Browsing by Author "Shih, Yen-Yu I."

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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.
Automatic segmentation of magnetic resonance images using a decision tree with spatial information
(2009-03-01)
Chao, Wen-Hung
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Chen, You-Yin
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Lin, Sheng-Huang
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Shih, Yen-Yu I.
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Tsang, Siny
Here we proposed an automatic segmentation method based on a decision tree to classify the brain tissues in magnetic resonance (MR) images. Two types of data - phantom MR images obtained from IBSR (http://www.cma.mgh.harvard.edu/ibsr) and simulated brain MR images obtained from BrainWeb (http://www.bic.mni.mcgill.ca/brainweb) - were segmented using an automatic decision tree algorithm to obtain images with improved visual rendition. Spatial information on the general gray level (G), spatial gray level (S), and two-dimensional wavelet transform (M was combined in-plane in two coordinate systems (Euclidean coordinates (x,y) or polar coordinates (r,theta)). The decision tree was constructed based on a binary tree with nodes created by splitting the distribution of input features of the tree. The spatial information obtained from MR images with different noise levels and inhomogeneities were segmented to compare whether the use of a decision tree improved the identification of human anatomical structures in a neuroimage. The average accuracy rates of segmentation for phantom images with a noise variation of 15 gray levels were 0.9999 and 0.9973 with spatial information (G, x,y, r, theta) and (S, x, y, r, theta), respectively, and 0.9999 and 0.9819 with spatial information (G, x, y, S, r, theta) and (W, x, y, G, r, theta). The average accuracy rates of segmentation for simulated MR images with a noise level of 5% were 0.9532 and 0.9439 with spatial information (G, x, y, r, theta) and (S, x, y, r, theta), respectively, and 0.9446 and 0.9287 with spatial information (G, x, y, S, r, theta) and (W, x, y, G, r, theta). The accuracy rates of segmentation were highest for both simulated phantom and brain MR images, having the lowest noise levels, from a reduction of overlapping gray levels in the images. The accuracies of segmentation were higher when the spatial information included the general gray level than when it included the spatial gray level, which in turn were higher than when it included the wavelet transform. Furthermore, the performance of segmentation was also evaluated with a boundary detection methodology that is based on the Hausdorff distance to compare with the mean computer to observer difference (COD) and mean interobserver difference (IOD) for gray matter (GM), white matter (WM), and all areas (ALL) from images segmented using the decision tree. The values of mean COD are similar and around 12 mm for GM segmented using the decision tree. Our segmentation method based on a decision tree algorithm presented an easy way to perform automatic segmentation for both phantom and tissue regions in brain MR images. (C) 2008 Published by Elsevier Ltd.
Automatic spike sorting for extracellular electrophysiological recording using unsupervised single linkage clustering based on grey relational analysis
(2011-06-01)
Lai, Hsin-Yi
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Chen, You-Yin
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Lin, Sheng-Huang
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Lo, Yu-Chun
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Tsang, Siny
Automatic spike sorting is a prerequisite for neuroscience research on multichannel extracellular recordings of neuronal activity. A novel spike sorting framework, combining efficient feature extraction and an unsupervised clustering method, is described here. Wavelet transform (WT) is adopted to extract features from each detected spike, and the Kolmogorov-Smirnov test (KS test) is utilized to select discriminative wavelet coefficients from the extracted features. Next, an unsupervised single linkage clustering method based on grey relational analysis (GSLC) is applied for spike clustering. The GSLC uses the grey relational grade as the similarity measure, instead of the Euclidean distance for distance calculation; the number of clusters is automatically determined by the elbow criterion in the threshold-cumulative distribution. Four simulated data sets with four noise levels and electrophysiological data recorded from the subthalamic nucleus of eight patients with Parkinson's disease during deep brain stimulation surgery are used to evaluate the performance of GSLC. Feature extraction results from the use of WT with the KS test indicate a reduced number of feature coefficients, as well as good noise rejection, despite similar spike waveforms. Accordingly, the use of GSLC for spike sorting achieves high classification accuracy in all simulated data sets. Moreover, J-measure results in the electrophysiological data indicating that the quality of spike sorting is adequate with the use of GSLC.
