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Showing papers in "Magnetic Resonance in Medicine in 2005"


Journal ArticleDOI
TL;DR: From the study of six healthy adult subjects, the excess diffusional kurtosis is found to be significantly higher in white matter than in gray matter, reflecting the structural differences between these two types of cerebral tissues.
Abstract: A magnetic resonance imaging method is presented for quantifying the degree to which water diffusion in biologic tissues is non-Gaussian. Since tissue structure is responsible for the deviation of water diffusion from the Gaussian behavior typically observed in homogeneous solutions, this method provides a specific measure of tissue structure, such as cellular compartments and membranes. The method is an extension of conventional diffusion-weighted imaging that requires the use of somewhat higher b values and a modified image postprocessing procedure. In addition to the diffusion coefficient, the method provides an estimate for the excess kurtosis of the diffusion displacement probability distribution, which is a dimensionless metric of the departure from a Gaussian form. From the study of six healthy adult subjects, the excess diffusional kurtosis is found to be significantly higher in white matter than in gray matter, reflecting the structural differences between these two types of cerebral tissues. Diffusional kurtosis imaging is related to q-space imaging methods, but is less demanding in terms of imaging time, hardware requirements, and postprocessing effort. It may be useful for assessing tissue structure abnormalities associated with a variety of neuropathologies. Magn Reson Med 53:1432–1440, 2005. © 2005 Wiley-Liss, Inc.

2,054 citations


Journal ArticleDOI
TL;DR: Methods are presented to map complex fiber architectures in tissues by imaging the 3D spectra of tissue water diffusion with MR, showing correspondence between the orientational maxima of the diffusion spectrum and those of the fiber orientation density at each location.
Abstract: Methods are presented to map complex fiber architectures in tissues by imaging the 3D spectra of tissue water diffusion with MR. First, theoretical considerations show why and under what conditions diffusion contrast is positive. Using this result, spin displacement spectra that are conventionally phase-encoded can be accurately reconstructed by a Fourier transform of the measured signal's modulus. Second, studies of in vitro and in vivo samples demonstrate correspondence between the orientational maxima of the diffusion spectrum and those of the fiber orientation density at each location. In specimens with complex muscular tissue, such as the tongue, diffusion spectrum images show characteristic local heterogeneities of fiber architectures, including angular dispersion and intersection. Cerebral diffusion spectra acquired in normal human subjects resolve known white matter tracts and tract intersections. Finally, the relation between the presented model-free imaging technique and other available diffusion MRI schemes is discussed.

1,374 citations


Journal ArticleDOI
TL;DR: The results provide a useful reference for optimization of pulse sequence parameters for MRI at 3 T and the phenomenological MT parameter, magnetization transfer ratio, MTR, was lower by approximately 2 to 10%.
Abstract: T1, T2, and magnetization transfer (MT) measurements were performed in vitro at 3 T and 37 degrees C on a variety of tissues: mouse liver, muscle, and heart; rat spinal cord and kidney; bovine optic nerve, cartilage, and white and gray matter; and human blood. The MR parameters were compared to those at 1.5 T. As expected, the T2 relaxation time constants and quantitative MT parameters (MT exchange rate, R, macromolecular pool fraction, M0B, and macromolecular T2 relaxation time, T2B) at 3 T were similar to those at 1.5 T. The T1 relaxation time values, however, for all measured tissues increased significantly with field strength. Consequently, the phenomenological MT parameter, magnetization transfer ratio, MTR, was lower by approximately 2 to 10%. Collectively, these results provide a useful reference for optimization of pulse sequence parameters for MRI at 3 T.

1,212 citations


Journal ArticleDOI
TL;DR: Close agreement between theoretical and experimental results obtained from an oil–water phantom was observed, demonstrating that the iterative least‐squares decomposition method is an efficient estimator.
Abstract: Chemical shift based methods are often used to achieve uniform water-fat separation that is insensitive to Bo inhomogeneities. Many spin-echo (SE) or fast SE (FSE) approaches acquire three echoes shifted symmetrically about the SE, creating time-dependent phase shifts caused by water-fat chemical shift. This work demonstrates that symmetrically acquired echoes cause artifacts that degrade image quality. According to theory, the noise performance of any water-fat separation method is dependent on the proportion of water and fat within a voxel, and the position of echoes relative to the SE. To address this problem, we propose a method termed "iterative decomposition of water and fat with echo asymmetric and least-squares estimation" (IDEAL). This technique combines asymmetrically acquired echoes with an iterative least-squares decomposition algorithm to maximize noise performance. Theoretical calculations predict that the optimal echo combination occurs when the relative phase of the echoes is separated by 2pi/3, with the middle echo centered at pi/2+pik (k=any integer), i.e., (-pi/6+pik, pi/2+pik, 7pi/6+pik). Only with these echo combinations can noise performance reach the maximum possible and be independent of the proportion of water and fat. Close agreement between theoretical and experimental results obtained from an oil-water phantom was observed, demonstrating that the iterative least-squares decomposition method is an efficient estimator.

