Jing-Huei Lee

Functional magnetic resonance imaging of motor, sensory, and posterior parietal cortical areas during performance of sequential typing movements

Abstract We investigated the activation of sensory and motor areas involved in the production of typing movements using functional magnetic resonance imaging (fMRI). Eleven experienced typists performed tasks, in which the spatial and temporal requirements as well as the number of digits involved were varied. These included a simple uni-digit repetitive task, a uni-digit sequential task, a dual-digit sequential task, a multi-digit sequential task, and typing text from memory. We found that the production of simple repetitive keypresses with the index finger primarily involved the activation of contralateral primary motor cortex (M1), although a small activation of the supplementary motor area (SMA) and other regions was sometimes observed as well. The sequencing of keypresses involved bilateral M1 and a stronger activation of the SMA and to a lesser extent the premotor area, cingulate gyrus, caudate, and lentiform nuclei. However, the activation of these areas did not exclusively depend on the complexity of the movements, since they were often activated during more simple movements, such as alternating two keypresses repeatedly. Somatosensory and parietal regions were also found to be activated during typing sequences. The activation of parietal areas did not exclusively depend on the spatial requirements of the task, since similar activation was observed during movements within intra-personal space (finger-thumb opposition) and may instead be related to the temporal requirements of the task. Our findings suggest that the assembly of well-learned, goal-directed finger movement sequences involves the SMA and other secondary motor areas as well as somatosensory and parietal areas.

Functional magnetic resonance imaging brain activation in bipolar mania: evidence for disruption of the ventrolateral prefrontal-amygdala emotional pathway.

BACKGROUND Bipolar I disorder is defined by the occurrence of mania. The presence of mania, coupled with a course of illness characterized by waxing and waning of affective symptoms, suggests that bipolar disorder arises from dysfunction of neural systems that maintain emotional arousal and homeostasis. We used functional magnetic resonance imaging (fMRI) to study manic bipolar subjects as they performed a cognitive task designed to examine the ventrolateral prefrontal emotional arousal network. METHODS We used fMRI to study regional brain activation in 40 DSM-IV manic bipolar I patients and 36 healthy subjects while they performed a continuous performance task with emotional and neutral distracters. Event-related region-of-interest analyses were performed to test the primary hypothesis. Voxelwise analyses were also completed. RESULTS Compared with healthy subjects, the manic subjects exhibited blunted activation to emotional and neutral images, but not targets, across most of the predefined regions of interest. Several additional brain regions identified in the voxelwise analysis also exhibited similar differences between groups, including right parahippocampus, right lingual gyrus, and medial thalamus. In addition to these primary findings, the manic subjects also exhibited increased activation in response to targets in a number of brain regions that were primarily associated with managing affective stimuli. Group differences did not appear to be secondary to medication exposure or other confounds. CONCLUSIONS Bipolar manic subjects exhibit blunted brain fMRI response to emotional cues throughout the ventrolateral prefrontal emotional arousal network. Disruption of this emotional network may contribute to the mood dysregulation of bipolar disorder.

Automated Vertebra Detection and Segmentation from the Whole Spine MR Images

Our algorithm contains two major steps: the intervertebral disk localization step, and the vertebra detection and segmentation step. In the first step, we apply a model-based searching method to approximately locate all the intervertebral disk clues between adjacent vertebrae of the whole spine and the best slice selection. A new approach using an intensity profile on a polynomial function for fitting all these disk clues on the best slice is then used to refine the disk search process. Vertebra centers are detected, and initial boundaries are extracted in the second step. The initial test of the algorithm on the five sets of 7 sagittal slices locates all 23 intervertebral disk centers for the best slice of all five sets. For the evaluation of the boundary extraction of 22 vertebrae, our algorithm successfully locates 100%, 96.6%, 93.2%, 95.5%, 87.5% vertebra corners in image set No.1, 2, 3, 4, and 5, respectively

