Door-to-unload: left ventricular unloading before reperfusion in ST-elevation myocardial infarction.

ST-elevation myocardial infarction treatment in the modern era has focused on minimizing time of ischemia by reducing door-to-balloon time to limit infarct size and improve survival. Although there have been significant improvements in minimizing time to coronary reperfusion, the incidence of heart failure following a myocardial infarction has remained high. Preclinical studies have shown that unloading the left ventricle for 30 min prior to coronary reperfusion can reduce infarct size and promote myocardial recovery. The DTU-STEMI randomized prospective trial will test the hypothesis that left ventricular unloading for at least 30 min prior to coronary reperfusion will improve infarct size and heart failure-related events as compared with the current standard of care.

Lay abstract Improvements in the treatment of heart attacks over the years have focused on rapidly opening the blocked vessel to limit the amount of heart muscle damage. Although there have been significant improvements in minimizing the time to treatment using various options from medications to balloons and stents, there continues to be a high incidence of heart failure following a heart attack with larger heart attacks leading to more heart failure. Recent studies in animal models have shown that unloading the work of the heart with a temporary heart pump can decrease the size of the heart attack and improve heart muscle recovery. The door-to-unload research program continues to investigate the treatment strategy of unloading the heart for at least 30 min prior to opening the blocked vessel to improve patient outcomes.

ABCs of the degenerative spine.

Degenerative changes in the spine have high medical and socioeconomic significance. Imaging of the degenerative spine is a frequent challenge in radiology. The pathogenesis of this degenerative process represents a biomechanically related continuum of alterations, which can be identified with different imaging modalities. The aim of this article is to review radiological findings involving the intervertebral discs, end plates, bone marrow changes, facet joints and the spinal canal in relation to the pathogenesis of degenerative changes in the spine. Findings are described in association with the clinical symptoms they may cause, with a brief review of the possible treatment options. The article provides an illustrated review on the topic for radiology residents. TEACHING POINTS: • The adjacent vertebrae, intervertebral disc, ligaments and facet joints constitute a spinal unit. • Degenerative change is a response to insults, such as mechanical or metabolic injury. • Spine degeneration is a biomechanically related continuum of alterations evolving over time.

Insights from Novel Noninvasive CT and ECG Imaging Modalities on Electromechanical Myocardial Activation in a Canine Model of Ischemic Dyssynchronous Heart Failure.

INTRODUCTION: The interplay between electrical activation and mechanical contraction patterns is hypothesized to be central to reduced effectiveness of cardiac resynchronization therapy (CRT). Furthermore, complex scar substrates render CRT less effective. We used novel cardiac computed tomography (CT) and noninvasive electrocardiographic imaging (ECGI) techniques in an ischemic dyssynchronous heart failure (DHF) animal model to evaluate electrical and mechanical coupling of cardiac function, tissue viability, and venous accessibility of target pacing regions. METHODS AND RESULTS: Ischemic DHF was induced in 6 dogs using coronary occlusion, left bundle ablation and tachy RV pacing. Full body ECG was recorded during native rhythm followed by volumetric first-pass and delayed enhancement CT. Regional electrical activation were computed and overlaid with segmented venous anatomy and scar regions. Reconstructed electrical activation maps show consistency with LBBB starting on the RV and spreading in a "U-shaped" pattern to the LV. Previously reported lines of slow conduction are seen parallel to anterior or inferior interventricular grooves. Mechanical contraction showed large septal to lateral wall delay (80 ± 38 milliseconds vs. 123 ± 31 milliseconds, P = 0.0001). All animals showed electromechanical correlation except dog 5 with largest scar burden. Electromechanical decoupling was largest in basal lateral LV segments. CONCLUSION: We demonstrated a promising application of CT in combination with ECGI to gain insight into electromechanical function in ischemic dyssynchronous heart failure that can provide useful information to study regional substrate of CRT candidates.

Three-dimensional whole-heart T2 mapping at 3T.

