Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 65
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Quant Imaging Med Surg ; 14(4): 2774-2787, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38617153

RESUMEN

Background: Magnetic resonance imaging (MRI) is a primary non-invasive imaging modality for tumor segmentation, leveraging its exceptional soft tissue contrast and high resolution. Current segmentation methods typically focus on structural MRI, such as T1-weighted post-contrast-enhanced or fluid-attenuated inversion recovery (FLAIR) sequences. However, these methods overlook the blood perfusion and hemodynamic properties of tumors, readily derived from dynamic susceptibility contrast (DSC) enhanced MRI. This study introduces a novel hybrid method combining density-based analysis of hemodynamic properties in time-dependent perfusion imaging with deep learning spatial segmentation techniques to enhance tumor segmentation. Methods: First, a U-Net convolutional neural network (CNN) is employed on structural images to delineate a region of interest (ROI). Subsequently, Hierarchical Density-Based Scans (HDBScan) are employed within the ROI to augment segmentation by exploring intratumoral hemodynamic heterogeneity through the investigation of tumor time course profiles unveiled in DSC MRI. Results: The approach was tested and evaluated using a cohort of 513 patients from the open-source University of Pennsylvania glioblastoma database (UPENN-GBM) dataset, achieving a 74.83% Intersection over Union (IoU) score when compared to structural-only segmentation. The algorithm also exhibited increased precision and localized predictions of heightened segmentation boundary complexity, resulting in a 146.92% increase in contour complexity (ICC) compared to the reference standard provided by the UPENN-GBM dataset. Importantly, segmenting tumors with the developed new approach uncovered a negative correlation of the tumor volume with the scores in the Karnofsky Performance Scale (KPS) clinically used for assessing the functional status of patients (-0.309), which is not observed with the prevailing segmentation standard. Conclusions: This work demonstrated that including hemodynamic properties of tissues from DSC MRI can improve existing structural or morphological feature-based tumor segmentation techniques with additional information on tumor biology and physiology. This approach can also be applied to other clinical indications that use perfusion MRI for diagnosis or treatment monitoring.

2.
Nat Commun ; 15(1): 2781, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555303

RESUMEN

Electrochemical research often requires stringent combinations of experimental parameters that are demanding to manually locate. Recent advances in automated instrumentation and machine-learning algorithms unlock the possibility for accelerated studies of electrochemical fundamentals via high-throughput, online decision-making. Here we report an autonomous electrochemical platform that implements an adaptive, closed-loop workflow for mechanistic investigation of molecular electrochemistry. As a proof-of-concept, this platform autonomously identifies and investigates an EC mechanism, an interfacial electron transfer (E step) followed by a solution reaction (C step), for cobalt tetraphenylporphyrin exposed to a library of organohalide electrophiles. The generally applicable workflow accurately discerns the EC mechanism's presence amid negative controls and outliers, adaptively designs desired experimental conditions, and quantitatively extracts kinetic information of the C step spanning over 7 orders of magnitude, from which mechanistic insights into oxidative addition pathways are gained. This work opens opportunities for autonomous mechanistic discoveries in self-driving electrochemistry laboratories without manual intervention.

3.
bioRxiv ; 2023 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-37873233

RESUMEN

Hypergraphs are powerful tools for modeling complex interactions across various domains, including biomedicine. However, learning meaningful node representations from hypergraphs remains a challenge. Existing supervised methods often lack generalizability, thereby limiting their real-world applications. We propose a new method, Pre-trained Hypergraph Convolutional Neural Networks with Self-supervised Learning (PhyGCN), which leverages hypergraph structure for self-supervision to enhance node representations. PhyGCN introduces a unique training strategy that integrates variable hyperedge sizes with self-supervised learning, enabling improved generalization to unseen data. Applications on multi-way chromatin interactions and polypharmacy side-effects demonstrate the effectiveness of PhyGCN. As a generic framework for high-order interaction datasets with abundant unlabeled data, PhyGCN holds strong potential for enhancing hypergraph node representations across various domains.

