Reliable assessment of perfusivity and diffusivity from diffusion imaging of the body.

Diffusion-weighted MRI of the body has the potential to provide important new insights into physiological and microstructural properties. The intra-voxel incoherent motion (IVIM) model relates the observed DW-MRI signal decay to parameters that reflect perfusivity (D*) and its volume fraction (f), and diffusivity (D). However, the commonly used voxel-wise fitting of the IVIM model leads to parameter estimates with poor precision, which has hampered their practical usage. In this work, we increase the estimates' precision by introducing a model of spatial homogeneity, through which we obtain estimates of model parameters for all of the voxels at once, instead of solving for each voxel independently. Furthermore, we introduce an efficient iterative solver which utilizes a model-based bootstrap estimate of the distribution of residuals and a binary graph cut to generate optimal model parameter updates. Simulation experiments show that our approach reduces the relative root mean square error of the estimated parameters by 80% for the D* parameter and by 50% for the f and D parameters. We demonstrated the clinical impact of our model in distinguishing between enhancing and nonenhancing ileum segments in 24 Crohn's disease patients. Our model detected the enhanced segments with 91%/92% sensitivity/specificity which is better than the 81%/85% obtained by the voxel-independent approach.

Quantitative body DW-MRI biomarkers uncertainty estimation using unscented wild-bootstrap.

We present a new method for the uncertainty estimation of diffusion parameters for quantitative body DW-MRI assessment. Diffusion parameters uncertainty estimation from DW-MRI is necessary for clinical applications that use these parameters to assess pathology. However, uncertainty estimation using traditional techniques requires repeated acquisitions, which is undesirable in routine clinical use. Model-based bootstrap techniques, for example, assume an underlying linear model for residuals rescaling and cannot be utilized directly for body diffusion parameters uncertainty estimation due to the non-linearity of the body diffusion model. To offset this limitation, our method uses the Unscented transform to compute the residuals rescaling parameters from the non-linear body diffusion model, and then applies the wild-bootstrap method to infer the body diffusion parameters uncertainty. Validation through phantom and human subject experiments shows that our method identify the regions with higher uncertainty in body DWI-MRI model parameters correctly with realtive error of -36% in the uncertainty values.

Developmental fMRI study of episodic verbal memory encoding in children.

BACKGROUND: Understanding the maturation and organization of cognitive function in the brain is a central objective of both child neurology and developmental cognitive neuroscience. This study focuses on episodic memory encoding of verbal information by children, a cognitive domain not previously studied using fMRI. METHODS: Children from 7 to 19 years of age were scanned at 1.5-T field strength using event-related fMRI while performing a novel verbal memory encoding paradigm in which words were incidentally encoded. A subsequent memory analysis was performed. SPM2 was utilized for whole brain and region-of-interest analyses of data. Both whole-sample intragroup analyses and intergroup analyses of the sample divided into 2 subgroups by age were conducted. RESULTS: Importantly, behavioral memory performance was equal across the age range of children studied. Encoding-related activation in the left hippocampus and bilateral basal ganglia declined as age increased. In addition, while robust blood oxygen level-dependent signal was found in left prefrontal cortex with task performance, no encoding-related age-modulated prefrontal activation was observed in either hemisphere. CONCLUSION: These data are consistent with a developmental pattern of verbal memory encoding function in which left hippocampal and bilateral basal ganglionic activations are more robust earlier in childhood but then decline with age. No encoding-related activation was found in prefrontal cortex which may relate to this region's recognized delay in biologic maturation in humans. These data represent the first fMRI demonstration of verbal encoding function in children and are relevant developmentally and clinically.

Factors affecting paramagnetic contrast enhancement in synovial fluid: effects of electrolytes, protein concentrations, and temperature on water proton relaxivities from Mn ions and Gd chelated contrast agents.

INTRODUCTION: Protein and electrolyte concentration of synovial fluid (SF) varies with the type of underlying arthritis. These characteristics can be utilized by magnetic resonance technology to provide a potentially significant diagnostic modality through quantitative assessments of inherent water relaxation rates and their response to contrast agents. METHODS: We evaluated the effect of a classic "in vitro" contrast agent, the Mn ion, and a common "in vivo" gadolinium based contrast agent, gadopentetate dimeglumine, on the water relaxation times of solutions with biochemical compositions simulating different types of arthritis along with similar studies of SF obtained from patients. RESULTS: The results demonstrate how protein and electrolyte concentrations play a significant role in the response of water relaxation to the Mn ion but much less so to chelated gadolinium contrast agents used clinically. DISCUSSION: A major challenge remains to develop paramagnetic agents with less toxicity than the Mn ion but with similar properties that can then serve as a tool to determine protein concentrations through imaging and thereby assist in the diagnosis of inflammatory arthrides and evaluation of therapeutic regimens.

