Selectively Probing the Magnetic Resonance Signals of γ-Aminobutyric Acid in Human Brains In Vivo.

BACKGROUND: Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in human brains, playing a role in the pathogenesis of various psychiatric disorders. Current methods have some non-neglectable shortcomings and noninvasive and accurate detection of GABA in human brains is long-term challenge. PURPOSE: To develop a pulse sequence capable of selectively detecting and quantifying the 1 H signal of GABA in human brains based on optimal controlled spin singlet order. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: A phantom of GABA (pH = 7.3 ± 0.1) and 11 healthy subjects (5 females and 6 males, body mass index: 21 ± 3 kg/m2 , age: 25 ± 4 years). FIELD STRENGTH/SEQUENCE: 7 Tesla, 3 Tesla, GABA-targeted magnetic resonance spectroscopy (GABA-MRS-7 T, GABA-MRS-3 T), magnetization prepared two rapid acquisition gradient echoes sequence. ASSESSMENT: By using the developed pulse sequences applied on the phantom and healthy subjects, the signals of GABA were successfully selectively probed. Quantification of the signals yields the concentration of GABA in the dorsal anterior cingulate cortex (dACC) in human brains. STATISTICAL TESTS: Frequency. RESULTS: The 1 H signals of GABA in the phantom and in the human brains of healthy subjects were successfully detected. The concentration of GABA in the dACC of human brains was 3.3 ± 1.5 mM. DATA CONCLUSION: The developed pulse sequences can be used to selectively probe the 1 H MR signals of GABA in human brains in vivo. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 1.

pH Mapping of Gliomas Using Quantitative Chemical Exchange Saturation Transfer MRI: Quasi-Steady-State, Spillover-, and MT-Corrected Omega Plot Analysis.

BACKGROUND: Quantitative in-situ pH mapping of gliomas is important for therapeutic interventions, given its significant association with tumor progression, invasion, and metastasis. Although chemical exchange saturation transfer (CEST) offers a noninvasive way for pH imaging based on the pH-dependent exchange rate (ksw ), the reliable quantification of ksw in glioma remains constrained due to technical challenges. PURPOSE: To quantify the pH of gliomas by measuring the proton exchange rate through optimized omega plot analysis. STUDY TYPE: Prospective. PHANTOMS/ANIMAL MODEL/SUBJECTS: Creatine and murine brain lysates phantoms, six rats with glioma xenograft model, and three patients with World Health Organization grade 2-4 gliomas. FIELD STRENGTH/SEQUENCE: 11.7 T, 7.0 T, CEST imaging, T2 -weighted (T2 W) imaging, and T1 -mapping. ASSESSMENT: Omega plot analysis, quasi-steady-state (QUASS) analysis, multi-pool Lorentzian fitting, amine and amide concentration-independent detection, pH enhanced method with the combination of amide and guanidyl (pHenh ), and magnetization transfer ratio (MTR) were utilized for pH metric quantification. The clinical outcomes were determined through radiologic follow-up and histopathological analysis. STATISTICAL TESTS: Mann-Whitney U test was performed to compare glioma with normal tissue, and Pearson's correlation analysis was used to assess the relationship between ksw and other parameters. RESULTS: In vitro experiments reveal that the determined ksw at 2 ppm increases exponentially with pH (creatine phantoms: ksw = 106 + 0.147 × 10(pH-4.198) ; lysates: ksw = 185.1 + 0.101 × 10(pH-3.914) ). Omega plot analysis exhibits a linear correlation between 1/MTRRex and 1/ω1 2 in the glioma xenografts (R2 > 0.98) and glioma patients (R2 > 0.99). The exchange rate in the rat glioma decreases compared to the contralateral normal tissue (349.46 ± 30.40 s-1 vs. 403.54 ± 51.01 s-1 , P = 0.025), while keeping independence from changes in concentration (r = 0.5037, P = 0.095). Similar pattern was observed in human data. DATA CONCLUSION: Utilizing QUASS-based, spillover-, and MT-corrected omega plot analysis for the measurement of exchange rates, offers a feasible method for quantifying pH within glioma. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 1.

An improved attention module based on nnU-Net for segmenting primary central nervous system lymphoma (PCNSL) in MRI images1.

