Vahid Vahdat

Improved Technique for Measurement of Regional Fractional Ventilation by Hyperpolarized 3He MRI

Quantitative measurement of regional lung ventilation is of great significance in assessment of lung function in many obstructive and restrictive pulmonary diseases. A new technique for regional measurement of fractional ventilation using hyperpolarized 3He MRI is proposed, addressing the shortcomings of an earlier approach that limited its use to small animals. The new approach allows for the acquisition of similar quantitative maps over a shortened period and requires substantially less 3He gas. This technique is therefore a better platform for implementation in large species, including humans. The measurements using the two approaches were comparable to a great degree, as verified in a healthy rat lung, and are very reproducible. Preliminary validation is performed in a lung phantom system. Volume dependency of measurements was assessed both in vivo and in vitro. A scheme for selecting an optimum flip angle is proposed. In addition, a dead space modeling approach is proposed to yield more accurate measurements of regional fractional ventilation using either method. Finally, sensitivity of the new technique to model parameters, noise, and number of included images were assessed numerically. As a prelude to application in humans, the technique was implemented in a large animal study successfully. Magn Reson Med, 2010.

Hyperpolarized 13C MRI of the pulmonary vasculature and parenchyma

The study of lung perfusion in normal and diseased subjects is of great interest to physiologists and physicians. In this work we demonstrate the application of a liquid‐phase hyperpolarized (HP) carbon‐13 (13C) tracer to magnetic resonance imaging (MRI) of the pulmonary vasculature and pulmonary perfusion in a porcine model. Our results show that high spatial and temporal resolution images of pulmonary perfusion can be obtained with this contrast technique. Traditionally, pulmonary perfusion measurement techniques have been challenging because of insufficient signal for quantitative functional assessments. The use of polarized 13C in MRI overcomes this limitation and may lead to a viable clinical method for studying the pulmonary vasculature and perfusion. Magn Reson Med 57:459–463, 2007.

Atomic-Scale Wear of Amorphous Hydrogenated Carbon during Intermittent Contact: A Combined Study Using Experiment, Simulation, and Theory

In this study, we explore the wear behavior of amplitude modulation atomic force microscopy (AM-AFM, an intermittent-contact AFM mode) tips coated with a common type of diamond-like carbon, amorphous hydrogenated carbon (a-C:H), when scanned against an ultra-nanocrystalline diamond (UNCD) sample both experimentally and through molecular dynamics (MD) simulations. Finite element analysis is utilized in a unique way to create a representative geometry of the tip to be simulated in MD. To conduct consistent and quantitative experiments, we apply a protocol that involves determining the tip-sample interaction geometry, calculating the tip-sample force and normal contact stress over the course of the wear test, and precisely quantifying the wear volume using high-resolution transmission electron microscopy imaging. The results reveal gradual wear of a-C:H with no sign of fracture or plastic deformation. The wear rate of a-C:H is consistent with a reaction-rate-based wear theory, which predicts an exponential dependence of the rate of atom removal on the average normal contact stress. From this, kinetic parameters governing the wear process are estimated. MD simulations of an a-C:H tip, whose radius is comparable to the tip radii used in experiments, making contact with a UNCD sample multiple times exhibit an atomic-level removal process. The atomistic wear events observed in the simulations are correlated with under-coordinated atomic species at the contacting surfaces.

A simple and low-cost device for generating hyperpolarized contrast agents using parahydrogen.

A detailed description of the construction and use of a device for hyperpolarization of select contrast agents is presented. The device is based on molecular incorporation of the spin‐order inherent to parahydrogen, followed by order transfer to a metastable heteronuclear alignment. Design considerations and experimental results relating to catalyst/solvent choice and handling, solvent heating, efficient gas entrainment and spin‐order transfer are described. The resulting degree of hyperpolarization is shown to be substantial, ranging from a few to over 50%, depending on the choice of target molecule. Finally, the use of the hyperpolarized agent is demonstrated in a series of in vivo images. Copyright

Quantitative assessment of emphysema using hyperpolarized 3He magnetic resonance imaging

In this experiment, Sprague–Dawley rats with elastase‐induced emphysema were imaged using hyperpolarized 3He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash‐in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague–Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients. Magn Reson Med 53:1341–1346, 2005.

Mechanics of interaction and atomic-scale wear of amplitude modulation atomic force microscopy probes.

Wear is one of the main factors that hinders the performance of probes for atomic force microscopy (AFM), including for the widely used amplitude modulation (AM-AFM) mode. Unfortunately, a comprehensive scientific understanding of nanoscale wear is lacking. We have developed a protocol for conducting consistent and quantitative AM-AFM wear experiments. The protocol involves controlling the tip-sample interaction regime during AM-AFM scanning, determining the tip-sample contact geometry, calculating the peak repulsive force and normal stress over the course of the wear test, and quantifying the wear volume using high-resolution transmission electron microscopy imaging. The peak repulsive tip-sample interaction force is estimated from a closed-form equation accompanied by an effective tip radius measurement procedure, which combines transmission electron microscopy and blind tip reconstruction. The contact stress is estimated by applying Derjaguin-Müller-Toporov contact mechanics model and also numerically solving a general contact mechanics model recently developed for the adhesive contact of arbitrary axisymmetric punch shapes. We discuss the important role that the assumed tip shape geometry plays in calculating both the interaction forces and the contact stresses. Contact stresses are significantly affected by the tip geometry while the peak repulsive force is mainly determined by experimentally controlled parameters, specifically, the free oscillation amplitude and amplitude ratio. The applicability of this protocol is demonstrated experimentally by assessing the performance of diamond-like carbon-coated and silicon-nitride-coated silicon probes scanned over ultrananocrystalline diamond substrates in repulsive mode AM-AFM. There is no sign of fracture or plastic deformation in the case of diamond-like carbon; wear could be characterized as a gradual atom-by-atom process. In contrast, silicon nitride wears through removal of the cluster of atoms and plastic deformation.

