Development of MRI Techniques for Drug-Abuse Applications

药物滥用领域 MRI 技术的发展

• 批准号: 8148518
• 负责人: Yihong Yang
• 金额: $ 119.4万
• 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/8148518
• 关键词: Development; Magnetic Resonance Imaging; Pharmaceutical Preparations; Techniques

1. Mesocorticolimbic circuits are impaired in chronic cocaine users as demonstrated by resting-state functional connectivity Cocaine dependent individuals manifest alterations in reward functioning that may relate to changes induced by cocaine or to pre-existing differences related to vulnerability to addiction. The circuit level manifestations of these drug-induced plastic changes and predispositions to drug dependence are poorly understood in preclinical models and virtually unknown in human drug dependence. Using whole-brain resting-state fMRI connectivity analysis with 'seed voxels' placed within individual nodes of the MCL system, we report network-specific functional connectivity strength decreases in cocaine users within distinct circuits of the system, including between ventral tegmental area (VTA) and a region encompassing thalamus/lentiform nucleus/nucleus accumbens, between amygdala and medial prefrontal cortex (mPFC), and between hippocampus and dorsal mPFC. Further, regression analysis on regions showing significant functional connectivity decrease in chronic cocaine users revealed that the circuit strength between VTA and thalamus/lentiform nucleus/nucleus accumbens was negatively correlated with years of cocaine use. This is the first evidence of circuit-related changes in human cocaine dependence and is consistent with the range of cognitive and behavioral disruptions seen in cocaine dependence. As potential circuit level biomarkers of cocaine dependence, these circuit alterations may be usefully applied in treatment development and monitoring treatment outcome. (NeuroImage 53:593-601, 2010) 2. Lower glutamate levels in rostral anterior cingulate of chronic cocaine users - A H-MRS study Previous studies have shown significantly lower metabolism and functional activity in the anterior cingulate cortex (ACC) of human cocaine addicts. The present study examined whether this ACC hypoactivity is associated with altered glutamate (Glu), the primary excitatory neurotransmitter in the central nervous system (CNS), which has been recently implicated in drug addiction. Participants comprised 14 chronic cocaine addicts and 14 matched healthy volunteers who were examined using (1)H magnetic resonance spectroscopy at 3 T. The concentrations of Glu as well as N-acetyl aspartate (NAA), total creatine (tCr), choline-containing compounds (tCho), and myo-inositol (Ins) were estimated from both groups. Glu/tCr was significantly lower in chronic cocaine users compared to control subjects and was significantly correlated with years of cocaine use. Glu/tCr was also positively correlated with NAA/tCr. NAA/tCr significantly decreased with age but was not significantly different between the two groups. These findings suggest a metabolic/neurotransmitter dysregulation associated with cocaine addiction and support a possible therapeutic intervention strategy aimed at normalizing the Glu transmission and function in the treatment of cocaine addiction. (Psychiatry Res 174:171-176, 2009) 3. A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction Whole-genome searches have identified nicotinic acetylcholine receptor