BACKGROUND: Accurate volumetric segmentation of primary central nervous system lymphoma (PCNSL) is essential for assessing and monitoring the tumor before radiotherapy and the treatment planning. The tedious manual segmentation leads to interindividual and intraindividual differences, while existing automatic segmentation methods cause under-segmentation of PCNSL due to the complex and multifaceted nature of the tumor. OBJECTIVE: To address the challenges of small size, diffused distribution, poor inter-layer continuity on the same axis, and tendency for over-segmentation in brain MRI PCNSL segmentation, we propose an improved attention module based on nnUNet for automated segmentation. METHODS: We collected 114 T1 MRI images of patients in the Huashan Hospital, Shanghai. Then randomly split the total of 114 cases into 5 distinct training and test sets for a 5-fold cross-validation. To efficiently and accurately delineate the PCNSL, we proposed an improved attention module based on nnU-Net with 3D convolutions, batch normalization, and residual attention (res-attention) to learn the tumor region information. Additionally, multi-scale dilated convolution kernels with different dilation rates were integrated to broaden the receptive field. We further used attentional feature fusion with 3D convolutions (AFF3D) to fuse the feature maps generated by multi-scale dilated convolution kernels to reduce under-segmentation. RESULTS: Compared to existing methods, our attention module improves the ability to distinguish diffuse and edge enhanced types of tumors; and the broadened receptive field captures tumor features of various scales and shapes more effectively, achieving a 0.9349 Dice Similarity Coefficient (DSC). CONCLUSIONS: Quantitative results demonstrate the effectiveness of the proposed method in segmenting the PCNSL. To our knowledge, this is the first study to introduce attention modules into deep learning for segmenting PCNSL based on brain magnetic resonance imaging (MRI), promoting the localization of PCNSL before radiotherapy.

EPI phase error correction with deep learning (PEC-DL) at 7 T.

PURPOSE: The phase mismatch between odd and even echoes in EPI causes Nyquist ghost artifacts. Existing ghost correction methods often suffer from severe residual artifacts and are ineffective with k-space undersampling data. This study proposed a deep learning-based method (PEC-DL) to correct phase errors for DWI at 7 Tesla. METHODS: The acquired k-space data were divided into 2 independent undersampled datasets according to their readout polarities. Then the proposed PEC-DL network reconstructed 2 ghost-free images using the undersampled data without calibration and navigator data. The network was trained with fully sampled images and applied to two- and fourfold accelerated data. Healthy volunteers and patients with Moyamoya disease were recruited to validate the efficacy of the PEC-DL method. RESULTS: The PEC-DL method was capable to mitigate the ghost artifacts in DWI in healthy volunteers as well as patients with Moyamoya disease. The fourfold accelerated results showed much less distortion in the lesions of the Moyamoya patient using high b-value DWI and the corresponding ADC maps. The ghost-to-signal ratios were significantly lower in PEC-DL images compared to conventional linear phase corrections, mini-entropy, and PEC-GRAPPA algorithms. CONCLUSION: The proposed method can effectively eliminate ghost artifacts for full sampled and up to fourfold accelerated EPI data without calibration and navigator data.

MRI-Based Investigation of Association Between Cerebrovascular Structural Alteration and White Matter Hyperintensity Induced by High Blood Pressure.

