OBJECTIVE:Pseudostenosis is a magnetic resonance angiography (MRA) artifact that mimics arterial stenosis. The study objective was to compare imaging and clinical aspects of stenosis and pseudostenosis in a cohort of large-vessel vasculitis (LVV), including giant cell arteritis (GCA) and Takayasu's arteritis (TAK). METHODS:Patients with LVV and comparator conditions (healthy or vasculopathies) underwent MRA of the aortic arch vessels. The subclavian and axillary arteries were systematically assessed for presence of stenosis and pseudostenosis by two independent readers. Serial and delayed imaging and clinical assessments were used to confirm suspected pseudostenoses. Multivariable regression analyses were used to identify associations between angiographic pathology and clinical findings. RESULTS:184 MRA scans were analyzed from patients with GCA (n=36), TAK (n=47), and comparators (n=25). Pseudostenoses were frequently observed (48/184 scans, 26%) in the distal subclavian artery only on the side of injection and were shorter in length compared to true stenoses (25 mm vs 78 mm, p<0.01). There was no difference in prevalence of pseudostenosis by diagnosis (GCA=33%, TAK=23%, comparator=20%, p=0.44), disease activity status (p=0.31), or treatment status (p=1.00). Percent and length of true stenosis was independently associated with pulse and blood pressure abnormalities in the upper extremity. Adjusting for length and stenosis degree, absence of collateral arteries was associated with arm claudication (odds ratio=2.37, p=0.03). CONCLUSION:While a pseudostenosis could be falsely interpreted an arterial stenosis, radiographic and associated clinical features can help distinguish true disease from arterial susceptibility artifacts. In addition, the peripheral vascular examination can help to confirm a suspected true stenosis, as specific aspects of angiographic pathology are associated with vascular examination abnormalities in large-vessel vasculitis.

To determine the feasibility of dual-contrast agent imaging of the heart using photon-counting detector (PCD) computed tomography (CT) to simultaneously assess both first-pass and late enhancement of the myocardium. An occlusion-reperfusion canine model of myocardial infarction was used. Gadolinium-based contrast was injected 10 min prior to PCD CT. Iodinated contrast was infused immediately prior to PCD CT, thus capturing late gadolinium enhancement as well as first-pass iodine enhancement. Gadolinium and iodine maps were calculated using a linear material decomposition technique and compared to single-energy (conventional) images. PCD images were compared to in vivo and ex vivo magnetic resonance imaging (MRI) and histology. For infarct versus remote myocardium, contrast-to-noise ratio (CNR) was maximal on late enhancement gadolinium maps (CNR 9.0 ± 0.8, 6.6 ± 0.7, and 0.4 ± 0.4, p < 0.001 for gadolinium maps, single-energy images, and iodine maps, respectively). For infarct versus blood pool, CNR was maximum for iodine maps (CNR 11.8 ± 1.3, 3.8 ± 1.0, and 1.3 ± 0.4, p < 0.001 for iodine maps, gadolinium maps, and single-energy images, respectively). Combined first-pass iodine and late gadolinium maps allowed quantitative separation of blood pool, scar, and remote myocardium. MRI and histology analysis confirmed accurate PCD CT delineation of scar. Simultaneous multi-contrast agent cardiac imaging is feasible with photon-counting detector CT. These initial proof-of-concept results may provide incentives to develop new k-edge contrast agents, to investigate possible interactions between multiple simultaneously administered contrast agents, and to ultimately bring them to clinical practice.

