Beta-adrenergic cardiac antibody in autoimmune myocarditis

Balb/c mice were immunized with homologous heart in complete Freund's adjuvant to induce autoimmune myocarditis. The myocarditis was characterized by lymphomononuclear infiltration, electrocardiographic abnormalities and antimuscle antibodies by indirect immunofluorescence. In this paper, we demonstrate that the IgG present in autoimmune myocarditis mice is able to bind to beta-adrenoreceptors of the heart and also induce a biological effect inhibiting the contractile action of exogenous norepinephrine. Auto-immune IgG inhibited the binding of (3H)-dyhidroalprenolol to a beta-adrenergic receptor of purified myocardial membranes behaving as non-competitive inhibitor. This IgG also exerted a non-competitive inhibition upon the mechanical effect of exogenous norepinephrine. The recognition appears to be organ specific, because the autoimmune myocarditis IgG did not bind to beta-lymphocyte, lung and fat adrenoreceptors. The autoimmune IgG inhibited the stimulatory action of isoproterenol on cAMP levels, behaving as a beta-adrenergic antagonist.     

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.     

Pulse sequence generated oblique magnetic resonance imaging: applications to cardiac imaging

A pulse sequence procedure for producing oblique magnetic resonance images is described. Using this procedure we present a new, accurate method to obtain true short-axis views and true long-axis views (both parallel and perpendicular to the septal plane) of the heart. The method is accurate regardless of the orientation of patient's heart. The method does not require the patient to be rotated, nor otherwise moved, and does not require any additional hardware. The method is experimentally verified with both human and phantom studies. The phantom study indicates accuracy of approximately 1 degree with a commercial scanner that reports angular measurements to a precision of 1 degree. Application of the short-axis views to measurement of left ventricular volume, and possible advantages of Gauss-Legendre integration for this measurement are discussed. Finally, multiphase oblique cardiac images are presented.     

The role of functional magnetic resonance imaging in understanding reading and dyslexia

Converging evidence from a number of lines of investigation indicates that dyslexia represents a disorder within the language system and more specifically within a particular subcomponent of that system, phonological processing. Recent advances in imaging technology, particularly the development of functional magnetic resonance imaging (fMRI), provide evidence of a neurobiological signature for dyslexia, specifically a disruption of 2 left hemisphere posterior brain systems, 1 parietal-temporal, the other occipital-temporal, with compensatory engagement of anterior systems around the inferior frontal gyrus and a posterior (right occipital-temporal) system. Furthermore, good evidence indicates a computational role for the left occipital-temporal system: the development of fluent (automatic) reading. In addition, fMRI studies of young adults with reading difficulties followed prospectively and longitudinally from age 5 through their mid 20s suggests that there may be 2 types of reading difficulties, 1 primarily reflecting a genetic basis, the other, and far more common, reflecting environmental influences. The brain systems for reading are malleable and their disruption in children with dyslexia may be remediated by provision of an evidence-based, effective reading intervention. These studies offer the promise for more precise identification and effective management of dyslexia in children, adolescents, and adults.     

The role of computed tomography and magnetic resonance imaging in the investigation of natural death

Public distaste for the traditional autopsy combined with disquiet about the variable quality of the coroner’s post-mortem have led to increasing pressure to find a less invasive alternative. There have been previous studies using computed tomography (CT) and magnetic resonance imaging (MRI) to determine cause of death but there is very little evidence of the accuracy or reproducibility of these techniques in non-forensic cases. In 2006 the Department of Health funded a validation study of post-mortem imaging in adults which is due to report this year. Preliminary results suggest that, if a confident imaging (MR and CT) diagnosis of the cause of death is made, the major error rate is close to that of clinical death certificates. There are major weaknesses in diagnosis of coronary heart disease and pulmonary thromboemboli on imaging. These weaknesses will need to be overcome if imaging is to replace the invasive post-mortem or systematic errors in mortality statistics will result.     

