Rapid three-dimensional quantification of high-intensity plaques from coronary atherosclerosis T1-weighted characterization to predict periprocedural myocardial injury.

BACKGROUND: High-intensity plaque (HIP) on magnetic resonance imaging (MRI) has been documented as a powerful predictor of periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI). Despite the recent proposal of three-dimensional HIP quantification to enhance the predictive capability, the conventional pulse sequence, which necessitates the separate acquisition of anatomical reference images, hinders accurate three-dimensional segmentation along the coronary vasculature. Coronary atherosclerosis T1-weighted characterization (CATCH) enables the simultaneous acquisition of inherently coregistered dark-blood plaque and bright-blood coronary artery images. We aimed to develop a novel HIP quantification approach using CATCH and to ascertain its superior predictive performance compared to the conventional two-dimensional assessment based on plaque-to-myocardium signal intensity ratio (PMR). METHODS: In this prospective study, CATCH MRI was conducted before elective stent implantation in 137 lesions from 125 patients. On CATCH images, dedicated software automatically generated tubular three-dimensional volumes of interest on the dark-blood plaque images along the coronary vasculature, based on the precisely matched bright-blood coronary artery images, and subsequently computed PMR and HIP volume (HIPvol). Specifically, HIPvol was calculated as the volume of voxels with signal intensity exceeding that of the myocardium, weighted by their respective signal intensities. PMI was defined as post-PCI cardiac troponin-T > 5 × the upper reference limit. RESULTS: The entire analysis process was completed within 3 min per lesion. PMI occurred in 44 lesions. Based on the receiver operating characteristic curve analysis, HIPvol outperformed PMR for predicting PMI (C-statistics, 0.870 [95% CI, 0.805-0.936] vs. 0.787 [95% CI, 0.706-0.868]; p = 0.001). This result was primarily driven by the higher sensitivity HIPvol offered: 0.886 (95% CI, 0.754-0.962) vs. 0.750 for PMR (95% CI, 0.597-0.868; p = 0.034). Multivariable analysis identified HIPvol as an independent predictor of PMI (odds ratio, 1.15 per 10-µL increase; 95% CI, 1.01-1.30, p = 0.035). CONCLUSIONS: Our semi-automated method of analyzing coronary plaque using CATCH MRI provided rapid HIP quantification. Three-dimensional assessment using this approach had a better ability to predict PMI than conventional two-dimensional assessment.

Motion-compensated T1 mapping in cardiovascular magnetic resonance imaging: a technical review.

T1 mapping is becoming a staple magnetic resonance imaging method for diagnosing myocardial diseases such as ischemic cardiomyopathy, hypertrophic cardiomyopathy, myocarditis, and more. Clinically, most T1 mapping sequences acquire a single slice at a single cardiac phase across a 10 to 15-heartbeat breath-hold, with one to three slices acquired in total. This leaves opportunities for improving patient comfort and information density by acquiring data across multiple cardiac phases in free-running acquisitions and across multiple respiratory phases in free-breathing acquisitions. Scanning in the presence of cardiac and respiratory motion requires more complex motion characterization and compensation. Most clinical mapping sequences use 2D single-slice acquisitions; however newer techniques allow for motion-compensated reconstructions in three dimensions and beyond. To further address confounding factors and improve measurement accuracy, T1 maps can be acquired jointly with other quantitative parameters such as T2, T2∗, fat fraction, and more. These multiparametric acquisitions allow for constrained reconstruction approaches that isolate contributions to T1 from other motion and relaxation mechanisms. In this review, we examine the state of the literature in motion-corrected and motion-resolved T1 mapping, with potential future directions for further technical development and clinical translation.

Locating causal hubs of memory consolidation in spontaneous brain network in male mice.

Memory consolidation after learning involves spontaneous, brain-wide network reorganization during rest and sleep, but how this is achieved is still poorly understood. Current theory suggests that the hippocampus is pivotal for this reshaping of connectivity. Using fMRI in male mice, we identify that a different set of spontaneous networks and their hubs are instrumental in consolidating memory during post-learning rest. We found that two types of spatial memory training invoke distinct functional connections, but that a network of the sensory cortex and subcortical areas is common for both tasks. Furthermore, learning increased brain-wide network integration, with the prefrontal, striatal and thalamic areas being influential for this network-level reconfiguration. Chemogenetic suppression of each hub identified after learning resulted in retrograde amnesia, confirming the behavioral significance. These results demonstrate the causal and functional roles of resting-state network hubs in memory consolidation and suggest that a distributed network beyond the hippocampus subserves this process.

