A customizable method (OPTIKS) for designing fast trajectory-constrained gradient waveforms with optimized time domain properties was developed. Given a specified multidimensional k-space trajectory, the method optimizes traversal speed (and therefore timing) with position along the trajectory. OPTIKS facilitates optimization of objectives dependent on the time domain gradient waveform and the arc-length domain k-space speed. OPTIKS is applied to design waveforms which limit peripheral nerve stimulation (PNS), minimize mechanical resonance excitation, and reduce acoustic noise. A variety of trajectory examples are presented including spirals, circular echo-planar-imaging, and rosettes. Design performance is evaluated based on duration, standardized PNS models, field measurements, gradient coil back-EMF measurements, and calibrated acoustic measurements. We show reductions in back-EMF of up to 94% and field oscillations up to 91.1%, acoustic noise decreases of up to 9.22 dB, and with efficient use of PNS models speed increases of up to 11.4%. The design method implementation is made available as an open source Python package through GitHub (https://github.com/mamccready/optiks).

PURPOSE:To push the speed and resolution limit of in vivo quantitative imaging and enable estimation of quantitative tissue parameters of subtle brain structures that were previously difficult to assess. METHODS:This study implemented an efficient quantitative imaging approach, 3D-SPI MRF, on the NexGen 7T scanner equipped with a high-performance head-only gradient and 96-channel receiver array. To address challenges associated with performing rapid mesoscale MRF on this system, acquisition and reconstruction mitigation methods were developed and incorporated into the MRF framework, including: (i) flip-angle-aware dictionary fitting to account for both B1 + inhomogeneity and voxel-specific RF frequency response, (ii) gradient imperfection corrections via Skope measurements that incorporates a new per-TR trajectory rewinder compensation, (iii) incorporation of rapid B1 + and B0 mappings into the MRF sequence, and (iv) high-temporal motion navigation. RESULTS:Whole-brain T1 and T2 maps were obtained at 560-μm isotropic resolution within 4 min, where ablation studies demonstrated the necessity of the various mitigation methods implemented in removing bias and artifacts. For comparison, MRF data were acquired using current state-of-the-art method but limited to typical whole-body gradient specifications to demonstrate that the proposed developments resulted in ∼3× shorter scan time while producing more accurate parameter maps. Data were also acquired at ∼3.8× smaller voxel size, 360-μm isotropic, using the developed technique, to achieve mesoscale multi-parameter quantitative mapping in vivo. CONCLUSION:Tailored 3D MRF acquisition and reconstruction were developed to enable fast and accurate T1 and T2 mapping across the whole-brain at mesoscale resolution on the NexGen 7T scanner.

PurposeField monitoring using field probes allows for accurate measurement of magnetic field perturbations, such as from eddy currents, during MRI scanning. However, errors may result when the spatial variation of the fields is not well-described by the conventionally used spherical harmonics model that has the maximum order constrained by the number of probes. The objective of this work was to develop and validate a field monitoring approach that compresses higher order spherical harmonics into a smaller set of new basis functions that can be characterized using fewer probes.MethodsField monitoring of acquisitions was repeated with probes in different locations. High-order field dynamics were computed from this "calibration" data assembled from provided scans, from which compression matrices could be devised using principal component analysis. Compression matrices were then used to fit field dynamics using "compressed" basis functions with data from 16 probes, which were then used in image reconstruction. Performance was evaluated by assessing the accuracy of computed field dynamics as well as in vivo image quality. Technique generalizability was also assessed by using various acquisition and diffusion encoding strategies in the calibration.ResultsQualitative and quantitative improvements in accuracy were observed when using the proposed fitting method compared to the conventional approach. However, compression effectiveness was influenced by the probe quantity and arrangement, and the specific acquisition data included in the calibration.ConclusionThe ability to tailor basis functions to more compactly describe the spatial variation of field perturbations enables improved characterization of fields with rapid spatial variations.