678 citations


Journal ArticleDOI
TL;DR: Results from both simulated and clinical diffusion data sets indicate that the RESTORE method improves tensor estimation compared to the commonly used linear and nonlinear least‐squares tensor fitting methods and a recently proposed method based on the Geman–McClure M‐estimator.
Abstract: Signal variability in diffusion weighted imaging (DWI) is influenced by both thermal noise and spatially and temporally varying artifacts such as subject motion and cardiac pulsation. In this paper, the effects of DWI artifacts on estimated tensor values, such as trace and fractional anisotropy, are analyzed using Monte Carlo simulations. A novel approach for robust diffusion tensor estimation, called RESTORE (for robust estimation of tensors by outlier rejection), is proposed. This method uses iteratively reweighted least-squares regression to identify potential outliers and subsequently exclude them. Results from both simulated and clinical diffusion data sets indicate that the RESTORE method improves tensor estimation compared to the commonly used linear and nonlinear least-squares tensor fitting methods and a recently proposed method based on the Geman–McClure M-estimator. The RESTORE method could potentially remove the need for cardiac gating in DWI acquisitions and should be applicable to other MR imaging techniques that use univariate or multivariate regression to fit MRI data to a model.

621 citations


Journal ArticleDOI
TL;DR: A new approach termed “controlled aliasing in parallel imaging results in higher acceleration” (CAIPIRINHA) is presented, which modifies the appearance of aliasing artifacts during the acquisition to improve the subsequent parallel image reconstruction procedure.
Abstract: In all current parallel imaging techniques, aliasing artifacts resulting from an undersampled acquisition are removed by means of a specialized image reconstruction algorithm. In this study a new approach termed "controlled aliasing in parallel imaging results in higher acceleration" (CAIPIRINHA) is presented. This technique modifies the appearance of aliasing artifacts during the acquisition to improve the subsequent parallel image reconstruction procedure. This new parallel multi-slice technique is more efficient compared to other multi-slice parallel imaging concepts that use only a pure postprocessing approach. In this new approach, multiple slices of arbitrary thickness and distance are excited simultaneously with the use of multi-band radiofrequency (RF) pulses similar to Hadamard pulses. These data are then undersampled, yielding superimposed slices that appear shifted with respect to each other. The shift of the aliased slices is controlled by modulating the phase of the individual slices in the multi-band excitation pulse from echo to echo. We show that the reconstruction quality of the aliased slices is better using this shift. This may potentially allow one to use higher acceleration factors than are used in techniques without this excitation scheme. Additionally, slices that have essentially the same coil sensitivity profiles can be separated with this technique.

593 citations


Journal ArticleDOI
TL;DR: The purpose of this article is to provide a nuts and bolts procedure for calculating scale factors used for reconstructing images directly in SNR units and to validate the method for SNR measurement with phantom data.
Abstract: The method for phased array image reconstruction of uniform noise images may be used in conjunction with proper image scaling as a means of reconstructing images directly in SNR units. This facilitates accurate and precise SNR measurement on a per pixel basis. This method is applicable to root-sum-of-squares magnitude combining, B(1)-weighted combining, and parallel imaging such as SENSE. A procedure for image reconstruction and scaling is presented, and the method for SNR measurement is validated with phantom data. Alternative methods that rely on noise only regions are not appropriate for parallel imaging where the noise level is highly variable across the field-of-view. The purpose of this article is to provide a nuts and bolts procedure for calculating scale factors used for reconstructing images directly in SNR units. The procedure includes scaling for noise equivalent bandwidth of digital receivers, FFTs and associated window functions (raw data filters), and array combining.

479 citations


Journal ArticleDOI
TL;DR: The new method addresses the problem of partial volume averaging in diffusion tensor imaging and provides a basis for more reliable estimates of fiber orientation and fractional anisotropy.
Abstract: High angular resolution measurements of diffusion are used to estimate the angular distribution and diffusion anisotropy of fibers in a voxel. A simple, axially symmetric model of diffusion in white matter fibers is used to relate diffusion measurements to fiber properties. The new technique is called fiber orientation estimated using continuous axially symmetric tensors (FORECAST). It is tested using both numerical simulation and in vivo measurements. The new method agrees with other methods in voxels containing single fibers, but resolves crossing fibers better, at least at the level of diffusion weighting used in this study (tr(b) = 1480 s/mm2). The simplifying assumptions of the model are tested by comparison with the "model-free" q-ball analysis of in vivo data and the results are shown to be in good agreement. The new method addresses the problem of partial volume averaging in diffusion tensor imaging and provides a basis for more reliable estimates of fiber orientation and fractional anisotropy.