Free-breathing 3D CEST MRI of human liver at 3.0 T.

PURPOSE: To develop a novel 3D abdominal CEST MRI technique at 3 T using MR multitasking, which enables entire-liver coverage with free-breathing acquisition. METHODS: k-Space data were continuously acquired with repetitive steady-state CEST (ss-CEST) modules. The stack-of-stars acquisition pattern was used for k-space sampling. MR multitasking was used to reconstruct motion-resolved 3D CEST images of 53 frequency offsets with entire-liver coverage and 2.0 × 2.0 × 6.0 mm3 spatial resolution. The total scan time was 9 min. The sensitivity of amide proton transfer (APT)-CEST (magnetization transfer asymmetry [MTRasym ] at 3.5 ppm) and glycogen CEST (glycoCEST) (mean MTRasym around 1.0 ppm) signals generated with the proposed method were tested with fasting experiments. RESULTS: Both APT-CEST and glycoCEST signals showed high sensitivity between post-fasting and post-meal acquisitions. APT-CEST and glycoCEST MTRasym signals from post-mean scans were significantly increased (APT-CEST: -0.019 ± 0.017 in post-fasting scans, 0.014 ± 0.021 in post-meal scans, p < 0.01; glycoCEST: 0.003 ± 0.009 in post-fasting scans, 0.027 ± 0.021 in post-meal scans, p < 0.01). CONCLUSION: The proposed 3D abdominal steady-state CEST method using MR multitasking can generate CEST images of the entire liver during free breathing.

Free-breathing, non-ECG, simultaneous myocardial T1 , T2 , T2 *, and fat-fraction mapping with motion-resolved cardiovascular MR multitasking.

PURPOSE: To develop a free-breathing, non-electrocardiogram technique for simultaneous myocardial T1 , T2 , T2 *, and fat-fraction (FF) mapping in a single scan. METHODS: The MR Multitasking framework is adapted to quantify T1 , T2 , T2 *, and FF simultaneously. A variable TR scheme is developed to preserve temporal resolution and imaging efficiency. The underlying high-dimensional image is modeled as a low-rank tensor, which allows accelerated acquisition and efficient reconstruction. The accuracy and/or repeatability of the technique were evaluated on static and motion phantoms, 12 healthy volunteers, and 3 patients by comparing to the reference techniques. RESULTS: In static and motion phantoms, T1 /T2 /T2 */FF measurements showed substantial consistency (R > 0.98) and excellent agreement (intraclass correlation coefficient > 0.93) with reference measurements. In human subjects, the proposed technique yielded repeatable T1 , T2 , T2 *, and FF measurements that agreed with those from references. CONCLUSIONS: The proposed free-breathing, non-electrocardiogram, motion-resolved Multitasking technique allows simultaneous quantification of myocardial T1 , T2 , T2 *, and FF in a single 2.5-min scan.

Simultaneous Multi-Slice Cardiac MR Multitasking for Motion-Resolved, Non-ECG, Free-Breathing T1-T2 Mapping.