Polymer beacons for luminescence and magnetic resonance imaging of DNA delivery

The delivery of nucleic acids with polycations offers tremendous potential for developing highly specific treatments for various therapeutic targets. Although materials have been developed and studied for polynucleotide transfer, the biological mechanisms and fate of the synthetic vehicle has remained elusive due to the limitations with current labeling technologies. Here, we have developed polymer beacons that allow the delivery of nucleic acids to be visualized at different biological scales. The polycations have been designed to contain repeated oligoethyleneamines, for binding and compacting nucleic acids into nanoparticles, and lanthanide (Ln) chelates [either luminescent europium (Eu3+) or paramagnetic gadolinium (Gd3+)]. The chelated Lns allow the visualization of the delivery vehicle both on the nm/μm scale via microscopy and on the sub-mm scale via MRI. We demonstrate that these delivery beacons effectively bind and compact plasmid (p)DNA into nanoparticles and protect nucleic acids from nuclease damage. These delivery beacons efficiently deliver pDNA into cultured cells and do not exhibit toxicity. Micrographs of cultured cells exposed to the nanoparticle complexes formed with fluorescein-labeled pDNA and the europium-chelated polymers reveal effective intracellular imaging of the delivery process. MRI of bulk cells exposed to the complexes formulated with pDNA and the gadolinium-chelated structures show bright image contrast, allowing visualization of effective intracellular delivery on the tissue-scale. Because of their versatility, these delivery beacons posses remarkable potential for tracking and understanding nucleic acid transfer in vitro, and have promise as in vivo theranostic agents.

A β-Cyclodextrin “Click Cluster” Decorated with Seven Paramagnetic Chelates Containing Two Water Exchange Sites

The development of novel macromolecular contrast agents that offer enhanced relaxivity profiles at high magnetic fields have the potential to greatly improve the diagnosis, understanding, and treatment of disease. To this end, we have designed a monodiperse paramagnetic beta-cyclodextrin click cluster decorated with seven paramagnetic arms. A novel alkyne-functionalized diethylenetriaminetetraacetic acid (DTTA) chelate (6) has been created and coupled to a per-azido-beta-cyclodextrin core (7) to yield the precursor macromolecule (8). After removal of the protecting groups and titrating with Gd (3+), the final paramagnetic click cluster, Gd10, was obtained. Luminescence measurements were carried out in H 2O and D 2O on an analogous structure, Eu10, and indicated that at each lanthanide has an average of 1.8 water exchange sites, which is important for enhancing relaxivity and MRI resolution. This discrete paramagnetic click cluster yields a high relaxivity profile (43.4 mM (-1) s (-1) per molecule and 6.2 mM (-1) s (-1) per Gd (3+) at 9.4 T) and enhanced contrast on a human MRI scanner as compared to a commercial agent, Magnevist (3.2 mM (-1) s (-1) at 9.4 T). Moreover, the useful inclusion properties exhibited by beta-cyclodextrin also make this an excellent host scaffold to functionalize via noncovalent assembly with receptor specific targeting moieties for biomolecular imaging.

Effects of Equilibrium Exchange on Diffusion-Weighted NMR Signals: The Diffusigraphic "Shutter-Speed"

A general picture is presented of the implications for diffusion‐weighted NMR signals of the parsimonious two‐site‐exchange (2SX) paradigm. In particular, it is shown that the diffusigraphic “shutter‐speed,” τ−1 ≡ |q2(DA – DB)|, is a useful concept. The “wave‐number” q has its standard definition (given in the text), and DA and DB are the apparent diffusion coefficients (ADCs) of molecules in the two “sites,” A and B, if there is no exchange between them. At low gradient strengths (center of q‐space), τ−1 is less than rate constants for intercompartmental water molecule exchange in most tissue cases. Thus, the exchange reaction appears fast. However, q is increased during the course of most experiments and, as it is, the shutter‐speed becomes “faster” and the exchange reaction, the kinetics of which do not change, appears to slow down. This causes a multiexponential behavior in the diffusion‐weighting dimension, b, which also has its standard definition. This picture is found to be in substantial agreement with a number of different experimental observations. It is applied here to literature 1H2O data from a yeast cell suspension and from the human and the rat brain. Since the equilibrium transcytolemmal water exchange reaction appears to be in the fast‐exchange‐limit at small b, the initial slope represents the weighted‐average of the ADCs of intra‐ and extracellular water. Of course, in tissue the former is in the significant majority. Furthermore, a consideration of reasonable values for the other 2SX parameters suggests that, for resting brain tissue, the intracellular water ADC may be larger than the extracellular water ADC. There are some independent inferences of this, which would have ramifications for many applications of diffusion‐weighted MRI. Magn Reson Med 49:450–458, 2003. Published 2003 Wiley‐Liss, Inc.

