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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., (© 2020 International Society for Magnetic Resonance in Medicine.)

Purpose: To determine the in vitro accuracy, test-retest repeatability, and interplatform reproducibility of T 1 quantification protocols used for dynamic contrast-enhanced MRI at 1.5 and 3 T., Methods: A T 1 phantom with 14 samples was imaged at eight centers with a common inversion-recovery spin-echo (IR-SE) protocol and a variable flip angle (VFA) protocol using seven flip angles, as well as site-specific protocols (VFA with different flip angles, variable repetition time, proton density, and Look-Locker inversion recovery). Factors influencing the accuracy (deviation from reference NMR T 1 measurements) and repeatability were assessed using general linear mixed models. Interplatform reproducibility was assessed using coefficients of variation., Results: For the common IR-SE protocol, accuracy (median error across platforms = 1.4-5.5%) was influenced predominantly by T 1 sample (P < 10 -6 ), whereas test-retest repeatability (median error = 0.2-8.3%) was influenced by the scanner (P < 10 -6 ). For the common VFA protocol, accuracy (median error = 5.7-32.2%) was influenced by field strength (P = 0.006), whereas repeatability (median error = 0.7-25.8%) was influenced by the scanner (P < 0.0001). Interplatform reproducibility with the common VFA was lower at 3 T than 1.5 T (P = 0.004), and lower than that of the common IR-SE protocol (coefficient of variation 1.5T: VFA/IR-SE = 11.13%/8.21%, P = 0.028; 3 T: VFA/IR-SE = 22.87%/5.46%, P = 0.001). Among the site-specific protocols, Look-Locker inversion recovery and VFA (2-3 flip angles) protocols showed the best accuracy and repeatability (errors < 15%)., Conclusions: The VFA protocols with 2 to 3 flip angles optimized for different applications achieved acceptable balance of extensive spatial coverage, accuracy, and repeatability in T 1 quantification (errors < 15%). Further optimization in terms of flip-angle choice for each tissue application, and the use of B 1 correction, are needed to improve the robustness of VFA protocols for T 1 mapping. Magn Reson Med 79:2564-2575, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To compare the fitting and tissue discrimination performance of biexponential, kurtosis, stretched exponential, and gamma distribution models for high b-factor diffusion-weighted images in prostate cancer., Methods: Diffusion-weighted images with 15 b-factors ranging from b = 0 to 3500 s/mm 2 were obtained in 62 prostate cancer patients. Pixel-wise signal decay fits for each model were evaluated with the Akaike Information Criterion (AIC). Parameter values for each model were determined within normal prostate and the index lesion. Their potential to differentiate normal from cancerous tissue was investigated through receiver operating characteristic analysis and comparison with Gleason score., Results: The biexponential slow diffusion fraction f slow , the apparent kurtosis diffusion coefficient ADC K , and the excess kurtosis factor K differ significantly among normal peripheral zone (PZ), normal transition zone (TZ), tumor PZ, and tumor TZ. Biexponential and gamma distribution models result in the lowest AIC, indicating a superior fit. Maximum areas under the curve (AUCs) of all models ranged from 0.93 to 0.96 for the PZ and from 0.95 to 0.97 for the TZ. Similar AUCs also result from the apparent diffusion coefficient (ADC) of a monoexponential fit to a b-factor sub-range up to 1250 s/mm 2 . For kurtosis and stretched exponential models, single parameters yield the highest AUCs, whereas for the biexponential and gamma distribution models, linear combinations of parameters produce the highest AUCs. Parameters with high AUC show a trend in differentiating low from high Gleason score, whereas parameters with low AUC show no such ability., Conclusion: All models, including a monoexponential fit to a lower-b sub-range, achieve similar AUCs for discrimination of normal and cancer tissue. The biexponential model, which is favored statistically, also appears to provide insight into disease-related microstructural changes. Magn Reson Med 79:2346-2358, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To demonstrate the use of anatomic MRI-visible three-dimensional (3D)-printed phantoms and to assess process accuracy and material MR signal properties., Methods: A cervical spine model was generated from computed tomography (CT) data and 3D-printed using an MR signal-generating material. Printed phantom accuracy and signal characteristics were assessed using 120 kVp CT and 3 Tesla (T) MR imaging. The MR relaxation rates and diffusion coefficient of the fabricated phantom were measured and 1 H spectra were acquired to provide insight into the nature of the proton signal. Finally, T 2 -weighted imaging was performed during cryoablation of the model., Results: The printed model produced a CT signal of 102 ± 8 Hounsfield unit, and an MR signal roughly 1/3 rd that of saline in short echo time/short repetition time GRE MRI (456 ± 36 versus 1526 ± 121 arbitrary signal units). Compared with the model designed from the in vivo CT scan, the printed model differed by 0.13 ± 0.11 mm in CT, and 0.62 ± 0.28 mm in MR. The printed material had T 2 ∼32 ms, T2*∼7 ms, T 1 ∼193 ms, and a very small diffusion coefficient less than olive oil. MRI monitoring of the cryoablation demonstrated iceball formation similar to an in vivo procedure., Conclusion: Current 3D printing technology can be used to print anatomically accurate phantoms that can be imaged by both CT and MRI. Such models can be used to simulate MRI-guided interventions such as cryosurgeries. Future development of the proposed technique can potentially lead to printed models that depict different tissues and anatomical structures with different MR signal characteristics. Magn Reson Med 77:613-622, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

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., (© 2015 Wiley Periodicals, Inc.)

