Advanced MR imaging techniques for evaluation of the heart and great vessels

A "one-stop shop" for evaluating cardiac disease with magnetic resonance (MR) imaging is progressing toward clinical reality and promises to have a major effect on the care of patients with cardiac disease. T1-weighted conventional spin-echo imaging gated to the cardiac cycle yields good anatomic detail but requires long imaging times and provides only static images of a single cardiac phase. Fast MR imaging with electrocardiographically (ECG) gated, low-flip-angle, segmented k-space gradient-recalled-echo (GRE) sequences provides excellent image quality with sufficiently high temporal resolution to "freeze" cardiac motion. Segmented k-space sequences improve on standard ECG-gated GRE sequences by allowing many cardiac phases, or frames of a cine sequence, to be imaged in a single breath hold with prospective cardiac gating. As commercial implementations of segmented k-space imaging become more widely available, the applications of this technique are expanding from research protocols to include many clinical applications in the heart and great vessels. Such applications include evaluation of vascular anatomy (coronary angiography, aortic disease, aberrant vessels, vascular access), cardiac anatomy (congenital anomalies, right ventricular dysplasia, constrictive pericarditis, valvular function), myocardial perfusion, and myocardial wall motion.     

The histopathology of nonsteroidal anti-inflammatory drug-associated colitis

We combined three techniques--mechanical testing, three-dimensional imaging, and finite-element modeling--to distinguish between the contributions of architecture and tissue modulus to mechanical function in human trabecular bone. The objectives of this study were 2-fold. The first was to assess the accuracy of micromechanical modeling of trabecular bone using high-contrast x-ray images of the trabecular architecture. The second was to combine finite-element calculations with mechanical testing to infer an average tissue modulus for the specimen. Specimens from five human L1 vertebrae were mechanically tested along the three anatomic axes. The specimens were then imaged by synchrotron x-ray tomography, and the elastic moduli of each specimen were calculated from the tomographic image by finite-element modeling. We found that 23-microm tomographic images resolved sufficient structural detail such that the calculated anisotropy in the elastic modulus was within the uncertainties of the experimental measurements in all cases. The tissue modulus of each specimen was then estimated by comparing the calculated mean stiffness of the specimen, averaged over the three anatomical directions, with the experimental measurement. The absolute values of the experimental elastic constants could be fitted, again within the uncertainties of the experimental measurements, by a single tissue modulus of 6.6 GPa, which was the average tissue modulus of the five specimens. These observations suggest that a combination of mechanical testing, three-dimensional imaging, and finite-element modeling might enable the physiological variations in tissue moduli to be determined as a function of age and gender.     

Myocyte proliferation in end-stage cardiac failure in humans

Introduced several decades ago, the dogma persists that cardiac myocytes are terminally differentiated cells and that division of muscle cells is impossible in the adult heart. More recently, nuclear mitotic divisions in myocytes occasionally were seen, but those observations were challenged on the assumption that the rate of cell proliferation was inconsequential for actual tissue regeneration. Moreover, mitoses were never detected in normal myocardium. However, the analysis of routine histologic preparations constituted the basis for the belief that myocytes were unable to reenter the cell cycle and divide, ignoring the limitations of these techniques. We report here by confocal microscopy that 14 myocytes per million were in mitosis in control human hearts. A nearly 10-fold increase in this parameter was measured in end-stage ischemic heart disease (152 myocytes per million) and in idiopathic dilated cardiomyopathy (131 myocytes per million). Because the left ventricle contains 5.8 x 10(9) myocytes, these mitotic indices imply that 81.2 x 10(3), 882 x 10(3), and 760 x 10(3) myocytes were in mitosis in the entire ventricular myocardium of control hearts and hearts affected by ischemic and idiopathic dilated cardiomyopathy, respectively. Additionally, mitosis lasts less than 1 hr, suggesting that large numbers of myocytes can be formed in the nonpathologic and pathologic heart with time. Evidence of cytokinesis in myocytes was obtained, providing unequivocal proof of myocyte proliferation.     

Solution structure of an oligodeoxynucleotide containing the human N-ras codon 12 sequence refined from 1H NMR using molecular dynamics restrained by nuclear Overhauser effects

A general model is developed for segmenting magnetic resonance images using vector decomposition and probability techniques. Each voxel is assigned fractional volumes of q tissues from p differently weighted images (q < or = p + 1) in the presence of partial-volume mixing, random noise, and other tissues. Compared with the eigenimage method, fewer differently weighted images are needed for segmenting the q tissues, and the contrast-to-noise ratio in the calculated fractional volumes is improved. The model can produce composite tissue-type images similar to that of the probability methods, by comparing the fractional volumes assigned to different tissues on each voxel. A three-tissue (p = 2, q = 3) model is illustrated for segmenting three tissues from dual-echo images. It provides statistical analysis to the algebraic method. A three-compartment phantom is segmented for validation. Two clinical examples are presented.     

