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Probing hippocampal stimulation in experimental temporal lobe epilepsy with functional MRI. 用功能磁共振成像探究实验性颞叶癫痫的海马刺激。
Pub Date : 2024-08-14 eCollection Date: 2024-01-01 DOI: 10.3389/fnimg.2024.1423770
Niels Schwaderlapp, Enya Paschen, Pierre LeVan, Dominik von Elverfeldt, Carola A Haas

Electrical neurostimulation is currently used to manage epilepsy, but the most effective approach for minimizing seizure occurrence is uncertain. While functional MRI (fMRI) can reveal which brain areas are affected by stimulation, simultaneous deep brain stimulation (DBS)-fMRI examinations in patients are rare and the possibility to investigate multiple stimulation protocols is limited. In this study, we utilized the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy (mTLE) to systematically examine the brain-wide responses to electrical stimulation using fMRI. We compared fMRI responses of saline-injected controls and epileptic mice during stimulation in the septal hippocampus (HC) at 10 Hz and demonstrated the effects of different stimulation amplitudes (80-230 μA) and frequencies (1-100 Hz) in epileptic mice. Motivated by recent studies exploring 1 Hz stimulation to prevent epileptic seizures, we furthermore investigated the effect of prolonged 1 Hz stimulation with fMRI. Compared to sham controls, epileptic mice showed less propagation to the contralateral HC, but significantly stronger responses in the ipsilateral HC and a wider spread to the entorhinal cortex and septal region. Varying the stimulation amplitude had little effect on the resulting activation patterns, whereas the stimulation frequency represented the key parameter and determined whether the induced activation remained local or spread from the hippocampal formation into cortical areas. Prolonged stimulation of epileptic mice at 1 Hz caused a slight reduction in local excitability. In this way, our study contributes to a better understanding of these stimulation paradigms.

目前,神经电刺激被用于控制癫痫,但最大限度减少癫痫发作的最有效方法尚不确定。虽然功能磁共振成像(fMRI)可以揭示哪些脑区受到刺激的影响,但同时对患者进行脑深部刺激(DBS)-fMRI检查的情况并不多见,而且研究多种刺激方案的可能性也很有限。在这项研究中,我们利用海马内凯恩酸盐中位颞叶癫痫(mTLE)小鼠模型,使用 fMRI 系统地检查了全脑对电刺激的反应。我们比较了生理盐水注射对照组和癫痫小鼠在隔侧海马(HC)受到 10 Hz 刺激时的 fMRI 反应,并证明了不同刺激幅度(80-230 μA)和频率(1-100 Hz)对癫痫小鼠的影响。最近有研究探索用 1 赫兹刺激来预防癫痫发作,受此启发,我们进一步用 fMRI 研究了长时间 1 赫兹刺激的效果。与假对照组相比,癫痫小鼠对对侧大脑皮质的传播较少,但对同侧大脑皮质的反应明显较强,对内侧皮质和隔区的传播也较广。改变刺激幅度对所产生的激活模式影响不大,而刺激频率则是关键参数,它决定了诱导的激活是保持在局部还是从海马形成扩散到皮层区域。对癫痫小鼠进行1赫兹的长时间刺激会导致局部兴奋性略微降低。因此,我们的研究有助于更好地理解这些刺激范式。
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引用次数: 0
The importance of brain mapping for rehabilitation in birth nonprogressive neuromuscular diseases 脑图谱对出生后非进行性神经肌肉疾病康复的重要性
