Molecular imaging in heart failure

Heart failure (HF), a heterogeneous syndrome of epidemic proportions, is increasingly defined by its underlying molecular and genomic alterations. Molecular cardiac imaging has emerged as a complementary discipline that has improved the understanding of the pathophysiologic principles governing experimental HF and has a potential to revolutionize assessment and management of HF in humans.     

Simulation of scanner- and patient-specific low-dose CT imaging from existing CT images

PurposeSimulating low-dose Computed Tomography (CT) facilitates in-silico studies into the required dose for a diagnostic task. Conventionally, low-dose CT images are created by adding noise to the projection data. However, in practice the raw data is often simply not available. This paper presents a new method for simulating patient-specific, low-dose CT images without the need of the original projection data.MethodsThe low-dose CT simulation method included the following: (1) computation of a virtual sinogram from a high dose CT image through a radon transform; (2) simulation of a ‘reduced’-dose sinogram with appropriate amounts of noise; (3) subtraction of the high-dose virtual sinogram from the reduced-dose sinogram; (4) reconstruction of a noise volume via filtered back-projection; (5) addition of the noise image to the original high-dose image. The required scanner-specific parameters, such as the apodization window, bowtie filter, the X-ray tube output parameter (reflecting the photon flux) and the detector read-out noise, were retrieved from calibration images of a water cylinder. The low-dose simulation method was evaluated by comparing the noise characteristics in simulated images with experimentally acquired data.ResultsThe models used to recover the scanner-specific parameters fitted accurately to the calibration data, and the values of the parameters were comparable to values reported in literature. Finally, the simulated low-dose images accurately reproduced the noise characteristics in experimentally acquired low-dose-volumes.ConclusionThe developed methods truthfully simulate low-dose CT imaging for a specific scanner and reconstruction using filtered backprojection. The scanner-specific parameters can be estimated from calibration data.     

Three-dimensional surface imaging from CT scans for the study of craniofacial dysmorphology

Computer-assisted medical imaging technologies provide new tools for the study of congenital craniofacial deformities. Three-dimensional surface reconstructions have been developed to simplify the interpretation and improve the utility of CT scans of the head. While 3-D reconstructions initially were applied to assist clinical management of craniofacial deformities, these images now are finding utility in the study of unique anomalies, the definition of group characteristics for dysmorphic heads, the differentiation of similar phenotypes, and the documentation of the effects of cranial surgery on craniofacial growth. These findings should assist the formulation and evaluation of hypotheses regarding mechanisms of congenital malformation and deformation.     

Joint dynamic imaging of morphogenesis and function in the developing heart

In the developing heart, time-lapse imaging is particularly challenging. Changes in heart morphology due to tissue growth or long-term reorganization are difficult to follow because they are much subtler than the rapid shape changes induced by the heartbeat. Therefore, imaging heart development usually requires slowing or stopping the heart. This, however, leads to information loss about the unperturbed heart shape and the dynamics of heart function. To overcome this limitation, we have developed a non-invasive heart imaging technique to jointly document heart function (at fixed stages of development) as well as its morphogenesis (at any fixed phase in the heartbeat) that does not require stopping or slowing the heart. We review the challenges for imaging heart development and our methodology, which is based on computationally combining and analyzing multiple high-speed image sequences acquired throughout the course of development. We present results obtained in the developing zebrafish heart. Image analysis of the acquired data yielded blood flow velocity maps and made it possible to follow the relative movement of individual cells over several hours.Key words: cardiac imaging, zebrafish, fluorescence imaging, heart development, registration, fast imaging     

Joint dynamic imaging of morphogenesis and function in the developing heart

In the developing heart, time-lapse imaging is particularly challenging. Changes in heart morphology due to tissue growth or long-term reorganization are difficult to follow because they are much subtler than the rapid shape changes induced by the heartbeat. Therefore, imaging heart development usually requires slowing or stopping the heart. This, however, leads to information loss about the unperturbed heart shape and the dynamics of heart function. To overcome this limitation, we have developed a non-invasive heart imaging technique to jointly document heart function (at fixed stages of development) as well as its morphogenesis (at any fixed phase in the heartbeat) that does not require stopping or slowing the heart. We review the challenges for imaging heart development and our methodology, which is based on computationally combining and analyzing multiple high-speed image sequences acquired throughout the course of development. We present results obtained in the developing zebrafish heart. Image analysis of the acquired data yielded blood flow velocity maps and made it possible to follow the relative movement of individual cells over several hours.     

