Advanced Pulmonary Physiomic Imaging Lab

APPIL seeks to broaden the understanding of basic physiology and pathophysiology of the lung along with pulmonary disease co-morbidities using quantitative imaging. APPIL also strives to rapidly use emerging insights for the translation of new image-based methodologies into tools that are applicable to the broader research community and clinical practice for the improved diagnosis, phenotyping, and treatment of lung disease.

Under the direction of Dr. Eric Hoffman within the Department of Radiology, APPIL is a lung imaging, research-based laboratory within I-CLIC and is founded upon more than 30 years of continuous funding. Both Dr. Hoffman and Dr. Newell (Radiologist and APPIL Director of Translational Research) are members of the Fleischner Society in recognition of their significant contributions to quantitative lung imaging dating back to the very beginning of x-ray computed tomography. Early studies served to validate CT as a tool for assessing lung volume, regional air content, regional lung expansion, airway segmentation and vessel segmentation. These works were focused upon the use of purpose built, one-of-a kind scanner systems (the Dynamic Spatial Reconstructor) and the electron beam CT scanner. With the emergence of multidetector-row CT scanners, the group was awarded a 5 year, $10M Bioengineering Research Partnership (successfully renewed for the maximum 10 years of total funding) by the NIH to establish MDCT as a comprehensive imaging modality to assess the structure and function of the human lung, establishing normal ranges of airway and parenchymal metrics along with regional characteristics of ventilation and perfusion assessed via dynamic axial CT imaging. Furthermore, APPIL serves as the Radiology Center for a number of NIH sponsored multi-center studies seeking to utilize imaging as a biomarker for assessing pathology and predicting outcomes. Studies include the National Emphysema Treatment Trial (NETT), the Severe Asthma Research Program (SARP), MESA-Lung, COPDGene, and more recently our lab serves as the Radiology Center for the NIH sponsored "SubPopulations and InteRemediate Outcome Measures in COPD Study" (SPIROMICS). A Bioengineering Research Partnership Grant serves as the current flagship of the lung imaging efforts. In this recently funded BRP (Hoffman, PI), investigators seek to establish protocols for functional dual energy computed tomographic imaging (taking advantage of multi-spectral CT capabilities to simplify protocols for integration into multi-center trials), to link CT phenotypes to quantitative measures of lung inflammation, in order to evolve lung modeling tools so that they can be applied to larger population studies and to provide tools for multi-center quality control.

While x-ray computed tomography (CT) is providing quantitative maps of lung destruction and airway remodeling, these anatomic markers may be insufficient to identify initial causal factors of emphysema that can drive new effective therapeutic interventions. The APPIL group has recently focused on the use of both dual energy CT (DECT) to assess indices of regional pulmonary blood flow (PBF) and single photon emission computed tomography (SPECT) to assess pulmonary inflammation in order to better define the mechanisms that lead to a smoking-associated COPD phenotype. Recent findings, published in the Preceedings of the National Academy of Science, have suggested that CT derived regional PBF parameters within inflamed lung parenchymal destruction in a subset of smokers susceptible to centrilobular emphysema. It is thought that the inability to maintain perfusion to inflamed lung regions may form the basis for a broad spectrum of inflammatory lung disorders.

The University of Iowa Carver College of Medicine has constructed a 2500 square foot CT imaging research facility for the support of the research efforts of the Iowa Comprehensive Lung Imaging Center, I-Clic. This spot is located strategically between the patient areas of the University of Iowa Hospitals and Clinics, the NIH supported Clinical Research Center, and the Animal Care Facilities of the College of Medicine. The space has been designed with a large control room, a MDCT scanner suite, a human preparation area, an animal preparation area, and a micro-CT room with an adjacent separate control room. The CT Scanning Research Facility is equipped with Polycom cameras within the CT suite, CT control room, animal surgery suite, and micro CT suite. It has a Polycom Server that allows multi-point conferencing and the ability for any of the remote sites to participate in live experiments. A Philips physiological monitoring system has been installed to match that in the Medical Intensive Care Unit in the University of Iowa Hospital. Data from the physiologic monitoring system are fed to a monitoring system running LabView software that interprets the physiology and sends signals to the MDCT scanner such that images are captured at a precise point within the physiologic signal of interest. The CT control room has a fifteen foot observation window into the CT suite, a conference table, and 7 computer equipped carrels for visiting scientists, the CT technologist and a study coordinator. Other major equipment includes Xe gas re-breathing delivery system (Diversified Diagnostic Products, Windfern, TX) high pressure Medrad Stellant contrast injector, a dual headed Bracco contrast injector, and a mobile digital fluoroscopy unit, allowing catheterization procedures in the scanner, human and animal preparation suites and at the scanner table. The facility includes a custom-built dual piston system that controls inspiration and expiration during human scanning such that exactly similar volumes of gas (xenon mixture) and exhalate are inspired from and exhaled into the two pistons with valves under computer control.

   Computational Cluster: Dr. Ching-long Lin and Dr. Hoffman received an NIH Shared Instrumentation Grant titled "Large-Scale Computing and Visualization for Cardiopulmonary Imaging" to purchase a computer cluster system of 60 compute nodes with 24 GB RAM per node (each node has 8 cores, thus having a total of 480 cores) for cardiopulmonary research.

   MicroCT Scanner: The Imtek (now Siemens) CAT II micro CT scanner (purchased under an NIH SIG) has the capability of imaging a mouse in vivo with approximately 20µ resolution in approximately 20 minutes. Jessica Sieren, PhD, has recently been awarded funding to add a ZEISS Xradia 520 Versa submicron 3D X-ray CT scanner that has been installed.

In addition to our CT lab area, there is a separate new space located immediately above for housing our computer clusters, large array data storage racks. Directly opposite the computer facility is the Environmental Health Sciences Research Center Exposure Chamber Facility with associated pulmonary function lab. Dr. Hoffman is the director of this facility. A few doors down is a dedicated fully equipped pulmonary function laboratory, including a body box (Nspire) and a gas chromatograph, allowing correlative studies using the Multiple Inert Gas Elimination Technique (MIGET). On this floor, as well as 2 floors above, resides the NIH supported CTSA Clinical Research Center. In addition, the I-CLIC has a customized microscopy facility with what has been dubbed the LIMA system consisting of a large stage microtome and microscope linked by computer control such that the cut surface of a specimen is digitized at microscopic resolution, the surface is scanned and images are merged before a thin section is cut, the microtome stage is adjusted such that the new surface remains in focus and the process is repeated. Dr. Hoffman's 2,500 square foot office and image analysis space reside on the 7^th floor above the scanner facility.