Evaluation of optimized breath-hold and free-breathing 3D ultrashort echo time contrast agent-free MRI of the human lung.

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.

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.

Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy.

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 microg/mL of nitroglycerin eliminated infusion-related infarction. Subsequent infusion experiments in 17 pigs with postinfarct left ventricular dysfunction showed CDC doses > or =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 (approximately 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.

Magnetic resonance-based anatomical analysis of scar-related ventricular tachycardia: implications for catheter ablation.

In catheter ablation of scar-related monomorphic ventricular tachycardia (VT), substrate voltage mapping is used to electrically define the scar during sinus rhythm. However, the electrically defined scar may not accurately reflect the anatomical scar. Magnetic resonance-based visualization of the scar may elucidate the 3D anatomical correlation between the fine structural details of the scar and scar-related VT circuits. We registered VT activation sequence with the 3D scar anatomy derived from high-resolution contrast-enhanced MRI in a swine model of chronic myocardial infarction using epicardial sock electrodes (n=6, epicardial group), which have direct contact with the myocardium where the electrical signal is recorded. In a separate group of animals (n=5, endocardial group), we also assessed the incidence of endocardial reentry in this model using endocardial basket catheters. Ten to 12 weeks after myocardial infarction, sustained monomorphic VT was reproducibly induced in all animals (n=11). In the epicardial group, 21 VT morphologies were induced, of which 4 (19.0%) showed epicardial reentry. The reentry isthmus was characterized by a relatively small volume of viable myocardium bound by the scar tissue at the infarct border zone or over the infarct. In the endocardial group (n=5), 6 VT morphologies were induced, of which 4 (66.7%) showed endocardial reentry. In conclusion, MRI revealed a scar with spatially complex structures, particularly at the isthmus, with substrate for multiple VT morphologies after a single ischemic episode. Magnetic resonance-based visualization of scar morphology would potentially contribute to preprocedural planning for catheter ablation of scar-related, unmappable VT.

Stenosis and Pseudostenosis of the Upper Extremity Arteries in Large-Vessel Vasculitis.

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.

The adult Göttingen minipig as a model for chronic heart failure after myocardial infarction: focus on cardiovascular imaging and regenerative therapies.

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.

Long-term adeno-associated viral vector-mediated expression of truncated TrkB in the adult rat facial nucleus results in motor neuron degeneration.

Adult facial motor neurons continue to express full-length TrkB tyrosine kinase receptor (TrkB.FL), the high-affinity receptor for the neurotrophins BDNF and neurotrophic factor-4/5 (NT-4/5), suggesting that they remain dependent on target-derived and locally produced neurotrophins in adulthood. Studies on the role of TrkB signaling in the adult CNS have been hampered by the early lethality of bdnf, nt-4/5, and trkB knock-out mice. We disrupted TrkB.FL signaling in adult facial motor neurons using adeno-associated viral vector-mediated overexpression of a naturally occurring dominant-negative TrkB receptor, TrkB.T1. Expression of TrkB.T1 resulted in neuronal atrophy and downregulation of NeuN (neuronal-specific nuclear protein) and ChAT expression in facial motor neurons. A subset of transduced neurons displayed signs of motor neuron degeneration that included dendritic beading and rounding of the soma at 2 months of TrkB.T1 expression. Cell counts revealed a significant reduction in motor neuron number in the facial nucleus at 4 months after onset of expression of TrkB.T1, suggesting that a proportion of TrkB.T1-expressing motor neurons became undetectable as a result of severe atrophy or was lost because of cell death. In contrast, overexpression of TrkB.FL did not result in a decrease in facial motor neuron number. Our results indicate that a subset of facial motor neurons remains dependent on TrkB ligands for the maintenance of structural and molecular characteristics in adulthood.

Cardiac and Respiratory Motion Correction for Simultaneous Cardiac PET/MR.

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.

Dual-contrast agent photon-counting computed tomography of the heart: initial experience.

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.

Atypical presentation of GNE myopathy with asymmetric hand weakness.

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.

Characterization of peri-infarct zone heterogeneity by contrast-enhanced multidetector computed tomography: a comparison with magnetic resonance imaging.

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.