BACKGROUND: High blood pressure (BP) is a common risk factor for cerebral small vessel disease including white matter hyperintensity (WMH). Whether increased BP exacerbates WMH by impacting cerebral vascular morphologies remains poorly studied. PURPOSE: To determine the relationships among high BP, cerebrovascular morphologies, and WMH in elderly individuals. STUDY TYPE: Cohort. SUBJECTS: Eight hundred sixty-three participants (54.2% female) from the Taizhou Imaging Study without clinical evidence of neurologic disorders were included in the analyses. FIELD STRENGTH/SEQUENCE: 3.0 T; time-of-flight magnetic resonance angiography (TOF MRA); T2 fluid-attenuated inversion recovery (FLAIR); T1 magnetization-prepared rapid gradient-echo; gradient echo T2*-weighted; diffusion tensor imaging; pulsed arterial spin labeling. ASSESSMENT: Cerebrovascular morphologic measurements were quantified based on the TOF MRA images, including vessel density, radius, tortuosity, and branch number. WMH lesion volumes (WMHV) and WMH lesion counts (WMHC) were calculated automatically based on the T2 FLAIR images. STATISTICAL TESTS: Multivariable linear regression analysis and path analysis with a linear single-mediator model were employed. A P value <0.05 was considered statistically significant. RESULTS: Higher BP, especially diastolic BP, was significantly correlated with lower cerebrovascular density (ß = -104) and lower branch numbers (ß = -0.02). Although decreased tortuosity (ß = -1.25) and increased radius (ß = 93.8) were correlated with BP, no significant relationship of tortuosity (ß = -4.6 × 10-4 , P = 0.58) or radius (ß = 0.03, P = 0.08) with BP in small vessels was found. The proportion of small vessels decreased as BP increased (SBP: ß = -6.6 × 10-4 ; DBP: ß = -9.0 × 10-4 ). Similarly, increased WMHV and WMHC were associated with decreased vessel density (volumes: ß = -24, counts: ß = -127), decreased tortuosity (volumes: ß = -0.08, counts: ß = -0.53), and increased radius (volumes: ß = 12.6, counts: ß = 86.6). Path analyses suggested an association between high BP and WMHs that were mediated by cerebrovascular morphologic changes. DATA CONCLUSION: Structural alterations of cerebral vessels induced by high BP are correlated with WMH. This result suggested that elevated BP might be one of the pathophysiological mechanisms involving in the co-occurrence of cerebrovascular alteration and small vessel disease. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 1.

Concurrent electrophysiological and hemodynamic measurements of evoked neural oscillations in human visual cortex using sparsely interleaved fast fMRI and EEG.

Electroencephalography (EEG) concurrently collected with functional magnetic resonance imaging (fMRI) is heavily distorted by the repetitive gradient coil switching during the fMRI acquisition. The performance of the typical template-based gradient artifact suppression method can be suboptimal because the artifact changes over time. Gradient artifact residuals also impede the subsequent suppression of ballistocardiography artifacts. Here we propose recording continuous EEG with temporally sparse fast fMRI (fast fMRI-EEG) to minimize the EEG artifacts caused by MRI gradient coil switching without significantly compromising the field-of-view and spatiotemporal resolution of fMRI. Using simultaneous multi-slice inverse imaging to achieve whole-brain fMRI with isotropic 5-mm resolution in 0.1 â€‹s, and performing these acquisitions once every 2 â€‹s, we have 95% of the duty cycle available to record EEG with substantially less gradient artifact. We found that the standard deviation of EEG signals over the entire acquisition period in fast fMRI-EEG was reduced to 54% of that in conventional concurrent echo-planar imaging (EPI) and EEG recordings (EPI-EEG) across participants. When measuring 15-Hz steady-state visual evoked potentials (SSVEPs), the baseline-normalized oscillatory neural response in fast fMRI-EEG was 2.5-fold of that in EPI-EEG. The functional MRI responses associated with the SSVEP delineated by EPI and fast fMRI were similar in the spatial distribution, the elicited waveform, and detection power. Sparsely interleaved fast fMRI-EEG provides high-quality EEG without substantially compromising the quality of fMRI in evoked response measurements, and has the potential utility for applications where the onset of the target stimulus cannot be precisely determined, such as epilepsy.

Design of a shim coil array matched to the human brain anatomy.

PURPOSE: The purpose of this study is to introduce a novel design method of a shim coil array specifically optimized for whole brain shimming and to compare the performance of the resulting coils to conventional spherical harmonic shimming. METHODS: The proposed design approach is based on the stream function method and singular value decomposition. Eighty-four field maps from 12 volunteers measured in seven different head positions were used during the design process. The cross validation technique was applied to find an optimal number of coil elements in the array. Additional 42 field maps from 6 further volunteers were used for an independent validation. A bootstrapping technique was used to estimate the required population size to achieve a stable coil design. RESULTS: Shimming using 12 and 24 coil elements outperforms fourth- and fifth-order spherical harmonic shimming for all measured field maps, respectively. Coil elements show novel coil layouts compared to the conventional spherical harmonic coils and existing multi-coils. Both leave-one-out and independent validation demonstrate the generalization ability of the designed arrays. The bootstrapping analysis predicts that field maps from approximately 140 subjects need to be acquired to arrive at a stable design. CONCLUSIONS: The results demonstrate the validity of the proposed method to design a shim coil array matched to the human brain anatomy, which naturally satisfies the laws of electrodynamics. The design method may also be applied to develop new shim coil arrays matched to other human organs.