PURPOSE: Detecting variations in myocardial water content with T2 mapping is superior to conventional T2 -weighted MRI since quantification enables direct observation of complicated pathology. Most commonly used T2 mapping techniques are limited in achievable spatial and/or temporal resolution, both of which reduce accuracy due to partial-volume averaging and misregistration between images. The goal of this study was to validate a novel free breathing T2 mapping sequence that overcomes these limitations. METHODS: The proposed technique was made insensitive to heart rate variability through the use of a saturation prepulse to reset magnetization every heartbeat. Respiratory navigator-gated, differentially T2 -weighted volumes were interleaved per heartbeat, guaranteeing registered images and robust voxel-by-voxel T2 maps. Free breathing acquisitions removed limits on spatial resolution and allowed short diastolic windows. Accuracy was quantified with simulations and phantoms. RESULTS: Homogeneous three-dimensional (3D) T2 maps were obtained from normal human subjects and swine. Normal human and swine left ventricular T2 values were 42.3 ± 4.0 and 43.5 ± 4.3 ms, respectively. The T2 value for edematous myocardium obtained from a swine model of acute myocardial infarction was 59.1 ± 7.1 ms. CONCLUSION: Free-breathing accurate 3D T2 mapping is feasible and may be applicable in myocardial assessment in lieu of current clinical black blood, T2 -weighted techniques.

Sildenafil does not improve cardiomyopathy in Duchenne/Becker muscular dystrophy.

OBJECTIVE: Duchenne and Becker muscular dystrophies (DBMD) are allelic disorders caused by mutations in dystrophin. Adults with DBMD develop life-threatening cardiomyopathy. Inhibition of phosphodiesterase 5 (PDE5) improves cardiac function in mouse models of DBMD. To determine whether the PDE5-inhibitor sildenafil benefits human dystrophinopathy, we conducted a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov, number NCT01168908). METHODS: Adults with DBMD and cardiomyopathy (ejection fraction ≤ 50%) were randomized to receive sildenafil (20mg 3× daily) or placebo for 6 months. All subjects received an additional 6 months of open-label sildenafil. The primary endpoint was change in left ventricular end-systolic volume (LVESV) on cardiac magnetic resonance imaging. Secondary cardiac endpoints, skeletal muscle function, and quality of life were also assessed. RESULTS: An interim analysis (performed after 15 subjects completed the blinded phase) revealed that 29% (4 of 14) of subjects had a ≥10% increase in LVESV after 6 months of sildenafil compared to 13% (1 of 8) of subjects receiving placebo. Subjects with LVESV > 120ml at baseline were more likely to worsen at 12 months regardless of treatment assignment (p = 0.035). Due to the higher number of subjects worsening on sildenafil, the data and safety monitoring board recommended early termination of the study. There were no statistically significant differences in outcome measures between treatment arms. INTERPRETATION: Due to the small sample size, comparisons between groups must be interpreted with caution. However, this trial suggests that sildenafil is unlikely to improve cardiac function in adults with DBMD.

Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction).

OBJECTIVES: This study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial. BACKGROUND: Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown. METHODS: Autologous CDCs (12.5 to 25 × 10(6)) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients. RESULTS: In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI. CONCLUSIONS: Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction [CADUCEUS]; NCT00893360).

Image-guided therapies for myocardial repair: concepts and practical implementation.

Cell- and molecule-based therapeutic strategies to support wound healing and regeneration after myocardial infarction (MI) are under development. These emerging therapies aim at sustained preservation of ventricular function by enhancing tissue repair after myocardial ischaemia and reperfusion. Such therapies will benefit from guidance with regard to timing, regional targeting, suitable candidate selection, and effectiveness monitoring. Such guidance is effectively obtained by non-invasive tomographic imaging. Infarct size, tissue characteristics, muscle mass, and chamber geometry can be determined by magnetic resonance imaging and computed tomography. Radionuclide imaging can be used for the tracking of therapeutic agents and for the interrogation of molecular mechanisms such as inflammation, angiogenesis, and extracellular matrix activation. This review article portrays the hypothesis that an integrated approach with an early implementation of structural and molecular tomographic imaging in the development of novel therapies will provide a framework for achieving the goal of improved tissue repair after MI.

A new twist on an old idea: a two-dimensional speckle tracking assessment of cyclosporine as a therapeutic alternative for heart failure with preserved ejection fraction.

