Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model

The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [18F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [18F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33–35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC–associated [18F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [18F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI

MRI as a reference standard for suspected scaphoid fractures

Objectives: Some have suggested that MRI might be the best reference standard for a true fracture among patients with suspected scaphoid fractures. The primary aim of this study was to determine the rate of false-positive diagnosis of an acute scaphoid fracture in a cohort of healthy volunteers. Methods: In a prospective study, 33 healthy volunteers were recruited and both wrists of each were scanned, except for 2 volunteers for whom only one wrist was scanned. To simulate the usual clinical context the 64 scans of healthy volunteers were mixed with 60 MRI scans of clinically suspected scaphoid fractures but normal scaphoid radiographs. These 124 MRI scans were blinded and randomly ordered. Five radiologists evaluated the MRI scans independently for the presence or absence of a scaphoid fracture and other injuries according to a standard protocol. Results: To answer the primary question, only the diagnoses from the 64 scans of healthy volunteers were used. The radiologists diagnosed a total of 13 scaphoid fractures; therefore, specificity for diagnosis of scaphoid fracture was 96% (95% confidence interval: range 94-98%). The 5 observers had a moderate interobserver agreement regarding diagnosis of scaphoid fracture in healthy volunteers (multirater kappa=0.44; p Conclusions: The specificity of MRI for scaphoid fractures is high (96%), but false-positives do occur. Radiologists have only moderate agreement when interpreting MRI scans from healthy volunteers. MRI is not an adequate reference standard for true fractures among patients with suspected scaphoid fractures

Impaired Global Longitudinal Strain Is Associated with Cardiovascular Events in Hodgkin Lymphoma Survivors

Background: Treatment with thoracic irradiation for classic Hodgkin lymphoma (CHL) leads to improved survival but also increases the risk of cardiovascular events. Left ventricular (LV) dysfunction is usually assessed by echocardiographic left ventricular ejection fraction (LVEF), whereas global longitudinal strain (GLS) can detect early subclinical LV dysfunction. The purpose of this study was to evaluate if conventional echocardiographic parameters and GLS are associated with cardiovascular events during long-term follow-up. Methods: 161 consecutive CHL patients treated with radiotherapy who underwent echocardiography > 10 years after diagnosis were assessed for eligibility. Multivariable cause-specific Cox regression was performed for a composite outcome of cardiac death and cardiovascular events and the competing outcome of noncardiac death. Results: 129 patients (61.2% female, N = 79) with a mean age of 46.3 ± 11.0 years at index visit were eligible for analysis. GLS was impaired in 51 patients (39.5%) and 10.9% had a LVEF of −16% showed a significant association with a near four-fold risk of the composite endpoint (HR = 3.95, 95% CI: 1.83–8.52, p p = 0.016) and E/e’ (HR = 1.16, p Conclusions: This study shows that LV dysfunction including impaired GLS in CHL survivors is associated with cardiovascular events and cardiac death