Development of MRI Techniques for Drug-Abuse Application

药物滥用领域 MRI 技术的发展

• 批准号: 7321118
• 负责人: Yihong Yang
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7321118
• 关键词: Development; MRI; Techniques; Drug; Abuse

1. Quantitative Blood Volume Measurement in Human Brain Like CBF, CBV is an important physiological parameter closely associated with brain activity and thus, noninvasive quantification of CBV during brain activation provides another opportunity to investigate the relationship between neuronal activity and hemodynamic changes. In this study, a new method is presented that is able to quantify CBV at rest and during activation. Specifically, using an inversion recovery pulse sequence, a set of brain images was collected at various inversion times (TIs). At each TI, functional images were acquired with a block design visual stimulation paradigm. A biophysical model comprised of multiple tissue components was developed and was utilized for the determination of CBV using the visual stimulation data. MRI experiments on five healthy volunteers showed that CBV was 5.0 ml blood/100 ml brain during rest and increased to 6.6 ml blood/100 ml brain following visual stimulation. Furthermore, experiments with visual stimulation at two frequencies (2 and 8 Hz) showed that the increases in CBV correlated with the strength of stimulation. This technique, with its ability to measure quantitative CBV values noninvasively, provides a valuable tool for quantifying hemodynamic signals associated with brain activation. 2. Analysis of the Accuracy of Fiber Orientation Identification using Diffusion Profiles Diffusion-based q-space imaging techniques and high angular resolution diffusion (HARD) imaging have shown promise to identify intravoxel multiple fibers. The measured orientation distribution function (ODF) and apparent diffusion coefficient (ADC) profiles can be used to identify the orientations of the actual intravoxel fibers. The present study aims to examine the accuracy of these profile-based orientation methods by comparing the angular deviations between the estimated local maxima of the profiles and the real fiber orientation for a "general fiber crossing" that is simulated with various intersection angles, signal fractions, under different b values in diffusion-weighted MRI experiments. Both noisy and noise-free environments were investigated. The results indicate that systematic angular deviations exist between the actual fiber orientations and the corresponding local maxima of either the ADC or ODF profiles. All methods are apt to underestimation of acute intersection and overestimation of obtuse intersection angle. In the noisy environment, the mean value of the deviation angles shows a high consistency with the corresponding deviation in the nose-free condition. For a typical slow-exchange fiber crossing, the ODF methods have a non-deviation zone around the 90o intersection. QBI method demonstrates a slight yet consistent advantage over the DSI method under the same conditions. 