Measuring transverse relaxation rates of the major brain metabolites from single-voxel PRESS acquisitions at a single TE.

PURPOSE: To compare transverse relaxation rates of brain metabolites estimated from single-TE PRESS acquisitions with more conventionally derived rates estimated from multiple-TE PRESS acquisitions. METHODS: Single-voxel (8 mL) PRESS data within white matter from 6 subjects were acquired at five different TEs. Transverse relaxation rates R2 of N-acetylaspartate, creatine, and choline were estimated from a single TE using full versus right-side-only sampling of the echo. These R2 values were compared with R2Hahn values obtained from the multiple-TE PRESS acquisitions. RESULTS: Following baseline subtraction and RMS weighting, interindividual mean R2 values from TE = 288 ms magnitude spectra for choline, creatine, and N-acetylaspartate were highly correlated with respective R2Hahn values (r2 = 0.99). Paired individual measurements at this TE showed less correlation (r2 = 0.48), primarily due to the N-acetylaspartate resonance. Using TE = 360 ms data for N-acetylaspartate and 288 ms for choline and creatine resulted in an improved correlation coefficient (r2 = 0.80). The average absolute intra-individual differences in the estimated R2 s between single-TE and Hahn method was 9.6 ± 7.7%. CONCLUSION: For the major brain metabolite singlets, R2Hahn values showed correlations with more fragile measurements of R2 from a single TE that are worthy of interest. Because the left side of long-TE spin echoes is available "for free" from an acquisition perspective, and although the single-TE method for estimating R2 values is associated with lower precision, the reduction in scan time may be clinically helpful.

Probing in vivo cortical myeloarchitecture in humans via line-scan diffusion acquisitions at 7 T with 250-500 micron radial resolution.

PURPOSE: The goal of this study was to measure diffusion signals within the cerebral cortex using the line-scan technique to achieve extremely high resolution in the radial direction (ie, perpendicular to the cortical surface) and to demonstrate the utility of these measurements for investigating laminar architecture in the living human brain. METHODS: Line-scan diffusion data with 250-500 micron radial resolution were acquired at 7 T on 8 healthy volunteers, with each line prescribed perpendicularly to primary somatosensory cortex (S1) and primary motor cortex (M1). Apparent diffusion coefficients, fractional anisotropy values, and radiality indices were measured as a function of cortical depth. RESULTS: In the deep layers of S1, we found evidence for high anisotropy and predominantly tangential diffusion, with low anisotropy observed in superficial S1. In M1, moderate anisotropy and predominantly radial diffusion was seen at almost all cortical depths. These patterns were consistent across subjects and were conspicuous without averaging data across different locations on the cortical sheet. CONCLUSION: Our results are in accord with the myeloarchitecture of S1 and M1, known from prior histology studies: in S1, dense bands of tangential myelinated fibers run through the deep layers but not the superficial ones, and in M1, radial myelinated fibers are prominent at most cortical depths. This work therefore provides support for the idea that high-resolution diffusion signals, measured with the line-scan technique and receiving a boost in SNR at 7 T, may serve as a sensitive probe of in vivo laminar architecture.

Spectrally-selective measurements of reversible and irreversible transverse relaxation rates from single spin-echo PRESS acquisitions in muscle.