Relative latency and temporal variability of hemodynamic responses at the human primary visual cortex.

The blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal is a robust surrogate for local neuronal activity. However, it has been shown to vary substantially across subjects, brain regions, and repetitive measurements. This variability represents a limit to the precision of the BOLD response and the ability to reliably discriminate brain hemodynamic responses elicited by external stimuli or behavior that are nearby in time. While the temporal variability of the BOLD signal at human visual cortex has been found in the range of a few hundreds of milliseconds, the spatial distributions of the average and standard deviation of this temporal variability have not been quantitatively characterized. Here we use fMRI measurements with a high sampling rate (10Hz) to map the latency, intra- and inter-subject variability of the evoked BOLD signal in human primary (V1) visual cortices using an event-related fMRI paradigm. The latency relative to the average BOLD signal evoked by 30 stimuli was estimated to be 0.03±0.20s. Within V1, the absolute value of the relative BOLD latency was found correlated to intra- and inter-subject temporal variability. After comparing these measures to retinotopic maps, we found that locations with V1 areas sensitive to smaller eccentricity have later responses and smaller inter-subject variabilities. These correlations were found from data with either short inter-stimulus interval (ISI; average 4s) or long ISI (average 30s). Maps of the relative latency as well as inter-/intra-subject variability were found visually asymmetric between hemispheres. Our results suggest that the latency and variability of regional BOLD signal measured with high spatiotemporal resolution may be used to detect regional differences in hemodynamics to inform fMRI studies. However, the physiological origins of timing index distributions and their hemispheric asymmetry remain to be investigated.

Mitigation of B1+ inhomogeneity using spatially selective excitation with jointly designed quadratic spatial encoding magnetic fields and RF shimming.

PURPOSE: The inhomogeneity of flip angle distribution is a major challenge impeding the application of high-field MRI. We report a method combining spatially selective excitation using generalized spatial encoding magnetic fields (SAGS) with radiofrequency (RF) shimming to achieve homogeneous excitation. This method can be an alternative approach to address the challenge of B1+ inhomogeneity using nonlinear gradients. METHODS: We proposed a two-step algorithm that jointly optimizes the combination of nonlinear spatial encoding magnetic fields and the combination of multiple RF transmitter coils and then optimizes the locations, RF amplitudes, and phases of the spokes. RESULTS: Our results show that jointly designed SAGS and RF shimming can provide a more homogeneous flip angle distribution than using SAGS or RF shimming alone. Compared with RF shimming alone, our approach can reduce the relative standard deviation of flip angle by 56% and 52% using phantom and human head data, respectively. CONCLUSION: The jointly designed SAGS and RF shimming method can be used to achieve homogeneous flip angle distributions when fully parallel RF transmission is not available. Magn Reson Med 78:577-587, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Rotary scanning acquisition in ultra-low-field MRI.

PURPOSE: To develop a method of achieving large field of view (FOV) imaging with a smaller amount of data in ultra-low-field (ULF) MRI. THEORY: In rotary scanning acquisition (RSA), data from the imaging object is acquired at multiple angles by rotating the object or the scanner. RSA is similar to radial-trajectory acquisition but simplifies the measurement and image reconstruction when concomitant fields are nonnegligible. METHODS: RSA was implemented to achieve large FOV with only three localized superconductive quantum interference device (SQUID) sensors at the ULF-MRI field of 50 µT. RESULTS: Simulations suggest benefits of RSA, including reduced concomitant field artifacts, large FOV imaging, and SNR improvement. Experimental data demonstrate the feasibility of reconstructing large FOV images using only three SQUID sensors with 33% of the amount of data collected using a Cartesian trajectory. CONCLUSION: RSA can be useful in low-field, low-weight, or portable MRI to generate large FOV images with only a few sensors. Magn Reson Med 75:2255-2264, 2016. © 2015 Wiley Periodicals, Inc.

Significant feed-forward connectivity revealed by high frequency components of BOLD fMRI signals.

