Characterization of the atherosclerotic carotid bifurcation using MRI, finite element modeling, and histology.

Atherogenesis is known to be associated with the stresses that act on or within the arterial wall. Still, the uneven distribution of atherosclerotic lesions and the impact of vessel remodeling on disease progression are poorly understood. A methodology is proposed to study the correlations between fluid dynamic parameters and histological markers of atherosclerosis. Trends suggested by preliminary data from four patients with advanced carotid bifurcation arterial disease are examined and compared to hypotheses in the literature. Four patients were scanned using MRI and ultrasound, and subsequently underwent carotid endarterectomy. For each patient. a geometric model and a numerical mesh were constructed from MR data, and velocity boundary conditions established. Computations yield values for average wall shear stress (WSS), maximum wall shear stress temporal gradient (WSSTG), and Oscillatory Shear Index (OSI). Following surgery, the excised plaques were sectioned, stained for smooth muscle cells (SMC), macrophages (M phi), lipid (LIP), and collagen (COL), and analyzed quantitatively. Correlations attempted between the various fluid dynamic variables and the biological markers were interesting but inconclusive. Tendencies of WSSTG and WSS to correlate negatively with M phi and LIP, and positively with COL and SMC, as well as tendencies of OSI to correlate positively with Mphi and LIP and negatively with COL and SMC, were observed. These trends agree with hypotheses in the literature, which are based on ex vivo and in vitro experimental studies.

Hemodynamics and wall mechanics in human carotid bifurcation and its consequences for atherogenesis: investigation of inter-individual variation.

Finite element simulations of fluid-solid interactions were used to investigate inter-individual variations in flow dynamics and wall mechanics at the carotid artery bifurcation, and its effects on atherogenesis, in three healthy humans (normal volunteers: NV1, NV2, NV4). Subject-specific calculations were based on MR images of structural anatomy and ultrasound measurements of flow at domain boundaries. For all subjects, the largest contiguous region of low wall shear stress (WSS) occurred at the carotid bulb, WSS was high (6-10 Pa) at the apex, and a small localized region of WSS > 10 Pa occurred close to the inner wall of the external carotid artery (ECA). NV2 and NV4 had a "spot" of low WSS distal to the bifurcation at the inner wall of the ECA. Low WSS patches in the common carotid artery (CCA) were contiguous with the carotid bulb low WSS region in NV1 and NV2, but not in NV4. In all three subjects, areas of high oscillatory shear index (OSI) were confined to regions of low WSS. Only NV4 exhibited high levels of OSI on the external adjoining wall of the ECA and CCA. For all subjects, the maximum wall shear stress temporal gradient (WSSTG) was highest at the flow divider (reaching 1,000 Pa/s), exceeding 300 Pa/s at the walls connecting the ECA and CCA, but remaining below 250 Pa/s outside of the ECA. In all subjects, (maximum principle) cyclic strain (CS) was greatest at the apex (NV1: 14%; NV2: 11%; NV4: 6%), and a second high CS region occurred at the ECA-CCA adjoining wall (NV1: 11%, NV2: 9%, NV4: 5%). Wall deformability was included in one simulation (NV2) to verify that it had little influence on the parameters studied. Location and magnitude of low WSS were similar, except for the apex (differences of up to 25%). Wall distensibility also influenced OSI, doubling it in most of the CCA, separating the single high OSI region of the carotid bulb into two smaller regions, and shrinking the ECA internal and external walls' high OSI regions. These observations provide further evidence that significant intra-subject variability exists in those factors thought to impact atherosclerosis.

A system for low field imaging of laser-polarized noble gas.

We describe a device for performing MRI with laser-polarized noble gas at low magnetic fields (<50 G). The system is robust, portable, inexpensive, and provides gas-phase imaging resolution comparable to that of high field clinical instruments. At 20.6 G, we have imaged laser-polarized (3)He (Larmor frequency of 67 kHz) in both sealed glass cells and excised rat lungs, using approximately 0.1 G/cm gradients to achieve approximately 1 mm(2) resolution. In addition, we measured (3)He T(2)(*) times greater than 100 ms in excised rat lungs, which is roughly 20 times longer than typical values observed at high ( approximately 2 T) fields. We include a discussion of the practical considerations for working at low magnetic fields and conclude with evidence of radiation damping in this system.

Consequences of (129)Xe-(1)H cross relaxation in aqueous solutions.