466 citations


Journal ArticleDOI
TL;DR: This work demonstrates with an appropriately conductive sphere phantom that destructive interferences are responsible for a weak B1 in the periphery, without a significant standing wave pattern, and suggests that measuring spatial B1 phase could help, within an MR session, to perform RF shimming in order to obtain more homogeneous B 1 in user‐defined areas of the brain.
Abstract: RF behavior in the human head becomes complex at ultrahigh magnetic fields. A bright center and a weak periphery are observed in images obtained with volume coils, while surface coils provide strong signal in the periphery. Intensity patterns reported with volume coils are often loosely referred to as "dielectric resonances," while modeling studies ascribe them to superposition of traveling waves greatly dampened in lossy brain tissues, raising questions regarding the usage of this term. Here we address this question experimentally, taking full advantage of a transceiver coil array that was used in volume transmit mode, multiple receiver mode, or single transmit surface coil mode. We demonstrate with an appropriately conductive sphere phantom that destructive interferences are responsible for a weak B(1) in the periphery, without a significant standing wave pattern. The relative spatial phase of receive and transmit B(1) proved remarkably similar for the different coil elements, although with opposite rotational direction. Additional simulation data closely matched our phantom results. In the human brain the phase patterns were more complex but still exhibited similarities between coil elements. Our results suggest that measuring spatial B(1) phase could help, within an MR session, to perform RF shimming in order to obtain more homogeneous B(1) in user-defined areas of the brain.

449 citations


Journal ArticleDOI
TL;DR: The clinical applicability of theDESPOT1 and DESPOT2 imaging methods for high‐resolution, whole‐brain, T1 and T2 mapping was investigated and demonstrated the clinical feasibility of the methods in the study of neurologic disease.
Abstract: Variations in the intrinsic T(1) and T(2) relaxation times have been implicated in numerous neurologic conditions. Unfortunately, the low resolution and long imaging time associated with conventional methods have prevented T(1) and T(2) mapping from becoming part of routine clinical evaluation. In this study, the clinical applicability of the DESPOT1 and DESPOT2 imaging methods for high-resolution, whole-brain, T(1) and T(2) mapping was investigated. In vivo, 1-mm(3) isotropic whole-brain T(1) and T(2) maps of six healthy volunteers were acquired at 1.5 T with an imaging time of <17 min each. Isotropic maps (0.34 mm(3)) of one volunteer were also acquired (time <21 min). Average signal-to-noise within the 1-mm(3) T(1) and T(2) maps was approximately 20 and approximately 14, respectively, with average repeatability standard deviations of 46.7 ms and 6.7 ms. These results demonstrate the clinical feasibility of the methods in the study of neurologic disease.

447 citations


Journal ArticleDOI
TL;DR: Spectrally selective RF pulses are used to excite and refocus the off‐resonance water surrounding the labeling cells so that only the fluid and tissue immediately adjacent to the labeled cells are visible in the image.
Abstract: Contrast agents incorporating superparamagnetic iron-oxide nanoparticles have shown promise as a means to visualize labeled cells using MRI. Labeled cells cause significant signal dephasing due to the magnetic field inhomogeneity induced in water molecules near the cell. With the resulting signal void as the means for detection, the particles behave as a negative contrast agent, which can suffer from partial-volume effects. In this paper, a new method is described for imaging labeled cells with positive contrast. Spectrally selective RF pulses are used to excite and refocus the off-resonance water surrounding the labeled cells so that only the fluid and tissue immediately adjacent to the labeled cells are visible in the image. Phantom, in vitro, and in vivo experiments show the feasibility of the new method. A significant linear correlation (r = 0.87, P < 0.005) between the estimated number of cells and the signal was observed.

Journal ArticleDOI
TL;DR: With both the four‐ and the eight‐channel arrays, parallel imaging with sensitivity encoding with high reduction numbers was feasible at 7 T in the human head.
Abstract: Transceive array coils, capable of RF transmission and independent signal reception, were developed for parallel, 1H imaging applications in the human head at 7 T (300 MHz). The coils combine the advantages of high-frequency properties of transmission lines with classic MR coil design. Because of the short wavelength at the 1H frequency at 300 MHz, these coils were straightforward to build and decouple. The sensitivity profiles of individual coils were highly asymmetric, as expected at this high frequency; however, the summed images from all coils were relatively uniform over the whole brain. Data were obtained with four- and eight-channel transceive arrays built using a loop configuration and compared to arrays built from straight stripline transmission lines. With both the four- and the eight-channel arrays, parallel imaging with sensitivity encoding with high reduction numbers was feasible at 7 T in the human head. A one-dimensional reduction factor of 4 was robustly achieved with an average g value of 1.25 with the eight-channel transmit/receive coils.