Cardiac PET is a versatile imaging technique providing important diagnostic information about ischemic heart diseases. Respiratory and cardiac motion of the heart can strongly impair image quality and therefore diagnostic accuracy of cardiac PET scans. The aim of this study was to investigate a new cardiac PET/MR approach providing respiratory and cardiac motion–compensated MR and PET images in less than 5 min. Methods: Free-breathing 3-dimensional MR data were acquired and retrospectively binned into multiple respiratory and cardiac motion states. Three-dimensional cardiac and respiratory motion fields were obtained with a nonrigid registration algorithm and used in motion-compensated MR and PET reconstructions to improve image quality. The improvement in image quality and diagnostic accuracy of the technique was assessed in simultaneous 18F-FDG PET/MR scans of a canine model of myocardial infarct and was demonstrated in a human subject. Results: MR motion fields were successfully used to compensate for in vivo cardiac motion, leading to improvements in full width at half maximum of the canine myocardium of 13% ± 5%, similar to cardiac gating but with a 90% ± 57% higher contrast-to-noise ratio between myocardium and blood. Motion correction led to an improvement in MR image quality in all subjects, with an increase in sharpness of the canine coronary arteries of 85% ± 72%. A functional assessment showed good agreement with standard MR cine scans with a difference in ejection fraction of −2% ± 3%. MR-based respiratory and cardiac motion information was used to improve the PET image quality of a human in vivo scan. Conclusion: The MR technique presented here provides both diagnostic and motion information that can be used to improve MR and PET image quality. Reliable respiratory and cardiac motion correction could make cardiac PET results more reproducible.

Cardiac PET is a versatile imaging technique providing important diagnostic information about ischemic heart diseases. Respiratory and cardiac motion of the heart can strongly impair image quality and therefore diagnostic accuracy of cardiac PET scans. The aim of this study was to investigate a new cardiac PET/MR approach providing respiratory and cardiac motion-compensated MR and PET images in less than 5 min. Methods: Free-breathing 3-dimensional MR data were acquired and retrospectively binned into multiple respiratory and cardiac motion states. Three-dimensional cardiac and respiratory motion fields were obtained with a nonrigid registration algorithm and used in motion-compensated MR and PET reconstructions to improve image quality. The improvement in image quality and diagnostic accuracy of the technique was assessed in simultaneous 18F-FDG PET/MR scans of a canine model of myocardial infarct and was demonstrated in a human subject. Results: MR motion fields were successfully used to compensate for in vivo cardiac motion, leading to improvements in full width at half maximum of the canine myocardium of 13% ± 5%, similar to cardiac gating but with a 90% ± 57% higher contrast-to-noise ratio between myocardium and blood. Motion correction led to an improvement in MR image quality in all subjects, with an increase in sharpness of the canine coronary arteries of 85% ± 72%. A functional assessment showed good agreement with standard MR cine scans with a difference in ejection fraction of -2% ± 3%. MR-based respiratory and cardiac motion information was used to improve the PET image quality of a human in vivo scan. Conclusion: The MR technique presented here provides both diagnostic and motion information that can be used to improve MR and PET image quality. Reliable respiratory and cardiac motion correction could make cardiac PET results more reproducible.

1292 Objectives Muscle-invasive bladder cancer (MIBC) is an aggressive disease that can be difficult to diagnose and stage with cross-sectional imaging. Treatment includes maximum transurethral resection of bladder tumor (TURBT) and neoadjuvant cisplatin-based chemotherapy in eligible patients followed by radical cystectomy and urinary diversion procedures, such as a neo-bladder, Indiana Pouch, or lleal conduits. The primary objective of this educational exhibit is to familiarize the viewer with the 18F-FDG PET-MRI techniques in local and distant metastatic staging of the bladder cancer, through several imaging examples. Methods Bladder cancer patients status-post a urinary diversion undergoing clinical 18F-FDG PET-MRI for local or metastatic staging were selected for this study. Morphological data was obtained using the high resolution T1 and T2 weighted images of the pelvis. For patients who undergo local staging for bladder cancer, inherent fat signal in the pelvis is used to provide contrast between the cancer and normal peri-vesical tissue, to distinguish bladder-confined lesions from muscular invasion. Functional data to obtain information regarding angiogenesis and cellularity of the mass is mainly derived from kinetic contrast enhancement and diffusion weighted imaging. Whole body evaluation for extent of metastatic bladder cancer is performed using STIR and Dixon sequences and pre and post T1 weighted images. Dynamic post contrast images were performed through the pelvis with delayed post contrast images though the chest and abdomen. Results We reviewed 18F-FDG PET-MRI images from 11 consecutive patients with bladder cancer from September 2014 to November 2015. Our review was consistent with the notion that 18F-FDG activity within the bladder or neo-bladder is a potential concern as an interfering factor for local staging of bladder cancer or diagnosis of metastatic pelvic disease. We will demonstrate ways to minimize the effect of bladder activity via adequate hydration as well as reviewing images with magnification. Recognizing intra-prostatic urethra tracer activity and/or identifying disease involvement in this location were also proved to be challenging. Case examples of 18F-FDG PET-MRI will be presented for various types of diversions. Conclusions MRI imaging can provide morphologic and functional information for staging of bladder cancer. PET-MRI has the potential to enhance the diagnostic power of the PET by adding exceptional anatomic resolution and soft-tissue contrast role in the management of MIBC patients. RESEARCH SUPPORT: None.