Granger causality analysis has been suggested as a method of estimating causal modulation without specifying the direction of information flow a priori. Using BOLD-contrast functional MRI (fMRI) data, such analysis has been typically implemented in the time domain. In this study, we used magnetic resonance inverse imaging, a method of fast fMRI enabled by massively parallel detection allowing up to 10 Hz sampling rate, to investigate the causal modulation at different frequencies up to 5 Hz. Using a visuomotor two-choice reaction-time task, both the spectral decomposition of Granger causality and isolated effective coherence revealed that the BOLD signal at frequency up to 3 Hz can still be used to estimate significant dominant directions of information flow consistent with results from the time-domain Granger causality analysis. We showed the specificity of estimated dominant directions of information flow at high frequencies by contrasting causality estimates using data collected during the visuomotor task and resting state. Our data suggest that hemodynamic responses carry physiological information related to inter-regional modulation at frequency higher than what has been commonly considered.

Combining parallel detection of proton echo planar spectroscopic imaging (PEPSI) measurements with a data-consistency constraint improves SNR.

One major challenge of MRSI is the poor signal-to-noise ratio (SNR), which can be improved by using a surface coil array. Here we propose to exploit the spatial sensitivity of different channels of a coil array to enforce the k-space data consistency (DC) in order to suppress noise and consequently to improve MRSI SNR. MRSI data were collected using a proton echo planar spectroscopic imaging (PEPSI) sequence at 3 T using a 32-channel coil array and were averaged with one, two and eight measurements (avg-1, avg-2 and avg-8). The DC constraint was applied using a regularization parameter λ of 1, 2, 3, 5 or 10. Metabolite concentrations were quantified using LCModel. Our results show that the suppression of noise by applying the DC constraint to PEPSI reconstruction yields up to 32% and 27% SNR gain for avg-1 and avg-2 data with λ = 5, respectively. According to the reported Cramer-Rao lower bounds, the improvement in metabolic fitting was significant (p < 0.01) when the DC constraint was applied with λ ≥ 2. Using the DC constraint with λ = 3 or 5 can minimize both root-mean-square errors and spatial variation for all subjects using the avg-8 data set as reference values. Our results suggest that MRSI reconstructed with a DC constraint can save around 70% of scanning time to obtain images and spectra with similar SNRs using λ = 5.

Whole-head rapid fMRI acquisition using echo-shifted magnetic resonance inverse imaging.

The acquisition time of BOLD contrast functional MRI (fMRI) data with whole-brain coverage typically requires a sampling rate of one volume in 1-3s. Although the volumetric sampling time of a few seconds is adequate for measuring the sluggish hemodynamic response (HDR) to neuronal activation, faster sampling of fMRI might allow for monitoring of rapid physiological fluctuations and detection of subtle neuronal activation timing information embedded in BOLD signals. Previous studies utilizing a highly accelerated volumetric MR inverse imaging (InI) technique have provided a sampling rate of one volume per 100 ms with 5mm spatial resolution. Here, we propose a novel modification of this technique, the echo-shifted InI, which allows TE to be longer than TR, to measure BOLD fMRI at an even faster sampling rate of one volume per 25 ms with whole-brain coverage. Compared with conventional EPI, echo-shifted InI provided an 80-fold speedup with similar spatial resolution and less than 2-fold temporal SNR loss. The capability of echo-shifted InI to detect HDR timing differences was tested empirically. At the group level (n=6), echo-spaced InI was able to detect statistically significant HDR timing differences of as low as 50 ms in visual stimulus presentation. At the level of individual subjects, significant differences in HDR timing were detected for 400 ms stimulus-onset differences. Our results also show that the temporal resolution of 25 ms is necessary for maintaining the temporal detecting capability at this level. With the capabilities of being able to distinguish the timing differences in the millisecond scale, echo-shifted InI could be a useful fMRI tool for obtaining temporal information at a time scale closer to that of neuronal dynamics.

Convolutional neural network to predict IDH mutation status in glioma from chemical exchange saturation transfer imaging at 7 Tesla.