alpha5-alpha3-beta4 subunit gene variants that are associated with smoking. How genes support this addictive and high-risk behavior through their expression in the brain remains poorly understood. Here we show that a key alpha5 gene variant Asp398Asn is associated with a dorsal anterior cingulate-ventral striatum/extended amygdala circuit, such that the "risk allele" decreases the intrinsic resting functional connectivity strength in this circuit. Importantly, this effect is observed independently in nonsmokers and smokers, although the circuit strength distinguishes smokers from nonsmokers, predicts addiction severity in smokers, and is not secondary to smoking per se, thus representing a trait-like circuitry biomarker. This same circuit is further impaired in people with mental illnesses, who have the highest rate of smoking. Identifying where and how brain circuits link genes to smoking provides practical neural circuitry targets for new treatment development. (Proc Natl Aced Sci USA. 107, 13509-13514, 2010) 4. Automated brain tissue segmentation based on fractional signal mapping from inversion recovery Look-Locker acquisition Most current automated segmentation methods are performed on T(1)- or T(2)-weighted MR images, relying on relative image intensity that is dependent on other MR parameters and sensitive to B(1) magnetic field inhomogeneity. Here, we propose an image segmentation method based on quantitative longitudinal magnetization relaxation time (T(1)) of brain tissues. Considering the partial volume effect, fractional volume maps of brain tissues (white matter, gray matter, and cerebrospinal fluid) were obtained by fitting the observed signal in an inversion recovery procedure to a linear combination of three exponential functions, which represents the relaxations of each of the tissue types. A Look-Locker acquisition was employed to accelerate the acquisition process. The feasibility and efficacy of this proposed method were evaluated using simulations and experiments. The potential applications of this method in the study of neurological disease as well as normal brain development and aging are discussed. (NeuroImage 52, 1347-1354, 2010) 5. Effects of CBV, CBF, and blood-brain barrier permeability on accuracy of PASL and VASO measurement Cerebral blood flow, cerebral blood volume (CBV), and water permeability through blood-brain barrier are important hemodynamic parameters in brain physiology. In the current work, the biophysical effects of CBV on pulsed arterial spin labeling and permeability on vascular-space occupancy signals are evaluated using a general two-compartment model. The dependence of these effects on the T(1) at various field strengths is also assessed by simulations. Results indicate that CBV has negligible to small influences on pulsed arterial spin labeling signal (<6.6% at 3 T) and permeability effects are negligible on vascular-space occupancy signal (<0.1% at 3 T) under normal physiologic conditions. In addition, CBV effect on pulsed arterial spin labeling is further diminished at high field strengths, but residual blood contamination in vascular-space occupancy signal may be enhanced at high fields due to the reduced difference between extra- and intravascular T(1) values. (Magn Reson Med, 2010, 63: 601-608) 6. Unbiased Group-Wise Image Registration: Applications in Brain Fiber Tract Atlas Construction and Functional Connectivity