Pub Date : 2024-07-15 DOI: 10.3389/fnimg.2024.1359491
Aleksandra Tolmacheva, Olga Agranovich, E. Blagovechtchenski
While motor mapping has been extensively studied in acquired motor conditions, a lack has been observed in terms of research on neurological disorders present since birth, with damage to the spinal cord and peripheral nerves (hence, defined in this study as nonprogressive neuromuscular diseases). Despite an injury at the level below the brain, the subsequent changes in the motor system involve cortical reorganization. In the scientific community, the need for a comprehensive approach targeting the brain is increasingly recognized for greater motor recovery in these patients. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are the most utilized techniques for motor mapping. The knowledge obtained through motor mapping may be used to develop effective individual neuromodulation therapy that helps in functional motor recovery. This brief review compares the results of the brain mapping of a few existing studies in individuals with nonprogressive motor disorders of nonbrain origin present at birth to the brain mapping of individuals with similar acquired motor conditions. The review reveals some particular features in terms of central adaptation in individuals with birth conditions compared to their acquired counterparts, such as the nonsomatotopic presentation of involved muscles in the sensorimotor cortex and nonadjacent cortical areas. This topic is undoubtedly intriguing, justifying further research in the field. This review also discusses the benefits these patients can obtain from neuromodulation therapy addressed to the central nervous system and the importance of individual neurophysiological assessment in designing rehabilitation therapy for children with birth motor disorders.
虽然运动图谱对获得性运动病症进行了广泛的研究,但对自出生以来就存在的、脊髓和周围神经受损的神经系统疾病(因此,本研究将其定义为非进行性神经肌肉疾病)的研究却很缺乏。尽管受伤部位在大脑以下,但随后运动系统的变化涉及大脑皮层的重组。在科学界,人们越来越认识到需要一种针对大脑的综合方法来促进这些患者的运动康复。经颅磁刺激(TMS)和功能磁共振成像(fMRI)是最常用的运动图谱绘制技术。通过绘制运动图谱获得的知识可用于开发有效的个体神经调控疗法,帮助患者实现功能性运动恢复。这篇简短的综述将现有的几项研究结果进行了比较,这些研究的对象是出生时即患有非脑源性非进行性运动障碍的患者,以及患有类似后天性运动障碍的患者。与获得性运动障碍患者相比,该综述揭示了先天性运动障碍患者在中枢适应方面的一些特殊特征,如受累肌肉在感觉运动皮层和非相邻皮层区域的非同位呈现。毫无疑问,这一话题非常引人关注,值得在该领域开展进一步研究。本综述还讨论了中枢神经系统神经调控疗法可为这些患者带来的益处,以及个体神经生理学评估在设计先天性运动障碍儿童康复疗法中的重要性。
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引用次数: 0
Dynamic off-resonance correction improves functional image analysis in fMRI of awake behaving non-human primates. 动态非共振校正改进了清醒状态下的非人灵长类 fMRI 功能图像分析。
Pub Date : 2024-06-25 eCollection Date: 2024-01-01 DOI: 10.3389/fnimg.2024.1336887
Mo Shahdloo, Nima Khalighinejad, Luke Priestley, Matthew Rushworth, Mark Chiew