Neuromagnetic recordings of the human peripheral nerve with planar SQUID gradiometers

Magnetic fields produced by a travelling volley in the human ulnar nerve have been successfully measured in a lightly shielded environment. Recordings of the tangential component of the magnetic field were made using a planar second-order gradiometer integrated with a first-order gradiometric superconducting quantum interference device (SQUID). Devices were fabricated in our clean-room facility at the University of Strathclyde and measurements taken in an eddy-current shielded room at the Wellcome Biomagnetism Unit. We use no additional shielding and no electronic differencing or field-nulling techniques. Evoked magnetic fields of 60 fT peak-to-peak were obtained after 1536 averages but they could be seen easily as early as 512 averages. Measurements were made over four points above the ulnar nerve on the upper arm and from these the conduction velocity was calculated as 60 m s(-1).     

Magnetic resonance imaging of perfusion in the isolated rat heart using spin inversion of arterial water

Measurement of regional myocardial perfusion is important for the diagnosis and treatment of coronary artery disease. Currently used methods for the measurement of myocardial tissue perfusion are either invasive or not quantitative. Here, we demonstrate a technique for the measurement of myocardial perfusion using magnetic resonance imaging (MRI) with spin tagging of arterial water. In addition, it is shown that changes in perfusion can be quantitated by measuring changes in tissue T1. Perfusion images are obtained in Langendorff-perfused, isolated rat hearts for perfusion rates ranging from 5 to 22 ml/g/min. The MRI-determined perfusion rates are in excellent agreement with perfusion rates determined from measurement of bulk perfusate flow (r = 0.98). The predicted linear dependence of the measured T1 (T1app) on perfusion is also demonstrated. The ability of perfusion imaging to measure regional variations in flow is demonstrated with hearts in which perfusion defects were created by ligation of a coronary artery. These results indicate that MRI of perfusion using spin inversion of arterial water gives quantitative maps of cardiac perfusion.     

Sensitivity distributions of EEG and MEG measurements

It is generally believed that because the skull has low conductivity to electric current but is transparent to magnetic fields, the measurement sensitivity of the magnetoencephalography (MEG) in the brain region should be more concentrated than that of the electroencephalography (EEG). It is also believed that the information recorded by these techniques is very different. If this were indeed the case, it might be possible to justify the cost of MEG instrumentation which is at least 25 times higher than that of EEG instrumentation. The localization of measurement sensitivity using these techniques was evaluated quantitatively in an inhomogeneous spherical head model using a new concept called half-sensitivity volume (HSV). It is shown that the planar gradiometer has a far smaller HSV than the axial gradiometer. However, using the EEG it is possible to achieve even smaller HSV's than with whole-head planar gradiometer MEG devices. The micro-superconducting quantum interference device (SQUID) MEG device does have HSV's comparable to those of the EEG. The sensitivity distribution of planar gradiometers, however, closely resembles that of dipolar EEG leads and, therefore, the MEG and EEG record the electric activity of the brain in a very similar way.     

Three-dimensional display of cardiac structures using reconstructed magnetic resonance imaging

It is sometimes difficult to understand the three-dimensional (3D) relationship of cardiac and mediastinal structures despite advances in magnetic resonance (MR) imaging techniques. We present a low-cost system for 3D reconstruction of the major mediastinal structures by processing the MR imaging data on a NeXT workstation. MR images of multisection, multiphase, spin-echo techniques stored in a picture archiving and communication system (PACS) data base were used for the reconstruction. The computer program obtained the contours of the multiple components of the mediastinal structures by the combination of automatic and manual procedure. The bundled software of a 3D kit was used for surface rendering of hidden surface removal, shading of the visible parts of the surfaces, perspective transformation, and motion parallax by rotation of the surfaces. 3D reconstruction was performed in 15 patients with cardiac diseases, and the 3D-reconstructed images were compared with the plain chest x rays of the patients. The 3D presentation clearly showed the complex anatomy of cardiovascular diseases and helped elucidate the misconceptions in the interpretation of the plain chest x rays. Our 3D images are used for education and should be viewed by medical students and beginners in radiology at an individual pace with plain chest radiographs, MR images, and legends. Although applied to the heart and the great vessels in this report, this system is also applicable to other structures.     

