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
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.
Dual Source Multiple Detector Computed Tomography Scanner: With our relationship with Siemens, we originally installed
a 16 slice MDCT scanner which was upgraded to a Sensation 64 and later to the 128 slice Definition Flash. The Definition Flash was a dual source, dual energy CT scanner with Stellar detectors and
Safire iterative reconstruction option. Most recently, in July 2015, the lab was upgraded to a SIEMENS SOMATOM Force. This new scanner allows for a reduced dose of up to 50% compared to other modern
CT systems. This is in conjunction with a considerable increase in sensitivity and specificity associated with Dual Source DE scanning. It is a 384 (2 X 192) slice scanner with the industry's highest
acquisition speed of 0.25 seconds per rotation. Additionally, the Force has unprecedented power reserves in the form of two 120 kW generators that enable scanning of patients at low kV from 70 to 90
SPECT scanner: We were awarded an instrumentation grant allowing us to purchase a Symbia E Dual (Siemens AG,
Malvern, PA). This system was installed in late summer 2011 in the I-CLIC research facility and we have recently decided to place the scanner within the clinical nuclear medicine area facility to
facilitate oversight by highly trained technologists and the nuclear medicine faculty.
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.
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.
As a member of the IIBI, the Iowa Comprehensive Lung Imaging Center represents a group of loosely knit collaborators who have joined together with a common interest in the use of quantitative
imaging techniques to better understand the normal lung and the permutations leading to and defining pathologic states. Each member of this group is well recognized in their own right and their
backgrounds are diverse, including Physiology, Medicine, Radiology, Anaesthesiology, Mathematics, Electrical Engineering, Biomedical Engineering, and more. While each of these individuals run
successful laboratories, there is a clear need for a dedicated imaging center, which serves as a gathering place and provides these individuals access to state-of-the-art facilities in which to
accomplish their research. This site provides a means of interacting with and influencing industrial partners in regards to the future directions of imaging technologies, and it provides a synergy
serving to rapidly advance both the field of lung imaging and our understanding of the lung. While primarily focusing on advanced CT imaging, areas of interest have also expanded to MRI and PET.
The mission of IIBI is to foster efficient and cooperative interdisciplinary and cross-college research and discovery in biomedical imaging, and to improve training and education within the
broader community at the University of Iowa.
One of several teams of investigators that is currently housed in the recently constructed Pappajohn Biomedical Discovery Building, the IIBI was formed in 2007 as an acknowledgement of a long
history of interdisciplinary collaboration at the University of Iowa. The formation of the interdisciplinary institute reflects a strong institutional support to biomedical imaging and image
analysis as well as translational medical research. The IIBI brings together more than 40 faculty members (out of which over 25 hold faculty positions in the Carver College of Medicine, 15 hold
faculty positions in the college of Engineering with a primary expertise in biomedical image analysis) and over 60 graduate students and postdoctoral fellows.