Purpose: To investigate the tissue-like multiexponential T2 signal decays in avian eggs., Methods: Transverse relaxation studies of raw, soft-boiled and hard-boiled eggs were performed at 3 Tesla using a three-dimensional Carr-Purcell-Meiboom-Gill imaging sequence. Signal decays over a TE range of 11 to 354 ms were fitted assuming single- and multicomponent signal decays with up to three separately decaying components. Fat saturation was used to facilitate spectral assignment of observed decay components., Results: Egg white, yolk and the centrally located latebra all demonstrate nonmonoexponential T2 decays. Specifically, egg white exhibits two-component decays with intermediate and long T2 times. Meanwhile, yolk and latebra are generally best characterized with triexponential decays, with short, intermediate and very long T2 decay times. Fat saturation revealed that the intermediate component of yolk could be attributed to lipids. Cooking of the egg profoundly altered the decay curves., Conclusion: Avian egg T2 decay curves cover a wide range of decay times. Observed T2 components in yolk and latebra as short as 10 ms, may prove valuable for testing clinical sequences designed to measure short T2 components, such as myelin-associated water in the brain. Thus we propose that the egg can be a versatile and widely available MR transverse relaxation phantom., (© 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., (© 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., (© 2014 Wiley Periodicals, Inc.)

Purpose: Simplified models of non-monoexponential diffusion signal decay are of great interest to study the basic constituents of complex diffusion behavior in tissues. The latebra, a unique structure uniformly present in the yolk of avian eggs, exhibits a non-monoexponential diffusion signal decay. This model is more complex than simple phantoms based on differences between water and lipid diffusion, but is also devoid of microscopic structures with preferential orientation or perfusion effects., Methods: Diffusion scans with multiple b-values were performed on a clinical 3 Tesla system in raw and boiled chicken eggs equilibrated to room temperature. Diffusion encoding was applied over the ranges 5-5,000 and 5-50,000 s/mm(2). A low read-out bandwidth and chemical shift was used for reliable lipid/water separation. Signal decays were fitted with exponential functions., Results: The latebra, when measured over the 5-5,000 s/mm(2) range, exhibited independent of preparation clearly biexponential diffusion, with diffusion parameters similar to those typically observed in in vivo human brain. For the range 5-50,000 s/mm(2), there was evidence of a small third, very slow diffusing water component., Conclusion: The latebra of the avian egg contains membrane structures, which may explain a deviation from a simple monoexponential diffusion signal decay, which is remarkably similar to the deviation observed in brain tissue., (Copyright © 2013 Wiley Periodicals, Inc.)

The purpose of this work was to evaluate a previously proposed approach that aims to improve the point spread function (PSF) of MR spectroscopic imaging (MRSI) to avoid corruption by lipid signal arising from neighboring voxels. Retrospective spatial filtering can be used to alter the PSF; however, this either reduces spatial resolution or requires extending the acquisition in k-space at the cost of increased imaging time. Alternatively, the method evaluated here, PSF-choice, can modify the PSF localization to reduce the contamination from adjacent lipids by conforming the signal response more closely to the desired MRSI voxel grid. This is done without increasing scan time or degrading SNR of important metabolites. PSF-choice achieves improvements in spatial localization through modifications to the radiofrequency excitation pulses. An implementation of this method is reported for MRSI of the prostate, where it is demonstrated that, in 13 of 16 pilot prostate MRSI scans, intravoxel spectral contamination from lipid was significantly reduced when using PSF-choice. Phantom studies were also performed that demonstrate, compared with MRSI with standard Fourier phase encoding, out-of-voxel signal contamination of spectra was significantly reduced in MRSI with PSF-choice.

An implantable MR contrast agent that can be covalently immobilized on tissue during surgery has been developed. The rationale is that a durable increase in tissue contrast using an implantable contrast agent can enhance postsurgical tissue differentiation using MRI. For small-vessel (e.g., vein graft) MRI, the direct benefit of such permanent "labeling" of the vessel wall by modification of its relaxation properties is to achieve more efficient imaging. This efficiency can be realized as either increased contrast leading to more accurate delineation of vessel wall and lesion tissue boundaries, or, faster imaging without penalizing contrast-to-noise ratio, or a combination thereof. We demonstrate, for the first time, stable long-term MRI enhancement using such an exogenous contrast mechanism based on immobilizing a modified diethylenetriaminepentaacetic acid gadolinium(3+) dihydrogen complex on a human vein using a covalent amide bond. Signal enhancement due to the covalently immobilized contrast agent is demonstrated for excised human vein specimens imaged at 3 T, and its long-term stability is demonstrated during a 4-month incubation period., (© 2010 Wiley-Liss, Inc.)

Neuronal currents produce local electromagnetic fields that can potentially modulate the phase of the magnetic resonance signal and thus provide a contrast mechanism tightly linked to neuronal activity. Previous work has demonstrated the feasibility of direct MRI of neuronal activity in phantoms and cell culture, but in vivo efforts have yielded inconclusive, conflicting results. The likelihood of detecting and validating such signals can be increased with (i) fast gradient-echo echo-planar imaging, with acquisition rates sufficient to resolve neuronal activity, (ii) subjects with epilepsy, who frequently experience stereotypical electromagnetic discharges between seizures, expressed as brief, localized, high-amplitude spikes (interictal discharges), and (iii) concurrent electroencephalography. This work demonstrates that both MR magnitude and phase show large-amplitude changes concurrent with electroencephalography spikes. We found a temporal derivative relationship between MR phase and scalp electroencephalography, suggesting that the MR phase changes may be tightly linked to local cerebral activity. We refer to this manner of MR acquisition, designed explicitly to track the electroencephalography, as encephalographic MRI (eMRI). Potential extension of this technique into a general purpose functional neuroimaging tool requires further study of the MR signal changes accompanying lower amplitude neuronal activity than those discussed here., (Copyright © 2010 Wiley-Liss, Inc.)

