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Introduction Diagnosis of very short-segment Hirschsprung's disease (vsHD) by rectal suction biopsy is challenging as its aganglionic zone (AZ) overlaps with physiologic hypoganglionic zone and calretinin-positive mucosal nerves may extend from the transition zone (TZ) into AZ. We studied whether an increasing trend/gradient of calretinin-positive mucosal nerves along the distance from AZ toward TZ aids in diagnosis of HD. Materials and Methods In this study, 46 rectal suction biopsies from non-HD and HD, and 15 pull-through specimens from short-segment HD were evaluated by mucosal calretinin immunostain (CI) and image processing and analysis (IPA) to measure pixel count (PC, the percentage of calretinin stained pixels in the mucosa). Consecutive longitudinal sections of proximal AZ toward distal TZ in HD pull-through specimens were utilized as a vsHD surrogate model. First, we studied variability of mucosal CI in non-HD biopsies along the distance from dentate line. Second, we determined a cutoff point of mucosal CI by IPA that separated non-HD versus HD and applied this cutoff to longitudinal sections from proximal AZ to distal TZ segments in HD pull-through specimens. Third, we studied whether an increasing trend of mucosal CI was universally observed in HD pull-through. Results Our findings included a significant variability in PC along the biopsy distance in non-HD cases. Positive mucosal CI was found in proximal AZ in 6 (43%) of 14 HD pull-through, among which 1 case lacked submucosal nerve hypertrophy in the proximal AZ. All 14 HD pull-through cases showed an increasing trend/gradient of PC from AZ toward TZ. Conclusion Based on our findings, the presence or absence of mucosal CI positivity and submucosal nerve hypertrophy may not reliably diagnose vsHD in rectal suction biopsy. While we acknowledge that the density of mucosal innervation in variable contexts and anatomical locations is unknown and yet to be explored, our study suggests that an increasing trend of positive mucosal CI from AZ toward TZ by IPA might prove to be a useful tool for the diagnosis of vsHD in the future.

Transcranial static magnetic field stimulation (tSMS) is a novel non-invasive brain stimulation technique that has been shown to locally increase alpha power in the parietal and occipital cortex. We investigated if tSMS locally increased alpha power in the left or right prefrontal cortex, as the balance of left/right prefrontal alpha power (frontal alpha asymmetry) has been linked to emotional processing and mood disorders. Therefore, altering frontal alpha asymmetry with tSMS may serve as a novel treatment to psychiatric diseases. We performed a crossover, double-blind, sham-controlled pilot study to assess the effects of prefrontal tSMS on neural oscillations. Twenty-four right-handed healthy participants were recruited and received left dorsolateral prefrontal cortex (DLPFC) tSMS, right DLPFC tSMS, and sham tSMS in a randomized order. Electroencephalography data were collected before (2 minutes eyes-closed, 2 minutes eyes-open), during (10 minutes eyes-open), and after (2 minutes eyes-open) stimulation. In contrast to our hypothesis, neither left nor right tSMS locally increased frontal alpha power. However, alpha power increased in occipital cortex during left DLPFC tSMS. Right DLPFC tSMS increased post-stimulation fronto-parietal theta power, indicating possible relevance to memory and cognition. Left and right DLPFC tSMS increased post-stimulation left hemisphere beta power, indicating possible changes to motor behavior. Left DLPFC tSMS also increased post-stimulation right frontal beta power, demonstrating complex network effects that may be relevant to aggressive behavior. We concluded that DLPFC tSMS modulated the network oscillations in regions distant from the location of stimulation and that tSMS has region specific effects on neural oscillations.

The neuroactive metabolites of the steroid hormones progesterone (P4) and testosterone (T) are GABAergic modulators that influence cognitive control, yet the specific effect of P4 and T on brain network activity remains poorly understood. Here, we investigated if a fundamental oscillatory network activity pattern related to cognitive control, frontal midline theta (FMT) oscillations, are modulated by steroids hormones, P4 and T. We measured the concentration P4 and T using salivary enzyme immunoassay and FMT oscillations using high-density electroencephalography (EEG) during the eyes-open resting state in fifty-five healthy female and male participants. Electrical brain activity was analyzed using Morlet wavelet convolution, beamformer source localization, background noise spectral fitting, and phase amplitude coupling analysis. Steroid hormone concentrations and biological sex were used as predictors for scalp and source-estimated theta oscillations and for top-down theta-gamma phase amplitude coupling. Elevated concentrations of P4 predicted increased FMT oscillatory amplitude across both sexes, and no relationship was found with T. The positive correlation with P4 was specific to the frontal-midline electrodes and survived correction for the background noise of the brain. Using source localization, FMT oscillations were localized to the frontal-parietal network. Additionally, theta amplitude within the frontal-parietal network, but not the default mode network, positively correlated with P4 concentration. Finally, P4 concentration correlated with increased coupling between FMT phase and posterior gamma amplitude. Our results suggest that P4 concentration modulates brain activity via upregulation of theta oscillations in the frontal-parietal network and increased top-down control over posterior cortical sites.Significance StatementThe neuroactive metabolites of the steroid hormones progesterone (P4) and testosterone (T) are GABAergic modulators that influence cognitive control, yet the specific effect of P4 and T on brain network activity remains poorly understood. Here, we investigated if a fundamental oscillatory network activity pattern related to cognitive control, frontal midline theta (FMT) oscillations, are modulated by steroids hormones, P4 and T. Our results suggest that P4 concentration modulates brain activity via upregulation of theta oscillations in the frontal-parietal network and increased top-down control over posterior cortical sites.

