Experimental Neuroimaging Laboratory
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Neurovascular coupling and uncoupling in the cortex and the striatum: We have recently developed multimodal MRI techniques to measure cerebral blood oxygenation, blood flow, blood volume, and oxygen metabolism changes in preclinical animal models (Shih et al., J Cereb Blood Flow and Metab, 2011). These techniques were used to investigate neurovascular function and functional MRI (fMRI) signal mechanisms in vivo. It is traditionally accepted that increased neural activity is accompanied by increases in hemodynamic responses. Our group challenged this general concept of functional brain imaging by demonstrating sustained negative fMRI signals along with increases in neuronal activity in the striatum by using a model that evokes endogenous neurotransmission via peripheral noxious stimulation (Shih et al., J Neurosci, 2009, Shih et al., Exp Neurol, 2012, Chen et al., Neurobiol Dis, 2013). These findings show that caution should be taken in the interpretation of perfusion-based functional imaging data, as the presence of vasoactive neurotransmitters may confound results. We plan to use multimodal MRI techniques to investigate the role of striatal vasoconstriction in pain and pain management. This striatal negative fMRI signal is also being used as an imaging marker for striatal functional recovery/reorganization in animal model of stroke and Parkinson’s disease.
                



fMRI and electrophysiology: Our lab is developing simultaneous fMRI/electrophysiology at high spatial resolution (ranged from 30 to 100 microns) to elucidate the neurophysiological origins of fMRI signals and the pathophysiological mechanisms of neurovascular diseases (Shih et al., Neuroimage, 2013). The MRI-compatible multichannel microelectrode array and micro-EEG cap are designed and fabricated using semiconductor production and microelectro-mechanical systems (MEMS) technology (Lai et al., J Neural Eng, 2012). Combing fMRI and electrophysiology provides additional neural information and has potential to complement current fMRI techniques that primarily measure hemodynamic responses.
 
 
Deep brain stimulation and optogenetic fMRI:
Deep brain stimulation (DBS) is a neurosurgical technique which is currently used to treat a variety of neurological and psychiatric disorders. The mechanism by which DBS alleviates neurological symptoms is still incompletely understood, limiting the generalizability of this procedure to new targets. The combination of DBS and fMRI enables the study of regional responses to stimulation as well as functional connectivity changes during stimulation, with the potential to optimize treatment parameters and monitor therapeutic outcomes (Lai et al., Neuroimage, 2013, Younce et al., J Vis Exp, 2013, Albaugh and Shih, Brain Connect, 2013). In addition, we are also developing neuroimaging techniques to study brain functional circuits using optogenetics, allowing high throughput measurement of genetically-defined neurovascular activity at a whole brain scale. Our goal is to use optogenetic modulation to dissect the DBS-induced changes in brain neural activity and connectivity in Parkinsonian animal models. 


 
Peri-infarct spreading depolarization in stroke:
Peri-infarct spreading depolarization describes a series of propagating electrical potentials that silence brain activity, alter cerebral blood flow, induce cell swelling, and appear during the hyperacute phase of stroke.
 PID has been shown to accelerate stroke progression, and suppressing PID is known to reduce infarct volume. Although PID is a potential therapeutic target for stroke, the spatiotemporal properties of PIDs remain to be characterized and how reperfusion affects PID signatures is largely unexplored.  Optical imaging and EEG/ECoG recording allow identification of PID, but both techniques are depth-limited and cannot provide volumetric tissue information with clinically relevant indices. To our knowledge, PID has not been systemically characterized by MRI due to technical constraints. Because PID appears immediately after stroke onset, we have developed a novel photothrombotic model that allows stroke induction inside the MRI system to capture the entire temporal evolution of PID features and stroke progression. Our goal is to quantitatively probe spatiotemporal PID signatures using perfusion and diffusion MRI in an experimental rat model with and without reperfusion. Our model can also induce an ischemic lesion in any predetermined brain area, which opens up new avenues for preclinical stroke research.
 
 

                        


Ocular MRI: Our group have developed and applied multimodal MRI techniques to investigate eye function and ocular circulation. Ocular MRI in small animal models is challenging due to limited spatial resolution and insufficient signal-to-noise ratio. We implemented ultra-high resolution MRI to resolve different retinal layers and choroid as well as their blood flow supply in quantitative units (Shih et al., J Magn Reson Imaging, 2013). We also investigated light-evoked functional hyperemia in the retina and choroid with laminar resolution (Shih et al., Invest Ophthalmol Vis Sci, 2011, Shih et al., Curr Eye Res, 2013) and revealed how retinal and choroidal circulations respond to pharmacological (Shih et al., Magn Reson Med, 2012) and gas challenges (Shih et al., Radiology, 2012). These techniques will be used to study eye diseases such as retinal ischemia, retinal degeneration and diabetic retinopathy.