A predictor-corrector phase unwrapping algorithm for temporally undersampled gradient-echo MRI.

PURPOSE: To develop a method for unwrapping temporally undersampled and nonlinear gradient recalled echo (GRE) phase. THEORY AND METHODS: Temporal unwrapping is performed as a sequential one step prediction of the echo phase, followed by a correction to the nearest integer wrap-count. A spatio-temporal extension of the 1D predictor corrector unwrapping (PCU) algorithm improves the prediction accuracy, and thereby maintains spatial continuity. The proposed method is evaluated using numerical phantom, physical phantom, and in vivo brain data at both 3 T and 9.4 T. The unwrapping performance is compared with the state-of-the-art temporal and spatial unwrapping algorithms, and the spatio-temporal iterative virtual-echo based Nyquist sampled (iVENyS) algorithm. RESULTS: Simulation results showed significant reduction in unwrapping errors at higher echoes compared with the state-of-the-art algorithms. Similar to the iVENyS algorithm, the PCU algorithm was able to generate spatially smooth phase images for in vivo data acquired at 3 T and 9.4 T, bypassing the use of additional spatial unwrapping step. A key advantage over iVENyS algorithm is the superior performance of PCU algorithm at higher echoes. CONCLUSION: PCU algorithm serves as a robust phase unwrapping method for temporally undersampled and nonlinear GRE phase, particularly in the presence of high field gradients.

Prediction of motion induced magnetic fields for human brain MRI at 3 T.

OBJECTIVE: Maps of B0 field inhomogeneities are often used to improve MRI image quality, even in a retrospective fashion. These field inhomogeneities depend on the exact head position within the static field but acquiring field maps (FM) at every position is time consuming. Here we propose a forward simulation strategy to obtain B0 predictions at different head-positions. METHODS: FM were predicted by combining (1) a multi-class tissue model for estimation of tissue-induced fields, (2) a linear k-space model for capturing gradient imperfections, (3) a dipole estimation for quantifying lower-body perturbing fields (4) and a position-dependent tissue mask to model FM alterations caused by large motion effects. The performance of the combined simulation strategy was compared with an approach based on a rigid body transformation of the FM measured in the reference position to the new position. RESULTS: The transformed FM provided inconsistent results for large head movements (> 5° rotation, approximately), while the simulation strategy had a superior prediction accuracy for all positions. The simulated FM was used to optimize B0 shims with up to 22.2% improvement with respect to the transformed FM approach. CONCLUSION: The proposed simulation strategy is able to predict movement-induced B0 field inhomogeneities yielding more precise estimates of the ground truth field homogeneity than the transformed FM.

Phase-based masking for quantitative susceptibility mapping of the human brain at 9.4T.

PURPOSE: To develop improved tissue masks for QSM. METHODS: Masks including voxels at the brain surface were automatically generated from the magnitude alone (MM) or combined with test functions from the first (PG) or second (PB) derivative of the sign of the wrapped phase. Phase images at 3T and 9.4T were simulated at different TEs and used to generate a mask, PItoh , with between-voxel phase differences less than π. MM, PG, and PB were compared with PItoh . QSM were generated from 3D multi-echo gradient-echo data acquired at 9.4T (21 subjects aged: 20-56y), and from the QSM2016 challenge 3T data using different masks, unwrapping, background removal, and dipole inversion algorithms. QSM contrast was quantified using age-based iron concentrations. RESULTS: Close to air cavities, phase wraps became denser with increasing field and echo time, yielding increased values of the test functions. Compared with PItoh , PB had the highest Dice coefficient, while PG had the lowest and MM the highest percentage of voxels outside PItoh. Artifacts observed in QSM at 9.4T with MM were mitigated by stronger background filters but yielded a reduced QSM contrast. With PB, QSM contrast was greater and artifacts diminished. Similar results were obtained with challenge data, evidencing larger effects of mask close to air cavities. CONCLUSION: Automatic, phase-based masking founded on the second derivative of the sign of the wrapped phase, including cortical voxels at the brain surface, was able to mitigate artifacts and restore QSM contrast across cortical and subcortical brain regions.

Developing formalin-based fixative agents for post mortem brain MRI at 9.4 T.

PURPOSE: To develop fixative agents for high-field MRI with suitable dielectric properties and measure MR properties in immersion-fixed brain tissue. METHODS: Dielectric properties of formalin-based agents were assessed (100 MHz-4.5 GHz), and four candidate fixatives with/without polyvinylpyrrolidone (PVP) and different salt concentrations were formulated. B1 field and MR properties (T1 , R2∗ , R2 , R2' , and magnetic susceptibility [QSM]) were observed in white and gray matter of pig brain samples during 0.5-35 days of immersion fixation. The kinetics were fitted using exponential functions. The immersion time required to reach maximum R2∗ values at different tissue depths was used to estimate the Medawar coefficient for fixative penetration. The effect of replacing the fixatives with Fluoroinert and phosphate-buffered saline as embedding media was also evaluated. RESULTS: The dielectric properties of formalin were nonlinearly modified by increasing amounts of additives. With 5% PVP and 0.04% NaCl, the dielectric properties and B1 field reflected in vivo conditions. The highest B1 values were found in white matter with PVP and varied significantly with tissue depth and embedding media, but not with immersion time. The MR properties depended on PVP yielding lower T1 , higher R2∗ , more paramagnetic QSM values, and a lower Medawar coefficient (0.9 mm/h ; without PVP: 1.5). Regardless of fixative, switching to phosphate-buffered saline as embedder caused a paramagnetic shift in QSM and decreased R2∗ that progressed during 1 month of storage, whereas no differences were found with Fluorinert. CONCLUSION: In vivo-like B1 fields can be achieved in formalin fixatives using PVP and a low salt concentration, yielding lower T1 , higher R2∗ , and more paramagnetic QSM than without additives. The kinetics of R2∗ allowed estimation of fixative tissue penetration.