Face perception is a highly developed function of the human visual system. Previous studies of event-related potentials (ERPs) have identified a face-selective ERP component (negative peak at about 170 milliseconds after stimulation onset, N170) in healthy participants. In contrast, patients with schizophrenia exhibit reduced amplitude of the N170, which may represent a pathological deficit in the neurophysiology of face perception. Interestingly, healthy humans with schizophrenia-like experiences (schizotypy) also exhibit abnormal processing of face perception. Yet, it has remained unknown how schizotypy in healthy humans is associated with the neurophysiological substrate of face perception. Here, we recruited 35 participants and assessed their schizotypy by the magical ideation rating scale. We used high-density electroencephalography to obtain ERPs elicited by a set of Mooney faces (face and non-face conditions). We divided the participants into two groups (high and low schizotypy) by a median split of schizotypy scores. We investigated mean reaction times and the N170 component in response to the stimuli. We found significant slowed reaction times and reduced amplitude of the N170 component in response to the face stimuli in the high-schizotypy group. In addition, across the full data set, we found that the schizotypy scores were significantly correlated with both the reaction times and the N170 amplitude. Our results thus support the model of schizotypy as a manifestation of a continuum between healthy individuals and patients with schizophrenia, where the N170 impairment serves as a biomarker for the degree of pathology along this continuum.

A major remaining challenge for magnetic resonance-based attenuation correction methods (MRAC) is their susceptibility to sources of MRI artifacts (e.g. implants, motion) and uncertainties due to the limitations of MRI contrast (e.g. accurate bone delineation and density, and separation of air/bone). We propose using a Bayesian deep convolutional neural network that, in addition to generating an initial pseudo-CT from MR data, also produces uncertainty estimates of the pseudo-CT to quantify the limitations of the MR data. These outputs are combined with MLAA reconstruction that uses the PET emission data to improve the attenuation maps. With the proposed approach (UpCT-MLAA), we demonstrate accurate estimation of PET uptake in pelvic lesions and show recovery of metal implants. In patients without implants, UpCT-MLAA had acceptable but slightly higher RMSE than Zero-echo-time and Dixon Deep pseudo-CT when compared to CTAC. In patients with metal implants, MLAA recovered the metal implant; however, anatomy outside the implant region was obscured by noise and crosstalk artifacts. Attenuation coefficients from the pseudo-CT from Dixon MRI were accurate in normal anatomy; however, the metal implant region was estimated to have attenuation coefficients of air. UpCT-MLAA estimated attenuation coefficients of metal implants alongside accurate anatomic depiction outside of implant regions., Comment: Accepted to the IEEE Transactions on Radiation and Plasma Medical Sciences on October 3, 2021. To be published under open access Creative Commons Attribution License (CC BY)

Background Single-pulse transcranial magnetic stimulation (TMS) elicits an evoked electroencephalography (EEG) potential (TMS-evoked potential, TEP), which is interpreted as direct evidence of cortical reactivity to TMS. Thus, combining TMS with EEG can be used to investigate the mechanism underlying brain network engagement in TMS treatment paradigms. However, controversy remains regarding whether TEP is a genuine marker of TMS-induced cortical reactivity or if it is confounded by responses to peripheral somatosensory and auditory inputs. Resolving this controversy is of great significance for the field and will validate TMS as a tool to probe networks of interest in cognitive and clinical neuroscience. Objective Here, we delineated the cortical origin of TEP by spatially and temporally localizing successive TEP components, and modulating them with transcranial direct current stimulation (tDCS) to investigate cortical reactivity elicited by single-pulse TMS and its causal relationship with cortical excitability. Methods We recruited 18 healthy participants in a double-blind, cross-over, sham-controlled design. We collected motor-evoked potentials (MEPs) and TEPs elicited by suprathreshold single-pulse TMS targeting the left primary motor cortex (M1). To causally test cortical and corticospinal excitability, we applied tDCS to the left M1. Results We found that the earliest TEP component (P25) was localized to the left M1. The following TEP components (N45 and P60) were largely localized to the primary somatosensory cortex, which may reflect afferent input by hand-muscle twitches. The later TEP components (N100, P180, and N280) were largely localized to the auditory cortex. As hypothesized, tDCS selectively modulated cortical and corticospinal excitability by modulating the pre-stimulus mu-rhythm oscillatory power. Conclusion Together, our findings provide causal evidence that the early TEP components reflect cortical reactivity to TMS.

