Volumetric Microscopy of the Pulmonary Airways
Volumetric OFDI images acquired from the left upper lobe of a swine in vivo. (A) Cross-sectional image with visible alveolar attachments (yellow arrowheads). (B) An airway bifurcation showing the epithelium (e), lamina propria (lp), the start of a cartilage plate (c) and alveolar attachments (arrowheads). (C) Cross-sectional image showing the clear delineation of the bronchial mucosal layers including the epithelium, lamina propria (lp), cartilage rings (c), perichondrium (p), vessels (v) and glands (g). (D) Volume rendering of the entire 5.84 cm pullback. Tick marks in A-C represent 500 µm.
Optical imaging technologies have many attractive properties that make them ideal for investigating the lung including that they are non-destructive, are amenable to implementation using flexible small diameter fiber-optic catheters, do not require a transducing medium, and in many cases rely on endogenous contrast. Of particular interest to our laboratory is the development, use and clinical translation of optical imaging systems and techniques, particularly optical frequency domain imaging (OFDI), to address challenges in pulmonary medicine. OFDI is a second-generation optical coherence tomography imaging technology that can be used to conduct volumetric microscopy in vivo. We are currently investigating the use of OFDI for studying lung cancer, asthma, and smoke inhalation injury in ex vivo, preclinical and clinical studies.
Melissa J. Suter, PhD, Principal Investigator
Chunmin (Alex) Chee, MD, Postdoctoral fellow
Lida Hariri, MD, PhD, Postdoctoral fellow
Khay Tan, PhD, Postdoctoral Fellow
Matthew Applegate, Research Technician
Brett Bouma, PhD (MGH Wellman Center for Photomedicine)
Colleen Channick, MD (MGH Pulmonary)
Charles Hales, MD (MGH Pulmonary)
R. Scott Harris, MD (MGH Pulmonary)
Carla Lamb, MD (Lahey Clinic, Pulmonary)
Eugene Mark, MD (MGH Pathology)
Benjamin Medoff, MD (MGH Pulmonary)
Mari Mino-Kenudson, MD (MGH Pathology)
Gary Tearney, MD, PhD (MGH Wellman Center for Photomedicine)
Jose Venegas, PhD (MGH Anesthesiology)
Tilo Winkler, PhD (MGH Anesthesiology)
Current Research Interests
The primary focus of the Pulmonary Optical Imaging Laboratory is the development and clinical translation of novel optical imaging technologies, particularly optical frequency domain imaging (OFDI), with the ultimate goal of improving patient.
Optical Coherence Tomography and Optical Frequency Domain Imaging
Optical coherence tomography (OCT) is a high-resolution optical imaging modality that provides cross-sectional images of tissue microstructure at a resolution comparable with low power bright-field microscopy (<10 µm). Optical frequency domain imaging (OFDI) is a second generation OCT technology that is capable of acquiring images at approximately 100x the speed of traditional time domain OCT systems while preserving the image quality. As OFDI is a fiber-optic imaging technology it is highly amenable to implementation through very narrow diameter, flexible catheters. With appropriate scanning techniques and the increased OFDI acquisition speeds it is therefore possible to conduct volumetric microscopy in vivo.
A large focus of our laboratory involves the development and refinement of optical frequency domain imaging (OFDI) instruments and techniques for investigating the lung. We are working towards developing new, and advancing existing, OFDI techniques for disease detection, diagnosis, and treatment, and for guiding and evaluating pulmonary interventions. In addition we are using these novel techniques to study respiratory physiology and pathophysiology including airway structure and function relationships. Examples of some of our ongoing preclinical, clinical and ex vivo imaging studies our outlined below.
Early Detection and in vivo Diagnosis of Lung Cancer
Watch a video of OFDI imaging
Endobronchial OFDI Pilot Clinical Study: OFDI, bronchoscopy and histopathology images obtained from a normal appearing airway of a patient undergoing bronchoscopy for the evaluation of possible lung cancer. e – epithelium, lp – lamina propria, red arrows – vessels, green arrows – glands. Tick marks represent 500 µm.
We are investigating the use of OFDI for the early detection and in vivo diagnosis of lung cancer both within the conducting airway and in the peripheral lung. This multidisciplinary work involves the development and in vivo testing of novel endobronchial catheters for volumetric imaging of the airways, and transbronchial needle catheters for imaging the peripheral lung. We are currently conducting preclinical safety and feasibility studies and pilot clinical studies using the developed endobronchial and transbronchial imaging catheters. By conducting volumetric microscopy of targeted tissue regions of interest we hope to guide biopsy acquisition to the most severe pathology and therefore increase the diagnostic yield of low-risk transbronchial biopsy. We additionally anticipate that, following the development of appropriate diagnostic criteria, OFDI will enable real-time in vivo diagnosis of pulmonary pathology.