1770 Objectives To determine the type and frequency of incidental FDG PET-MRI findings in patients with Psoriasis enrolled in a prospective cohort study. Methods As part of the Psoriasis Atherosclerosis Cardiometabolic disease Initiative cohort study (NCT: 01778569), patients with psoriasis undergo FDG PET-MRI to detect subclinical aortic inflammation and wall thickness. We evaluated patients enrolled in the past 4 months to characterize incidental findings (n=35) detected by FDG PET-MRI (uptake time 146 minutes) and PET-CT (uptake time 60 minutes), and by time of meeting will have data analyzed in 150 patients. Results The mean age of the sample was 50 (+/- 11 years), who had mild to moderate psoriasis for an average of 13 years. Table 2 demonstrates that the most frequent findings were gynecologic (GYN), followed by lung nodules which were not FDG avid. Renal incidental findings included renal masses and cysts.Table-1: Table-2: Incidental findings in consecutive sample of most recent patients with psoriasis detected by FDG PET MRI Conclusions In our preliminary analysis, we show a higher frequency of incidental findings in this sample of psoriasis patients. These findings suggest that FDG PET-MRI has the potential to enhance the diagnostic power of the PET by augmenting anatomic resolution and soft-tissue contrast.

Gadolinium-based contrast agents (GBCAs) are currently approved by the FDA for use in conjunction with MRI. GBCAs are indispensable adjuncts to MRI, with numerous studies showing their efficacy in improving the accuracy of MRI studies, and they have a positive cumulative safety record to date. For example, acute adverse reactions have been reported in only approximately 0.079% of all administrations, of which 91% were classified as mild reactions [ 1 Jung J.W. Kang H.R. Kim M.H. et al. Immediate hypersensitivity reaction to gadolinium-based MR contrast media. Radiology. 2012; 264: 414-422 Crossref PubMed Scopus (178) Google Scholar ]. Despite the positive safety profile immediately after the injection of GBCAs, there has been recent attention to reports of gadolinium deposition in the brains of patients who received multiple doses of GBCAs [ 2 Kanda T. Fukusato T. Matsuda M. et al. Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology. 2015; 276: 228-232 Crossref PubMed Scopus (642) Google Scholar , 3 Kanda T. Ishii K. Kawaguchi H. Kitajima K. Takenaka D. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology. 2014; 270: 834-841 Crossref PubMed Scopus (913) Google Scholar , 4 Kanda T. Osawa M. Oba H. et al. High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology. 2015; 275: 803-809 Crossref PubMed Scopus (382) Google Scholar , 5 McDonald R.J. McDonald J.S. Kallmes D.F. et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology. 2015; 275: 772-782 Crossref PubMed Scopus (996) Google Scholar , 6 Radbruch A. Weberling L.D. Kieslich P.J. et al. Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology. 2015; 275: 783-791 Crossref PubMed Scopus (461) Google Scholar ]. Although it is not yet known if there is a clinical implication of brain deposition of gadolinium, concerns for patient safety are of paramount importance, and thus internal review of institutional policies on GBCA use are warranted. The purposes of this perspective are to (1) summarize the literature regarding GBCA deposition in the brain and (2) determine any potential impact of that knowledge on how GBCA-enhanced MRI may be performed to minimize patient risk. MRI With Gadolinium-Based Contrast Agents: Practical Help to Ensure Patient SafetyJournal of the American College of RadiologyVol. 13Issue 8PreviewMalayeri et al [1] write, "At present, there is no evidence suggesting that gadolinium deposition in the brain alters neurologic function." Where is the evidence for this statement? Free gadolinium is highly toxic. Even though no clinical implications can be drawn from the reported hyperintensities in the dentate nucleus, globus pallidus, pons, and thalamus, the findings are worrisome. Primum non nocere. We must ensure that we do not confuse the lack of results with safety. The precautionary principle must be prevalent. Full-Text PDF

