Improved temporal resolution for functional studies with reduced number of segments with three-dimensional echo planar imaging.

PURPOSE: To introduce a new k-space traversal strategy for segmented three-dimensional echo planar imaging (3D EPI) that encodes two partitions per radiofrequency excitation, effectively reducing the number excitations used to acquire a 3D EPI dataset by half. METHODS: The strategy was evaluated in the context of functional MRI applications for: image quality compared with segmented 3D EPI, temporal signal-to-noise ratio (tSNR) (the ability to detect resting state networks compared with multislice two-dimensional (2D) EPI and segmented 3D EPI, and temporal resolution (the ability to separate cardiac- and respiration-related fluctuations from the desired blood oxygen level-dependent signal of interest). RESULTS: Whole brain images with a nominal voxel size of 2 mm isotropic could be acquired with a temporal resolution under half a second using traditional parallel imaging acceleration up to 4× in the partition-encode direction and using novel data acquisition speed-up of 2× with a 32-channel coil. With 8× data acquisition speed-up in the partition-encode direction, 3D reduced excitations (RE)-EPI produced acceptable image quality without introduction of noticeable additional artifacts. Due to increased tSNR and better characterization of physiological fluctuations, the new strategy allowed detection of more resting state networks compared with multislice 2D-EPI and segmented 3D EPI. CONCLUSION: 3D RE-EPI resulted in significant increases in temporal resolution for whole brain acquisitions and in improved physiological noise characterization compared with 2D-EPI and segmented 3D EPI. Magn Reson Med 72:786-792, 2014. © 2013 Wiley Periodicals, Inc.

Improved SNR efficiency in gradient echo coronary MRA with high temporal resolution using parallel imaging.

Contemporary coronary magnetic resonance angiography techniques suffer from signal-to-noise ratio (SNR) constraints. We propose a method to enhance SNR in gradient echo coronary magnetic resonance angiography by using sensitivity encoding (SENSE). While the use of sensitivity encoding to improve SNR seems counterintuitive, it can be exploited by reducing the number of radiofrequency excitations during the acquisition window while lowering the signal readout bandwidth, therefore improving the radiofrequency receive to radiofrequency transmit duty cycle. Under certain conditions, this leads to improved SNR. The use of sensitivity encoding for improved SNR in three-dimensional coronary magnetic resonance angiography is investigated using numerical simulations and an in vitro and an in vivo study. A maximum 55% SNR enhancement for coronary magnetic resonance angiography was found both in vitro and in vivo, which is well consistent with the numerical simulations. This method is most suitable for spoiled gradient echo coronary magnetic resonance angiography in which a high temporal and spatial resolution is required.

Cardiovascular magnetic resonance imaging techniques for motion-suppressed multi-dimensional coronary artery imaging with high spatial and temporal resolution