4.
Proc Natl Acad Sci U S A ; 120(18): e2207537120, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-37098064

RESUMEN

Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Incertidumbre , Brotes de Enfermedades/prevención & control , Salud Pública , Pandemias/prevención & control
5.
CNS Neurosci Ther ; 29(7): 1776-1784, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36852447

RESUMEN

BACKGROUND: Dysfunction of iron metabolism, especially in substantia nigra (SN), is widely acknowledged in Parkinson's disease (PD), but the genetic influence on iron deposition remains largely unknown. Thus, in this study, we aimed to investigate potential genetic impacts on iron deposition in PD. METHODS: Seventy-four subjects, including 38 patients with PD and 36 age-matched normal controls, participated in this study. Imaging genetic association analysis was used to identify the specific influence of single nucleotide polymorphism (SNP) on iron-related quantitative traits (QT). Genetic effects on iron deposition at the disease level, SNP level, and their interactive effect were highlighted. RESULTS: Four strong SNP-QT associations were detected: rs602201-susceptibility of bilateral SN, rs198440-susceptibility of left SN, and rs7895403-susceptibility of left caudate head. Detailed analyses showed that: (1) significant iron deposition was exclusively found in bilateral SN in PD; (2) altered polymorphisms of the A allele/A- genotype of rs602201 and G allele/G- genotype of rs198440 and rs7895403 were more frequently observed in PD; (3) for rs602201, among all subjects, A- genotype carriers showed significantly increased iron content than TT genotype in bilateral SN; for rs198440 and rs7895403, G- carriers showed increased iron content than AA genotype in left SN and left caudate head, respectively; and (4) rs602201 exhibited significant SNP-by-disease interaction in bilateral SN. CONCLUSIONS: This study shows that rs602201 and rs198440 have a stimulative impact on nigral iron deposition in PD, which provides improved understanding of iron-related pathogenesis in PD, and specifically, that vulnerability to iron deposition in SN is genetic-based.


Asunto(s)
Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Imagen por Resonancia Magnética/métodos , Sustancia Negra/diagnóstico por imagen , Hierro/metabolismo , Polimorfismo de Nucleótido Simple/genética
6.
ACS Meas Sci Au ; 2(6): 595-604, 2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-36573074

RESUMEN

For decades, employing cyclic voltammetry for mechanistic investigation has demanded manual inspection of voltammograms. Here, we report a deep-learning-based algorithm that automatically analyzes cyclic voltammograms and designates a probable electrochemical mechanism among five of the most common ones in homogeneous molecular electrochemistry. The reported algorithm will aid researchers' mechanistic analyses, utilize otherwise elusive features in voltammograms, and experimentally observe the gradual mechanism transitions encountered in electrochemistry. An automated voltammogram analysis will aid the analysis of complex electrochemical systems and promise autonomous high-throughput research in electrochemistry with minimal human interference.

7.
Quant Imaging Med Surg ; 12(7): 3603-3624, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35782263

RESUMEN

Background: Although cigarette smoking is a risk factor for multiple disorders, it has long been thought to protect against Parkinson's disease (PD). Quantitative susceptibility mapping (QSM) is a novel magnetic resonance imaging (MRI)-based technique for assessing iron accumulation in vivo that has been widely applied in PD studies. This study aimed to investigate how cigarette smoking affects clinical performance of PD using quantified iron deposition as a proxy for PD pathology. Methods: In this observational study, we enrolled 35 male PD patients and 47 male healthy controls (HCs) and divided them into four groups. We performed an enhanced T2 star-weighted angiography (ESWAN) MRI sequence to measure the iron content of the nuclei within the nigrostriatal pathway. With the age and total intracranial volume (TIV) controlled as covariates, we performed inter-group comparisons of QSM values and moderation analyses for PD patients using smoking status and the smoking index (SI), respectively, as moderator variables. Results: The 2-way multivariate analysis of covariance (MANCOVA) results showed higher QSM values in the left red nucleus (P=0.024) in PD patients compared with those in HCs, and in the bilateral globi pallidi [left/right (L/R): P=0.009/0.003], substantia nigra pars compacta (SNc; L/R: P=0.001/0.037), and right substantia nigra pars reticulata (SNr; P=0.002) in non-smokers compared with smokers, with no marked interaction effect between PD and smoking status observed when applying the Bonferroni adjustment for multiple comparisons. Using cigarette smoking status and the SI as separate moderator variables, the moderation was shown up by a significant interaction effect in a disordinal and double-edged form. In our results, smoking-moderated protection for PD movement deficits emerged when PD was progressed. Among the affected deep brain nuclei, the nuclei most moderated by the impact of cigarette smoking on the interaction between brain iron and PD symptoms were the thalamus [smoking status associated with the Unified Parkinson's Disease Rating Scale (UPDRS) total score, P=0.04 (L); rigidity, P=0.03 (L); SI associated with UPDRS-III, P (L/R) =0.049/0.0497; rigidity, P (L/R) =0.01/0.02; bradykinesia, P (L/R) =0.048/0.04], the right red nucleus (SI associated with rigidity, P=0.04; bradykinesia, P=0.02), and the left SNc [smoking status associated with the Hoehn and Yahr (H&Y) stage, P=0.01]. Conclusions: This was the first study investigating the impacts of current cigarette smoking on PD using quantified iron deposition. Our study confirmed the protective role of cigarette smoking against PD, consistent with the findings of previous studies. Furthermore, neuroprotection was present only when the PD pathology had progressed to a certain extent. In the interaction between iron deposition and clinical PD symptoms, our findings suggest that the thalamus, red nucleus, and SNc are likely to be the most affected nuclei moderated by cigarette smoking.