Parallel magnetic resonance imaging

Parallel imaging has been the single biggest innovation in magnetic resonance imaging in the last decade. The use of multiple receiver coils to augment the time consuming Fourier encoding has reduced acquisition times significantly. This increase in speed comes at a time when other approaches to acquisition time reduction were reaching engineering and human limits. A brief summary of spatial encoding in MRI is followed by an introduction to the problem parallel imaging is designed to solve. There are a large number of parallel reconstruction algorithms; this article reviews a cross-section, SENSE, SMASH, g-SMASH and GRAPPA, selected to demonstrate the different approaches. Theoretical (the g-factor) and practical (coil design) limits to acquisition speed are reviewed. The practical implementation of parallel imaging is also discussed, in particular coil calibration. How to recognize potential failure modes and their associated artefacts are shown. Well-established applications including angiography, cardiac imaging and applications using echo planar imaging are reviewed and we discuss what makes a good application for parallel imaging. Finally, active research areas where parallel imaging is being used to improve data quality by repairing artefacted images are also reviewed.     

Flow-enhanced magnetic resonance imaging

A new technique for detecting blood flow in magnetic resonance imaging is proposed. This technique is tailored to enhance areas containing flow while suppressing static and nonsignal areas with the objective of optimizing the contrast of vascularized tumors. Unlike flow phase imaging, in-plane flow directionality (parallel versus antiparallel to applied flow gradient) is removed by the proposed method to reduce phase cancellation of flow signals. This signal loss is apt to occur in instances of complicated vascularity patterns consisting of many small vessels having multiple flow directions. The new flow-enhanced imaging method is compared to flow phase imaging by computer simulation of simple objects containing many small vessels. The results indicate that flow-enhanced imaging yields significantly greater detectability of regions of complicated small-vessel patterns than phase imaging.     

Molecular magnetic resonance imaging

Molecular MRI (mMRI) is a special implementation of Molecular Imaging for the non-invasive visualisation of biological processes at the cellular and molecular level. More specifically, mMRI comprises the contrast agent-mediated alteration of tissue relaxation times for the detection and localisation of molecular disease markers (such as cell surface receptors, enzymes or signaling molecules), cells (e.g. lymphocytes, stem cells) or therapeutic drugs (e.g. liposomes, viral particles). MRI yields topographical, anatomical maps; functional MRI (fMRI) provides rendering of physiologic functions and magnetic resonance spectroscopy (MRS) reveals the distribution patterns of some specific metabolites. mMRI provides an additional level of information at the molecular or cellular level, thus extending MRI further beyond the anatomical and physiological level. These advances brought by mMRI are mandatory for MRI to be competitive in the age of molecular medicine. mMRI is already today increasingly used for research purposes, e.g. to facilitate the examination of cell migration, angiogenesis, apoptosis or gene expression in living organisms. In medical diagnostics, mMRI will pave the way toward a significant improvement in early detection of disease, therapy planning or monitoring of outcome and will therefore bring significant improvement in the medical treatment for patients.In general, Molecular Imaging demands high sensitivity equipment, capable of quantitative measurements to detect probes that interact with targets at the pico- or nanomolar level. The challenge to detect such sparse targets can be exemplified with cell surface receptors, a common target for molecular imaging. At high expression levels (bigger than 106 per cell) the receptor concentration is approx. 10(15) per ml, i.e. the concentration is in the micromole range. Many targets, however, are expressed in even considerably lower concentrations. Therefore the most sensitive modalities, namely nuclear imaging (PET and SPECT) have always been at the forefront of Molecular Imaging, and many nuclear probes in clinical use today are already designed to detect molecular mechanisms (such as FDG, detecting high glucose metabolism). In recent years however, Molecular Imaging has commanded attention from beyond the field of nuclear medicine. Further imaging modalities to be considered for molecular imaging primarily include optical imaging, MRI and ultrasound.     

Characterization of murine autoimmune myocarditis induced by self and foreign cardiac myosin

Previously we showed that autoimmune myocarditis could be induced in mice by immunization with purified murine cardiac myosin (MCM). In this study, we found that identical disease could also be induced in genetically susceptible mice by immunization with porcine cardiac myosin (PCM). The cardiac lesions induced by both antigens were characterized by extensive infiltration of the myocardium accompanied by myocyte necrosis. A novel finding was the presence of multinucleated giant cells and eosinophils in the cardiac infiltrates, in addition to a mixture of mononuclear cells and polymorphonuclear cells described previously. Immunohistochemical staining demonstrated that the mononuclear cells consisted predominantly of macrophages, CD4+ T cells and, to a lesser extent, CD8+ T cells and B cells. In addition, increased cardiac expression of adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) were demonstrated in mice that developed myocarditis as compared with those that did not develop disease upon immunization with either PCM or MCM. The levels of TNFalpha detected in spleen cell culture supernatant were found to be higher in mice that developed myocarditis than in those that did not develop the disease. Mice immunized with PCM generated T cells and B cells reactive not only with PCM but also with MCM, and vice versa. In addition, the serum levels of IgG1 anti-MCM antibodies produced in mice immunized with PCM as well as MCM were found to correlate positively with the development of myocarditis. Such a detailed characterization of the murine model of autoimmune myocarditis induced by PCM or MCM allowed us to compare the disease process induced by homologous self and foreign antigens.     