Molecular imaging of the embryonic heart: Fables and facts on 3D imaging of gene expression patterns

Molecular imaging, which is the three-dimensional (3D) visualization of gene expression patterns, is indispensable for the study of the function of genes in cardiac development. The instrumentation, as well as the development of specific contrast agents for molecular imaging, has shown spectacular advances in the last decade. In this review, the spatial resolutions, contrast agents, and applications of these imaging methods in the field of cardiac embryology are discussed. Apart from 3D reconstructions from histological sections, not many of these methods have been applied in embryological research. This review shows that, for most methods, neither the spatial resolutions nor the specificity and applicability of the contrast agents are adequate for the reliable imaging of specific gene expression at the microscopic resolution required for embryological studies of small organs like the developing heart. Although a 3D reconstruction from sections will always suffer from imperfections, the resulting reconstructions meet the aim of most biological studies, especially since the original microscopic images are linked. With respect to imaging of gene expression, only histological sections and laser scanning microscopy provide the required resolution and specificity at the tissue and cellular level. Episcopic fluorescence image capturing and optical projection tomography are being used for microscopic phenotyping and lineage analysis, and both show potential for detailed molecular imaging. Other methods can be used very efficiently in rapid evaluation of biological experiments and high-throughput screens of large-scale gene expression profiling efforts when high spatial resolution is not required.     

CT imaging with iopromide liposomes in a rabbit model

The aim of this study was to evaluate the computed tomography (CT)-imaging potential of iopromide-carrying liposomes (SPC/CH/SPG, 6:3:1) of approximately 200?nm in diameter in healthy rabbits and in rabbits with implanted liver tumors in an intraindividual comparison with iopromide. Normal rabbits and animals with VX2 tumors implanted into the liver received iopromide (600?mg of iodine/kg, bolus injection) and, 1 or 2 days later, iopromide liposomes (300?mg of iodine/kg, bolus injection or 10-minute infusion). CT imaging up to 1 hour after administration was performed, focusing on the aorta, vena cava, kidney, spleen, and liver. Pharmacokinetic parameters for CT enhancement were calculated. Detectability and delineation of liver lesions were assessed on a 4-grade scale, and differences were evaluated statistically. Using half the iodine dose, iopromide liposomes achieved similar blood-pool enhancement as iopromide. Detectability and delineation of liver lesions were easy/good in the arterial phase after iopromide injection, but poor in the venous and equilibration phases. Iopromide liposomes resulted in a long-lasting, good detectability and delineation of liver lesions similar or superior to that observed after iopromide in the arterial phase.     

Progress in noninvasive coronary artery imaging using multislice CT

Conventional coronary angiography (CAG) has been the reference standard for the assessment of coronary artery disease since its introduction in 1958. However, several studies have shown that diagnostic CAG has an average morbidity of 2% and a mortality of approximately 0.1%.In the last decade, progress in medical imaging has opened the way to noninvasive assessment of the coronary arteries at lower cost and risk. Of the different modalities, multislice CT (MSCT) has made the biggest step forward. At the 2005 European Congress of Radiology (ECR), experiences with the latest developments in noninvasive coronary artery imaging were reported. This report summarises the advances in the use of MSCT in coronary stenosis detection, emergency decision-making, plaque imaging, and the analysis of cardiac function and late enhancement. Also, attention is paid to new strategies to reduce MSCT-related radiation exposure.     

CT fractional flow reserve: the next level in non-invasive cardiac imaging

The haemodynamic effect of a coronary artery stenosis is a better predictor of prognosis than anatomical lumen obstruction. Until recently, no individual non-invasive test could provide both accurate coronary anatomy and lesion-specific myocardial ischaemia. However, computer tomography (CT) fractional flow reserve, which can be calculated from a standard CT coronary angiogram, was recently demonstrated to accurately detect and rule out the haemodynamic significance of individual coronary artery stenoses.     