1290 Objectives A single institution experience on a wide range of clinical PET-MRI image artifacts are presented; ranging from inconsequential to severe cases, mimicking visceral organ metastasis. To identify and alleviate such artifacts, practical solutions and related Root-cause analysis are offered. Methods PET-MRI has the potential to add exceptional anatomic resolution and soft-tissue contrast while lowering total patient radiation exposure. However, in addition to MRI motion artifacts due to cardiac, respiratory, and involuntary patient motion, which may lead to same technical registration limitations in PET-MRI as in PET-CT, numerous MR related new type imaging artifacts may occur; commons are illustrated with case examples. Simultaneous PET-MR imaging reduce registration errors providing accurate co-registered PET MR images, and shorten the ‘total acquisition times’ since many functional MR images are acquired during PET acquisition. For quantitative PET imaging, the γ-photon attenuation correction of the reconstructed data is a must. However, unlike in PET-CT, direct measurement of linear attenuation coefficients is not possible in integrated PET-MR systems. Since there is no simple relation between MR image intensity and attenuation coefficients, attenuation maps (µ-maps) can be estimated by segmenting MR images and assigning attenuation coefficients to the compartments. This limitation is usually addressed, by converting the MR information to linear attenuation coefficients. However, because the MR signal in the body relates to the tissues proton density instead of to γ-photon attenuation, this conversion is challenging. There are 3 types of MR based attenuation correction categories: a) segmentation based method, which segment the MR data into 3-4 tissue classes and assign uniform linear attenuation coefficients to each tissue class b) co-registered MR images and corresponding µ-maps are utilized for AC c) methods that create attenuation maps using PET emission data and MR anatomic information. The AC possibilities depend on the subject of study, and the requirements differ between clinical and preclinical imaging Results Because of the short T2 relaxation times of bone tissue, standard MR sequences do not permit to delineate bone tissue only based on the intensity of single voxels. Although time consuming, ultrashort echo time (UTE) sequences allow us to create µ-maps utilizing bone signals. For clinical whole-body (WB) MRI studies bone detection utilizing current UTE sequences are quite time consuming, and since WB applications are less affected when bone tissue is not accurately discriminated from soft tissue in attenuation maps, for WB MR-based AC, segmentation based methods that do not account for the bone gained popularity, without compromising the quantification accuracy for regions that are not close to bone tissue. Dixon technique is more popular, and has also enabled differentiation between soft and adipose tissues. Soft-tissue and adipose-tissue decomposition is achieved using a 3-point Dixon-like decomposition. Predefined linear attenuation coefficients are assigned to classified voxels to generate MRI-based AC (µ) -maps. Conclusions In addition spatial deformation inherent to certain MR sequences, as in Echo-planar imaging based sequences and inaccurate AC µ-map related PET-MRI image artifacts, the following list of conditions illustrated with case examples: - Artifacts related to non-PET optimized MRI coils, and their locations during imaging - Patient respiratory, cardiac motions and unintentional body movements. - Bowel motion related - MRI susceptibility image artifacts either from objects extrinsic or intrinsic to the patient, resulting in PET image artifacts. - MRI wrap and pulsation artifacts RESEARCH SUPPORT: None