We have investigated the transfer of polarization from (129)Xe to solute protons in aqueous solutions to determine the feasibility of using hyperpolarized xenon to enhance (1)H sensitivity in aqueous systems at or near room temperatures. Several solutes, each of different molecular weight, were dissolved in deuterium oxide and although large xenon polarizations were created, no significant proton signal enhancement was detected in l-tyrosine, alpha-cyclodextrin, beta-cyclodextrin, apomyoglobin, or myoglobin. Solute-induced enhancement of the (129)Xe spin-lattice relaxation rate was observed and depended on the size and structure of the solute molecule. The significant increase of the apparent spin-lattice relaxation rate of the solution phase (129)Xe by alpha-cyclodextrin and apomyoglobin indicates efficient cross relaxation. The slow relaxation of xenon in beta-cyclodextrin and l-tyrosine indicates weak coupling and inefficient cross relaxation. Despite the apparent cross-relaxation effects, all attempts to detect the proton enhancement directly were unsuccessful. Spin-lattice relaxation rates were also measured for Boltzmann (129)Xe in myoglobin. The cross-relaxation rates were determined from changes in (129)Xe relaxation rates in the alpha-cyclodextrin and myoglobin solutions. These cross-relaxation rates were then used to model (1)H signal gains for a range of (129)Xe to (1)H spin population ratios. These models suggest that in spite of very large (129)Xe polarizations, the (1)H gains will be less than 10% and often substantially smaller. In particular, dramatic (1)H signal enhancements in lung tissue signals are unlikely.

Low-field MRI of laser polarized noble gas.

NMR images of laser polarized 3He gas were obtained at 21 G using a simple, homebuilt instrument. At such low fields magnetic resonance imaging (MRI) of thermally polarized samples (e.g., water) is not practical. Low-field noble gas MRI has novel scientific, engineering, and medical applications. Examples include portable systems for diagnosis of lung disease, as well as imaging of voids in porous media and within metallic systems.

MR imaging and spectroscopy using hyperpolarized 129Xe gas: preliminary human results.

Using a new method of xenon laser-polarization that permits the generation of liter quantities of hyperpolarized 129Xe gas, the first 129Xe imaging results from the human chest and the first 129Xe spectroscopy results from the human chest and head have been obtained. With polarization levels of approximately 2%, cross-sectional images of the lung gas-spaces with a voxel volume of 0.9 cm3 (signal-to-noise ratio (SNR), 28) were acquired and three dissolved-phase resonances in spectra from the chest were detected. In spectra from the head, one prominent dissolved-phase resonance, presumably from brain parenchyma, was detected. With anticipated improvements in the 129Xe polarization system, pulse sequences, RF coils, and breathing maneuvers, these results suggest the possibility for 129Xe gas-phase imaging of the lungs with a resolution approaching that of current conventional thoracic proton imaging. Moreover, the results suggest the feasibility of dissolved-phase imaging of both the chest and brain with a resolution similar to that obtained with the gas-phase images.

1H magnetic cross-relaxation between multiple solvent components and rotationally immobilized protein.

Magnetic cross-relaxation spectra or Z-spectra are presented for water, acetone, methanol, dimethylsulfoxide, and acetonitrile in cross-linked bovine serum albumin gels. Each solvent studied, reports the same Z-spectrum linewidth and shape for the solid component that follows from solutions of the coupled relaxation equations. The Z-spectra demonstrate competition among solvents for specific protein binding sites. The rate of magnetization transfer in the rotationally immobilized protein environment is approximated by 1/T2 for the solid component, which is shown to account for the observed magnetization transfer rates in the systems studied. The temperature dependence of the Z-spectra are different for water compared with the organic solvents. The cross-relaxation efficiency in the organic solvents decreases with increasing temperature because molecules bind less well at high temperature. For water, the hydrogen exchange path becomes increasingly important relative to the whole molecule path with increasing temperature, which improves the net cross-relaxation efficiency.

Simultaneous measurement of vesicle diffusion coefficients and trapping efficiencies by means of diffusion ordered 2D NMR spectroscopy.

It is demonstrated that the fraction of sucrose entrapped in the aqueous compartment of phospholipid vesicles and the tracer diffusion coefficient of the vesicles can be determined simultaneously with diffusion ordered 2D NMR spectroscopy (DOSY). The sizes of the vesicles are related to the diffusion coefficients by the Stokes-Einstein equation. This method displays 1H-NMR peaks for sucrose in the diffusion dimension at positions corresponding to free and entrapped sucrose, and the areas of these peaks are proportional to the amount of free and entrapped sucrose, respectively. The results were verified by a 1D NMR experiment in which the sucrose peaks were integrated before and after dialysis to remove the external sucrose.