L'imagerie par résonance magnétique (IRM) peut fournir aux cardiologues des informations diagnostiques importantes sur l'état de la maladie de l'artère coronarienne dans les patients. Le défi majeur pour l'IRM cardiaque est de gérer toutes les sources de mouvement qui peuvent affecter la qualité des images en réduisant l'information diagnostique. Cette thèse a donc comme but de développer des nouvelles techniques d'acquisitions des images IRM, en changeant les techniques de compensation du mouvement, pour en augmenter l'efficacité, la flexibilité, la robustesse et pour obtenir plus d'information sur le tissu et plus d'information temporelle. Les techniques proposées favorisent donc l'avancement de l'imagerie des coronaires dans une direction plus maniable et multi-usage qui peut facilement être transférée dans l'environnement clinique. La première partie de la thèse s'est concentrée sur l'étude du mouvement des artères coronariennes sur des patients en utilisant la techniques d'imagerie standard (rayons x), pour mesurer la précision avec laquelle les artères coronariennes retournent dans la même position battement après battement (repositionnement des coronaires). Nous avons découvert qu'il y a des intervalles dans le cycle cardiaque, tôt dans la systole et à moitié de la diastole, où le repositionnement des coronaires est au minimum. En réponse nous avons développé une nouvelle séquence d'acquisition (T2-post) capable d'acquérir les données aussi tôt dans la systole. Cette séquence a été testée sur des volontaires sains et on a pu constater que la qualité de visualisation des artère coronariennes est égale à celle obtenue avec les techniques standard. De plus, le rapport signal sur bruit fourni par la séquence d'acquisition proposée est supérieur à celui obtenu avec les techniques d'imagerie standard. La deuxième partie de la thèse a exploré un paradigme d'acquisition des images cardiaques complètement nouveau pour l'imagerie du coeur entier. La technique proposée dans ce travail acquiert les données sans arrêt (free-running) au lieu d'être synchronisée avec le mouvement cardiaque. De cette façon, l'efficacité de la séquence d'acquisition est augmentée de manière significative et les images produites représentent le coeur entier dans toutes les phases cardiaques (quatre dimensions, 4D). Par ailleurs, l'auto-navigation de la respiration permet d'effectuer cette acquisition en respiration libre. Cette technologie rend possible de visualiser et évaluer l'anatomie du coeur et de ses vaisseaux ainsi que la fonction cardiaque en quatre dimensions et avec une très haute résolution spatiale et temporelle, sans la nécessité d'injecter un moyen de contraste. Le pas essentiel qui a permis le développement de cette technique est l'utilisation d'une trajectoire d'acquisition radiale 3D basée sur l'angle d'or. Avec cette trajectoire, il est possible d'acquérir continûment les données d'espace k, puis de réordonner les données et choisir les paramètres temporel des images 4D a posteriori. L'acquisition 4D a été aussi couplée avec un algorithme de reconstructions itératif (compressed sensing) qui permet d'augmenter la résolution temporelle tout en augmentant la qualité des images. Grâce aux images 4D, il est possible maintenant de visualiser les artères coronariennes entières dans chaque phase du cycle cardiaque et, avec les mêmes données, de visualiser et mesurer la fonction cardiaque. La qualité des artères coronariennes dans les images 4D est la même que dans les images obtenues avec une acquisition 3D standard, acquise en diastole Par ailleurs, les valeurs de fonction cardiaque mesurées au moyen des images 4D concorde avec les valeurs obtenues avec les images 2D standard. Finalement, dans la dernière partie de la thèse une technique d'acquisition a temps d'écho ultra-court (UTE) a été développée pour la visualisation in vivo des calcifications des artères coronariennes. Des études récentes ont démontré que les acquisitions UTE permettent de visualiser les calcifications dans des plaques athérosclérotiques ex vivo. Cepandent le mouvement du coeur a entravé jusqu'à maintenant l'utilisation des techniques UTE in vivo. Pour résoudre ce problème nous avons développé une séquence d'acquisition UTE avec trajectoire radiale 3D et l'avons testée sur des volontaires. La technique proposée utilise une auto-navigation 3D pour corriger le mouvement respiratoire et est synchronisée avec l'ECG. Trois échos sont acquis pour extraire le signal de la calcification avec des composants au T2 très court tout en permettant de séparer le signal de la graisse depuis le signal de l'eau. Les résultats sont encore préliminaires mais on peut affirmer que la technique développé peut potentiellement montrer les calcifications des artères coronariennes in vivo. En conclusion, ce travail de thèse présente trois nouvelles techniques pour l'IRM du coeur entier capables d'améliorer la visualisation et la caractérisation de la maladie athérosclérotique des coronaires. Ces techniques fournissent des informations anatomiques et fonctionnelles en quatre dimensions et des informations sur la composition du tissu auparavant indisponibles. CORONARY artery magnetic resonance imaging (MRI) has the potential to provide the cardiologist with relevant diagnostic information relative to coronary artery disease of patients. The major challenge of cardiac MRI, though, is dealing with all sources of motions that can corrupt the images affecting the diagnostic information provided. The current thesis, thus, focused on the development of new MRI techniques that change the standard approach to cardiac motion compensation in order to increase the efficiency of cardioavscular MRI, to provide more flexibility and robustness, new temporal information and new tissue information. The proposed approaches help in advancing coronary magnetic resonance angiography (MRA) in the direction of an easy-to-use and multipurpose tool that can be translated to the clinical environment. The first part of the thesis focused on the study of coronary artery motion through gold standard imaging techniques (x-ray angiography) in patients, in order to measure the precision with which the coronary arteries assume the same position beat after beat (coronary artery repositioning). We learned that intervals with minimal coronary artery repositioning occur in peak systole and in mid diastole and we responded with a new pulse sequence (T2~post) that is able to provide peak-systolic imaging. Such a sequence was tested in healthy volunteers and, from the image quality comparison, we learned that the proposed approach provides coronary artery visualization and contrast-to-noise ratio (CNR) comparable with the standard acquisition approach, but with increased signal-to-noise ratio (SNR). The second part of the thesis explored a completely new paradigm for whole- heart cardiovascular MRI. The proposed techniques acquires the data continuously (free-running), instead of being triggered, thus increasing the efficiency of the acquisition and providing four dimensional images of the whole heart, while respiratory self navigation allows for the scan to be performed in free breathing. This enabling technology allows for anatomical and functional evaluation in four dimensions, with high spatial and temporal resolution and without the need for contrast agent injection. The enabling step is the use of a golden-angle based 3D radial trajectory, which allows for a continuous sampling of the k-space and a retrospective selection of the timing parameters of the reconstructed dataset. The free-running 4D acquisition was then combined with a compressed sensing reconstruction algorithm that further increases the temporal resolution of the 4D dataset, while at the same time increasing the overall image quality by removing undersampling artifacts. The obtained 4D images provide visualization of the whole coronary artery tree in each phases of the cardiac cycle and, at the same time, allow for the assessment of the cardiac function with a single free- breathing scan. The quality of the coronary arteries provided by the frames of the free-running 4D acquisition is in line with the one obtained with the standard ECG-triggered one, and the cardiac function evaluation matched the one measured with gold-standard stack of 2D cine approaches. Finally, the last part of the thesis focused on the development of ultrashort echo time (UTE) acquisition scheme for in vivo detection of calcification in the coronary arteries. Recent studies showed that UTE imaging allows for the coronary artery plaque calcification ex vivo, since it is able to detect the short T2 components of the calcification. The heart motion, though, prevented this technique from being applied in vivo. An ECG-triggered self-navigated 3D radial triple- echo UTE acquisition has then been developed and tested in healthy volunteers. The proposed sequence combines a 3D self-navigation approach with a 3D radial UTE acquisition enabling data collection during free breathing. Three echoes are simultaneously acquired to extract the short T2 components of the calcification while a water and fat separation technique allows for proper visualization of the coronary arteries. Even though the results are still preliminary, the proposed sequence showed great potential for the in vivo visualization of coronary artery calcification. In conclusion, the thesis presents three novel MRI approaches aimed at improved characterization and assessment of atherosclerotic coronary artery disease. These approaches provide new anatomical and functional information in four dimensions, and support tissue characterization for coronary artery plaques.