Comparison of parallel MRI reconstruction methods for accelerated 3D fast spin-echo imaging.

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.

Targeted dendrimer-based contrast agents for articular cartilage assessment by MR imaging.

OBJECTIVE: Magnetic resonance (MR) imaging with contrast media has shown promise for articular cartilage assessment. Dendrimer-linked nitroxides, a new family of MR contrast agents targeted to glycosaminoglycan, may improve cartilage evaluation. This study is designed to determine the ability of dendrimer-linked nitroxides to enhance articular cartilage and measure the intra-articular life-time of these agents. DESIGN: Cartilage T(1) was evaluated using immature bovine patella in solutions of five different dendrimer-linked nitroxides, saline or Gd-DTPA at 1.5T. The "relaxivity per dose" (change in cartilage 1/T(1) produced by a given concentration of agent) was calculated. The half-life of joint fluid enhancement was measured at 2T after solutions of three dendrimer-linked nitroxides, Gd-DTPA, and saline were injected into rabbit stifle joints. Twenty-four hours after injection, the joints were examined grossly and by histology for toxicity. RESULTS: All but the largest dendrimer-linked nitroxide were able to intensely enhance articular cartilage on MR. Relaxivity per dose measurements were between 3.5 and 68 times greater than Gd-DTPA. The largest nitroxide appeared to be excluded from articular cartilage. Intra-articular half-lives of the dendrimer-linked nitroxides were sufficiently long (160-208 min) for in vivo MR imaging to be performed. Histological assessments of joints showed minimal synovial inflammatory and necrosis scores 1 day post-injection that were similar for all agents, including Gd-DTPA. CONCLUSION: Dendrimer-linked nitroxides strongly enhance cartilage and are promising as articular cartilage-specific MR contrast agents. The intra-articular life-time is sufficient for imaging studies and, in initial evaluation, the agents exhibit minimal toxicity in rabbit joints.

Reinvestigating hyperpolarized (129)Xe longitudinal relaxation time in the rat brain with noise considerations.

The longitudinal relaxation time of hyperpolarized (HP) (129)Xe in the brain is a critical parameter for developing HP (129)Xe brain imaging and spectroscopy and optimizing the pulse sequences, especially in the case of cerebral blood flow measurements. Various studies have produced widely varying estimates of HP (129)Xe T(1) in the rat brain. To make improved measurements of HP (129)Xe T(1) in the rat brain and investigate how low signal-to-noise ratio (SNR) contributes to these discrepancies, we developed a multi-pulse protocol during the washout of (129)Xe from the brain. Afterwards, we applied an SNR threshold theory to both the multi-pulse protocol and an existing two-pulse protocol. The two protocols yielded mean +/- SD HP (129)Xe T(1) values in the rat brain of 15.3 +/- 1.2 and 16.2 +/- 0.9 s, suggesting that the low SNR might be a key reason for the wide range of T(1) values published in the literature, a problem that might be easily alleviated by taking SNR levels into account.

Magnetic resonance imaging and T2 relaxometry of human median nerve at 7 Tesla.

Measurements of T2 relaxation times in tissues have provided a unique, noninvasive method to investigate the microenvironment of water molecules in vivo. As more clinical imaging is performed at higher field strengths, tissue relaxation times need to be reassessed in order to optimize tissue contrast. The purpose of this study was to investigate the water proton T2 relaxation time in human median nerve at 7 T. High-resolution images of the wrist were obtained using a home-built dedicated microstrip coil. Gradient echo images provided a good anatomical delineation of the wrist structure, with a clear definition of the median nerve, tendons, bone, and connective tissue within the wrist in an acquisition time of 2 min. Measurements of the T2 relaxation time were performed with a spin echo imaging sequence. The T2 relaxation time of the median nerve was 18.3 +/- 1.9 ms, which is significantly shorter than the T2 measured in previous studies performed at 1.5 T and 3 T. Further, the T2 relaxation time of the median nerve is shorter than the T2 relaxation time of other tissues, such as brain tissue, at the same field strength. Since the T2 relaxation time of water protons is sensitive to the water microenvironment, relaxation measurements and, in general, a more quantitative magnetic resonance imaging approach might help in detecting and investigating diseases of peripheral nervous system, such as compressive and inflammatory neuropathies, in humans.

The Neuroimaging Center of the Pediatric Brain Tumor Consortium-collaborative neuroimaging in pediatric brain tumor research: a work in progress.