PURPOSE:To develop a framework that jointly estimates rigid motion and polarizing magnetic field (B0 ) perturbations ( δ B 0 $$ \delta {\mathbf{B}}_{\mathbf{0}} $$ ) for brain MRI using a single navigator of a few milliseconds in duration, and to additionally allow for navigator acquisition at arbitrary timings within any type of sequence to obtain high-temporal resolution estimates. THEORY AND METHODS:Methods exist that match navigator data to a low-resolution single-contrast image (scout) to estimate either motion or δ B 0 $$ \delta {\mathbf{B}}_{\mathbf{0}} $$ . In this work, called QUEEN (QUantitatively Enhanced parameter Estimation from Navigators), we propose combined motion and δ B 0 $$ \delta {\mathbf{B}}_{\mathbf{0}} $$ estimation from a fast, tailored trajectory with arbitrary-contrast navigator data. To this end, the concept of a quantitative scout (Q-Scout) acquisition is proposed from which contrast-matched scout data is predicted for each navigator. Finally, navigator trajectories, contrast-matched scout, and δ B 0 $$ \delta {\mathbf{B}}_{\mathbf{0}} $$ are integrated into a motion-informed parallel-imaging framework. RESULTS:Simulations and in vivo experiments show the need to model δ B 0 $$ \delta {\mathbf{B}}_{\mathbf{0}} $$ to obtain accurate motion parameters estimated in the presence of strong δ B 0 $$ \delta {\mathbf{B}}_{\mathbf{0}} $$ . Simulations confirm that tailored navigator trajectories are needed to robustly estimate both motion and δ B 0 $$ \delta {\mathbf{B}}_{\mathbf{0}} $$ . Furthermore, experiments show that a contrast-matched scout is needed for parameter estimation from multicontrast navigator data. A retrospective, in vivo reconstruction experiment shows improved image quality when using the proposed Q-Scout and QUEEN estimation. CONCLUSIONS:We developed a framework to jointly estimate rigid motion parameters and δ B 0 $$ \delta {\mathbf{B}}_{\mathbf{0}} $$ from navigators. Combing a contrast-matched scout with the proposed trajectory allows for navigator deployment in almost any sequence and/or timing, which allows for higher temporal-resolution motion and δ B 0 $$ \delta {\mathbf{B}}_{\mathbf{0}} $$ estimates.

PURPOSE:To develop a 3D spherical EPTI (sEPTI) acquisition and a comprehensive reconstruction pipeline for rapid high-quality whole-brain submillimeter T 2 * $$ {\mathrm{T}}_2^{\ast } $$ and QSM quantification. METHODS:For the sEPTI acquisition, spherical k-space coverage is utilized with variable echo-spacing and maximum kx ramp-sampling to improve efficiency and signal incoherency compared to existing EPTI approaches. For reconstruction, an iterative rank-shrinking B0 estimation and odd-even high-order phase correction algorithms were incorporated into the reconstruction to better mitigate artifacts from field imperfections. A physics-informed unrolled network was utilized to boost the SNR, where 1-mm and 0.75-mm isotropic whole-brain imaging were performed in 45 and 90 s at 3 T, respectively. These protocols were validated through simulations, phantom, and in vivo experiments. Ten healthy subjects were recruited to provide sufficient data for the unrolled network. The entire pipeline was validated on additional five healthy subjects where different EPTI sampling approaches were compared. Two additional pediatric patients with epilepsy were recruited to demonstrate the generalizability of the unrolled reconstruction. RESULTS:sEPTI achieved 1.4 × $$ \times $$ faster imaging with improved image quality and quantitative map precision compared to existing EPTI approaches. The B0 update and the phase correction provide improved reconstruction performance with lower artifacts. The unrolled network boosted the SNR, achieving high-quality T 2 * $$ {\mathrm{T}}_2^{\ast } $$ and QSM quantification with single average data. High-quality reconstruction was also obtained in the pediatric patients using this network. CONCLUSION:sEPTI achieved whole-brain distortion-free multi-echo imaging and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ and QSM quantification at 0.75 mm in 90 s which has the potential to be useful for wide clinical applications.

