Electrophysiological Neuroimaging . Cortical Imaging Technique Cortical potential maps are of clinical importance for the presurgical diagnosis in epilepsy patients. Comparing with scalp potential, i.e. electroencephalogram (EEG), it has the substantially increased spatial resolution, which, however, is only available by means of invasive sub-dural electrode recordings, i.e. electrocorticogram (ECoG) in a clinical setting. A novel cortical imaging technique has been developed in our laboratory to estimate cortical potential maps, which reflect well the cortical source distributions, directly from scalprecorded EEG signals in a realistic geometry inhomogeneous head model by means of the boundary element method (He et al. 1999, pdf). This technique provides a unique inverse solution to the EEG inverse problem and offers an important capability of noninvasively estimating cortical potentials. The validity of this technique has been rigorously validated in a group of epilepsy patients (He et al. 2002, pdf). Recently, we further advanced the technique with the use of finite element method, which enable us to incorporate highly inhomogeneous and anisotropic media into our head model. We thus are able to further evaluate and validate this technique with simultaneously recorded EEG and ECoG data (Zhang et al., 2006, pdf) during the same session. Our cortical imaging results demonstrate its capability of imaging cortical regions displaying epileptiform activity as confirmed by neurosurgical treatment in the same patients (Zhang et al. 2003, pdf). . 3D Current Source Imaging and Connectivity Imaging It is of importance to develop a high resolution spatio-temporal imaging modality to directly image spatially distributed neuronal electrical current flow. EEG provides unique insights into the dynamic behavior of the human brain as it has the ability to follow changes in neural activity on a millisecond timescale. On the other hand, raw head surface potential recording cannot provide the satisfactory assessment and interpretation of brain function because of its comparatively low spatial resolution and limited penetration. We have been developing a subspace source localization approach - FINE, for localizing brain electrical current sources in 3D brain space (Xu et al. 2004, pdf) with high spatial resolution, and further advanced by considering the realistic geometry inhomogeneous head model (Ding & He, 2006, pdf). Our current source imaging results have indicates its applicability in localizing neural sources responsible for evoked potentials and spontaneous activity (Ding et al., 2006, pdf) as supported by other imaging modalities, such as MRI and ECoG. Furthermore, we have been developing connectivity imaging techniques based on the outcomes from 3D current source imaging to infer the dynamic behavior and functional relationship among the current sources. One of such techniques integrated with FINE has demonstrates its capability in distinguish neural sources for seizure initiation and those for seizure propagation in epilepsy (Ding et al., 2006, pdf). Multimodal Neuroimaging . Experimental Multimodal Imaging Dramatic advancements in brain research have been fueled by increasingly sophisticated neuroimaging technology. Functional MRI (fMRI) using endogenous blood oxygenation level dependent (BOLD) contrast is a well established technique for mapping human brain function, which is being used extensively in human neuroscience research and is rapidly entering clinical practice. On the other hand, the benefits of EEG are almost precisely the obverse of those of fMRI, in that it provides millisecond level temporal resolution but with limited spatial resolution. We have been investigating the simultaneous EEG and fMRI during the same experimental session and have demonstrated the feasibility in a 3T MRI system. We have been investigating the effects of simultaneous recording on EEG, fMRI, and EEG-fMRI integrated source imaging results. The developed experimental multimodal imaging framework have greatly facilitated our investigations on brain functions, such as the retinotopic mapping in human visual system (Im et al, J Neurosci Meth, 2006, pdf) and the cortical visual pathways and dynamic visual interactions. . Multimodal Integration: EEG-fMRI Neuroimaging The EEG and fMRI techniques are complementary instead of competitive in functional neuroimaging considering their different emphases in spatial and time domains. Experimental multimodal imaging is good at investigating neuroscience problems. However, different imaging techniques in this framework are lack of unified and consistent spatial and temporal responses and, thus usually provide information in different contexts. Towards this end, we have developed a novel algorithm based on the Twomey regularization to address the potential spatial mismatches between the fMRI response and the EEG neural source activity (Liu et al, Clin Neurophsiol, 2006, pdf). We have been investigating multimodal integration techniques for EEG-fMRI neuroimaging. Such multimodal techniques hold a unified