High-fidelity mesoscale in-vivo diffusion MRI through gSlider-BUDA and circular EPI with S-LORAKS reconstruction.

PURPOSE: To develop a high-fidelity diffusion MRI acquisition and reconstruction framework with reduced echo-train-length for less T2* image blurring compared to typical highly accelerated echo-planar imaging (EPI) acquisitions at sub-millimeter isotropic resolution. METHODS: We first proposed a circular-EPI trajectory with partial Fourier sampling on both the readout and phase-encoding directions to minimize the echo-train-length and echo time. We then utilized this trajectory in an interleaved two-shot EPI acquisition with reversed phase-encoding polarity, to aid in the correction of off-resonance-induced image distortions and provide complementary k-space coverage in the missing partial Fourier regions. Using model-based reconstruction with structured low-rank constraint and smooth phase prior, we corrected the shot-to-shot phase variations across the two shots and recover the missing k-space data. Finally, we combined the proposed acquisition/reconstruction framework with an SNR-efficient RF-encoded simultaneous multi-slab technique, termed gSlider, to achieve high-fidelity 720 µm and 500 µm isotropic resolution in-vivo diffusion MRI. RESULTS: Both simulation and in-vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide distortion-corrected diffusion imaging at the mesoscale with markedly reduced T2*-blurring. The in-vivo results of 720 µm and 500 µm datasets show high-fidelity diffusion images with reduced image blurring and echo time using the proposed approaches. CONCLUSIONS: The proposed method provides high-quality distortion-corrected diffusion-weighted images with ∼40% reduction in the echo-train-length and T2* blurring at 500µm-isotropic-resolution compared to standard multi-shot EPI.

Measuring brain beats: Cardiac-aligned fast functional magnetic resonance imaging signals.

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.

Convergence, preliminary findings and future directions across the four human connectome projects investigating mood and anxiety disorders.

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.

The human connectome project for disordered emotional states: Protocol and rationale for a research domain criteria study of brain connectivity in young adult anxiety and depression.

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.

Combined T2 -preparation and multidimensional outer volume suppression for coronary artery imaging with 3D cones trajectories.

PURPOSE: To develop a modular magnetization preparation sequence for combined T2 -preparation and multidimensional outer volume suppression (OVS) for coronary artery imaging. METHODS: A combined T2 -prepared 1D OVS sequence with fat saturation was defined to contain a 90°-60 180°60 composite nonselective tip-down pulse, two 180°Y hard pulses for refocusing, and a -90° spectral-spatial sinc tip-up pulse. For 2D OVS, 2 modules were concatenated, selective in X and then Y. Bloch simulations predicted robustness of the sequence to B0 and B1 inhomogeneities. The proposed sequence was compared with a T2 -prepared 2D OVS sequence proposed by Luo et al, which uses a spatially selective 2D spiral tip-up. The 2 sequences were compared in phantom studies and in vivo coronary artery imaging studies with a 3D cones trajectory. RESULTS: Phantom results demonstrated superior OVS for the proposed sequence compared with the Luo sequence. In studies on 15 healthy volunteers, the proposed sequence had superior image edge profile acutance values compared with the Luo sequence for the right (P < .05) and left (P < .05) coronary arteries, suggesting superior vessel sharpness. The proposed sequence also had superior signal-to-noise ratio (P < .05) and passband-to-stopband ratio (P < .05). Reader scores and reader preference indicated superior coronary image quality of the proposed sequence for both the right (P < .05) and left (P < .05) coronary arteries. CONCLUSION: The proposed sequence with concatenated 1D spatially selective tip-ups and integrated fat saturation has superior image quality and suppression compared with the Luo sequence with 2D spatially selective tip-up.

Slice profile effects on nCPMG SS-FSE.

PURPOSE: To determine the effects of the RF refocusing pulse profile on the magnitude of the transverse signal smoothness throughout the echo train in non-Carr-Purcell-Meiboom-Gill (nCPMG) single-shot fast spin echo (SS-FSE) imaging and to design an RF refocusing pulse that provides improved signal stability. THEORY AND METHODS: nCPMG SS-FSE quadratic phase modulation requires sufficiently high and uniform refocusing flip angle to achieve a stable signal. Typically, refocusing pulses used in SS-FSE sequences are designed for minimum duration to minimize echo spacing and as a consequence have poor selectivity. However, delay-insensitive variable rate excitation Shinnar-Le Roux (DV-SLR) refocusing pulses can achieve both improved selectivity as well as a short duration. This class of RF pulse is compared against a traditional low time-bandwidth refocusing pulse in a nCPMG SS-FSE in simulation, phantom, and in vivo. RESULTS: DV-SLR pulses achieve a more stable signal in simulation, phantom, and in vivo cases while maintaining an appropriately short duration as well as not dramatically increasing specific absorption rate (SAR) accumulation. CONCLUSION: The nCPMG SS-FSE method demonstrates improved robustness when a more selective refocusing pulse is used. Refocusing pulses that use a time-varying excitation gradient can achieve this selectivity while maintaining short echo spacing. Magn Reson Med 79:430-438, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Body diffusion-weighted imaging using magnetization prepared single-shot fast spin echo and extended parallel imaging signal averaging.