3. Simultaneous Detection of Resolved Glutamate, Glutamine, and GAMA at 4 Tesla A novel technique is introduced to simultaneously detect resolved glutamate (Glu), glutamine (Gln), and GABA using a standard STEAM localization pulse sequence with the optimized sequence timing parameters. This approach is based on the concept that the C4 multiplet resonances of Glu around 2.35 ppm, Gln around 2.45 ppm, and the C2 multiplet resonance of GABA around 2.28 ppm can become virtual singlets simultaneously at specific sequence timing parameters, i.e., {TE, TM}, at 4 Tesla by exploiting the similarity and difference of the Glu, Gln, and GABA spectral characteristics. Simulation, in vitro, and in vivo experiments were carried out for verification of the concept. The results have demonstrated that the Glln, Glu, and GABA signals at 2.2-2.5 ppm can be well resolved using a standard STEAM sequence with the optimized sequence timing parameters around {82 ms, 48 ms} at 4T when concentrations of the targeted metabolites are sufficiently high, while the other main metabolites, such as Choline (Cho), Creatine (tCr), N-acetyl Aspartate (NAA), are still reserved in the same spectrum. The technique can be easily implemented and should prove to be a useful tool for the basic and clinical studies associated with metabolism of Glu, Gln, and GABA. 4. Consistent Brain Resting-State Networks across Five Sessions Revealed by Group Independent Component Analysis Independent component analysis (ICA), a multivariate data-driven method, has been used to reveal task-induced brain activation and recently resting-state brain networks without a prior knowledge about the pattern of the fMRI time course. In this study, we used group-level ICA to assess the repeatability of intrinsic brain activity across 5 sessions (within 16 days) and across 14 subjects. Results of this study should provide a valuable guidance for longitudinal group studies using resting-state fMRI. Experiments were performed on 14 healthy male right-handed volunteers (30!O6 yrs) in five sessions (over 2 weeks) on a 3T scanner. In each session, whole brain resting-state images were acquired, with the subjects instructed to close their eyes and not to think anything in particular. EPI was used with a TR of 2160 ms, and 90 repetitions. Data were spatially normalized and temporally filtered by a low-pass filter (0.1 Hz). Group ICA was performed separately for each session on temporally concatenated data sets. Classification methods based on spatial cross-correlation and K-means were used to cluster the component maps. Our analyses yielded 8 consistent maps, including a) medial occipital cortices, b) bilateral motor regions, c) temporal cortices and anterior cingulate cortex, d) posterior cingulate cortex, anterior cingulate cortex, and bilateral inferior parietal cortex, e) right medial and lateral frontal cortices, and f) left medial and lateral frontal cortices. Additional consistent maps include cerebellar and thalamic regions. The experimental results showed that gICA can extract consistent patterns of brain connectivity across several sessions of group resting-state fMRI data. 5.Resting-State Brain Activity at Different Anesthesia Level in Rats In this study, we measured resting-state functional connectivity on rats at 9.4T using contrast-agent (Combidex) based functional signal, with the assumption that the influence of cardiac pulsation through blood is minimal due to very short T2 of venous blood under this condition. In the first experiment (n=4), resting-state data were acquired using a gradient-echo EPI sequence and a total of 270 volumes were collected in 270 sec. For comparison, conventional fMRI data with a block-design forepaw stimulation were