Multi-echo gradient-recalled-echo phase unwrapping using a Nyquist sampled virtual echo train in the presence of high-field gradients.

PURPOSE: To develop a spatio-temporal approach to accurately unwrap multi-echo gradient-recalled echo phase in the presence of high-field gradients. THEORY AND METHODS: Using the virtual echo-based Nyquist sampled (VENyS) algorithm, the temporal unwrapping procedure is modified by introduction of one or more virtual echoes between the first lower and the immediate higher echo, so as to reinstate the Nyquist condition at locations with high-field gradients. An iterative extension of the VENyS algorithm maintains spatial continuity by adjusting the phase rotations to make the neighborhood phase differences less than π. The algorithm is evaluated using simulated data, Gadolinium contrast-doped phantom, and in vivo brain, abdomen, and chest data sets acquired at 3 T and 9.4 T. The unwrapping performance is compared with the standard temporal unwrapping algorithm used in the morphology-enabled dipole inversion-QSM pipeline as a benchmark for validation. RESULTS: Quantitative evaluation using numerical phantom showed significant reduction in unwrapping errors in regions of large field gradients, and the unwrapped phase revealed an exact match with the linear concentration profile of vials in a gadolinium contrast-doped phantom data acquired at 9.4 T. Without the need for additional spatial unwrapping, the iterative VENyS algorithm was able to generate spatially continuous phase images. Application to in vivo data resulted in better unwrapping performance, especially in regions with large susceptibility changes such as the air/tissue interface. CONCLUSION: The iterative VENyS algorithm serves as a robust unwrapping method for multi-echo gradient-recalled echo phase in the presence of high-field gradients.

Depth relationships and measures of tissue thickness in dorsal midbrain.

Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest-neighbor Euclidean distance from one reference surface, while the second used a level-set approach that combines signed distances from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for delineating depth for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level-set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth-mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi.

In-vivo quantitative structural imaging of the human midbrain and the superior colliculus at 9.4T.

We explored anatomical details of the superior colliculus (SC) by in vivo magnetic resonance imaging (MRI) at 9.4T. The high signal-to-noise ratio allowed the acquisition of high resolution, multi-modal images with voxel sizes ranging between 176 × 132 × 600 µm and (800)3µm. Quantitative mapping of the longitudinal relaxation rate R1, the effective transverse relaxation rate R2*, and the magnetic susceptibility QSM was performed in 14 healthy volunteers. The images were analyzed in native space as well as after normalization to a common brain space (MNI). The coefficient-of-variation (CoV) across subjects was evaluated in prominent regions of the midbrain, reaching the best reproducibility (CoV of 5%) in the R2* maps of the SC in MNI space, while the CoV in the QSM maps remained high regardless of brain-space. To investigate whether more complex neurobiological architectural features could be detected, depth profiles through the SC layers towards the red nucleus (RN) were evaluated at different levels of the SC along the rostro-caudal axis. This analysis revealed alterations of the quantitative MRI parameters concordant with previous post mortem histology studies of the cyto- and myeloarchitecture of the SC. In general, the R1 maps were hyperintense in areas characterized by the presence of abundant myelinated fibers, and likely enabled detection of the deep white layer VII of the SC adjacent to the periaqueductal gray. While R1 maps failed to reveal finer details, possibly due to the relatively coarse spatial sampling used for this modality, these could be recovered in R2* maps and in QSM. In the central part of the SC along its rostro-caudal axis, increased R2* values and decreased susceptibility values were observed 2 mm below the SC surface, likely reflecting the myelinated fibers in the superficial optic layer (layer III). Towards the deeper layers, a second increase in R2* was paralleled by a paramagnetic shift in QSM suggesting the presence of an iron-rich layer about 3 mm below the surface of the SC, attributed to the intermediate gray layer (IV) composed of multipolar neurons. These results dovetail observations in histological specimens and animal studies and demonstrate that high-resolution multi-modal MRI at 9.4T can reveal several microstructural features of the SC in vivo.

"Wrong Way Up": Temporal and Spatial Dynamics of the Networks for Body Motion Processing at 9.4 T.

Body motion delivers a wealth of socially relevant information. Yet display inversion severely impedes biological motion (BM) processing. It is largely unknown how the brain circuits for BM are affected by display inversion. As upright and upside-down point-light BM displays are similar, we addressed this issue by using ultrahigh field functional MRI at 9.4 T providing for high sensitivity and spatial resolution. Whole-brain analysis along with exploration of the temporal dynamics of the blood-oxygen-level-dependent response reveals that in the left hemisphere, inverted BM activates anterior networks likely engaged in decision making and cognitive control, whereas readily recognizable upright BM activates posterior areas solely. In the right hemisphere, multiple networks are activated in response to upright BM as compared with scarce activation to inversion. With identical visual input with display inversion, a large-scale network in the right hemisphere is detected in perceivers who do not constantly interpret displays as shown the "wrong way up." For the first time, we uncover (1) (multi)functional involvement of each region in the networks underpinning BM processing and (2) large-scale ensembles of regions playing in unison with distinct temporal dynamics. The outcome sheds light on the neural circuits underlying BM processing as an essential part of the social brain.