Correction of inhomogeneous magnetic resonance images using multiscale retinex for segmentation accuracy improvement
(2012-03-01)
Chao, Wen-Hung
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Lai, Hsin-Yi
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Shih, Yen-Yu I.
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Chen, You-Yin
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Lo, Yu-Chun
The purpose of this study was to improve the accuracy of tissue segmentation on brain magnetic resonance (MR) images preprocessed by multiscale retinex (MSR), segmented with a combined boosted decision tree (BDT) and MSR algorithm (hereinafter referred to as the MSRBDT algorithm). Simulated brain MR (SBMR) T1-weighted images of different noise levels and RF inhomogeneities were adopted to evaluate the outcome of the proposed method; the MSRBDT algorithm was used to identify the gray matter (GM), white matter (WM), and cerebral-spinal fluid (CSF) in the brain tissues. The accuracy rates of GM, WM, and CSF segmentation, with spatial features (G, x, y, r, theta), were respectively greater than 0.9805, 0.9817, and 0.9871. In addition, images segmented with the MSRBDT algorithm were better than those obtained with the expectation maximization (EM) algorithm; brain tissue segmentation in MR images was significantly more precise. The proposed MSRBDT algorithm could be beneficial in clinical image segmentation. (C) 2011 Elsevier Ltd. All rights reserved.
Design, simulation and experimental validation of a novel flexible neural probe for deep brain stimulation and multichannel recording
(2012-06-01)
Lai, Hsin-Yi
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Liao, Lun-De
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Lin, Chin-Teng
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Hsu, Jui-Hsiang
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He, Xin
An implantable micromachined neural probe with multichannel electrode arrays for both neural signal recording and electrical stimulation was designed, simulated and experimentally validated for deep brain stimulation (DBS) applications. The developed probe has a rough three-dimensional microstructure on the electrode surface to maximize the electrode-tissue contact area. The flexible, polyimide-based microelectrode arrays were each composed of a long shaft (14.9 mm in length) and 16 electrodes (5 mu m thick and with a diameter of 16 mu m). The ability of these arrays to record and stimulate specific areas in a rat brain was evaluated. Moreover, we have developed a finite element model (FEM) applied to an electric field to evaluate the volume of tissue activated (VTA) by DBS as a function of the stimulation parameters. The signal-to-noise ratio ranged from 4.4 to 5 over a 50 day recording period, indicating that the laboratory-designed neural probe is reliable and may be used successfully for long-term recordings. The somatosensory evoked potential (SSEP) obtained by thalamic stimulations and in vivo electrode-electrolyte interface impedance measurements was stable for 50 days and demonstrated that the neural probe is feasible for long-term stimulation. A strongly linear (positive correlation) relationship was observed among the simulated VTA, the absolute value of the SSEP during the 200 ms post-stimulus period (Sigma SSEP) and c-Fos expression, indicating that the simulated VTA has perfect sensitivity to predict the evoked responses (c-Fos expression). This laboratory-designed neural probe and its FEM simulation represent a simple, functionally effective technique for studying DBS and neural recordings in animal models.
Imaging brain hemodynamic changes during rat forepaw electrical stimulation using functional photoacoustic microscopy
(2010-08-15)
Liao, Lun-De
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Li, Meng-Lin
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Lai, Hsin-Yi
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Shih, Yen-Yu I.
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Lo, Yu-Chun
The present study reported the development of a novel functional photoacoustic microscopy (fPAM) system for investigating hemodynamic changes in rat cortical vessels associated with electrical forepaw stimulation. Imaging of blood optical absorption by fPAM at multiple appropriately-selected and distinct wavelengths can be used to probe changes in total hemoglobin concentration (HbT, i.e., cerebral blood volume [CBV]) and hemoglobin oxygen saturation (SO(2)). Changes in CBV were measured by images acquired at a wavelength of 570 nm (lambda(570)), an isosbestic point of the molar extinction spectra of oxy- and deoxy-hemoglobin, whereas SO(2) changes were sensed by pixel-wise normalization of images acquired at lambda(560) or lambda(600) to those at lambda(570). We demonstrated the capacity of the fPAM system to image and quantify significant contralateral changes in both SO(2) and CBV driven by electrical forepaw stimulation. The fPAM system complements existing imaging techniques, with the potential to serve as a favorable tool for explicitly studying brain hemodynamics in animal models. (C) 2010 Elsevier Inc. All rights reserved.