Adiabatic Bloch-Siegert B1+ mapping method addresses the long TE and high RF power deposition problems of conventional Bloch-Siegert B1+ mapping by introducing short frequency-swept ABS pulses with maximum sensitivity. Here, it is shown how maximum signal to noise ratio can be achieved in adiabatic Bloch-Siegert B1+ mapping. Signal to noise ratio of B1+ maps is maximized by optimizing the adiabatic pulse parameters such as width, amplitude and shape of the Bloch-Siegert pulse within a specified scan time and under approved SAR guidelines. Equations for optimized Bloch-Siegert pulse parameters are derived, which are dependent on the base pulse sequence used for B1+ mapping as well as tissue properties and transmit coil configuration. It is shown that by this optimization it is more efficient to increase TR rather than using the averaging method to increase signal to noise ratio.

A 2D-line-scan MRI sequence has been reported to directly measure neural responses to stimuli (the "DIANA response"). Attempts to replicate the DIANA response have failed, even with higher field strength and more repetitions. Part of this discrepancy is likely due to a limited understanding of how physiological noise manifests in 2D-line-scan acquisition sequences. Specifically, it is unclear what the consequences are of breaking the assumption that the imaging substrate remains constant between each line acquisition. To answer this question, we collected 2D-line-scan data at 3T from human subjects viewing a blank screen. We found temporal fluctuations in the reconstructed time series that could easily be confused with neural responses to stimuli. These fluctuations were present both in the head and in the surrounding empty volume along the span of the phase-encoding direction from the head. The timing of these fluctuations varied systematically and smoothly along the phase-encoding direction. These artifacts are similar to well-known phase-encoding artifacts in EPI and GRE images, but are exacerbated due to longer acquisition times in the 2D-line-scan sequence (seconds vs. milliseconds). We explain these artifacts with a model that accounts for the acquisition sequence and incorporates time-varying contrast fluctuations and movement in the imaging substrate. Using the model, we quantify the amount of cortical- and scan-averaging one might need to reliably distinguish a DIANA response from noise, and show that navigator echoes might help in reducing phase-encode noise in the 2D-line-scan sequence.

BUDA-cEPI combines a circular-EPI (cEPI) trajectory with Blip-Up and Down Acquisition (BUDA), to achieve high-fidelity diffusion imaging. It employs full-ramp-sampling to efficiently cover a circular k-space to shorten the readout-train and mitigate T 2 *-blurring. For further readout-shortening, a combined phase-encoding(PE) & readout(RO) partial-Fourier (pF) is employed, where PE-pF is resolved via opposing the blip-up and down EPI-shots, and S-LORAKS reconstruction is used to effectively fill-out the remaining k-space. This resulted in an acquisition with markedly-reduced TE and ~40% reduced echo-train-length and T 2 *-blurring compared to standard-EPI at the same R inplane and PE-pF. To achieve high-SNR, BUDA-cEPI is also combined with a gSlider-multi-slab acquisition.

PURPOSE This study aims to develop a high-efficiency and high-resolution 3D imaging approach for simultaneous mapping of multiple key tissue parameters for routine brain imaging, including T1 , T2 , proton density (PD), ADC, and fractional anisotropy (FA). The proposed method is intended for pushing routine clinical brain imaging from weighted imaging to quantitative imaging and can also be particularly useful for diffusion-relaxometry studies, which typically suffer from lengthy acquisition time. METHODS To address challenges associated with diffusion weighting, such as shot-to-shot phase variation and low SNR, we integrated several innovative data acquisition and reconstruction techniques. Specifically, we used M1-compensated diffusion gradients, cardiac gating, and navigators to mitigate phase variations caused by cardiac motion. We also introduced a data-driven pre-pulse gradient to cancel out eddy currents induced by diffusion gradients. Additionally, to enhance image quality within a limited acquisition time, we proposed a data-sharing joint reconstruction approach coupled with a corresponding sequence design. RESULTS The phantom and in vivo studies indicated that the T1 and T2 values measured by the proposed method are consistent with a conventional MR fingerprinting sequence and the diffusion results (including diffusivity, ADC, and FA) are consistent with the spin-echo EPI DWI sequence. CONCLUSION The proposed method can achieve whole-brain T1 , T2 , diffusivity, ADC, and FA maps at 1-mm isotropic resolution within 10 min, providing a powerful tool for investigating the microstructural properties of brain tissue, with potential applications in clinical and research settings.

