Assessment of acridine orange and SYTO 16 for in vivo imaging of the peritoneal tissues in mice.

The effect of peritoneal injection of acridine orange and SYTO 16 in mice was investigated. Images of peritoneal tissues stained with these dyes and obtained through a confocal micro-endoscope are presented. Seventy-five Balb/c mice were split into five groups and given peritoneal injections of dye or saline. The proportions of negative outcomes in each group were compared using confidence intervals and the Fisher's exact statistical test. A statistically significant increase in adverse events due to dye injection was not observed. These data provide an initial investigation into the safety of acridine orange and SYTO 16 for in vivo imaging.

Spatially varying steady state longitudinal magnetization in distant dipolar field-based sequences.

Sequences based on the distant dipolar field (DDF) have shown great promise for novel spectroscopy and imaging. Unless spatial variation in the longitudinal magnetization, Mz(s), is eliminated by relaxation, diffusion, or spoiling techniques by the end of a single repetition, unexpected results can be obtained due to spatial harmonics in the steady state MzSS(s) profile. This is true even in a homogeneous single-component sample. We have developed an analytical expression for the MzSS(s) profile that occurs in DDF sequences when smearing by diffusion is negligible in the TR period. The expression has been verified by directly imaging the MzSS(s) profile after establishing the steady state.

Cortical mechanisms for acquisition and performance of bimanual motor sequences.

We used functional magnetic resonance imaging to investigate the cortical mechanisms contributing to the acquisition and performance of a complex, bimanual motor sequence. To that aim, five subjects were trained on a difficult, asymmetrical finger opposition task. Their performance rate almost doubled in the course of training and approached the performance rate in an untrained, symmetrical finger opposition task. Before training, performance of the asymmetrical sequence was associated with activity in M1, premotor cortex, supplementary motor cortex, and parietal cortex. After training, performance of the asymmetrical sequence was associated mainly with activity in M1, and little activity outside M1 remained. The latter pattern of cortical activation resembled that observed during the execution of symmetrical sequences, which was unaffected by practice with the asymmetrical sequence. The activation pattern obtained with the symmetrical bimanual sequence was indistinguishable from the combined activation measured in contralateral hemispheres during unimanual control sequences. The data indicate that cortical regions previously implicated in the acquisition of difficult unimanual motor sequences also contribute to the acquisition of asymmetrical bimanual sequences. We found no evidence for an expansion of activity in M1 after acquisition of the asymmetrical sequence (while this has been reported after acquisition of unimanual sequences). In the context of existing literature, the data suggest that the acquisition of unimanual and bimanual motor sequences may rely on similar cortical mechanisms, but that the formation of long-term, procedural memories for the two types of sequences might at least in part depend on different mechanisms.

Sleep-disordered breathing, pharyngeal size and soft tissue anatomy in children.

We tested the hypothesis that pharyngeal geometry and soft tissue dimensions correlate with the severity of sleep-disordered breathing. Magnetic resonance images of the pharynx were obtained in 18 awake children, 7-12 yr of age, with obstructive apnea-hypopnea index (OAHI) values ranging from 1.81 to 24.2 events/h. Subjects were divided into low-OAHI (n = 9) and high-OAHI (n = 9) groups [2.8 +/- 0.7 and 13.5 +/- 4.9 (SD) P < 0.001]. The OAHI correlated positively with the size of the tonsils (r2 = 0.42, P = 0.024) and soft palate (r2 = 0.33, P = 0.049) and inversely with the volume of the oropharyx (r2 = 0.42, P = 0.038). The narrowest point in the pharyngeal airway was smaller in the high-compared with the low-OAHI group (4.4 +/- 1.2 vs. 6.0 +/- 1.3 mm; P = 0.024), and this point was in the retropalatal airway in all but two subjects. The airway cross-sectional area (CSA)-airway length relation showed that the high-OAHI group had a narrower retropapatal airway than the low-OAHI group, particularly in the retropalatal region where the soft palate, adenoids, and tonsils overlap (P = 0.001). The "retropalatal air space," which we defined as the ratio of the retropalatal airway CSA to the CSA of the soft palate, correlated inversely with the OAHI (r2 = 0.49, P = 0.001). We conclude that 7- to 12-yr-old children with a narrow retropalatal air space have significantly more apneas and hypopneas during sleep compared with children with relatively unobstructed retropalatal airways.

Chemical-shift imaging utilizing the positional shifts along the readout gradient direction.