Our objective was to determine clinically the value of time-of-flight (TOF) information in reducing PET artifacts and improving PET image quality and accuracy in simultaneous TOF PET/MR scanning. A total 65 patients who underwent a comparative scan in a simultaneous TOF PET/MR scanner were included. TOF and non-TOF PET images were reconstructed, clinically examined, compared and scored. PET imaging artifacts were categorized as large or small implant-related artifacts, as dental implant-related artifacts, and as implant-unrelated artifacts. Differences in image quality, especially those related to (implant) artifacts, were assessed using a scale ranging from 0 (no artifact) to 4 (severe artifact). A total of 87 image artifacts were found and evaluated. Four patients had large and eight patients small implant-related artifacts, 27 patients had dental implants/fillings, and 48 patients had implant-unrelated artifacts. The average score was 1.14 ± 0.82 for non-TOF PET images and 0.53 ± 0.66 for TOF images (p

Background/Aims: In exploring human factors, stereoscopic 3D images have been used to investigate the neural responses associated with excessive depth, texture complexity, and other factors. However, the cortical oscillation associated with the complexity of stereoscopic images has been studied rarely. Here, we demonstrated that the oscillatory responses to three differently shaped 3D images (circle, star, and bat) increase as the complexity of the image increases. Methods: We recorded simultaneous EEG/MEG for three different stimuli. Spatio-temporal and spatio-spectro-temporal features were investigated by non-parametric permutation test. Results: The results showed that N300 and alpha inhibition increased in the ventral area as the shape complexity of the stereoscopic image increased. Conclusion: It seems that the relative disparity in complex stereoscopic images may increase cognitive processing (N300) and cortical load (alpha inhibition) in the ventral area.

Transcranial alternating current stimulation (tACS) modulates endogenous neural oscillations in healthy human participants by the application of a low-amplitude electrical current with a periodic stimulation waveform. Yet, it is unclear if tACS can modulate and restore neural oscillations that are reduced in patients with psychiatric illnesses such as schizophrenia. Here, we asked if tACS modulates network oscillations in schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast tACS with transcranial direct current stimulation (tDCS) and sham stimulation in 22 schizophrenia patients with auditory hallucinations. We used high-density electroencephalography to investigate if a five-day, twice-daily 10Hz-tACS protocol enhances alpha oscillations and modulates network dynamics that are reduced in schizophrenia. We found that 10Hz-tACS enhanced alpha oscillations and modulated functional connectivity in the alpha frequency band. In addition, 10Hz-tACS enhanced the 40Hz auditory steady-state response (ASSR), which is reduced in patients with schizophrenia. Importantly, clinical improvement of auditory hallucinations correlated with enhancement of alpha oscillations and the 40Hz-ASSR. Together, our findings suggest that tACS has potential as a network-level approach to modulate reduced neural oscillations related to clinical symptoms in patients with schizophrenia.

Performance variation is a critical issue in motor imagery brain–computer interface (MI-BCI), and various neurophysiological, psychological, and anatomical correlates have been reported in the literature. Although the main aim of such studies is to predict MI-BCI performance for the prescreening of poor performers, studies which focus on the user’s sense of the motor imagery process and directly estimate MI-BCI performance through the user’s self-prediction are lacking. In this study, we first test each user’s self-prediction idea regarding motor imagery experimental datasets. Fifty-two subjects participated in a classical, two-class motor imagery experiment and were asked to evaluate their easiness with motor imagery and to predict their own MI-BCI performance. During the motor imagery experiment, an electroencephalogram (EEG) was recorded; however, no feedback on motor imagery was given to subjects. From EEG recordings, the offline classification accuracy was estimated and compared with several questionnaire scores of subjects, as well as with each subject’s self-prediction of MI-BCI performance. The subjects’ performance predictions during motor imagery task showed a high positive correlation (r = 0.64, p < 0.01). Interestingly, it was observed that the self-prediction became more accurate as the subjects conducted more motor imagery tasks in the Correlation coefficient (pre-task to 2nd run: r = 0.02 to r = 0.54, p < 0.01) and root mean square error (pre-task to 3rd run: 17.7% to 10%, p < 0.01). We demonstrated that subjects may accurately predict their MI-BCI performance even without feedback information. This implies that the human brain is an active learning system and, by self-experiencing the endogenous motor imagery process, it can sense and adopt the quality of the process. Thus, it is believed that users may be able to predict MI-BCI performance and results may contribute to a better understanding of low performance and advancing BCI.

