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Advanced Pulmonary Physiomic Imaging Lab


  News Flash

Press Release. May 12, 2016

Woodruff PG, Barr RG, Bleecker E, Christenson SA, Couper D, Curtis JL, Gouskova NA, Hansel NN, Hoffman EA, Kanner RE, Kleerup E, Lazarus SC, Martinez FJ, Paine R 3rd, Rennard S, Tashkin DP, Han MK; SPIROMICS Research Group. Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function. N Engl J Med. 2016 May 12;374(19):1811-1821. PubMed PMID: 27168432.

The New England Journal of Medicine Article

In a finding that could lead to better treatment of smoking-related lung diseases, a group of scientists from institutions across the country – including the University of Iowa – is reporting that about half of current or former smokers have respiratory symptoms similar to COPD and an increased risk for exacerbations or “flare ups” of their symptoms despite normal lung function and a lack of COPD diagnosis. Many of these individuals show COPD-like symptoms, such as shortness of breath and difficulty exercising. They also have a high rate of respiratory medication use despite a lack of data from clinical trials about appropriate treatment of this particular patient population, the researchers note.

In addition to raising the question of whether the definition of COPD should be adjusted, the researchers say that the study highlights a large, understudied patient population who might nevertheless benefit from early treatment intervention. Their study, published May 11 in the New England Journal of Medicine, was funded by both the National Heart, Lung, and Blood Institute (NHLBI) and the Foundation for the National Institutes of Health (FNIH).
COPD, or chronic obstructive pulmonary disease, is the third leading cause of death in the United States. It is a progressive lung disease that makes it hard to breathe. Cigarette smoking is the leading cause of COPD. While researchers estimate that millions of Americans have COPD, many have the disease and do not know it. The condition is currently diagnosed using spirometry, a test that measures how much air you breathe out and how fast. Researchers have long observed that some current and former smokers appear to have respiratory symptoms associated with COPD—such as coughing and shortness of breath—despite having a normal spirometry test. However, the extent and clinical implications of this problem were unknown until now.

For the current study, the research team led by scientists at several institutions, including the University of California at San Francisco and the University of Michigan, conducted an observational study called SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). It includes patient data collected between 2010 and 2015. The scientists examined respiratory symptoms and measured lung function with spirometry among 2,736 participants -- current or former smokers, aged between 40 and 80 years old, as well as controls who had never smoked. They found that respiratory symptoms were present in about half of the current or former smokers despite normal spirometry readings. Participants who had respiratory symptoms despite normal spirometry had an increased rate of exacerbations or “flare ups” of their symptoms. Using computed tomographic (CT) imaging scans of the lung, overseen by the SPIROMICS Radiology Center at the University of Iowa and analyzed at the VIDA Diagnostics Core Lab in the Bioventures Center of the University of Iowa, the researchers also found a high incidence of thickening of the airways, a sign of lung disease.

“These findings demonstrate that there is a large group of smokers who have COPD symptoms including associated flare-ups who have gone unclassified because of the reliance on pulmonary (lung) function tests. The study shows that quantitative CT scans can provide insights into underlying lung disease processes, and suggests that lung function tests should not necessarily serve as the only test for diagnosing COPD and guiding treatment,” says Eric Hoffman, PhD, director of the Advanced Pulmonary Physiomic Imaging Laboratory (APPIL) within the UI Health Care Department of Radiology, and home to the SPIROMICS Radiology Center.

Hoffman says the CT scans were important in this study because the scans were able to detect lung abnormalities even when standard pulmonary function tests were normal. Additionally, the scans helped differentiate between airway disease – the airway wall thickening – and emphysema. Hoffman says CT may provide a mechanism for following disease progression in addition to identifying targets for treatment. CT imaging may also be useful for assessing outcomes associated with interventions.

About APPIL and VIDA:

The Advanced Pulmonary Physiomic Imaging Laboratory, within the Department of Radiology at the University of Iowa’s Carver College of Medicine directed by Dr. Eric Hoffman PhD, is an internationally recognized leader in the field quantitative lung imaging. The laboratory has served as the radiology center for a growing number of national and international multi-center studies for which lung imaging was a major component of the protocol. As such, more than 30,000 data sets have been sent to the laboratory for quality assessment and quantification. Hoffman and his research group has worked on lung imaging methods for nearly 40 years and he has led lung imaging research at the UI for 24 of those years. Standard pulmonary function testing has lumped many diseases into single entities and masked the presence of others. Imaging is allowing physicians to identify disease processes early and differentiate the processes, and thus is providing the hopes for better, earlier in the treatment of disease before the disease brings patients to the late stages of debilitation.

Through a $2 million grant from the National Institutes of Health and support by the University of Iowa, a state-of-the-art CT scanner built of Siemens known as the Somatom Force, has been installed within APPIL. This scanner enables researchers to generate CT images with up to 10 times lower x-ray dose, bringing the dose down to that of a pair of more traditional chest films while maintaining the high quality of image used in the study under discussion. With this scanner in place, the UI Laboratory is in the process of establishing a new set of protocols which will be implemented in future such studies.

VIDA Diagnostics, Inc., is a company that evolved out of the University of Iowa and currently resides in the research park on the Oakdale Campus of the University of Iowa. VIDA provides software for the visualization and assessment of CT images of the lung and a core lab which provides the quality control over-sight necessary to assure that the measurement reliability. The company was founded by Eric Hoffman, PhD (Professor of Radiology, Medicine and Biomedical Engineering) along with his colleagues Milan Sonka, PhD, (Electrical and Computer Engineering), Joseph Reinhardt, PhD (Biomedical Engineering) and Geoffrey McLennan, MD (Pulmonary Medicine), who passed away in 2010.
Disclosure: The founders remain shareholders within VIDA Diagnostics.

  Advanced Pulmonary Physiomic Imaging Laboratory: APPIL


Mission Statement

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.


Background

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.



  Iowa Comprehensive Lung Imaging Center: I-Clic (APPIL is a sub-unit of I-Clic)

I-Clic image


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 Iowa Institute for Biological Imaging: IIBI (I-Clic is a sub-unit of IIBI)

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Pappajohn Biomedical Discovery Building
Mission

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.


Background

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.




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