We recently reported that mitochondrial dysfunction, characterized by increased mitochondrial permeability transition (MPT), was present in a translational swine model of heart failure with preserved ejection fraction (HFpEF). Cyclophilin D is a key component of the MPT pore, therefore, the purpose of this study was to test the efficacy of a novel cyclosporine (CsA) dosing scheme as a therapeutic alternative for HFpEF. Computed tomography (CT), two-dimensional speckle tracking two-dimensional speckle tracking (2DST), and invasive hemodynamics were used to evaluate cardiac function. CT imaging showed 14 weeks of CsA treatment caused eccentric myocardial remodeling (contrasting concentric remodeling in untreated HF animals) and elevated systemic pressures. 2DST detected left ventricular (LV) mechanics associated with systolic and diastolic dysfunction prior to the onset of significantly increased LV end diastolic pressure including: (1) decreased systolic apical rotation rate, longitudinal displacement, and longitudinal/radial/circumferential strain; (2) decreased early diastolic untwisting and longitudinal strain rate; and (3) increased late diastolic radial/circumferential mitral strain rate. LV mechanics associated with systolic and diastolic impairment was enhanced to a greater extent than seen in untreated HF animals following CsA treatment. In conclusion, CsA treatment accelerated the development of heart failure, including dilatory LV remodeling and impaired systolic and diastolic mechanics. Although our findings do not support CsA as a viable therapy for HFpEF, 2DST was effective in differentiating between progressive gradations of developing HF and detecting diastolic impairment prior to the development of overt diastolic dysfunction.

Molecular hybrid positron emission tomography/computed tomography imaging of cardiac angiotensin II type 1 receptors.

OBJECTIVES: The goal of this study was to explore the feasibility of targeted imaging of the angiotensin II type 1 receptor (AT1R) in cardiac tissue, using clinical hybrid positron emission tomography/computed tomography (PET/CT). BACKGROUND: AT1R is an attractive imaging target due to its key role in various cardiac pathologies, including post-infarct left ventricular remodeling. METHODS: Using the novel AT1R ligand [(11)C]-KR31173, dynamic PET/CT was performed in young farm pigs under healthy conditions (n = 4) and 3 to 4 weeks after experimental myocardial infarction (n = 5). Ex vivo validation was carried out by immunohistochemistry and polymerase chain reaction. First-in-man application was performed in 4 healthy volunteers at baseline and under AT1R blocking. RESULTS: In healthy pigs, myocardial KR31173 retention was detectable, regionally homogeneous, and specific for AT1R, as confirmed by blocking experiments. Metabolism in plasma was low (85 ± 2% of intact tracer after 60 min). After myocardial infarction, KR31173 retention, corrected for regional perfusion, revealed AT1R up-regulation in the infarct area relative to remote myocardium, whereas retention was elevated in both regions when compared with myocardium of healthy controls (8.7 ± 0.8% and 7.1 ± 0.3%/min vs. 5.8 ± 0.4%/min for infarct and remote, respectively, vs. healthy controls; p < 0.01 each). Postmortem analysis confirmed AT1R up-regulation in remote and infarct tissue. First-in-man application was safe, and showed detectable and specific myocardial KR31173 retention, albeit at a lower level than pigs (left ventricular average retention: 1.2 ± 0.1%/min vs. 4.4 ± 1.2%/min for humans vs. pigs; p = 0.04). CONCLUSIONS: Noninvasive imaging of cardiac AT1R expression is feasible using clinical PET/CT technology. Results provide a rationale for broader clinical testing of AT1R-targeted molecular imaging.

Cardiovascular magnetic resonance characterization of peri-infarct zone remodeling following myocardial infarction.

BACKGROUND: Clinical studies implementing late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) studies suggest that the peri-infarct zone (PIZ) contains a mixture of viable and non-viable myocytes, and is associated with greater susceptibility to ventricular tachycardia induction and adverse cardiac outcomes. However, CMR data assessing the temporal formation and functional remodeling characteristics of this complex region are limited. We intended to characterize early temporal changes in scar morphology and regional function in the PIZ. METHODS AND RESULTS: CMR studies were performed at six time points up to 90 days after induction of myocardial infarction (MI) in eight minipigs with reperfused, anterior-septal infarcts. Custom signal density threshold algorithms, based on the remote myocardium, were applied to define the infarct core and PIZ region for each time point. After the initial post-MI edema subsided, the PIZ decreased by 54% from day 10 to day 90 (p = 0.04). The size of infarct scar expanded by 14% and thinned by 56% from day 3 to 12 weeks (p = 0.004 and p < 0.001, respectively). LVEDV increased from 34.7. ± 2.2 ml to 47.8 ± 3.0 ml (day 3 and week 12, respectively; p < 0.001). At 30 days post-MI, regional circumferential strain was increased between the infarct scar and the PIZ (-2.1 ± 0.6 and -6.8 ± 0.9, respectively;* p < 0.05). CONCLUSIONS: The PIZ is dynamic and decreases in mass following reperfused MI. Tensile forces in the PIZ undergo changes following MI. Remodeling characteristics of the PIZ may provide mechanistic insights into the development of life-threatening arrhythmias and sudden cardiac death post-MI.