Temporal SNR characteristics in segmented 3D-EPI at 7T.

Three-dimensional segmented echo planar imaging (3D-EPI) is a promising approach for high-resolution functional magnetic resonance imaging, as it provides an increased signal-to-noise ratio (SNR) at similar temporal resolution to traditional multislice 2D-EPI readouts. Recently, the 3D-EPI technique has become more frequently used and it is important to better understand its implications for fMRI. In this study, the temporal SNR characteristics of 3D-EPI with varying numbers of segments are studied. It is shown that, in humans, the temporal variance increases with the number of segments used to form the EPI acquisition and that for segmented acquisitions, the maximum available temporal SNR is reduced compared to single shot acquisitions. This reduction with increased segmentation is not found in phantom data and thus likely due to physiological processes. When operating in the thermal noise dominated regime, fMRI experiments with a motor task revealed that the 3D variant outperforms the 2D-EPI in terms of temporal SNR and sensitivity to detect activated brain regions. Thus, the theoretical SNR advantage of a segmented 3D-EPI sequence for fMRI only exists in a low SNR situation. However, other advantages of 3D-EPI, such as the application of parallel imaging techniques in two dimensions and the low specific absorption rate requirements, may encourage the use of the 3D-EPI sequence for fMRI in situations with higher SNR.

Chemical genetic analysis of cdc2p : new insights into the regulation of cytokinesis in "Schizosaccharomyces pombe"