In this work, we describe a method that uses the linear phase acquired during the readout period due to chemical shift to generate individual magnetic resonance (MR) images of chemically shifted species. The method utilizes sets of Fourier (or k-space) data acquired with different directions of the readout gradient and a postprocessing algorithm to generate chemical shift images. The methodology is developed for both Cartesian data acquisition and for radial data acquisition. The method is presented here for two chemically shifted species but it can be extended to more species. In this work, we present the theory, show the results in phantoms and in human images, and discuss the artifacts and signal-to-noise ratio of the images obtained with the technique.

MRI study of pharyngeal airway changes during stimulation of the hypoglossal nerve branches in rats.

The medial branch (Med) of the hypoglossal nerve innervates the tongue protrudor muscles, whereas the lateral branch (Lat) innervates tongue retractor muscles. Our previous finding that pharyngeal airflow increased during either selective Med stimulation or whole hypoglossal nerve (WHL) stimulation (coactivation of protrudor and retractor muscles) led us to examine how WHL, Med, or Lat stimulation affected tongue movements and nasopharyngeal (NP) and oropharyngeal (OP) airway volume. Electrical stimulation of either WHL, Med, or Lat nerves was performed in anesthetized, tracheotomized rats while magnetic resonance images of the NP and OP were acquired (slice thickness 0.5 mm, in-plane resolution 0.25 mm). NP and OP volume was greater during WHL and Med stimulation vs. no stimulation (P < 0.05). Ventral tongue depression (measured in the midsagittal images) and OP volume were greater during Med stimulation than during WHL stimulation (P < 0.05). Lat stimulation did not alter NP volume (P = 0.39). Our finding that either WHL or Med stimulation dilates the NP and OP airways sheds new light on the control of pharyngeal airway caliber by extrinsic tongue muscles and may lead to new treatments for patients with obstructive sleep apnea.

Adaptive reconstruction of phased array MR imagery.

An adaptive implementation of the spatial matched filter and its application to the reconstruction of phased array MR imagery is described. Locally relevant array correlation statistics for the NMR signal and noise processes are derived directly from the set of complex individual coil images, in the form of sample correlation matrices. Eigen-analysis yields an optimal filter vector for the estimated signal and noise array correlation statistics. The technique enables near-optimal reconstruction of multicoil MR imagery without a-priori knowledge of the individual coil field maps or noise correlation structure. Experimental results indicate SNR performance approaching that of the optimal matched filter. Compared to the sum-of-squares technique, the RMS noise level in dark image regions is reduced by as much as the square root of N, where N is the number of coils in the array. The technique is also effective in suppressing localized motion and flow artifacts.

Reconstruction of MR images from data acquired on a general nonregular grid by pseudoinverse calculation.

A minimum-norm least-squares image-reconstruction method for the reconstruction of magnetic resonance images from non-Cartesian sampled data is proposed. The method is based on a general formalism for continuous-to-discrete mapping and pseudoinverse calculation. It does not involve any regridding or interpolation of the data and therefore the methodology differs fundamentally from existing regridding-based methods. Moreover, the method uses a continuous representation of objects in the image domain instead of a discretized representation. Simulations and experiments show the possibilities of the method in both radial and spiral imaging. Simulations revealed that minimum-norm least-squares image reconstruction can result in a drastic decrease of artifacts compared with regridding-based reconstruction. Besides, both in vivo and phantom experiments showed that minimum-norm least-squares image reconstruction leads to contrast improvement and increased signal-to-noise ratio compared with image reconstruction based on regridding. As an appendix, an analytical calculation of the raw data corresponding to the well-known Shepp and Logan software head phantom is presented.

Multispectral imaging with a confocal microendoscope.

The concept of a multispectral confocal microscope for in vivo imaging is introduced. To demonstrate the concept we modified a slit-scan fluorescence confocal microendoscope incorporating a fiber-optic catheter for in vivo imaging to record multispectral images. The system was designed to examine cellular structures during optical biopsy and to exploit the diagnostic information contained within the spectral domain. Preliminary experiments were carried out in phantoms and cell cultures to demonstrate the potential of the technique.

High-resolution diffusion imaging with DIFRAD-FSE (diffusion-weighted radial acquisition of data with fast spin-echo) MRI.