The goal of this study was to test a new formalism for extracting reversible and irreversible transverse relaxation rates from resonances within typical proton muscle spectra using only a single spin echo as acquired with routine single-voxel, point-resolved echo spectroscopy (PRESS) acquisitions. Single-voxel, non-water-suppressed PRESS acquisitions within the calf muscles of four healthy subjects were performed at 1.5 T using six echo times ranging from 30 to 576 ms. Novel transverse relaxation analyses of water, choline, creatine, and lipid resonances were performed based upon the disparate relaxation sensitivities of the left versus the right sides of spectroscopically sampled spin echoes. Irreversible and reversible transverse relaxation rates R2 and R2 ' were extracted for water, metabolites, and lipids using echo times of 288 ms and longer. The R2 values so obtained were compared with more conventional "gold standard" Hahn values, R2Hahn , evaluated from the echo-time dependence of spectral peak areas generated from right-side sampling alone. Water resonances displayed biexponential Hahn signal decays, consistent with observations of decreasing R2 values with increasing echo time via the new approach. Choline and creatine resonances displayed monoexponential echo-time decays, with R2Hahn values in reasonable agreement with R2 values obtained from the single-echo analyses at the longer echo times. Lipid methylene and methyl R2 values extracted from the new approach were also in reasonable accord with R2Hahn values. Further validation of the technique was provided through PRESS acquisitions on a water phantom to which various levels of gadolinium were added in order to manipulate transverse relaxation rates, yielding excellent agreement between water-resonance R2Hahn and single-echo R2 values. In summary, this work demonstrates the feasibility of measuring reversible and irreversible transverse relaxation rates for individual spectral peaks from single-echo PRESS acquisitions, enabling a reduction in overall scan time relative to the use of multiple acquisitions with varying echo time.

In vivo measurements of irreversible and reversible transverse relaxation rates in human basal ganglia at 7 T: making inferences about the microscopic and mesoscopic structure of iron and calcification deposits.

The goal of this study was to measure irreversible and reversible transverse relaxation rates in the globus pallidus and putamen at 7 T, and to use these rates to make inferences about the sub-voxel structure of iron and calcification deposits. Gradient Echo Sampling of a Spin Echo (GESSE) data were acquired at 7 T on eighteen volunteers spanning a large range of ages (23-85 years), with calcifications in the globus pallidus incidentally observed in one volunteer. Maps of transverse relaxation rates were derived from the GESSE data, and the mean value of these rates in globus pallidus and putamen was estimated for each volunteer. Both irreversible and reversible transverse relaxation rates increased with the expected age-dependent iron content in these structures, except for the individual with calcifications for whom extremely large reversible relaxation rates but normal irreversible relaxation rates were found in the globus pallidus. Given the sensitivity of irreversible and reversible transverse relaxation rates to microscopic and mesoscopic field variations, respectively, our findings suggest that joint consideration of these rates may yield information not only about the amount of iron and calcification deposited in the brain, but also about the sub-voxel structure of these deposits, perhaps revealing certain aspects of their geometry and cellular distribution.

Spectroscopic sampling of the left side of long-TE spin echoes: a free lunch?

OBJECTIVE: Use of spectroscopically-acquired spin echoes typically involves Fourier transformation of the right side of the echo while largely neglecting the left side. For sufficiently long echo times, the left side may have enough spectral resolution to offer some utility. Since the acquisition of this side is "free", we deemed it worthy of attention and investigated the spectral properties and information content of this data. MATERIALS AND METHODS: Theoretical expressions for left- and right-side spectra were derived assuming Lorentzian frequency distributions. For left-side spectra, three regimes were identified based upon the relative magnitudes of reversible and irreversible transverse relaxation rates, R 2' and R 2, respectively. Point-resolved spectroscopy (PRESS) data from muscle, fat deposit and bone marrow were acquired at 1.5 T to test aspects of the theoretical expressions. RESULTS: For muscle water or methylene marrow resonances, left-side signals were substantially or moderately larger than right-side signals but were similar in magnitude for muscle choline and creatine resonances. Left- versus right-side spectral-peak amplitude ratios depend sensitively on the relative values of R 2 and R 2' , which can be estimated given this ratio and a right-side linewidth measurement. CONCLUSION: Left-side spectra can be used to augment signal-to-noise and to estimate spectral R 2 and R 2' values under some circumstances.

Fast myelin water fraction estimation using 2D multislice CPMG.