Introduction: Use of functional MRI in awake non-human primate (NHPs) has recently increased. Scanning animals while awake makes data collection possible in the absence of anesthetic modulation and with an extended range of possible experimental designs. Robust awake NHP imaging however is challenging due to the strong artifacts caused by time-varying off-resonance changes introduced by the animal's body motion. In this study, we sought to thoroughly investigate the effect of a newly proposed dynamic off-resonance correction method on brain activation estimates using extended awake NHP data.

Methods: We correct for dynamic B0 changes in reconstruction of highly accelerated simultaneous multi-slice EPI acquisitions by estimating and correcting for dynamic field perturbations. Functional MRI data were collected in four male rhesus monkeys performing a decision-making task in the scanner, and analyses of improvements in sensitivity and reliability were performed compared to conventional image reconstruction.

Results: Applying the correction resulted in reduced bias and improved temporal stability in the reconstructed time-series data. We found increased sensitivity to functional activation at the individual and group levels, as well as improved reliability of statistical parameter estimates.

Conclusions: Our results show significant improvements in image fidelity using our proposed correction strategy, as well as greatly enhanced and more reliable activation estimates in GLM analyses.

介绍:最近,在清醒的非人灵长类动物(NHPs)中使用功能磁共振成像的情况有所增加。在清醒状态下对动物进行扫描,可以在没有麻醉调节的情况下收集数据,并扩大了实验设计的范围。然而,由于动物身体运动带来的时变非共振变化会产生强烈的伪影,因此对清醒状态下的非人灵长类动物进行稳健成像具有挑战性。在这项研究中,我们试图利用扩展的清醒 NHP 数据彻底研究新提出的动态非共振校正方法对大脑激活估计的影响:方法:我们通过估计和校正动态场扰动,在重建高度加速的同步多切片 EPI 采集时校正动态 B0 变化。我们收集了四只雄性恒河猴在扫描仪中执行决策任务时的功能磁共振成像数据,并分析了与传统图像重建相比灵敏度和可靠性的改善情况:结果:采用校正后,重建的时间序列数据偏差减少,时间稳定性提高。我们发现个体和群体层面的功能激活灵敏度提高了,统计参数估计的可靠性也提高了:我们的研究结果表明,使用我们提出的校正策略,图像的保真度有了明显提高,在 GLM 分析中的激活估计值也大大增强,更加可靠。
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引用次数: 0
Neuroimaging evaluation of the long term impact of a novel paired meditation practice on brain function 新型配对冥想练习对大脑功能长期影响的神经影像学评估
Pub Date : 2024-06-10 DOI: 10.3389/fnimg.2024.1368537
Andrew B. Newberg, N. Wintering, Chloe Hriso, Faezeh Vedaei, Sara Gottfried, Reneita Ross
A growing number of advanced neuroimaging studies have compared brain structure and function in long term meditators to non-meditators. The goal is to determine if there may be long term effects on the brain from practicing meditation. In this paper, we present new data on the long term effects of a novel meditation practice in which the focus is on clitoral stimulation. The findings from such a study have implications for potential therapeutic uses with regard to various neurological or psychiatric conditions.We evaluated the cerebral glucose metabolism in 40 subjects with an extended history (>1 year of practice, 2–3 times per week) performing the meditation practice called Orgasmic Meditation (OM) and compared their brains to a group of non-meditating healthy controls (N = 19). Both meditation and non-meditation subjects underwent brain PET after injection with 148 to 296 MBq of FDG using a standard imaging protocol. Resting FDG PET scans of the OM group were compared to the resting scans of healthy, non-meditating, controls using statistical parametric mapping.The OM group showed significant differences in metabolic activity at rest compared to the controls. Specifically, there was significantly lower metabolism in select areas of the frontal, temporal, and parietal lobes, as well as the anterior cingulate, insula, and thalamus, in the OM group compared to the controls. In addition, there were notable distinctions between the males and females with the females demonstrating significantly lower metabolism in the thalamus and insula.Overall, these findings suggest that the long term meditation practitioners of OM have different patterns of resting brain metabolism. Since these areas of the brain in which OM practitioners differ from controls are involved in cognition, attention, and emotional regulation, such findings have implications for understanding how this meditation practice might affect practitioners over long periods of time.
越来越多的高级神经成像研究对长期冥想者和非冥想者的大脑结构和功能进行了比较。目的是确定冥想练习是否会对大脑产生长期影响。在本文中,我们介绍了一种新的冥想练习的长期影响的新数据,这种冥想练习的重点是阴蒂刺激。我们评估了 40 名长期(超过 1 年的练习时间,每周 2-3 次)进行名为 "高潮冥想"(OM)的冥想练习的受试者的大脑葡萄糖代谢情况,并将他们的大脑与一组未进行冥想的健康对照组(N = 19)进行了比较。冥想和非冥想受试者在注射 148 至 296 MBq 的 FDG 后,都按照标准成像方案进行了脑 PET 扫描。使用统计参数映射法将 OM 组的静息 FDG PET 扫描与非冥想健康对照组的静息扫描进行比较。具体来说,与对照组相比,OM 组的额叶、颞叶、顶叶以及前扣带回、岛叶和丘脑等特定区域的代谢率明显较低。此外,男性和女性之间也有明显区别,女性丘脑和岛叶的新陈代谢明显较低。总之,这些研究结果表明,OM 的长期冥想练习者具有不同的静息大脑新陈代谢模式。由于 OM 练习者与对照组不同的这些大脑区域涉及认知、注意力和情绪调节,因此这些发现对于了解这种冥想练习如何长期影响练习者具有重要意义。
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引用次数: 0
3D inversion recovery ultrashort echo time MRI can detect demyelination in cuprizone-treated mice. 三维反转恢复超短回波时间核磁共振成像可检测铜绿素治疗小鼠的脱髓鞘现象。
Pub Date : 2024-05-09 eCollection Date: 2024-01-01 DOI: 10.3389/fnimg.2024.1356713
Adam C Searleman, Yajun Ma, Srihari Sampath, Srinath Sampath, Robert Bussell, Eric Y Chang, Lisa Deaton, Andrew M Schumacher, Jiang Du

Purpose: To test the ability of inversion-recovery ultrashort echo time (IR-UTE) MRI to directly detect demyelination in mice using a standard cuprizone mouse model.