Volumetric Assessment of Pulmonary Pathology
Watch a video of OFDI imaging
OFDI of airway dynamics: Cross-sectional OFDI imaging of airway dynamics in sheep. A larger lumen area is observed during an end inspiration breath hold (blue box) when compared to the same cross-sectional location and airway pressure during tidal breathing (red box). The green box indicates the same location during an end expiration breath hold. Tick marks represent 500 µm.
Accurate interpretation of in vivo OFDI images of pulmonary pathology requires the development and validation of image interpretation criteria. We are currently compiling a comprehensive library of correlated OFDI and histopathology image pairs of pulmonary pathology. This library will ultimately be used as training and testing sets for developing OFDI diagnostic criteria and will additionally be available as a reference tool. In order to ensure direct registration of the OFDI and histopathology images given the small size of non-surgical biopsy specimens, all OFDI imaging is conducted on surgical and autopsy specimens in close collaboration with the MGH pathology department.
Evaluation of the Normal and Asthmatic Airway
The long-term goal of this work is to develop a relatively non-invasive means of assessing airway inflammation, remodeling and hyperresponsiveness in vivo to increase the current understanding of the mechanisms involved in the asthmatic airway, to assess the severity of the disease in patients, and to assess the response to treatment. We are currently using OFDI, and other novel optical imaging techniques, to dynamically image the airways with sufficiently high spatial and temporal resolution to enable the real-time evaluation of the airway structure including the interaction and response of individual layers of the airway wall in both preclinical and pilot clinical studies. Information derived from these imaging studies may provide valuable insight to the complex behavior of both the normal and the asthmatic lung.
Assessment of Smoke Inhalation Injury
Assessment of Smoke Inhalation Injury:
OFDI and corresponding histopathology images of the sheep trachea pre, and 30 minutes post, exposure to cooled cotton smoke. (A) The epithelium (blue arrowheads) is tightly adhered to the basement membrane and the underlying lamina propria (green arrowheads) in the normal airway. (B) 30 minutes post smoke exposure separation of the epithelium is visible in the OFDI images consistent with the sloughed epithelium visible in the H&E stained histology slide (inset – black arrowheads). The yellow arrows indicate the increased mucus accumulation within the airway. Tick marks represent 500 µm.
While the devastating effects of smoke inhalation injury are well documented, accurate diagnosis of patients with smoke inhalation injury remains problematic. We are therefore investigating the use of OFDI to quantify mucosal injury in preclinical animal models. OFDI metrics of smoke inhalation injury include epithelial disruption, PMN infiltrate, increased mucus production, and increased mucosal thickness. We anticipate that volumetric OFDI imaging of the airways will enable us to not only quantitatively assess the initial extent of smoke inhalation injury in patients, but will additionally facilitate monitoring the progression or healing of the injury over time, and may ultimately provide new insight into the clinical management of patients.
We are always looking for postdoctoral fellows with expertise in biomedical optics or pulmonary medicine. Interested applicants should send their detailed curriculum vitae, a cover letter describing relevant training and research experience, and the names and contact information of three referees to Dr. Melissa Suter.
Suter MJ, Nadkarni SK, Weisz G, Tanaka A, Jaffer FA, Bouma BE, Tearney GJ. Intravascular Imaging Technologies for Investigating the Coronary Artery. Journal of the American College of Cardiology Imaging 2011; 4:1022-1039.
Choma MA, Suter MJ, Vakoc BJ, Bouma BE, Tearney GJ. Phsiological homology between Drosophila melanogaster and vertebrate cardiovascular systems. Disease Models and Mechanisms 2011; 4(3):411-20.
Choma MA, Suter MJ, Vakoc BJ, Bouma BE, Tearney GJ. Heart wall velocimetry and exogenous contrast-based cardiac flow imaging in Drosophila melanogaster using Doppler optical coherence tomography. Journal of Biomedical Optics 2010; 15(5): 056020.
Meyerholz DK, Stoltz DA, Namati E, Ramachandran S, Pezzulo AA, Smith AR, Rector M, Suter MJ, Kao S, McLennan G, Tearney GJ, Zabner J, McCray PB, Welsh MJ. Loss of CFTR function produces abnormalities in tracheal development in neonatal pigs and young children. American Journal of Respiratory and Critical Care Medicine, 2010; 182(10):1251-61.
Hariri LP, Bouma BE, Waxman S, Shishkov M, Vakoc BJ, Suter MJ, Freilich MI, Oh W-Y, Rosenberg M, Tearney GJ. An Automatic Image Processing Algorithm for Initiating and Terminating Intracoronary OFDI Pullback. Biomedical Optics Express 2010; 1(2): 566-573.
