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PURPOSE: The goal of this study was to measure diffusion signals within cerebral cortex using the line-scan technique to achieve extremely high resolution in the radial direction (i.e., 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 7T on eight healthy volunteers, with each line prescribed perpendicularly to primary somatosensory cortex (S1) and primary motor cortex (M1). Apparent diffusion coefficients (ADCs), fractional anisotropy (FA) 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 signal-to-noise ratio at 7T, may serve as a sensitive probe of in vivo laminar architecture.

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—R(2) and R(2)’, respectively—with extremely high resolution (250 μm) in the radial direction, perpendicular to the cortical surface. Eight healthy human subjects were scanned at 7T 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 R(2) 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 R(2)’ values as a function of cortical depth. The intracortical R(2) 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.

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.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.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 ¼ RF wavelength, consistent with the antenna effect.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 ¼ 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.

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.

Purpose To assess whether R2* mapping with a standard Mono-Exponential (ME) or a Gaussian Augmentation of the Mono-Exponential (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 non-invasive identification of intra-tumoral hypoxia.

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.

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 in . Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

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. Magn Reson Med 74:1145–1155, 2015. © 2014 Wiley Periodicals, Inc.

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.

Lung parenchyma is challenging to image with proton MRI. The large air space results in ~l/5th as many signal-generating protons compared to other organs. Air/tissue magnetic susceptibility differences lead to strong magnetic field gradients throughout the lungs and to broad frequency distributions, much broader than within other organs. Such distributions have been the subject of experimental and theoretical analyses which may reveal aspects of lung microarchitecture useful for diagnosis. Their most immediate relevance to current imaging practice is to cause rapid signal decays, commonly discussed in terms of short T2* values of 1 ms or lower at typical imaging field strengths. Herein we provide a brief review of previous studies describing and interpreting proton lung spectra. We then link these broad frequency distributions to rapid signal decays, though not necessarily the exponential decays generally used to define T2* values. We examine how these decays influence observed signal intensities and spatial mapping features associated with the most prominent torso imaging sequences, including spoiled gradient and spin echo sequences. Effects of imperfect refocusing pulses on the multiple echo signal decays in single shot fast spin echo (SSFSE) sequences and effects of broad frequency distributions on balanced steady state free precession (bSSFP) sequence signal intensities are also provided. The theoretical analyses are based on the concept of explicitly separating the effects of reversible and irreversible transverse relaxation processes, thus providing a somewhat novel and more general framework from which to estimate lung signal intensity behavior in modern imaging practice.

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.

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.

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.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.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.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.

We propose that a simple, closed-form mathematical expression—the Wedge–Dipole mapping—provides a concise approximation to the full-field, two-dimensional topographic structure of macaque V1, V2, and V3. A single map function, which we term a map complex, acts as a simultaneous descriptor of all three areas. Quantitative estimation of the Wedge–Dipole parameters is provided via 2DG data of central-field V1 topography and a publicly available data set of full-field macaque V1 and V2 topography. Good quantitative agreement is obtained between the data and the model presented here. The increasing importance of fMRI-based brain imaging motivates the development of more sophisticated two-dimensional models of cortical visuotopy, in contrast to the one-dimensional approximations that have been in common use. One reason is that topography has traditionally supplied an important aspect of “ground truth,” or validation, for brain imaging, suggesting that further development of high-resolution fMRI will be facilitated by this data analysis. In addition, several important insights into the nature of cortical topography follow from this work. The presence of anisotropy in cortical magnification factor is shown to follow mathematically from the shared boundary conditions at the V1–V2 and V2–V3 borders, and therefore may not causally follow from the existence of columnar systems in these areas, as is widely assumed. An application of the Wedge–Dipole model to localizing aspects of visual processing to specific cortical areas—extending previous work in correlating V1 cortical magnification factor to retinal anatomy or visual psychophysics data—is briefly discussed.

Lung parenchyma is challenging to image with proton MRI. The large air space results in ~l/5th as many signal-generating protons compared to other organs. Air/tissue magnetic susceptibility differences lead to strong magnetic field gradients throughout the lungs and to broad frequency distributions, much broader than within other organs. Such distributions have been the subject of experimental and theoretical analyses which may reveal aspects of lung microarchitecture useful for diagnosis. Their most immediate relevance to current imaging practice is to cause rapid signal decays, commonly discussed in terms of short T2* values of 1 ms or lower at typical imaging field strengths. Herein we provide a brief review of previous studies describing and interpreting proton lung spectra. We then link these broad frequency distributions to rapid signal decays, though not necessarily the exponential decays generally used to define T2* values. We examine how these decays influence observed signal intensities and spatial mapping features associated with the most prominent torso imaging sequences, including spoiled gradient and spin echo sequences. Effects of imperfect refocusing pulses on the multiple echo signal decays in single shot fast spin echo (SSFSE) sequences and effects of broad frequency distributions on balanced steady state free precession (bSSFP) sequence signal intensities are also provided. The theoretical analyses are based on the concept of explicitly separating the effects of reversible and irreversible transverse relaxation processes, thus providing a somewhat novel and more general framework from which to estimate lung signal intensity behavior in modern imaging practice.

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.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.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.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.

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.

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.

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.

Tenenbaum et al . ([1][1]) presented an algorithm, Isomap, for computing a quasi-isometric, low-dimensional embedding of a set of high-dimensional data points. Two issues need to be raised concerning this work. First, the basic approach presented by Tenenbaum et al . is not new, having been

We describe an improved methodology for recording human visual topography in striate and extra-striate cortex via fMRI at 3 T and 7 T field strengths, as well as the first fit of a two-dimensional map function which jointly models the visuotopic structure within cortical areas V1, V2, and V3 to fMRI visual topography data. We discuss five methodological improvements for fMRI visual topography studies. (1) We constructed a custom multi-channel surface coil covering occipital cortex for an improvement in signal-to-noise ratio relative to standard head coil systems. (2) Real-time feedback to subjects, based on psychometrically established eye fixation performance for individual subjects, motivated subjects to maintain fixation. This enabled us to verify accurate long-term fixation and to discard trials where performance was poor. (3) We developed a phase encoding stimulus paradigm where the standard M-factor scaling of a black-and-white checkerboard pattern is replaced with a dynamic spatial noise pattern, in which the correlation length of the noise is matched to cortical magnification factor and thus scales with distance from the center of the visual field. (4) Least-squares optimal quasiisometric brain flattening was used to obtain flat representations of the two-dimensional cortical surface without relaxation cuts through V1 or any other retinotopic area. (5) Finally, we fit a recently developed model of the structure of V1, V2, and V3 visual topography (Balasubramanian et al., Neural Networks, 15:1157–1163, 2002) to our data. This mathematical model allows for shear (i.e., anisotropy) in the cortical map and uses a small number of parameters (two global parameters and one additional parameter each for V1, V2, and V3 shear). Results of this new methodology and data analysis are presented on five human subjects, four collected at 3 T field strength and one collected at 7 T field strength. Presented at Vision Sciences Society 2005 Annual Meeting. Abstract number 901. Support Contributed By: NIH/NIBIB EB001550 Contact info: Jonathan Polimeni, Computer Vision and Computational Neuroscience Lab, 677 Beacon St., Boston, MA, 02215. URL: http://eslab.bu.edu, Email: jonnyreb@cns.bu.edu