Journal ArticleDOI
TL;DR: This analysis describes a technique to extend the reconstruction to anisotropic elastic properties in terms of a so‐called transversely isotropic model, which is capable of describing elastic shear anisotropy of parallel fibers.
Abstract: MR-elastography is a new technique for assessing the viscoelastic properties of tissue. One current focus of elastography is the provision of new physical parameters for improving the specificity in breast cancer diagnosis. This analysis describes a technique to extend the reconstruction to anisotropic elastic properties in terms of a so-called transversely isotropic model. Viscosity is treated as being isotropic. The particular model chosen for the anisotropy is appealing because it is capable of describing elastic shear anisotropy of parallel fibers. The dependence of the reconstruction on the particular choice of Poisson's ratio is eliminated by extracting the compressional displacement contribution using the Helmholtz-Hodge decomposition. Results are presented for simulations, a polyvinyl alcohol breast phantom, excised beef muscle, and measurements in two patients with breast lesions (invasive ductal carcinoma and fibroadenoma). The results show enhanced anisotropic and viscous properties inside the lesions and an indication for preferred fiber orientation.

Journal ArticleDOI
TL;DR: A theoretical framework based on the modified Bloch equations that relates the chemical properties of a CEST agent and various NMR parameters to the measured CEST effect was formulated, and results were in excellent agreement with experimental Z‐spectra obtained with an aqueous solution of a paramagnetic CESTAgent containing two different types of bound protons.
Abstract: Paramagnetic lanthanide complexes that display unusually slow water exchange between an inner sphere coordination site and bulk water may serve as a new class of MRI contrast agents with the use of chemical exchange saturation transfer (CEST) techniques. To aid in the design of paramagnetic CEST agents for reporting important biological indices in MRI measurements, we formulated a theoretical framework based on the modified Bloch equations that relates the chemical properties of a CEST agent (e.g., water exchange rates and bound water chemical shifts) and various NMR parameters (e.g., relaxation rates and applied B(1) field) to the measured CEST effect. Numerical solutions of this formulation for complex exchanging systems were readily obtained without algebraic manipulation or simplification. For paramagnetic CEST agents of the type used here, the CEST effect is relatively insensitive to the bound proton relaxation times, but requires a sufficiently large applied B(1) field to highly saturate the Ln(3+)-bound water protons. This in turn requires paramagnetic complexes with large Ln(3+)-bound water chemical shifts to avoid direct excitation of the exchanging bulk water protons. Although increasing the exchange rate of the bound protons enhances the CEST effect, this also causes exchange broadening and increases the B(1) required for saturation. For a given B(1), there is an optimal exchange rate that results in a maximal CEST effect. This numerical approach, which was formulated for a three-pool case, was incorporated into a MATLAB nonlinear least-square optimization routine, and the results were in excellent agreement with experimental Z-spectra obtained with an aqueous solution of a paramagnetic CEST agent containing two different types of bound protons (bound water and amide protons).

Journal ArticleDOI
TL;DR: These measurements indicate that micron‐sized iron oxide particles (MPIOs) should be useful for improving cell tracking by MRI, and demonstrate that these large particles and the cells labeled with them can be detected by spin echo (SE)‐based imaging methods.
Abstract: There is rapidly increasing interest in the use of MRI to track cell migration in intact animals. Currently, cell labeling is usually accomplished by endocytosis of nanometer-sized, dextran-coated iron oxide particles. The limitations of using nanometer-sized particles, however, are that millions of particles are required to achieve sufficient contrast, the label can be diluted beyond observability by cell division, and the label is biodegradable. These problems make it difficult to label cells other than macrophages in vivo, and to conduct long-term engraftment studies. It was recently demonstrated that micron-sized iron oxide particles (MPIOs) can be taken up by a number of cell types. In this study we examined the MRI properties of single MPIOs with sizes of 0.96, 1.63, 2.79, 4.50, and 5.80 μm. Furthermore, the capacity of cells to endocytose these MPIOs was investigated, and the MRI properties of the labeled cells at 7.0 and 11.7 Tesla were measured as a function of image resolution and echo time (TE). Cells labeled with MPIOs generally contained iron levels of ∼100 pg, which is approximately threefold higher than those obtained with the best strategies to label cells using nanometer-sized particles. On occasion, some cells had levels as high as ∼400 pg. We demonstrate that these large particles and the cells labeled with them can be detected by spin echo (SE)-based imaging methods. These measurements indicate that MPIOs should be useful for improving cell tracking by MRI. Magn Reson Med 53:329–338, 2005. Published 2005 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: Two practical methods for the measurement of signal‐to‐noise‐ratio (SNR) performance in parallel imaging are described and the g‐factor shows qualitative agreement with theoretical predictions from the literature.
Abstract: In this work, two practical methods for the measurement of signal-to-noise-ratio (SNR) performance in parallel imaging are described. Phantoms and human studies were performed with a 32-channel cardiac coil in the context of ultrafast cardiac CINE imaging at 1.5 T using steady-state free precession (SSFP) and TSENSE. SNR and g-factor phantom measurements using a "multiple acquisition" method were compared to measurements from a "difference method". Excellent agreement was seen between the two methods, and the g-factor shows qualitative agreement with theoretical predictions from the literature. Examples of high temporal (42.6 ms) and spatial (2.1x2.1x8 mm3) resolution cardiac CINE SSFP images acquired from human volunteers using TSENSE are shown for acceleration factors up to 7. Image quality agrees qualitatively with phantom SNR measurements, suggesting an optimum acceleration of 4. With this acceleration, a cardiac function study consisting of 6 image planes (3 short-axis views, 3 long-axis views) was obtained in an 18-heartbeat breath-hold.