RÉSUMÉ La protéine kinase cyciine-cdc2p (Cdk) joue un rôle fondamental dans la progression du cycle cellulaire dans la levure de fission Schizosaccharomyces pombe. Nous avons étudié le rôle de cdc2p dans la régulation de la cascade de septation ou SIN (septation initiation network) en mitose et en méiose. Le SIN contrôle l'initiation de la cytokinèse à la fin de la mitose, et est supposé être négativement régulé par cdc2p. Nous avons mutagénéisé le site actif de cdc2p afin qu'il puisse lier un analogue de l'ATP (PP1) qui agit comme inhibiteur. Cet analogue ne peut pas lier la kinase de type sauvage. Cette approche dite «chemical genetics» permet une meilleure résolution temporelle comparée à l'approche classique utilisant les mutants sensibles à une température élevée. Nous avons montré que ce mutant cdc2-as (analogue sensitive) est fonctionnel et que, in vitro, l'activité kinase est inhibée en présence de l'analogue. Les cellules portant cette mutation, contrairement aux cellules de type sauvage s'arrêtent de manière irréversible soit en G2 soit en G1 et G2, suivant la concentration de l'inhibiteur. L'inactivation de cdc2p-as dans des cellules arrêtées en métaphase conduit au recrutement asymétrique des protéines du SIN sur le pôle du fuseau mitotique et au recrutement des composants du SIN, ainsi que de la ß-(1,3)glucan synthase à l'anneau contractile. De plus, nos résultats montrent que l'orthologue de la phosphatase cdc14p dans S. pombe, fip1p/clp1p, joue un rôle dans la régulation de la localisation des protéines du SIN suite à l'inactivation de cdc2p. Finalement, l'activité de cdc2p est requise pour maintenir la polo-like kinase plo1p sur les pôles du fuseau mitotique dans les premiers stages de la mitose. C'est pourquoi nous concluons que l'inactivation de cdc2p est suffisante pour activer le SIN et promouvoir la cytokinèse. Dans une étude séparée, nous avons caractérisé des potentiellement nouveaux composants ou régulateurs du SIN qui ont été isolés dans deux criblages génétiques visant à isoler des mutants atténuants la signalisation du SIN. Summary : The cyclin dependent protein kinase (Cdk) cdc2p plays a central role in the cell cycle progression of fission yeast Schizosaccharomyces pombe. We have studied the role of cdc2p in regulating the septation initiation network (SIN) in mitosis and meiosis. The SIN regulates the initiation of cytokinesis at the end of mitosis and is thought to be inhibited by cdc2p. We have mutated the active site of cdc2p to permit binding of an inhibitory ATP analogue (PP1), which is unable to bind unmodified kinases. This "chemical genetic" approach provides a much higher temporal resolution than it can be achieved with classical temperature-sensitive mutants. We demonstrate that cdc2-as (analogue sensitive) is functional and that addition of PP1 inhibits cdc2p kinase activity in vitro. Cells carrying the cdc2-as allele, but not cdc2+, undergo reversible cell cycle arrest following addition of PP1 either in G2, or at both major commitment points in the cell cycle (G1 and G2), depending upon the concentration of PP1. Inactivation of cdc2p-as in cells arrested in early mitosis promotes both the asymmetric recruitment of SIN proteins to the spindle pole bodies (SPBs), and the recruitment of the most downstream SIN components and ß-(1,3)-glucan synthase to the contractile ring. Furthermore, our results indicate that the S. pombe orthologue of Cdc14p, flp1p/clp1p, plays a role in regulating the relocalisation of SIN proteins following inactivation of cdc2p, and that cdc2p activity is required to retain the polo like kinase plot p on the SPBs in early mitosis. Thus, we conclude that inactivation of cdc2p is sufficient to activate the SIN and to promote cytokinesis. In a separate study, we have initially characterised potential novel components or regulators of the SIN pathway identified by two genetic screens for mutants attenuating SIN signaling.

Motion compensation strategies in magnetic resonance imaging.

Image quality in magnetic resonance imaging (MRI) is considerably affected by motion. Therefore, motion is one of the most common sources of artifacts in contemporary cardiovascular MRI. Such artifacts in turn may easily lead to misinterpretations in the images and a subsequent loss in diagnostic quality. Hence, there is considerable research interest in strategies that help to overcome these limitations at minimal cost in time, spatial resolution, temporal resolution, and signal-to-noise ratio. This review summarizes and discusses the three principal sources of motion: the beating heart, the breathing lungs, and bulk patient movement. This is followed by a comprehensive overview of commonly used compensation strategies for these different types of motion. Finally, a summary and an outlook are provided.

A two-compartment mathematical model of neuroglial metabolism using [1-(11)C] acetate.