Improving segmentation accuracy for magnetic resonance imaging using a boosted decision tree
(2008-11-15)
Chao, Wen-Hung
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Chen, You-Yin
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Cho, Chien-Wen
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Lin, Sheng-Huang
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Shih, Yen-Yu I.
The purpose of this study was to improve the accuracy rate of brain tissue classification in magnetic resonance (MR) imaging using a boosted decision tree segmentation algorithm. Herein. we examined simulated phantom MR (SPMR) images, simulated brain MR (SBMR) images, and a real data. The accuracy rate and k index when classifying brain tissues as gray matter (GM), white matter (WM), or cerebral-spinal fluid (CSF) were better when using the boosted decision tree algorithm combined with a fuzzy threshold than when using a statistical region-growing (SRG) algorithm [Wolf 1, Vetter M, Wegner 1, Bottger T, Nolden M, Schobinger M, et al. The medical imaging interaction toolkit. Med Imag Anal 2005;9:594-604] and an adaptive segmentation (AS) algorithm [Wells WM, Crimson WEL, Kikinis R, Jolesz FA. Adaptive segmentation of MRI data. IEEE Trans Med Imag 1996; 15:429-42]. The segmentation performance when using this algorithm on real data from brain MR images was also better than those of SRG and AS algorithm. Segmentation of a real data using the boosted decision tree produced particularly clear brain MR imaging and permitted more accurate brain tissue segmentation. In conclusion, a decision tree with appropriate boost trials successfully improved the accuracy rate of MR brain tissue segmentation. Crown Copyright (C) 2008 Published by Elsevier B.V. All rights reserved.
Investigation of the cerebral hemodynamic response function in single blood vessels by functional photoacoustic microscopy
(2012-06-01)
Liao, Lun-De
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Lin, Chin-Teng
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Shih, Yen-Yu I.
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Lai, Hsin-Yi
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Zhao, Wan-Ting
The specificity of the hemodynamic response function (HRF) is determined spatially by the vascular architecture and temporally by the evolution of hemodynamic changes. Here, we used functional photoacoustic microscopy (fPAM) to investigate single cerebral blood vessels of rats after left forepaw stimulation. In this system, we analyzed the spatiotemporal evolution of the HRFs of the total hemoglobin concentration (HbT), cerebral blood volume (CBV), and hemoglobin oxygen saturation (SO2). Changes in specific cerebral vessels corresponding to various electrical stimulation intensities and durations were bilaterally imaged with 36 x 65-mu m(2) spatial resolution. Stimulation intensities of 1, 2, 6, and 10 mA were applied for periods of 5 or 15 s. Our results show that the relative functional changes in HbT, CBV, and SO2 are highly dependent not only on the intensity of the stimulation, but also on its duration. Additionally, the duration of the stimulation has a strong influence on the spatiotemporal characteristics of the HRF as shorter stimuli elicit responses only in the local vasculature (smaller arterioles), whereas longer stimuli lead to greater vascular supply and drainage. This study suggests that the current fPAM system is reliable for studying relative cerebral hemodynamic changes, as well as for offering new insights into the dynamics of functional cerebral hemodynamic changes in small animals. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [ DOI: 10.1117/1.JBO.17.6.061210]
MicroPET imaging of noxious thermal stimuli in the conscious rat brain
(2010)
Chen, You-Yin
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Shih, Yen-Yu I.