A novel MRI method, DIFRAD-FSE (diffusion-weighted radial acquisition of data with fast spin-echo), is demonstrated that enables rapid, high-resolution multi-shot diffusion-weighted MRI without significant artifacts due to motion. Following a diffusion-weighting spin-echo preparation period, multiple radial lines of Fourier data are acquired using spin-echo refocusing. Images can be reconstructed from the radial data set using a magnitude-only filtered back-projection reconstruction algorithm that removes phase errors due to motion. Results from human brain imaging demonstrate the ability of DIFRAD-FSE to acquire multiple radial lines of Fourier data each TR period without significant artifacts due to relaxation and to produce high-resolution diffusion-weighted MRI images without significant artifacts from motion.

Quantitative phase contrast images to quantitate flow in a rat model of microgravity.

A magnetic resonance angiographic (MRA) technique for noninvasive measurement of flow in the inferior vena cava (IVC) was used to study blood flow changes in a simulated microgravity model. Microgravity was simulated in adult male Fischer 344 rats (n = 12, with each rat acting as its own control) using a tail harness to elevate the hindquarters, producing a non-weight bearing hindlimb (NWH) model. Quantitative phase contrast images of flow within the IVC were obtained initially and after a 2-week NWH protocol. Inferior vena cava blood flow was determined by converting the intensity at the respective magnetic resonance pixels into a corresponding flow by Doppler techniques. Average values for flow determined with MR angiography were 351.8 (SEM = 49) mm3 x s(-1) initially and 524.5 (SEM = 46) mm3 x s(-1) after exposure to 2 weeks of the NWH protocol. Post 2-week NWH flow increased 49.1% over the initial NWH value. Using a paired t-test, a significant difference was found between the rats' IVC flow values in the initial and post-NWH groups (p < 0.004). The changes in IVC blood flow due to 45 degrees NWH may contribute to the overall changes observed in the cardiovascular system during simulated microgravity.

Slit-scanning confocal microendoscope for high-resolution in vivo imaging.

We discuss the design and construction of a novel imaging system in which a fiber-optic imaging bundle and miniature optical and mechanical components are used to allow confocal fluorescence microscopy in remote locations. The instrumentation has been developed specifically for cellular examination of tissue for optical biopsy. Miniaturization of various components makes the device usable in a clinical setting. The numerical aperture of the beam in the tissue is 0.5, and the field of view is 430 microm. The measured lateral resolution of the system is 3.0 microm. The axial point and the axial planar response functions of the confocal system were measured with a FWHM of 10 and 25 microm, respectively. In vitro and in vivo images obtained with cell cultures, human tissue specimens, and animal models indicate that the performance of the device is adequate for microscopic evaluation of cells.

Image manipulation and error estimation for MRI analysis.

Manipulation of MRI images prior to volumetric analysis is a common practice that may unwittingly lead to errors in measurement. In this study, we examine the effects of two types of image manipulation: changes in the total number of slices used to obtain volume estimates (slice sampling rate) and image rotation. A phantom containing two regularly-shaped and two irregularly-shaped regions of interest (ROIs) was scanned using an SPGR sequence and 1-mm slices. Changes in slice sampling rate produced marked effects on volume estimation of irregularly-shaped ROls. Comparatively little error was associated with changes in slice sampling rates for regularly-shaped ROIs. In addition, there was an interaction between image rotation in non-orthogonal planes and slice sampling rate. The data suggests that the ability to detect anatomical effects may be influenced by an investigator's choices concerning the number of slices included in a region of interest and image rotation when estimating volumes.

MRI and NMR spectroscopy of the lipids of atherosclerotic plaque in rabbits and humans.

The early stages of atherosclerosis are characterized by the deposition of cholesteryl esters and triglycerides into the arterial wall. In the excised human atherosclerotic plaque these lipids are in a liquid-like state at body temperature and observable via MRI and NMR spectroscopy. To assess the ability of MRI to quantitatively image the lipids of atherosclerotic plaque in vivo, we have investigated eight New Zealand White rabbits fed atherogenic diets (2 weight (wt)% cholesterol, 1 wt% cholesterol + 6 wt% peanut oil, and 1 wt% cholesterol + 6 wt% com oil). Postmortem examination indicated that all rabbits developed atherosclerosis in the aorta. Except for one animal, magnetic resonance angiography showed no noticeable obstruction in the aorta. MRI was carried out in an attempt to image atherosclerotic plaque lipids directly, but no signal was detected in vivo. However, a plaque lipid signal was observed from excised tissue using a small diameter RF coil. 1H NMR spectroscopy of the atherosclerotic plaque from excised aortas indicated that the major fraction of plaque lipids in rabbits is not in a liquid state at physiological temperature and are only marginally MRI-visible compared to human plaque lipid. The differences in the MRI characteristics of rabbit and human plaque are due to differences in the fatty acid profile of the cholesteryl esters, chiefly a decrease of linoleic acid in rabbit lesions.