Differential roles of p300 and PCAF acetyltransferases in muscle differentiation

To determine the possibility of discriminating multi-sources in the brain by 3D vector magnetic field measurement of a magnetoencephalogram (MEG), measurements were made of magnetic fields produced by two current dipoles implanted in a spherical head model. The 3D vector magnetic field measurements were made by using a 3D second-order gradiometer connected to three rf-SQUIDs, which can detect magnetic field components perpendicular to and tangential to the scalp. The MEG distribution measuring the magnetic field perpendicular to the scalp was not helpful in estimating the location and number of sources because of the lack of a dipole pattern. By referring to the MEG distribution measuring the magnetic field distribution tangential to the scalp, however, two current sources could be clearly discriminated in a spherical head model. It was found that this MEG distribution measuring tangential to the scalp could provide information on new constraint conditions for the calculation of inverse problems with multi-sources. These results were also confirmed by measurement of the mixed somatosensory evoked fields elicited by simultaneous electric stimulation to the median nerve and the thumb.     

Simulation of two-dimensional tagged MRI

MR tagging is a recent imaging development that, in cardiac applications, makes possible the tracking of points in the myocardium during the cardiac cycle. Researchers have developed semiautomated, computer-based methods for analyzing tagged images, but the images are complex and present a challenge to automated tracking systems. Simulation can provide an inexhaustible supply of images for testing and validation of tag tracking software and preview the effect of parameter changes in acquisition. SIMTAG is an interactive computer program that simulates two-dimensional tagged-MR experiments. The mathematic model used in the simulation and algorithms for simulating image noise and object deformation are described. Examples of the use of simulated images in SPAMM parameter selection, a comparison of tag contrast in signal-averaged SPAMM and CSPAMM, and simulated images as test sets for tag-tracking software are presented.     

Finite-Element Analysis of Inclined Piezocone Penetration Test in Clays

A three-dimensional finite-element analysis was performed to analyze the effect of soil anisotropy on the inclined piezocone penetration test in normally consolidated clay. The piezocone penetration was numerically simulated based on a large strain formulation using the commercial finite-element code ABAQUS, and the anisotropic modified cam clay model (AMCCM) was chosen and implemented into ABAQUS through the user subroutine UMAT. For verification purposes, numerical simulations were first performed on previously conducted calibration chamber tests, and the predicted results were compared with the measured values. For different initial stress conditions and different penetration angles, the cone tip resistance profile; excess pore pressure profile at the cone tip; typical stress, strain and excess pore pressure distributions around the cone; and excess pore pressure dissipation at the cone tip are provided. This study shows that when the initial stress state is anisotropic, the soil behavior is different under different angles of penetration.     

Comparison of four motion correction techniques in SPECT imaging of the heart: a cardiac phantom study

The aim of this study was to evaluate the accuracy of four different motion correction techniques in SPECT imaging of the heart. METHODS: We evaluated three automated techniques: the cross-correlation (CC) method, diverging squares (DS) method and two-dimensional fit method and one manual shift technique (MS) using a cardiac phantom. The phantom was filled with organ concentrations of 99mTc closely matching those seen in patient studies. The phantom was placed on a small sliding platform connected to a computer-controlled stepping motor. Linear, random, sinusoidal and bounce motions of magnitude up to 2 cm in the axial direction were simulated. Both single- and dual-detector 90 degrees acquisitions were acquired using a dual 90 degrees detector system. Data were acquired over 180 degrees with 30 or 15 frames/detector (single-/dual-head) at 30 sec/frame in a 64x64 matrix. RESULTS: The simulated single-detector system, CC method, failed to accurately correct for any of the simulated motions. The DS technique overestimated the magnitude of phantom motion, particularly for images acquired between 45 degrees left anterior oblique and 45 degrees left posterior oblique. The two-dimensional and MS techniques accurately corrected for motion. The simulated dual 90 degrees detector system, CC method, only partially tracked random or bounce cardiac motion and failed to detect sinusoidal motion. The DS technique overestimated motion in the latter half of the study. Both the two-dimensional and MS techniques provided superior tracking, although no technique was able to accurately track the rapid changes in cardiac location simulated in the random motion study. Average absolute differences between true and calculated position of the heart on single- and dual 90 degrees -detectors were 1.7 mm and 1.5 mm for the two-dimensional and MS techniques, respectively. The corresponding values for the DS and CC techniques were 5.7 and 8.9 mm, respectively. CONCLUSION: Of the four techniques evaluated, manual correction by an experienced technologist proved to be the most accurate, although results were not significantly different from those observed with the two-dimensional method. Both techniques accurately determined cardiac location and permitted artifact-free reconstruction of the simulated cardiac studies.     