A new method for cardiac computed tomography regional function assessment: stretch quantifier for endocardial engraved zones (SQUEEZ).

BACKGROUND: Quantitative assessment of regional myocardial function has important diagnostic implications in cardiac disease. Recent advances in CT imaging technology have allowed fine anatomic structures, such as endocardial trabeculae, to be resolved and potentially used as fiducial markers for tracking local wall deformations. We developed a method to detect and track such features on the endocardium to extract a metric that reflects local myocardial contraction. METHODS AND RESULTS: First-pass CT images and contrast-enhanced cardiovascular magnetic resonance images were acquired in 8 infarcted and 3 healthy pigs. We tracked the left ventricle wall motion by segmenting the blood from myocardium and calculating trajectories of the endocardial features seen on the blood cast. The relative motions of these surface features were used to represent the local contraction of the endocardial surface with a metric we call stretch quantifier of endocardial engraved zones (SQUEEZ). The average SQUEEZ value and the rate of change in SQUEEZ were calculated for both infarcted and healthy myocardial regions. SQUEEZ showed a significant difference between infarct and remote regions (P<0.0001). No significant difference was observed between normal myocardium (noninfarcted hearts) and remote regions (P=0.8). CONCLUSIONS: We present a new quantitative method for measuring regional cardiac function from high-resolution volumetric CT images, which can be acquired during angiography and myocardial perfusion scans. Quantified measures of regional cardiac mechanics in normal and abnormally contracting regions in infarcted hearts were shown to correspond well with noninfarcted and infarcted regions as detected by delayed enhancement cardiovascular magnetic resonance images.

Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial.

BACKGROUND: Cardiosphere-derived cells (CDCs) reduce scarring after myocardial infarction, increase viable myocardium, and boost cardiac function in preclinical models. We aimed to assess safety of such an approach in patients with left ventricular dysfunction after myocardial infarction. METHODS: In the prospective, randomised CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial, we enrolled patients 2-4 weeks after myocardial infarction (with left ventricular ejection fraction of 25-45%) at two medical centres in the USA. An independent data coordinating centre randomly allocated patients in a 2:1 ratio to receive CDCs or standard care. For patients assigned to receive CDCs, autologous cells grown from endomyocardial biopsy specimens were infused into the infarct-related artery 1·5-3 months after myocardial infarction. The primary endpoint was proportion of patients at 6 months who died due to ventricular tachycardia, ventricular fibrillation, or sudden unexpected death, or had myocardial infarction after cell infusion, new cardiac tumour formation on MRI, or a major adverse cardiac event (MACE; composite of death and hospital admission for heart failure or non-fatal recurrent myocardial infarction). We also assessed preliminary efficacy endpoints on MRI by 6 months. Data analysers were masked to group assignment. This study is registered with ClinicalTrials.gov, NCT00893360. FINDINGS: Between May 5, 2009, and Dec 16, 2010, we randomly allocated 31 eligible participants of whom 25 were included in a per-protocol analysis (17 to CDC group and eight to standard of care). Mean baseline left ventricular ejection fraction (LVEF) was 39% (SD 12) and scar occupied 24% (10) of left ventricular mass. Biopsy samples yielded prescribed cell doses within 36 days (SD 6). No complications were reported within 24 h of CDC infusion. By 6 months, no patients had died, developed cardiac tumours, or MACE in either group. Four patients (24%) in the CDC group had serious adverse events compared with one control (13%; p=1·00). Compared with controls at 6 months, MRI analysis of patients treated with CDCs showed reductions in scar mass (p=0·001), increases in viable heart mass (p=0·01) and regional contractility (p=0·02), and regional systolic wall thickening (p=0·015). However, changes in end-diastolic volume, end-systolic volume, and LVEF did not differ between groups by 6 months. INTERPRETATION: We show intracoronary infusion of autologous CDCs after myocardial infarction is safe, warranting the expansion of such therapy to phase 2 study. The unprecedented increases we noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes. FUNDING: US National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center.

