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Development of a Bayesian multimodal model to detect biomarkers in neuroimaging studies. 开发贝叶斯多模态模型,用于检测神经影像学研究中的生物标志物。
Pub Date : 2023-01-01 DOI: 10.3389/fnimg.2023.1147508
Dulal K Bhaumik, Yue Wang, Pei-Shan Yen, Olusola A Ajilore

In this article, we developed a Bayesian multimodal model to detect biomarkers (or neuromarkers) using resting-state functional and structural data while comparing a late-life depression group with a healthy control group. Biomarker detection helps determine a target for treatment intervention to get the optimal therapeutic benefit for treatment-resistant patients. The borrowing strength of the structural connectivity has been quantified for functional activity while detecting the biomarker. In the biomarker searching process, thousands of hypotheses are generated and tested simultaneously using our novel method to control the false discovery rate for small samples. Several existing statistical approaches, frequently used in analyzing neuroimaging data have been investigated and compared via simulation with the proposed approach to show its excellent performance. Results are illustrated with a live data set generated in a late-life depression study. The role of detected biomarkers in terms of cognitive function has been explored.

在本文中,我们开发了一个贝叶斯多模态模型,利用静息状态功能和结构数据来检测生物标志物(或神经标志物),同时将晚年抑郁症组与健康对照组进行比较。生物标志物检测有助于确定治疗干预的目标,以获得治疗耐药患者的最佳治疗效果。在检测生物标志物时,结构连通性的借用强度已被量化为功能活性。在生物标记物搜索过程中,使用我们的新方法同时生成和测试数千个假设,以控制小样本的错误发现率。研究了现有的几种常用的神经影像学数据分析统计方法,并与本文提出的方法进行了仿真比较,以显示其优异的性能。结果用一个在晚年抑郁症研究中产生的实时数据集来说明。检测到的生物标志物在认知功能方面的作用已经被探索。
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引用次数: 0
Measuring white matter microstructure in 1,457 cannabis users and 1,441 controls: A systematic review of diffusion-weighted MRI studies. 测量1457名大麻使用者和1441名对照者的白质微观结构:弥散加权MRI研究的系统回顾。
Pub Date : 2023-01-01 DOI: 10.3389/fnimg.2023.1129587
Emily Anne Robinson, John Gleeson, Arush Honnedevasthana Arun, Adam Clemente, Alexandra Gaillard, Maria Gloria Rossetti, Paolo Brambilla, Marcella Bellani, Camilla Crisanti, H Valerie Curran, Valentina Lorenzetti

Introduction: Cannabis is the most widely used regulated substance by youth and adults. Cannabis use has been associated with psychosocial problems, which have been partly ascribed to neurobiological changes. Emerging evidence to date from diffusion-MRI studies shows that cannabis users compared to controls show poorer integrity of white matter fibre tracts, which structurally connect distinct brain regions to facilitate neural communication. However, the most recent evidence from diffusion-MRI studies thus far has yet to be integrated. Therefore, it is unclear if white matter differences in cannabis users are evident consistently in selected locations, in specific diffusion-MRI metrics, and whether these differences in metrics are associated with cannabis exposure levels.

Methods: We systematically reviewed the results from diffusion-MRI imaging studies that compared white matter differences between cannabis users and controls. We also examined the associations between cannabis exposure and other behavioral variables due to changes in white matter. Our review was pre-registered in PROSPERO (ID: 258250; https://www.crd.york.ac.uk/prospero/).

Results: We identified 30 diffusion-MRI studies including 1,457 cannabis users and 1,441 controls aged 16-to-45 years. All but 6 studies reported group differences in white matter integrity. The most consistent differences between cannabis users and controls were lower fractional anisotropy within the arcuate/superior longitudinal fasciculus (7 studies), and lower fractional anisotropy of the corpus callosum (6 studies) as well as higher mean diffusivity and trace (4 studies). Differences in fractional anisotropy were associated with cannabis use onset (4 studies), especially in the corpus callosum (3 studies).

