Browsing by Author "Chang, Chen"

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A New Scenario for Negative Functional Magnetic Resonance Imaging Signals: Endogenous Neurotransmission
(2009-03-11)
Shih, Yen-Yu I.
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Chen, Chiao-Chi V.
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Shyu, Bai-Chuang
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Lin, Zi-Jun
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Chiang, Yun-Chen
Functional magnetic resonance imaging (fMRI) has revolutionized investigations of brain functions. Increases in fMRI signals are usually correlated with neuronal activation, but diverse explanations have been proposed for negative fMRI responses, including decreases in neuronal activity, the vascular-steal effect, and large increases in oxygen consumption. These possible scenarios, although encompassing a wide range of potential neurovascular responses, cannot yet be used to interpret certain types of negative fMRI signals. Recent studies have found that intravenous injection of dopamine D(2) receptor (D2DR) agonist reduced the hemodynamic responses in the caudate-putamen (CPu); however, whether endogenous dopaminergic neurotransmission contributes to fMRI signals remains obscure. Since it has been suggested that the D2DR is involved in pain modulation, and the CPu shows equivocal fMRI signals during noxious stimulation, the present study established an animal model based on graded electrical stimulation to elicit different levels of nociception, and aimed to determine whether nociception-induced endogenous dopaminergic neurotransmission is sufficient to generate negative fMRI responses. Our results from cerebral blood volume (CBV)-weighted fMRI, Fos immunohistochemistry, and electro-physiological recording demonstrated a salient bilateral CBV decreases associated with heightened neuronal activity in the CPu induced by unilateral noxious electrical stimulation. In addition, preinjection of D2DR antagonist reduced the observed CBV decreases. Our findings reveal the role of the D2DR in regulating striatal vascular responses and suggest that endogenous neurotransmission-induced CBV decreases underlie negative fMRI signals. Hence, the influence of endogenous neurotransmission should be considered when interpreting fMRI data, especially in an area involved in strong vasoactive neurotransmission.
DYNAMIC MAPPING OF AMPHETAMINE RESPONSE IN THE RAT BRAIN USING BOLD AND IRON TECHNIQUES
(2007-06-01)
Shih, Yen-Yu
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Chen, You-Yin
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Hsieh, Wen-Yuan
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Huang, Ying-Yuan
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Chang, Chen
Conventional blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) has been wildly used in neuroscience studies. Even though the BOLD method offers the functional information, the low signal-to-noise ratio could not provide an activated brain area accurately and the signal could not be easily inspected from the complicated neuronal interactions. In this regard, the present study aims to use an ultra-small super-paramagnetic iron oxide (USPIO) nanoparticle coated with covalently bound bifunctional poly(ethylene glycol) polymers to enhance the brain functional responses by the IRON (increased relaxation with iron oxide nanoparticles) technique. The R1 and R2 of this USPIO were 53.6 mMsec-1 and 359.8mMsec-1, respectively, and both were higher than most of the commercial products under 0.47 T nuclear magnetic resonance measurement. In this study, the time activity curves in responsive brain areas were evaluated following USPIO injection (3 mg of Fe/kg). The amphetamine (2 mg/kg) was used as a functional stimulator to reveal the changes of relative cerebral blood volume in different brain areas. All imaging experiments were performed by Bruker Biospec BMT 47/40 4.7 T MRI system. The results show that, compared to the BOLD signals; significant event related responses were observed in striatum, insular cortex, nucleus accumbens, somatosensory cortices, and lateral thalamus using the IRON technique. Furthermore, the usability of this USPIO in detecting rCBV responses was confirmed by comparing with previous researches.
Exploring nociceptive response by BOLD MRI in alpha-chloraRose anesthetized rats
(2006-01-01)
Shih, Yen-Yu
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Chen, You-Yin
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Chen, Jin-May
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Lung, Yun
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Chen, Jun-Ying
The technique of blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to provide a spatial-temporal mapping of nociceptive activation in brain. We contrived to obtain an illustration of the pain related regions by injecting formalin at the hindpaw using a 4.7 T MR system in a-chloralose anesthetized rats. In order to obtain the pain response, we avoided any invasive surgery on animals to purify the signal of nociception. The dynamic data were analyzed by mapping correlation coefficient and the time activity curves were calculated by atlas-based region of interest selection. The BOLD signals showed obvious difference in anterior cingulated cortex, somatosensory cortex, medial thalamus, and striatum after stimulation. The results not only show the global somatotopic organization of noxious stimulation on hindpaw in rats, but also provided invaluable information for neuroscience research.