The aim of this study is to simultaneously quantify T1/T2 across three slices of the left-ventricular myocardium without breath-holds or ECG monitoring, all within a 3 min scan. Radial simultaneous multi-slice (SMS) encoding, self-gating, and image reconstruction was incorporated into the cardiovascular magnetic resonance (CMR) Multitasking framework to simultaneously image three short-axis slices. A T2prep-IR FLASH sequence with two flip angles was designed and implemented to allow B1+-robust T1 and T2 mapping. The proposed Multitasking-SMS method was validated in a standardized phantom and 10 healthy volunteers, comparing T1 and T2 measurements and scan-rescan repeatability against corresponding reference methods in one layer of phantom vials and in 16 American Heart Association (AHA) myocardial segments. In phantom, Multitasking-SMS T1/T2 measurements showed substantial correlation (R 2 > 0.996) and excellent agreement [intraclass correlation coefficients (ICC) ≥ 0.999)] with reference measurements. In healthy volunteers, Multitasking-SMS T1/T2 maps reported similar myocardial T1/T2 values (1,215 ± 91.0/41.5 ± 6.3 ms) to the reference myocardial T1/T2 values (1,239 ± 67.5/42.7 ± 4.1 ms), with P = 0.347 and P = 0.296, respectively. Bland-Altman analyses also demonstrated good in vivo repeatability in both the multitasking and references, with segment-wise coefficients of variation of 4.7% (multitasking T1), 8.9% (multitasking T2), 2.4% [modified look-locker inversion recovery (MOLLI)], and 4.6% (T2-prep FLASH), respectively. In summary, multitasking-SMS is feasible for free-breathing, non-ECG, myocardial T1/T2 quantification in 16 AHA segments over 3 short-axis slices in 3 min. The method shows the great potential for reducing exam time for quantitative CMR without ECG or breath-holds.

Whole-brain steady-state CEST at 3 T using MR Multitasking.

PURPOSE: To perform fast 3D steady-state CEST (ss-CEST) imaging using MR Multitasking. METHODS: A continuous acquisition sequence with repetitive ss-CEST modules was developed. Each ss-CEST module contains a single-lobe Gaussian saturation pulse, followed by a spoiler gradient and eight FLASH readouts (one "training line" + seven "imaging lines"). Three-dimensional Cartesian encoding was used for k-space acquisition. Reconstructed CEST images were quantified with four-pool Lorentzian fitting. RESULTS: Steady-state CEST with whole-brain coverage was performed in 5.6 s per saturation frequency offset at the spatial resolution of 1.7 × 1.7 × 3.0 mm3 . The total scan time was 5.5 min for 55 different frequency offsets. Quantitative CEST maps from multipool fitting showed consistent image quality across the volume. CONCLUSION: Three-dimensional ss-CEST with whole-brain coverage can be done at 3 T within 5.5 min using MR Multitasking.

Optimizing diffusion MRI acquisition efficiency of rodent brain using simultaneous multislice EPI.

Diffusion tensor imaging (DTI) of the brain provides essential information on the white matter integrity and structural connectivity. However, it suffers from a low signal-to-noise ratio (SNR) and requires a long scan time to achieve high spatial and/or diffusion resolution and wide brain coverage. With recent advances in parallel and simultaneous multislice (multiband) imaging, the SNR efficiency has been improved by reducing the repetition time (TR ). However, due to the limited number of RF coil channels available on preclinical MRI scanners, simultaneous multislice acquisition has not been practical. In this study, we demonstrate the ability of multiband DTI to acquire high-resolution data of the mouse brain with 84 slices covering the whole brain in 0.2 mm isotropic resolution without a coil array at 9.4 T. Hadamard-encoding four-band pulses were used to acquire four slices simultaneously, with the reduction in the TR maximizing the SNR efficiency. To overcome shot-to-shot phase variations, Hadamard decoding with a self-calibrated phase was developed. Compared with single-band DTI acquired with the same scan time, the multiband DTI leads to significantly increased SNR by 40% in the white matter. This SNR gain resulted in reduced variations in fractional anisotropy, mean diffusivity, and eigenvector orientation. Furthermore, the cerebrospinal fluid signal was attenuated, leading to reduced free-water contamination. Without the need for a high-density coil array or parallel imaging, this technique enables highly efficient preclinical DTI that will facilitate connectome studies.

Ultrafast fMRI of the rodent brain using simultaneous multi-slice EPI.