The purpose of this study was to develop a two-compartment metabolic model of brain metabolism to assess oxidative metabolism from [1-(11)C] acetate radiotracer experiments, using an approach previously applied in (13)C magnetic resonance spectroscopy (MRS), and compared with an one-tissue compartment model previously used in brain [1-(11)C] acetate studies. Compared with (13)C MRS studies, (11)C radiotracer measurements provide a single uptake curve representing the sum of all labeled metabolites, without chemical differentiation, but with higher temporal resolution. The reliability of the adjusted metabolic fluxes was analyzed with Monte-Carlo simulations using synthetic (11)C uptake curves, based on a typical arterial input function and previously published values of the neuroglial fluxes V(tca)(g), V(x), V(nt), and V(tca)(n) measured in dynamic (13)C MRS experiments. Assuming V(x)(g)=10 × V(tca)(g) and V(x)(n)=V(tca)(n), it was possible to assess the composite glial tricarboxylic acid (TCA) cycle flux V(gt)(g) (V(gt)(g)=V(x)(g) × V(tca)(g)/(V(x)(g)+V(tca)(g))) and the neurotransmission flux V(nt) from (11)C tissue-activity curves obtained within 30 minutes in the rat cortex with a beta-probe after a bolus infusion of [1-(11)C] acetate (n=9), resulting in V(gt)(g)=0.136±0.042 and V(nt)=0.170±0.103 μmol/g per minute (mean±s.d. of the group), in good agreement with (13)C MRS measurements.

Neuroimaging techniques in Alzheimer's disease

Neuroimaging techniques provide valuable tools for diagnosing Alzheimer's disease (AD), monitoring disease progression and evaluating responses to treatment. There is currently a wide array of techniques available including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and, for recording electrical brain activity, electroencephalography (EEG). The choice of technique depends on the contrast between tissues of interest, spatial resolution, temporal resolution, requirements for functional data and the probable number of scans required. For example, while PET, CT and MRI can be used to differentiate between AD and other dementias, MRI is safer and provides better contrast of soft tissues. Neuroimaging is a technique spanning many disciplines and requires effective communication between doctors requesting a scan of a patient or group of patients and those with technical expertise. Consideration and discussion of the most suitable type of scan and the necessary settings to achieve the best results will help ensure appropriate techniques are chosen and used effectively. Neuroimaging techniques are currently expanding understanding of the structural and functional changes that occur in dementia. Further research may allow identification of early neurological signs ofAD, before clinical symptoms are evident, providing the opportunity to test preventative therapies. CombiningMRI and machine learning techniques may be a powerful approach to improve diagnosis ofAD and to predict clinical outcomes.

Standardization of Stroke Perfusion CT for Reperfusion Therapy

With the advances in terms of perfusion imaging, the "time is brain" approach used for acute reperfusion therapy in ischemic stroke patients is slowly being replaced by a "penumbra is brain" or "imaging is brain" approach. But the concept of penumbra-guided reperfusion therapy has not been validated. The lack of standardization in penumbral imaging is one of the main contributing factors for this absence of validation. This article reviews the issues underlying the lack of standardization of perfusion-CT for penumbra imaging, and offers avenues to remedy this situation

24 Hours in the Life of HIV-1 in a T Cell Line.

HIV-1 infects CD4+ T cells and completes its replication cycle in approximately 24 hours. We employed repeated measurements in a standardized cell system and rigorous mathematical modeling to characterize the emergence of the viral replication intermediates and their impact on the cellular transcriptional response with high temporal resolution. We observed 7,991 (73%) of the 10,958 expressed genes to be modulated in concordance with key steps of viral replication. Fifty-two percent of the overall variability in the host transcriptome was explained by linear regression on the viral life cycle. This profound perturbation of cellular physiology was investigated in the light of several regulatory mechanisms, including transcription factors, miRNAs, host-pathogen interaction, and proviral integration. Key features were validated in primary CD4+ T cells, and with viral constructs using alternative entry strategies. We propose a model of early massive cellular shutdown and progressive upregulation of the cellular machinery to complete the viral life cycle.

Early processing in the human lateral occipital complex is highly responsive to illusory contours but not to salient regions.

Human electrophysiological studies support a model whereby sensitivity to so-called illusory contour stimuli is first seen within the lateral occipital complex. A challenge to this model posits that the lateral occipital complex is a general site for crude region-based segmentation, based on findings of equivalent hemodynamic activations in the lateral occipital complex to illusory contour and so-called salient region stimuli, a stimulus class that lacks the classic bounding contours of illusory contours. Using high-density electrical mapping of visual evoked potentials, we show that early lateral occipital cortex activity is substantially stronger to illusory contour than to salient region stimuli, whereas later lateral occipital complex activity is stronger to salient region than to illusory contour stimuli. Our results suggest that equivalent hemodynamic activity to illusory contour and salient region stimuli probably reflects temporally integrated responses, a result of the poor temporal resolution of hemodynamic imaging. The temporal precision of visual evoked potentials is critical for establishing viable models of completion processes and visual scene analysis. We propose that crude spatial segmentation analyses, which are insensitive to illusory contours, occur first within dorsal visual regions, not the lateral occipital complex, and that initial illusory contour sensitivity is a function of the lateral occipital complex.