PURPOSE: T2 relaxometry based on multiexponential fitting to a single slice multiecho sequence has been the most common MRI technique for myelin water fraction mapping, where the short T2 is associated with myelin water. However, very long acquisition times and physically unrealistic models for T2 distribution are limitations of this approach. We present a novel framework for myelin imaging which substantially increases the imaging speed and myelin water fraction estimation accuracy. METHOD: We used the 2D multislice Carr-Purcell-Meiboom-Gill sequence to increase the volume coverage. To compensate for nonideal slice profiles, we numerically solved the Bloch equations for a range of T2 and B1 inhomogeneity scales to construct the bases for the estimation of the T2 distribution. We used a finite mixture of continuous parametric distributions to describe the complete T2 spectrum and used the constrained variable projection optimization algorithm to estimate myelin water fraction. To validate our model, synthetic, phantom, and in vivo brain experiments were conducted. RESULTS: Using the Bloch equations, we can model the slice profile and construct the forward model of the T2 curve. Our method estimated myelin water fraction with smaller error than the nonnegative least squares algorithm. CONCLUSIONS: The proposed framework can be used for reliable whole brain myelin imaging with a resolution of 2×2×4 mm3 in ≈17 min. Magn Reson Med 76:1301-1313, 2016. © 2015 Wiley Periodicals, Inc.

Bone marrow segmentation based on a combined consideration of transverse relaxation processes and Dixon oscillations.

The aim of this study was to demonstrate that gradient-echo sampling of single spin echoes can be used to isolate the signal from trabecular bone marrow, with high-quality segmentation and surface reconstructions resulting from the application of simple post-processing strategies. Theoretical expressions of the time-domain single-spin-echo signal were used to simulate signals from bone marrow, non-bone fatty deposits and muscle. These simulations were compared with and used to interpret signals obtained by the application of the gradient-echo sampling of a spin-echo sequence to image the knee and surrounding tissues at 1.5 T. Trabecular bone marrow has a much higher reversible transverse relaxation rate than surrounding non-bone fatty deposits and other musculoskeletal tissues. This observation, combined with a choice of gradient-echo spacing that accentuates Dixon-type oscillations from chemical-shift interference effects, enabled the isolation of bone marrow signal from surrounding tissues through the use of simple image subtraction and thresholding. Three-dimensional renderings of the marrow surface were then readily generated with this approach - renderings that may prove useful for bone morphology assessment, e.g. for the measurement of femoral anteversion. In conclusion, understanding the behavior of signals from bone marrow and surrounding tissue as a function of time through a spin echo facilitates the segmentation and reconstruction of bone marrow surfaces using straightforward post-processing strategies that are typically available on modern radiology workstations.

Characterization of gradient echo signal decays in healthy and cancerous prostate at 3T improves with a Gaussian augmentation of the mono-exponential (GAME) model.

A biomarker of cancer aggressiveness, such as hypoxia, could substantially impact treatment decisions in the prostate, especially radiation therapy, by balancing treatment morbidity (urinary incontinence, erectile dysfunction, etc.) against mortality. R2 (*) mapping with Mono-Exponential (ME) decay modeling has shown potential for identifying areas of prostate cancer hypoxia at 1.5T. However, Gaussian deviations from ME decay have been observed in other tissues at 3T. The purpose of this study is to assess whether gradient-echo signal decays are better characterized by a standard ME decay model, or a Gaussian Augmentation of the Mono-Exponential (GAME) decay model, in the prostate at 3T. Multi-gradient-echo signals were acquired on 20 consecutive patients with a clinical suspicion of prostate cancer undergoing MR-guided prostate biopsies. Data were fitted with both ME and GAME models. The information contents of these models were compared using Akaike's information criterion (second order, AICC ), in skeletal muscle, the prostate central gland (CG), and peripheral zone (PZ) regions of interest (ROIs). The GAME model had higher information content in 30% of the prostate on average (across all patients and ROIs), covering up to 67% of cancerous PZ ROIs, and up to 100% of cancerous CG ROIs (in individual patients). The higher information content of GAME became more prominent in regions that would be assumed hypoxic using ME alone, reaching 50% of the PZ and 70% of the CG as ME R2 (*) approached 40 s(-1) . R2 (*) mapping may have important applications in MRI; however, information lost due to modeling could mask differences in parameters due to underlying tissue anatomy or physiology. The GAME model improves characterization of signal behavior in the prostate at 3T, and may increase the potential for determining correlates of fit parameters with biomarkers, for example of oxygenation status.