PURPOSE:To evaluate an optimized stack of radials ultrashort echo time (UTE) 3D magnetic resonance imaging (MRI) sequence for breath-hold and free-breathing imaging of the human lung. MATERIALS AND METHODS:A 3D stack of ultrashort echo time radials trajectory was optimized for coronal and axial lower-resolution breath-hold and higher-resolution free-breathing scans using Bloch simulations. The sequence was evaluated in 10 volunteers, without the use of contrast agents. Signal-to-noise ratio (SNR) mean and 95% confidence interval (CI) were determined from separate signal and noise images in a semiautomated fashion. The four scanning schemes were evaluated for significant differences in image quality using Student's t-test. Ten clinical patients were scanned with the sequence and findings were compared with concomitant computed tomography (CT) in nine patients. Breath-hold 3D spokes images were compared with 3D stack of radials in five volunteers. A Mann-Whitney U-test was performed to test significance in both cases. RESULTS:Breath-hold imaging of the entire lung in volunteers was performed with SNR (mean = 42.5 [CI]: 35.5-49.5; mean = 34.3 [CI]: 28.6-40) in lung parenchyma for coronal and axial scans, respectively, which can be used as a quick scout scan. Longer respiratory triggered free-breathing scan enabled high-resolution UTE scanning with mean SNR of 14.2 ([CI]: 12.9-15.5) and 9.2 ([CI]: 8.2-10.2) for coronal and axial scans, respectively. Axial free-breathing scans showed significantly higher image quality (P = 0.008) than the three other scanning schemes. The mean score for comparison with CT was 1.67 (score 0: n = 0; 1: n = 3; 2: n = 6). There was no significant difference between CT and MRI (P = 0.25). 3D stack of radials images were significantly better than 3D spokes images (P < 0.001). CONCLUSION:The optimized 3D stack of radials trajectory was shown to provide high-quality MR images of the lung parenchyma without the use of MRI contrast agents. The sequence may offer the possibility of breath-hold imaging and provides greater flexibility in trading off slice thickness and parallel imaging for scan time.

GNE myopathy is a rare autosomal recessive muscle disease caused by mutations in GNE, the gene encoding the rate-limiting enzyme in sialic acid biosynthesis. GNE myopathy usually manifests in early adulthood with distal myopathy that progresses slowly and symmetrically, first involving distal muscles of the lower extremities, followed by proximal muscles with relative sparing of the quadriceps. Upper extremities are typically affected later in the disease. We report a patient with GNE myopathy who presented with asymmetric hand weakness. He had considerably decreased left grip strength, atrophy of the left anterior forearm and fibro-fatty tissue replacement of left forearm flexor muscles on T1-weighted magnetic resonance imaging. The patient was an endoscopist and thus the asymmetric hand involvement may be associated with left hand overuse in daily repetitive pinching and gripping movements, highlighting the possible impact of environmental factors on the progression of genetic muscle conditions.

