Perpendicular fibre tracking for neural fibre bundle analysis using diffusion MRI.

Information on the directionality and structure of axonal fibres in neural tissue can be obtained by analysing diffusion-weighted MRI data sets. Several fibre tracking algorithms have been presented in the literature that trace the underlying field of principal orientations of water diffusion, which correspond to the local primary eigenvectors of the diffusion tensor field. However, the majority of the existing techniques ignore the secondary and tertiary orientations of diffusion, which contain significant information on the local patterns of diffusion. In this paper, we introduce the idea of perpendicular fibre tracking and present a novel dynamic programming method that traces surfaces, which are locally perpendicular to the axonal fibres. This is achieved by using a cost function, with geometric and fibre orientation constraints, that is evaluated dynamically for every voxel in the image domain starting from a given seed point. The proposed method is tested using synthetic and real DW-MRI data sets. The results conclusively demonstrate the accuracy and effectiveness of our method.

Considerations for numerical modeling of the pulmonary circulation--a review with a focus on pulmonary hypertension.

Both in academic research and in clinical settings, virtual simulation of the cardiovascular system can be used to rapidly assess complex multivariable interactions between blood vessels, blood flow, and the heart. Moreover, metrics that can only be predicted with computational simulations (e.g., mechanical wall stress, oscillatory shear index, etc.) can be used to assess disease progression, for presurgical planning, and for interventional outcomes. Because the pulmonary vasculature is susceptible to a wide range of pathologies that directly impact and are affected by the hemodynamics (e.g., pulmonary hypertension), the ability to develop numerical models of pulmonary blood flow can be invaluable to the clinical scientist. Pulmonary hypertension is a devastating disease that can directly benefit from computational hemodynamics when used for diagnosis and basic research. In the present work, we provide a clinical overview of pulmonary hypertension with a focus on the hemodynamics, current treatments, and their limitations. Even with a rich history in computational modeling of the human circulation, hemodynamics in the pulmonary vasculature remains largely unexplored. Thus, we review the tasks involved in developing a computational model of pulmonary blood flow, namely vasculature reconstruction, meshing, and boundary conditions. We also address how inconsistencies between models can result in drastically different flow solutions and suggest avenues for future research opportunities. In its current state, the interpretation of this modeling technology can be subjective in a research environment and impractical for clinical practice. Therefore, considerations must be taken into account to make modeling reliable and reproducible in a laboratory setting and amenable to the vascular clinic. Finally, we discuss relevant existing models and how they have been used to gain insight into cardiopulmonary physiology and pathology.

Dose broadening due to target position variability during fractionated breath-held radiation therapy.

Recent advances in Stereotactic Radiosurgery/Conformal Radiotherapy have made it possible to deliver surgically precise radiation therapy to small lesions while preserving the surrounding tissue. However, because of physiologic motion, the application of conformal radiotherapy to extra-cranial tumors is, at present, geared toward slowing the progression of disease rather than obtaining a cure. At the University of Rochester, we are investigating the use of patient breath-holding to reduce respiratory-derived motion in fractional radiotherapy. The primary targeting problem then becomes the small variation in tumor location over repeated breath-holds. This paper describes the effects of residual target position uncertainty on the dose distribution observed by small extra-cranial tumors and their neighboring tissues during fractional radiation treatment using breath holding. We employ two computational methods to study these effects: numerical analysis via Monte Carlo simulation and analytical computation using three-dimensional convolution. These methods are demonstrated on a 2-arc, 10-fraction treatment plan used to treat a representative lung tumor in a human subject. In the same human subject, the variability in position of a representative lung tumor was measured over repeated end-expiration breath-holds using volumetric imaging. For the 7 x 7 x 10 mm margin used to treat this 12 mm diameter tumor and the measured target position variability, we demonstrated that the entire tumor volume was irradiated to at least 48 Gy-well above the tumoricidal threshold. The advantages, in terms of minimizing the volume of surrounding lung tissue that is radiated to high dose during treatment, of using end-expiration breath holding compared with end-inspiration breath-holding are demonstrated using representative tumor size and position variability parameters. It is hoped that these results will ultimately lead to improved, if not curative, treatment for small (5-20 mm diameter) lung, liver, and other extra-cranial lesions.

Left ventricular motion reconstruction from planar tagged MR images: a comparison.