8.
Neural Regen Res ; 17(12): 2743-2749, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35662223

RESUMEN

Brain radiomics can reflect the characteristics of brain pathophysiology. However, the value of T1-weighted images, quantitative susceptibility mapping, and R2* mapping in the diagnosis of Parkinson's disease (PD) was underestimated in previous studies. In this prospective study to establish a model for PD diagnosis based on brain imaging information, we collected high-resolution T1-weighted images, R2* mapping, and quantitative susceptibility imaging data from 171 patients with PD and 179 healthy controls recruited from August 2014 to August 2019. According to the inclusion time, 123 PD patients and 121 healthy controls were assigned to train the diagnostic model, while the remaining 106 subjects were assigned to the external validation dataset. We extracted 1408 radiomics features, and then used data-driven feature selection to identify informative features that were significant for discriminating patients with PD from normal controls on the training dataset. The informative features so identified were then used to construct a diagnostic model for PD. The constructed model contained 36 informative radiomics features, mainly representing abnormal subcortical iron distribution (especially in the substantia nigra), structural disorganization (e.g., in the inferior temporal, paracentral, precuneus, insula, and precentral gyri), and texture misalignment in the subcortical nuclei (e.g., caudate, globus pallidus, and thalamus). The predictive accuracy of the established model was 81.1 ± 8.0% in the training dataset. On the external validation dataset, the established model showed predictive accuracy of 78.5 ± 2.1%. In the tests of identifying early and drug-naïve PD patients from healthy controls, the accuracies of the model constructed on the same 36 informative features were 80.3 ± 7.1% and 79.1 ± 6.5%, respectively, while the accuracies were 80.4 ± 6.3% and 82.9 ± 5.8% for diagnosing middle-to-late PD and those receiving drug management, respectively. The accuracies for predicting tremor-dominant and non-tremor-dominant PD were 79.8 ± 6.9% and 79.1 ± 6.5%, respectively. In conclusion, the multiple-tissue-specific brain radiomics model constructed from magnetic resonance imaging has the ability to discriminate PD and exhibits the advantages for improving PD diagnosis.

9.
Netw Neurosci ; 6(2): 552-569, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35733432

RESUMEN

Hierarchical brain organization, in which the rich club and diverse club situate in core position, is critical for global information integration in the human brain network. Parkinson's disease (PD), a common movement disorder, has been conceptualized as a network disorder. Levodopa is an effective treatment for PD. Whether there is a functional divergence in the hierarchical brain system under PD pathology, and how this divergence is regulated by immediate levodopa therapy, remains unknown. We constructed a functional network in 61 PD patients and 89 normal controls and applied graph theoretical analyses to examine the neural mechanism of levodopa short response from the perspective of brain hierarchical configuration. The results revealed the following: (a) PD patients exhibited disrupted function within rich-club organization, while the diverse club preserved function, indicating a differentiated brain topological organization in PD. (b) Along the rich-club derivate hierarchical system, PD patients showed impaired network properties within rich-club and feeder subnetworks, and decreased nodal degree centrality in rich-club and feeder nodes, along with increased nodal degree in peripheral nodes, suggesting distinct functional patterns in different types of nodes. And (c) levodopa could normalize the abnormal network architecture of the rich-club system. This study provides evidence for levodopa effects on the hierarchical brain system with divergent functions.