Background and goal: Noninvasive prediction of isocitrate dehydrogenase (IDH) mutation status in glioma guides surgical strategies and individualized management. We explored the capability on preoperatively identifying IDH status of combining a convolutional neural network (CNN) and a novel imaging modality, ultra-high field 7.0 Tesla (T) chemical exchange saturation transfer (CEST) imaging. Method: We enrolled 84 glioma patients of different tumor grades in this retrospective study. Amide proton transfer CEST and structural Magnetic Resonance (MR) imaging at 7T were performed preoperatively, and the tumor regions are manually segmented, leading to the "annotation" maps that offers the location and shape information of the tumors. The tumor region slices in CEST and T1 images were further cropped out as samples and combined with the annotation maps, which were inputted to a 2D CNN model for generating IDH predictions. Further comparison analysis to radiomics-based prediction methods was performed to demonstrate the crucial role of CNN for predicting IDH based on CEST and T1 images. Results: A fivefold cross-validation was performed on the 84 patients and 4090 slices. We observed a model based on only CEST achieved accuracy of 74.01% ± 1.15%, and the area under the curve (AUC) of 0.8022 ± 0.0147. When using T1 image only, the prediction performances dropped to accuracy of 72.52% ± 1.12% and AUC of 0.7904 ± 0.0214, which indicates no superiority of CEST over T1. However, when we combined CEST and T1 together with the annotation maps, the performances of the CNN model were further boosted to accuracy of 82.94% ± 1.23% and AUC of 0.8868 ± 0.0055, suggesting the importance of a joint analysis of CEST and T1. Finally, using the same inputs, the CNN-based predictions achieved significantly improved performances above those from radiomics-based predictions (logistic regression and support vector machine) by 10% to 20% in all metrics. Conclusion: 7T CEST and structural MRI jointly offer improved sensitivity and specificity of preoperative non-invasive imaging for the diagnosis of IDH mutation status. As the first study of CNN model on imaging acquired at ultra-high field MR, our results could demonstrate the potential of combining ultra-high-field CEST and CNN for facilitating decision-making in clinical practice. However, due to the limited cases and B1 inhomogeneities, the accuracy of this model will be improved in our further study.

Automatic bundle-specific white matter fiber tracking tool using diffusion tensor imaging data: A pilot trial in the application of language-related glioma resection.

Cerebral neoplasms like gliomas may cause intracranial pressure increasing, neural tract deviation, infiltration, or destruction in peritumoral areas, leading to neuro-functional deficits. Novel tracking technology, such as DTI, can objectively reveal and visualize three-dimensional white matter trajectories; in combination with intraoperative navigation, it can help achieve maximum resection whilst minimizing neurological deficit. Since the reconstruction of DTI raw data largely relies on the technical engineering and anatomical experience of the operator; it is time-consuming and prone to operator-induced bias. Here, we develop new user-friendly software to automatically segment and reconstruct functionally active areas to facilitate precise surgery. In this pilot trial, we used an in-house developed software (DiffusionGo) specially designed for neurosurgeons, which integrated a reliable diffusion-weighted image (DWI) preprocessing pipeline that embedded several functionalities from software packages of FSL, MRtrix3, and ANTs. The preprocessing pipeline is as follows: 1. DWI denoising, 2. Gibbs-ringing removing, 3. Susceptibility distortion correction (process if opposite polarity data were acquired), 4. Eddy current and motion correction, and 5. Bias correction. Then, this fully automatic multiple assigned criteria algorithms for fiber tracking were used to achieve easy modeling and assist precision surgery. We demonstrated the application with three language-related cases in three different centers, including a left frontal, a left temporal, and a left frontal-temporal glioma, to achieve a favorable surgical outcome with language function preservation or recovery. The DTI tracking result using DiffusionGo showed robust consistency with direct cortical stimulation (DCS) finding. We believe that this fully automatic processing pipeline provides the neurosurgeon with a solution that may reduce time costs and operating errors and improve care quality and surgical procedure quality across different neurosurgical centers.

Ultrafast inverse imaging techniques for fMRI.

Inverse imaging (InI) supercharges the sampling rate of traditional functional MRI 10-100 fold at a cost of a moderate reduction in spatial resolution. The technique is inspired by similarities between multi-sensor magnetoencephalography (MEG) and highly parallel radio-frequency (RF) MRI detector arrays. Using presently available 32-channel head coils at 3T, InI can be sampled at 10 Hz and provides about 5-mm cortical spatial resolution with whole-brain coverage. Here we discuss the present applications of InI, as well as potential future challenges and opportunities in further improving its spatiotemporal resolution and sensitivity. InI may become a helpful tool for clinicians and neuroscientists for revealing the complex dynamics of brain functions during task-related and resting states.