Analysis and comparison of motion-correction techniques in diffusion-weighted imaging.

Motion continues to be a significant problem in MRI, producing image artifacts that can severely degrade image quality. In diffusion-weighted imaging (DWI), the problem is amplified by the presence of large gradient fields used to produce the diffusion weighting. Three correction methods applicable for correction of specific classes of motion are described and compared. The first is based on a generalised projection onto convex sets (GPOCS) postprocessing algorithm. The second technique uses the collection of navigator echoes to track phase errors. The third technique is based on a radial-scan data acquisition combined with a modified projection-reconstruction algorithm. Although each technique corrects well for translations, the radial-scan method proves to be more robust when more complex motions are present. A detailed description of the causes of MR data errors caused by rigid body motion is included as an appendix.

Hemodialysis increases apparent diffusion coefficient of brain water in nephrectomized rats measured by isotropic diffusion-weighted magnetic resonance imaging.

The nature of brain edema in dialysis disequilibrium syndrome (DDS) was investigated by diffusion-weighted magnetic resonance imaging (DWI). DWI was performed on normal or bilaterally nephrectomized rats before, and immediately after, hemodialysis. Hemodialysis was performed with a custom-made dialyzer (surface area 150 cm2) against a bicarbonate-buffered bath for 90 min with or without 70 mM urea. Hemodialysis with non-urea bath decreased plasma urea by 21 mM, and plasma osmolality by 22 mosmol/kg H2O, and increased brain water content by 8.0% (all < 0.05), while hemodialysis with urea bath did not affect plasma urea, osmolality, or brain water content. Three sets of axial DWI images of the brain were obtained at different gradient weighing factors with an in-plane resolution of 0.39 mm2. The apparent diffusion coefficient (Dapp) of the brain water was not affected by bilateral nephrectomy, or by hemodialysis in normal rats. In nephrectomized rats, brain Dapp was significantly increased after dialysis with non-urea bath (1.15 +/- 0.08 vs 0.89 +/- 0.07 x 10(-9)m2/sec, P < 0.01). No significant changes of brain water Dapp could be observed after dialysis with urea bath. The increased Dapp associated with DDS indicates that brain extracellular water increases and/or intracellular water decreases after hemodialysis. Our results strongly suggest that the brain edema induced by hemodialysis in uremic rats is due to interstitial edema rather than cytotoxic edema. Furthermore, our results support a primary role for the "reverse urea effect" in the pathogenesis of brain edema in DDS.DWI may be a useful diagnostic tool for DDS in patients with end-stage renal disease.

Microbubbles as novel pressure-sensitive MR contrast agents.

Magnetic resonance imaging contrast agents that are sensitive to pressure would be useful for evaluating cardiovascular function. One such potential contrast agent consists of gas-filled liposome microbubbles. The magnetic susceptibility of the microbubbles locally perturb the static magnetic field, which influences the transverse-relaxation properties of the surrounding medium. Changes in the pressure alter the bubble dimensions, which affects the magnetic field perturbations and, hence, the transverse-relaxation. The effect of these microbubbles on the T2 relaxation times of a water-based medium was measured for liposomes filled with different gases-nitrogen, argon, air, oxygen, xenon, neon, perfluoropentane, perfluorobutane, and sulfur hexafluoride. The air-filled, perfluoropentane-filled and the oxygen-filled liposomes demonstrated the largest effect on transverse-relaxation. The influence of pressure on both gradient-echo and spin-echo signal intensities for air-filled microbubbles was also evaluated. Pressure-induced changes in signal intensity were consistently observed for both the spin-echo and gradient-echo pulses sequences.

A real-time reconstruction system for magnetic resonance imaging.

A digital-electronic reconstruction system for MRI has been designed and demonstrated. The system is capable of reconstructing a 128 x 128 pixel image from complex-valued data in approximately 8 ms (122 frames per second) or a 256 x 256 pixel image in 32 ms (30 frames per second) using the standard 2D FFT reconstruction algorithm. Real-time MR imaging can be obtained when this reconstruction system is coupled with fast continuous echo-planar type data acquisition. This provides the unique potential for real-time monitoring of interventional procedures or for rapid patient positioning. The real-time reconstruction system presented here consists of four main subsystems: an analog to digital converter, an interface memory, the Fourier processor, and the display processor. The basic design of this reconstruction system is presented along with results, demonstrating the capability of the system.