Analysis We propose an unbiased implicit-reference group-wise (IRG) image registration method and demonstrate its applications in the construction of a brain white matter fiber tract atlas and the analysis of resting-state functional MRI (fMRI) connectivity. Most image registration techniques pair-wise align images to a selected reference image and group analyses are performed in the reference space, which may produce bias. The proposed method jointly estimates transformations, with an elastic deformation model, registering all images to an implicit reference corresponding to the group average. The unbiased registration is applied to build a fiber tract atlas by registering a group of diffusion tensor images. Compared to reference-based registration, the IRG registration improves the fiber track overlap within the group. After applying the method in the fMRI connectivity analysis, results suggest a general improvement in functional connectivity maps at a group level in terms of larger cluster size and higher average t-scores. (J Med Syst, 2010, in press)

1. 静息态功能连接表明，慢性可卡因使用者的中皮质边缘回路受损 可卡因依赖者表现出奖赏功能的改变，这可能与可卡因引起的变化或与成瘾脆弱性相关的预先存在的差异有关。这些药物引起的塑性变化和药物依赖倾向的回路水平表现在临床前模型中知之甚少，并且在人类药物依赖中几乎未知。通过对 MCL 系统各个节点内放置的“种子体素”进行全脑静息态 fMRI 连接分析，我们报告了系统不同回路内可卡因使用者的网络特异性功能连接强度下降，包括腹侧被盖区 (VTA) 和包含丘脑/豆状核/伏核的区域之间、杏仁核和内侧前额叶之间 皮层 (mPFC)，以及海马体和背侧 mPFC 之间。此外，对显示长期可卡因使用者功能连接显着下降的区域的回归分析表明，VTA 和丘脑/豆状核/伏隔核之间的回路强度与可卡因使用年限呈负相关。这是人类可卡因依赖中与回路相关的变化的第一个证据，并且与可卡因依赖中所见的认知和行为破坏的范围一致。作为可卡因依赖的潜在回路水平生物标志物，这些回路改变可有效应用于治疗开发和监测治疗结果。 (神经影像 53:593-601, 2010) 2. 长期吸食可卡因的头侧前扣带回谷氨酸水平较低 - H-MRS 研究 先前的研究表明，人类可卡因成瘾者前扣带皮层（ACC）的代谢和功能活动显着降低。本研究检验了这种 ACC 活性低下是否与谷氨酸 (Glu) 的改变有关，谷氨酸是中枢神经系统 (CNS) 中的主要兴奋性神经递质，最近与毒瘾有关。参与者包括 14 名慢性可卡因成瘾者和 14 名匹配的健康志愿者，他们在 3 T 下使用 (1)H 磁共振波谱进行检查。对两组的 Glu 以及 N-乙酰天冬氨酸 (NAA)、总肌酸 (tCr)、含胆碱化合物 (tCho) 和肌醇 (Ins) 的浓度进行了估计。与对照受试者相比，长期可卡因使用者的 Glu/tCr 显着降低，并且与可卡因使用年限显着相关。 Glu/tCr 也与 NAA/tCr 呈正相关。 NAA/tCr 随着年龄的增长而显着下降，但两组之间没有显着差异。这些发现表明代谢/神经递质失调与可卡因成瘾相关，并支持一种可能的治疗干预策略，旨在使可卡因成瘾治疗中的 Glu 传输和功能正常化。 (精神病学研究 174:171-176, 2009) 3. 基因调节的内在扣带回路支持人类尼古丁成瘾 全基因组搜索已鉴定出与吸烟相关的烟碱乙酰胆碱受体α5-α3-β4亚基基因变异。基因如何通过在大脑中的表达来支持这种成瘾和高风险的行为仍然知之甚少。在这里，我们表明关键的 alpha5 基因变体 Asp398Asn 与背侧前扣带回腹侧纹状体/扩展杏仁核回路相关，因此“风险等位基因”降低了该回路中内在的静息功能连接强度。重要的是，这种效应在非吸烟者和吸烟者中独立观察到，尽管回路强度将吸烟者与非吸烟者区分开来，预测吸烟者成瘾的严重程度，并且并不继发于吸烟本身，因此代表了一种类似特征的回路生物标志物。在患有精神疾病的人中，这一回路进一步受损，而他们的吸烟率最高。确定大脑回路在何处以及如何将基因与吸烟联系起来，为新疗法的开发提供了实用的神经回路目标。 （美国国家科学院院刊。107, 13509-13514, 2010） 4. 基于反转恢复 Look-Locker 采集的分数信号映射的自动脑组织分割 目前大多数自动分割方法都是在 T(1) 或 T(2) 加权 MR 图像上执行，依赖于相对图像强度，而相对图像强度依赖于其他 MR 参数并对 B(1) 磁场不均匀性敏感。在这里，我们提出了一种基于脑组织定量纵向磁化弛豫时间（T（1））的图像分割方法。考虑到部分体积效应，通过将反转恢复过程中观察到的信号拟合到三个指数函数的线性组合（代表每种组织类型的松弛），获得了脑组织（白质、灰质和脑脊液）的分数体积图。采用 Look-Locker 收购来加速收购过程。通过模拟和实验评估了该方法的可行性和有效性。讨论了该方法在神经系统疾病以及正常大脑发育和衰老研究中的潜在应用。 (神经图像 52, 1347-1354, 2010) 5. CBV、CBF和血脑屏障通透性对PASL和VASO测量准确性的影响 脑血流量、脑血容量（CBV）和血脑屏障的水渗透性是脑生理学中重要的血流动力学参数。在目前的工作中，使用通用的两室模型评估了 CBV 对脉冲动脉自旋标记和血管空间占用信号通透性的生物物理影响。还通过模拟评估了在不同场强下这些效应对 T(1) 的依赖性。结果表明，在正常生理条件下，CBV 对脉冲动脉自旋标记信号（3 T 时<6.6%）的影响可以忽略不计，并且渗透性对血管空间占用信号的影响可以忽略不计（3 T 时<0.1%）。此外，CBV 对脉冲动脉自旋标记的影响在高场强下进一步减弱，但由于血管外和血管内 T(1) 值之间的差异减小，血管空间占用信号中的残留血液污染可能在高场下增强。 （磁共振医学，2010，63：601-608） 6. 无偏群体图像配准：在脑纤维束图谱构建和功能连接分析中的应用 我们提出了一种无偏隐式参考分组（IRG）图像配准方法，并展示了其在大脑白质纤维束图谱构建和静息态功能磁共振成像（fMRI）连接分析中的应用。大多数图像配准技术将图像与选定的参考图像成对对齐，并在参考空间中执行组分析，这可能会产生偏差。所提出的方法使用弹性变形模型联合估计变换，将所有图像配准到与组平均值相对应的隐式参考。通过配准一组扩散张量图像，应用无偏配准来构建纤维束图集。与基于参考的配准相比，IRG 配准改善了组内的光纤轨迹重叠。在功能磁共振成像连接分析中应用该方法后，结果表明，在更大的簇大小和更高的平均 t 分数方面，群体水平的功能连接图得到了普遍改善。 （《医学系统杂志》，2010 年，出版中）