Noise and filtration in magnetic resonance imaging

Noise in two-dimensional Fourier transform magnetic resonance images has been investigated using noise power spectra and measurements of standard deviation. The measured effects of averaging, spatial filtering, temporal filtering, and sampling have been compared with theoretical calculations. The noise of unfiltered images is found to be white, as expected, and the choice of the temporal filter and sampling interval affects the noise in a manner predicted by sampling theory. The shapes of the imager's spatial frequency filters are extracted using noise power spectra.     

Noninvasive tracking of cardiac embryonic stem cells in vivo using magnetic resonance imaging techniques

Despite rapid advances in the stem cell field, the ability to identify and track transplanted or migrating stem cells in vivo is limited. To overcome this limitation, we used magnetic resonance imaging (MRI) to detect and follow transplanted stem cells over a period of 28 days in mice using an established myocardial infarction model. Pluripotent mouse embryonic stem (mES) cells were expanded and induced to differentiate into beating cardiomyocytes in vitro. The cardiac-differentiated mES cells were then loaded with superparamagnetic fluorescent microspheres (1.63 microm in diameter) and transplanted into ischemic myocardium immediately following ligation and subsequent reperfusion of the left anterior descending coronary artery. To identify the transplanted stem cells in vivo, MRI was performed using a Varian Inova 4.7 Tesla scanner. Our results show that (a) the cardiac-differentiated mES were effectively loaded with superparamagnetic microspheres in vitro, (b) the microsphere-loaded mES cells continued to beat in culture prior to transplantation, (c) the transplanted mES cells were readily detected in the heart in vivo using noninvasive MRI techniques, (d) the transplanted stem cells were detected in ischemic myocardium for the entire 28-day duration of the study as confirmed by MRI and post-mortem histological analyses, and (e) concurrent functional MRI indicated typical loss of cardiac function, although significant amelioration of remodeling was noted after 28 days in hearts that received transplanted stem cells. These results demonstrate that it is feasible to simultaneously track transplanted stem cells and monitor cardiac function in vivo over an extended period using noninvasive MRI techniques.     

Developing diagnostic techniques: The role of magnetic resonance imaging in tumour staging

Magnetic resonance (MR) is a state-of-the art imaging modality which does not use ionizing radiation. It is now widely available as an imaging technique in the U.K. and is no longer confined to specialist centres. MR has now become part of the clinician's diagnostic armamentarium and is not merely a research utility. A magnetic field and radio-frequency waves are used to excite protons and produce an image. Protons exist in many different environments but for imaging purposes the hydrogen protons in fat and water are used. The rate at which excited protons relax is described by two characteristic times, T₁ and T₂, which vary in different tissues. T₁-weighted images show normal anatomy, whilst T₂-weighted images generally highlight abnormal tissue. Injection of a paramagnetic gadolinium-based contrast agent enhances T₁-weighted images by reducing relaxation times. Initially it was felt that MR would be tissue-specific,¹ enabling correlation with histopathological findings. Unfortunately, research and clinical use has shown that MR does not fulfil these expectations at present.² Future developments such as spectroscopy may improve tissue specificity and hence diagnostic accuracy. The value of MR for imaging the neuro-axis and musculo-skeletal system is well established. New developments are increasing its applications in breast, thorax, and liver imaging. There has been much research into the role of MR in staging malignant tumours, particularly in the areas of bladder and lung carcinomas. The present article concentrates on this specific application.     