Recently, neurophysiological findings about social interaction have been investigated widely, and hardware has been developed that can measure multiple subjects' brain activities simultaneously. These hyperscanning studies have enabled us to discover new and important evidences of interbrain interactions. Yet, very little is known about verbal interaction without any visual input. Therefore, we conducted a new hyperscanning study based on verbal, interbrain turn-taking interaction using simultaneous EEG/MEG, which measures rapidly changing brain activities. To establish turn-taking verbal interactions between a pair of subjects, we set up two EEG/MEG systems (19 and 146 channels of EEG and MEG, respectively) located ∼100 miles apart. Subjects engaged in verbal communication via condenser microphones and magnetic-compatible earphones, and a network time protocol synchronized the two systems. Ten subjects participated in this experiment and performed verbal interaction and noninteraction tasks separately. We found significant oscillations in EEG alpha and MEG alpha/gamma bands in several brain regions for all subjects. Furthermore, we estimated phase synchronization between two brains using the weighted phase lag index and found statistically significant synchronization in EEG and MEG data. Our novel paradigm and neurophysiological findings may foster a basic understanding of the functional mechanisms involved in human social interactions. Hum Brain Mapp 39:171-188, 2018. © 2017 Wiley Periodicals, Inc.

Purpose To investigate proton density (PD)-weighted zero TE (ZT) imaging for morphological depiction and segmentation of cranial bone structures. Methods A rotating ultra-fast imaging sequence (RUFIS) type ZT pulse sequence was developed and optimized for 1) efficient capture of short T2 bone signals and 2) flat PD response for soft-tissues. An inverse logarithmic image scaling (i.e., −log(image)) was used to highlight bone and differentiate it from surrounding soft-tissue and air. Furthermore, a histogram-based bias-correction method was developed for subsequent threshold-based air, soft-tissue, and bone segmentation. Results PD-weighted ZT imaging in combination with an inverse logarithmic scaling was found to provide excellent depiction of cranial bone structures. In combination with bias correction, also excellent segmentation results were achieved. A two-dimensional histogram analysis demonstrates a strong, approximately linear correlation between inverse log-scaled ZT and low-dose CT for Hounsfield units (HU) between −300 HU and 1,500 HU (corresponding to soft-tissue and bone). Conclusions PD-weighted ZT imaging provides robust and efficient depiction of bone structures in the head, with an excellent contrast between air, soft-tissue, and bone. Besides structural bone imaging, the presented method is expected to be of relevance for attenuation correction in positron emission tomography (PET)/MR and MR-based radiation therapy planning. Magn Reson Med 75:107–114, 2016. © 2015 Wiley Periodicals, Inc.

Multi-modal integration, which combines multiple neurophysiological signals, is gaining more attention for its potential to supplement single modality’s drawbacks and yield reliable results by extracting complementary features. In particular, integration of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) is cost-effective and portable, and therefore is a fascinating approach to brain-computer interface (BCI). However, outcomes from the integration of these two modalities have yielded only modest improvement in BCI performance because of the lack of approaches to integrate the two different features. In addition, mismatch of recording locations may hinder further improvement. In this literature review, we surveyed studies of the integration of EEG/fNIRS in BCI thoroughly and discussed its current limitations. We also suggested future directions for efficient and successful multi-modal integration of EEG/fNIRS in BCI systems.

Due to the recent explosion in various forms of 3D content, the evaluation of such content from a neuroscience perspective is quite interesting. However, existing investigations of cortical oscillatory responses in stereoscopic depth perception are quite rare. Therefore, we investigated spatiotemporal and spatio-temporo-spectral features at four different stereoscopic depths within the comfort zone. We adopted a simultaneous EEG/MEG acquisition technique to collect the oscillatory responses of eight participants. We defined subject-specific retinal disparities and designed a single trial-based stereoscopic viewing experimental paradigm. In the group analysis, we observed that, as the depth increased from Level 1 to Level 3, there was a time-locked increase in the N200 component in MEG and the P300 component in EEG in the occipital and parietal areas, respectively. In addition, initial alpha and beta event-related desynchronizations (ERD) were observed at approximately 500 to 1000 msec, while theta, alpha, and beta event-related synchronizations (ERS) appeared at approximately 1000 to 2000 ms. Interestingly, there was a saturation point in the increase in cognitive responses, including N200, P300, and alpha ERD, even when the depth increased only within the comfort zone. Meanwhile, the magnitude of low beta ERD decreased in the dorsal pathway as depth increased. From these findings, we concluded that cognitive responses are likely to become saturated in the visual comfort zone, while perceptual load may increase with depth.