Through recent development of MR techniques, it is now possible to assess regional myocardial wall function in a non-invasive way. Using MR tagging, space is marked with planes which deform with the tissue, providing markers for tracking the local motion of the myocardium. Numerous methods to reconstruct the three-dimensional displacement field have been developed. The aim of this article is to provide a framework to quantitatively compare the performance of four methods the authors have developed. Five sets of experiments are described, and their results are reported. Instructions are also provided to perform similar tests on any method using the same data. The experiments show that some characteristic properties of the methods, such as sensitivity to noise or spatial resolution, can be quantitatively classified. Cross-comparison of performances show what range values for these properties can be considered acceptable.

Imaging three-dimensional cardiac function.

The three-dimensional (3-D) nature of myocardial deformations is dependent on ventricular geometry, muscle fiber architecture, wall stresses, and myocardial-material properties. The imaging modalities of X-ray angiography, echocardiography, computed tomography, and magnetic resonance (MR) imaging (MRI) are described in the context of visualizing and quantifying cardiac mechanical function. The quantification of ventricular anatomy and cavity volumes is then reviewed, and surface reconstructions in three dimensions are demonstrated. The imaging of myocardial wall motion is discussed, with an emphasis on current MRI and tissue Doppler imaging techniques and their potential clinical applications. Calculation of 3-D regional strains from motion maps is reviewed and illustrated with clinical MRI tagging results. We conclude by presenting a promising technique to assess myocardial-fiber architecture, and we outline its potential applications, in conjunction with quantification of anatomy and regional strains, for the determination of myocardial stress and work distributions. The quantification of multiple components of 3-D cardiac function has potential for both fundamental-science and clinical applications.

Doing more with less: using silent in-services for staff development.

A unit's greatest asset is nurses who are up-to-date in their practice. Time and money constraints demand innovative and creative educational methods. Silent inservices teach and empower while encompassing multiple learning styles in a cost-efficient manner.

Three-dimensional residual strain in midanterior canine left ventricle.

All previous studies of residual strain in the ventricular wall have been based on one- or two-dimensional measurements. Transmural distributions of three-dimensional (3-D) residual strains were measured by biplane radiography of columns of lead beads implanted in the midanterior free wall of the canine left ventricle (LV). 3-D bead coordinates were reconstructed with the isolated arrested LV in the zero-pressure state and again after local residual stress had been relieved by excising a transmural block of tissue. Nonhomogeneous 3-D residual strains were computed by finite element analysis. Mean +/- SD (n = 8) circumferential residual strain indicated that the intact unloaded myocardium was prestretched at the epicardium (0.07 +/- 0.06) and compressed in the subendocardium (-0.04 +/- 0.05). Small but significant longitudinal shortening and torsional shear residual strains were also measured. Residual fiber strain was tensile at the epicardium (0.05 +/- 0.06) and compressive in the subendocardium (-0.01 +/- 0.04), with residual extension and shortening, respectively, along structural axes parallel and perpendicular to the laminar myocardial sheets. Relatively small residual shear strains with respect to the myofiber sheets suggest that prestretching in the plane of the myocardial laminae may be a primary mechanism of residual stress in the LV.

Anterior and posterior left ventricular sarcomere lengths behave similarly during ejection.

Previous studies of regional differences in myocardial deformation between the anterior and posterior walls of the canine left ventricle were based on strain, which is not an absolute measure of deformation. We thus compared sarcomere lengths at anterior and posterior sites during ejection in isolated dog hearts. Cineradiographic imaging of regional deformation with radiopaque markers implanted near the midwall in five hearts and just below the epicardium in six hearts, combined with postmortem histology, allowed sarcomere length reconstruction throughout the cardiac cycle. The amount of sarcomere shortening accompanying left ventricular ejection was similar in both walls of the left ventricle for sarcomeres located at epicardial and midwall sites. The mean sarcomere length (taken at the middle of the ejecting range) was also similar between the anterior and posterior sites when averaged over all hearts. The similarity of sarcomere function held not only at end systole but throughout ejection and over wide ranges of ventricular pre- and afterloads. Hence functional measurements of relative myocardial shortening may not be indicative of regional sarcomere length heterogeneity.

A phased array coil for human cardiac imaging.

A prototype cardiac phased array receiver coil was constructed that comprised a cylindrical array and a separate planar array. Both arrays had two coil loops with the same coil dimensions. Data acquisition with the cylindrical array placed on the human chest, and the planar array placed under the back, yielded an overall enhancement of the signal-to-noise ratio (SNR) over the entire heart by a factor of 1.1-2.85 over a commercially available flexible coil and a commercially available four-loop planar phased array coil. This improvement in SNR can be exploited in cardiac imaging to increase the spatial resolution and reduce the image acquisition time.

Three-dimensional myocardial deformations: calculation with displacement field fitting to tagged MR images.