As an essential part of the National Cancer Institute (NCI)-funded Pediatric Brain Tumor Consortium (PBTC), the Neuroimaging Center (NIC) is dedicated to infusing the study of pediatric brain tumors with imaging "best practice" by producing a correlative research plan that 1) resonates with novel therapeutic interventions being developed by the wider PBTC, 2) ensures that every PBTC protocol incorporates an imaging "end point" among its objectives, 3) promotes the widespread implementation of standardized technical protocols for neuroimaging, and 4) facilitates a quality assurance program that complies with the highest standards for image data transfer, diagnostic image quality, and data integrity. To accomplish these specific objectives, the NIC works with the various PBTC sites (10 in all, plus NCI/ National Institute of Neurological Diseases and Stroke representation) to ensure that the overarching mission of the consortium--to better understand tumor biology and develop new therapies for central nervous system tumors in children--is furthered by creating a uniform body of imaging techniques, technical protocols, and standards. Since the inception of the NIC in 2003, this broader mandate has been largely accomplished through a series of site visits and meetings aimed at assessing prevailing neuroimaging practices against NIC-recommended protocols, techniques, and strategies for achieving superior image quality and executing the secure transfer of data to the central PBTC. These ongoing evaluations periodically examine investigations into targeted drug therapies. In the future, the NIC will concentrate its efforts on improving image analysis for MR imaging and positron-emission tomography (PET) and on developing new ligands for PET; imaging markers for radiation therapy; and novel systemic, intrathecal, and intralesional therapeutic interventions.

Magnetic resonance and the human brain: anatomy, function and metabolism.

The introduction and development, over the last three decades, of magnetic resonance (MR) imaging and MR spectroscopy technology for in vivo studies of the human brain represents a truly remarkable achievement, with enormous scientific and clinical ramifications. These effectively non-invasive techniques allow for studies of the anatomy, the function and the metabolism of the living human brain. They have allowed for new understandings of how the healthy brain works and have provided insights into the mechanisms underlying multiple disease processes which affect the brain. Different MR techniques have been developed for studying anatomy, function and metabolism. The primary focus of this review is to describe these different methodologies and to briefly review how they are being employed to more fully appreciate the intricacies associated with the organ, which most distinctly differentiates the human species from the other animal forms on earth.

Echo-time independent signal modulations using PRESS sequences: a new approach to spectral editing of strongly coupled AB spin systems.

In clinical MR spectroscopy, double spin-echo point resolved spectroscopy (PRESS) sequences are routinely used for volume selection. For strongly coupled AB spin systems under PRESS excitation, the dependence of the signal on the echo time TE has been thoroughly investigated, whereas less attention has been paid to the signal modulation which occurs at constant TE with varying interpulse delays. A substantial TE-independent J modulation is here predicted from analytical solutions of the Liouville equation and density matrix simulations, and verified with experiments on citrate at 1.5 and 3T. It is also shown that this modulation effect could be exploited for editing of strongly coupled AB resonances or for removal of singlets in spectra-by means of difference spectroscopy-just using a standard PRESS sequence. The applicability in vivo of this new spectral editing approach is also demonstrated, with selective detection of citrate resonances in the human prostate. This novel approach has the advantages of being simple, and directly applicable on standard clinical MR scanners, provided that the exact behavior of the resonance is known.

DTI and MTR abnormalities in schizophrenia: analysis of white matter integrity.

Diffusion tensor imaging (DTI) studies in schizophrenia demonstrate lower anisotropic diffusion within white matter due either to loss of coherence of white matter fiber tracts, to changes in the number and/or density of interconnecting fiber tracts, or to changes in myelination, although methodology as well as localization of such changes differ between studies. The aim of this study is to localize and to specify further DTI abnormalities in schizophrenia by combining DTI with magnetization transfer imaging (MTI), a technique sensitive to myelin and axonal alterations in order to increase specificity of DTI findings. 21 chronic schizophrenics and 26 controls were scanned using Line-Scan-Diffusion-Imaging and T1-weighted techniques with and without a saturation pulse (MT). Diffusion information was used to normalize co-registered maps of fractional anisotropy (FA) and magnetization transfer ratio (MTR) to a study-specific template, using the multi-channel daemon algorithm, designed specifically to deal with multidirectional tensor information. Diffusion anisotropy was decreased in schizophrenia in the following brain regions: the fornix, the corpus callosum, bilaterally in the cingulum bundle, bilaterally in the superior occipito-frontal fasciculus, bilaterally in the internal capsule, in the right inferior occipito-frontal fasciculus and the left arcuate fasciculus. MTR maps demonstrated changes in the corpus callosum, fornix, right internal capsule, and the superior occipito-frontal fasciculus bilaterally; however, no changes were noted in the anterior cingulum bundle, the left internal capsule, the arcuate fasciculus, or inferior occipito-frontal fasciculus. In addition, the right posterior cingulum bundle showed MTR but not FA changes in schizophrenia. These findings suggest that, while some of the diffusion abnormalities in schizophrenia are likely due to abnormal coherence, or organization of the fiber tracts, some of these abnormalities may, in fact, be attributed to or coincide with myelin/axonal disruption.