Methods: Non-aqueous myelin protons have ultrashort T2s and are "invisible" with conventional MRI sequences but can be detected with UTE sequences. The IR-UTE sequence uses an adiabatic inversion-recovery preparation to suppress the long T2 water signal so that the remaining signal is from the ultrashort T2 myelin component. In this study, eight 8-week-old C57BL/6 mice were fed cuprizone (n = 4) or control chow (n = 4) for 5 weeks and then imaged by 3D IR-UTE MRI. The differences in IR-UTE signal were compared in the major white matter tracts in the brain and correlated with the Luxol Fast Blue histochemical marker of myelin.

Results: IR-UTE signal decreased in cuprizone-treated mice in white matter known to be sensitive to demyelination in this model, such as the corpus callosum, but not in white matter known to be resistant to demyelination, such as the internal capsule. These findings correlated with histochemical staining of myelin content.

Conclusions: 3D IR-UTE MRI was sensitive to cuprizone-induced demyelination in the mouse brain, and is a promising noninvasive method for measuring brain myelin content.

目的:测试反转恢复超短回波时间(IR-UTE)核磁共振成像(MRI)使用标准铜绿素小鼠模型直接检测小鼠脱髓鞘的能力:方法:非水髓鞘质子具有超短 T2,在传统磁共振成像序列中 "看不见",但在 UTE 序列中可以检测到。IR-UTE序列使用绝热反转恢复准备来抑制长T2水信号,使剩余信号来自超短T2髓鞘成分。在这项研究中,8只8周大的C57BL/6小鼠被喂食铜绿素(n = 4)或对照组饲料(n = 4)5周,然后通过三维IR-UTE MRI成像。比较了大脑主要白质束中 IR-UTE 信号的差异,并将其与髓鞘的 Luxol Fast Blue 组织化学标记物相关联:结果:经杯三氮处理的小鼠,在该模型中对脱髓鞘敏感的白质(如胼胝体)中,IR-UTE信号下降,而在对脱髓鞘有抵抗力的白质(如内囊)中,IR-UTE信号则没有下降。这些发现与髓鞘含量的组织化学染色结果相关:结论:三维红外UTE磁共振成像对铜绿素诱导的小鼠大脑脱髓鞘很敏感,是一种很有前途的测量大脑髓鞘含量的无创方法。
{"title":"3D inversion recovery ultrashort echo time MRI can detect demyelination in cuprizone-treated mice.","authors":"Adam C Searleman, Yajun Ma, Srihari Sampath, Srinath Sampath, Robert Bussell, Eric Y Chang, Lisa Deaton, Andrew M Schumacher, Jiang Du","doi":"10.3389/fnimg.2024.1356713","DOIUrl":"10.3389/fnimg.2024.1356713","url":null,"abstract":"<p><strong>Purpose: </strong>To test the ability of inversion-recovery ultrashort echo time (IR-UTE) MRI to directly detect demyelination in mice using a standard cuprizone mouse model.</p><p><strong>Methods: </strong>Non-aqueous myelin protons have ultrashort T<sub>2</sub>s and are \"invisible\" with conventional MRI sequences but can be detected with UTE sequences. The IR-UTE sequence uses an adiabatic inversion-recovery preparation to suppress the long T<sub>2</sub> water signal so that the remaining signal is from the ultrashort T<sub>2</sub> myelin component. In this study, eight 8-week-old C57BL/6 mice were fed cuprizone (<i>n</i> = 4) or control chow (<i>n</i> = 4) for 5 weeks and then imaged by 3D IR-UTE MRI. The differences in IR-UTE signal were compared in the major white matter tracts in the brain and correlated with the Luxol Fast Blue histochemical marker of myelin.</p><p><strong>Results: </strong>IR-UTE signal decreased in cuprizone-treated mice in white matter known to be sensitive to demyelination in this model, such as the corpus callosum, but not in white matter known to be resistant to demyelination, such as the internal capsule. These findings correlated with histochemical staining of myelin content.</p><p><strong>Conclusions: </strong>3D IR-UTE MRI was sensitive to cuprizone-induced demyelination in the mouse brain, and is a promising noninvasive method for measuring brain myelin content.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"3 ","pages":"1356713"},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089409","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: A structural connectivity atlas of limbic brainstem nuclei. 更正:边缘脑干核团结构连接图谱。
Pub Date : 2024-04-30 eCollection Date: 2024-01-01 DOI: 10.3389/fnimg.2024.1405806
Simon Levinson, Michelle Miller, Ahmed Iftekhar, Monica Justo, Daniel Arriola, Wenxin Wei, Saman Hazany, Josue M Avecillas-Chasin, Taylor P Kuhn, Andreas Horn, Ausaf A Bari

[This corrects the article DOI: 10.3389/fnimg.2022.1009399.].