Regional cardiac function assessment in 4D CT: comparison between SQUEEZ and ejection fraction.

Recent advances in computed tomography (CT) imaging technology allow fine anatomical structures such as endocardial trabeculae to be resolved. We have developed a method to detect and track such features on the endocardium to extract a measure that reflects local myocardial contraction with minimal human operator interaction. The relative motion of these surface features were used to represent the local contraction of the endocardial surface with a metric we termed "stretch quantifier of endocardial engraved zones" (SQUEEZ). The results were compared against CT function analysis software available through the scanner vendor. SQUEEZ showed significant difference between infarct and remote regions (p<0.0001) as verified by delayed enhanced magnetic resonance imaging. The vendor software showed inferior spatial resolution and stair-step artifacts in regional function maps.

Upregulation of arginase-II contributes to decreased age-related myocardial contractile reserve.

Arginase-II (Arg-II) reciprocally regulates nitric oxide synthase (NOS) and offsets basal myocardial contractility. Furthermore, decreased or absent myocardial NOS activity is associated with a depression in myocardial contractile reserve. We therefore hypothesized that upregulation of Arg-II might in part be responsible for depressed myocardial contractility associated with age. We studied arginase activity/expression, NOS expression, NO production in the presence and absence of the arginase inhibitor S-(2-boronoethyl)-L: -cysteine (BEC) in old (22 months) and young (3 months) rat hearts and myocytes. The spatial confinement of Arg-II and NOS was determined with immuno-electron-miocrographic (IEM) and immuno-histochemical studies. We tested the effect of BEC on the force frequency response (FFR) in myocytes, as well as NOS abundance and activity. Arginase activity and Arg-II expression was increased in old hearts (2.27 ± 0.542 vs. 0.439 ± 0.058 nmol urea/mg protein, p = 0.02). This was associated with a decrease in NO production, which was restored with BEC (4.54 ± 0.582 vs. 12.88 ± 0.432 µmol/mg, p < 0.01). IEM illustrates increased mitochondrial density in old myocytes (51.7 ± 1.8 vs. 69 ± 2.2 × 10(6)/cm(2), p < 0.01), potentially contributing to increased Arg-II abundance and activity. Immunohistochemistry revealed an organized pattern of mitochondria and Arg-II that appears disrupted in old myocytes. The FFR was significantly depressed in old myocytes (61.42 ± 16.04 vs. -5.15 ± 5.65%), while inhibition of Arg-II restored the FFR (-5.15 ± 5.65 vs. 70.98 ± 6.10%). NOS-2 is upregulated sixfold in old hearts contributing to increased production of reactive oxygen species which is attenuated with NOS-2 inhibition by 1400 W (4,735 ± 427 vs. 4,014 ± 314 RFU/min/mg protein, p = 0.005). Arg-II upregulation in aging rat hearts contributes to age-related decreased contractile function.

CT for evaluation of myocardial cell therapy in heart failure: a comparison with CMR imaging.

OBJECTIVES: The aim of this study was to use multidetector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies. BACKGROUND: Cell transplantation is being widely investigated as a potential therapy in heart failure. Noninvasive imaging techniques are frequently used to investigate therapeutic effects of cell therapies in the preclinical and clinical settings. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF). METHODS: Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n = 9) or 200 million mesenchymal stem cells (MSC, n = 13) 12 weeks after myocardial infarction (MI). Cardiac magnetic resonance and MDCT acquisitions were performed before randomization (12 weeks after MI induction) and at the study endpoint 24 weeks after MI induction. None of the animals received medication to control the intrinsic heart rate during first-pass acquisitions for assessment of LV volumes and LVEF. Delayed-enhancement MDCT imaging was performed 10 min after contrast delivery. Two blinded observers analyzed MDCT acquisitions. RESULTS: MDCT demonstrated that MSC therapy resulted in a reduction of infarct size from 14.3 ± 1.2% to 10.3 ± 1.5% of LV mass (p = 0.005), whereas infarct size increased in nontreated animals (from 13.8 ± 1.3% to 16.5 ± 1.5%; p = 0.02) (placebo vs. MSC; p = 0.003). Both observers had excellent agreement for infarct size (r = 0.96; p < 0.001). LVEF increased from 32.6 ± 2.2% to 36.9 ± 2.7% in MSC-treated animals (p = 0.03) and decreased in placebo animals (from 33.3 ± 1.4% to 29.1 ± 1.5%; p = 0.01; at week 24: placebo vs. MSC; p = 0.02). Infarct size, end-diastolic LV volume, and LVEF assessed by MDCT compared favorably with those assessed by cardiac magnetic resonance acquisitions (r = 0.70, r = 0.82, and r = 0.902, respectively; p < 0.001). CONCLUSIONS: This study demonstrated that cardiac MDCT can be used to evaluate infarct size, LV volumes, and LVEF after intramyocardial-delivered MSC therapy. These findings support the use of cardiac MDCT in preclinical and clinical studies for novel myocardial therapies.