Orbital volume measurements in enophthalmos using three-dimensional CT imaging

The purpose of this study was to investigate enophthalmos by measuring the volume of various orbital structures using off-line computer techniques on images generated by a CT scanner. Eleven patients with enophthalmos had CT scans of the orbits consisting of 30 to 40 adjacent 1.5-mm slices. The data from the scans were analyzed on a Nova 830 stand-alone computer system using software programs that allowed measurement of total bony orbital volume, total soft-tissue volume, globe volume, orbital fat volume, neuromuscular tissue volume, and apex-to-globe distance in the horizontal plane. These data were analyzed comparing the volumes in the normal eye with the volumes in the enophthalmic eye in each patient. The analysis demonstrated a statistically significant increase in bony orbital volume in the enophthalmic eye, but the total soft-tissue volume, fat volume, neuromuscular tissue volume, and globe volume were the same as in the normal eye. The apex-to-globe distance, a measure of the degree of enophthalmos, was less in the enophthalmic eye than in the normal eye. These results suggest that in the majority of patients, the cause of posttraumatic enophthalmos is increased bony orbital volume rather than by soft-tissue loss or fat necrosis. (Several patients showed no volume discrepancies, and it is likely that cicatricial contracture is responsible for the enophthalmos in these cases.) This study suggests that the objective of surgery for correction of enophthalmos in patients with a volume discrepancy should be to decrease the volume of the bony orbit and to increase the anterior projection of the globe.     

Cardiac MIBG imaging at the edge of clinical application in heart failure

Neuronal innervation plays a crucial role in cardiac function. The heart is richly innervated with sympathetic and parasympathetic fibers that work in conjunction with circulating catecholamine mediators, such as norepinephrine (NE), to tightly regulate cardiac output at rest and during periods of increased cardiac demand. An impairment of cardiac autonomic function, most often the result of cardiac disease (ischemic or nonischemic cardiomyopathy), can reflect the severity of the condition, and in many cases is associated with and likely contributing to worsening of the clinical condition, increasing the potential for life-threatening cardiac arrhythmias and death. Because cardiac autonomic function involves numerous molecular processes, use of radiotracers for imaging is an ideal method of assessment.     

High-throughput multiple-mouse imaging with micro-PET/CT for whole-skeleton assessment

Recent studies have proven that skeleton-wide functional assessment is essential to comprehensively understand physiological aspects of the skeletal system. Therefore, in contrast to regional imaging studies utilizing a multiple-animal holder (mouse hotel), we attempted to develop and characterize a multiple-mouse imaging system with micro-PET/CT for high-throughput whole-skeleton assessment. Using items found in a laboratory, a simple mouse hotel that houses four mice linked with gas anesthesia was constructed. A mouse-simulating phantom was used to measure uniformity in a cross sectional area and flatness (A_max/A_min*100) along the axial, radial and tangential directions, where A_max and A_min are maximum and minimum activity concentration in the profile, respectively. Fourteen mice were used for single- or multiple-micro-PET/CT scans. NaF uptake was measured at eight skeletal sites (skull to tibia). Skeletal ¹⁸F activities measured with mice in the mouse hotel were within 1.6 ± 4% (mean ± standard deviation) of those measured with mice in the single-mouse holder. Single-holder scanning yields slightly better uniformity and flatness over the hotel. Compared to use of the single-mouse holder, scanning with the mouse hotel reduced study time (by 65%), decreased the number of scans (four-fold), reduced cost, required less computer storage space (40%), and maximized ¹⁸F usage. The mouse hotel allows high-throughput, quantitatively equivalent scanning compared to the single-mouse holder for micro-PET/CT imaging for whole-skeleton assessment of mice.     