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Lo, Yu-Chun
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Lu, Pen-Li
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Tsang, Siny
Small animal positron emission tomography (microPET) has been utilized in the investigation of nociception. However, a possible drawback from previous studies is the reduced activation pattern due to the application of anesthesia. The purpose of the present study was to demonstrate a potential means of avoiding anesthesia during stimulation, as well as minimizing the confounding anesthetic effect. Sodium pentobarbital and ketamine were first evaluated to determine their effect on microPET images in the current study. [(18)F]-Fluorodeoxyglucose ((18)F-FDG) was an appropriate radiotracer to reveal activated regions in rat brains. Pentobarbital anesthesia significantly reduced (18)F-FDG uptake in neural tissues, blurrier to lower contrast; therefore, ketamine was used to anesthetize animals during microPET. After the rats were anesthetized and secured in a laboratory-made stereotaxic frame, a simple, noninvasive stereotaxic technique was used to position their heads in the microPET scanner and to roughly conform the images in the stereotaxic atlas. For functional imaging, conscious rats were restrained in cages with minimal ambient noise; short repetitive thermal stimuli were applied to each rat's tail subsequently. The rats were adequately anesthetized with ketamine following 30 min of scanning without stimulation. An activation index (AI) was calculated from microPET data to quantify the local metabolic activity changes according to the normalized (18)F-FDG dosage. The average AI indicated a side-to-side difference for all innocuous stimulations in the thalamus. However, such side-to-side difference was only observed for noxious heat and cold stimulations in primary somatosensory cortex (SI), secondary somatosensory cortex (SII), and agranular insular cortex (AIC). The present study demonstrated the feasibility of the microPET technique to image metabolic functions of the conscious rat brain, offering better rationale and protocol designs for future pain studies.
MicroPET study of brain neuronal metabolism under electrical and mechanical stimulation of the rat tail
(2009-03-01)
Chen, You-Yin
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Shih, Yen-Yu I.
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Chien, Chia-Nan
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Chou, Ta-Wei
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Lee, Tee-Wei
Objective Small-animal positron emission tomography (microPET) has been widely used for measuring various molecular processes in the rodent brain. The somatotopic projection, however, has not been identified earlier using microPET under electrical stimulation (ES) and mechanical stimulation (MS). This study aimed to utilize microPET to investigate the glucose metabolism of cortical and thalamic responses to ES and MS of the rat tail. Methods The rats were anesthetized by ketamine and a custom-built stereotaxic frame was used to fix the rat head to ensure that the scanned images were concordant with an atlas. [(18)F]-fluorodeoxyglucose (FDG) was used as a radiotracer to reveal the brain metabolic changes. An activation index (AI) was calculated from microPET data o quantify the changes in local metabolic activities normalized to variations in FDG dosage between animals. Results The results showed that ES increased FDG uptake in both the contralateral thalamus (AI=18) and cortex (AI=12.5), with significant side-to-side differences (P<0.05, paired t-test). MS also significantly increased FDG uptake in both cortical and thalamic regions, although lateralization was absent in the thalamus. Conclusion This study indicated that microPET can be used to elucidate the functional and quantitative neuronal activities of brain structures of rodents under peripheral stimulation, and could be applied in investigations of brain sensory functions. Nucl Med Commun 30:188-193 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Transcranial imaging of functional cerebral hemodynamic changes in single blood vessels using in vivo photoacoustic microscopy
(2012-06-01)
Liao, Lun-De
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Lin, Chin-Teng
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Shih, Yen-Yu I.
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Duong, Timothy Q.
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Lai, Hsin-Yi
Optical imaging of changes in total hemoglobin concentration (HbT), cerebral blood volume (CBV), and hemoglobin oxygen saturation (SO2) provides a means to investigate brain hemodynamic regulation. However, high-resolution transcranial imaging remains challenging. In this study, we applied a novel functional photoacoustic microscopy technique to probe the responses of single cortical vessels to left forepaw electrical stimulation in mice with intact skulls. Functional changes in HbT, CBV, and SO2 in the superior sagittal sinus and different-sized arterioles from the anterior cerebral artery system were bilaterally imaged with unambiguous 36x65-mu m(2) spatial resolution. In addition, an early decrease of SO2 in single blood vessels during activation (i.e., 'the initial dip') was observed. Our results indicate that the initial dip occurred specifically in small arterioles of activated regions but not in large veins. This technique complements other existing imaging approaches for the investigation of the hemodynamic responses in single cerebral blood vessels. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 938-951; doi:10.1038/jcbfm.2012.42; published online 4 April 2012
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.