Defining an Acidosis-Based Ischemic Penumbra from pH-Weighted MRI.

It has been proposed that the spatial mismatch between deficits on perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) in MRI can be used to decide regarding thrombolytic treatment in acute stroke. However, uncertainty remains about the meaning and reversibility of the perfusion deficit and even part of the diffusion deficit. Thus, there remains a need for continued development of imaging technology that can better define a potentially salvageable ischemic area at risk of infarction.

In vivo multicolor molecular MR imaging using diamagnetic chemical exchange saturation transfer liposomes.

A variety of (super)paramagnetic contrast agents are available for enhanced MR visualization of specific tissues, cells, or molecules. To develop alternative contrast agents without the presence of metal ions, liposomes were developed containing simple bioorganic and biodegradable compounds that produce diamagnetic chemical exchange saturation transfer MR contrast. This diamagnetic chemical exchange saturation transfer contrast is frequency-dependent, allowing the unique generation of "multicolor" images.

Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans.

Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts.

Using frequency-labeled exchange transfer to separate out conventional magnetization transfer effects from exchange transfer effects when detecting ParaCEST agents.

Paramagnetic chemical exchange saturation transfer agents combine the benefits of a large chemical shift difference and a fast exchange rate for sensitive MRI detection. However, the in vivo detection of these agents is hampered by the need for high B(1) fields to allow sufficiently fast saturation before exchange occurs, thus causing interference of large magnetization transfer effects from semisolid macromolecules. A recently developed approach named frequency-labeled exchange transfer utilizes excitation pulses instead of saturation pulses for detecting the exchanging protons.

The BOLD post-stimulus undershoot, one of the most debated issues in fMRI.

This paper provides a brief overview of how we got involved in fMRI work and of our efforts to elucidate the mechanisms underlying BOLD signal changes. The phenomenon discussed here in particular is the post-stimulus undershoot (PSU), the interpretation of which has captivated many fMRI scientists and is still under debate to date. This controversy is caused both by the convoluted physiological origin of the BOLD effect, which allows many possible explanations, and the lack of comprehensive data in the early years.

CEST phase mapping using a length and offset varied saturation (LOVARS) scheme.

Chemical exchange saturation transfer MRI is a promising new technique for cellular and molecular imaging. This contrast allows the detection of tumors and ischemia without the use of gadolinium as well as the design of microenvironment-sensitive probes that can be discriminated based on their exchange contrast properties and saturation frequency. Current acquisition schemes to detect and analyze this contrast suffer from sensitivity to spatial B0 inhomogeneity and low contrast-to-noise-ratio, which is an obstacle to widespread adoption of the technology.

A review of the development of Vascular-Space-Occupancy (VASO) fMRI.

Vascular-Space-Occupancy (VASO) fMRI is a non-invasive technique to detect brain activation based on changes in Cerebral Blood Volume (CBV), as opposed to conventional BOLD fMRI, which is based on changes in blood oxygenation. This technique takes advantage of the T1 difference between blood and surrounding tissue, and uses an inversion recovery pulse sequence to null blood signal while maintaining part of the tissue signal. The VASO signal intensity can thus be considered proportional to 1-CBV.

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).

Diffusion tensor imaging of the optic nerve in multiple sclerosis: association with retinal damage and visual disability.

Background And Purpose: There is a well-known relationship between MS and damage to the optic nerve, but advanced, quantitative MR imaging methods have not been applied to large cohorts. Our objective was to determine whether a short imaging protocol (< 10 minutes), implemented with standard hardware, could detect abnormal water diffusion in the optic nerves of patients with MS.

Materials And Methods: We examined water diffusion in human optic nerves via DTI in the largest MS cohort reported to date (104 individuals, including 38 optic nerves previously affected by optic neuritis).

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.