[This corrects the article DOI: 10.3389/fnimg.2022.1009399.].
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引用次数: 0
Construction and evaluation of a neurofeedback system using finger tapping and near-infrared spectroscopy 利用手指敲击和近红外光谱构建和评估神经反馈系统
Pub Date : 2024-04-25 DOI: 10.3389/fnimg.2024.1361513
Shingo Takahashi, Daishi Takahashi, Yuki Kuroiwa, Noriko Sakurai, Naoki Kodama
Neurofeedback using near-infrared spectroscopy (NIRS) has been used in patients with stroke and other patients, but few studies have included older people or patients with cognitive impairment.We constructed a NIRS-based neurofeedback system and used finger tapping to investigate whether neurofeedback can be implemented in older adults while finger tapping and whether brain activity improves in older adults and healthy participants. Our simple neurofeedback system was constructed using a portable wearable optical topography (WOT-HS) device. Brain activity was evaluated in 10 older and 31 healthy young individuals by measuring oxygenated hemoglobin concentration during finger tapping and neurofeedback implementation.During neurofeedback, the concentration of oxygenated hemoglobin increased in the prefrontal regions in both the young and older participants.The results of this study demonstrate the usefulness of neurofeedback using simple NIRS devices for older adults and its potential to mitigate cognitive decline.
我们构建了一个基于近红外光谱(NIRS)的神经反馈系统,并使用手指敲击来研究是否可以在老年人手指敲击时实施神经反馈,以及老年人和健康参与者的大脑活动是否有所改善。我们使用便携式可穿戴光学地形图(WOT-HS)设备构建了简单的神经反馈系统。通过测量手指敲击和神经反馈实施过程中的氧合血红蛋白浓度,对 10 名老年人和 31 名健康年轻人的大脑活动进行了评估。在神经反馈过程中,年轻人和老年人前额叶区域的氧合血红蛋白浓度都有所增加。
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引用次数: 0
Evaluation of partial volume correction and analysis of longitudinal [18F]GTP1 tau PET imaging in Alzheimer's disease using linear mixed-effects models 使用线性混合效应模型评估部分体积校正和分析阿尔茨海默病的纵向[18F]GTP1 tau PET 成像
Pub Date : 2024-03-28 DOI: 10.3389/fnimg.2024.1355402
S. S. Sanabria Bohórquez, Suzanne Baker, P. Manser, Matteo Tonietto, Christopher Galli, Kristin R. Wildsmith, Yixuan Zou, G. Kerchner, R. Weimer, E. Teng
We evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [18F]GTP1 tau positron-emission tomography (PET) in Alzheimer's disease and the suitability of describing the tau pathology burden temporal trajectories using linear mixed-effects models (LMEM).We applied van Cittert iterative deconvolution (VC), 2-compartment, and 3-compartment, and the geometric transfer matrix plus region-based voxelwise methods to data acquired in an Alzheimer's disease natural history study over 18 months at a single imaging site. We determined the optimal PVC method by comparing the standardized uptake value ratio change (%ΔSUVR) between diagnostic and tau burden–level groups and the longitudinal repeatability derived from the LMEM. The performance of LMEM analysis for calculating %ΔSUVR was evaluated in a natural history study and in a multisite clinical trial of semorinemab in prodromal to mild Alzheimer's disease by comparing results to traditional per-visit estimates.The VC, 2-compartment, and 3-compartment PVC methods had similar performance, whereas region-based voxelwise overcorrected regions with a higher