PURPOSE: This work demonstrates a magnetization prepared diffusion-weighted single-shot fast spin echo (SS-FSE) pulse sequence for the application of body imaging to improve robustness to geometric distortion. This work also proposes a scan averaging technique that is superior to magnitude averaging and is not subject to artifacts due to object phase. THEORY AND METHODS: This single-shot sequence is robust against violation of the Carr-Purcell-Meiboom-Gill (CPMG) condition. This is achieved by dephasing the signal after diffusion weighting and tipping the MG component of the signal onto the longitudinal axis while the non-MG component is spoiled. The MG signal component is then excited and captured using a traditional SS-FSE sequence, although the echo needs to be recalled prior to each echo. Extended Parallel Imaging (ExtPI) averaging is used where coil sensitivities from the multiple acquisitions are concatenated into one large parallel imaging (PI) problem. The size of the PI problem is reduced by SVD-based coil compression which also provides background noise suppression. This sequence and reconstruction are evaluated in simulation, phantom scans, and in vivo abdominal clinical cases. RESULTS: Simulations show that the sequence generates a stable signal throughout the echo train which leads to good image quality. This sequence is inherently low-SNR, but much of the SNR can be regained through scan averaging and the proposed ExtPI reconstruction. In vivo results show that the proposed method is able to provide diffusion encoded images while mitigating geometric distortion artifacts compared to EPI. CONCLUSION: This work presents a diffusion-prepared SS-FSE sequence that is robust against the violation of the CPMG condition while providing diffusion contrast in clinical cases. Magn Reson Med 79:3032-3044, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Technique development of 3D dynamic CS-EPSI for hyperpolarized 13 C pyruvate MR molecular imaging of human prostate cancer.

PURPOSE: The purpose of this study was to develop a new 3D dynamic carbon-13 compressed sensing echoplanar spectroscopic imaging (EPSI) MR sequence and test it in phantoms, animal models, and then in prostate cancer patients to image the metabolic conversion of hyperpolarized [1-13 C]pyruvate to [1-13 C]lactate with whole gland coverage at high spatial and temporal resolution. METHODS: A 3D dynamic compressed sensing (CS)-EPSI sequence with spectral-spatial excitation was designed to meet the required spatial coverage, time and spatial resolution, and RF limitations of the 3T MR scanner for its clinical translation for prostate cancer patient imaging. After phantom testing, animal studies were performed in rats and transgenic mice with prostate cancers. For patient studies, a GE SPINlab polarizer (GE Healthcare, Waukesha, WI) was used to produce hyperpolarized sterile GMP [1-13 C]pyruvate. 3D dynamic 13 C CS-EPSI data were acquired starting 5 s after injection throughout the gland with a spatial resolution of 0.5 cm3 , 18 time frames, 2-s temporal resolution, and 36 s total acquisition time. RESULTS: Through preclinical testing, the 3D CS-EPSI sequence developed in this project was shown to provide the desired spectral, temporal, and spatial 5D HP 13 C MR data. In human studies, the 3D dynamic HP CS-EPSI approach provided first-ever simultaneously volumetric and dynamic images of the LDH-catalyzed conversion of [1-13 C]pyruvate to [1-13 C]lactate in a biopsy-proven prostate cancer patient with full gland coverage. CONCLUSION: The results demonstrate the feasibility to characterize prostate cancer metabolism in animals, and now patients using this new 3D dynamic HP MR technique to measure kPL , the kinetic rate constant of [1-13 C]pyruvate to [1-13 C]lactate conversion.

Measuring B1 distributions by B1 phase encoding.

PURPOSE: We propose a method to acquire B1 distribution plots by encoding in B1 instead of image space. Using this method, B1 data is acquired in a different way from traditional spatial B1 mapping, and allows for quick measurement of high dynamic range B1 data. METHODS: To encode in B1, we acquire multiple projections of a slice, each along the same direction, but using a different phase sensitivity to B1. Using a convex optimization formulation, we reconstruct histograms of the B1 distribution estimates of the slice. RESULTS: We verify in vivo B1 distribution measurements by comparing measured distributions to distributions calculated from reference spatial B1 maps using the Earth Mover's Distance. Phantom measurements using a surface coil show that for increased spatial B1 variations, measured B1 distributions using the proposed method more accurately estimate the distribution than a low-resolution spatial B1 map, resulting in a 37% Earth Mover's Distance decrease while using fewer measurements. CONCLUSION: We propose and validate the performance of a method to acquire B1 distribution information directly without acquiring a spatial B1 map. The method may provide faster estimates of a B1 field for applications that do not require spatial B1 localization, such as the transmit gain calibration of the scanner, particularly for high dynamic B1 ranges. Magn Reson Med 77:229-236, 2017. © 2016 Wiley Periodicals, Inc.

Lowering the B1 threshold for improved BEAR B1 mapping.

PURPOSE: Accurate measurement of the nonuniform transmit radiofrequency field is necessary for magnetic resonance imaging applications. The radiofrequency field excitation amplitude (B1) is often obtained by acquiring a B1 map. We modify the B1 estimation using adiabatic refocusing (BEAR) method to extend its range to lower B1 magnitudes. THEORY AND METHODS: The BEAR method is a phase-based B1 mapping method, wherein hyperbolic secant pulses induce a phase sensitivity to B1. The measurable B1 range is limited due to the adiabatic threshold of the pulses. We redesign the method to use flattened hyperbolic secant pulses, which have lower adiabatic thresholds. We optimize the flattened hyperbolic secant parameters to minimize phase sensitivity to frequency variations. RESULTS: We validate the performance of the new method via simulation and in vivo at 3T, and show that for n ≤ 8, accurate B1 maps can be acquired using reduced nominal peak B1 values. CONCLUSION: The adiabatic threshold for the BEAR method is reduced with flattened hyperbolic secant pulses, which are optimized for accurate phase-to-B1 mapping over a frequency range, and allow for lower nominal B1 values. At 3T, the nominal B1 is decreased by 52% and the sensitivity to B1 is increased by a factor of 3.8. This can improve the method's applicability for measurement of low B1.