With the promise of new treatments for Duchenne muscular dystrophy (DMD), there is a need for development of noninvasive biomarkers to assess pharmacologic response to study drugs. Magnetic resonance imaging (MRI) is a valuable tool for measuring the changes in the fat and water signal characteristics in dystrophic muscle. We performed a prospective imaging study of skeletal, cardiac, and respiratory muscles as part of a phase 2, placebo-controlled study of oligonucleotide GSK2401968-induced exon skipping in ambulatory boys with DMD. Muscles in the legs from the hips to the ankles were imaged using T1w, T2w, and 3-point Dixon sequences. Cardiac MRI measures of left ventricle (LV) mass, volume, thickness, fat/water quantitation of the myocardium, LV strain, stroke volume, and ejection fraction were also obtained. In addition, we applied recent and exploratory MRI methods including IDEAL/CPMG, diffusion weighted MRI, and dynamic breathing MRI for muscle fat and water quantitation, sarcolemmal disruption, and the dynamics of diaphragm movement and lung volume changes across the respiratory cycle, respectively. The MRI measures were compared between boys with DMD at baseline (n = 13) and age range-matched healthy boys (n = 20). A subset of DMD subjects (n = 9) participated in the GSK2401968 study and had follow-up MRI studies at the 12, 24, and 48 weeks time points. All subjects underwent a standardized exercise of ankle dorsiflexion during each visit and had MRI of the lower leg muscles repeated after the exercise. The analysis of the imaging data is currently ongoing by blinded investigators and will be presented. With the promise of new treatments for Duchenne muscular dystrophy (DMD), there is a need for development of noninvasive biomarkers to assess pharmacologic response to study drugs. Magnetic resonance imaging (MRI) is a valuable tool for measuring the changes in the fat and water signal characteristics in dystrophic muscle. We performed a prospective imaging study of skeletal, cardiac, and respiratory muscles as part of a phase 2, placebo-controlled study of oligonucleotide GSK2401968-induced exon skipping in ambulatory boys with DMD. Muscles in the legs from the hips to the ankles were imaged using T1w, T2w, and 3-point Dixon sequences. Cardiac MRI measures of left ventricle (LV) mass, volume, thickness, fat/water quantitation of the myocardium, LV strain, stroke volume, and ejection fraction were also obtained. In addition, we applied recent and exploratory MRI methods including IDEAL/CPMG, diffusion weighted MRI, and dynamic breathing MRI for muscle fat and water quantitation, sarcolemmal disruption, and the dynamics of diaphragm movement and lung volume changes across the respiratory cycle, respectively. The MRI measures were compared between boys with DMD at baseline (n = 13) and age range-matched healthy boys (n = 20). A subset of DMD subjects (n = 9) participated in the GSK2401968 study and had follow-up MRI studies at the 12, 24, and 48 weeks time points. All subjects underwent a standardized exercise of ankle dorsiflexion during each visit and had MRI of the lower leg muscles repeated after the exercise. The analysis of the imaging data is currently ongoing by blinded investigators and will be presented.

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.

OBJECTIVES:This study examined whether multidetector computed tomography (MDCT) improves the ability to define peri-infarct zone (PIZ) heterogeneity relative to magnetic resonance imaging (MRI). BACKGROUND:The PIZ as characterized by delayed contrast-enhancement (DE)-MRI identifies patients susceptible to ventricular arrhythmias and predicts outcome after myocardial infarction (MI). METHODS:Fifteen mini-pigs underwent coronary artery occlusion followed by reperfusion. Both MDCT and MRI were performed on the same day approximately 6 months after MI induction, followed by animal euthanization and ex vivo MRI (n = 5). Signal density threshold algorithms were applied to MRI and MDCT datasets reconstructed at various slice thicknesses (1 to 8 mm) to define the PIZ and to quantify partial volume effects. RESULTS:The DE-MDCT reconstructed at 8-mm slice thickness showed excellent correlation of infarct size with post-mortem pathology (r2 = 0.97; p < 0.0001) and MRI (r2 = 0.92; p < 0.0001). The DE-MDCT and -MRI were able to detect a PIZ in all animals, which correlates to a mixture of viable and nonviable myocytes at the PIZ by histology. The ex vivo DE-MRI PIZ volume decreased with slice thickness from 0.9 +/- 0.2 ml at 8 mm to 0.2 +/- 0.1 ml at 1 mm (p = 0.01). The PIZ volume/mass by DE-MDCT increased with decreasing slice thickness because of declining partial volume averaging in the PIZ, but was susceptible to increased image noise. CONCLUSIONS:A DE-MDCT provides a more detailed assessment of the PIZ in chronic MI and is less susceptible to partial volume effects than MRI. This increased resolution best reflects the extent of tissue mixture by histopathology and has the potential to further enhance the ability to define the substrate of malignant arrhythmia in ischemic heart disease noninvasively.