Intrascan subject movement in clinical MR spectroscopic examinations may result in inconsistent water suppression that distorts the metabolite signals, frame-to-frame variations in spectral phase and frequency, and consequent reductions in the signal-to-noise ratio due to destructive averaging. Frame-to-frame phase/frequency corrections, although reported to be successful in achieving constructive averaging, rely on consistent water suppression, which may be difficult in the presence of intrascan motion. In this study, motion correction using non-water-suppressed data acquisition is proposed to overcome the above difficulties. The time-domain matrix-pencil postprocessing method was used to extract water signals from the non-water-suppressed spectroscopic data, followed by phase and frequency corrections of the metabolite signals based on information obtained from the water signals. From in vivo experiments on seven healthy subjects at 3.0 T, quantification of metabolites using the unsuppressed water signal as a reference showed improved correlation with water-suppressed data acquired in the absence of motion (R(2) = 0.9669; slope = 0.94). The metabolite concentrations derived using the proposed approach were in good agreement with literature values. Computer simulations under various degrees of frequency and phase variations further demonstrated robust performance of the time-domain postprocessing approach., ((c) 2009 Wiley-Liss, Inc.)

Lower extremity peripheral vein bypass grafts (LE-PVBG) imaged with high-resolution black blood three-dimensional (3D) inner-volume (IV) fast spin echo (FSE) MRI at 1.5 Tesla possess a two-layer appearance in T1W images while only the inner layer appears visible in the corresponding T2W images. This study quantifies this difference in six patients imaged 6 months after implantation, and attributes the difference to the T(2) relaxation rates of vessel wall tissues measured ex vivo in two specimens with histologic correlation. The visual observation of two LE-PVBG vessel wall components imaged in vivo is confirmed to be significant (P < 0.0001), with a mean vessel wall area difference of 6.8 +/- 2.7 mm(2) between contrasts, and a ratio of T1W to T2W vessel wall area of 1.67 +/- 0.28. The difference is attributed to a significantly (P < 0.0001) shorter T(2) relaxation in the adventitia (T(2) = 52.6 +/- 3.5 ms) compared with the neointima/media (T(2) = 174.7 +/- 12.1 ms). Notably, adventitial tissue exhibits biexponential T(2) signal decay (P < 0.0001 vs monoexponential). Our results suggest that high-resolution black blood 3D IV-FSE can be useful for studying the biology of bypass graft wall maturation and pathophysiology in vivo, by enabling independent visualization of the relative remodeling of the neointima/media and adventitia.

Parallel MRI (pMRI) achieves imaging acceleration by partially substituting gradient-encoding steps with spatial information contained in the component coils of the acquisition array. Variable-density subsampling in pMRI was previously shown to yield improved two-dimensional (2D) imaging in comparison to uniform subsampling, but has yet to be used routinely in clinical practice. In an effort to reduce acquisition time for 3D fast spin-echo (3D-FSE) sequences, this work explores a specific nonuniform sampling scheme for 3D imaging, subsampling along two phase-encoding (PE) directions on a rectilinear grid. We use two reconstruction methods-2D-GRAPPA-Operator and 2D-SPACE RIP-and present a comparison between them. We show that high-quality images can be reconstructed using both techniques. To evaluate the proposed sampling method and reconstruction schemes, results via simulation, phantom study, and in vivo 3D human data are shown. We find that fewer artifacts can be seen in the 2D-SPACE RIP reconstructions than in 2D-GRAPPA-Operator reconstructions, with comparable reconstruction times.

A recently developed method for exact density compensation of non uniformly arranged samples relies on the analytically known cross-correlations of Fourier basis functions corresponding to the traced k-space trajectory. This method produces a linear system whose solution represents compensated samples that normalize the contribution of each independent element of information that can be expressed by the underlying trajectory. Unfortunately, linear system-based density compensation approaches quickly become computationally demanding with increasing number of samples (i.e., image resolution). Here, it is shown that when a trajectory is composed of rotationally symmetric interleaves, such as spiral and PROPELLER trajectories, this cross-correlations method leads to a highly simplified system of equations. Specifically, it is shown that the system matrix is circulant block-Toeplitz so that the linear system is easily block-diagonalized. The method is described and demonstrated for 32-way interleaved spiral trajectories designed for 256 image matrices; samples are compensated non iteratively in a few seconds by solving the small independent block-diagonalized linear systems in parallel. Because the method is exact and considers all the interactions between all acquired samples, up to a 10% reduction in reconstruction error concurrently with an up to 30% increase in signal to noise ratio are achieved compared to standard density compensation methods., ((c) 2008 Wiley-Liss, Inc.)

