In vivo three-dimensional whole-brain pulsed steady-state chemical exchange saturation transfer at 7 T.

Chemical exchange saturation transfer (CEST) is a technique to indirectly detect pools of exchangeable protons through the water signal. To increase its applicability to human studies, it is needed to develop sensitive pulse sequences for rapidly acquiring whole-organ images while adhering to stringent amplifier duty cycle limitations and specific absorption rate restrictions. In addition, the interfering effects of direct water saturation and conventional magnetization transfer contrast complicate CEST quantification and need to be reduced as much as possible.

Monitoring enzyme activity using a diamagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent.

Chemical exchange saturation transfer (CEST) is a new approach for generating magnetic resonance imaging (MRI) contrast that allows monitoring of protein properties in vivo. In this method, a radiofrequency pulse is used to saturate the magnetization of specific protons on a target molecule, which is then transferred to water protons via chemical exchange and detected using MRI. One advantage of CEST imaging is that the magnetizations of different protons can be specifically saturated at different resonance frequencies.

Gradient enhanced spectroscopy.

This paper provides a brief overview of the personal recollections of the authors regarding their contributions to the introduction of shielded gradient technology into NMR spectroscopy during the late 1980s and early 1990s. It provides some background into early probe design and details some of the early technical progress with the use of shielded magnetic field gradients for coherence selection in high resolution NMR and describes the developments at General Electric, the National Institutes of Health, Georgetown University and Johns Hopkins University School of Medicine that ultimately led to this technology becoming commonplace in modern NMR spectroscopy. Most of this early technical work was published in the Journal of Magnetic Resonance.

Multi-modal MRI analysis with disease-specific spatial filtering: initial testing to predict mild cognitive impairment patients who convert to Alzheimer's disease.

Background: Alterations of the gray and white matter have been identified in Alzheimer's disease (AD) by structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). However, whether the combination of these modalities could increase the diagnostic performance is unknown.

Methods: Participants included 19 AD patients, 22 amnestic mild cognitive impairment (aMCI) patients, and 22 cognitively normal elderly (NC).

Using the water signal to detect invisible exchanging protons in the catalytic triad of a serine protease.

Chemical Exchange Saturation Transfer (CEST) is an MRI approach that can indirectly detect exchange broadened protons that are invisible in traditional NMR spectra. We modified the CEST pulse sequence for use on high-resolution spectrometers and developed a quantitative approach for measuring exchange rates based upon CEST spectra. This new methodology was applied to the rapidly exchanging Hδ1 and Hε2 protons of His57 in the catalytic triad of bovine chymotrypsinogen-A (bCT-A).

Inflow-based vascular-space-occupancy (iVASO) MRI.

Vascular-space-occupancy (VASO) MRI, a blood nulling approach for assessing changes in cerebral blood volume (CBV), is hampered by low signal-to-noise ratio (SNR) because only 10-20% of tissue signal is recovered when using nonselective inversion for blood nulling. A new approach, called inflow-VASO (iVASO), is introduced in which only blood flowing into the slice has experienced inversion, thereby keeping tissue and cerebrospinal fluid (CSF) signal in the slice maximal and reducing CSF partial volume effects. SNR increases of 198% ± 12% and 334% ± 9% (mean ± SD, n = 7) with respect to VASO were found at TR values of 5 s and 2 s, respectively.

Measurement of absolute arterial cerebral blood volume in human brain without using a contrast agent.

Arterial cerebral blood volume (CBV(a) ) is a vital indicator of tissue perfusion and vascular reactivity. We extended the recently developed inflow vascular-space-occupancy (iVASO) MRI technique, which uses spatially selective inversion to suppress the signal from blood flowing into a slice, with a control scan to measure absolute CBV(a) using cerebrospinal fluid (CSF) for signal normalization. Images were acquired at multiple blood nulling times to account for the heterogeneity of arterial transit times across the brain, from which both CBV(a) and arterial transit times were quantified.

Calibration and validation of TRUST MRI for the estimation of cerebral blood oxygenation.