Discussion: The mechanisms underscoring white matter differences are unclear, and they may include effects of cannabis use onset during youth, neurotoxic effects or neuro adaptations from regular exposure to tetrahydrocannabinol (THC), which exerts its effects by binding to brain receptors, or a neurobiological vulnerability predating the onset of cannabis use. Future multimodal neuroimaging studies, including recently developed advanced diffusion-MRI metrics, can be used to track cannabis users over time and to define with precision when and which region of the brain the white matter changes commence in youth cannabis users, and whether cessation of use recovers white matter differences.

Systematic review registration: www.crd.york.ac.uk/prospero/, identifier: 258250.

大麻是青少年和成年人最广泛使用的管制物质。大麻的使用与社会心理问题有关,这在一定程度上归因于神经生物学的变化。迄今为止,来自扩散核磁共振成像研究的新证据表明,与对照组相比,大麻使用者的白质纤维束的完整性较差,而白质纤维束在结构上连接不同的大脑区域,以促进神经交流。然而,迄今为止,来自弥散mri研究的最新证据尚未得到整合。因此,目前尚不清楚大麻使用者的白质差异是否在特定的扩散- mri指标中一致明显,以及这些指标的差异是否与大麻暴露水平有关。方法:我们系统地回顾了扩散mri成像研究的结果,比较了大麻使用者和对照组之间的白质差异。我们还研究了大麻暴露与白质变化引起的其他行为变量之间的关系。我们的综述在PROSPERO预注册(ID: 258250;https://www.crd.york.ac.uk/prospero/).Results:我们确定了30项弥散mri研究,包括1457名大麻使用者和1441名16至45岁的对照组。除了6项研究外,所有研究都报告了白质完整性的组间差异。大麻使用者和对照组之间最一致的差异是弓形/上纵束的分数各向异性较低(7项研究),胼胝体的分数各向异性较低(6项研究),以及较高的平均扩散率和痕迹(4项研究)。分数各向异性的差异与大麻的使用有关(4项研究),特别是在胼胝体中(3项研究)。讨论:强调白质差异的机制尚不清楚,可能包括青年时期开始使用大麻的影响,定期接触四氢大麻酚(THC)的神经毒性作用或神经适应性,THC通过与大脑受体结合发挥作用,或者在开始使用大麻之前存在神经生物学脆弱性。未来的多模态神经成像研究,包括最近开发的先进弥散- mri指标,可用于长期跟踪大麻使用者,并精确定义青年大麻使用者的大脑白质变化何时和哪个区域开始,以及停止使用是否恢复白质差异。系统评审注册:www.crd.york.ac.uk/prospero/,标识符:258250。
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引用次数: 1
Editorial: Deep learning in neuroimaging-based neurological disease analysis. 社论:基于神经成像的神经疾病分析中的深度学习。
Pub Date : 2023-01-01 DOI: 10.3389/fnimg.2023.1127719
Xiaoxiao Li, Yu Zhang, Qingyu Zhao
COPYRIGHT © 2023 Li, Zhang and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Deep learning in neuroimaging-based neurological disease analysis
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引用次数: 0
Generating dynamic carbon-dioxide traces from respiration-belt recordings: Feasibility using neural networks and application in functional magnetic resonance imaging. 从呼吸带记录中生成动态二氧化碳痕迹:使用神经网络和在功能磁共振成像中的应用的可行性。
Pub Date : 2023-01-01 DOI: 10.3389/fnimg.2023.1119539
Vismay Agrawal, Xiaole Z Zhong, J Jean Chen

Introduction: In the context of functional magnetic resonance imaging (fMRI), carbon dioxide (CO2) is a well-known vasodilator that has been widely used to monitor and interrogate vascular physiology. Moreover, spontaneous fluctuations in end-tidal carbon dioxide (PETCO2) reflects changes in arterial CO2 and has been demonstrated as the largest physiological noise source for denoising the low-frequency range of the resting-state fMRI (rs-fMRI) signal. However, the majority of rs-fMRI studies do not involve CO2 recordings, and most often only heart rate and respiration are recorded. While the intrinsic link between these latter metrics and CO2 led to suggested possible analytical models, they have not been widely applied.

Methods: In this proof-of-concept study, we propose a deep-learning (DL) approach to reconstruct CO2 and PETCO2 data from respiration waveforms in the resting state.

