Clinical situations for which 3D printing is considered an appropriate representation or extension of data contained in a medical imaging examination: pediatric congenital heart disease conditions.

BACKGROUND: The use of medical 3D printing (focusing on anatomical modeling) has continued to grow since the Radiological Society of North America's (RSNA) 3D Printing Special Interest Group (3DPSIG) released its initial guideline and appropriateness rating document in 2018. The 3DPSIG formed a focused writing group to provide updated appropriateness ratings for 3D printing anatomical models across a variety of congenital heart disease. Evidence-based- (where available) and expert-consensus-driven appropriateness ratings are provided for twenty-eight congenital heart lesion categories. METHODS: A structured literature search was conducted to identify all relevant articles using 3D printing technology associated with pediatric congenital heart disease indications. Each study was vetted by the authors and strength of evidence was assessed according to published appropriateness ratings. RESULTS: Evidence-based recommendations for when 3D printing is appropriate are provided for pediatric congenital heart lesions. Recommendations are provided in accordance with strength of evidence of publications corresponding to each cardiac clinical scenario combined with expert opinion from members of the 3DPSIG. CONCLUSIONS: This consensus appropriateness ratings document, created by the members of the RSNA 3DPSIG, provides a reference for clinical standards of 3D printing for pediatric congenital heart disease clinical scenarios.

Simulating Cardiac Fluid Dynamics in the Human Heart.

Cardiac fluid dynamics fundamentally involves interactions between complex blood flows and the structural deformations of the muscular heart walls and the thin, flexible valve leaflets. There has been longstanding scientific, engineering, and medical interest in creating mathematical models of the heart that capture, explain, and predict these fluid-structure interactions. However, existing computational models that account for interactions among the blood, the actively contracting myocardium, and the cardiac valves are limited in their abilities to predict valve performance, resolve fine-scale flow features, or use realistic descriptions of tissue biomechanics. Here we introduce and benchmark a comprehensive mathematical model of cardiac fluid dynamics in the human heart. A unique feature of our model is that it incorporates biomechanically detailed descriptions of all major cardiac structures that are calibrated using tensile tests of human tissue specimens to reflect the heart's microstructure. Further, it is the first fluid-structure interaction model of the heart that provides anatomically and physiologically detailed representations of all four cardiac valves. We demonstrate that this integrative model generates physiologic dynamics, including realistic pressure-volume loops that automatically capture isovolumetric contraction and relaxation, and predicts fine-scale flow features. None of these outputs are prescribed; instead, they emerge from interactions within our comprehensive description of cardiac physiology. Such models can serve as tools for predicting the impacts of medical devices or clinical interventions. They also can serve as platforms for mechanistic studies of cardiac pathophysiology and dysfunction, including congenital defects, cardiomyopathies, and heart failure, that are difficult or impossible to perform in patients.

Organ dose variability and trends in tomosynthesis and radiography.

The purpose of this study was to investigate relationships between patient attributes and organ dose for a population of computational phantoms for 20 tomosynthesis and radiography protocols. Organ dose was estimated from 54 adult computational phantoms (age: 18 to 78 years, weight 52 to 117 kg) using a validated Monte-Carlo simulation (PENELOPE) of a system capable of performing tomosynthesis and radiography. The geometry and field of view for each exam were modeled to match clinical protocols. For each protocol, the energy deposited in each organ was estimated by the simulations, converted to dose units, and then normalized by exposure in air. Dose to radiosensitive organs was studied as a function of average patient thickness in the region of interest and as a function of body mass index. For tomosynthesis, organ doses were also studied as a function of x-ray tube position. This work developed comprehensive information for organ dose dependencies across a range of tomosynthesis and radiography protocols. The results showed a protocol-dependent exponential decrease with an increasing patient size. There was a variability in organ dose across the patient population, which should be incorporated in the metrology of organ dose. The results can be used to prospectively and retrospectively estimate organ dose for tomosynthesis and radiography.

Measuring progress in neglected disease drug development.

BACKGROUND: Since the late 1990s, funding for development of neglected disease drugs has increased with an influx of resources from product development partnerships (PDPs). Previous research showed modest gains in drug approvals and products in Phase III of clinical development in the period 2000-2008. OBJECTIVE: We assessed the 2009-2013 period in terms of numbers of products in Phase III development and numbers of approvals. Subsequently, we calculated the PDP share in terms of sponsorship of new approvals. We also identified the numbers of 2000-2013 approvals included in the World Health Organization's Essential Drug List (EDL). METHODS: We identified new approvals and Phase III products targeting neglected diseases in the period 2009-2013 by searching ClinicalTrials.gov, IMS R&D Focus, and Investigational Drugs Database, as well as drug regulatory agency websites. Subsequently, we determined which products approved between 2000 and 2013 have been included in the most recent version of the EDL. RESULTS: We found 20 new approvals targeting neglected diseases in the period 2009-2013. PDPs were the primary sponsor of 57% of new approvals in this time frame. Approvals included 1 new molecular entity, 5 vaccines, 2 new indications, 9 fixed-dose combinations, and 3 new formulations. HIV/AIDS (pediatric indications) and malaria accounted for 60% of approvals in 2009-2013. The average number of new approvals per year for neglected diseases rose from 2.6 in 2000-2008 to 4.9 in 2009-2013. The World Health Organization included 44% of 2000-2013 approved products on the EDL. We found 18 products currently in Phase III of clinical development. Products in Phase III testing included 3 new molecular entities, 6 vaccines, 2 fixed-dose combinations, 5 new indications, and 2 new formulations. CONCLUSIONS: Increased funding through PDPs for neglected disease drug development seems to be producing results. Approvals and products in Phase III testing have shown a steady increase since 2000, with nearly a doubling of products in 2009-2013, compared with 2000-2008, in terms of the annual average yield. However, only 3 new molecular entities have been approved in 14 years. In addition, malaria and HIV (pediatric indications) seem to have benefited most from increased funding, whereas less success has occurred with other diseases. Inclusion of newly approved products on the EDL has been slow and limited, with only 44% of new approvals added to the list. Uneven progress suggests funding could be better targeted. In addition, PDPs could do more to facilitate access, in particular by working closely with the World Health Organization to assess the clinical effectiveness and cost-effectiveness of new approvals.