10.
Brain Imaging Behav ; 16(3): 1234-1245, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34973120

RESUMEN

Tremor in Parkinson's disease (PD) has distinct responsiveness to dopamine, which is supposed not be exclusively related to dopamine deficiency but has a close relationship with cholinergic system. This phenomenon indicates that cholinergic system may be an important regulatory for distinct dopamine responsiveness of parkinsonian tremor. Through investigating the alterations of cholinergic and dopaminergic network during levodopa administration, we aimed at exploring the mechanisms of differed dopamine responsiveness of parkinsonian tremor. Fifty-two PD patients with tremor were enrolled. MRI scanning, UPDRS III and its sub-symptom scores were collected in OFF and ON status (dopaminergic challenge test). Then, patients were divided into two groups (dopamine-resistant tremor and dopamine-responsive tremor) according to the tremor change rate median score. Dopaminergic and cholinergic network were obtained. LASSO regression was conducted to identify functional connectivity with distinct reactivity during levodopa administration between groups. Afterwards, detailed group comparisons, interaction and correlation analyses were performed. The reactivity of cholinergic connectivity showed the highest possibility to distinguish two groups, especially connectivity of right basal forebrain 123 to right parietal operculum cortex (R.BF123-R.PO). After levodopa administration, connectivity of R.BF123-R.PO was decreased for dopamine-responsive tremor while which remained unchanged for dopamine-resistant tremor. The reactivity of R.BF123-R.PO was negatively correlated with tremor change rate. Reduced cholinergic connectivity to parietal operculum may be an underlying mechanism for the responsive tremor in PD and the distinct cholinergic reactivity of parietal operculum to levodopa may be a core pathophysiology for the differed DA responsiveness of tremor in PD.


Asunto(s)
Enfermedad de Parkinson , Temblor , Antiparkinsonianos/uso terapéutico , Colinérgicos , Dopamina , Humanos , Levodopa/uso terapéutico , Imagen por Resonancia Magnética , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/tratamiento farmacológico , Temblor/diagnóstico por imagen , Temblor/tratamiento farmacológico
11.
Hum Brain Mapp ; 43(5): 1598-1610, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34904766

RESUMEN

Parkinson's disease (PD) is primarily characterized by the loss of dopaminergic cells and atrophy in subcortical regions. However, the impact of these pathological changes on large-scale dynamic integration and segregation of the cortex are not well understood. In this study, we investigated the effect of subcortical dysfunction on cortical dynamics and cognition in PD. Spatiotemporal dynamics of the phase interactions of resting-state blood-oxygen-level-dependent signals in 159 PD patients and 152 normal control (NC) individuals were estimated. The relationships between subcortical atrophy, subcortical-cortical fiber connectivity impairment, cortical synchronization/metastability, and cognitive performance were then assessed. We found that cortical synchronization and metastability in PD patients were significantly decreased. To examine whether this is an effect of dopamine depletion, we investigated 45 PD patients both ON and OFF dopamine replacement therapy, and found that cortical synchronization and metastability are significantly increased in the ON state. The extent of cortical synchronization and metastability in the OFF state reflected cognitive performance and mediates the difference in cognitive performance between the PD and NC groups. Furthermore, both the thalamic volume and thalamocortical fiber connectivity had positive relationships with cortical synchronization and metastability in the dopaminergic OFF state, and mediate the difference in cortical synchronization between the PD and NC groups. In addition, thalamic volume also reflected cognitive performance, and cortical synchronization/metastability mediated the relationship between thalamic volume and cognitive performance in PD patients. Together, these results highlight that subcortical dysfunction and reduced dopamine levels are responsible for decreased cortical synchronization and metastability, further affecting cognitive performance in PD. This might lead to biomarkers being identified that can predict if a patient is at risk of developing dementia.


Asunto(s)
Enfermedad de Parkinson , Atrofia , Cognición , Sincronización Cortical , Dopamina , Humanos , Pruebas Neuropsicológicas , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología
12.
Front Oncol ; 11: 701113, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34956856