Results: We demonstrate that the one-to-one mapping between respiration and CO2 recordings can be well predicted using fully convolutional networks (FCNs), achieving a Pearson correlation coefficient (r) of 0.946 ± 0.056 with the ground truth CO2. Moreover, dynamic PETCO2 can be successfully derived from the predicted CO2, achieving r of 0.512 ± 0.269 with the ground truth. Importantly, the FCN-based methods outperform previously proposed analytical methods. In addition, we provide guidelines for quality assurance of respiration recordings for the purposes of CO2 prediction.

Discussion: Our results demonstrate that dynamic CO2 can be obtained from respiration-volume using neural networks, complementing the still few reports in DL of physiological fMRI signals, and paving the way for further research in DL based bio-signal processing.

简介:在功能磁共振成像(fMRI)的背景下,二氧化碳(CO2)是一种众所周知的血管扩张剂,已被广泛用于监测和询问血管生理。此外,潮汐末二氧化碳(PETCO2)的自发波动反映了动脉二氧化碳的变化,并已被证明是最大的生理噪声源,用于去噪静息状态fMRI (rs-fMRI)信号的低频范围。然而,大多数rs-fMRI研究不涉及二氧化碳记录,大多数情况下只记录心率和呼吸。虽然后一种量度与二氧化碳之间的内在联系导致提出了可能的分析模型,但它们尚未得到广泛应用。方法:在这个概念验证研究中,我们提出了一种深度学习(DL)方法来重建静息状态下呼吸波形的CO2和PETCO2数据。结果:我们证明,呼吸和二氧化碳记录之间的一对一映射可以使用全卷积网络(fcv)很好地预测,与地面真实CO2的Pearson相关系数(r)为0.946±0.056。此外,动态PETCO2可以成功地从预测的CO2中导出,与地面真值的r值为0.512±0.269。重要的是,基于fcn的方法优于先前提出的分析方法。此外,我们还提供了用于二氧化碳预测目的的呼吸记录质量保证指南。讨论:我们的研究结果表明,利用神经网络可以从呼吸量中获得动态CO2,补充了生理fMRI信号的深度学习报道,并为进一步研究基于深度学习的生物信号处理铺平了道路。
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引用次数: 0
Toward deep learning replacement of gadolinium in neuro-oncology: A review of contrast-enhanced synthetic MRI. 神经肿瘤学中钆的深度学习替代:对比增强合成MRI的综述。
Pub Date : 2023-01-01 DOI: 10.3389/fnimg.2023.1055463
Elisa Moya-Sáez, Rodrigo de Luis-García, Carlos Alberola-López

Gadolinium-based contrast agents (GBCAs) have become a crucial part of MRI acquisitions in neuro-oncology for the detection, characterization and monitoring of brain tumors. However, contrast-enhanced (CE) acquisitions not only raise safety concerns, but also lead to patient discomfort, the need of more skilled manpower and cost increase. Recently, several proposed deep learning works intend to reduce, or even eliminate, the need of GBCAs. This study reviews the published works related to the synthesis of CE images from low-dose and/or their native -non CE- counterparts. The data, type of neural network, and number of input modalities for each method are summarized as well as the evaluation methods. Based on this analysis, we discuss the main issues that these methods need to overcome in order to become suitable for their clinical usage. We also hypothesize some future trends that research on this topic may follow.

钆基对比剂(gbca)已成为神经肿瘤学MRI采集的重要组成部分,用于检测、表征和监测脑肿瘤。然而,对比增强(CE)采集不仅会引起安全问题,而且会导致患者不适,需要更多熟练的人力和成本增加。最近,一些提出的深度学习工作打算减少甚至消除对gbca的需求。本研究回顾了已发表的有关低剂量和/或其天然非CE对应物合成CE图像的研究成果。总结了每种方法的数据、神经网络类型、输入模态数量以及评估方法。在此基础上,我们讨论了这些方法需要克服的主要问题,以使其适合临床使用。我们还假设了关于这一主题的研究可能遵循的一些未来趋势。
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引用次数: 0
Resting-State fMRI Can Detect Alterations in Seizure Onset and Spread Regions in Patients with Non-Lesional Epilepsy: A Pilot Study. 静息状态fMRI可以检测非病变性癫痫患者癫痫发作和扩散区域的改变:一项初步研究。
Pub Date : 2023-01-01 DOI: 10.3389/fnimg.2023.1109546
Anish V Sathe, Caio M Matias, Michael Kogan, Isaiah Ailes, Mashaal Syed, KiChang Kang, Jingya Miao, Kiran Talekar, Scott Faro, Feroze B Mohamed, Joseph Tracy, Ashwini Sharan, Mahdi Alizadeh