tau burden. The lowest within-subject variability and acceptable group separation scores were observed without PVC. The LMEM-derived %ΔSUVR values were similar to the per-visit estimates with lower variability.The results indicate that the tested PVC methods do not offer a clear advantage or improvement over non-PVC images for the quantification of longitudinal [18F]GTP1 PET data. LMEM offers a robust framework for the longitudinal tau PET quantification with low longitudinal test–retest variability.NCT02640092 and NCT03289143.
我们评估了部分容积校正(PVC)方法对阿尔茨海默病纵向[18F]GTP1 tau正电子发射断层扫描(PET)量化的影响,以及使用线性混合效应模型(LMEM)描述tau病理负担时间轨迹的适宜性。我们将 Van Cittert 迭代解卷积 (VC)、2 室和 3 室以及几何转移矩阵加基于区域的体素方法应用于一项阿尔茨海默病自然史研究中在单个成像站点获取的 18 个月的数据。我们通过比较诊断组和 tau 负担水平组之间的标准化摄取值比变化(%ΔSUVR)以及 LMEM 得出的纵向可重复性,确定了最佳 PVC 方法。在一项自然史研究和一项针对前驱期至轻度阿尔茨海默病的semorinemab多点临床试验中,通过将结果与传统的每次探访估计值进行比较,评估了LMEM分析法计算%ΔSUVR的性能。在不使用PVC的情况下,受试者内变异性最低,组间分离得分也可接受。结果表明,在纵向[18F]GTP1 PET 数据的量化方面,测试的 PVC 方法与非 PVC 图像相比没有明显的优势或改进。LMEM为纵向tau PET量化提供了一个稳健的框架,纵向测试-再测试变异性较低。
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引用次数: 0
Down-sampling in diffusion MRI: a bundle-specific DTI and NODDI study 弥散核磁共振成像中的下采样:特定束 DTI 和 NODDI 研究
Pub Date : 2024-03-28 DOI: 10.3389/fnimg.2024.1359589
Federico Spagnolo, Susanna Gobbi, E. Zsoldos, Manon Edde, Matthias Weigel, C. Granziera, Maxime Descoteaux, M. Barakovic, Stefano Magon
Multi-shell diffusion Magnetic Resonance Imaging (dMRI) data has been widely used to characterise white matter microstructure in several neurodegenerative diseases. The lack of standardised dMRI protocols often implies the acquisition of redundant measurements, resulting in prolonged acquisition times. In this study, we investigate the impact of the number of gradient directions on Diffusion Tensor Imaging (DTI) and on Neurite Orientation Dispersion and Density Imaging (NODDI) metrics.Data from 124 healthy controls collected in three different longitudinal studies were included. Using an in-house algorithm, we reduced the number of gradient directions in each data shell. We estimated DTI and NODDI measures on six white matter bundles clinically relevant for neurodegenerative diseases.Fractional Anisotropy (FA) measures on bundles where data were sampled at the 30% rate, showed a median L1 distance of up to 3.92% and a 95% CI of (1.74, 8.97)% when compared to those obtained at reference sampling. Mean Diffusivity (MD) reached up to 4.31% and a 95% CI of (1.60, 16.98)% on the same premises. At a sampling rate of 50%, we obtained a median of 3.90% and a 95% CI of (1.99, 16.65)% in FA, and 5.49% with a 95% CI of (2.14, 21.68)% in MD. The Intra-Cellular volume fraction (ICvf) median L1 distance was up to 2.83% with a 95% CI of (1.98, 4.82)% at a 30% sampling rate and 3.95% with a 95% CI of (2.39, 7.81)% at a 50% sampling rate. The volume difference of the reconstructed white matter at reference and 50% sampling reached a maximum of (2.09 ± 0.81)%.In conclusion, DTI and NODDI measures reported at reference sampling were comparable to those obtained when the number of dMRI volumes was reduced by up to 30%. Close to reference DTI and NODDI metrics were estimated with a significant reduction in acquisition time using three shells, respectively with: 4 directions at a b value of 700 s/mm2, 14 at 1000 s/mm2, and 32 at 2000 s/mm2. The study revealed aspects that can be important for large-scale clinical studies on bundle-specific diffusion MRI.