Dairy cream as a phantom material for biexponential diffusion decay.

Commercially available aliquots of dairy cream are shown to have diffusion decay curves characterized by biexponential functions when studied over a wide range of b-factors. The fast and slow diffusion components responsible for the biexponential decay are attributed to water and lipid protons, respectively. The fast diffusion coefficient and relative fast and slow diffusion component fractions obtained from biexponential fits of cream phantoms over a wide range of b-factors up to 3,000 s/mm2 are similar to those obtained previously for brain. The slow diffusion coefficient from lipid protons is smaller than that found in the brain. Overall, however, the results suggest that dairy cream can serve as a widely available phantom material for testing software and hardware components designed to perform quantitative, biexponential diffusion decay studies.

Prolonged T*2 values in newborn versus adult brain: Implications for fMRI studies of newborns.

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.

Biexponential apparent diffusion coefficient parametrization in adult vs newborn brain.

The decay of brain water signal with b-factor in adult and newborn brains has been measured over an extended b-factor range. Measurements of the apparent diffusion coefficient (ADC) decay curves were made at 16 b-factors from 100 to 5000 s/mm(2) along three orthogonal directions using a line scan diffusion imaging (LSDI) sequence to acquire data from 0.09 ml voxels in a mid-brain axial slice. Regions-of-interest (ROIs) in cortical gray (CG) and white matter in the internal capsule (IC) were selected for ADC decay curve analyses using a biexponential fitting model over this extended b-factor range. Measures of the fast and slow ADC component amplitudes and the traces of the fast and slow diffusion coefficients were obtained from CG and IC ROIs in both adults and newborns. The ADC decay curves from the newborn brain regions were found to have a significantly higher fraction of the fast diffusion ADC component than corresponding regions in the adult brain. The results demonstrate that post-natal brain development has a profound affect on the biexponential parameters which characterize the decay of water signal over an extended b-factor range in both gray and white matter.

Fast three-point Dixon MR imaging of the retrobulbar space with low-resolution images for phase correction: comparison with fast spin-echo inversion recovery imaging.

A new phase-correction algorithm for three-point Dixon (3PD) MR imaging allows on-line image reconstruction of three images per section: pure water, pure fat, and water plus fat. When combined with fast spin-echo acquisition, the sequence is suitable for routine MR imaging of the retrobulbar space. The 3PD pure water images have double the image signal-to-noise ratio of fast spin-echo inversion recovery images. The dramatic contrast-to-noise ratio of the 3PD pure fat images may offer improved lesion detection.

Fast three-point dixon MR imaging using low-resolution images for phase correction: a comparison with chemical shift selective fat suppression for pediatric musculoskeletal imaging.

OBJECTIVE: The purpose of this study is to describe and to implement a new fast three-point Dixon MR imaging sequence with online image reconstruction, and to compare this sequence with conventional chemical shift selective (CHESS) suppression of fat in pediatric musculoskeletal imaging. SUBJECTS AND METHODS: A three-point Dixon technique using a fast spin-echo sequence with a new phase-correction algorithm providing online image reconstruction was implemented on a 1.5-T scanner. Twelve pediatric patients and young adults were imaged with both the new three-point Dixon and conventional CHESS sequences. Three radiologists un-aware of imaging parameters and clinical information independently scored the homogeneity of fat suppression and conspicuity of abnormality using a four-point system. An additional comparison between the two techniques was made using a phantom. RESULTS: The three-point Dixon method showed superior fat suppression and lesion conspicuity (p < 0.001), particularly in the hands and feet, where CHESS is prone to inconsistent fat suppression. The phantom study showed no significant difference in the ratio of suppressed fat signal to background noise and more homogeneous fat suppression using the three-point Dixon method. CONCLUSION: Compared with CHESS, the new fast three-point Dixon sequence with online image reconstruction provides superior fat suppression and lesion conspicuity and can be routinely used in pediatric musculoskeletal imaging.

Osmotic effects on the T2 relaxation decay of in vivo muscle.

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.

Dynamic imaging with multiple resolutions along phase-encode and slice-select dimensions.

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.

Normal brain and brain tumor: multicomponent apparent diffusion coefficient line scan imaging.

Magnetic resonance line scan diffusion imaging of the brain, with diffusion weighting between 5 and 5,000 sec/mm(2), was performed in healthy subjects and patients with a 1.5-T machine. For each voxel, biexponential signal decay fits produced two apparent diffusion constants and respective signal amplitudes. Images based on these parameters show potential for use in the differentiation of gray and white matter, edema, and tumor.