Recently, a T(2) -Relaxation-Under-Spin-Tagging (TRUST) MRI technique was developed to quantitatively estimate blood oxygen saturation fraction (Y) via the measurement of pure blood T(2) . This technique has shown promise for normalization of fMRI signals, for the assessment of oxygen metabolism, and in studies of cognitive aging and multiple sclerosis. However, a human validation study has not been conducted.

Fast measurement of blood T1 in the human jugular vein at 3 Tesla.

Current T(1) values for blood at 3T largely came from in vitro studies on animal blood or freshly drawn human blood. Measurement of blood T(1) in vivo could provide more specific information, e.g.

Physiological origin for the BOLD poststimulus undershoot in human brain: vascular compliance versus oxygen metabolism.

The poststimulus blood oxygenation level-dependent (BOLD) undershoot has been attributed to two main plausible origins: delayed vascular compliance based on delayed cerebral blood volume (CBV) recovery and a sustained increased oxygen metabolism after stimulus cessation. To investigate these contributions, multimodal functional magnetic resonance imaging was employed to monitor responses of BOLD, cerebral blood flow (CBF), total CBV, and arterial CBV (CBV(a)) in human visual cortex after brief breath hold and visual stimulation. In visual experiments, after stimulus cessation, CBV(a) was restored to baseline in 7.

A framework on surface-based connectivity quantification for the human brain.

Quantifying the connectivity between arbitrary surface patches in the human brain cortex can be used in studies on brain function and to characterize clinical diseases involving abnormal connectivity. Cortical regions of human brain in their natural forms can be represented in surface formats. In this paper, we present a framework to quantify connectivity using cortical surface segmentation and labeling from structural magnetic resonance images, tractography from diffusion tensor images, and nonlinear inter-subject registration.

On the relationship between seed-based and ICA-based measures of functional connectivity.

Brain functional connectivity (FC) refers to inter-regional synchrony of low frequency fluctuations in blood oxygenation level dependent functional magnetic resonance imaging. FC has been evaluated both during task performance and in the "resting" state, yielding reports of FC differences correlated with behavior and diagnosis. Two methodologies are widely used for evaluating FC from blood oxygenation level dependent functional magnetic resonance imaging data: Temporal correlation with a specified seed voxel or small region of interest; and spatial independent component analysis.

Chemical exchange saturation transfer (CEST): what is in a name and what isn't?

Chemical exchange saturation transfer (CEST) imaging is a relatively new magnetic resonance imaging contrast approach in which exogenous or endogenous compounds containing either exchangeable protons or exchangeable molecules are selectively saturated and after transfer of this saturation, detected indirectly through the water signal with enhanced sensitivity. The focus of this review is on basic magnetic resonance principles underlying CEST and similarities to and differences with conventional magnetization transfer contrast. In CEST magnetic resonance imaging, transfer of magnetization is studied in mobile compounds instead of semisolids.

Multi-contrast human neonatal brain atlas: application to normal neonate development analysis.

MRI is a sensitive method for detecting subtle anatomic abnormalities in the neonatal brain. To optimize the usefulness for neonatal and pediatric care, systematic research, based on quantitative image analysis and functional correlation, is required. Normalization-based image analysis is one of the most effective methods for image quantification and statistical comparison.

Determination of whole-brain oxygen extraction fractions by fast measurement of blood T(2) in the jugular vein.

The oxygen extraction fraction of the brain reports on the balance between oxygen delivery and consumption and can be used to assess deviations in physiological homeostasis. This is relevant clinically as well as for calibrating blood oxygen level-dependent functional MRI responses. Oxygen extraction fraction is reflected in the arteriovenous difference in oxygen saturation fraction (Y(v) - Y(a) ), which can be determined from venous T(2) values when arterial oxygenation is known.

Blood oxygenation level-dependent (BOLD) total and extravascular signal changes and ΔR2* in human visual cortex at 1.5, 3.0 and 7.0 T.

The characterisation of the extravascular (EV) contribution to the blood oxygenation level-dependent (BOLD) effect is important for understanding the spatial specificity of BOLD contrast and for modelling approaches that aim to extract quantitative metabolic parameters from the BOLD signal. Using bipolar crusher gradients, total (b = 0 s/mm(2) ) and predominantly EV (b = 100 s/mm(2) ) gradient echo BOLD ΔR(2)* and signal changes (ΔS/S) in response to visual stimulation (flashing checkerboard; f = 8 Hz) were investigated sequentially (within < 3 h) at 1.5, 3.

