Joseph S. Gillen

Water saturation shift referencing (WASSR) for chemical exchange saturation transfer (CEST) experiments.

Chemical exchange saturation transfer (CEST) is a contrast mechanism that exploits exchange‐based magnetization transfer (MT) between solute and water protons. CEST effects compete with direct water saturation and conventional MT processes, and generally can only be quantified through an asymmetry analysis of the water saturation spectrum (Z‐spectrum) with respect to the water frequency, a process that is exquisitely sensitive to magnetic field inhomogeneities. Here it is shown that direct water saturation imaging allows measurement of the absolute water frequency in each voxel, allowing proper centering of Z‐spectra on a voxel‐by‐voxel basis independently of spatial B0 field variations. Optimal acquisition parameters for this “water saturation shift referencing” (WASSR) approach were estimated using Monte Carlo simulations and later confirmed experimentally. The optimal ratio of the WASSR sweep width to the linewidth of the direct saturation curve was found to be 3.3–4.0, requiring a sampling of 16–32 points. The frequency error was smaller than 1 Hz at signal‐to‐noise ratios of 40 or higher. The WASSR method was applied to study glycogen, where the chemical shift difference between the hydroxyl (OH) protons and bulk water protons at 3T is so small (0.75–1.25 ppm) that the CEST spectrum is inconclusive without proper referencing. Magn Reson Med, 2008.

Magnetic Resonance Imaging of Children Without Sedation: Preparation With Simulation

OBJECTIVE It was hypothesized that a scanner simulator that replicates the magnetic resonance imaging (MRI) environment could be used to prepare pediatric subjects for successful completion of a diagnostic-quality MRI examination without pharmacological sedation. METHOD Sixteen healthy children, 6 to 17 years of age, were matched for age and sex with 16 psychotropic medication-naive children with obsessive-compulsive disorder. Distress was measured throughout simulation and scanning procedures using heart rate and a self-report distress scale. Ten healthy children, 6 to 17 years of age, also underwent the same actual MRI scanning procedure but did not undergo the simulation scanning procedure. RESULTS Significant decreases in heart rate and self-reported distress level were observed in all subjects during the simulator session that were maintained to the end of the actual scanner experience. All subjects successfully completed MRI examinations without chemical restraint. Subjects who were not trained in the simulator had higher heart rates and self-reported distress levels in the actual scanner than did simulation-trained subjects. CONCLUSIONS Simulation without pharmacological sedation successfully prepared pediatric subjects in this pilot study for high-quality MRI studies. Subject preparation may be an alternative procedure to sedation for routine MRI examination in healthy and anxious children 6 years of age and older.

Venous blood effects in spin-echo fMRI of human brain.

The spin‐echo response to visual activation was studied as a function of spatial resolution at a field of 1.5 T. The results showed that the increase in absolute T2 upon activation was as large as 22.8 ± 3.1% (P < 0.05) at the highest resolution (5.3 mm3), while it was as small as 3.5 ± 0.2% (P < 0.05) at the lowest resolution (42.2 mm3). In addition, upon increasing resolution, the spin‐echo signal decay as a function of echo time changed from monoexponential to nonexponential. These data indicate that, when using the standard resolution for fMRI studies at 1.5 T, the effects of spin‐echo changes in the draining veins are of major contribution to the total blood oxygenation level‐dependent (BOLD) signal changes measured in voxels encompassing the activated brain areas. The data can be quantitatively accounted for using a model based on the intravascular origin of the spin‐echo effect including both macrovascular and microvascular effects. Existing theories for the spin‐echo BOLD effect based on diffusion through field gradients predict negligible spin‐echo effects inside the large vessels and are therefore incompatible with the data. Magn Reson Med 42:617–626, 1999.

