Leadership Circle Members: Thank you so much to the Leadership Circle for all that you do to make these outstanding projects possible. We look forward to updating you on their progress in the coming year!
The request for support from this Leadership Circle Grant is to enable PCH to be the first pediatric hospital in the United States to test and validate the clinical utility of a new non-contrast-based MRI approach for tumor assessment and characterization. This new approach, referred to as Amide Proton Transfer (APT) MRI, has the potential to reduce and possibly eliminate the need for Gadolinium-based contrast agent injections. By obviating the need for contrast agents, APT MRI will be particularly beneficial to pediatric patients, especially to those who receive multiple MRI exams throughout the course of their tumor diagnosis and treatment therapy.
Support is requested to facilitate Phoenix Children’s Hospital’s (PCH) Department of Radiology becoming a leading clinical research group within the state, nationally, and also internationally, in the evaluation of pediatric tumors using a non-invasive, non-contrast (i.e., non-dye) magnetic resonance imaging (MRI) technique called Amide Proton Transfer (APT). Current MRI protocols for assessing tumors require an intravenous injection of a Gadolinium-based contrast agent (often referred to as “dye” by patients). The contrast agent makes tumor tissue more conspicuous on imaging. This is because of increased uptake of contrast in the tumor tissue compared to normal tissue. This increased uptake is related to blood supply and to the breakdown of the blood brain barrier. Additionally, the wash-in and wash-out rates of the contrast, referred to as contrast kinetics, provides information on the tumor’s metabolic activity, membrane permeability, and the severity (i.e., grade) of the tumor. For all these beneficial reasons Gadolinium contrast is used very frequently in tumor MRI protocols. Nevertheless, Gadolinium is a heavy metal and can be toxic to the body.
Applicant: Toni Gross, MD, MPH
Division: Emergency and Trauma Department
Request: Base Hospital Medical Command Communication System
Obtaining the equipment that is standard in other Base Hospitals will allow PCH Emergency physicians to provide the highest quality of customer service to our EMS partners, which will translate to the best health care and safety for the patients they care for. This equipment will ensure that children cared for by EMS have the same access to quality medical direction as adults. EMS paramedics encounter pediatric patients far less frequently than adult patients, making the availability of real-time medical direction communication for children even more important.
When PCH becomes a Base Hospital, it will be the only hospital dedicated 100% to children that can provide medical direction to EMS paramedics. This service, which is currently provided by Arizona Base Hospitals without pediatric expertise, allows physicians in the PCH Emergency Department to directly communicate with the paramedics that are treating sick and injured children in route to the hospital. Pediatric specialized emergency physicians are able to ensure that the patient receives the correct medications at the correct doses, and that the special needs of children are addressed appropriately. Physicians are also able to communicate with the family on scene. As a state-approved Base Hospital, PCH will be able to communicate medical direction to EMS agencies caring for children across the entire state.
The request is to support the first clinical trial regarding the efficacy of 3D printed models in improving surgical outcomes. This trial represents the first attempt at describing the statistically significant benefits of planning surgeries based on 3D printed models We are requesting this grant to perform the clinical trial that will demonstrate, for the first time, the statistically significant benefits of planning CHD repairs based on 3D printed models. The trial has already been planned, and it includes three of the nation’s top pediatric medical institutions: Phoenix Children’s Hospital (PCH), Children’s Hospital of Philadelphia, and Children’s National Medical Center. Initial projections estimate that 190 patient cases will be required to demonstrate statistical significance in surgical outcomes including surgical time, duration of hospital stay, and 30-day mortality.
At the cost of $500 per model, the requested funds will allow for completion of the PCH-funded component of the trial with the added support of engineers from Arizona State University, PCH’s new research alliance partner. The results of this landmark trial have the potential to demonstrate to the world that 3D printing is the future of surgical planning for CHD repairs; thus in future CHD repairs, more babies born with CHDs will survive.
Applicant: Benjamin Wright, MD
Division: Department of Medicine, Division of Pulmonology
Request: Diagnosis and management of eosinophilic esophagitis with a throat swab: a translational effort to develop a novel, non-invasive marker of eosinophilic inflammation
This grant would allow for objective elimination of specific dietary triggers and reduce the need for endoscopic biopsies, substantially decreasing associated costs and morbidity. The current standard of care requires the diagnosis of eosinophilic esophagitis (EoE) be confirmed by histologic evidence acquired by invasive means – upper endoscopy with esophageal biopsies. Efforts to validate rapid, non-invasive, diagnostic markers of EoE thus far have been unsuccessful. The inflammatory activities of eosinophils are largely attributed to the release of several cationic granule proteins that also serve as useful surrogates of disease activity in tissue-specific eosinophilic disorders.
We have developed a novel immunoassay using monoclonal antibodies to detect levels of the eosinophil-specific granule protein eosinophil peroxidase (EPX). We have established that EPX staining of esophageal tissue correlates with disease symptoms in EoE. Moreover, we have demonstrated that EPX levels detected from nasal swabs correlate with sputum eosinophils on subjects with asthma. We hypothesize that measurement of EPX from throat swabs of subjects undergoing upper endoscopy for esophageal dysfunction will correlate with esophageal eosinophilia and identify individuals with EoE. Our development and validation of this diagnostic strategy would provide a rapid clinical screening test for EoE useful not only for diagnosis, but also for monitoring response to therapy.