theoretical basis and promise to combine the complementary advantages of EEG and fMRI, as well, by providing high resolutions in both temporal and spatial domains. A neuroimaging technique has been developed to reconstruct cortical current source distribution based on cortical current density (CCD) model by fusing EEG and fMRI measurements. With such CCD reconstruction, we are able to analyze the complex spatiotemporal neural dynamics and sophisticated neural interaction (Babiloni et al., 2005, pdf). The availability of such high-resolution spatio-temporal functional neuroimaging technology would provide an important advancement in brain research, and improve clinical diagnosis and management of neurological and psychiatric disorders. Neural Interfacing . Spatial-Time-Frequency Approach to Brain-Computer-Interface Electroencephalography (EEG) is an important technique for studying the temporal dynamics of neural activities and interactions. The state-of-the-art EEG mapping includes a high-density array of sensors that record electrical potentials over the scalp, giving rise to a spatiotemporal dataset. Our lab has developed a variety of signal processing techniques to obtain the signature of brain activity spanned in time, frequency and spatial domains (Wang & He, 2004, pdf). Statistical approaches such as principal component analysis (PCA) and independent component analysis (ICA) are used for denoising and isolating signal sources from the raw EEG data. Spatial filtering technique such as Laplacian operator allows the enhancement of spatial resolution of EEG mapping. Time-frequency analysis using Morlet wavelet decomposition and short-time Fourier transform has been demonstrated capable of characterizing event-related (de)synchronization (ERD/ERS) associated with motor imagery tasks. We have been investigating the exploitation of these ERD/ERS signals for high accuracy pattern recognition and classification in the brain-computer-interface application (Yamawaki & He, 2006, pdf). The high efficiency could be achieved by such novel spatial-time-frequency approach through optimizing the information extraction in multi-channel EEGs. Figure 1. The evolution of a piece of raw EEG (first row) through a series of EEG processing steps. Time 0 indicates the preparation cue onset moment. Values from 0 to 2 second were used for classification. Second row shows Laplacian filtered EEG signals. Rhythmical power variations along time course are delineated by its envelopes (third row), which constitutes an original feature description. By averaging these envelopes of one mental state over all trials, clear ERD/ERS patterns can be observed (fourth row). Fig 2 Time–frequency weight distributions of 9 subjects for the case montage IV and QZ4. See detail in Wang & He, 2004. . Inverse imaging in Brain-Computer-Interface A Brain-Computer-Interface (BCI) is a method of communication based on voluntary neural activity generated by the brain and independent of its normal output pathways of peripheral nerves and muscles. The neural activity used in BCI can be recorded using invasive or noninvasive techniques. EEG signals, because of their relatively short time constants, are widely used in BCI systems. BCI can provide the brain with a new, non-muscular communication and control channel for conveying messages and commands to the external world. We have been investigating new means of extracting useful information using from scalp recorded single trials of EEG signals corresponding to motor imagery tasks through neural source imaging techniques, which offers high sensitivity of detecting the intent of human subject (Qin, Ding, & He, J of Neural Eng, 2004, pdf; Kamousi & He, 2005, pdf). Such investigation on the source dimensions of brain activity underlying BCI is promising to help us understanding its control mechanism and possibly leads to the further development and advancement of new BCI system. Fig. 1 Schematic diagram of a BCI system (Vallabhaneni, Wang & He, 2005). Figure 2 The upper two rows are examples of equivalent dipole solutions of different trials in a human subject during imagination of left or right hand in α band. (A, B, C, D, E—left-hand movement imagery; F, G, H, I, J—right-hand movement imagery.) The lower two rows are examples of cortical current density distributions of different trials in a human subject during motor imagination. (A, B, C, D, E—left-hand movement imagery; F, G, H, I, J—right-hand movement imagery.) The results were estimated from single trial scalp EEG data. Cardiac Electrical Imaging . 