Differentiation of Glucose transport in human brain gray and white matter

Localized 1H nuclear magnetic resonance spectroscopy has been applied to determine human brain gray matter and white matter glucose transport kinetics by measuring the steady-state glucose concentration under normoglycemia and two levels of hyperglycemia. Nuclear magnetic resonance spectroscopic measurements were simultaneously performed on three 12-mL volumes, containing predominantly gray or white matter. The exact volume compositions were determined from quantitative T1 relaxation magnetic resonance images. The absolute brain glucose concentration as a function of the plasma glucose level was fitted with two kinetic transport models, based on standard (irreversible) or reversible Michaelis-Menten kinetics. The steady-state brain glucose levels were similar for cerebral gray and white matter, although the white matter levels were consistently 15% to 20% higher. The ratio of the maximum glucose transport rate, Vmax, to the cerebral metabolic utilization rate of glucose, CMRGlc, was 3.2 ± 0.10 and 3.9 ± 0.15 for gray matter and white matter using the standard transport model and 1.8 ± 0.10 and 2.2 ± 0.12 for gray matter and white matter using the reversible transport model. The Michaelis-Menten constant Km was 6.2 ± 0.85 and 7.3 ± 1.1 mmol/L for gray matter and white matter in the standard model and 1.1 ± 0.66 and 1.7 ± 0.88 mmol/L in the reversible model. Taking into account the threefold lower rate of CMRGlc in white matter, this finding suggests that blood–brain barrier glucose transport activity is lower by a similar amount in white matter. The regulation of glucose transport activity at the blood–brain barrier may be an important mechanism for maintaining glucose homeostasis throughout the cerebral cortex.

Spectroscopic imaging of glutamate C4 turnover in human brain.

One‐dimensional spectroscopic imaging of 13C‐4‐glutamate turnover is performed in the human brain with a 6 cc nominal voxel resolution at 4T. Data were acquired with an indirect detection approach using a short spin echo single quantum 1H‐13C heteronuclear editing method and a 7 cm surface coil with quadrature 13C decoupling coils. To analyze the data as a function of tissue type, T1‐based image segmentation through the surface coil was performed to determine the gray and white matter contributions to each voxel. The tricarboxylic acid (TCA) cycle rate in gray and white matter was then determined using a two‐compartment model with the tissue fractionation derived from the image segmentation. The mean values for the TCA cycle rate for occipital gray and white matter from three volunteers was 0.88 ± 0.12 and 0.28 ± 0.13 respectively, in agreement with literature data. Magn Reson Med 44:673–679, 2000.

Magnetic resonance imaging brain activation in first-episode bipolar mania during a response inhibition task.

Aims: Impulsivity is common in bipolar disorder, especially during mania. Understanding the functional neuroanatomy of response inhibition, one component of impulsivity, might clarify the neural substrate of bipolar disorder.

Myelin water mapping by spatially regularized longitudinal relaxographic imaging at high magnetic fields

Magnetic resonance T1‐weighted images are routinely used for human brain segmentation, brain parcellation, and clinical diagnosis of demyelinating diseases. Myelin is thought to influence the longitudinal relaxation commonly described by a mono‐exponential recovery, although reports of bi‐exponential longitudinal relaxation have been published. The purpose of this work was to investigate if a myelin water T1 contribution could be separated in geometrically sampled Look‐Locker trains of low flip angle gradient echoes.