Introduction: Epilepsy is defined as non-lesional (NLE) when a lesion cannot be localized via standard neuroimaging. NLE is known to have a poor response to surgery. Stereotactic electroencephalography (sEEG) can detect functional connectivity (FC) between zones of seizure onset (OZ) and early (ESZ) and late (LSZ) spread. We examined whether resting-state fMRI (rsfMRI) can detect FC alterations in NLE to see whether noninvasive imaging techniques can localize areas of seizure propagation to potentially target for intervention.

Methods: This is a retrospective study of 8 patients with refractory NLE who underwent sEEG electrode implantation and 10 controls. The OZ, ESZ, and LSZ were identified by generating regions around sEEG contacts that recorded seizure activity. Amplitude synchronization analysis was used to detect the correlation of the OZ to the ESZ. This was also done using the OZ and ESZ of each NLE patient for each control. Patients with NLE were compared to controls individually using Wilcoxon tests and as a group using Mann-Whitney tests. Amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree of centrality (DoC), and voxel-mirrored homotopic connectivity (VMHC) were calculated as the difference between NLE and controls and compared between the OZ and ESZ and to zero. A general linear model was used with age as a covariate with Bonferroni correction for multiple comparisons.

Results: Five out of 8 patients with NLE showed decreased correlations from the OZ to the ESZ. Group analysis showed patients with NLE had lower connectivity with the ESZ. Patients with NLE showed higher fALFF and ReHo in the OZ but not the ESZ, and higher DoC in the OZ and ESZ. Our results indicate that patients with NLE show high levels of activity but dysfunctional connections in seizure-related areas.

Discussion: rsfMRI analysis showed decreased connectivity directly between seizure-related areas, while FC metric analysis revealed increases in local and global connectivity in seizure-related areas. FC analysis of rsfMRI can detect functional disruption that may expose the pathophysiology underlying NLE.