Characterizing gradient echo signal decays in gynecologic cancers at 3T using a Gaussian augmentation of the monoexponential (GAME) model.

PURPOSE: To assess whether R2* mapping with a standard Monoexponential (ME) or a Gaussian Augmentation of the Monoexponential (GAME) decay model better characterizes gradient-echo signal decays in gynecological cancers after external beam radiation therapy at 3T, and evaluate implications of modeling for noninvasive identification of intratumoral hypoxia. MATERIALS AND METHODS: Multi-gradient-echo signals were acquired on 25 consecutive patients with gynecologic cancers and three healthy participants during inhalation of different oxygen concentrations at 3T. Data were fitted with both ME and GAME models. Models were compared using F-tests in tumors and muscles in patients, muscles, cervix, and uterus in healthy participants, and across oxygenation levels. RESULTS: GAME significantly improved fitting over ME (P < 0.05): Improvements with GAME covered 34% of tumor regions-of-interest on average, ranging from 6% (of a vaginal tumor) to 68% (of a cervical tumor) in individual tumors. Improvements with GAME were more prominent in areas that would be assumed hypoxic based on ME alone, reaching 90% as ME R2* approached 100 Hz. Gradient echo decay parameters at different oxygenation levels were not significantly different (P = 0.81). CONCLUSION: R2* may prove sensitive to hypoxia; however, inaccurate representations of underlying data may limit the success of quantitative assessments. Although the degree to which R2 or σ values correlate with hypoxia remains unknown, improved characterization with GAME increases the potential for determining any correlates of fit parameters with biomarkers, such as oxygenation status. J. MAGN. RESON. IMAGING 2016;44:1020-1030.

On the lorentzian versus Gaussian character of time-domain spin-echo signals from the brain as sampled by means of gradient-echoes: Implications for quantitative transverse relaxation studies.

PURPOSE: To determine whether Lorentzian or Gaussian intra-voxel frequency distributions are better suited for modeling data acquired with gradient-echo sampling of single spin-echoes for the simultaneous characterization of irreversible and reversible relaxation rates. Clinical studies (e.g., of brain iron deposition) using such acquisition schemes have typically assumed Lorentzian distributions. THEORY AND METHODS: Theoretical expressions of the time-domain spin-echo signal for intra-voxel Lorentzian and Gaussian distributions were used to fit data from a human brain scanned at both 1.5 Tesla (T) and 3T, resulting in maps of irreversible and reversible relaxation rates for each model. The relative merits of the Lorentzian versus Gaussian model were compared by means of quality of fit considerations. RESULTS: Lorentzian fits were equivalent to Gaussian fits primarily in regions of the brain where irreversible relaxation dominated. In the multiple brain regions where reversible relaxation effects become prominent, however, Gaussian fits were clearly superior. CONCLUSION: The widespread assumption that a Lorentzian distribution is suitable for quantitative transverse relaxation studies of the brain should be reconsidered, particularly at 3T and higher field strengths as reversible relaxation effects become more prominent. Gaussian distributions offer alternate fits of experimental data that should prove quite useful in general. Magn Reson Med 74:51-62, 2015. © 2014 Wiley Periodicals, Inc.

Magnetic resonance imaging of ionic currents in solution: the effect of magnetohydrodynamic flow.

PURPOSE: Reliably detecting MRI signals in the brain that are more tightly coupled to neural activity than blood-oxygen-level-dependent fMRI signals could not only prove valuable for basic scientific research but could also enhance clinical applications such as epilepsy presurgical mapping. This endeavor will likely benefit from an improved understanding of the behavior of ionic currents, the mediators of neural activity, in the presence of the strong magnetic fields that are typical of modern-day MRI scanners. THEORY: Of the various mechanisms that have been proposed to explain the behavior of ionic volume currents in a magnetic field, only one-magnetohydrodynamic flow-predicts a slow evolution of signals, on the order of a minute for normal saline in a typical MRI scanner. METHODS: This prediction was tested by scanning a volume-current phantom containing normal saline with gradient-echo-planar imaging at 3 T. RESULTS: Greater signal changes were observed in the phase of the images than in the magnitude, with the changes evolving on the order of a minute. CONCLUSION: These results provide experimental support for the MHD flow hypothesis. Furthermore, MHD-driven cerebrospinal fluid flow could provide a novel fMRI contrast mechanism.

