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. 人脑血容量定量测量 与 CBF 一样，CBV 是与大脑活动密切相关的重要生理参数，因此，大脑激活过程中 CBV 的无创定量为研究神经元活动与血流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，能够量化静息和激活期间的 CBV。具体来说，使用反转恢复脉冲序列，在不同的反转时间（TI）收集一组大脑图像。在每个 TI 中，通过块设计视觉刺激范例获取功能图像。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确定 CBV。对五名健康志愿者进行的 MRI 实验表明，休息时 CBV 为 5.0 毫升血液/100 毫升大脑，在视觉刺激后增加至 6.6 毫升血液/100 毫升大脑。此外，两种频率（2 赫兹和 8 赫兹）视觉刺激的实验表明，CBV 的增加与刺激强度相关。该技术能够无创地测量定量 CBV 值，为量化与大脑激活相关的血流动力学信号提供了有价值的工具。 2. 利用扩散剖面识别纤维取向的准确性分析 基于扩散的 q 空间成像技术和高角分辨率扩散 (HARD) 成像已显示出识别体素内多纤维的前景。测量的方向分布函数 (ODF) 和表观扩散系数 (ADC) 轮廓可用于识别实际体素内纤维的方向。本研究旨在通过比较轮廓的估计局部最大值与“一般纤维交叉”的真实纤维取向之间的角度偏差来检查这些基于轮廓的取向方法的准确性，该“一般纤维交叉”是在扩散加权 MRI 实验中的不同 b 值下用各种交叉角、信号分数进行模拟的。对噪声环境和无噪声环境进行了研究。结果表明，实际光纤取向与 ADC 或 ODF 轮廓的相应局部最大值之间存在系统角度偏差。所有方法都容易低估锐角交叉点和高估钝角交叉角。在噪声环境下，偏差角的平均值与无鼻子条件下的相应偏差表现出高度的一致性。对于典型的慢速交换光纤交叉，ODF 方法在 90o 交叉点周围有一个无偏差区。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. 在 4 特斯拉同时检测溶解的谷氨酸、谷氨酰胺和 GAMA 引入了一种新技术，使用具有优化序列计时参数的标准 STEAM 定位脉冲序列来同时检测解析的谷氨酸 (Glu)、谷氨酰胺 (Gln) 和 GABA。该方法基于以下概念：通过利用 Glu、Gln 和 GABA 的相似性和差异，在 4 Tesla 下，Glu 约 2.35 ppm、Gln 约 2.45 ppm 的 C4 多重共振和 GABA 约 2.28 ppm 的 C2 多重共振可以同时成为虚拟单线态。 光谱特性。为了验证这一概念，进行了模拟、体外和体内实验。结果表明，当目标代谢物浓度足够高时，使用标准 STEAM 序列可以很好地解析 2.2-2.5 ppm 的 Glln、Glu 和 GABA 信号，优化的序列定时参数在 4T 时约为 {82 ms, 48 ms}，而其他主要代谢物，如胆碱 (Cho)、肌酸 (tCr)、N-乙酰天门冬氨酸 （NAA），仍然保留在相同的频谱中。该技术易于实施，并且应该被证明是与 Glu、Gln 和 GABA 代谢相关的基础和临床研究的有用工具。 4. 组独立成分分析揭示了五个会话中一致的大脑静息状态网络 独立成分分析 (ICA) 是一种多变量数据驱动方法，已被用于揭示任务诱发的大脑激活和最近静息状态的大脑网络，而无需事先了解功能磁共振成像时间过程的模式。在这项研究中，我们使用组级 ICA 来评估 14 名受试者在 5 个疗程（16 天内）内的内在大脑活动的可重复性。这项研究的结果应该为使用静息态功能磁共振成像的纵向分组研究提供有价值的指导。对 14 名健康男性右利手志愿者（30 岁）在 3T 扫描仪上进行了五次实验（超过 2 周）。在每次治疗中，都会获取整个大脑的静息状态图像，并指示受试者闭上眼睛，不要特别思考任何事情。使用 EPI，TR 为 2160 毫秒，重复 90 次。数据经过空间归一化并通过低通滤波器（0.1 Hz）进行时间滤波。组 ICA 是在时间级联的数据集上针对每个会话单独执行的。基于空间互相关和 K 均值的分类方法用于对成分图进行聚类。我们的分析产生了 8 个一致的图，包括 a) 内侧枕叶皮质，b) 双侧运动区，c) 颞叶皮质和前扣带皮层，d) 后扣带皮层，前扣带皮层和双侧下顶叶皮质，e) 右侧内侧和外侧额叶皮质，以及 f) 左侧内侧和外侧额叶皮质。其他一致的地图包括小脑和丘脑区域。实验结果表明，gICA 可以在多个组静息态 fMRI 数据中提取一致的大脑连接模式。 5. 大鼠不同麻醉水平下的静息态脑活动 在本研究中，我们使用基于造影剂 (Combidex) 的功能信号测量了 9.4T 大鼠的静息态功能连接，并假设由于在此条件下静脉血的 T2 非常短，心脏搏动通过血液的影响最小。在第一个实验 (n=4) 中，使用梯度回波 EPI 序列获取静息态数据，并在 270 秒内收集了总共 270 个体积。为了进行比较，还在 320 秒内收集了采用块设计前爪刺激的传统 fMRI 数据。在第二个实验（n=4）中，将阿法氯醛糖的麻醉剂量调整为30、70和100 mg/kg 3个水平，并使用与上述类似的参数获取静息态和前爪刺激数据。第一个实验的结果显示对侧前爪体感皮层的活动增加。使用从激活图中选择的体素作为种子点，两个半球体感皮层之间的功能连接在静息状态功能连接图中清晰地显示。第二个实验表明，刺激诱导的激活和静息态连接都随着麻醉剂量的增加而减少。这项研究表明，静息态功能磁共振成像在阿法氯醛糖麻醉的大鼠中是可行的，并且体感皮层两侧之间的连接可以通过麻醉水平进行调节。该动物模型对于进一步研究静息态 fMRI 信号的潜在机制应该非常有用。