Determination of Oxygen Extraction Ratios by Magnetic Resonance Imaging

The oxygen extraction ratio (OER) of a tissue describes the interplay between oxygen delivery and consumption and, as such, directly reflects the viability and activity of any organ. It is shown that OER can be quantified using a single magnetic resonance imaging observable, namely the relaxation time T2 of venous blood draining from the tissue. This principle is applied to study local OER changes in the brain on visual stimulation in humans, unambiguously demonstrating a mismatch between changes in blood flow and oxygen metabolism on activation.

Comparison of the Rates of Adverse Drug Reactions: Ionic Contrast Agents, Ionic Agents Combined with Steroids, and Nonionic Agents

The influence of ionic agents alone, of diatrizoate plus two oral doses of methylprednisolone premedication, and of a nonionic agent (iohexol) upon the frequency and severity of adverse drug reactions (ADRs) was compared in ten hospitals during three separate time periods from 1985 to 1989. Nonionic agents were found to reduce significantly total ADRs; 52 of 8857 patients receiving nonionic agents experienced reactions, versus 263 of 6006 patients for ionics (P less than .0001). The frequency of reactions classed as mild (2.9% for ionic agents versus 0.476 for nonionic agents: P less than .001), moderate (1.2% versus 0.1%; P less than .001), or severe (0.37% versus 0.01%; P less than .001), also favored nonionic agents. Steroid premedication provided some protection, but iohexol was significantly better with respect to mild reactions (2.9% versus 0.4%, P less than .001), moderate reactions (0.9% versus 0.1%, P less than .01), and severe reactions (0.25% versus 0.01%, P less than .01). The contrast medium was the greatest risk factor for adverse reaction (odds ratio 7.3), while prior contrast reaction (odds ratio 6.25), and hay fever (odds ratio 2.3) were found to be significant independent risks. We conclude that nonionic agents are safer for intravenous use than ionic agents given alone or with corticosteroid premedication.

Optimization of SABRE for polarization of the tuberculosis drugs pyrazinamide and isoniazid

Hyperpolarization produces nuclear spin polarization that is several orders of magnitude larger than that achieved at thermal equilibrium thus providing extraordinary contrast and sensitivity. As a parahydrogen induced polarization (PHIP) technique that does not require chemical modification of the substrate to polarize, Signal Amplification by Reversible Exchange (SABRE) has attracted a lot of attention. Using a prototype parahydrogen polarizer, we polarize two drugs used in the treatment of tuberculosis, namely pyrazinamide and isoniazid. We examine this approach in four solvents, methanol-d4, methanol, ethanol and DMSO and optimize the polarization transfer magnetic field strength, the temperature as well as intensity and duration of hydrogen bubbling to achieve the best overall signal enhancement and hence hyperpolarization level.

MRI Magnetic Field Stimulates Rotational Sensors of the Brain

Vertigo in and around magnetic resonance imaging (MRI) machines has been noted for years [1, 2]. Several mechanisms have been suggested to explain these sensations [3, 4], yet without direct, objective measures, the cause is unknown. We found that all of our healthy human subjects developed a robust nystagmus while simply lying in the static magnetic field of an MRI machine. Patients lacking labyrinthine function did not. We use the pattern of eye movements as a measure of vestibular stimulation to show that the stimulation is static (continuous, proportional to static magnetic field strength, requiring neither head movement nor dynamic change in magnetic field strength) and directional (sensitive to magnetic field polarity and head orientation). Our calculations and geometric model suggest that magnetic vestibular stimulation (MVS) derives from a Lorentz force resulting from interaction between the magnetic field and naturally occurring ionic currents in the labyrinthine endolymph fluid. This force pushes on the semicircular canal cupula, leading to nystagmus. We emphasize that the unique, dual role of endolymph in the delivery of both ionic current and fluid pressure, coupled with the cupulas function as a pressure sensor, makes magnetic-field-induced nystagmus and vertigo possible. Such effects could confound functional MRI studies of brain behavior, including resting-state brain activity.