Increasing spatial and temporal resolutions of functional MRI (fMRI) measurement has been shown to benefit the study of neural dynamics and functional interaction. However, acceleration of rodent brain fMRI using parallel and simultaneous multi-slice imaging techniques is hampered by the lack of high-density phased-array coils for the small brain. To overcome this limitation, we adapted phase-offset multiplanar and blipped-controlled aliasing echo planar imaging (EPI) to enable simultaneous multi-slice fMRI of the mouse brain using a single loop coil on a 9.4T scanner. Four slice bands of 0.3 × 0.3 × 0.5 mm3 resolution can be simultaneously acquired to cover the whole brain at a temporal resolution of 300 ms or the whole cerebrum in 150 ms. Instead of losing signal-to-noise ratio (SNR), both spatial and temporal SNR can be increased due to the increased k-space sampling compared to a standard single-band EPI. Task fMRI using a visual stimulation shows close to 80% increase of z-score and 4 times increase of activated area in the visual cortex using the multiband EPI due to the highly increased temporal samples. Resting-state fMRI shows reliable detection of bilateral connectivity by both single-band and multiband EPI, but no significant difference was found. Without the need of a dedicated hardware, we have demonstrated a practical method that can enable unparallelly fast whole-brain fMRI for preclinical studies. This technique can be used to increase sensitivity, distinguish transient response or acquire high spatiotemporal resolution fMRI.

Evaluation of nuisance removal for functional MRI of rodent brain.

Functional MRI (fMRI) has become an important translational tool for studying brain activity and connectivity in animal models and humans. For accurate and reliable measurement of functional connectivity, nuisance removal strategies developed for human brain, such as regressing motion parameters, cerebrospinal fluid (CSF)/white matter-derived signals and the global signal, have been applied to rodent. However, due to the very different anatomy, with the majority of the rodent brain being gray matter, and experimental conditions, in which animals are anesthetized and head-fixed, these methods may not be suitable for rodent fMRI. In this study, we assessed various nuisance regression methods and the effects of motion correction on a large dataset of both task and resting fMRI of anesthetized rat brain. Sensitivity and specificity were assessed in the somatosensory pathway under forepaw stimulation and resting state. Reproducibility at various sample sizes was simulated by randomly subsampling the dataset. To overcome the difficulty in extracting nuisance from the brain, a method using principal components estimated from tissues outside the brain was evaluated. Our results showed that neither detrend, motion correction, motion regression nor CSF signal regression could improve specificity despite increasing temporal signal-to-noise ratios. Although global signal regression increased the specificity of task activation and functional connectivity, the sensitivity and connectivity strength was drastically reduced, likely due to its strong correlation with the cortical signal. Motion parameters also correlated with task activation and the global signal, indicating that motion correction detected intensity variations in the brain. The nuisance estimated from tissues outside the brain produced a moderate improvement in specificity. In conclusion, nuisance removal suitable for human fMRI may not be optimal for rodents. While further development is needed, estimating nuisance from tissues outside the brain may be an alternative.

Remodeling of Sensorimotor Brain Connectivity in Gpr88-Deficient Mice.

Recent studies have demonstrated that orchestrated gene activity and expression support synchronous activity of brain networks. However, there is a paucity of information on the consequences of single gene function on overall brain functional organization and connectivity and how this translates at the behavioral level. In this study, we combined mouse mutagenesis with functional and structural magnetic resonance imaging (MRI) to determine whether targeted inactivation of a single gene would modify whole-brain connectivity in live animals. The targeted gene encodes GPR88 (G protein-coupled receptor 88), an orphan G protein-coupled receptor enriched in the striatum and previously linked to behavioral traits relevant to neuropsychiatric disorders. Connectivity analysis of Gpr88-deficient mice revealed extensive remodeling of intracortical and cortico-subcortical networks. Most prominent modifications were observed at the level of retrosplenial cortex connectivity, central to the default mode network (DMN) whose alteration is considered a hallmark of many psychiatric conditions. Next, somatosensory and motor cortical networks were most affected. These modifications directly relate to sensorimotor gating deficiency reported in mutant animals and also likely underlie their hyperactivity phenotype. Finally, we identified alterations within hippocampal and dorsal striatum functional connectivity, most relevant to a specific learning deficit that we previously reported in Gpr88-/- animals. In addition, amygdala connectivity with cortex and striatum was weakened, perhaps underlying the risk-taking behavior of these animals. This is the first evidence demonstrating that GPR88 activity shapes the mouse brain functional and structural connectome. The concordance between connectivity alterations and behavior deficits observed in Gpr88-deficient mice suggests a role for GPR88 in brain communication.

The connectomics of brain demyelination: Functional and structural patterns in the cuprizone mouse model.