Calcium imaging of odor-evoked responses in the Drosophila antennal lobe.

The antennal lobe is the primary olfactory center in the insect brain and represents the anatomical and functional equivalent of the vertebrate olfactory bulb. Olfactory information in the external world is transmitted to the antennal lobe by olfactory sensory neurons (OSNs), which segregate to distinct regions of neuropil called glomeruli according to the specific olfactory receptor they express. Here, OSN axons synapse with both local interneurons (LNs), whose processes can innervate many different glomeruli, and projection neurons (PNs), which convey olfactory information to higher olfactory brain regions. Optical imaging of the activity of OSNs, LNs and PNs in the antennal lobe - traditionally using synthetic calcium indicators (e.g. calcium green, FURA-2) or voltage-sensitive dyes (e.g. RH414) - has long been an important technique to understand how olfactory stimuli are represented as spatial and temporal patterns of glomerular activity in many species of insects. Development of genetically-encoded neural activity reporters, such as the fluorescent calcium indicators G-CaMP and Cameleon, the bioluminescent calcium indicator GFP-aequorin, or a reporter of synaptic transmission, synapto-pHluorin has made the olfactory system of the fruitfly, Drosophila melanogaster, particularly accessible to neurophysiological imaging, complementing its comprehensively-described molecular, electrophysiological and neuroanatomical properties. These reporters can be selectively expressed via binary transcriptional control systems (e.g. GAL4/UAS, LexA/LexAop, Q system) in defined populations of neurons within the olfactory circuitry to dissect with high spatial and temporal resolution how odor-evoked neural activity is represented, modulated and transformed. Here we describe the preparation and analysis methods to measure odor-evoked responses in the Drosophila antennal lobe using G-CaMP. The animal preparation is minimally invasive and can be adapted to imaging using wide-field fluorescence, confocal and two-photon microscopes.

Mammalian genes are transcribed with widely different bursting kinetics.

In prokaryotes and eukaryotes, most genes appear to be transcribed during short periods called transcriptional bursts, interspersed by silent intervals. We describe how such bursts generate gene-specific temporal patterns of messenger RNA (mRNA) synthesis in mammalian cells. To monitor transcription at high temporal resolution, we established various gene trap cell lines and transgenic cell lines expressing a short-lived luciferase protein from an unstable mRNA, and recorded bioluminescence in real time in single cells. Mathematical modeling identified gene-specific on- and off-switching rates in transcriptional activity and mean numbers of mRNAs produced during the bursts. Transcriptional kinetics were markedly altered by cis-regulatory DNA elements. Our analysis demonstrated that bursting kinetics are highly gene-specific, reflecting refractory periods during which genes stay inactive for a certain time before switching on again.

Spiral MR myocardial tagging.

In the present study, complementary spatial modulation of magnetization (CSPAMM) myocardial tagging was extended with an interleaved spiral imaging sequence. The use of a spiral sequence enables the acquisition of grid-tagged images with a tagline distance as low as 4 mm in a single breath-hold. Alternatively, a high temporal resolution of 77 frames per second was obtained with 8-mm grid spacing. Ten healthy adult subjects were studied. With this new approach, high-quality images can be obtained and the tags persist throughout the entire cardiac cycle.

Imaging of the unstable plaque: how far have we got?

Rupture of unstable plaques may lead to myocardial infarction or stroke and is the leading cause of morbidity and mortality in western countries. Thus, there is a clear need for identifying these vulnerable plaques before the rupture occurs. Atherosclerotic plaques are a challenging imaging target as they are small and move rapidly, especially in the coronary tree. Many of the currently available imaging tools for clinical use still provide minimal information about the biological characteristics of plaques, because they are limited with respect to spatial and temporal resolution. Moreover, many of these imaging tools are invasive. The new generation of imaging modalities such as magnetic resonance imaging, nuclear imaging such as positron emission tomography and single photon emission computed tomography, computed tomography, fluorescence imaging, intravascular ultrasound, and optical coherence tomography offer opportunities to overcome some of these limitations. This review discusses the potential of these techniques for imaging the unstable plaque.