Directions in magnetic resonance imaging technology

Over the past few years there have been substantial improvements in the performance of magnetic resonance (MR) imagers. As image quality improved it became possible to perform studies in less time, increasing the throughput and the availability of the technique. A crucial contributor has been improvements in signal/noise. Techniques can now give signal/noise levels that a few years ago would have required much longer imaging times. With partial flip angle imaging techniques, it is possible to maintain image contrast and signal/noise while using reduced values of TR which decrease imaging time. It is also possible to decrease the number of acquired data lines and replace these lines mathematically at reconstruction time. Signal/noise is sacrificed, but the benefit is almost a factor of two in acquisition time. Echo planar techniques provide even higher speed imaging. In addition to the trade-off of signal/noise versus acquisition time, signal/noise can be traded for reduction in magnetic field strength. This results in reduced cost, improved patient access and also offers reduction in motion artifacts.     

Signal-to-noise efficiency in magnetic resonance imaging

The dependence of signal-to-noise ratio (SNR) on the analog filter, the sampling rate and the number and dimensions of voxels is derived for magnetic resonance imaging (MRI). It is shown that the object signal-to-noise ratio scales directly with the voxel volume and the square root of the number of voxels. Defining an efficiency figure of merit as the SNR divided by the square root of the imaging time, it is shown that efficiency is always improved when imaging with the lowest possible resolution (largest voxel dimensions) consistent with viewing the desired anatomical detail. The results directly imply the relative efficiency of 3-D (volume), 2-D (plane), 1-D (line) and 0-D (point) imaging techniques. It is shown that spatial averaging is an inefficient method of noise reduction in MRI. As long as voxel size is maintained constant, one can image as many pixels in the readout direction as desired with no loss in SNR; that is, the number of pixels in the readout direction has no effect on the image SNR. Further, multiple sampling of each phase encoding value (to improve SNR) has no advantage over increasing the number of pixels in the phase encoding direction while leaving the voxel size constant. Some experimental observations are given.     

Optimal preservation of porcine cardiac tissue prior to diffusion tensor magnetic resonance imaging

The effects of ex vivo preservation techniques on the quality of diffusion tensor magnetic resonance imaging in hearts are poorly understood, and the optimal handling procedure prior to investigation remains to be determined. Therefore, 24 porcine hearts were examined in six groups treated with different preservation techniques, including chemical fixation and freezing. Diffusion properties of each heart were assessed with diffusion tensor imaging in terms of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr). Tractography was performed to visualize the course of the cardiomyocytes, assuming greater diffusivity in the longitudinal than the transverse axis of individual cardiomyocytes. Significant differences in MD, Da and Dr were found, as well as in FA between groups (P < 0.001). Freezing of specimens resulted in the lowest mean FA of 0.21 (0.06) and highest Dr of 8.92 (1.5) mm² s⁻¹. The highest mean FA was found to be 0.43 (0.11) in hearts perfusion-fixed with formalin. Calculated tractographies were indistinguishable among groups except in frozen specimens, where no fibres could be tracked. Perfusion fixation with formalin provided the best tractography, but immersion fixation yielded diffusion data most similar to fresh hearts. These findings suggest that parameters derived from diffusion tensor imaging in ex vivo hearts are sensitive to fixation and storage methods. In particular, freezing of specimens should be avoided prior to diffusion tensor imaging investigation due to significant changes in diffusion parameters and subsequent image deteriorations.     

Exploring the frontiers of magnetic resonance imaging

New developments in magnetic resonance imaging are highlighted, including multiecho-multislice high-resolution imaging, special purpose coils, multiplanar imaging, thin slices, hybrid imaging processing, flow imaging, heart gating, paramagnetic contrast material, and wider application of spectroscopy.     

Oblique magnetic resonance imaging of the bronchi

The trachea and main bronchi of a supine patient in a magnetic resonance (MR) scanner are not contained in a single standard coronal plane, but instead intersect this coronal plane at some angle, usually 20 degrees - 35 degrees. We have developed a new MR imaging protocol to determine the oblique imaging plane which best contains the trachea and main bronchi. The resulting oblique images simplify anatomical identification, and allow the user to select additional oblique planes which cut any desired portion of main bronchus in true cross section. Accurate lumen shapes and areas may then be extracted from these cross-sectional images. The method does not require the patient to be moved or rotated, and does not require hardware modification. We demonstrate the clinical application of the protocol with both a normal volunteer and a patient with an endobronchial tumor. The use of gradient echo pulse sequences together with this protocol to distinguish between vessels and bronchi is presented. We provide phantom verification to demonstrate the quantitative accuracy of the method to provide lumen areas.