In vivo irreversible and reversible transverse relaxation rates in human cerebral cortex via line scans at 7 T with 250 micron resolution perpendicular to the cortical surface.

Understanding how and why MR signals and their associated relaxation rates vary with cortical depth could ultimately enable the noninvasive investigation of the laminar architecture of cerebral cortex in the living human brain. However, cortical gray matter is typically only a few millimeters thick, making it challenging to sample many cortical depths with the voxel sizes commonly used in MRI studies. Line-scan techniques provide a way to overcome this challenge and here we implemented a novel line-scan GESSE pulse sequence that allowed us to measure irreversible and reversible transverse relaxation rates-R2 and R2´, respectively-with extremely high resolution (250 µm) in the radial direction, perpendicular to the cortical surface. Eight healthy human subjects were scanned at 7 T using this sequence, with primary visual cortex (V1) targeted in three subjects and primary motor (M1) and somatosensory cortex (S1) targeted in the other five. In all three cortical areas, a peak in R2 values near the central depths was seen consistently across subjects-an observation that has not been made before, to our knowledge. On the other hand, no consistent pattern was apparent for R2´ values as a function of cortical depth. The intracortical R2 peak reported here is unlikely to be explained by myelin content or by deoxyhemoglobin in the microvasculature; however, this peak is in accord with the laminar distribution of non-heme iron in these cortical areas, known from prior histology studies. Obtaining information about tissue microstructure via measurements of transverse relaxation (and other quantitative MR contrast mechanisms) at the extremely high radial resolutions achievable through the use of line-scan techniques could therefore bring us closer to being able to perform "in vivo histology" of the cerebral cortex.

Near-isometric flattening of brain surfaces.

Flattened representations of brain surfaces are often used to visualize and analyze spatial patterns of structural organization and functional activity. Here, we present a set of rigorous criteria and accompanying test cases with which to evaluate flattening algorithms that attempt to preserve shortest-path distances on the original surface. We also introduce a novel flattening algorithm that is the first to satisfy all of these criteria and demonstrate its ability to produce accurate flat maps of human and macaque visual cortex. Using this algorithm, we have recently obtained results showing a remarkable, unexpected degree of consistency in the shape and topographic structure of visual cortical areas within humans and macaques, as well as between these two species.

Locating the functional and anatomical boundaries of human primary visual cortex.

The primary visual cortex (V1) can be delineated both functionally by its topographic map of the visual field and anatomically by its distinct pattern of laminar myelination. Although it is commonly assumed that the specialized anatomy V1 exhibits corresponds in location with functionally defined V1, demonstrating this in human has not been possible thus far due to the difficulty of determining the location of V1 both functionally and anatomically in the same individual. In this study we use MRI to measure the anatomical and functional V1 boundaries in the same individual and demonstrate close agreement between them. Functional V1 location was measured by parcellating occipital cortex of 10 living humans into visual cortical areas based on the topographic map of the visual field measured using functional MRI. Anatomical V1 location was estimated for these same subjects using a surface-based probabilistic atlas derived from high-resolution structural MRI of the stria of Gennari in 10 intact ex vivo human hemispheres. To ensure that the atlas prediction was correct, it was validated against V1 location measured using an observer-independent cortical parcellation based on the laminar pattern of cell density in serial brain sections from 10 separate individuals. The close agreement between the independent anatomically and functionally derived V1 boundaries indicates that the whole extent of V1 can be accurately predicted based on cortical surface reconstructions computed from structural MRI scans, eliminating the need for functional localizers of V1. In addition, that the primary cortical folds predict the location of functional V1 suggests that the mechanism giving rise to V1 location is tied to the development of the cortical folds.

The intrinsic shape of human and macaque primary visual cortex.