A 3D inner-volume fast spin echo (3D IV-FSE) sequence was developed for ECG-gated, black-blood, T1- and T2-weighted vessel wall imaging of peripheral vein bypass grafts (PVBG). The sequence utilizes nonselective refocusing excitations to minimize echo spacings and a highly selective IV excitation scheme to minimize the need for oversampling of z-encode slice selections. The method was tested in eight PVBG patients who also underwent 2D FSE graft imaging. High-quality 3D imaging was achieved in all subjects, with significant spatial resolution and volume coverage gains compared to the more conventional 2D FSE sequences normalized for signal-to-noise ratios (SNRs) and scan times. Compared to previously proposed 3D IV-FSE methods, nonselective refocusing resulted in a more than 20% FSE echo train sampling efficiency increase while the use of highly selective IV excitation resulted in a 30% improvement in slice oversampling efficiency., ((c) 2008 Wiley-Liss, Inc.)

A line-scan echo planar spectroscopic imaging (LSEPSI) sequence was used to serially acquire spectra from 4,096 voxels every 6.4 s throughout the breasts of nine female subjects in vivo. Data from the serial acquisitions were analyzed to determine the potential of the technique to characterize temperature changes using either the water frequency alone or the water-methylene frequency difference. Fluctuations of the apparent temperature change under these conditions of no heating were smallest using the water-methylene frequency difference, most probably due to a substantial reduction of motion effects both within and without the imaged plane. The approach offers considerable advantages over other methods for temperature change monitoring in the breast with magnetic resonance but suffers from some limitations, including the unavailability of lipid and water resonances in some voxels as well as a surprisingly large distribution of water-methylene frequency differences, which may preclude absolute temperature measurement., ((c) 2007 Wiley-Liss, Inc.)

The problem of k-space sample density compensation is restated as the normalization of the independent information that can be expressed by the ensemble of Fourier basis functions corresponding to the trajectory. Specifically, multiple samples (complex exponential functions) may be contributing to each independent information element (independent basis function). Normalization can be accomplished by solving a linear system based on the cross-correlation matrix of the underlying Fourier basis functions. The solution to this system is straightforward and can be obtained without resorting to discretization since the cross-correlations of Fourier basis functions are analytically known. Furthermore, no restrictions are placed on the k-space trajectory and its point-spread function. Additionally, the linear system can be used to elucidate key trade-offs involved in k-space trajectory design. The approach can be used to compensate samples acquired for image reconstruction or designed for low flip angle radiofrequency (RF) excitation. Here it is demonstrated for the latter application, using reversed spiral trajectories. In this case the linear system approach enables one to easily incorporate additional constraints such as smoothness to the solution. For typical RF excitation durations (<20 ms) it is shown that density compensation can even be achieved without numerical iteration., (Copyright (c) 2007 Wiley-Liss, Inc.)

Quantitative T2 relaxation and diffusion imaging studies of a rat muscle edema model were performed in order to determine the effects of intra- and extracellular water compartmentation on the respective decay curves. The right hind paw of rats was injected with a carrageenan solution to generate edematous muscle. A Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence was used to acquire T2 relaxation decay curves from both paws. A line scan diffusion imaging (LSDI) sequence was then used to acquire diffusion decay curves from the same paws over a wide b-factor range. Measurements were made from both edematous muscle (EM) and control muscle (CM). The EM and CM T2 relaxation decay curves were best fit with biexponential functions. The fraction of the fast T2 component dropped dramatically from approximately 0.95 in CM to 0.45 in EM, consistent with a water compartmentation model in which the fast and slow T2 components reflect intra- and extracellular water, respectively. Both CM and EM diffusion decay curves required biexponential fitting functions, and the diffusion coefficients of the fast and slow components were substantially larger in EM than CM. The fraction of the fast diffusion component, however, was not radically altered between CM and EM conditions (0.84 versus 0.89 for CM versus EM). Assuming a model in which intra- and extracellular water compartments are responsible for the fast and slow T2-decay components and for the slow and fast diffusion decay components, respectively, leads to fractional sizes of the diffusion components that are not supported by experiment. We conclude that intra- and extracellular water compartmentation is a reasonable interpretation for the two T2-decay components in both CM and EM but that other factors, such as restricted diffusion and/or alternate forms of water compartmentation like surface versus volume water, most probably have profound influences on the precise shapes of the diffusion decay curves, a complete understanding of which will require significant theoretical work., (Copyright (c) 2005 Wiley-Liss, Inc.)

An imaging method to obtain arbitrary point-spread functions (PSFs) in phase-encoding dimensions is described. This method, called PSF-Choice, is particularly relevant for applications, such as spectroscopic imaging, in which only a very few phase encodes are acquired and ringing artifact can be a serious problem. PSF-Choice uses partial 2D RF excitations to produce aliased excitations that are encoded using standard phase-encoding gradients. Theoretically, the PSF of the reconstructed result depends only on the RF excitation profile. Simulations demonstrate that a Gaussian-like PSF can be achieved, eliminating the side lobes that are associated with ringing artifact. It is further shown that neither the spatial resolution (as represented by the width of the PSF) nor the signal-to-noise ratio (SNR) of the method is adversely affected when compared to standard phase encoding. In the sense that the same number of encodes are required as with standard phase encoding, temporal resolution is also maintained. Phantom experiments demonstrate the initial feasibility of the method to eliminate ringing artifact.