Journal ArticleDOI
TL;DR: Evidence is presented that the SNR can be improved by using arterial spin labeling in combination with single‐shot 3D readout techniques, which yields a 2.8‐fold increase in SNR compared to 2D EPI at the same nominal resolution.
Abstract: Arterial spin labeling (ASL) can be used to measure perfusion without the use of contrast agents. Due to the small volume fraction of blood vessels compared to tissue in the human brain (typ. 3-5%) ASL techniques have an intrinsically low signal-to-noise ratio (SNR). In this publication, evidence is presented that the SNR can be improved by using arterial spin labeling in combination with single-shot 3D readout techniques. Specifically, a single-shot 3D-GRASE sequence is presented, which yields a 2.8-fold increase in SNR compared to 2D EPI at the same nominal resolution. Up to 18 slices can be acquired in 2 min with an SNR of 10 or more for gray matter perfusion. A method is proposed to increase the reliability of perfusion quantification using QUIPSS II derivates by acquiring low-resolution maps of the bolus arrival time, which allows differentiation between lack of perfusion and delayed arrival of the labeled blood. For arterial spin labeling, single-shot 3D imaging techniques are optimal in terms of efficiency and might prove beneficial to improve reliability of perfusion quantitation in a clinical setup.

Journal ArticleDOI
TL;DR: Anisotropic brain tumor growth simulations provide a means to determine the initial location of a low‐grade glioma as well as its cell diffusion tensor, both of which might reflect the biological characteristics of invasion.
Abstract: A recent computational model of brain tumor growth, developed to better describe how gliomas invade through the adjacent brain parenchyma, is based on two major elements: cell proliferation and isotropic cell diffusion. On the basis of this model, glioma growth has been simulated in a virtual brain, provided by a 3D segmented MRI atlas. However, it is commonly accepted that glial cells preferentially migrate along the direction of fiber tracts. Therefore, in this paper, the model has been improved by including anisotropic extension of gliomas. The method is based on a cell diffusion tensor derived from water diffusion tensor (as given by MRI diffusion tensor imaging). Results of simulations have been compared with two clinical examples demonstrating typical growth patterns of low-grade gliomas centered around the insula. The shape and the kinetic evolution are better simulated with anisotropic rather than isotropic diffusion. The best fit is obtained when the anisotropy of the cell diffusion tensor is increased to greater anisotropy than the observed water diffusion tensor. The shape of the tumor is also influenced by the initial location of the tumor. Anisotropic brain tumor growth simulations provide a means to determine the initial location of a low-grade glioma as well as its cell diffusion tensor, both of which might reflect the biological characteristics of invasion.

Journal ArticleDOI
TL;DR: It is suggested that slow magnetization transfer in blood, either with bound water or macromolecular protons, dominates the inversion inefficiency in blood.
Abstract: Background suppression strategies for arterial spin labeling (ASL) MRI offer reduced noise from motion and other system instabilities. However, the inversion pulses used for suppression can also attenuate the ASL signal, which may offset the advantages of background suppression. Numerical simulations were used to optimize the inversion efficiency of four candidate pulses over a range of radiofrequency (RF) and static magnetic field variations typical of in vivo imaging. Optimized pulses were then used within a pulsed ASL sequence to assess the pulses' in vivo inversion efficiencies for ASL. The measured in vivo inversion efficiency was significantly lower than theoretical predictions (e.g., 93% experimental compared to 99% theoretical) for the tangent hyperbolic pulse applied in a background suppression scheme. This inefficiency was supported by an in vitro study of human blood. These results suggest that slow magnetization transfer (MT) in blood, either with bound water or macromolecular protons, dominates the inversion inefficiency in blood. Despite the attenuated signal relative to unsuppressed ASL, the signal-to-noise ratio (SNR) with suppression was improved by 23-110% depending on the size of the region measured. Knowledge of efficiency will aid optimization of the number of suppression pulses and provide more accurate quantification of blood flow.