Several groups have reported using 2D line-scan MRI sequences in humans and mice to directly measure neural responses to stimuli (the “DIANA response”). Other groups have been unable to replicate the DIANA response, even with higher field strength and more repetitions. Part of this discrepancy is likely due to a limited understanding of the noise profile of the line-scan MRI sequence: specifically, the consequences of deviations from the assumption of stationarity between each line acquisition. Here, we collected data using an MRI line-scan method while human subjects viewed a blank screen with the purpose of studying noise unique to the acquisition sequence. We found temporal fluctuations in the reconstructed time series from localized groups of voxels that could easily be confused with neural responses to stimuli. These fluctuations were present both in the head and in the surrounding empty volume along the span of the phase-encoding direction from the head. The timing of these fluctuations varied systematically and smoothly along the phase-encoding direction. These features can be explained by a model that accounts for the acquisition sequence and incorporates time-varying contrast fluctuations in the imaging substrate. Using the model, we quantify the amount of cortical- and scan-averaging one might need to reliably distinguish a DIANA response from noise.

Blood and cerebrospinal fluid (CSF) pulse and flow throughout the brain, driven by the cardiac cycle. These fluid dynamics, which are essential to healthy brain function, are characterized by several noninvasive magnetic resonance imaging (MRI) methods. Recent developments in fast MRI, specifically simultaneous multislice acquisition methods, provide a new opportunity to rapidly and broadly assess cardiac‐driven flow, including CSF spaces, surface vessels and parenchymal vessels. We use these techniques to assess blood and CSF flow dynamics in brief (3.5 min) scans on a conventional 3 T MRI scanner in five subjects. Cardiac pulses are measured with a photoplethysmography (PPG) on the index finger, along with functional MRI (fMRI) signals in the brain. We, retrospectively, align the fMRI signals to the heartbeat. Highly reliable cardiac‐gated fMRI temporal signals are observed in CSF and blood on the timescale of one heartbeat (test–retest reliability within subjects R2 > 50%). In blood vessels, a local minimum is observed following systole. In CSF spaces, the ventricles and subarachnoid spaces have a local maximum following systole instead. Slower resting‐state scans with slice timing, retrospectively, aligned to the cardiac pulse, reveal similar cardiac‐gated responses. The cardiac‐gated measurements estimate the amplitude and phase of fMRI pulsations in the CSF relative to those in the arteries, an estimate of the local intracranial impedance. Cardiac aligned fMRI signals can provide new insights about fluid dynamics or diagnostics for diseases where these dynamics are important.

Purpose: This study aims to develop a high-resolution whole-brain multi-parametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T1, T2, and proton-density (PD), all within a clinically feasible scan time. Methods: We developed 3D ViSTa-MRF, which combined Visualization of Short Transverse relaxation time component (ViSTa) technique with MR Fingerprinting (MRF), to achieve high-fidelity whole-brain MWF and T1/T2/PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling spiral-projection acquisition and joint spatial-temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa-MRF approach, high-fidelity direct MWF mapping was achieved without a need for multi-compartment fitting that could introduce bias and/or noise from additional assumptions or priors. Results: The in-vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi-parametric mapping with high SNR and good quality. The in-vivo results of 1mm- and 0.66mm-iso datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30x slower with lower SNR. Furthermore, we applied the proposed method to enable 5-minute whole-brain 1mm-iso assessment of MWF and T1/T2/PD mappings for infant brain development and for post-mortem brain samples. Conclusions: In this work, we have developed a 3D ViSTa-MRF technique that enables the acquisition of whole-brain MWF, quantitative T1, T2, and PD maps at 1mm and 0.66mm isotropic resolution in 5 and 15 minutes, respectively. This advancement allows for quantitative investigations of myelination changes in the brain.