Right atrial metastatic melanoma in a patient with transient ischemic attacks

A 65-year-old-man was admitted for evaluation of a transient ischemic attack. A 4.5 x 5.3-cm right atrial mass and a patent foramen ovale were identified by echocardiography. A 0.5-cm lesion was identified in the left temporal lobe of the brain by magnetic resonance imaging. Positron emission tomography was used to differentiate a tumor from an infarct in the brain. The cardiac and the brain lesions were successfully resected. Histopathologic study of the atrial and cerebral tissue demonstrated that these were metastases from a previously excised scalp desmoplastic malignant melanoma. The patient remains well at 14 months' follow-up.     

Segmentation of brain tissue from magnetic resonance images

Segmentation of medical imagery is a challenging problem due to the complexity of the images, as well as to the absence of models of the anatomy that fully capture the possible deformations in each structure. The brain is a particularly complex structure, and its segmentation is an important step for many problems, including studies in temporal change detection of morphology, and 3-D visualizations for surgical planning. We present a method for segmentation of brain tissue from magnetic resonance images that is a combination of three existing techniques from the computer vision literature: expectation/maximization segmentation, binary mathematical morphology, and active contour models. Each of these techniques has been customized for the problem of brain tissue segmentation such that the resultant method is more robust than its components. Finally, we present the results of a parallel implementation of this method on IBM's supercomputer Power Visualization System for a database of 20 brain scans each with 256 x 256 x 124 voxels and validate those results against segmentations generated by neuroanatomy experts.     

Finite-Element Model Updating for the Kap Shui Mun Cable-Stayed Bridge

This paper presents the implementation of the finite-element model updating for the Kap Shui Mun Bridge, a 430 m main span double-deck cable-stayed bridge in Hong Kong. The dynamic characteristics of the bridge have been studied through both three-dimensional finite-element prediction and field vibration measurement previously. In this paper, the developed finite-element model is updated based on the field measured dynamic properties. A comprehensive sensitivity study to demonstrate the effects of various structural parameters (including the connections and boundary conditions) on the modes of concern is first performed, according to which a set of structural parameters are then selected for adjustment. The finite-element model is updated in an iterative fashion so as to minimize the differences between the predicted and the measured natural frequencies. The final updated finite-element model for the Kap Shui Mun Bridge is able to produce natural frequencies in good agreement with the measured ones, and can be helpful for a more precise dynamic response prediction.     

Three-dimensional visualization of physiologically based kinetic model outputs

Outputs from a physiologically based toxicokinetic (PB-TK) model for fish were visualized by mapping time-series data for specific tissues onto a three-dimensional representation of a rainbow trout. The trout representation was generated in stepwise fashion: 1) cross-section images were obtained from an anesthetized fish using a magnetic resonance imaging system, 2) images were processed to classify tissue types and eliminate unnecessary detail. 3) processed images were imported to a visualization software package (Application Visualization System) to create a three-dimensional representation of the fish, encapsulating five volumes corresponding to the liver, kidney, muscle, gastrointestinal tract, and fat, Kinetic data for the disposition of pentachloroethane in trout were generated using a PB-TK model. Model outputs were mapped onto corresponding tissues volumes, representing chemical concentration as color intensity. The workstation software was then used to animate the images, illustration the accumulation of pentachloroethane in each tissue during a continuous branchial (gill) exposure.     

French CF family genotype analysis shows that the R297Q mutation is a rare polymorphism

Body surface mapping (BSM) has now become a feasible clinical technique, providing useful information applicable to the diagnosis of cardiac arrhythmias and their treatment by surgical and endocardial catheter ablation. In WPW patients, validation of preexcitation patterns has been obtained by computer simulation and by direct epicardial mapping at surgery. BSM pacemapping has subsequently been developed to be used during radiofrequency catheter ablation. This method has been evaluated prospectively and its predictive accuracy assessed. The recognition of two distinct BSM patterns in idiopathic ventricular tachycardia, has led to the application of successful pacemapping for radiofrequency catheter ablation. The use of a realistic tri-dimensional heart-torso computer model has shown that specific sites of endocardial stimulation are related to distinct thoracic map patterns.     