Background-Cardiosphere- derived cells (CDCs) isolated from human endomyocardial biopsies reduce infarct size and improve cardiac function in mice. Safety and efficacy testing in large animals is necessary for clinical translation.Methods and Results-Mesenchymal stem cells, which resemble CDCs in size and thrombogenicity, have been associated with infarction after intracoronary infusion. To maximize CDC engraftment while avoiding infarction, we optimized the infusion protocol in 19 healthy pigs. A modified cocktail of CDCs in calcium-free PBS, 100 U/mL of heparin, and 250 mu g/mL of nitroglycerin eliminated infusion- related infarction. Subsequent infusion experiments in 17 pigs with postinfarct left ventricular dysfunction showed CDC doses >= 10(7) but <2.5 X 10(7) result in new myocardial tissue formation without infarction. In a pivotal randomized study, 7 infarcted pigs received 300 000 CDCs/ kg (approximate to 10(7) total) and 7 received placebo (vehicle alone). Cardiac magnetic resonance imaging 8 weeks later showed CDC treatment decreased relative infarct size (19.2% to 14.2% of left ventricle infarcted, P = 0.01), whereas placebo did not (17.7% to 15.3%, P = 0.22). End-diastolic volume increased in placebo, but not in CDC-treated animals. Hemodynamically, the rate of pressure change (dP/dt) maximum and dP/dt minimum were significantly better with CDC infusion. There was no difference between groups in the ability to induce ventricular tachycardia, nor was there any tumor or ectopic tissue formation.Conclusions-Intracoronary delivery of CDCs in a preclinical model of postinfarct left ventricular dysfunction results in formation of new cardiac tissue, reduces relative infarct size, attenuates adverse remodeling, and improves hemodynamics. The evidence of efficacy without obvious safety concerns at 8 weeks of follow-up motivates human studies in patients after myocardial infarction and in chronic ischemic cardiomyopathy. (Circulation. 2009; 120: 1075-1083.)

Porcine models have become increasingly popular in cardiovascular research. The standard farm pig rapidly increases in body weight and size, potentially confounding serial measurements of cardiac function and morphology. We developed an adult porcine model that does not show physiologic increases in heart mass during the study period and is suitable for long-term study. We compared adult minipigs with the commonly used adolescent Yorkshire swine. Myocardial infarction was induced in adult Göttingen minipigs and adolescent Yorkshire swine by occlusion of the left anterior descending coronary artery followed by reperfusion. At 8 wk after infarction, the left ventricular ejection fraction was 34.1 +/- 2.3% in minipigs and 30.7 +/- 2.0% in Yorkshire swine. The left ventricular end-diastolic mass in Yorkshire pigs assessed by magnetic resonance imaging increased 17 +/- 5 g, from 42.6 +/- 4.3 g at week 1 after infarction to 52.8 +/- 6.6 g at week 8, whereas it remained unchanged in minipigs. Cardiac anatomy and physiology in adult minipigs were evaluated invasively by angiography and noninvasively by Multidetector Computed Tomography and by Magnetic Resonance Imaging at 1.5 T and 3 T prior to myocardial infarction and during folow-up. This porcine heart failure model is reproducible, mimics the pathophysiology in patients who have experienced myocardial infarction, and is suitable for imaging studies. New heart failure therapies and devices can be tested preclinically in this adult animal model of chronic heart failure.

Background: Clinical studies using delayed enhanced magnetic resonance imaging (de-MRI) suggest 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, data characterizing the temporal formation and remodeling characteristics of the PIZ do not exist. We hypothesized that the PIZ undergoes spatial/temporal changes in parallel with structural ventricular remodeling following reperfused myocardial infarction (MI). Methods: Ten mini-pigs underwent coronary occlusion followed by reperfusion. Functional and de-MRI studies were performed prior and at five time points after MI induction. Custom signal density threshold algorithms based on the remote myocardium were applied to define the infarct core and PIZ region. Results: LVEDV increased from 34.7. ± 2.2 ml to 47.8± 3.0 ml (day 3 and week 12, respectively; p<0.001). The size of infarct scar expanded by 14% and thinned by 56% from day3 to 12 weeks ( p =0.004 and p <0.001, respectively). Though, there was no change in total scar volume (11.0±0.8 ml and 9.2±1.2 ml, day 3 and week 12, respectively; p =NS), the PIZ volume showed significant changes over 12 weeks (figure ) parallel to the structural remodeling of the left ventricle. After the initial post-MI edema subsided the PIZ decreased further by 54% from day 10 to week 12 ( p =0.04) Conclusions : The PIZ is dynamic and decreases in volume following reperfused MI. Remodeling characteristics of the PIZ may provide mechanistic insights into the development of life-threatening arrhythmias and sudden cardiac death post-MI.