Diffuse abnormality of low to moderately organized white matter in schizophrenia.

Increasing evidence suggests that abnormal white matter is central to the pathophysiology and, potentially, the pathogenesis of schizophrenia (SCZ). The spatial distribution of observed abnormalities and the type of white matter involved remain to be elucidated. Seventeen chronically ill individuals with SCZ and 17 age- and gender-matched controls were studied using a 3T magnetic resonance imaging diffusion tensor imaging protocol designed to examine the abnormalities of white matter by region and by level of architectural infrastructure as assessed by fractional anisotropy (FA) in native space.

Superficially located white matter structures commonly seen in the human and the macaque brain with diffusion tensor imaging.

The white matter of the brain consists of fiber tracts that connect different regions of the brain. Among these tracts, the intrahemispheric cortico-cortical connections are called association fibers. The U-fibers are short association fibers that connect adjacent gyri.

Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides.

It remains difficult to distinguish tumor recurrence from radiation necrosis after brain tumor therapy. Here we show that these lesions can be distinguished using the amide proton transfer (APT) magnetic resonance imaging (MRI) signals of endogenous cellular proteins and peptides as an imaging biomarker. When comparing two models of orthotopic glioma (SF188/V+ glioma and 9L gliosarcoma) with a model of radiation necrosis in rats, we could clearly differentiate viable glioma (hyperintense) from radiation necrosis (hypointense to isointense) by APT MRI.

Multi-parametric neuroimaging reproducibility: a 3-T resource study.

Modern MRI image processing methods have yielded quantitative, morphometric, functional, and structural assessments of the human brain. These analyses typically exploit carefully optimized protocols for specific imaging targets. Algorithm investigators have several excellent public data resources to use to test, develop, and optimize their methods.

Quantitative analysis of brain pathology based on MRI and brain atlases--applications for cerebral palsy.

We have developed a new method to provide a comprehensive quantitative analysis of brain anatomy in cerebral palsy patients, which makes use of two techniques: diffusion tensor imaging and automated 3D whole brain segmentation based on our brain atlas and a nonlinear normalization technique (large-deformation diffeomorphic metric mapping). This method was applied to 13 patients and normal controls. The reliability of the automated segmentation revealed close agreement with the manual segmentation.

Fast 3D chemical exchange saturation transfer (CEST) imaging of the human brain.

Chemical exchange saturation transfer magnetic resonance imaging can detect low-concentration compounds with exchangeable protons through saturation transfer to water. This technique is generally slow, as it requires acquisition of saturation images at multiple frequencies. In addition, multislice imaging is complicated by saturation effects differing from slice to slice because of relaxation losses.

High-throughput screening of chemical exchange saturation transfer MR contrast agents.

A new high-throughput MRI method for screening chemical exchange saturation transfer (CEST) agents is demonstrated, allowing simultaneous testing of multiple samples with minimal attention to sample configuration and shimming of the main magnetic field (B(0)). This approach, which is applicable to diamagnetic, paramagnetic and liposome CEST agents, employs a set of inexpensive glass or plastic capillary tubes containing CEST agents put together in a cheap plastic tube holder, without the need for liquid between the tubes to reduce magnetic susceptibility effects. In this setup, a reference image of direct water saturation spectra is acquired in order to map the absolute water frequency for each volume element (voxel) in the sample image, followed by an image of saturation transfer spectra to determine the CEST properties.

Atlas-guided tract reconstruction for automated and comprehensive examination of the white matter anatomy.

Tractography based on diffusion tensor imaging (DTI) is widely used to quantitatively analyze the status of the white matter anatomy in a tract-specific manner in many types of diseases. This approach, however, involves subjective judgment in the tract-editing process to extract only the tracts of interest. This process, usually performed by manual delineation of regions of interest, is also time-consuming, and certain tracts, especially the short cortico-cortical association fibers, are difficult to reconstruct.