Journal ArticleDOI
TL;DR: This work demonstrates that a time‐interleaved sampling scheme, in combination with autocalibrated GRAPPA (referred to as TGRAPPA), allows one to easily update the coil weights for the GRAPpa algorithm dynamically, thereby improving the acquisition efficiency.
Abstract: Current parallel imaging techniques for accelerated imaging require a fully encoded reference data set to estimate the spatial coil sensitivity information needed for reconstruction. In dynamic parallel imaging a time-interleaved acquisition scheme can be used, which eliminates the need for separately acquiring additional reference data, since the signal from directly adjacent time frames can be merged to build a set of fully encoded full-resolution reference data for coil calibration. In this work, we demonstrate that a time-interleaved sampling scheme, in combination with autocalibrated GRAPPA (referred to as TGRAPPA), allows one to easily update the coil weights for the GRAPPA algorithm dynamically, thereby improving the acquisition efficiency. This method may update coil sensitivity estimates frame by frame, thereby tracking changes in relative coil sensitivities that may occur during the data acquisition. Magn Reson Med 53:981–985, 2005. Published 2005 Wiley-Liss, Inc. †

Journal ArticleDOI
TL;DR: The present study lowers the limit previously reported for detecting sparse biomarkers with molecular MRI in vivo, and may be employed to noninvasively detect very small regions of angiogenesis associated with nascent melanoma tumors, and to phenotype and stage early melanoma in a clinical setting.
Abstract: Neovascularization is a critical component in the progression of malignant melanoma. The objective of this study was to determine whether alpha(nu)beta(3)-targeted paramagnetic nanoparticles can detect and characterize sparse alpha(nu)beta integrin expression on neovasculature induced by nascent melanoma xenografts ( approximately 30 mm(3)) at 1.5T. Athymic nude mice bearing human melanoma tumors were intravenously injected with alpha(v)beta(3)-integrin-targeted paramagnetic nanoparticles, nontargeted paramagnetic nanoparticles, or alpha(v)beta(3)-targeted-nonparamagnetic nanoparticles 2 hr before they were injected with alpha(v)beta(3)-integrin-targeted paramagnetic nanoparticles (i.e., in vivo competitive blockade) and imaged with MRI. Contrast enhancement of neovascularity in animals that received alpha(nu)beta(3)-targeted paramagnetic nanoparticles increased 173% by 120 min. Signal contrast with nontargeted paramagnetic nanoparticles was approximately 50% less than that in the targeted group (P < 0.05). Molecular MRI results were corroborated by histology. In a competitive cell adhesion assay, incubation of alpha(nu)beta(3)-expressing cells with targeted nanoparticles significantly inhibited binding to a vitronectin-coated surface, confirming the bioactivity of the targeted nanoparticles. The present study lowers the limit previously reported for detecting sparse biomarkers with molecular MRI in vivo. This technique may be employed to noninvasively detect very small regions of angiogenesis associated with nascent melanoma tumors, and to phenotype and stage early melanoma in a clinical setting.

Journal ArticleDOI
TL;DR: The proposed method was implemented and shown to significantly improve the algorithm's immunity to field inhomogeneity and improvement in stability is achieved using a low‐resolution reconstruction to guide the selection of the starting pixels for the region growing.
Abstract: Robust fat suppression techniques are required for many clinical applications. Multi-echo water-fat separation methods are relatively insensitive to B(0) field inhomogeneity compared to the fat saturation method. Estimation of this field inhomogeneity, or field map, is an essential and important step, which is well known to have ambiguity. For an iterative water-fat decomposition method recently proposed, ambiguities still exist, but are more complex in nature. They were studied by analytical expressions and simulations. To avoid convergence to incorrect field map solutions, an initial guess closer to the true field map is necessary. This can be achieved using a region growing process, which correlates the estimation among neighboring pixels. Further improvement in stability is achieved using a low-resolution reconstruction to guide the selection of the starting pixels for the region growing. The proposed method was implemented and shown to significantly improve the algorithm's immunity to field inhomogeneity.

Journal ArticleDOI
TL;DR: The results of this work will aid in the design of cellular imaging experiments by defining the lower limit of SPIO labeling required for single cell detection at any given resolution and SNR.
Abstract: MRI of superparamagnetic iron oxide (SPIO)-labeled cells has become a valuable tool for studying the in vivo trafficking of transplanted cells. Cellular detection with MRI is generally considered to be orders of magnitude less sensitive than other techniques, such as positron emission tomography (PET), single photon emission-computed tomography (SPECT), or optical fluorescence microscopy. However, an analytic description of the detection threshold for single SPIO-labeled cells and the parameters that govern detection has not been adequately provided. In the present work, the detection threshold for single SPIO-labeled cells and the effect of resolution and SNR were studied for a balanced steady-state free precession (SSFP) sequence (3D-FIESTA). Based on the results from both theoretical and experimental analyses, an expression that predicts the minimum detectable mass of SPIO (mc) required to detect a single cell against a uniform signal background was derived: mc ! 5v/(Kfsl ! SNR), where v is the voxel volume, SNR is the image signal-to-noise ratio, and Kfsl is an empirical constant measured to be 6.2 " 0.5 # 10 ‐5 $ l/pgFe. Using this expression, it