简介:当病变不能通过标准神经成像定位时,癫痫被定义为非病变性(NLE)。众所周知,NLE对手术的反应很差。立体定向脑电图(sEEG)可以检测癫痫发作区(OZ)与早期(ESZ)和晚期(LSZ)扩散区之间的功能连通性(FC)。我们研究了静息状态功能磁共振成像(rsfMRI)是否可以检测NLE中FC的改变,以观察非侵入性成像技术是否可以定位癫痫发作传播区域,从而成为潜在的干预目标。方法:对8例接受sEEG电极植入的难治性NLE患者和10例对照患者进行回顾性研究。通过在sEEG接触点周围生成记录癫痫发作活动的区域来识别OZ、ESZ和LSZ。振幅同步分析用于检测OZ与ESZ的相关性。这也是使用每个NLE患者的每个对照的OZ和ESZ完成的。NLE患者与对照组分别使用Wilcoxon试验和Mann-Whitney试验进行比较。低频波动幅度(ALFF)、分数ALFF (fALFF)、区域均匀性(ReHo)、中心性度(DoC)和体素镜像同伦连通性(VMHC)作为NLE与对照组之间的差异计算,并将OZ与ESZ之间的差异与零进行比较。采用一般线性模型,以年龄为协变量,采用Bonferroni校正进行多重比较。结果:8例NLE患者中有5例显示从OZ到ESZ的相关性降低。组分析显示,NLE患者与ESZ的连通性较低。NLE患者在OZ区有较高的fALFF和ReHo,而在ESZ区没有,在OZ区和ESZ区有较高的DoC。我们的研究结果表明,NLE患者在癫痫相关区域表现出高水平的活动,但功能失调的连接。讨论:rsfMRI分析显示癫痫相关区域之间的直接连通性下降,而FC度量分析显示癫痫相关区域的局部和全局连通性增加。rsfMRI的FC分析可以检测到可能暴露NLE病理生理基础的功能破坏。
{"title":"Resting-State fMRI Can Detect Alterations in Seizure Onset and Spread Regions in Patients with Non-Lesional Epilepsy: A Pilot Study.","authors":"Anish V Sathe,&nbsp;Caio M Matias,&nbsp;Michael Kogan,&nbsp;Isaiah Ailes,&nbsp;Mashaal Syed,&nbsp;KiChang Kang,&nbsp;Jingya Miao,&nbsp;Kiran Talekar,&nbsp;Scott Faro,&nbsp;Feroze B Mohamed,&nbsp;Joseph Tracy,&nbsp;Ashwini Sharan,&nbsp;Mahdi Alizadeh","doi":"10.3389/fnimg.2023.1109546","DOIUrl":"https://doi.org/10.3389/fnimg.2023.1109546","url":null,"abstract":"<p><strong>Introduction: </strong>Epilepsy is defined as non-lesional (NLE) when a lesion cannot be localized via standard neuroimaging. NLE is known to have a poor response to surgery. Stereotactic electroencephalography (sEEG) can detect functional connectivity (FC) between zones of seizure onset (OZ) and early (ESZ) and late (LSZ) spread. We examined whether resting-state fMRI (rsfMRI) can detect FC alterations in NLE to see whether noninvasive imaging techniques can localize areas of seizure propagation to potentially target for intervention.</p><p><strong>Methods: </strong>This is a retrospective study of 8 patients with refractory NLE who underwent sEEG electrode implantation and 10 controls. The OZ, ESZ, and LSZ were identified by generating regions around sEEG contacts that recorded seizure activity. Amplitude synchronization analysis was used to detect the correlation of the OZ to the ESZ. This was also done using the OZ and ESZ of each NLE patient for each control. Patients with NLE were compared to controls individually using Wilcoxon tests and as a group using Mann-Whitney tests. Amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree of centrality (DoC), and voxel-mirrored homotopic connectivity (VMHC) were calculated as the difference between NLE and controls and compared between the OZ and ESZ and to zero. A general linear model was used with age as a covariate with Bonferroni correction for multiple comparisons.</p><p><strong>Results: </strong>Five out of 8 patients with NLE showed decreased correlations from the OZ to the ESZ. Group analysis showed patients with NLE had lower connectivity with the ESZ. Patients with NLE showed higher fALFF and ReHo in the OZ but not the ESZ, and higher DoC in the OZ and ESZ. Our results indicate that patients with NLE show high levels of activity but dysfunctional connections in seizure-related areas.</p><p><strong>Discussion: </strong>rsfMRI analysis showed decreased connectivity directly between seizure-related areas, while FC metric analysis revealed increases in local and global connectivity in seizure-related areas. FC analysis of rsfMRI can detect functional disruption that may expose the pathophysiology underlying NLE.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10194331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9496973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial: Brain imaging techniques to measure treatment related effect. 社论:脑成像技术测量治疗相关效果。
Pub Date : 2023-01-01 DOI: 10.3389/fnimg.2023.1238295
Natalie M Zahr, Assaf Harel, Efrat Sasson
COPYRIGHT © 2023 Zahr, Harel and Sasson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Brain imaging techniques to measure treatment related e ect
{"title":"Editorial: Brain imaging techniques to measure treatment related effect.","authors":"Natalie M Zahr,&nbsp;Assaf Harel,&nbsp;Efrat Sasson","doi":"10.3389/fnimg.2023.1238295","DOIUrl":"https://doi.org/10.3389/fnimg.2023.1238295","url":null,"abstract":"COPYRIGHT © 2023 Zahr, Harel and Sasson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Brain imaging techniques to measure treatment related e ect","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"2 ","pages":"1238295"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10332276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum: autohrf-an R package for generating data-informed event models for general linear modeling of task-based fMRI data. 更正:autohrf-一个R包,用于生成数据知情的事件模型,用于基于任务的fMRI数据的一般线性建模。
Pub Date : 2023-01-01 DOI: 10.3389/fnimg.2023.1158159
Nina Purg, Jure Demšar, Alan Anticevic, Grega Repovš

[This corrects the article DOI: 10.3389/fnimg.2022.983324.].