Previous studies have reported considerable variability in primary visual cortex (V1) shape in both humans and macaques. Here, we demonstrate that much of this variability is due to the pattern of cortical folds particular to an individual and that V1 shape is similar among individual humans and macaques as well as between these 2 species. Human V1 was imaged ex vivo using high-resolution (200 microm) magnetic resonance imaging at 7 T. Macaque V1 was identified in published histological serial section data. Manual tracings of the stria of Gennari were used to construct a V1 surface, which was computationally flattened with minimal metric distortion of the cortical surface. Accurate flattening allowed investigation of intrinsic geometric features of cortex, which are largely independent of the highly variable cortical folds. The intrinsic shape of V1 was found to be similar across human subjects using both nonparametric boundary matching and a simple elliptical shape model fit to the data and is very close to that of the macaque monkey. This result agrees with predictions derived from current models of V1 topography. In addition, V1 shape similarity suggests that similar developmental mechanisms are responsible for establishing V1 shape in these 2 species.

Exact geodesics and shortest paths on polyhedral surfaces.

We present two algorithms for computing distances along convex and non-convex polyhedral surfaces. The first algorithm computes exact minimal-geodesic distances and the second algorithm combines these distances to compute exact shortest-path distances along the surface. Both algorithms have been extended to compute the exact minimal-geodesic paths and shortest paths. These algorithms have been implemented and validated on surfaces for which the correct solutions are known, in order to verify the accuracy and to measure the run-time performance, which is cubic or less for each algorithm. The exact-distance computations carried out by these algorithms are feasible for large-scale surfaces containing tens of thousands of vertices, and are a necessary component of near-isometric surface flattening methods that accurately transform curved manifolds into flat representations.

RF Heating of Gold Cup and Conductive Plastic Electrodes during Simultaneous EEG and MRI.

PURPOSE: To investigate the heating of EEG electrodes during magnetic resonance imaging (MRI) scans and to better understand the underlying physical mechanisms with a focus on the antenna effect. MATERIALS AND METHODS: Gold cup and conductive plastic electrodes were placed on small watermelons with fiberoptic probes used to measure electrode temperature changes during a variety of 1.5T and 3T MRI scans. A subset of these experiments was repeated on a healthy human volunteer. RESULTS: The differences between gold and plastic electrodes did not appear to be practically significant. For both electrode types, we observed heating below 4°C for straight wires whose lengths were multiples of ½ the radiofrequency (RF) wavelength and stronger heating (over 15°C) for wire lengths that were odd multiples of » RF wavelength, consistent with the antenna effect. CONCLUSIONS: The antenna effect, which has received little attention so far in the context of EEG-MRI safety, can play as significant a role as the loop effect (from electromagnetic induction) in the heating of EEG electrodes, and therefore wire lengths that are odd multiples of » RF wavelength should be avoided. These results have important implications for the design of EEG electrodes and MRI studies as they help to minimize the risk to patients undergoing MRI with EEG electrodes in place.

High-resolution fMRI investigations of the fingertip somatotopy and variability in BA3b and BA1 of the primary somatosensory cortex.

The fingertip somatotopy in BA1 and BA3b of monkeys exhibits characteristic differences with a more discrete separation of the body parts in BA3b and a continuous orientation column-like structure in BA1. We present evidence for similar differences in the human somatotopy using BOLD fMRI for the investigations. Though the variability between the individual maps was large, we found a group-wide somatotopic representation in BA3b and BA1. The variability due to anatomical differences was small in our sample. This was demonstrated by comparing exact shortest distances in the individual brains and after nonlinear normalization to the group space template, for the removal of the individual anatomical variability. Distance mapping along Dijkstra paths was found to be a valid approximation to exact shortest paths only in the individual brains. The degree of fine-scale detail mapping was improved if valid surface distances instead of 3D Euclidean distances were applied. A further improvement was achieved by mapping the distances between all neighboring fingertips instead of only the outer fingertips. Taking into account all optimizations we found mirror symmetry of the somatotopy with respect to the interhemispheric gap.