Journal ArticleDOI
TL;DR: The ability to image cardiomyocyte apoptosis in vivo with high‐resolution MRI with the novel nanoparticle AnxCLIO‐Cy5.5 is demonstrated to facilitate the development of novel cardioprotective therapies.
Abstract: The ability to image cardiomyocyte apoptosis in vivo with high-resolution MRI could facilitate the development of novel cardioprotective therapies. The sensitivity of the novel nanoparticle AnxCLIO-Cy5.5 for cardiomyocyte apoptosis was thus compared in vitro to that of annexin V-FITC and showed a high degree of colocalization. MRI was then performed, following transient coronary artery (LAD) occlusion, in five mice given AnxCLIO-Cy5.5 and in four mice given an identical dose (2 mg Fe/kg) of CLIO-Cy5.5. MR signal intensity and myocardial T2* were evaluated, in vivo, in hypokinetic regions of myocardium in the LAD distribution. Ex vivo fluorescence imaging was performed to confirm the in vivo findings. Myocardial T2* was significantly lower in the mice given AnxCLIO-Cy5.5 (8.1 versus 13.2 ms, P<0.01), and fluorescence target to background ratio was significantly higher (2.1 versus 1.1, P<0.01). This study thus demonstrates the feasibility of obtaining high-resolution MR images of cardiomyocyte apoptosis in vivo with the novel nanoparticle, AnxCLIO-Cy5.5.

Journal ArticleDOI
TL;DR: Within anisotropic regions, two consistent and dominant orientations were identified, supporting published results from histological studies and providing strong evidence that the tertiary eigenvector of the diffusion tensor (DT) defines the sheet normal.
Abstract: A three-dimensional (3D) diffusion-weighted imaging (DWI) method for measuring cardiac fiber structure at high spatial resolution is presented. The method was applied to the ex vivo reconstruction of the fiber architecture of seven canine hearts. A novel hypothesis-testing method was developed and used to show that distinct populations of secondary and tertiary eigenvalues may be distinguished at reasonable confidence levels (P < or = 0.01) within the canine ventricle. Fiber inclination and sheet angles are reported as a function of transmural depth through the anterior, lateral, and posterior left ventricle (LV) free wall. Within anisotropic regions, two consistent and dominant orientations were identified, supporting published results from histological studies and providing strong evidence that the tertiary eigenvector of the diffusion tensor (DT) defines the sheet normal.

Journal ArticleDOI
TL;DR: The results indicate that it is now possible to correct for nonrigid types of motion that are representative of many types of patient motion, although computation times remain an issue.
Abstract: Motion of an object degrades MR images, as the acquisition is time-dependent, and thus k-space is inconsistently sampled. This causes ghosts. Current motion correction methods make restrictive assumptions on the type of motions, for example, that it is a translation or rotation, and use special properties of k-space for these transformations. Such methods, however, cannot be generalized easily to nonrigid types of motions, and even rotations in multiple shots can be a problem. Here, a method is presented that can handle general nonrigid motion models. A general matrix equation gives the corrupted image from the ideal object. Thus, inversion of this system allows us to get the ideal image from the corrupted one. This inversion is possible by efficient methods mixing Fourier transforms with the conjugate gradient method. A faster but empirical inversion is discussed as well as methods to determine the motion. Simulated three-dimensional affine data and two-dimensional pulsation data and in vivo nonrigid data are used for demonstration. All examples are multishot images where the object moves between shots. The results indicate that it is now possible to correct for nonrigid types of motion that are representative of many types of patient motion, although computation times remain an issue.

Journal ArticleDOI
TL;DR: A self‐navigated, free‐breathing, whole‐heart 3D coronary MRI technique that would overcome shortcomings and improve the ease‐of‐use of coronary MRI is developed and implemented.
Abstract: Respiratory motion is a major source of artifacts in cardiac magnetic resonance imaging (MRI). Free-breathing techniques with pencil-beam navigators efficiently suppress respiratory motion and minimize the need for patient cooperation. However, the correlation between the measured navigator position and the actual position of the heart may be adversely affected by hysteretic effects, navigator position, and temporal delays between the navigators and the image acquisition. In addition, irregular breathing patterns during navigator-gated scanning may result in low scan efficiency and prolonged scan time. The purpose of this study was to develop and implement a self-navigated, free-breathing, whole-heart 3D coronary MRI technique that would overcome these shortcomings and improve the ease-of-use of coronary MRI. A signal synchronous with respiration was extracted directly from the echoes acquired for imaging, and the motion information was used for retrospective, rigid-body, through-plane motion correction. The images obtained from the self-navigated reconstruction were compared with the results from conventional, prospective, pencil-beam navigator tracking. Image quality was improved in phantom studies using self-navigation, while equivalent results were obtained with both techniques in preliminary in vivo studies.

