) leading to inappropriate treatment and downstream complications for many bipolar sufferers. In this study, we evaluated whether neuromelanin-MR signal and volume changes in the substantia nigra (SN) can be used as potential biomarkers to differentiate BD-II from UD. The signal intensities and volumes of the SN regions were measured, and contrast-to-noise ratio (CNR) to the decussation of the superior cerebellar peduncles were calculated and compared between healthy controls (HC), BD-II and UD subjects. Results showed that compare to HC, both BD-II and UD subjects had significantly decreased CNR and increased volume on the right and left sides. Moreover, the volume in BD-II group was significantly increased compared to UD group. The area under the receiver operating characteristic curve (AUC) for discriminating BD from HC was the largest for the Volume-L (AUC, 0.85; 95% confidence interval [CI]: 0.77, 0.93). The AUC for discriminating UD from HC was the largest for the Volume-L (AUC, 0.76; 95% CI: 0.65, 0.86). Furthermore, the AUC for discriminating BD from UD was the largest for the Volume-R (AUC, 0.73; 95% CI: 0.62, 0.84). Our findings suggest that neuromelanin-sensitive magnetic resonance imaging techniques can be used to differentiate BD-II from UD.
Assuntos
Transtorno Bipolar , Transtorno Depressivo , Melaninas , Humanos , Transtorno Bipolar/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Substância Negra/diagnóstico por imagemRESUMO
This study aimed to determine the patterns of changes in structure, function, and cognitive ability in early-onset and late-onset older adults with focal epilepsy (OFE). This study first utilized the deformation-based morphometry analysis to identify structural abnormalities, which were used as the seed region to investigate the functional connectivity with the whole brain. Next, a correlation analysis was performed between the altered imaging findings and neuropsychiatry assessments. Finally, the potential role of structural-functional abnormalities in the diagnosis of epilepsy was further explored by using mediation analysis. Compared with healthy controls (n = 28), the area of reduced structural volume was concentrated in the bilateral cerebellum, right thalamus, and right middle cingulate cortex, with frontal, temporal, and occipital lobes also affected in early-onset focal epilepsy (n = 26), while late-onset patients (n = 31) displayed cerebellar, thalamic, and cingulate atrophy. Furthermore, correlation analyses suggest an association between structural abnormalities and cognitive assessments. Dysfunctional connectivity in the cerebellum, cingulate cortex, and frontal gyrus partially mediates the relationship between structural abnormalities and the diagnosis of early-onset focal epilepsy. This study identified structural and functional abnormalities in early-onset and late-onset focal epilepsy and explored characters in cognitive performance. Structural-functional coupling may play a potential role in the diagnosis of epilepsy.
Assuntos
Idade de Início , Encéfalo , Epilepsias Parciais , Imageamento por Ressonância Magnética , Humanos , Masculino , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/patologia , Feminino , Pessoa de Meia-Idade , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Testes Neuropsicológicos , AdultoRESUMO
The hippocampus is one of the brain regions most vulnerable to inflammatory insults, and the relationships between peripheral inflammation and hippocampal subfields in patients with schizophrenia remain unclear. In this study, forty-six stably medicated patients with schizophrenia and 48 demographically matched healthy controls (HCs) were recruited. The serum levels of IL - 1ß, IL-6, IL-10, and IL-12p70 were measured, and 3D high-resolution T1-weighted magnetic resonance imaging was performed. The IL levels and hippocampal subfield volumes were both compared between patients and HCs. The associations of altered IL levels with hippocampal subfield volumes were assessed in patients. Patients with schizophrenia demonstrated higher serum levels of IL-6 and IL-10 but lower levels of IL-12p70 than HCs. In patients, the levels of IL-6 were positively correlated with the volumes of the left granule cell layer of the dentate gyrus (GCL) and cornu Ammonis (CA) 4, while the levels of IL-10 were negatively correlated with the volumes of those subfields. IL-6 and IL-10 might have antagonistic roles in atrophy of the left GCL and CA4. This suggests a complexity of peripheral cytokine dysregulation and the potential for its selective effects on hippocampal substructures, which might be related to the pathophysiology of schizophrenia.
Assuntos
Hipocampo , Imageamento por Ressonância Magnética , Esquizofrenia , Humanos , Esquizofrenia/patologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/sangue , Masculino , Feminino , Hipocampo/patologia , Hipocampo/diagnóstico por imagem , Adulto , Interleucinas/sangue , Interleucinas/metabolismo , Pessoa de Meia-Idade , Tamanho do ÓrgãoRESUMO
Normative ferret brain development was characterized using magnetic resonance imaging. Brain growth was longitudinally monitored in 10 ferrets (equal numbers of males and females) from postnatal day 8 (P8) through P38 in 6-d increments. Template T2-weighted images were constructed at each age, and these were manually segmented into 12 to 14 brain regions. A logistic growth model was used to fit data from whole brain volumes and 8 of the individual regions in both males and females. More protracted growth was found in males, which results in larger brains; however, sex differences were not apparent when results were corrected for body weight. Additionally, surface models of the developing cortical plate were registered to one another using the anatomically-constrained Multimodal Surface Matching algorithm. This, in turn, enabled local logistic growth parameters to be mapped across the cortical surface. A close similarity was observed between surface area expansion timing and previous reports of the transverse neurogenic gradient in ferrets. Regional variation in the extent of surface area expansion and the maximum expansion rate was also revealed. This characterization of normative brain growth over the period of cerebral cortex folding may serve as a reference for ferret studies of brain development.
Assuntos
Encéfalo , Furões , Imageamento por Ressonância Magnética , Animais , Furões/crescimento & desenvolvimento , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Encéfalo/crescimento & desenvolvimento , Encéfalo/diagnóstico por imagem , Encéfalo/anatomia & histologia , Estudos Longitudinais , Caracteres SexuaisRESUMO
Studies of the development and asymmetry of the corpus striatum and thalamus in early childhood are rare. Studies investigating these structures across the lifespan have not presented their changes during childhood and adolescence in detail. For these reasons, this study investigated the effect of age and sex factors on the development and asymmetry of the corpus striatum and thalamus in the 1-18 age group. In this retrospective study, we included 652 individuals [362 (56%) males] aged 1-18 years with normal brain MRI between 2012 and 2021. Absolute and relative volumes of the corpus striatum and thalamus were obtained by segmentation of three-dimensional T1-weighted MRIs with volBrain1.0. We created age-specific volume data and month-based development models with the help of SPSS (ver.28). The corpus striatum and thalamus had cubic absolute volumetric developmental models. The relative volume of the caudate and thalamus (only males) is consistent with the decreasing "growth" model, the others with the decreasing cubic model. The absolute volumes of the males' bilateral corpus striatum and thalamus and the relative volumes of the caudate and thalamus of the females were significantly larger (P < 0.05). The caudate showed right > left lateralization; putamen, globus pallidus, and thalamus showed left > right lateralization.