Technical Report Scintigraphic Evaluation of Bone Formation in Göttingen Minipigs

In experiments and processes requiring the application of nuclear tracers in large animals, statutory provisions  and safety standards as well as a variety of techniques have to be regarded and employed. In order to sufficiently analyze questions pertaining to osseointegration as well as the possibility of ectopic  bone formation in Göttingen minipigs, we decided to use scintigraphic examinations using 99mTc-HDP  (Technetium - hydroxymethane diphosphonate). In this study, metallic implants coated in different forms  with rhBMP-2 (recombinant human bone morphogenetic protein-2) were surgically introduced into the  pigs’ femora. A total of 26 adult female minipigs (Ellegard, Dalmose, Denmark) averaging 40 months in  age were post-surgically evaluated through the application of a radionuclide and its subsequent distribution  using a scintillation camera. Each animal received approximately 10 MBq/kg BW (mega Becquerel per  kilogram bodyweight). This paper describes the procedures of anaesthesia, the quite challenging transvaginal- urethral catheterization,  the application of a catheter in the jugular vein, the radionuclide injection and the disposal of the  sacrificed animals under statutory provisions and safety standards. The technical report reveals that the scintigraphic evaluation in large animal experiments is a practicable  – yet sophisticated – method of examination and also strives to encourage further research groups to implement  this elegant procedure.

Atlas-based measures of left ventricular shape may improve characterization of adverse remodeling in anthracycline-exposed childhood cancer survivors: a cross-sectional imaging study.

BackgroundAdverse cardiac remodeling is an important precursor to anthracycline-related cardiac dysfunction, however conventional remodeling indices are limited. We sought to examine the utility of statistical atlas-derived measures of ventricular shape to improve the identification of adverse anthracycline-related remodeling in childhood cancer survivors.MethodsWe analyzed cardiac magnetic resonance imaging from a cross-sectional cohort of 20 childhood cancer survivors who were treated with low (< 250 mg/m2 [N = 10]) or high (≥250 mg/m2 [N = 10]) dose anthracyclines, matched 1:1 by sex and age between dose groups. We reconstructed 3D computational models of left ventricular end-diastolic shape for each subject and assessed the ability of conventional remodeling indices (volume, mass, and mass to volume ratio) vs. shape modes derived from a statistical shape atlas of an asymptomatic reference population to stratify anthracycline-related remodeling. We compared conventional parameters and five atlas-based shape modes: 1) between survivors and the reference population (N = 1991) using multivariable linear regression, and 2) within survivors by anthracycline dose (low versus high) using two-sided T-tests, multivariable logistic regression, and receiver operating characteristic curves.ResultsCompared with the reference population, survivors had differences in conventional measures (lower volume and mass) and shape modes (corresponding to lower overall size and lower sphericity; all p < 0.001). Among survivors, differences in a shape mode corresponding to increased basal cavity size and altered mitral annular orientation in the high-dose group were observed (p = 0.039). Collectively, atlas-based shape modes in conjunction with conventional measures discriminated survivors who received low vs. high anthracycline dosage (area under the curve [AUC] 0.930, 95% confidence interval 0.816, 1.00) significantly better than conventional measures alone (AUC 0.710, 95% confidence interval 0.473, 0.947; AUC comparison p = 0.0498).ConclusionsCompared with a reference population, heart size is smaller in anthracycline-exposed childhood cancer survivors. Atlas-based measures of left ventricular shape may improve the detection of anthracycline dose-related remodeling differences