ISPMER: Integrated system for combined PET, MRI, and electrophysiological recording in somatosensory studies in rats
(2007-10-01)
Shih, Yen-Yu
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Chen, You-Yin
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Chen, Jyh-Cheng
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Chang, Chen
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Jaw, Fu-Shan
The present study developed an integrated system for use in combined PET, MRI, and electrophysiological recording in somatosensory studies in rats, called ISPMER. A stereotaxic frame was designed for animal positioning that could be used in all three measurement modalities, and its dimensions complied with the gold standard of the Paxinos and Watson rat brain atlas. A graphical user interface was developed for analyzing the data using several signal processing algorithms. This integrated system provides a novel interface for the recording and processing of three-dimensional neuronal signals in three modalities. (c) 2007 Elsevier B.V. All rights reserved.
Neuroimaging Spectrum at Pre-, Early, and Late Symptomatic Stages of SCA17 Mice
(1970-01-01)
Chen, Chiao-Chi
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Yao, Nai-Wei
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Lin, Chia-Wei
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Su, Wei-Shuo
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Wu, Chin-Tien
Spinocerebellar ataxia (SCA) is a hereditary neurodegenerative disease. We have generated SCA17 transgenic mice bearing human TBP with 109 CAG repeats under the Purkinje cell-specific L7/pcp2 promoter. These mice recapitulate the patients' phenotypes and are suitable for the study of the SCA17 pathomechanism. Magnetic resonance imaging (MRI) and immunostainings were performed to identify the neuroimaging spectrum during disease progression. The results indicate that despite an overall normal appearance at birth, postnatal brain damage takes place rapidly in SCA17. Cerebellar atrophy, fourth-ventricle enlargement, and reduced cerebellar N-acetylaspartate levels were detected at the presymptomatic stage, when the mice were juvenile. The aberrations, which included reductions in body weight; cerebral size; striatal size; and the mean, radial, and axial diffusivities of the cerebellum, became more salient as the disease progressed to the old, late-symptomatic stage. Phosphorylated H2A histone family, member X (gamma H2AX) immunostaining revealed that the cerebellum underwent severe cell senescence in the old stage while the striatum appeared relatively unaffected by aging. Morphometric analysis indicated that the cerebellar atrophy occurred in all subregions with aging. The data establish that the SCA17 mouse brain appears normal at birth but becomes aberrant at the presymptomatic/juvenile stage. More widespread deficits add to the pathological spectrum at the old stage. The study provides information for the expression and expansion of L7/pcp2 promoter and implies the disease progression of SCA17 patients.
Whole-brain functional magnetic resonance imaging mapping of acute nociceptive responses induced by formalin in rats using atlas registration-based event-related analysis
(2008-06-01)
Shih, Yen-Yu I.
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Chen, You-Yin
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Chen, Chiao-Chi V.
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Chen, Jyh-Cheng
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Chang, Chen
Nociceptive neuronal activation in subcortical regions has not been well investigated in functional magnetic resonance imaging (fMRI) studies. The present report aimed to use the blood oxygenation level-dependent (BOLD) fMRI technique to map nociceptive responses in both subcortical and cortical regions by employing a refined data processing method, the atlas registration-based event-related (ARBER) analysis technique. During fMRI acquisition, 5% formalin (50 mu l) was injected into the left hindpaw to induce nociception. ARBER was then used to normalize the data among rats, and images were analyzed using automatic selection of the atlas-based region of interest. It was found that formalin-induced nociceptive processing increased BOLD signals in both cortical and subcortical regions. The cortical activation was distributed over the cingulate, motor, somatosensory, insular, and visual cortices, and the subcortical activation involved the caudate putamen, hippocampus, periaqueductal gray, superior colliculus, thalamus, and hypothalamus. With the aid of ARBER, the present study revealed a detailed activation pattern that possibly indicated the recruitment of various parts of the nociceptive system. The results also demonstrated the utilization of ARBER in establishing an fMRI-based whole-brain nociceptive map. The formalin induced nociceptive images may serve as a template of central nociceptive responses, which can facilitate the future use of fIVIRI in evaluation of new drugs and preclinical therapies for pain. (c) 2008 Wiley-Liss, Inc.