Fat fractions and spectral T2 values of fat and water within the vertebral marrow of non-HIV- and HIV-infected men were measured with the use of a Carr-Purcell-Meiboom-Gill (CPMG) line scan spectroscopic imaging sequence. The fat fraction for the HIV-infected men (0.29 +/- 0.08) was significantly lower (P < 0.05, Student's unpaired t-test) than the fat fraction found in non-HIV-infected men (0.40 +/- 0.12). The mean water and fat T2 values did not differ between the two groups, and did not show any systematic dependence on fat fraction over the wide range of fat fractions encountered in this study. The marrow water and fat T2 values measured with the CPMG approach were markedly longer than the spectral T2 values reported by other groups using the more common point-resolved spectroscopy (PRESS) and stimulated-echo acquisition mode (STEAM) acquisitions. Proton spectroscopic studies of vertebral marrow revealed differences between non-HIV- and HIV-infected men that may prove useful for studying the effects of this disease and/or antiretroviral agents on body composition., (Copyright 2004 Wiley-Liss, Inc.)

The neonatal brain possesses higher water content, lower macromolecular concentration, and reduced synaptic density than is found in the brain of a 1-year-old child. Changes in MRI characteristics of brain such as relaxation times accompany rapid changes in brain during early postnatal development. It was hypothesized that T(*)(2) values found in newborns would be significantly higher than those found in 9-month-old children and adults as measured at 1.5 T. Spoiled gradient echo measurements of T(*)(2) within the brains of newborns, 9-month-olds, and adults confirmed this hypothesis. The results have implications with regard to functional MRI studies in newborns since, in general, BOLD signal optimization is achieved when echo times TE are set equal to the T(*)(2) values of the tissue of interest. Since significantly longer T(*)(2) values are found in newborns, it is suggested that the TE values employed for fMRI studies of newborns should be increased to maximize BOLD signal intensity changes and improve the overall reliability of fMRI results in newborns., (Copyright 2004 Wiley-Liss, Inc.)

Continuous arterial spin labeling (CASL) was used to obtain an index of cerebral blood flow (ICBF) in the normal mouse brain and in an orthotopic mouse model of human U87 high-grade glioma at 8.5 T. Under the assumption of a constant tissue:blood partition coefficient for water in different tissues, the mean ICBF (n = 14) was found to be 50 +/- 9 mL/100g/min for tumor core and 209 +/- 11 mL/100g/min for normal tissue. The apparent T(1) (T(1app)) was 2.01 +/- 0.06 sec for tumor core and 1.66 +/- 0.03 sec for normal tissue. The ICBF and the T(1app) values were significantly different (P < 0.001) between these two regions. The detailed changes of ICBF and T(1app) in the transition from the tumor core through the tumor periphery to surrounding tissue were studied. Immunohistochemistry indicated that tumor vascularity was not uniform, with microvessel density highest in normal brain and the tissue surrounding the tumor and lowest in the tumor core. The large difference in ICBF between the tumor core and normal tissue suggests that this index might be useful for the assessment of the efficacy of antiangiogenic therapy., (Copyright 2004 Wiley-Liss, Inc.)

Several studies have shown that in tissues over an extended range of b-factors, the signal decay deviates significantly from the basic monoexponential model. The true nature of this departure has to date not been identified. For the current study, line scan diffusion images of brain suitable for biexponential diffusion tensor analysis were acquired in normal subjects on a clinical MR system. For each of six noncollinear directions, 32 images with b-factors ranging from 5 to 5000 s/mm2 were collected. Biexponential fits yielded parameter maps for a fast and a slow diffusion component. A subset of the diffusion data, consisting of the images obtained at the conventional range of b-factors between 5 and 972 s/mm2, was used for monoexponential diffusion tensor analysis. Fractional anisotropy (FA) of the fast-diffusion component and the monoexponential fit exhibited no significant difference. FA of the slow-diffusion biexponential component was significantly higher, particularly in areas of lower fiber density. The principal diffusion directions for the two biexponential components and the monoexponential solution were largely the same and in agreement with known fiber tracts. The second and third diffusion eigenvector directions also appeared to be aligned, but they exhibited significant deviations in localized areas., (Copyright 2004 Wiley-Liss, Inc.)

The relaxivity and bioreduction rates of eight dendrimer-linked nitroxides varying in the number of nitroxides per molecule were measured and the potential use of these compounds as MR contrast agents was demonstrated. The T(1) and T(2) relaxivities, measured at room temperature and 1.5 T, varied linearly with the number of nitroxides per molecule for compounds with up to 16 nitroxides per molecule. Fourth-generation polypropylenimide- (DAB) and third-generation polyamidoamine- (PAMAM) dendrimer-linked nitroxides were found to have greater relaxivity than gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). The greater number of nitroxides per dendrimer increased relaxivity over that of a single nitroxide, allowing a decreased dose to achieve differential contrast with MR evaluations. Rates of nitroxide bioreduction were below detection threshold using EPR spectroscopy for generation 2 dendrimers and higher. A pilot assessment of in vivo cartilage uptake that compared intraarticular injection of three structurally different dendrimer-linked nitroxides with Gd-DTPA and with saline demonstrated high affinity of the DAB-dendrimer-linked nitroxides for normal rabbit articular cartilage. From these results, it is evident that target-specific dendrimer-linked nitroxides can be designed., (Copyright 2002 Wiley-Liss, Inc.)