Microdosimetric analysis of radiation from a clinical mammography machine using realistic breast phantoms and a miniature proportional counter

We have measured the microdosimetric spectra of a Senographe 600T mammography machine employing an Mo target with 0.8 mm Be inherent filtration and 0.03 mm Mo added filtration, giving a half-value layer of 0.35 mm A1 at 28 kVp. In all of our measurements a large collimator producing a 24 cm x 30 cm field at 65 cm was used. Two different phantom compositions differing in the ratio of adipose to fibroglandular tissue were compared, using simulated breast material from Nuclear Associates. Spectra were taken at various depths and locations in simulated breasts of 3.4 and 5 cm thickness. The detector used was a miniature proportional counter having outer dimensions of 5 cm x 1.8 cm diameter, with a sensitive volume 0.5 mm x 0.5 mm. The small dimensions of the counter and the cavity allowed total embedding in the breast material with minimal disturbance of the photon and secondary electron spectrum. Our results show that there can be changes in the radiation quality amounting to as much as 17% (as measured by the dose mean lineal energy. yD) between breasts of different thickness, at the same relative position within the breast. There is little difference due to breast composition.     

Isolation and experimental transmission of Sarcocystis moulei Neveu-Lemaire, 1912

Of 44 several years old goats slaughtered in Kabul/Afghanistan 16 proved to be infected ith Sarcocystis moulei. The large white cysts measuring 2-16 x 1-9 mm were found exclusively in oesophageal muscle tissues of the animals. A total of 4 million sporocysts were harvested from mucosal scrapings of the small intestines of two young cats which had been killed 11 or 14 days after being fed with S. moulei-containing oesophagi of those goats. For transmission experiments in Berlin 11 kids from a S. moulei-free goat breeding as well as 5 Sarcocystis-free cats were used. In a preliminary experiment 3 young goats were orally inoculated with 200 or 2000 sporocysts from Kabul. In further consecutive trials each of the 8 remaining kids received 1000 sporocysts, which were isolated from the intestines of cats after feeding them S. moulei-cysts from successfully infected goats of the first experiment in Berlin. No cysts could be detected in oesophageal muscle tissues of two goats which were slaughtered 4 or 6 months after sporocyst application. Also no sporocysts were excreted by two cats which were fed with the oesophagi of those two animals. In oesophageal muscle tissues of the 9 remaining goats, which were slaughtered 19, 25, 43, 44, 59 or 86 months after infection, 17 to 140 macroscopically visible cysts of S. moulei were found. A definite correlation between age and size of cysts was observed. 19 months p.i. cysts measured 1-2 x 0.5-1 mm, at 43 or 44 months p.i. they were already 1-8 x 1-4 mm, and finally 86 months p.i. they reached a size of 7-13 x 5-8 mm. In H.E. stained histological sections cysts appeared to be subdivided into honeycomb like chambers by very prominent septae. In smaller cysts all chambers were filled with sickle shaped cystozoites, whereas in larger cysts only the chambers at the periphery contained cystozoites. Groups of metrocytes were seen within the cyst groundsubstance at the periphery of cysts indicating further growth, even of very large cysts. Cyst walls measured up to 10 microns in thickness and were composed of a primary and a secondary cyst wall. The thin primary cyst wall was folded irregularly to give cauliflower like protrusions, which were up to 4.4 microns high. The parasitized host cell formed a thick surrounding layer of 6 to 7.5 microns, which was covered by a 2 to 2.5 microns thick layer of connective tissue. All three cats which were fed with S. moulei-cysts in Berlin excreted S. moulei-sporocysts with their faeces. Prepatency was 10 days. A total of 100 sporocysts measured 11.6-13.1 x 8.7-9.4 microns.     

A computational model for tracking subsurface tissue deformation during stereotactic neurosurgery

Recent advances in the field of stereotactic neurosurgery have made it possible to coregister preoperative computed tomography (CT) and magnetic resonance (MR) images with instrument locations in the operating field. However, accounting for intraoperative movement of brain tissue remains a challenging problem. While intraoperative CT and MR scanners record concurrent tissue motion, there is motivation to develop methodologies which would be significantly lower in cost and more widely available. The approach we present is a computational model of brain tissue deformation that could be used in conjunction with a limited amount of concurrently obtained operative data to estimate subsurface tissue motion. Specifically, we report on the initial development of a finite element model of brain tissue adapted from consolidation theory. Validations of the computational mathematics in two and three dimensions are shown with errors of 1%-2% for the discretizations used. Experience with the computational strategy for estimating surgically induced brain tissue motion in vivo is also presented. While the predicted tissue displacements differ from measured values by about 15%, they suggest that exploiting a physics-based computational framework for updating preoperative imaging databases during the course of surgery has considerable merit. However, additional model and computational developments are needed before this approach can become a clinical reality.