In this work, we developed ViSTa-MRF, which combined Visualization of Short Transverse relaxation time component (ViSTa) technique with MR Fingerprinting (MRF), to achieve high-fidelity whole-brain myelin-water fraction (MWF) and T1/T2/PD mapping at sub-millimeter isotropic resolution on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling (TGAS) spiral-projection acquisition and stochastic subspace reconstruction with optimized k-space diagonal preconditioning. With the proposed ViSTa-MRF method, high-fidelity direct MWF mapping was achieved without a need for multi-compartment fitting.

Blood and cerebrospinal fluid (CSF) pulse and flow throughout the brain, driven by the cardiac cycle. These fluid dynamics, which are essential to healthy brain function, are characterized by several noninvasive magnetic resonance imaging (MRI) methods. Recent developments in fast MRI, specifically simultaneous multislice (SMS) acquisition methods, provide a new opportunity to rapidly and broadly assess cardiac-driven flow, including CSF spaces, surface vessels and parenchymal vessels. We use these techniques to assess blood and CSF flow dynamics in brief (3.5 minute) scans on a conventional 3T MRI scanner. Cardiac pulses are measured with a photoplethysmograph (PPG) on the index finger, along with fMRI signals in the brain. We retrospectively analyze the fMRI signals gated to the heart beat. Highly reliable cardiac-gated fMRI temporal signals are observed in CSF and blood on the timescale of one heartbeat (test-retest reliability within subjects R 2 >0.50). Cardiac pulsations with a local minimum following systole are observed in blood vessels, with earlier extrema in the carotid and basilar arteries and in branches of the anterior, posterior and middle cerebral arteries and extrema ∼200 ms later in the superior sagittal, transverse and straight sinuses. CSF spaces in the ventricles and subarachnoid space showed cardiac pulsations with a local maximum following systole instead. Similar responses are observed, with less temporal detail, in slower resting state scans with slice timing retrospectively aligned to the cardiac pulse in the same manner. The SMS measurements rapidly, noninvasively and reliably sample brain-wide fMRI signal pulsations aligned to the heartbeat. The measurements estimate the amplitude and phase of cardiac driven fMRI pulsations in the CSF relative to those in the arteries, which is thought to be an estimate of the local intracranial impedance. Cardiac aligned fMRI signals can provide new insights about fluid dynamics or diagnostics for diseases where these dynamics are important.

In this paper we provide an overview of the rationale, methods, and preliminary results of the four Connectome Studies Related to Human Disease investigating mood and anxiety disorders. The first study, “Dimensional connectomics of anxious misery” (HCP-DAM), characterizes brain-symptom relations of a transdiagnostic sample of anxious misery disorders. The second study, “Human connectome Project for disordered emotional states” (HCP-DES), tests a hypothesis-driven model of brain circuit dysfunction in a sample of untreated young adults with symptoms of depression and anxiety. The third study, “Perturbation of the treatment resistant depression connectome by fast-acting therapies” (HCP-MDD), quantifies alterations of the structural and functional connectome as a result of three fast-acting interventions: electroconvulsive therapy, serial ketamine therapy, and total sleep deprivation. Finally, the fourth study, “Connectomes related to anxiety and depression in adolescents” (HCP-ADA), investigates developmental trajectories of subtypes of anxiety and depression in adolescence.The four projects use comparable and standardized Human Connectome Project magnetic resonance imaging (MRI) protocols, including structural MRI, diffusion-weighted MRI, and both task and resting state functional MRI. All four projects also conducted comprehensive and convergent clinical and neuropsychological assessments, including (but not limited to) demographic information, clinical diagnoses, symptoms of mood and anxiety disorders, negative and positive affect, cognitive function, and exposure to early life stress. The first round of analyses conducted in the four projects offered novel methods to investigate relations between functional connectomes and self-reports in large datasets, identified new functional correlates of symptoms of mood and anxiety disorders, characterized the trajectory of connectome-symptom profiles over time, and quantified the impact of novel treatments on aberrant connectivity.Taken together, the data obtained and reported by the four Connectome Studies Related to Human Disease investigating mood and anxiety disorders describe a rich constellation of convergent biological, clinical, and behavioral phenotypes that span the peak ages for the onset of emotional disorders. These data are being prepared for open sharing with the scientific community following screens for quality by the Connectome Coordinating Facility (CCF). The CCF also plans to release data from all projects that have been pre-processed using identical state-of-the-art pipelines. The resultant dataset will give researchers the opportunity to pool complementary data across the four projects to study circuit dysfunctions that may underlie mood and anxiety disorders, to map cohesive relations among circuits and symptoms, and to probe how these relations change as a function of age and acute interventions. This large and combined dataset may also be ideal for using data-driven analytic approaches to inform neurobiological targets for future clinical trials and interventions focused on clinical or behavioral outcomes.