Saline solutions are commonly employed as a vehicle for drugs administered intramuscularly. In this study, in vivo measurements of spin-spin relaxation (T2) processes by magnetic resonance imaging (MRI) were performed to investigate the distribution of water in rat masseter muscle tissue after intramuscular injection of saline solutions of varying tonicity. Prior to saline injection, image-based T2 relaxation decay of muscle was monoexponential. After injection of saline, the T2 relaxation decay became multiexponential. Non-negative least squares (NNLS) analysis of the decay curves revealed two relaxation components: a fast component (T2 = 20-40 ms) and a slow component (T2 = 150-400 ms), which are assigned to intra- and extracellular water protons, respectively. Injection of hypertonic saline solutions significantly increased the extracellular water component in muscle tissue compared to isotonic saline solutions, an effect which lasted for more than 60 min. These findings suggest that MRI techniques may be useful to investigate the effect of hyper- or hypotonic solutions on muscle tissue in vivo., (Copyright 2001 Wiley-Liss, Inc.)

An implementation is reported of an imaging method to obtain MUltiple Resolutions along Phase-encode and Slice-select dimensions (MURPS), which enables dynamic imaging of focal changes using a graded, multiresolution approach. MURPS allows one to trade spatial resolution in part of the volume for improved temporal resolution in dynamic imaging applications. A unique method of Hadamard slice encoding is used, enabling the varying of the phase encode and slice resolution while maintaining a constant effective TR throughout the entire 3-D volume. MURPS was implemented using a gradient-recalled echo sequence, and its utility was demonstrated for MR temperature monitoring. In this preliminary work, it has been shown that changes throughout a large volume can be effectively monitored in times that would normally only permit dynamic imaging in one or a very few slices., (Copyright 2001 Wiley-Liss, Inc.)

A line scan echo planar spectroscopic imaging (LSEPSI) sequence is presented which can rapidly produce 2D chemical shift imaging (CSI) data with minimal relaxation weighting and motion-related artifacts. The technique is based on successive "snapshot" 1D CSI acquisitions of individual tissue columns, and avoids T(1) saturation problems associated with the short TR periods needed for very rapid scanning with either conventional or echo planar-based 2D CSI methods. Potential applications include rapid fat/water spectral quantitation in the abdomen and internally referenced temperature monitoring for interventional procedures.

In vivo measurements of the human brain tissue water signal decay with b-factor over an extended b-factor range up to 6,000 s/mm(2) reveal a nonmonoexponential decay behavior for both gray and white matter. Biexponential parametrization of the decay curves from cortical gray (CG) and white matter voxels from the internal capsule (IC) of healthy adult volunteers describes the decay process and serves to differentiate between these two tissues. Inversion recovery experiments performed in conjunction with the extended b-factor signal decay measurements are used to make separate measurements of the spin-lattice relaxation times of the fast and slow apparent diffusion coefficient (ADC) components. Differences between the spin-lattice relaxation times of the fast and slow ADC components were not statistically significant in either the CG or IC voxels. It is possible that the two ADC components observed from the extended b-factor measurements arise from two distinct water compartments with different intrinsic diffusion coefficients. If so, then the relaxation results are consistent with two possibilities. Either the spin-lattice relaxation times within the compartments are similar or the rate of water exchange between compartments is "fast" enough to ensure volume averaged T(1) relaxation yet "slow" enough to allow for the observation of biexponential ADC decay curves over an extended b-factor range. Magn Reson Med 44:292-300, 2000., (Copyright 2000 Wiley-Liss, Inc.)

A new parallel imaging technique was implemented which can result in reduced image acquisition times in MRI. MR data is acquired in parallel using an array of receiver coils and then reconstructed simultaneously with multiple processors. The method requires the initial estimation of the 2D sensitivity profile of each coil used in the receiver array. These sensitivity profiles are then used to partially encode the images of interest. A fraction of the total number of k-space lines is consequently acquired and used in a parallel reconstruction scheme, allowing for a substantial reduction in scanning and display times. This technique is in the family of parallel acquisition schemes such as simultaneous acquisition of spatial harmonics (SMASH) and sensitivity encoding (SENSE). It extends the use of the SMASH method to allow the placement of the receiver coil array around the object of interest, enabling imaging of any plane within the volume of interest. In addition, this technique permits the arbitrary choice of the set of k-space lines used in the reconstruction and lends itself to parallel reconstruction, hence allowing for real-time rendering. Simulated results with a 16-fold increase in temporal resolution are shown, as are experimental results with a 4-fold increase in temporal resolution. Magn Reson Med 44:301-308, 2000., (Copyright 2000 Wiley-Liss, Inc.)

The aim of the study was to test the hypothesis that fast spin echo T(1)-weighted images can be used to quantify the temperature in fat during thermal therapy in vivo. An MR compatible positioning device was used to manipulate focused ultrasound transducers in an MRI scanner. This system was used to sonicate fat tissue around the kidneys of 12 rabbits at various power levels for 10 to 20 sec. The scan parameters of T(1)-weighted fast spin echo (FSE) sequence were varied to optimize signal intensity characteristics while maintaining short scan times. An invasive optical probe was used to calibrate the temperature related signal intensity changes. For the T(1)-weighted FSE sequence, the signal intensity decreased with the temperature elevation at the rate of 0.97+/-0.02%/ degrees C. The single focused transducer produced a contrast-to-noise ratio more than 10 at power levels below the tissue damage threshold. The signal intensity was linearly dependent on the power, despite the measured temperatures being well above the coagulation threshold. This study demonstrates that T(1)-weighted FSE MRI sequences can be used to quantify the temperature elevation in fat in vivo during short focused ultrasound exposures. This can be very important for breast tumor surgery, fat ablation, and for treating deep seated tumors through superficial fat layers. Magn Reson Med 43:901-904, 2000., (Copyright 2000 Wiley-Liss, Inc.)