Connectomics of brain disorders seeks to reveal how altered brain function emerges from the architecture of cerebral networks; however the causal impact of targeted cellular damage on the whole brain functional and structural connectivity remains unknown. In the central nervous system, demyelination is typically the consequence of an insult targeted at the oligodendrocytes, the cells forming and maintaining the myelin. This triggered perturbation generates cascades of pathological events that most likely alter the brain connectome. Here we induced oligodendrocyte death and subsequent demyelinating pathology via cuprizone treatment in mice and combining mouse brain resting state functional Magnetic Resonance Imaging and diffusion tractography we established functional and structural pathology-to-network signatures. We demonstrated that demyelinated brain fundamentally reorganizes its intrinsic functional connectivity paralleled by widespread damage of the structural scaffolding. We evidenced default mode-like network as core target of demyelination-induced connectivity modulations and hippocampus as the area with strongest connectional perturbations.

Enhanced subject-specific resting-state network detection and extraction with fast fMRI.

Resting-state networks have become an important tool for the study of brain function. An ultra-fast imaging technique that allows to measure brain function, called Magnetic Resonance Encephalography (MREG), achieves an order of magnitude higher temporal resolution than standard echo-planar imaging (EPI). This new sequence helps to correct physiological artifacts and improves the sensitivity of the fMRI analysis. In this study, EPI is compared with MREG in terms of capability to extract resting-state networks. Healthy controls underwent two consecutive resting-state scans, one with EPI and the other with MREG. Subject-level independent component analyses (ICA) were performed separately for each of the two datasets. Using Stanford FIND atlas parcels as network templates, the presence of ICA maps corresponding to each network was quantified in each subject. The number of detected individual networks was significantly higher in the MREG data set than for EPI. Moreover, using short time segments of MREG data, such as 50 seconds, one can still detect and track consistent networks. Fast fMRI thus results in an increased capability to extract distinct functional regions at the individual subject level for the same scan times, and also allow the extraction of consistent networks within shorter time intervals than when using EPI, which is notably relevant for the analysis of dynamic functional connectivity fluctuations. Hum Brain Mapp 38:817-830, 2017. © 2016 Wiley Periodicals, Inc.

Deletion of the mu opioid receptor gene in mice reshapes the reward-aversion connectome.

Connectome genetics seeks to uncover how genetic factors shape brain functional connectivity; however, the causal impact of a single gene's activity on whole-brain networks remains unknown. We tested whether the sole targeted deletion of the mu opioid receptor gene (Oprm1) alters the brain connectome in living mice. Hypothesis-free analysis of combined resting-state fMRI diffusion tractography showed pronounced modifications of functional connectivity with only minor changes in structural pathways. Fine-grained resting-state fMRI mapping, graph theory, and intergroup comparison revealed Oprm1-specific hubs and captured a unique Oprm1 gene-to-network signature. Strongest perturbations occurred in connectional patterns of pain/aversion-related nodes, including the mu receptor-enriched habenula node. Our data demonstrate that the main receptor for morphine predominantly shapes the so-called reward/aversion circuitry, with major influence on negative affect centers.

Fine-grained mapping of mouse brain functional connectivity with resting-state fMRI.

Understanding the intrinsic circuit-level functional organization of the brain has benefited tremendously from the advent of resting-state fMRI (rsfMRI). In humans, resting-state functional network has been consistently mapped and its alterations have been shown to correlate with symptomatology of various neurological or psychiatric disorders. To date, deciphering the mouse brain functional connectivity (MBFC) with rsfMRI remains a largely underexplored research area, despite the plethora of human brain disorders that can be modeled in this specie. To pave the way from pre-clinical to clinical investigations we characterized here the intrinsic architecture of mouse brain functional circuitry, based on rsfMRI data acquired at 7T using the Cryoprobe technology. High-dimensional spatial group independent component analysis demonstrated fine-grained segregation of cortical and subcortical networks into functional clusters, overlapping with high specificity onto anatomical structures, down to single gray matter nuclei. These clusters, showing a high level of stability and reliability in their patterning, formed the input elements for computing the MBFC network using partial correlation and graph theory. Its topological architecture conserved the fundamental characteristics described for the human and rat brain, such as small-worldness and partitioning into functional modules. Our results additionally showed inter-modular interactions via "network hubs". Each major functional system (motor, somatosensory, limbic, visual, autonomic) was found to have representative hubs that might play an important input/output role and form a functional core for information integration. Moreover, the rostro-dorsal hippocampus formed the highest number of relevant connections with other brain areas, highlighting its importance as core structure for MBFC.