RESUMEN

BACKGROUND: Diffuse midline glioma with H3K27-altered (DMG-H3K27a) is a novel tumor entity of the pediatric-type diffuse high-grade tumor in the latest WHO CNS 5. It mostly affects children and is only rarely found in adults. The tumor has a high level of aggressiveness, with a rapid progression and bad prognosis. In adults, the spinal cord is the most common site of DMG-H3K27a. Rare adult cases of primary DMG-H3K27a in the spinal cord were reported in this study, together with clinico-histopathologico-radiographic data. METHODS: From January 2016 to December 2020, we conducted a retrospective study of five adults with primary DMG-H3K27a in the spinal cord, analyzing their clinical, pathohistological, and radiographic datasets from the first diagnosis to follow-up. RESULTS: All five patients were diagnosed for the first time and were given full treatment. In three of the five patients, post-operative follow-up revealed tumor recurrence. The longest survival of the five patients was 45 months at the time of report submission, while the longest progression-free survival (PFS) following surgery was 20 months. Immunohistochemical studies showed the tumors featured aggressive behavior (grade 4) and were positive for the H3K27M mutation. The radiographic appearances were varied, but they were all initially mistaken as benign. DMG-H3K27a in the spinal cord was characterized by isointense/hyperintense on T1WI and isointense/hyperintense on T2WI, as well as cystic necrosis and peripheral spinal cord edema, as well as central canal enlargement and other types of enhancement. CONCLUSION: This is the first case report focusing on adult DMG-H3K27a of the pediatric-type diffuses high-grade gliomas in the spinal cord. In our cases, we discovered the following: 1) adults had a better prognosis with a longer PFS compared with prior pediatric reports; 2) despite aggressive behavior under the microscope, radiographic appearances of the tumors were less aggressive; and 3) adjuvant treatment, including TCM, may have played a role in the prognosis.

13.
Neuroimage Clin ; 32: 102873, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34749290

RESUMEN

Degeneration of the locus coeruleus (LC) is recognized as a critical hallmark of Parkinson's disease (PD). Recent studies have reported that noradrenaline produced from the LC has critical effects on brain functional organization. However, it is unknown if LC degeneration in PD contributes to cognitive/motor manifestations through modulating brain functional organization. This study enrolled 94 PD patients and 68 healthy controls, and LC integrity was measured using the contrast-to-noise ratio of the LC (CNRLC) calculated from T1-weighted magnetic resonance imaging. We used graph-theory-based network analysis to characterize brain functional organization. The relationships among LC degeneration, network disruption, and cognitive/motor manifestations in PD were assessed. Whether network disruption was a mediator between LC degeneration and cognitive/motor impairments was assessed further. In addition, an independent PD subgroup (n = 35) having functional magnetic resonance scanning before and after levodopa administration was enrolled to evaluate whether LC degeneration-related network deficiencies were independent of dopamine deficiency. We demonstrated that PD patients have significant LC degeneration compared to healthy controls. CNRLC was positively correlated with Montreal Cognitive Assessment score and the nodal efficiency (NE) of several cognitive-related regions. Lower NE of the superior temporal gyrus was a mediator between LC degeneration and cognitive impairment in PD. However, levodopa treatment could not normalize the reduced NE of the superior temporal gyrus (mediator). In conclusion, we provided evidence for the relationship between LC degeneration and extensive network disruption in PD, and highlight the role of network disorganization in LC degeneration-related cognitive impairment.


Asunto(s)
Enfermedad de Parkinson , Encéfalo , Humanos , Levodopa , Locus Coeruleus , Imagen por Resonancia Magnética
14.
Prev Med ; 153: 106860, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34687733

RESUMEN

Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P < 0.001), with >80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19-2.51) and dose 2 (1.76, 1.28-2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last <2 days. Appreciable post-vaccine symptoms are associated with female sex, prior COVID-19, younger age, and hypertension. This information can aid clinicians in advising patients on the safety and expected symptomatology associated with vaccination.


Asunto(s)
COVID-19 , SARS-CoV-2 , Vacunas contra la COVID-19 , Femenino , Humanos , ARN Mensajero , Vacunación
15.
J Parkinsons Dis ; 11(4): 1631-1640, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34366373

