Establishing a Fetal Lamb Model for Hypoplastic Left Heart Syndrome—A Feasibility Pilot Study
Bibliographic record
Abstract
All articles of this category (opens in new window) Background: A major bottleneck for evaluating and developing different medical and surgical management strategies for the hypoplastic left heart syndrome (HLHS) consists in the lack of a large fetal animal model of HLHS. To this end, we present a feasibility pilot study to implement a recently developed fetal animal model for HLHS in Switzerland.[ 1 ] Methods: Eight pregnant ewes (four with twins) with a mean (SD) body weight 69.5 ± 10.8 kg were anesthetized and intubated at two time points: (A) at mid of gestation (0.5) for percutaneous left atrial (LA) coil implantation guided by fetal ultrasound to induce a mitral valve stenosis with reduced filling of the left ventricle, and (B) at late gestation before birth (0.9) for cardiac and cerebral magnetic resonance imaging (MRI). For twin fetuses only one fetus underwent coil implantation and the other served as control. Successful development of HLHS was determined by functional cardiac MRI on a 3T scanner and 2D quantitative flow MRI at the ductus arteriosus and the proximal ascending aorta. Furthermore, high resolution ex vivo cerebral imaging was performed on a 1.5T system including T2 weighted fast spin echo anatomical imaging and microstructural imaging by means of diffusion tensor imaging. Results: The LA size at coil implantation was 5.4 ± 1.8 mm. Two to four coils with a mean loop diameter of 6.6 ± 1.4 mm and length of 5.6 ± 2.9 mm were implanted per LA. Two ewes died due to periprocedural complications. At (B), mother’s body weight increased to 77.6 ± 13.0 kg ( p = 0.01), and all nine fetal lambs survived (three with twins). Out of the nine fetal lambs three fetal lambs developed LV hypoplasia. The left ventricular end-diastolic volume in the LV hypoplasia group was decreased with 0.32 mL/kg (±0.05) versus 0.46 mL/kg (±0.05) in controls. The flow in the proximal ascending aorta was reduced with 26.7 mL/kg/min (± 0.2) versus 184.1 mL/kg/min (± 45.0) in controls. This was also associated with increased flow in the ductus arteriosus 215.6 (± 43.0) vs 164.0 (± 54.1). Cerebral findings were analyzed in post mortem T2 weighted fast spin echo anatomical imaging as well as DTI. Conclusion: Beside a dropout rate due to periprocedural complication of 25%, this large animal model is feasible and offers in the future a sustainable research platform for better understanding of the cardiac, circulatory and cerebral physiology to support the development of new therapeutic strategies improving cardiac and neurocognitive outcome of HLHS. Publication History Article published online: 13 February 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".