Compressed sensing has empowered quality image reconstruction with fewer data samples than previously thought possible. These techniques rely on a sparsifying linear transformation. The Daubechies wavelet transform is commonly used for this purpose. In this work, we take advantage of the structure of this wavelet transform and identify an affine transformation that increases the sparsity of the result. After inclusion of this affine transformation, we modify the resulting optimization problem to comply with the form of the Basis Pursuit Denoising problem. Finally, we show theoretically that this yields a lower bound on the error of the reconstruction and present results where solving this modified problem yields images of higher quality for the same sampling patterns using both magnetic resonance and optical images.

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.

Through the Human Connectome Project (HCP) our understanding of the functional connectome of the healthy brain has been dramatically accelerated. Given the pressing public health need, we must increase our understanding of how connectome dysfunctions give rise to disordered mental states. Mental disorders arising from high levels of negative emotion or from the loss of positive emotional experience affect over 400 million people globally. Such states of disordered emotion cut across multiple diagnostic categories of mood and anxiety disorders and are compounded by accompanying disruptions in cognitive function. Not surprisingly, these forms of psychopathology are the leading cause of disability worldwide. The Research Domain Criteria (RDoC) initiative spearheaded by NIMH offers a framework for characterizing the relations among connectome dysfunctions, anchored in neural circuits and phenotypic profiles of behavior and self-reported symptoms. Here, we report on our Connectomes Related to Human Disease protocol for integrating an RDoC framework with HCP protocols to characterize connectome dysfunctions in disordered emotional states, and present quality control data from a representative sample of participants. We focus on three RDoC domains and constructs most relevant to depression and anxiety: 1) loss and acute threat within the Negative Valence System (NVS) domain; 2) reward valuation and responsiveness within the Positive Valence System (PVS) domain; and 3) working memory and cognitive control within the Cognitive System (CS) domain. For 29 healthy controls, we present preliminary imaging data: functional magnetic resonance imaging collected in the resting state and in tasks matching our constructs of interest ("Emotion", "Gambling" and "Continuous Performance" tasks), as well as diffusion-weighted imaging. All functional scans demonstrated good signal-to-noise ratio. Established neural networks were robustly identified in the resting state condition by independent component analysis. Processing of negative emotional faces significantly activated the bilateral dorsolateral prefrontal and occipital cortices, fusiform gyrus and amygdalae. Reward elicited a response in the bilateral dorsolateral prefrontal, parietal and occipital cortices, and in the striatum. Working memory was associated with activation in the dorsolateral prefrontal, parietal, motor, temporal and insular cortices, in the striatum and cerebellum. Diffusion tractography showed consistent profiles of fractional anisotropy along known white matter tracts. We also show that results are comparable to those in a matched sample from the HCP Healthy Young Adult data release. These preliminary data provide the foundation for acquisition of 250 subjects who are experiencing disordered emotional states. When complete, these data will be used to develop a neurobiological model that maps connectome dysfunctions to specific behaviors and symptoms.