Journal ArticleDOI
TL;DR: While MEP was harmful at higher voltages or pulse durations, the procedure could be properly calibrated using a pulse of 130 V and 17 ms, and may be ideally suitable for bedside implementation.
Abstract: For cellular MR imaging, conventional approaches to intracellular magnetic labeling of nonphagocytic cells rely on the use of secondary compounds such as transfection agents and prolonged incubation of cells. Magnetoelectroporation (MEP) was investigated as an alternative method to achieve instant (<1 s) endosomal labeling with the FDA-approved formulation Feridex, without the need for adjunct agents or initiating cell cultures. While MEP was harmful at higher voltages or pulse durations, the procedure could be properly calibrated using a pulse of 130 V and 17 ms. Labeling was demonstrated for stem cells from mice, rats, and humans; the uptake of iron was in the picogram range and comparable to values obtained using transfection agents. MEP-labeled stem cells exhibited an unaltered viability, proliferation, and mitochondrial metabolic rate. Labeled mesenchymal stem cells (MSCs) and neural stem cells (NSCs) differentiated into adipogenic, osteogenic, and neural lineages in an identical fashion as unlabeled cells, while containing Feridex particles as demonstrated by double immunofluorescent staining. MEP-labeled NSCs proliferated normally following intrastriatal transplantation and could be readily detected by MR imaging in vivo. As MEP circumvents the use of secondary agents, obviating the need for clinical approval, MEP labeling may be ideally suitable for bedside implementation.

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TL;DR: It is shown that the idea of GRAPPA can be applied in k‐t space to take advantage of the correlations and interpolate the missing data in k •t space and generate high spatial resolution reconstruction without significant loss of temporal resolution.
Abstract: A novel technique called "k-t GRAPPA" is introduced for the acceleration of dynamic magnetic resonance imaging. Dynamic magnetic resonance images have significant signal correlations in k-space and time dimension. Hence, it is feasible to acquire only a reduced amount of data and recover the missing portion afterward. Generalized autocalibrating partially parallel acquisitions (GRAPPA), as an important parallel imaging technique, linearly interpolates the missing data in k-space. In this work, it is shown that the idea of GRAPPA can also be applied in k-t space to take advantage of the correlations and interpolate the missing data in k-t space. For this method, no training data, filters, additional parameters, or sensitivity maps are necessary, and it is applicable for either single or multiple receiver coils. The signal correlation is locally derived from the acquired data. In this work, the k-t GRAPPA technique is compared with our implementation of GRAPPA, TGRAPPA, and sliding window reconstructions, as described in Methods. The experimental results manifest that k-t GRAPPA generates high spatial resolution reconstruction without significant loss of temporal resolution when the reduction factor is as high as 4. When the reduction factor becomes higher, there might be a noticeable loss of temporal resolution since k-t GRAPPA uses temporal interpolation. Images reconstructed using k-t GRAPPA have less residue/folding artifacts than those reconstructed by sliding window, much less noise than those reconstructed by GRAPPA, and wider temporal bandwidth than those reconstructed by GRAPPA with residual k-space. k-t GRAPPA is applicable to a wide range of dynamic imaging applications and is not limited to imaging parts with quasi-periodic motion. Since only local information is used for reconstruction, k-t GRAPPA is also preferred for applications requiring real time reconstruction, such as monitoring interventional MRI.

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TL;DR: The Crámer–Rao bound (CRB) was used to study the variance of the estimates of the magnitude, phase, and field map by computing the maximum effective number of signals averaged (NSA) for any choice of echo time shifts.
Abstract: The noise analysis for three-point decomposition of water and fat was extended to account for the uncertainty in the field map. This generalization leads to a nonlinear estimation problem. The Cramer-Rao bound (CRB) was used to study the variance of the estimates of the magnitude, phase, and field map by computing the maximum effective number of signals averaged (NSA) for any choice of echo time shifts. The analysis shows that the noise properties of the reconstructed magnitude, phase, and field map depend not only on the choice of echo time shifts but also on the amount of fat and water in each voxel and their alignment at the echo. The choice of echo time shifts for spin-echo, spoiled gradient echo, and steady-state free precession imaging techniques were optimized using the CRB. The noise analysis for the magnitude explains rough interfaces seen clinically in the boundary of fat and water with source images obtained symmetrically about the spin-echo. It also provides a solution by choosing appropriate echo time shifts (-pi/6+pik, pi/2+pik, 7pi/6+pik), with k an integer. With this choice of echo time shifts it is possible to achieve the maximum NSA uniformly across all fat:water ratios. The optimization is also carried out for the estimation of phase and field map. These theoretical results were verified using Monte Carlo simulations with a newly developed nonlinear least-squares reconstruction algorithm that achieves the CRB.