[这更正了文章DOI: 10.3389/fnimg.2022.983324.]。
{"title":"Corrigendum: autohrf-an R package for generating data-informed event models for general linear modeling of task-based fMRI data.","authors":"Nina Purg,&nbsp;Jure Demšar,&nbsp;Alan Anticevic,&nbsp;Grega Repovš","doi":"10.3389/fnimg.2023.1158159","DOIUrl":"https://doi.org/10.3389/fnimg.2023.1158159","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnimg.2022.983324.].</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"2 ","pages":"1158159"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10332277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Imaging mitochondria through bone in live mice using two-photon fluorescence microscopy with adaptive optics. 利用自适应光学双光子荧光显微镜对活小鼠骨内线粒体成像。
Pub Date : 2023-01-01 DOI: 10.3389/fnimg.2023.959601
Tianyi Zheng, Adrian R Liversage, Kayvan F Tehrani, Jarrod A Call, Peter A Kner, Luke J Mortensen

Introduction: Mitochondria are extremely important organelles in the regulation of bone marrow and brain activity. However, live imaging of these subcellular features with high resolution in scattering tissues like brain or bone has proven challenging.

Methods: In this study, we developed a two-photon fluorescence microscope with adaptive optics (TPFM-AO) for high-resolution imaging, which uses a home-built Shack-Hartmann wavefront sensor (SHWFS) to correct system aberrations and a sensorless approach for correcting low order tissue aberrations.

Results: Using AO increases the fluorescence intensity of the point spread function (PSF) and achieves fast imaging of subcellular organelles with 400 nm resolution through 85 μm of highly scattering tissue. We achieved ~1.55×, ~3.58×, and ~1.77× intensity increases using AO, and a reduction of the PSF width by ~0.83×, ~0.74×, and ~0.9× at the depths of 0, 50 μm and 85 μm in living mouse bone marrow respectively, allowing us to characterize mitochondrial health and the survival of functioning cells with a field of view of 67.5× 67.5 μm. We also investigate the role of initial signal and background levels in sample correction quality by varying the laser power and camera exposure time and develop an intensity-based criteria for sample correction.

Discussion: This study demonstrates a promising tool for imaging of mitochondria and other organelles in optically distorting biological environments, which could facilitate the study of a variety of diseases connected to mitochondrial morphology and activity in a range of biological tissues.

线粒体是调节骨髓和大脑活动的极其重要的细胞器。然而,在脑或骨等分散组织中对这些亚细胞特征进行高分辨率的实时成像被证明是具有挑战性的。方法:采用自制的Shack-Hartmann波前传感器(SHWFS)校正系统像差,采用无传感器校正低阶组织像差的方法,研制了一种高分辨率自适应光学双光子荧光显微镜(TPFM-AO)。结果:AO提高了点扩散函数(PSF)的荧光强度,通过85 μm的高散射组织实现了400 nm分辨率的亚细胞细胞器快速成像。我们在活体小鼠骨髓的0、50 μm和85 μm深度分别实现了~1.55×、~3.58×和~1.77×的强度增加,PSF宽度分别减少了~0.83×、~0.74×和~0.9×,使我们能够在67.5× 67.5 μm的视野范围内表征线粒体健康和功能细胞的存活。我们还通过改变激光功率和相机曝光时间来研究初始信号和背景水平在样品校正质量中的作用,并制定了基于强度的样品校正标准。讨论:这项研究展示了一种在光学扭曲的生物环境中对线粒体和其他细胞器进行成像的有前途的工具,这可能有助于研究一系列生物组织中与线粒体形态和活性相关的各种疾病。
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引用次数: 0
Resting-state functional MRI in treatment-resistant schizophrenia. 难治性精神分裂症的静息状态功能MRI。
Pub Date : 2023-01-01 DOI: 10.3389/fnimg.2023.1127508
Noora Tuovinen, Alex Hofer

Background: Abnormalities in brain regions involved in the pathophysiology of schizophrenia (SCZ) may present insight into individual clinical symptoms. Specifically, functional connectivity irregularities may provide potential biomarkers for treatment response or treatment resistance, as such changes can occur before any structural changes are visible. We reviewed resting-state functional magnetic resonance imaging (rs-fMRI) findings from the last decade to provide an overview of the current knowledge on brain functional connectivity abnormalities and their associations to symptoms in treatment-resistant schizophrenia (TRS) and ultra-treatment-resistant schizophrenia (UTRS) and to look for support for the dysconnection hypothesis.