RESUMEN

BACKGROUND: The widely divergent responsiveness of Parkinson's disease (PD) patients to levodopa is an important clinical issue because of its relationship with quality of life and disease prognosis. Preliminary animal experiments have suggested that degeneration of the locus coeruleus (LC) attenuates the efficacy of levodopa treatment. OBJECTIVE: To explore the relationship between LC degeneration and levodopa responsiveness in PD patients in vivo. METHODS: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a good indicator of LC and substantia nigra (SN) degeneration, and levodopa challenge tests were conducted in 57 PD patients. Responsiveness to levodopa was evaluated by the rates of change of the Unified Parkinson's Disease Rating Scale Part III score and somatomotor network synchronization calculated from resting-state functional MRI before and after levodopa administration. Next, we assessed the relationship between the contrast-to-noise ratio of LC (CNRLC) and levodopa responsiveness. Multiple linear regression analysis was conducted to rule out the potential influence of SN degeneration on levodopa responsiveness. RESULTS: A significant positive correlation was found between CNRLC and the motor improvement after levodopa administration (R = 0.421, p = 0.004). CNRLC also correlated with improvement in somatomotor network synchronization (R = -0.323, p = 0.029). Furthermore, the relationship between CNRLC and levodopa responsiveness was independent of SN degeneration. CONCLUSION: LC degeneration might be an essential factor for levodopa resistance. LC evaluation using NM-MRI might be an alternative tool for predicting levodopa responsiveness and for helping to stratify patients into clinical trials aimed at improving the efficacy of levodopa.


Asunto(s)
Levodopa , Enfermedad de Parkinson , Animales , Humanos , Levodopa/uso terapéutico , Locus Coeruleus , Imagen por Resonancia Magnética , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/tratamiento farmacológico , Calidad de Vida , Estudios Retrospectivos
16.
Parkinsonism Relat Disord ; 88: 82-89, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34147950

RESUMEN

OBJECTIVES: To explore the microstructural alterations in subcortical nuclei in Parkinson's disease (PD) at different stages with diffusion kurtosis imaging (DKI) and tensor imaging and to test the performance of diffusion metrics in identifying PD. METHODS: 108 PD patients (64 patients in early-stage PD group (EPD) and 44 patients in moderate-late-stage PD group (MLPD)) and 64 healthy controls (HC) were included. Tensor and kurtosis metrics in the subcortical nuclei were compared. Partial correlation was used to correlate the diffusion metrics and Unified Parkinson's Disease Rating Scale part-III (UPDRS-III) score. Logistic regression and receiver operating characteristic analysis were applied to test the diagnostic performance of the diffusion metrics. RESULTS: Compared with HC, both EPD and MLPD patients showed higher fractional anisotropy and axial diffusivity, lower mean kurtosis (MK) and axial kurtosis in substantia nigra, lower MK and radial kurtosis (RK) in globus pallidus (GP) and thalamus (all p < 0.05). Compared with EPD, MLPD patients showed lower MK and RK in GP and thalamus (all p < 0.05). MK and RK in GP and thalamus were negatively correlated with UPDRS-III score (all p < 0.01). The logistic regression model combining kurtosis and tensor metrics showed the best performance in diagnosing PD, EPD, and MLPD (areas under curve were 0.817, 0.769, and 0.914, respectively). CONCLUSIONS: PD has progressive microstructural alterations in the subcortical nuclei. DKI is sensitive to detect microstructural alterations in GP and thalamus during PD progression. Combining kurtosis and tensor metrics can achieve a good performance in diagnosing PD.


Asunto(s)
Imagen de Difusión por Resonancia Magnética/normas , Globo Pálido/patología , Enfermedad de Parkinson/patología , Tálamo/patología , Anciano , Imagen de Difusión Tensora/normas , Progresión de la Enfermedad , Femenino , Globo Pálido/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Tálamo/diagnóstico por imagen
17.
J Magn Reson Imaging ; 54(4): 1098-1106, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33949744

RESUMEN

BACKGROUND: Excessive iron accumulation is one of the main pathogeneses of Parkinson's disease (PD). Ceruloplasmin plays an important role in keeping the iron homoeostasis. PURPOSE: To explore the association between serum ceruloplasmin depletion and subcortical iron distribution in PD. STUDY TYPE: Prospective. POPULATION: One hundred and twenty-one normal controls, 34 PD patients with low serum ceruloplasmin (PD-LC), and 28 patients with normal serum ceruloplasmin (PD-NC). SEQUENCE: Enhanced susceptibility-weighted angiography (ESWAN) on a 3 T scanner. ASSESSMENT: Quantitative susceptibility mapping was employed to quantify the regional iron content by using a semi-automatic method. Serum ceruloplasmin concentration was measured from peripheral blood sample. Clinical assessments were conducted by a neurologist. STATISTICAL TESTS: General linear model was used to compare the intergroup difference of region iron distribution among groups, and the statistics was adjusted by Bonferroni method (P < 0.01). Partial correlation analysis was used to detect the association between regional iron distribution and serum ceruloplasmin concentration (P < 0.05). RESULTS: Compared with normal controls, significant iron accumulation in substantia nigra, putamen, and red nucleus was observed in PD-LC, while the only region showing significant iron accumulation was SN in PD-NC. Between PD-NC and PD-LC, the iron accumulation in putamen remained significantly different, which had a negative correlation with serum ceruloplasmin in whole PD patients (r = -0.338, P = 0.008). DATA CONCLUSION: Nigral iron accumulation characterizes PD patients without significant association with serum ceruloplasmin. Differentially, when PD patients appear with reduced serum ceruloplasmin, more widespread iron accumulation would be expected with additionally involving putamen and red nucleus. All these findings provide insightful evidence for the abnormal iron metabolism behind the ceruloplasmin depletion in PD. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: 2.


