Robert Evers

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 &mgr;g/mL of nitroglycerin eliminated infusion-related infarction. Subsequent infusion experiments in 17 pigs with postinfarct left ventricular dysfunction showed CDC doses ≥107 but <2.5×107 result in new myocardial tissue formation without infarction. In a pivotal randomized study, 7 infarcted pigs received 300 000 CDCs/kg (≈107 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.

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.

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

BackgroundClinical 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 resultsCMR 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 (day3 and week12, 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).ConclusionsThe 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.

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.

PACS and Unread Images

In many circles, the justification for purchasing a picture archiving and communication system (PACS) has already been settled because of the proliferation of image data. A PACS is used to acquire medical images digitally from the various modalities, such as computed tomography (CT), magnetic resonance (MR) imaging, ultrasound, nuclear medicine, and digital radiography (1). The need to manage, transfer, and transport thousands of images effectively has led to medical and legal arguments for storing such data electronically rather than producing each image on film. Moreover, with the dissemination of imaging centers—as well as one’s referral base, which may extend beyond state or country boundaries—a PACS becomes an integral part of running an efficient department. The transfer of images to all-night reading stations for subsequent consolidation of emergency room coverage and the centralization of reading areas within a hospital or an enterprise-wide multisite radiology group, has also made life without PACS nearly impossible. Without the improvements in speed and bandwidth for the data transfer, however, these consolidations would be severely limited. Nonetheless, at a local level, one must still justify the huge investment in capital for a PACS to the financial planners of a hospital or outpatient group practice. We are facing an ever-challenging situation of dwindling budgets, increasing cost pressure, and growing demands to increase the efficiency and quality of related services (2). Typically, reductions in film cost and film library personnel are cited as a means of “financing” the PACS. PACS eliminates the film-associated workload, which includes processing, filing, and manual retrieval of previous studies from film storage. These steps constitute a considerable part of the total radiology turnaround time (3). The economics of PACS are characterized by higher fixed costs for the digital infrastructure and lower variable or marginal costs related to savings in film and personnel (1). Yet another source of savings in converting to a PACS is the greater capture of studies obtained within the department when film is not relied on as the primary means of viewing images. Heretofore, a common complaint in radiology departments was that clinicians would remove film images from the department before the radiologist could interpret them, rendering these examinations “nonbillable” without the cost of refilming. This is a common occurrence in most emergency room radiography departments, where images may be sequestered by the treating physician before being accessioned for billing or accounting. Not only do patients lose an opportunity for expert radiologic interpretation, but these lost films typically will not be available for future comparative studies (4). Accountability for them is particularly problematic without an integrated radiology information system (RIS). The number of lost studies will theoretically be reduced after integration of the RIS and PACS. When the radiology team and referring clinicians have simultaneous access to all patients’ digital data, patient care will improve. Therefore, in addition to decreasing the number of unread images, the use of PACS should help decrease the overall report turnaround time, permitting referring clinicians to make swift decisions on treatment options and health care delivery (4). At the Johns Hopkins Hospital, Baltimore, Md, the radiology department elected to implement the PACS in a piecemeal fashion because of funding considerations. For a time, the outpatient MR imaging service used a PACS and soft-copy reading to transfer and interpret images, while the inpatient MR imaging service continued to use hard-copy film reading. We were therefore able to compare the rates at which studies were lost with a PACS and remote reading (the outpatient service) and a film-based Acad Radiol 2002; 9:1326–1330

2098 Magnetic resonance imaging at 3 Tesla to quantify regional myocardial blood flow after myocardial infarction: comparison with 13N-ammonia positron emission tomography and microspheres

Methods MI was induced in 5 minipigs by a 120-min occlusion of the LAD followed by reperfusion. PET and 3T-MRI studies were performed on the same day 1 or 3 days post MI. Microspheres were injected directly after the MR perfusion acquisition. First pass contrast enhanced myocardial MR images were obtained at rest after a 0.05 mmol/kg BW Gdinjection with a FLASH sequence on a 3 Tesla magnet (TIM Trio, Siemens Medical Solutions). Myocardial perfusion (ml/min/g) was quantified from arterial input and myocardial output function by using a Patlak plot analysis. From dynamic 13N-ammonia PET studies, MBF was quantified by fitting to a validated 3-compartment model. Quantitative MBF measurements from 3T-MRI were compared to that of PET using a modified 17 segment AHA model. A total of 64 segments were evaluated. Post mortem the pig hearts were harvested and cut into 8 mm slices according to the short axis MRI prescription. Eight sectors per slice were used to compare matching microsphere flow measurements and MRI values.

Cranial Nerve I

This unit presents the basic protocol for imaging cranial nerve I. The olfactory bulbs and tracts mediate the sense of smell from the nasal cavity to the brain. Unfortunately they are located in a precarious position for MR imaging, above the air‐filled nasal cavity and ethmoid sinuses at a bone‐air‐soft tissue interface. This creates problems with susceptibility artifact. This issue, plus the very small size of the structures to be studied and the superimposed eye motion artifact makes imaging of the olfactory system a technical challenge.

Cranial Nerves VII To VIII

Cranial nerves VII and VIII are easily visualized within cerebrospinal fluid (CSF) in most patients and are the nerves most commonly involved with neurogenic neoplasms. The reasons for performing contrast‐enhanced scans are explained in this unit, but revolve around pathologies other than schwannomas of the nerves.

Cranial Nerves IX To XII

Cranial nerves IX to XII are rarely affected by pathology compared with cranial nerves III, V, VII, and VIII. Nonetheless, their evaluation is challenging, since lesions of these nerves span the gamut from intracranial to extracranial sites. Imaging of these cranial nerves requires a focused approach based on clinical symptomatology and signs. This unit presents the basic protocol for imaging cranial nerves IX to XII. An alternate protocol is presented for cases where non‐neoplastic lesions are considered.