Methods: PubMed database was searched for articles published in the last 10 years applying rs-fMRI in TRS patients, i.e., who had not responded to at least two adequate treatment trials with different antipsychotic drugs.

Results: Eighteen articles were selected for this review involving 648 participants (TRS and control cohorts). The studies showed frontal hypoconnectivity before the initiation of treatment with CLZ or riluzole, an increase in frontal connectivity after riluzole treatment, fronto-temporal hypoconnectivity that may be specific for non-responders, widespread abnormal connectivity during mixed treatments, and ECT-induced effects on the limbic system.

Conclusion: Probably due to the heterogeneity in the patient cohorts concerning antipsychotic treatment and other clinical variables (e.g., treatment response, lifetime antipsychotic drug exposure, duration of illness, treatment adherence), widespread abnormalities in connectivity were noted. However, irregularities in frontal brain regions, especially in the prefrontal cortex, were noted which are consistent with previous SCZ literature and the dysconnectivity hypothesis. There were major limitations, as most studies did not differentiate between TRS and UTRS (i.e., CLZ-resistant schizophrenia) and investigated heterogeneous cohorts treated with mixed treatments (with or without CLZ). This is critical as in different subtypes of the disorder an interplay between dopaminergic and glutamatergic pathways involving frontal, striatal, and hippocampal brain regions in separate ways is likely. Better definitions of TRS and UTRS are necessary in future longitudinal studies to correctly differentiate brain regions underlying the pathophysiology of SCZ, which could serve as potential functional biomarkers for treatment resistance.

背景:参与精神分裂症(SCZ)病理生理的大脑区域的异常可能为个体临床症状提供见解。具体来说,功能连接异常可能为治疗反应或治疗耐药性提供潜在的生物标志物,因为这些变化可能在任何结构变化可见之前发生。我们回顾了过去十年静息状态功能磁共振成像(rs-fMRI)的发现,概述了目前对脑功能连接异常及其与治疗抵抗性精神分裂症(TRS)和超治疗抵抗性精神分裂症(UTRS)症状的关系的了解,并寻找连接异常假说的支持。方法:检索PubMed数据库,检索近10年来发表的应用rs-fMRI治疗TRS患者的文章,即对至少两种不同抗精神病药物治疗试验没有反应的患者。结果:本综述选择了18篇文章,涉及648名参与者(TRS和对照队列)。研究显示,在CLZ或利鲁唑治疗开始前,额叶连通性低下,利鲁唑治疗后额叶连通性增加,额颞叶连通性低下可能是无反应者特有的,混合治疗期间广泛的异常连通性,以及ect诱导的边缘系统影响。结论:可能由于患者队列在抗精神病药物治疗和其他临床变量(如治疗反应、终生抗精神病药物暴露、疾病持续时间、治疗依从性)方面的异质性,注意到广泛的连接异常。然而,在大脑额叶区域,特别是在前额叶皮层的不规则性被注意到,这与先前的SCZ文献和连接障碍假说一致。主要的局限性是,大多数研究没有区分TRS和UTRS(即CLZ抗性精神分裂症),并且调查了使用混合治疗(含或不含CLZ)的异质队列。这是至关重要的,因为在该疾病的不同亚型中,多巴胺能和谷氨酸能通路可能以不同的方式相互作用,涉及额叶、纹状体和海马脑区域。在未来的纵向研究中,更好地定义TRS和UTRS是必要的,以正确区分SCZ病理生理背后的大脑区域,这可能作为治疗耐药性的潜在功能生物标志物。
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引用次数: 0
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Frontiers in neuroimaging
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