Thoracic Insufficiency Syndrome (TIS) is a group of serious disorders of the pediatric thorax resulting in an inability of the thorax to support respiration or lung growth. TIS is associated with at least 28 pediatric syndromes, with an estimated health care cost per patient that can easily exceed a million dollars. In TIS, three-dimensional deformity of the thoracic components anatomically and functionally reduces the volume available for ventilation. Pediatric specialists dealing with TIS currently face several serious challenges: (a) The complex interplay among dynamic and growing thoracic structures and its influence on thoracic function and growth are not understood at present. (b) The prime outcome measure for the corrective procedures has remained the radiographic Cobb angle of the spine, a 60-year old metric with poor correlation with lung dynamic function and limited true health assessment value. (c) A normative imaging database with functional metrics describing dynamics and growth of the thoracic structures of the normal pediatric population does not exist. Due to these hurdles, innovations in growth-modulating surgical techniques are difficult to achieve. Supported by extensive preliminary results based on dynamic MRI (dMRI) of patients and normal subjects, the overarching goal of this proposal is to develop novel dynamic functional metrics for TIS by establishing a normative database of dMRI images and anatomic and functional models and metrics, and to translate these to develop markers of TIS and of its corrective-surgery outcomes. The project has three aims.
Aim 1 : To develop a new methodology called The Virtual Growing Child (VGC) consisting of 4 key components: a) To build a normative database of dMRI images prospectively gathered from 200 normal children divided into 10 groups. b) To build population anatomic models involving key thoraco-abdominal objects following an established automatic anatomy recognition (AAR) technology and deep learning (DL) techniques. c) To develop and validate joint AAR-DL algorithms to segment these objects in dMRI images of TIS patients. d) To build a normative database of measurements derived from dMRI images describing normal thoracic architecture, dynamic function, and growth. The database will also include a full battery of Pulmonary Function Testing data and anthropometric measurements.
Aim 2 : To test retrospectively the utility of the VGC ensemble in deriving markers of TIS and its surgical treatment effects on a cohort of 100 TIS patients.
Aim 3 : To retrospectively test the utility of the VGC approach for planning surgery in 30 TIS patients by comparing VGC-guided surgical planning to the current planning method. The post-operative key dMRI parameters of patients whose surgical plan would have changed due to VGC data will be compared to those of patients whose plan did not change. Expected outcomes: (i) A unique registry of thoracic dMRI of 200 normal pediatric subjects, segmented objects, and the associated anatomic, dynamic, and developmental parameters. (ii) A validated VGC approach for studying TIS which can also be utilized for studying other pediatric and adult thoracic disorders.

Public Health Relevance

Thoracic Insufficiency Syndrome (TIS) is a group of serious disorders of the pediatric thorax. Currently there are no reliable and scientific functional metrics to describe these disorders and their treatment effects. This grant application proposes to build an innovative methodology called the Virtual Growing Child (VGC) based on dynamic MRI of the thorax, construct a comprehensive normative database of MRI images and associated measurements, and utilize the VGC methodology to scientifically characterize TIS and arrive at innovative surgical planning methods.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Imaging Guided Interventions and Surgery Study Section (IGIS)
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Natarajan, Aruna R
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University of Pennsylvania
Schools of Medicine
United States
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