3D Model-based Electrocardiac Tomography It is of significance to noninvasively image cardiac electrical activity throughout the three dimensional (3D) myocardium. The availability of such an electrocardiac tomography technology may provide critically important information for a better understanding of the mechanisms of cardiac arrhythmia, and clinical diagnosis and management of a variety of cardiac disease. We have developed 3D electrocardiac tomography techniques to image cardiac current density distributions within the myocardium (He & Wu, 2001, pdf), and a heartmodel based tomographic imaging approach to localize the site of origin of cardiac activation (Li & He, 2001, pdf; Li et al., 2003, pdf), image cardiac activation sequence (He et al., 2002, pdf), and image the transmembrane potential distribution (He et al., 2003, pdf) within the 3D anisotropic myocardium in a realistic geometry inhomogeneous heart-torso model. We have been conducting the validation studies of these imaging techniques on both animal models (Zhang et al., 2005, pdf) and human subjects. The ultimate goal is to develop cardiac functional imaging techniques which can image and localize sites of arrhythmogenesis and their activation pattern. Fig. 1 Schematic diagram of 3D electrocardiographic activation imaging. ig. 2 An example of electrocardiographic localization in a patient with implanted pacemaker. The tip of the pacing lead (red dot) was estimated (green dot) with a localization error of 5.2 mm. Fig. 1. A: measured body-surface potential maps following ventricular pacing at a right ventricular site in rabbit experiment. Time refers to the time instant since pacing. B: 3-D AS derived from intracardiac electrograms. Sections are arranged sequentially from base to midlevel (1–11, top row) and from midlevel to apex (13–23, bottom row). C: 3-D AS estimated noninvasively by means of 3-dimensional electrocardiographic imaging. See details in Zhang et al., 2005, pdf . 3D Inverse Cardiac Activation Imaging We have also developed a novel ECG inverse approach for imaging the 3D ventricular activation sequence, which is based on the estimation of the equivalent current density throughout the entire volume of ventricular myocardium (Liu et al, IEEE Trans Med Imaging, 2006, pdf). The spatio-temporal coherence of ventricular excitation process has been utilized to derive the activation time from the estimated time course of equivalent current density defined as the spatial gradient of transmembrane potential. Our pilot results in a computer simulation study have demonstrated the feasibility in imaging 3D cardiac activation sequences. The new technique is promising to provide the important clinical value as well as our 3D model-based electrocardiac tomography techniques. Figure 2: Illustration of the proposed 3-D activation imaging approach. See details in Liu et al, IEEE Trans Med Imaging, 2006. Bioimpedance Imaging Electrical impedance information is useful not only for characterizing biological tissues, but also providing important information aiding electrical source imaging. Novel means are being investigated to image electrical impedance distribution of the biological tissues. . Magnetoacoustic Tomography We have developed a novel methodology -- magnetoacoustic tomography with magnetic induction (MAT-MI) -- by integrating magnetism and ultrasound. MATMI generates magnetic stimulation and then measures ultrasound response for bioimpedance imaging. In MAT-MI, the object is placed in a static magnetic field and a pulsed magnetic field. The pulsed magnetic field induces eddy current in the object. Consequently, the object will emit ultrasonic waves through the Lorenz force produced by the combination of the eddy current and the static magnetic field. The acoustic waves are then collected by the detectors located around the object for image reconstruction. Theoretical (Xu & He, 2005, pdf) and experimental (Li, Xu, He, 2006, pdf) studies indicate that MAT-MI promises to provide high spatial resolution in imaging electrical impedance distribution. Our simulation results further demonstrate the feasibility to reconstruct conductivity distribution with great contrast without the sacrifice of spatial resolution (Li, Xu, He, 2007, pdf). Our future research is undergoing on investigating its physical mechanism and new experimental system, and developing novel image reconstruction for MAT-MI. . Magnetic Resonance Electrical Impedance Tomography (Gao et al 2006) Magnetic Resonance Electrical Impedance Tomography (MREIT) is a newly developed imaging modality that reconstructs the electrical impedance distribution from the magnetic flux density generated by the injected current into a volume conductor. In MREIT, a low frequency current is usually used through a pair of electrodes, and its induced magnetic flux density can be measured by a MRI scanner distributed over the entire conductive media. Such magnetic flux distribution depends on the electrical impedance distribution of the media and, thus, the electrical impedance tomography within the entire media can be reconstructed noninvasively. We have investigating novel MREIT reconstruction algorithms (Gao, Zhu & He, 2005, pdf; Gao, Zhu & He, 2006, pdf), which use only one directional measurement of the magnetic flux density. Electrical impedance distribution of biological tissues can provide useful information about their physiological and pathological status, such as in breast cancer. The future development of MREIT is to improve its sensitivity to small electrical impedance changes and its robustness to measurement noises.