Simultaneous measurement of pulmonary partial pressure of oxygen and apparent diffusion coefficient by hyperpolarized 3He MRI

Hyperpolarized 3He (HP 3He) MRI shows promise to assess structural and functional pulmonary parameters in a sensitive, regional, and noninvasive way. Structural HP 3He MRI has applied the apparent diffusion coefficient (ADC) for the detection of disease‐induced lung microstructure changes at the alveolar level, and HP 3He pulmonary partial pressure of oxygen (pO2) imaging measures the oxygen transfer efficiency between the lung and blood stream. Although both parameters are affected in chronic obstructive pulmonary disease (COPD), a quantitative assessment of the regional correlation of the two parameters has not been reported in the literature. In this work, a single acquisition technique for the simultaneous measurement of ADC and pO2 is presented. This technique is based on the multiple regression method, in which a general linear estimator is used to retrieve the values of ADC and pO2 from a series of measurements. The measurement uncertainties are also analytically derived and used to find an optimal measurement scheme. The technique was first tested on a phantom model, and then on an in vivo normal pig experiment. A case study was performed on a COPD patient, which showed that in a region of interest ADC was 29% higher while oxygen depletion rate was 61% lower than the corresponding global average values. Magn Reson Med, 2009.

Measurement of Pulmonary Partial Pressure of Oxygen and Oxygen Depletion Rate with Hyperpolarized Helium-3 MRI: A Preliminary Reproducibility Study on Pig Model

RATIONAL AND OBJECTIVES Pulmonary partial pressure of oxygen (pO(2)) and oxygen depletion rate (R) are two important parameters of lung function. The dependence of hyperpolarized (3)He (HP (3)He) T(1) on local oxygen concentration provides the basis for high-resolution mapping of the regional distributions of pO(2) and R in the lung. Although the oxygen-sensitive HP (3)He magnetic resonance imaging technique has been applied in human subjects and several animal species, reproducibility studies are rarely reported in the literature. This work presents a preliminary reproducibility study on a pig model. In this study, important scan parameters, such as measurement timing and flip angle, are optimized to minimize the noise-induced measurement uncertainty. MATERIALS AND METHODS In the in vivo study, five normal pigs and one diseased pig with simulated pulmonary emboli were scanned with a small flip angle gradient echo sequence. The pulmonary oxygen measurement was repeated two to four times in each pig. In each measurement, a series of six images were acquired with optimal timing and flip angle. The parametric maps were generated using a bin-based data processing procedure that applied the multiple regression fitting method to extract the pO(2) and R. Variations of global mean, percentiles, and regions of interest were calculated from the maps to analyze reproducibility. RESULTS The global statistical analyses show that average variation of global mean is 10.7% for pO(2) and 23.8% for R, and that the average variation of percentiles (10th, 25th, 50th, 75th, and 90th) and interquartile range is 14.8% for pO(2) and 30.4% for R. The region-of-interest analysis on the manually selected regions shows that the average variation of mean is 12.6% for pO(2) and 21.9% for R. CONCLUSION In this work, a preliminary study on the reproducibility of measuring pO(2) and R with HP (3)He magnetic resonance imaging on a pig model is presented.

Optimization of scan parameters in pulmonary partial pressure oxygen measurement by hyperpolarized 3He MRI

The dependence of hyperpolarized (HP) 3He T1 on local oxygen concentration provides the basis for measuring the partial pressure of oxygen (pO2) and oxygen depletion rate (R) in the lungs. Precise measurements of this type are difficult because the oxygen effect manifests itself through a decay of signal, leading to noisy images at the end of the series. The depolarization caused by RF excitation pulses further complicates the problem. It is therefore important to optimize scan parameters, such as measurement timing and flip angle, to obtain accurate and reproducible measurements. This work presents a new single‐acquisition technique in conjunction with the multiple regression fitting method for data evaluation. Analytical expressions for the measurement uncertainties are derived. A total of four types of single‐acquisition timing schemes are investigated; simulation shows a large uncertainty variation between these schemes (pO2: 7.5–30.2%; R: 47.4–173.7%). A basic procedure for optimizing scan parameters is then described. A phantom experiment was conducted to verify the simulation results. Repeated in vivo measurements with the optimal scheme in a rabbit experiment showed that average variation of global mean is 6.2% for pO2 and 12.0% for R, and that the average variation of percentiles (10th, 25th, 50th, 75th, and 90th) is 8.7% for pO2 and 19.0% for R. Magn Reson Med, 2007.

Advances in Manufacturing of Molded Tips for Scanning Probe Microscopy

A common method for producing sharp tips used in scanning probe microscopy (SPM) and other applications involving nanoscale tips is to deposit thin-film materials, such as metals, silicon nitride, or diamond-based films, into four-faceted pyramidal molds that are formed by anisotropic etching into a (100) silicon substrate. This well-established method is capable of producing tips with radii as small as a few nanometers. However, the shape of the tip apex is difficult to control with this method, and wedge-shaped tips that are elongated in one dimension are often obtained. This limitation arises due to the practical difficulty of having four planes intersecting at a single point. Here, a new method for producing three-sided molds for SPM tips is demonstrated through the use of etching in (311) silicon wafers. It is shown that silicon nitride and ultrananocrystalline diamond tips fabricated with this new method are wedge free and sharp (<; 10 nm radius), thereby restoring tip molding as a well-controlled manufacturing process for producing ultrasharp SPM tips.