PURPOSE: To reconstruct three-dimensional (3D) myocardial deformations from orthogonal sets of parallel-tagged magnetic resonance (MR) images. MATERIALS AND METHODS: Displacement information in the direction normal to the undeformed tag planes was obtained at points along tag lines. Three independent sets of one-dimensional displacement data were used to fit an analytical series expression to describe 3D displacement as a function of deformed position. The technique was demonstrated with computer-generated models of the deformed left ventricle with data from healthy human volunteers. RESULTS: Model deformations were reconstructed with a 3D tracking error of less than 0.3 mm. Error between estimated and observed one-dimensional displacements along the tags in 10 human subjects was 0.00 mm +/- 0.36 (mean +/- standard deviation). Robustness to noise in the tag displacement data was demonstrated by using a Monte Carlo simulation. CONCLUSION: The combination of rapidly acquired parallel-tagged MR images and field-fitting analysis is a valuable tool in cardiac mechanics research and in the clinical assessment of cardiac mechanical function.

A modified quadrupole gradient set for use in high resolution MRI tagging.

A special purpose gradient set with a Cos(2 theta) current distribution has been constructed for high resolution MR imaging of small samples in a clinical Signa 1.5 T scanner using the existing gradient amplifiers. The X, Y, and Z gradient coils can attain gradient field strengths of 11.3, 4.7, and 15.2 G/cm at 100 amps current, respectively, with a slew rate of 20 G/cm/ms and usable ramp time of 150 microseconds. Field distortions are less than 2% over the central 8 cm of the bore, suitable for high resolution tagging of isolated canine hearts.

Calculation of three-dimensional left ventricular strains from biplanar tagged MR images.

The noninvasive measurement of time-resolved three-dimensional (3D) strains throughout the myocardium could greatly improve the clinical evaluation of cardiac disease and the ability to mathematically model the heart. On the basis of orthogonal arrays of tagged magnetic resonance (MR) images taken at several times during systole, such strains can be determined, but only after heart motion through the image planes is taken into account. An iterative material point-tracking algorithm is presented to solve this problem. It is tested by means of mathematical models of the heart with cylindric and spherical geometries that undergo deformations and bulk motions. Errors introduced by point-tracking interpolation were found to be negligible compared with those due to marker identification on the images. In a human heart studied with this technique, the corrected radial strains at the left ventricular base were approximately 2.5 times the two-dimensional estimates derived from the fixed image planes. The authors conclude that material point tracking allows accurate, time-resolved 3D strains to be calculated from tagged MR images, and that prior correction for motion of the heart through image planes is necessary.

Splenomegaly and reticulocytosis caused by Babesia microti infections in natural populations of the montane vole, Microtus montanus.

A survey for Babesia microti in rodents was conducted at six sites within Grand Teton National Park, Wyoming. Blood and spleen smears, hematocrits, and reticulocyte counts were made on all of the animals to evaluate parameters for the diagnosis of babesiosis. Ticks were removed for identification. Of 257 Microtus montanus, 103 were infected with B. microti. In addition, five of 12 Microtus pennsylvanicus and one of three Arvicola richardsoni were parasitized by B. microti. Peromyscus maniculatus (n = 40) were not infected. Concurrent infections by Hepatozoon sp., Trypanosoma sp., and the bacterium, Grahamella sp., were noted in blood smears from a number of M. montanus. Splenomegaly and reticulocytosis were significant parameters associated with babesiosis while decreased hematocrit was not. Ticks removed from the voles were identified as Ixodes eastoni and were the probable vectors of the B. microti.

Unique strain history during ejection in canine left ventricle.

Understanding the relationship between structure and function in the heart requires a knowledge of the connection between the local behavior of the myocardium (e.g., shortening) and the pumping action of the left ventricle. We asked the question, how do changes in preload and afterload affect the relationship between local myocardial deformation and ventricular volume? To study this, a set of small radiopaque beads was implanted in approximately 1 cm3 of the isolated canine heart left ventricular free wall. Using biplane cineradiography, we tracked the motion of these markers through various cardiac cycles (controlling pre- and afterload) using the relative motion of six markers to quantify the local three dimensional Lagrangian strain. Two different reference states (used to define the strains) were considered. First, we used the configuration of the heart at end diastole for that particular cardiac cycle to define the individual strains (which gave the local "shortening fraction") and the ejection fraction. Second, we used a single reference state for all cardiac cycles i.e., the end-diastolic state at maximum volume, to define absolute strains (which gave local fractional length) and the volume fraction. The individual strain versus ejection fraction trajectories were dependent on preload and afterload. For any one heart, however, each component of absolute strain was more tightly correlated to volume fraction. Around each linear regression, the individual measurements of absolute strain scattered with standard errors that averaged less than 7% of their range. Thus the canine hearts examined had a preferred kinematic (shape) history during ejection, different from the kinematics of filling and independent or pre-or afterload and of stroke volume.