Moyamoya disease: A human model for chronic hypoperfusion and intervention in Alzheimer's disease.

Introduction: Chronic cerebral hypoperfusion has been considered the etiology for sporadic Alzheimer's disease (AD). However, no valid clinical evidence exists due to the similar risk factors between cerebrovascular disease and AD. Methods: We used moyamoya disease (MMD) as a model of chronic hypoperfusion and cognitive impairment, without other etiology interference. Results: Based on the previous reports and preliminary findings, we hypothesized that chronic cerebral hypoperfusion could be an independent upstream crucial variable, resulting in AD, and induce pathological hallmarks such as amyloid beta peptide and hyperphosphorylated tau accumulation. Discussion: Timely intervention with revascularisation would help reverse the brain damage with AD hallmarks and lead to cognitive improvement.

Feature-dependent intrinsic functional connectivity across cortical depths in the human auditory cortex.

Frequency preference and spectral tuning are two cardinal features of information processing in the auditory cortex. However, sounds should not only be processed in separate frequency bands because information needs to be integrated to be meaningful. One way to better understand the integration of acoustic information is to examine the functional connectivity across cortical depths, as neurons are already connected differently across laminar layers. Using a tailored receiver array and surface-based cortical depth analysis, we revealed the frequency-preference as well as tuning-width dependent intrinsic functional connectivity (iFC) across cortical depths in the human auditory cortex using functional magnetic resonance imaging (fMRI). We demonstrated feature-dependent iFC in both core and noncore regions at all cortical depths. The selectivity of frequency-preference dependent iFC was higher at deeper depths than at intermediate and superficial depths in the core region. Both the selectivity of frequency-preference and tuning-width dependent iFC were stronger in the core than in the noncore region at deep cortical depths. Taken together, our findings provide evidence for a cortical depth-specific feature-dependent functional connectivity in the human auditory cortex.

Decoupled dynamic magnetic field measurements improves diffusion-weighted magnetic resonance images.

Field probes are miniature receiver coils with localized NMR-active samples inside. They are useful in monitoring magnetic field. This information can be used to improve magnetic resonance image quality. While field probes are coupled to each other marginally in most applications, this coupling can cause incorrect resonance frequency estimates and image reconstruction errors. Here, we propose a method to reduce the coupling between field probes in order to improve the accuracy of magnetic field estimation. An asymmetric sensitivity matrix describing the coupling between channels of field probes and NMR active droplets within field probes was empirically measured. Localized signal originating from each probe was derived from the product of the inverse of the sensitivity matrix and the coupled probe measurements. This method was used to estimate maps of dynamic magnetic fields in diffusion weighted MRI. The estimated fields using decoupled probe measurement led to images more robust to eddy currents caused by diffusion sensitivity gradients along different directions.

Simultaneous multi-slice inverse imaging of the human brain.

Ultrafast functional magnetic resonance imaging (fMRI) can measure blood oxygen level dependent (BOLD) signals with high sensitivity and specificity. Here we propose a novel method: simultaneous multi-slice inverse imaging (SMS-InI) - a combination of simultaneous multi-slice excitation, simultaneous echo refocusing (SER), blipped controlled aliasing in parallel imaging echo-planar imaging (EPI), and regularized image reconstruction. Using a 32-channel head coil array on a 3 T scanner, SMS-InI achieves nominal isotropic 5-mm spatial resolution and 10 Hz sampling rate at the whole-brain level. Compared with traditional inverse imaging, we found that SMS-InI has higher spatial resolution with lower signal leakage and higher time-domain signal-to-noise ratio with the optimized regularization parameter in the reconstruction. SMS-InI achieved higher effective resolution and higher detection power in detecting visual cortex activity than InI. SMS-InI also detected subcortical fMRI signals with the similar sensitivity and localization accuracy like EPI. The spatiotemporal resolution of SMS-InI was used to reveal that presenting visual stimuli with 0.2 s latency between left and right visual hemifield led to 0.2 s relative hemodynamic response latency between the left and right visual cortices. Together, these results indicate that SMS-InI is a useful tool in measuring cortical and subcortical hemodynamic responses with high spatiotemporal resolution.