The large number of automobile accidents due to driver drowsiness is a critical concern of many countries. To solve this problem, numerous methods of countermeasure have been proposed. However, the results were unsatisfactory due to inadequate accuracy of drowsiness detection. In this study, we introduce a new approach, a combination of EEG and NIRS, to detect driver drowsiness. EEG, EOG, ECG and NIRS signals have been measured during a simulated driving task, in which subjects underwent both awake and drowsy states. The blinking rate, eye closure, heart rate, alpha and beta band power were used to identify subject’s condition. Statistical tests were performed on EEG and NIRS signals to find the most informative parameters. Fisher’s linear discriminant analysis method was employed to classify awake and drowsy states. Time series analysis was used to predict drowsiness. The oxy-hemoglobin concentration change and the beta band power in the frontal lobe were found to differ the most between the two states. In addition, these two parameters correspond well to an awake to drowsy state transition. A sharp increase of the oxy-hemoglobin concentration change, together with a dramatic decrease of the beta band power, happened several seconds before the first eye closure.

Chronic pain is associated with maladaptive reorganization of the central nervous system. Recent studies have suggested that disorganization of large-scale electrical brain activity patterns, such as neuronal network oscillations in the thalamocortical system, plays a key role in the pathophysiology of chronic pain. Yet, little is known about whether and how such network pathologies can be targeted with noninvasive brain stimulation as a nonpharmacological treatment option. We hypothesized that alpha oscillations, a prominent thalamocortical activity pattern in the human brain, are impaired in chronic pain and can be modulated with transcranial alternating current stimulation (tACS). We performed a randomized, crossover, double-blind, sham-controlled study in patients with chronic low back pain (CLBP) to investigate how alpha oscillations relate to pain symptoms for target identification and whether tACS can engage this target and thereby induce pain relief. We used high-density electroencephalography to measure alpha oscillations and found that the oscillation strength in the somatosensory region at baseline before stimulation was negatively correlated with pain symptoms. Stimulation with alpha-tACS compared to sham (placebo) stimulation significantly enhanced alpha oscillations in the somatosensory region. The stimulation-induced increase of alpha oscillations in the somatosensory region was correlated with pain relief. Given these findings of successful target identification and engagement, we propose that modulating alpha oscillations with tACS may represent a target-specific, nonpharmacological treatment approach for CLBP. This trial has been registered in ClinicalTrials.gov (NCT03243084). Perspective This study suggests that a rational design of transcranial alternating current stimulation, which is target identification, engagement, and validation, could be a nonpharmacological treatment approach for patients with CLBP.

Background: Most investigators of brain–computer interface (BCI) research believe that BCI can be achieved through induced neuronal activity from the cortex, but not by evoked neuronal activity. Motor imagery (MI)–based BCI is one of the standard concepts of BCI, in that the user can generate induced activity by imagining motor movements. However, variations in performance over sessions and subjects are too severe to overcome easily; therefore, a basic understanding and investigation of BCI performance variation is necessary to find critical evidence of performance variation. Here we present not only EEG datasets for MI BCI from 52 subjects, but also the results of a psychological and physiological questionnaire, EMG datasets, the locations of 3D EEG electrodes, and EEGs for non-task-related states. Findings: We validated our EEG datasets by using the percentage of bad trials, event-related desynchronization/synchronization (ERD/ERS) analysis, and classification analysis. After conventional rejection of bad trials, we showed contralateral ERD and ipsilateral ERS in the somatosensory area, which are well-known patterns of MI. Finally, we showed that 73.08% of datasets (38 subjects) included reasonably discriminative information. Conclusions: Our EEG datasets included the information necessary to determine statistical significance; they consisted of well-discriminated datasets (38 subjects) and less-discriminative datasets. These may provide researchers with opportunities to investigate human factors related to MI BCI performance variation, and may also achieve subject-to-subject transfer by using metadata, including a questionnaire, EEG coordinates, and EEGs for non-task-related states.

Investigations of the neuro-physiological correlates of mental loads, or states, have attracted significant attention recently, as it is particularly important to evaluate mental fatigue in drivers operating a motor vehicle. In this research, we collected multimodal EEG/ECG/EOG and fNIRS data simultaneously to develop algorithms to explore neuro-physiological correlates of drivers' mental states. Each subject performed simulated driving under two different conditions (well-rested and sleep-deprived) on different days. During the experiment, we used 68 electrodes for EEG/ECG/EOG and 8 channels for fNIRS recordings. We extracted the prominent features of each modality to distinguish between the well-rested and sleep-deprived conditions, and all multimodal features, except EOG, were combined to quantify mental fatigue during driving. Finally, a novel driving condition level (DCL) was proposed that distinguished clearly between the features of well-rested and sleep-deprived conditions. This proposed DCL measure may be applicable to real-time monitoring of the mental states of vehicle drivers. Further, the combination of methods based on each classifier yielded substantial improvements in the classification accuracy between these two conditions.