Echo planar imaging of isolated perfused rat hearts at 4.7 T: a comparison of Langendorff and working heart preparations.

The implementation of echo planar imaging at 4.7 T is demonstrated using a homebuilt gradient and radiofrequency assembly. The application of such a technique to the study of the isolated perfused rat heart is demonstrated. Langendorff and working heart perfusion preparations are compared and changes in the left ventricular volume shown are to be much larger in the working heart preparation. Such a methodology is expected to provide a useful model for the study of cardiac function and dynamics in the normal and diseased states under controlled perfusion conditions.

Redescription of flagellar arrangement in the duck intestinal flagellate, Cochlosoma anatis and description of a new species, Cochlosoma soricis n. sp. from shrews.

Cochlosoma anatis Kotlán (Zoomastigophorea, Retortamonadida, Cochlosomidae), isolated from the large intestines of domestic Rouen ducks, and Cochlosoma soricis n. sp., isolated from the small intestines of shrews, were observed by light and scanning electron microscopy. In both organisms, a single flagellum inserted on the dorsal surface at the same level as the insertion of 4 other flagella on the ventral surface. The 4 ventro-lateral flagella emerged from the left side of the anterior attachment disk below the margin and just above the lateral groove which extended the length of the organism. A 6th flagellum emerged from the margin of the attachment disk. The proximal ends of the flagella formed a bundle with the distal ends becoming unraveled like a rope. During motility, the bundle portion extended straight out from the cell and the free ends of the flagella produced a whipping motion. In C. anatis, the dorsal surface was covered with knob-like lumps and small pits and the cells had an axostyle that emerged slightly to the right of the midline in the posterior 1/3 of the body. The axostylar tip was shorter and thicker than the flagella and in most cells it also had an irregular, knobby appearance. The irregular cell surface and axostyle were absent from C. soricis. The margin of the attachment disk curved toward the center and terminated in C. anatis as a straight edge while in C. soricis it continued as a spiral. Indentations in the mucosal brush border similar to those produced by Giardia, but distinctly belonging to Cochlosoma, were interpreted as points of attachment to the host.

Intestinal parasites of small mammals from Grand Teton National Park.

A study of the prevalence and identity of Giardia spp. in small mammals of Grand Teton National Park was undertaken. All 90 montane voles examined were positive for Giardia, as were 4 pocket gophers, 1 water shrew, 4 water voles, and 2 meadow voles. How and why these findings contrast with the findings of others are discussed.

In vitro and in vivo activity of 5-fluorocytosine on Acanthamoeba.

The results of our studies indicated that the avirulent Neff strain of Acanthamoeba was more susceptible to the activity of the anti-metabolite 5-fluorocytosine (5-FC) than was the virulent A-1 strain or a mouse brain reisolate of this strain, designated A-3. Results of competition experiments in which cultures were exposed simultaneously to 5-FC and either uracil, thymidine, or both uracil and thymidine demonstrated that the drug was directed against both deoxyribonucleic acid and ribonucleic acid in the avirulent strain, whereas ribonucleic acid was mainly affected in the virulent amebas. Concentrations >10 mug of 5-FC per ml were amebicidal to the avirulent strain; lower concentrations of the drug, which only affected growth slightly, significantly impaired the capacity of the cells to spontaneously encyst in stationary-phase cultures. On the other hand, the virulent strains were capable of growing in the presence of 5-FC (40 mug/ml) after an initial period of susceptibility. After a few transfers in growth medium lacking the drug, 5-FC-treated virulent amebas exhibited growth parameters typical of untreated cells. However, after successive subcultures in drug-free medium, 5-FC-treated cells lost their resistance and were again susceptible to the drug. This result suggested that the capacity of the cells to develop resistance resulted from a drug-induced mechanism. Spontaneous encystment, which was normally minimal in stationary-phase A-1 or A-3 cultures, was enhanced in A-3 but not A-1 cultures treated with 5-FC (>30 mug/ml). Results obtained from experiments to determine the effectiveness of 5-FC in protecting mice experimentally infected with either A-1 or A-3 amebas indicated that the clinical usefulness of 5-FC may be limited by the capacity of the amebas to develop resistance.