An echo-planar spectroscopic imaging method of temperature mapping is proposed. This method is sufficiently faster than the so-called 3D magnetic resonance spectroscopic imaging (3D-MRSI) method and does not require image subtractions, unlike the conventional phase mapping method when an internal reference signal is detectable. The water proton chemical shift measured by using the tissue lipid as an internal reference clearly visualized the temperature change in a porcine liver sample in vitro. It was also demonstrated that the internally referenced echo-planar spectroscopic imaging method could markedly reduce a temperature error caused by a simple, translational motion between scans compared with the phase-mapping method.

Strategies to optimize flip angles for chemical shift selective fat suppression are discussed. Mathematical models for fat suppression in spoiled gradient recalled acquisition, spin echo, and RARE, which incorporate steady state conditions and multiple spectral components of fat, are developed. The optimal suppression flip angle is found to be larger than that determined with a single fat component model by more than 10 degrees due to contributions from unflipped components such as olefinic and glycerol protons that lie outside the suppression band.

The advantages and limitations of multiple spin-echo sequences for non-Fourier encoding are investigated. Complications caused by improper encoding of alternate magnetization pathways due to imperfect refocusing pulses are analyzed. It is shown that mirror image ghosts result if the encoding RF pulse matrix is real-valued. These ghosts can be avoided as long as the rows of the RF pulse matrix are conjugate symmetric, which implies that spatial profiles are real valued. Non-Fourier encoding using bases derived from wavelet, Hadamard, and other real-valued orthogonal functions does not result in a mirror ghost artifact. A RARE sequence for non-Fourier encoding has been implemented on a clinical imaging system and successfully applied for brain imaging.

The citrate signal at field strengths of whole body imagers arises from two sets of two strongly coupled methylene protons. This causes citrate spectra acquired with standard in vivo localization schemes like the double-echo point resolved echo spectroscopy (PRESS) sequence to have complicated dependencies on timing parameters. A homonuclear J-refocused version of the double-echo PRESS sequence that has previously been shown to completely remove J-modulations from weakly coupled AX systems is considered for its potential in acquiring signal from the strongly coupled AB system of citrate. An analytic solution to the problem is derived with the density matrix formalism and verified both numerically and experimentally for 7 T conditions. The general expression for the AB signal is applied to study the 1.5 T citrate signal where a substantial signal enhancement over conventional double-echo PRESS sequences is predicted and verified for echo times in the 150 to 300 ms range.

A novel line scan diffusion imaging sequence (LSDI) is introduced. LSDI is inherently insensitive to motion artifacts and high quality diffusion maps of the brain can be obtained rapidly without the use of head restraints or cardiac gating. Results from a stroke study and abdominal diffusion images are presented. The results indicate that it is feasible to use the LSDI technique for clinical evaluation of acute ischemic stroke. In contrast to echo-planar diffusion imaging, LSDI does not require modified gradient hardware and can be implemented on conventional scanners. Thus, LSDI should dramatically increase the general availability of robust clinical diffusion imaging.

Rapid acquisition relaxation-enhanced (RARE) sequences (Hennig et al., Magn. Reson. Med. 3, 823 (1986)) utilize one or several Carr-Purcell-Meiboom-Gill (CPMG) echo trains to sample a number of k-space lines each repetition time TR. The technique can rapidly generate multislice T2-weighted images which, as a rule, are strikingly similar in contrast to conventional T2-weighted spin-echo (SE) images. An exception to this rule is the appearance of very bright signal from fat in T2-weighted RARE images as compared to conventional T2-weighted SE images. To reduce this fat signal, we introduce a time delay, tau c, between the 90 degrees x and first 180 degrees y pulse of each echo train such that a phase angle of pi/2 develops between fat and the reference (water) line at echo maxima. The technique leads to single-acquisition fat suppression without the use of frequency-selective saturation pulses and concomitant loss of slices per TR. A Bloch equation analysis is used to identify two major mechanisms contributing to suppression of off-resonance spins such that w tau c = pi/2. Namely, the CPMG sequence becomes a CP sequence with no self-correction properties for imperfect 180 degrees pulses leading to enhanced signal decay, and the raw k-space data matrix become segmented into blocks alternately multiplied by +/- i, leading to signal dispersion following Fourier transformation.

The fast acquisition interleaved spin-echo (FAISE) sequence and its dual-echo version (DEFAISE) are partial RF echo-planar methods which utilize a specific phase-encode reordering algorithm to manipulate T2 contrast via an operator-controlled pseudo-echo time, pTE. The repetition time, TR, between successive applications of the Carr-Purcell-Meiboom-Gill (CPMG) echo trains used in FAISE may be reduced to introduce T1 weighting. To quantitatively determine the extent to which FAISE T1 and T2 contrast characteristics agree with spin-echo methods, signal intensities from FAISE acquisitions were compared with signal intensities from equivalent CPMG acquisitions. In phantoms and in human heads, the contrast characteristics of FAISE are found to be highly correlated with that obtained with equivalent CPMG sequences. However, conventional SE sequences generally utilize longer echo spacings than employed with FAISE/CPMG. Thus, echo spacing-dependent mechanisms such as spin-spin coupling and magnetic susceptibility lead to some differences in contrast between conventional SE and FAISE. Finally, FAISE appears to be more sensitive to magnetization transfer effects than conventional SE sequences since more off-resonance irradiation is applied to individual slices during multislice acquisitions.