CT-based myocardial perfusion imaging-practical considerations: acquisition, image analysis, interpretation, and challenges.

Methods for non-invasive, cardiac risk assessment have historically relied on exercise stress testing with or without echocardiography or radionuclide imaging and pharmacological stress testing when appropriate. More recently, CT-based modalities like CT angiography (CTA) have been shown to reliably differentiate low from high-risk coronary disease. The advent of newer CT technology now allows for CT-based myocardial perfusion imaging (CTP) that provides functional information, that when analyzed with anatomic data from CTA, can provide a comprehensive risk assessment strategy. In this review, we discuss the research and implementation; as well as the quantitative, semiquantitative, and qualitative methods of image analysis of CT-based perfusion. We also discuss the present state of technology and challenges associated with the methodology. In each section, when appropriate, we provide some information regarding the translation of these methods being utilized in the international, multicenter CORE320 study that is evaluating the combined CT-based imaging (CTA and CTP) strategy of risk assessment in comparison to the combined reference standard of radionuclide myocardial perfusion imaging and invasive angiography.

Applications of cardiac multidetector CT beyond coronary angiography.

Noninvasive imaging of the coronary arteries using multidetector CT (MDCT) represents one of the most promising diagnostic imaging advances in contemporary cardiology. This challenging application has driven a rapid and impressive advancement in CT technology over the past 10 years; leading to increased spatial and temporal resolution, decreased scan times and substantial reductions in radiation dose. Recent technological improvements have not only improved the status of CT coronary angiography but have also enabled new functional myocardial applications that are gaining a foothold in clinical practice as adjuncts or replacements for conventional coronary angiographic studies. Wide-detector CT designs along with prospective ECG-triggered protocols have opened the possibility of performing multiple complementary myocardial measurements during a coronary CT exam with acceptable radiation and contrast exposure. In this Review, we discuss recent technical developments in cardiac MDCT and outline newly enabled noncoronary cardiac applications including viability assessment, myocardial perfusion and molecular imaging.

Integration of infarct size, tissue perfusion, and metabolism by hybrid cardiac positron emission tomography/computed tomography: evaluation in a porcine model of myocardial infarction.

BACKGROUND: Hybrid positron emission tomography/computed tomography (PET-CT) allows for combination of PET perfusion/metabolism imaging with infarct detection by CT delayed contrast enhancement. We used this technique to obtain biomorphological insights into the interrelation between tissue damage, inflammation, and microvascular obstruction early after myocardial infarction. METHODS AND RESULTS: A porcine model of left anterior descending coronary artery occlusion/reperfusion was studied. Seven animals underwent PET-CT within 3 days of infarction, and a control group of 3 animals was scanned at >4 weeks. Perfusion and glucose uptake were assessed by [(13)N]-ammonia/[(18)F]-deoxyglucose (FDG), and 64-slice CT delayed contrast enhancement was measured. In the acute infarct model, CT revealed a no-reflow phenomenon suggesting microvascular obstruction in 80% of all infarct segments. PET showed increased FDG uptake in 68% of the CT-defined infarct segments. Ex vivo staining and histology showed active inflammation in the acute infarct area as an explanation for increased glucose uptake. In chronic infarction, CT showed no microvascular obstruction and agreed well with matched perfusion/metabolism defects on PET. CONCLUSIONS: Perfusion/metabolism PET and delayed enhancement CT can be combined within a single hybrid PET-CT session. Increased regional FDG uptake in the acute infarct area is frequently observed. In contrast to the chronic infarct setting, this indicates tissue inflammation that is commonly associated with microvascular obstruction as identified by no reflow on CT. The consequences of these pathophysiological findings for subsequent ventricular remodeling should be explored in further studies.