Accurate and robust attenuation correction remains challenging in hybrid PET/MR particularly for torsos because it is difficult to segment bones, lungs and internal air in MR images. Additionally, MR suffers from susceptibility artifacts when a metallic implant is present. Recently, joint estimation (JE) of activity and attenuation based on PET data, also known as maximum likelihood reconstruction of activity and attenuation, has gained considerable interest because of (1) its promise to address the challenges in MR-based attenuation correction (MRAC), and (2) recent advances in time-of-flight (TOF) technology, which is known to be the key to the success of JE. In this paper, we implement a JE algorithm using an MR-based prior and evaluate the algorithm using whole-body PET/MR patient data, for both FDG and non-FDG tracers, acquired from GE SIGNA PET/MR scanners with TOF capability. The weight of the MR-based prior is spatially modulated, based on MR signal strength, to control the balance between MRAC and JE. Large prior weights are used in strong MR signal regions such as soft tissue and fat (i.e. MR tissue classification with a high degree of certainty) and small weights are used in low MR signal regions (i.e. MR tissue classification with a low degree of certainty). The MR-based prior is pragmatic in the sense that it is convex and does not require training or population statistics while exploiting synergies between MRAC and JE. We demonstrate the JE algorithm has the potential to improve the robustness and accuracy of MRAC by recovering the attenuation of metallic implants, internal air and some bones and by better delineating lung boundaries, not only for FDG but also for more specific non-FDG tracers such as 68Ga-DOTATOC and 18F-Fluoride.

Attenuation correction is critical to accurate PET quantitation. However, it is challenging to extract accurate attenuation from MR data because of distinct physics of MR and PET. The goal of this study is to achieve robust and accurate attenuation correction in PET/MR. We combine an MR-segmentation based approach and a joint estimation approach synergistically by using an MR-segmentation based attenuation map as an MR-based prior for joint estimation. We evaluate the joint estimation algorithm with MR-based priors using time-of-flight (TOF) PET/MR clinical data. It is demonstrated that the joint estimation method using MR-based priors can recover the attenuation of metal implants, internal air cavities and bones in a robust way.

Ordered subset expectation maximization (OSEM) is the most widely used algorithm for clinical PET image reconstruction. OSEM is usually stopped early and post-filtered to control image noise and does not necessarily achieve optimal quantitation accuracy. As an alternative to OSEM, we have recently implemented a penalized likelihood (PL) image reconstruction algorithm for clinical PET using the relative difference penalty with the aim of improving quantitation accuracy without compromising visual image quality. Preliminary clinical studies have demonstrated visual image quality including lesion conspicuity in images reconstructed by the PL algorithm is better than or at least as good as that in OSEM images. In this paper we evaluate lesion quantitation accuracy of the PL algorithm with the relative difference penalty compared to OSEM by using various data sets including phantom data acquired with an anthropomorphic torso phantom, an extended oval phantom and the NEMA image quality phantom; clinical data; and hybrid clinical data generated by adding simulated lesion data to clinical data. We focus on mean standardized uptake values and compare them for PL and OSEM using both time-of-flight (TOF) and non-TOF data. The results demonstrate improvements of PL in lesion quantitation accuracy compared to OSEM with a particular improvement in cold background regions such as lungs.

Ordered Subset Expectation Maximization (OSEM) is currently the most widely used image reconstruction algorithm for clinical PET. However, OSEM does not necessarily provide optimal image quality, and a number of alternative algorithms have been explored. We have recently shown that a penalized likelihood image reconstruction algorithm using the relative difference penalty, block sequential regularized expectation maximization (BSREM), achieves more accurate lesion quantitation than OSEM, and importantly, maintains acceptable visual image quality in clinical wholebody PET. The goal of this work was to evaluate lesion detectability with BSREM versus OSEM. We performed a twoalternative forced choice study using 81 patient datasets with lesions of varying contrast inserted into the liver and lung. At matched imaging noise, BSREM and OSEM showed equivalent detectability in the lungs, and BSREM outperformed OSEM in the liver. These results suggest that BSREM provides not only improved quantitation and clinically acceptable visual image quality as previously shown but also improved lesion detectability compared to OSEM. We then modeled this detectability study, applying both nonprewhitening (NPW) and channelized Hotelling (CHO) model observers to the reconstructed images. The CHO model observer showed good agreement with the human observers, suggesting that we can apply this model to future studies with varying simulation and reconstruction parameters.

