Semiautomated Skeletonization of the Pulmonary Arterial Tree in Micro-CT Images

We present a simple and robust approach that utilizes planar images at different angular rotations combined with unfiltered back-projection to locate the central axes of the pulmonary arterial tree. Three-dimensional points are selected interactively by the user. The computer calculates a sub- volume unfiltered back-projection orthogonal to the vector connecting the two points and centered on the first point. Because more x-rays are absorbed at the thickest portion of the vessel, in the unfiltered back-projection, the darkest pixel is assumed to be the center of the vessel. The computer replaces this point with the newly computer-calculated point. A second back-projection is calculated around the original point orthogonal to a vector connecting the newly-calculated first point and user-determined second point. The darkest pixel within the reconstruction is determined. The computer then replaces the second point with the XYZ coordinates of the darkest pixel within this second reconstruction. Following a vector based on a moving average of previously determined 3- dimensional points along the vessel\u27s axis, the computer continues this skeletonization process until stopped by the user. The computer estimates the vessel diameter along the set of previously determined points using a method similar to the full width-half max algorithm. On all subsequent vessels, the process works the same way except that at each point, distances between the current point and all previously determined points along different vessels are determined. If the difference is less than the previously estimated diameter, the vessels are assumed to branch. This user/computer interaction continues until the vascular tree has been skeletonized

Measuring the effect of airway pressure on pulmonary arterial diameter in the intact rat lung

To study the relationship between transpulomnary pressure (Ptp), intravascular pressure (Pv), and the pulmonary arterial tree structure, morphometric measurements of pulmonary arterial trees were made in intact lungs from Sprague-Dawley rats. Using cone beam micro-CT and techniques we developed for imaging small animal lungs, volumetric CT data were acquired for Ptp from 0 - 12 mmHg and Pv from 5 - 30 mmHg. The diameter, D (measured range approximately 0.08-2.0 mm), vs. pressure, P, relation can be described by D(P) = D(0)(1+ α P), where α is a distensibility coefficient. Unlike studies performed in larger animals, where changes in either Ptp or Pv had nearly identical effect on vessel distensibility, we found that there is only a small dependence of arterial diameter on Ptp in the rat. For example, using the above relation where P=Ptp and Pv is held constant at 12mmHg, alpha = 0.55±0.42(SE) %/mmHg, compared with when P=Pv and Ptp is held at 12mmHg, alpha = 2.59±0.17(SE) %/mmHg

Post-Acquisition Small-Animal Respiratory Gated Imaging Using Micro Cone-Beam CT

On many occasions, it is desirable to image lungs in vivo to perform a pulmonary physiology study. Since the lungs are moving, gating with respect to the ventilatory phase has to be performed in order to minimize motion artifacts. Gating can be done in real time, similar to cardiac imaging in clinical applications, however, there are technical problems that have lead us to investigate different approaches. The problems include breath-to-breath inconsistencies in tidal volume, which makes the precise detection of ventilatory phase difficult, and the relatively high ventilation rates seen in small animals (rats and mice have ventilation rates in the range of a hundred cycles per minute), which challenges the capture rate of many imaging systems (this is particularly true of our system which utilizes cone-beam geometry and a 2 dimensional detector). Instead of pre-capture ventilation gating we implemented a method of post-acquisition gating. We acquire a sequence of projections images at 30 frames per second for each of 360 viewing angles. During each capture sequence the rat undergoes multiple ventilation cycles. Using the sequence of projection images, an automated region of interest algorithm, based on integrated grayscale intensity, tracts the ventilatory phase of the lungs. In the processing of an image sequence, multiple projection images are identified at a particular phase and averaged to improve the signal-to-ratio. The resulting averaged projection images are input to a Feldkamp cone-beam algorithm reconstruction algorithm in order to obtain isotropic image volumes. Minimal motion artifact data sets improve qualitative and quantitative analysis techniques useful in physiologic studies of pulmonary structure and function

Estimation of Pulmonary Arterial Volume Changes in the Normal and Hypertensive Fawn-Hooded Rat from 3D Micro-CT data