Proton spectroscopic imaging of human brain

Abstract Signals from water and fat can cause artifacts in proton spectroscopic imaging in the human brain. The major problem is variation of the B0 field over a range of several ppm within the sensitive volume of the standard whole-head coil. Here, the coherence-pathway formalism is used to describe and evaluate the origin of artifacts in a double spin-echo (PRESS) sequence. The attenuation of unwanted coherences using pulsed field gradients is described for homogeneous and inhomogeneous B0 fields. The effect of the following parameters on the quality of the spectroscopic images is analyzed: (a) directional order of plane selection, (b) positioning of phase-encode gradients in the sequence, (c) postprocessing spatial windowing, and (d) motion. It is shown that, for a typical echo time of 272 ms, it is not necessary to first select a region of interest within the brain borders when sufficient phase-encode steps are used. Examples of 2D proton spectroscopic images with a nominal voxel volume of 0.85 ml are given for a healthy volunteer and a patient with a low-grade glioma.

fMRI Evidence for Multisensory Recruitment Associated With Rapid Eye Movements During Sleep

We studied the neural correlates of rapid eye movement during sleep (REM) by timing REMs from video recording and using rapid event‐related functional MRI. Consistent with the hypothesis that REMs share the brain systems and mechanisms with waking eye movements and are visually‐targeted saccades, we found REM‐locked activation in the primary visual cortex, thalamic reticular nucleus (TRN), ‘visual claustrum’, retrosplenial cortex (RSC, only on the right hemisphere), fusiform gyrus, anterior cingulate cortex, and the oculomotor circuit that controls awake saccadic eye movements (and subserves awake visuospatial attention). Unexpectedly, robust activation also occurred in non‐visual sensory cortices, motor cortex, language areas, and the ascending reticular activating system, including basal forebrain, the major source of cholinergic input to the entire cortex. REM‐associated activation of these areas, especially non‐visual primary sensory cortices, TRN and claustrum, parallels findings from waking studies on the interactions between multiple sensory data, and their ‘binding’ into a unified percept, suggesting that these mechanisms are also shared in waking and dreaming and that the sharing goes beyond the expected visual scanning mechanisms. Surprisingly, REMs were associated with a decrease in signal in specific periventricular subregions, matching the distribution of the serotonergic supraependymal plexus. REMs might serve as a useful task‐free probe into major brain systems for functional brain imaging. Hum Brain Mapp 2009.

Noninvasive quantification of total sodium concentrations in acute reperfused myocardial infarction using 23Na MRI

The transport of sodium and potassium between the intra‐ and extracellular pools and the maintenance of the transmembrane concentration gradients are important to cell function and integrity. The early disruption of the sodium pump in myocardial infarction in response to the exhaustion of energy reserves following ischemia and reperfusion results in increased intracellular (and thus total) sodium levels. In this study a method for noninvasively quantifying myocardial sodium levels directly from sodium (23Na) MRI is presented. It was used to measure total myocardial sodium on a clinical 1.5T system in six normal dogs and five dogs with experimentally‐induced myocardial infarction (MI). The technique was validated by comparing total sodium content measured by 23Na MRI with that measured by atomic absorption spectrophotometry (AAS) in biopsied tissue. Total sodium measured by 23Na MRI was significantly elevated in regions of infarction (81.3 ± 14.3 mmol/kg wet wt, mean ± SD) compared to noninfarcted myocardial tissue from both infarcted dogs (36.2 ± 1.1, P < 0.001) and from normal controls (34.4 ± 2.8, P < 0.0001). Myocardial tissue sodium content as measured by 23Na MRI did not vary regionally in the lateral, anterior, or inferior regions in normal hearts (ANOVA, P = NS). Sodium content measured by 23Na MRI agreed with the mean AAS estimates of 31.3 ± 5.6 mmol/kg wet wt (P = NS) in normal hearts, and did not differ significantly from AAS measurements in MI (P = NS). Thus, local tissue sodium levels can be accurately quantified noninvasively using 23Na MRI in normal and acutely reperfused MI. The detection of regional myocardial sodium elevations may help differentiate viable from nonviable, infarcted tissue. Magn Reson Med 46:1144–1151, 2001.