Most positron emission tomography (PET) emission scans are corrected for accidental coincidence (AC) events by real-time subtraction of delayed-window coincidences, leaving only the randoms-precorrected data available for image reconstruction. The real-time randoms precorrection compensates in mean for AC events but destroys the Poisson statistics. The exact log-likelihood for randoms-precorrected data is inconvenient, so practical approximations are needed for maximum likelihood or penalized-likelihood image reconstruction. Conventional approximations involve setting negative sinogram values to zero, which can induce positive systematic biases, particularly for scans with low counts per ray. We propose new likelihood approximations that allow negative sinogram values without requiring zero-thresholding. With negative sinogram values, the log-likelihood functions can be nonconcave, complicating maximization; nevertheless, we develop monotonic algorithms for the new models by modifying the separable paraboloidal surrogates and the maximum-likelihood expectation-maximization (ML-EM) methods. These algorithms ascend to local maximizers of the objective function. Analysis and simulation results show that the new shifted Poisson (SP) model is nearly free of systematic bias yet keeps low variance. Despite its simpler implementation, the new SP performs comparably to the saddle-point model which has shown the best performance (as to systematic bias and variance) in randoms-precorrected PET emission reconstruction.

The accuracy of the source localisation using EEG measurements depends on the noise as well as the computational model, so the improvement of localisation performance by using a very realistic model is limited. In this reported work, the source localisation effects of various human head models with different geometrical deformation for low signal-to-noise ratio (SNR) measurement are investigated. Assuming the most dense mesh as a model without model mismatch, it was found that some error due to the model mismatch was tolerably small in the range of low SNRs less than 0 dB. This provides a cost-effective strategy of head model generation, depending on a given tolerable level of localisation error.

Attenuation correction is critical to positron emission tomography (PET) quantitation. Errors in an attenuation map propagate into PET image reconstruction, subsequently affecting PET quantitation. It is important to understand quantitatively how the errors in the attenuation map impact on PET reconstruction in order to avoid misinterpretation of PET images in the presence of such errors and to set a specification on the accuracy of attenuation maps. In this study we present a computationally efficient method to predict the perturbation in the reconstructed PET image due to a perturbation in the attenuation map for time-of-flight (TOF) PET, which is known to be more robust to modeling inaccuracy than non-TOF PET. Building on existing methods that focus on non-TOF PET, we derive an analytical expression to predict the propagated errors for TOF PET by using a stationary point analysis applied to penalized-likelihood image reconstruction. We calculate the analytical expression efficiently in Fourier space without additional image reconstruction or matrix inversion. In addition, we demonstrate the propagated errors in PET quantitation are proportional to TOF timing resolution. The analytical method enables one to quickly examine the effects of inaccuracies in an attenuation map on PET quantitation. Its applications include analysis of MR-based attenuation correction in PET/MR, where MR-based attenuation maps often have inaccuracies in bones, lungs and implants.

In most brain computer interface (BCI) systems, some target users have significant difficulty in using BCI systems. Such target users are called 'BCI-illiterate'. This phenomenon has been poorly investigated, and a clear understanding of the BCI-illiteracy mechanism or a solution to this problem has not been reported to date. In this study, we sought to demonstrate the neurophysiological differences between two groups (literate, illiterate) with a total of 52 subjects. We investigated recordings under non-task related state (NTS) which is collected during subject is relaxed with eyes open. We found that high theta and low alpha waves were noticeable in the BCI-illiterate relative to the BCI-literate people. Furthermore, these high theta and low alpha wave patterns were preserved across different mental states, such as NTS, resting before motor imagery (MI), and MI states, even though the spatial distribution of both BCI-illiterate and BCI-literate groups did not differ. From these findings, an effective strategy for pre-screening subjects for BCI illiteracy has been determined, and a performance factor that reflects potential user performance has been proposed using a simple combination of band powers. Our proposed performance factor gave an r = 0.59 (r(2) = 0.34) in a correlation analysis with BCI performance and yielded as much as r = 0.70 (r(2) = 0.50) when seven outliers were rejected during the evaluation of whole data (N = 61), including BCI competition datasets (N = 9). These findings may be directly applicable to online BCI systems.

We have previously developed a convergent penalized likelihood (PL) image reconstruction algorithm using the relative difference prior (RDP) and showed that it achieves more accurate lesion quantitation compared to ordered subsets expectation maximization (OSEM). We evaluated the detectability of low-contrast liver and lung lesions using the PL-RDP algorithm compared to OSEM. We performed a two-alternative forced choice study using a channelized Hotelling observer model that was previously validated against human observers. Lesion detectability showed a stronger dependence on lesion size for PL-RDP than OSEM. Lesion detectability was improved using time-of-flight (TOF) reconstruction, with greater benefit for the liver compared to the lung and with increasing benefit for decreasing lesion size and contrast. PL detectability was statistically significantly higher than OSEM for 20 mm liver lesions when contrast was [Formula: see text] ([Formula: see text]), and TOF PL detectability was statistically significantly higher than TOF OSEM for 15 and 20 mm liver lesions with contrast [Formula: see text] and [Formula: see text], respectively. For all other cases, there was no statistically significant difference between PL and OSEM ([Formula: see text]). For the range of studied lesion properties, lesion detectability using PL-RDP was equivalent or improved compared to using OSEM.