also collected in 320 sec. In the second experiment (n=4), the anesthetia dose of alfa-chloralose was adjusted at 3 levels, 30, 70 and 100 mg/kg, and resting-state and forepaw stimulation data were acquired with similar parameters as above. The results of the first experment showed increased activity in the contralateral forepaw somatosensory cortex. Using a voxel selected from the activation map as a seed point, functional connections between the somatosensory cortices on both hemispheres is clearly shown in the resting-state functional connectivity maps. The second experiment showed that both stimulus-induced activation and resting-state connectivity are reduced with increased of anesthetia dose. This study demonstrated that resting-state fMRI is feasible in rats anesthetized with alfa-chloralose, and the connectivity between the two sides of the somatosensory cortices can be modulated by anesthetia level. This animal model should be very useful for further investigate the underlying mechanisms of the resting-state fMRI signal.

1。人脑中的定量血容量测量 像CBF一样，CBV是与大脑活性密切相关的重要生理参数，因此，在大脑激活过程中对CBV的无创量化为研究神经元活性与血液动力学变化之间的关系提供了另一个机会。在这项研究中，提出了一种新方法，能够在静止和激活期间量化CBV。具体而言，使用反转恢复脉冲序列，在各种反转时间（TIS）中收集了一组脑图像。在每个Ti中，使用块设计视觉刺激范式获取功能图像。开发了由多个组织成分组成的生物物理模型，并用于使用视觉刺激数据来测定CBV。对五名健康志愿者进行的MRI实验表明，静止期CBV为5.0 mL血液/100 mL大脑，视觉刺激后增加到6.6 ml血液/100 mL大脑。此外，在两个频率（2和8 Hz）上进行视觉刺激的实验表明，CBV的增加与刺激强度相关。该技术具有非侵入性测量定量CBV值的能力，它为量化与脑激活相关的血液动力学信号提供了有价值的工具。 2。使用扩散曲线分析纤维取向识别的准确性 基于扩散的Q空间成像技术和高角度分辨率扩散（硬）成像已显示出识别出射流多个纤维的希望。测得的方向分布函数（ODF）和明显的扩散系数（ADC）曲线可用于识别实际的内内室纤维的方向。本研究的目的是通过比较图谱的估计局部最大值与“通用纤维交叉”的真实纤维方向之间的角度偏差来检查这些基于概况的取向方法的准确性，该方法与各种相交角度，信号级数模拟的“通用纤维交叉”（在扩散型MRI实验中不同的B值下）模拟。研究了嘈杂的环境和无噪声环境。结果表明，实际的纤维方向与ADC或ODF轮廓的相应局部最大值之间存在系统的角度偏差。所有方法都易于低估急性交叉点和钝化交点角度的高估。在嘈杂的环境中，偏差角的平均值与无鼻子条件下的相应偏差具有很高的一致性。对于典型的慢速纤维交叉，ODF方法在90o交叉路口附近具有非偏差区。在相同条件下，QBI方法比DSI方法表现出轻微但一致的优势。 3。同时检测4特斯拉的已解决的谷氨酸，谷氨酰胺和Gama 引入了一种新型技术，该技术使用标准的蒸汽定位脉冲序列，同时检测分辨的谷氨酸（GLU），谷氨酰胺（GLN）和GABA，并具有优化的序列时正时正时正时正时正时正时正时正时正时正时正时正时正时的定位脉冲序列。这种方法基于以下概念：GLU大约2.35 ppm，GLN约2.45 ppm左右，GABA大约2.28 ppm的C2多重谐振可以同时在特定的序列时正时正时变为虚拟单线，即{光谱特征。进行了模拟，体外和体内实验以验证该概念。结果表明，使用标准的蒸汽序列可以通过标准的蒸汽序列进行很好的解决，即在{82 ms，48 ms，48 ms，48 ms}左右时，当目标代谢的浓度足够高时，可以很好地解决glln，glu和gaba信号。 （NAA）仍然保留在相同的频谱中。该技术可以轻松实施，并且应该被证明是与GLU，GLN和GABA代谢相关的基本和临床研究的有用工具。 4。跨小组独立组件分析揭示的五个会话的一致脑静止状态网络 独立组件分析（ICA）是一种多元数据驱动的方法，已用于揭示任务引起的大脑激活和近期静止状态的大脑网络，而没有有关fMRI时间课程模式的先验知识。在这项研究中，我们使用组级ICA评估了5个会话（16天之内）和14名受试者的内在脑活动的重复性。这项研究的结果应为使用静止状态fMRI的纵向小组研究提供宝贵的指导。在3T扫描仪的五个会议（超过2周）中，对14位健康男性右手志愿者（30岁）进行了实验。在每个会话中，都获取了整个大脑静止状态的图像，并指示受试者闭上眼睛，而不是特别思考。 EPI与2160毫秒的TR一起使用，重复90次。数据被空间归一化，并通过低通滤波器（0.1 Hz）进行时间过滤。对于时间串联的数据集，为每个会话分别执行ICA组。基于空间互相关和K-均值的分类方法用于聚集组件图。我们的分析产生了8个一致的图，包括a）内侧枕骨皮质，b）双侧运动区域，c）颞皮层和前扣带回皮质，d）后扣带皮质，前扣带回皮层，前扣带回皮层，皮层和双侧皮质层，e）右手层和后期的额定叶子和后期的cortrices和后期的cortrices和frialal cortrices和frials cortrices和frial cortrices和frial cortrices＆frail cortal and frail corte and corte＆f）和f）f。其他一致的地图包括小脑和丘脑区域。实验结果表明，GICA可以在组静止状态fMRI数据的几个会话中提取一致的大脑连通性模式。 5.在大鼠不同麻醉水平下的脑大脑活动 在这项研究中，我们使用基于对比剂（Combidex）的功能信号测量了9.4T大鼠对大鼠的静息态连通性，并假设由于在这种情况下，由于非常短的静脉血液T2，通过血液通过血液的影响很小。在第一个实验（n = 4）中，使用梯度回声EPI序列获得静止状态数据，并在270秒内收集了270卷。为了进行比较，还在320秒内收集了具有块刺激刺激的常规fMRI数据。在第二个实验中（n = 4），以3个水平，30、70和100 mg/kg的形式调整了α-氯糖的麻醉剂量，并以与上述相似的参数获取了静止状态和前爪刺激数据。第一个实验的结果表明，对侧前毛体感皮质的活性增加。使用从激活图作为种子点选择的体素，在两个半球上的体感皮层之间的功能连接清楚地显示在静息状态功能连接图中。第二个实验表明，随着麻醉剂量的增加，刺激诱导的激活和静息状态连通性均降低。这项研究表明，在用α-氯酸盐麻醉的大鼠中，静止状态fMRI是可行的，并且可以通过麻醉水平调节体感皮质的两侧之间的连通性。该动物模型对于进一步研究静止状态fMRI信号的潜在机制应该非常有用。