多壳扩散磁共振成像(dMRI)数据已被广泛用于描述多种神经退行性疾病的白质微观结构特征。由于缺乏标准化的 dMRI 方案,往往需要采集多余的测量数据,导致采集时间延长。在这项研究中,我们调查了梯度方向的数量对扩散张量成像(DTI)和神经元定向弥散与密度成像(NODDI)指标的影响。我们使用内部算法减少了每个数据壳中梯度方向的数量。我们估算了与神经退行性疾病临床相关的六个白质束的 DTI 和 NODDI 测量值。与参考采样时的测量值相比,数据采样率为 30% 的白质束的分数各向异性(FA)测量值显示中位 L1 距离增加了 3.92%,95% CI 为 (1.74, 8.97)%。在同一地点,平均扩散率(MD)高达 4.31%,95% CI 为 (1.60, 16.98)%。在采样率为 50%的情况下,我们得到的 FA 中值为 3.90%,95% CI 为 (1.99, 16.65)%;MD 中值为 5.49%,95% CI 为 (2.14, 21.68)%。细胞内体积分数(ICvf)中位数 L1 距离在采样率为 30% 时为 2.83%,95% CI 为 (1.98, 4.82)%;在采样率为 50% 时为 3.95%,95% CI 为 (2.39, 7.81)%。总之,参考采样时的 DTI 和 NODDI 测量结果与 dMRI 体积数量最多减少 30% 时获得的结果相当。在使用三个壳体的情况下,可显著减少采集时间,分别估算出接近参考的 DTI 和 NODDI 指标:4 个方向的 b 值为 700 s/mm2,14 个方向的 b 值为 1000 s/mm2,32 个方向的 b 值为 2000 s/mm2。该研究揭示了对束特异性弥散磁共振成像大规模临床研究非常重要的一些方面。
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引用次数: 0
Characterizing the binding of TC-5619 and encenicline on the alpha7 nicotinic acetylcholine receptor using PET imaging in the pig 利用猪 PET 成像研究 TC-5619 和安格尼林与 alpha7 尼古丁乙酰胆碱受体的结合特性
Pub Date : 2024-03-27 DOI: 10.3389/fnimg.2024.1358221
J. H. Magnussen, A. Ettrup, S. Lehel, Dan Peters, A. Dyssegaard, M. S. Thomsen, Jens D. Mikkelsen, G. Knudsen
The alpha7 nicotinic acetylcholine receptor (α7-nAChR) has has long been considered a promising therapeutic target for addressing cognitive impairments associated with a spectrum of neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, despite this potential, clinical trials employing α7-nAChR (partial) agonists such as TC-5619 and encenicline (EVP-6124) have fallen short in demonstrating sufficient efficacy. We here investigate the target engagement of TC-5619 and encenicline in the pig brain by use of the α7-nAChR radioligand 11C-NS14492 to characterize binding both with in vitro autoradiography and in vivo occupancy using positron emission tomography (PET). In vitro autoradiography demonstrates significant concentration-dependent binding of 11C-NS14492, and both TC-5619 and encenicline can block this binding. Of particular significance, our in vivo investigations demonstrate that TC-5619 achieves substantial α7-nAChR occupancy, effectively blocking approximately 40% of α7-nAChR binding, whereas encenicline exhibits more limited α7-nAChR occupancy. This study underscores the importance of preclinical PET imaging and target engagement analysis in informing clinical trial strategies, including dosing decisions.
长期以来,α7-烟碱乙酰胆碱受体(α7-nAChR)一直被认为是解决与阿尔茨海默病和精神分裂症等一系列神经和精神疾病有关的认知障碍的一个很有前景的治疗靶点。然而,尽管α7-nAChR(部分)激动剂(如TC-5619和encenicline (EVP-6124))具有这样的潜力,但其临床试验并未显示出足够的疗效。在此,我们使用α7-nAChR放射性配体11C-NS14492研究了TC-5619和encenicline在猪脑中的靶点参与情况,通过体外自显影和体内正电子发射断层扫描(PET)鉴定了结合的特征。体外自显影表明,11C-NS14492 的结合具有显著的浓度依赖性,TC-5619 和安塞尼西林都能阻断这种结合。尤其重要的是,我们的体内研究表明,TC-5619 可实现大量的 α7-nAChR 占位,有效阻断约 40% 的 α7-nAChR 结合,而 encenicline 的 α7-nAChR 占位则较为有限。这项研究强调了临床前 PET 成像和靶点参与分析在为临床试验策略(包括剂量决策)提供信息方面的重要性。
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Frontiers in neuroimaging
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