Fluorescence tomography has become increasingly popular for detecting molecular targets for imaging gene expression and other cellular processes in vivo in small animal studies. In this imaging modality, multiple sets of data are acquired by illuminating the animal surface with different excitation patterns, each of which produces a distinct spatial pattern of fluorescence. This work addresses one of the most intriguing, yet unsolved, problems of fluorescence tomography, which is to determine how to optimally illuminate the animal surface so as to maximize the information content in the acquired data. The key idea of this work is to parameterize the illumination pattern and to maximize the information content in the data by improving the conditioning of the Fisher information matrix. We formulate our problem as a constrained optimization problem. We compare the performance of different geometric illumination schemes with those generated by this optimization approach using the Digimouse atlas.

We have developed a three dimensional (3D) multispectral fluorescence optical tomography small animal imaging system with an innovative geometry using a truncated conical mirror, allowing simultaneous viewing of the entire surface of the animal by an EMCCD camera. A conical mirror collects photons approximately three times more efficiently than a flat mirror. An x-y mirror scanning system makes it possible to scan a collimated excitation laser beam to any location on the mouse surface. A pattern of structured light incident on the small animal surface is used to extract the surface geometry for reconstruction. A finite element based algorithm is applied to model photon propagation in the turbid media and a preconditioned conjugate gradient (PCG) method is used to solve the large linear system matrix. The reconstruction algorithm and the system feasibility are evaluated by phantom experiments. These experiments show that multispectral measurements improve the spatial resolution of reconstructed images. Finally, an in vivo imaging study of a xenograft tumor in a mouse shows good correlation of the reconstructed image with the location of the fluorescence probe as determined by subsequent optical imaging of cryosections of the mouse.

We have designed a three dimensional (3D) fluorescence optical tomography system for small animal imaging based on an innovative system geometry that uses a truncated conical mirror which permits the entire surface of the animal to be viewed simultaneously by a single CCD camera. Compared with traditional approaches that employ a flat mirror, the conical mirror system has approximately 3 times better measurement sensitivity. By utilizing a fast switching filter wheel (switching time < 100 milliseconds), emission data at multiple wavelengths can be efficiently collected. An array of appropriately shaped neutral density filters, mounted on a linear stage, can be used to increase the system measurement dynamic range by 3 orders of magnitude. An x-y galvo mirror scanning system makes it possible to scan a collimated laser beam to any location on the mouse surface. A pattern of structured light incident on the animal surface is used to extract the surface geometry. A finite element based algorithm is applied to model photon propagation in the turbid media and a preconditioned conjugate gradient (PCG) method is used to solve the large linear system matrix. The reconstruction algorithm and the system performance are evaluated by phantom experiments.

We investigate fast iterative image reconstruction methods for fully 3D multispectral optical bioluminescence tomography where inhomogeneous optical properties are modeled using the finite element method (FEM). We compare two approaches to incorporating the forward model into the solution of the inverse problem. In the direct calculation approach we compute the full forward model by repeated solution of the PEM problem, once for each potential source location. In the on-the-fly approach, we do not explicitly solve for the full forward model. Instead, the solution to the forward problem is included implicitly in the formulation of the inverse problem, and the FEM is solved once at each iteration for the current image estimate. In both approaches we use reordered Cholesky factorization and substitution (CFS) to solve the FEM problem. We compare the computation cost of these two approaches, concluding that the on-the-fly approach can lead to substantial reductions in cost when combined with a rapidly converging iterative algorithm

Objective. We propose a new hybrid brain–computer interface (BCI) system that integrates two different EEG tasks: tactile selective attention (TSA) using a vibro-tactile stimulator on the left/right finger and motor imagery (MI) of left/right hand movement. Event-related desynchronization (ERD) from the MI task and steady-state somatosensory evoked potential (SSSEP) from the TSA task are retrieved and combined into two hybrid senses. Approach. One hybrid approach is to measure two tasks simultaneously; the features of each task are combined for testing. Another hybrid approach is to measure two tasks consecutively (TSA first and MI next) using only MI features. For comparison with the hybrid approaches, the TSA and MI tasks are measured independently. Main results. Using a total of 16 subject datasets, we analyzed the BCI classification performance for MI, TSA and two hybrid approaches in a comparative manner; we found that the consecutive hybrid approach outperformed the others, yielding about a 10% improvement in classification accuracy relative to MI alone. It is understood that TSA may play a crucial role as a prestimulus in that it helps to generate earlier ERD prior to MI and thus sustains ERD longer and to a stronger degree; this ERD may give more discriminative information than ERD in MI alone. Significance. Overall, our proposed consecutive hybrid approach is very promising for the development of advanced BCI systems.