Single shot whole brain imaging using spherical stack of spirals trajectories.

MR-encephalography allows the observation of functional signal in the brain at a frequency of 10 Hz, permitting filtering of physiological "noise" and the detection of single event activations. High temporal resolution is achieved by the use of undersampled non-Cartesian trajectories, parallel imaging and regularized image reconstruction. MR-encephalography is based on 3D-encoding, allowing undersampling in two dimensions and providing advantages in terms of signal to noise ratio. Long readout times, which are necessary for single shot whole brain imaging (up to 75 ms), cause off-resonance artifacts. To meet this issue, a spherical stack of spirals trajectory is proposed in this work. By examining the trajectories in local k-space, it is shown that in areas of strong susceptibility gradients spatial information is fundamentally lost, making a meaningful image reconstruction impossible in the affected areas. It is shown that the loss of spatial information is reduced when using a stack of spirals trajectory compared to concentric shells.

Tracking dynamic resting-state networks at higher frequencies using MR-encephalography.

Current resting-state network analysis often looks for coherent spontaneous BOLD signal fluctuations at frequencies below 0.1 Hz in a multiple-minutes scan. However hemodynamic signal variation can occur at a faster rate, causing changes in functional connectivity at a smaller time scale. In this study we proposed to use MREG technique to increase the temporal resolution of resting-state fMRI. A three-dimensional single-shot concentric shells trajectory was used instead of conventional EPI, with a TR of 100 ms and a nominal spatial resolution of 4 × 4 × 4 mm(3). With this high sampling rate we were able to resolve frequency components up to 5 Hz, which prevents major physiological noises from aliasing with the BOLD signal of interest. We used a sliding-window method on signal components at different frequency bands, to look at the non-stationary connectivity maps over the course of each scan session. The aim of the study paradigm was to specifically observe visual and motor resting-state networks. Preliminary results have found corresponding networks at frequencies above 0.1 Hz. These networks at higher frequencies showed better stability in both spatial and temporal dimensions from the sliding-window analysis of the time series, which suggests the potential of using high temporal resolution MREG sequences to track dynamic resting-state networks at sub-minute time scale.

Use of simulated annealing for the design of multiple repetition time balanced steady-state free precession imaging.

Balanced steady-state free precession is an ultrafast sequence with high signal-to-noise efficiency, but it also generates a strong fat signal which can mask important features. One method of fat suppression is to modify the balanced steady-state free precession spectrum using multiple repetition times to create a wide stopband over the fat frequency. However, with three or more pulse repetition times, the number of parameters creates a vast search space with many local minima of a cost function. We report on the initial results of using simulated annealing to find optimal sequences for two applications of multiple-pulse repetition time balanced steady-state free precession: positive contrast imaging and fat suppression.

Single shot concentric shells trajectories for ultra fast fMRI.

MR-encephalography is a technique that allows real-time observation of functional changes in the brain with a time-resolution of 100 ms. The high sampling rate is enabled by the use of undersampled image acquisition with regularized reconstruction. The article describes a novel imaging method for fast three-dimensional-MR-encephalography whole brain coverage based on undersampled, single-shot concentric shells trajectories and the use of multiple small receiver coils. The technique allows the observation of changes in blood oxygenation level dependent signal as a measure of brain physiology at very high temporal resolution.

Fast undersampled functional magnetic resonance imaging using nonlinear regularized parallel image reconstruction.

In this article we aim at improving the performance of whole brain functional imaging at very high temporal resolution (100 ms or less). This is achieved by utilizing a nonlinear regularized parallel image reconstruction scheme, where the penalty term of the cost function is set to the L(1)-norm measured in some transform domain. This type of image reconstruction has gained much attention recently due to its application in compressed sensing and has proven to yield superior spatial resolution and image quality over e.g. Tikhonov regularized image reconstruction. We demonstrate that by using nonlinear regularization it is possible to more accurately localize brain activation from highly undersampled k-space data at the expense of an increase in computation time.