Development of MRI Techniques for Drug-Abuse Application

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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.