In the study of pulmonary vascular remodeling, much can be learned from observing the morphological changes undergone in the pulmonary arteries of the rat lung when exposed to chronic hypoxia or other challenges which elicit a remodeling response. Remodeling effects include thickening of vessel walls, and loss of wall compliance. Morphometric data can be used to localize the hemodynamic and functional consequences. We developed a CT imaging method for measuring the pulmonary arterial tree over a range of pressures in rat lungs. X-ray micro-focal isotropic volumetric imaging of the arterial tree in the intact rat lung provides detailed information on the size, shape and mechanical properties of the arterial network. In this study, we investigate the changes in arterial volume with step changes in pressure for both normoxic and hypoxic Fawn-Hooded (FH) rats. We show that FH rats exposed to hypoxia tend to have reduced arterial volume changes for the same preload when compared to FH controls. A secondary objective of this work is to quantify various phenotypes to better understand the genetic contribution of vascular remodeling in the lungs. This volume estimation method shows promise in high throughput phenotyping, distinguishing differences in the pulmonary hypertensive rat model

Changes in Pulmonary Arterial Wall Mechanical Properties and Lumenal Architecture with Induced Vascular Remodeling

To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling

Quantification of Pulmonary Arterial Wall Distensibility Using Parameters Extracted from Volumetric Micro-CT Images

Stiffening, or loss of distensibility, of arterial vessel walls is among the manifestations of a number of vascular diseases including pulmonary arterial hypertension. We are attempting to quantify the mechanical properties of vessel walls of the pulmonary arterial tree using parameters derived from high-resolution volumetric x-ray CT images of rat lungs. The pulmonary arterial trees of the excised lungs are filled with a contrast agent. The lungs are imaged with arterial pressures spanning the physiological range. Vessel segment diameters are measured from the inlet to the periphery, and distensibilities calculated from diameters as a function of pressure. The method shows promise as an adjunct to other morphometric techniques such as histology and corrosion casting. It possesses the advantages of being nondestructive, characterizing the vascular structures while the lungs are imaged rapidly and in a near-physiological state, and providing the ability to associate mechanical properties with vessel location in the intact tree hierarchy

SPECT Imaging of Pulmonary Blood Flow in a Rat

Small animal imaging is experiencing rapid development due to its importance in providing high-throughput phenotypic data for functional genomics studies. We have developed a single photon emission computed tomography (SPECT) system to image the pulmonary perfusion distribution in the rat. A standard gamma camera, equipped with a pinhole collimator, was used to acquire SPECT projection images at 40 sec/view of the rat thorax following injection of Tc99m labeled albumin that accumulated in the rat\u27s lungs. A voxel-driven, ordered-subset expectation maximization reconstruction was implemented. Following SPECT imaging, the rat was imaged using micro-CT with Feldkamp conebeam reconstruction. The two reconstructed image volumes were fused to provide a structure/function image of the rat thorax. Reconstruction accuracy and performance were evaluated using numerical simulations and actual imaging of an experimental phantom consisting of Tc99m filled chambers with known diameters and count rates. Full-width half-maximum diameter measurement errors decreased with increasing chamber diameter, ranging from \u3c 6% down to 0.1%. Errors in the ratio of count rate estimates between tubes were also diameter dependent but still relatively small. This preliminary study suggests that SPECT will be useful for imaging and quantifying the pulmonary blood flow distribution and the distribution of Tc99m labeled ligands in the lungs of small laboratory animals

Fault-tolerant quantum computation with cluster states

The one-way quantum computing model introduced by Raussendorf and Briegel [Phys. Rev. Lett. 86 (22), 5188-5191 (2001)] shows that it is possible to quantum compute using only a fixed entangled resource known as a cluster state, and adaptive single-qubit measurements. This model is the basis for several practical proposals for quantum computation, including a promising proposal for optical quantum computation based on cluster states [M. A. Nielsen, arXiv:quant-ph/0402005, accepted to appear in Phys. Rev. Lett.]. A significant open question is whether such proposals are scalable in the presence of physically realistic noise. In this paper we prove two threshold theorems which show that scalable fault-tolerant quantum computation may be achieved in implementations based on cluster states, provided the noise in the implementations is below some constant threshold value. Our first threshold theorem applies to a class of implementations in which entangling gates are applied deterministically, but with a small amount of noise. We expect this threshold to be applicable in a wide variety of physical systems. Our second threshold theorem is specifically adapted to proposals such as the optical cluster-state proposal, in which non-deterministic entangling gates are used. A critical technical component of our proofs is two powerful theorems which relate the properties of noisy unitary operations restricted to act on a subspace of state space to extensions of those operations acting on the entire state space.Comment: 31 pages, 54 figure