Novel imaging strategies for the detection of prosthetic heart valve obstruction and endocarditis

Prosthetic heart valve (PHV) dysfunction remains difficult to recognise correctly by two-dimensional (2D) transthoracic and transoesophageal echocardiography (TTE/TEE). ECG-triggered multidetector-row computed tomography (MDCT), 18-fluorine-fluorodesoxyglucose positron emission tomography including low-dose CT (FDG-PET) and three-dimensional transoesophageal echocardiography (3D-TEE) may have additional value. This paper reviews the role of these novel imaging tools in the field of PHV obstruction and endocarditis.For acquired PHV obstruction, MDCT is of additional value in mechanical PHVs to differentiate pannus from thrombus as well as to dynamically study leaflet motion and opening/closing angles. For biological PHV obstruction, additional imaging is not beneficial as it does not change patient management. When performed on top of 2D-TTE/TEE, MDCT has additional value for the detection of both vegetations and pseudoaneurysms/abscesses in PHV endocarditis. FDG-PET has no complementary value for the detection of vegetations; however, it appears more sensitive in the early detection of pseudoaneurysms/abscesses. Furthermore, FDG-PET enables the detection of metastatic and primary extra-cardiac infections. Evidence for the additional value of 3D-TEE is scarce.As clinical implications are major, clinicians should have a low threshold to perform additional MDCT in acquired mechanical PHV obstruction. For suspected PHV endocarditis, both FDG-PET and MDCT have complementary value.     

Dynamic imaging of zebrafish heart with multi-planar light sheet microscopy

Light sheet fluorescence microscopy has become a research hotspot in biomedicine because of low phototoxicity, high speed, and high resolution. However, the conventional methods to acquire three-dimensional spatial information are mainly based on scanning, which inevitably increases photodamage and is not real-time. Here, we propose a method to generate controllable multi-planar illumination with a dielectric isosceles triangular array and a design of multi-planar light sheet fluorescence microscopy system. We carry out experiments of three-dimensional illumination beam measurement, volumetric imaging of fluorescent microspheres, and dynamic in vivo imaging of zebrafish heart to evaluate the performance of this system. In addition, we apply this system to study the effects of bisphenol fluorene on the heart shape and heart-beating rate of zebrafish. Our experiment results indicate that the multi-planar light sheet microscopy system provides a novel and feasible method for three-dimensional selected plane imaging and low-phototoxicity in vivo imaging.     

Cardiac magnetic resonance imaging in stable ischaemic heart disease

Cardiac magnetic resonance imaging (CMR) is a new robust versatile non-invasive imaging technique that can detect global and regional myocardial dysfunction, presence of myocardial ischaemia and myocardial scar tissue in one imaging session without radiation, with superb spatial and temporal resolution, inherited three-dimensional data collection and with relatively safe contrast material. The reproducibility of CMR is high which makes it possible to use this technique for serial assessment to evaluate the effect of revascularisation therapy in patients with ischaemic heart disease.     

Investigation of the dose distribution for a cone beam CT system dedicated to breast imaging

Cone-beam breast Computed Tomography (bCT) is an X-ray imaging technique for breast cancer diagnosis, in principle capable of delivering a much more homogeneous dose spatial pattern to the breast volume than conventional mammography, at dose levels comparable to two-view mammography. We present an investigation of the three-dimensional dose distribution for a cone-beam CT system dedicated to breast imaging. We employed Monte Carlo simulations for estimating the dose deposited within a breast phantom having a hemiellipsoidal shape placed on a cylinder of 3.5 cm thickness that simulates the chest wall. This phantom represents a pendulant breast in a bCT exam with the average diameter at chest wall, assumed to correspond to a 5-cm-thick compressed breast in mammography. The phantom is irradiated in a circular orbit with an X-ray cone beam selected from four different techniques: 50, 60, 70, and 80 kVp from a tube with tungsten anode, 1.8 mm Al inherent filtration and additional filtration of 0.2 mm Cu. Using the Monte Carlo code GEANT4 we simulated a system similar to the experimental apparatus available in our lab. Simulations were performed at a constant free-in-air air kerma at the isocenter (1 μGy); the corresponding total number of photon histories per scan was 288 million at 80 kVp. We found that the more energetic beams provide a more uniform dose distribution than at low energy: the 50 kVp beam presents a frequency distribution of absorbed dose values with a coefficient of variation almost double than that for the 80 kVp beam. This is confirmed by the analysis of the relative dose profiles along the radial (i.e. parallel to the “chest wall”) and longitudinal (i.e. from “chest wall” to “nipple”) directions. Maximum radial deviations are on the order of 25% for the 80 kVp beam, whereas for the 50 kVp beam variations around 43% were observed, with the lowest dose values being found along the central longitudinal axis of the phantom.