Asunto(s)
Ceruloplasmina , Enfermedad de Parkinson , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Ceruloplasmina/metabolismo , Humanos , Hierro/metabolismo , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Enfermedad de Parkinson/diagnóstico por imagen , Estudios Prospectivos , Sustancia Negra
18.
Brain Imaging Behav ; 15(4): 1955-1965, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32974850

RESUMEN

Nicotine addiction is characterized as a neural circuit dysfunction, particularly with regard to the alterations in central reward pathways. The insula, a cortical region that is thought to play a central role in this reward circuitry, has been implicated in the maintenance of nicotine addiction. However, it remains largely unclear about the white matter (WM) microstructural alterations of insula in nicotine addiction and whether the WM alterations of insula could predict smoking cessation outcomes. In this study, 58 male nicotine-dependent smokers and 34 matched male nonsmoking controls were recruited. After a 12-week smoking cessation treatment with varenicline, 38 smokers relapsed, and 20 did not relapse. Diffusion tensor imaging and probabilistic tractography were used to investigate the differences of WM tracts of insula between smokers and nonsmokers. Relative to nonsmokers, in the left hemisphere, smokers showed lower fractional anisotropy (FA) in the fiber tracts of anterior insula cortex-to-nucleus accumbens and posterior insula cortex-to-nucleus accumbens; in the right hemisphere, smokers showed higher FA, and lower axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in the fiber tracts of anterior insula cortex-to-medial orbitofrontal cortex, posterior insula cortex-to-medial orbitofrontal cortex, and posterior insula cortex-to-nucleus accumbens. However, there were no differences of WM diffusion properties between relapsers and nonrelapsers. This study is the first using probabilistic tractography to exclusively clarify the precise roles of insular WM tracts in smokers, which may provide new insights into the underlying neurobiology of nicotine addiction.


Asunto(s)
Sustancia Blanca , Anisotropía , Imagen de Difusión Tensora , Humanos , Imagen por Resonancia Magnética , Masculino , Fumadores , Sustancia Blanca/diagnóstico por imagen
19.
Front Aging Neurosci ; 12: 572086, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33328954

RESUMEN

BACKGROUND: The corpus callosum (CC) is an important feature of Parkinson's disease (PD) not only in motor but also in non-motor functions. However, CC is not a homogeneous component, and the damage of specific subsection may contribute to corresponding clinical deficit. OBJECTIVE: The objective of the study is to investigate the structural alterations of different callosal subsections cross-sectionally and longitudinally in PD and evaluate their relationships to clinical performance. METHODS: Thirty-nine PD patients who had been longitudinally reexamined and 82 normal controls (NC) were employed. According to their specific callosal-cortical connectivity, 3D CC was divided into five subsections (including prefrontal, premotor, motor, somatosensory, and temporal-parietal-occipital subsection). The fractional anisotropy (FA), mean diffusivity (MD), and volume of whole CC and its subsections were computed and compared between groups. Regression model was constructed to explore the relationships between callosal structure and clinical performance. RESULTS: At baseline, PD did not show any significant macro/microstructural difference compared with NC. During disease course, there was a decreased FA and increased MD of whole CC as well as its subsections (except temporal-parietal-occipital subsection), and the volume of motor subsection was decreased. Moreover, the FA of temporal-parietal-occipital subsection and volume of motor subsection were correlated with the mood domain at baseline, and the MD of somatosensory subsection was associated with the motor domain at follow-up. CONCLUSION: The structure of CC and its connectivity-specific subsections remain preserved at a relatively early stage in PD and are progressively disrupted during disease course. Besides, different callosal subsections possess specific associations with clinical performance in PD.

20.
medRxiv ; 2020 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-33173914

RESUMEN

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...