The fast acquisition interleaved spin-echo (FAISE) method is a partial RF echo-planar technique which utilizes a specific phase-encode reordering algorithm to manipulate image contrast (Melki et al., J. Magn. Reson. Imaging 1:319, 1991). The technique can generate "spin-echo" like images up to 16 times faster than conventional spin-echo methods. However, the presence of T2 decay throughout the variable k-space trajectories used to manipulate T2 contrast ensures the presence of image artifacts, especially along the phase-encode direction. In this work, we experimentally and theoretically examine the type and extent of artifacts associated with the FAISE technique. We demonstrate the existence of well-defined minima of phase-encode ghost noise for selected k-space trajectories, examine the extent of blurring and edge enhancement artifacts, demonstrate the influence of matrix size and number of echoes per train on phase-encode artifact, and show how proper choice of FAISE sequence parameters can lead to proton density brain images which are practically indistinguishable from conventional spin-echo proton density images. A comparison of contrast between FAISE and standard spin-echo methods is presented in a companion article referred to as II.

Magnetization transfer effects are demonstrated to be significant in determining the signal intensity from brain tissues on images acquired with multislice rapid acquisition relaxation enhanced (RARE) sequences. We report studies designed to determine how the signal intensities vary with slice number or, equivalently, off-resonance power deposition. The results obtained in fat, gray matter, and white matter are similar in form to those reported in kidney tissues during classic magnetization transfer experiments (J. Eng, T. L. Ceckler, and R. S. Balaban, Magn. Reson. Med. 17, 304 (1991)). Of clinical significance to RARE practitioners is the increase of contrast-to-noise ratios between gray and white matter on proton density-weighted images with increasing slice number.

A Carr-Purcell-Meiboom-Gill imaging sequence consisting of 128 echoes is used to extract transverse magnetization decay curves (TDCs) at 1.9 T from 1.7 x 1.7 x 5-mm3 voxels within the cortex, outer medulla, and inner medulla of perfused rabbit kidneys. The spatially localized TDCs within each tissue type are found to be better approximated by biexponential, as opposed to monoexponential, functions. The biexponential parameters characterizing the TDCs demonstrate an improved degree of tissue specificity over that available from monoexponential analyses. The fraction of the quickly relaxing TDC component and the relaxation rate of this component are observed to decrease from cortex to inner medulla. A two-site exchange analysis is used to convert biexponential TDC parameters into water volume fractions and exchange rates. The exchange rates between the fast and slowly relaxing pools increased from cortex to inner medulla. All exchange rates were less than 1.5 Hz, indicating a relatively slow water exchange process. The imaging methods and subsequent analyses offer the potential to generate unconventional MR images with tissue contrast dependent upon water compartmentation and exchange.

Two-dimensional Fourier transform Carr-Purcell-Meiboom-Gill (CPMG) imaging sequences were implemented on 1.9-T and 1.5-T imaging systems in order to test their ability to characterize in vivo transverse decay curves (TDCs). Both hard- and soft-pulse CPMG imaging sequences, consisting of up to 128 echoes with echo spacings of approximately 10 ms were developed, implemented, and tested. These sequences provide one of the most detailed samplings of TDCs from image data sets reported to date. Good agreement between image-extracted T2 values and spectroscopically obtained T2 values of NiCl2-doped saline solutions was found with both hard- and soft-pulse sequences. In vivo TDCs were extracted from rabbit and human image data sets. For several tissues, biexponential TDC fits provided considerable improvement over monoexponential fits and the sensitivity of the fitting parameters to positive baseline offsets was examined. With the time coverage of the relaxation decay curves available from these sequences, the TDCs from white matter in humans appear largely monoexponential while those from cortical grey matter demonstrate biexponential behavior.

We demonstrate a formalism for determining whether 1H longitudinal and transverse magnetic relaxation decay curves are compatible with a model of proton exchange between two sites with inherently different relaxation rates. We apply the method to published data in which both decay curves have been fit to normalized biexponential functions, a prediction of the simplest two-site exchange model. The analysis is applied to relaxation data of adsorbed water vapor on silica gel (J.R. Zimmerman and J.A. Lasater, J. Phys. Chem. 62, 1157 (1958] and to relaxation data reported in mycelia of Botrytis cinerea Persoon and pupae of the tobacco cutworm (M. Yoshida and K. Nose, Agric. Biol. Chem. 51, 3399 (1987]. Exchange parameters are calculated form these data sets and the compatibility of the two-site exchange model with the data is discussed for each case. The sensitivity of the calculated exchange parameters to errors in the bioexponential fitting parameters is treated in some detail.

Proton T2 relaxation and its biexponential components have been determined in rabbit skeletal muscle in the presence and absence of GdDTPA. The effect of GdDTPA, which distributes only in the extracellular space, was greatest in the longer-relaxing T2 component (T22). A 27% reduction in T22 was measured for slow-twitch (red) muscle and 17% for fast-twitch (white) muscle, consistent with the larger extracellular space of the former. Magnetic resonance images demonstrated apparent contrast between red and white rabbit muscles. This contrast was instantaneously enhanced by administration of GdDTPA and returned to near normal levels after approximately 30 min. These functional changes in tissue contrast are consistent with differences in blood perfusion and biological water compartmentation between fast- and slow-twitch skeletal muscles.