Waxman S, Freilich MI, Suter MJ, Shishkov M, Bilazarian S, Virmani R, Bouma BE, Tearney GJ. A Case of Lipid Core Plaque Progression and Rupture at the Edge of a Coronary Stent: Elucidating the Mechanisms of Drug-Eluting Stent Failure. Circulation Cardiovascular Interventions 2010; 3(2): 193-196.
Kang D, Suter MJ, Boudoux C, Yachimski PS, Nishioka NS, Mino-Kenudson M, Lauwers GY, Bouma BE, Tearney GJ. Combined spectrally-endcoded confocal microscopy and optical frequency domain imaging system. Journal of Microscopy, 2010; 239(2): 87-91.
Suter MJ, Tearney GJ, Oh WY, Bouma BE. Progress in intravascular optical coherence tomography. IEEE Journal of Selected Topics in Quantum Electronics Special Issue on Biophotonics, 2010; 16(4): 706-714.
Kang D, Suter MJ, Boudoux C, Yoo H, Yachimski PS, Puricelli WP, Nishioka NS, Mino-Kenudson M, Lauwers GY, Bouma BE, Tearney GJ. Comprehensive imaging of gastrointestinal biopsy samples by spectrally-encoded confocal microscopy. Gastrointestinal Endoscopy, 2010; 71(1): 35-43.
Suter MJ, Jillella PA, Vakoc BJ, Halpern E, Mino-Kenudson M, Lauwers G, Bouma BE, Nishioka NS, Tearney GJ. Image-guided biopsy in the esophagus through comprehensive optical frequency domain imaging and laser marking: a study in living swine. Gastrointestinal Endoscopy, 2010; 71(2): 346-353.
Goldberg BD, Vakoc BJ, Oh WY, Suter MJ, Waxman S, Freilich MI, Bouma BE, Tearney GJ. Performance of Reduced Bit-depth Acquisition for Optical Frequency Domain Imaging. Optics Express, 2009; 17(19): 16957-68.
Bouma BE, Yun SH, Vakoc BJ, Suter MJ, Tearney GJ. Fourier-domain optical coherence tomography: recent advances towards clinical utility. Current Opinion in Biotechnology, 2009; 20:1-8.
Desjardins AE, Vakoc BJ, Suter MJ, Yun SH, Tearney GJ, Bouma BE. Efficient FPGA reconstruction algorithm for optical frequency domain imaging. IEEE Transactions on Medical Imaging, 2009; 28(9): 1468-72.
Boudoux C, Leuin SC, Oh WY, Suter MJ, Desjardins AE, Vakoc BJ, Bouma BE, Hartnick CJ, Tearney GJ. Optical microscopy of pediatric vocal fold. Archives of Otolaryngology: Head and Neck Surgery, 2009; 135(1):53-64.
Tearney GJ, Waxman S, Shishkov M, Vakoc BJ, Suter MJ, Frielich M, Desjardins AE, Oh WY, Bartlett LA, Rosenberg M, Bouma BE. Three-Dimensional Coronary Artery Microscopy by Intracoronary Optical Frequency Domain Imaging. Journal of the American College Cardiology Imaging, 2008; 1:752-761.
Suter MJ, Vakoc BJ, Yachimski PS, Shishkov M, Lauwers GY, Mino-Kenudson M, Bouma BE, Nishioka NS, Tearney GJ. Comprehensive Microscopy of the Esophagus in Human Patients with Optical Frequency Domain Imaging. Gastrointestinal Endoscopy, 2008; 68(4): 745-753.
Suter MJ, Reinhardt JM, McLennan G. Integrated CT/Bronchoscopy for the assessment of lung cancer: Preliminary Results. Academic Radiology, 2008; 15(6): 786-798.
Boudoux C, Leuin SC, Oh WY, Suter MJ, Desjardins AE, Vakoc BJ, Bouma BE, Hartnick CJ, Tearney GJ. Preliminary evaluation of non-invasive microscopic imaging techniques for the study of vocal fold development. Journal of Voice, 2008: 18346865
McLennan G, Namati E, Gantra J, Suter M, O’Brien EE, Lecamwasam K, van Beek EJR, Hoffman EA. Virtual Bronchoscopy. Imaging Decisions MRI, 2007; 11(1): 10-20.
Vakoc BJ, Shishkov M, Yun SH, Oh WY, Suter MJ, Desjardins AE, Evans JA, Nishioka NS, Tearney GJ, Bouma BE. Comprehensive esophageal microscopy with optical frequency-domain imaging. Gastrointestinal Endoscopy, 2007; 65(6): 898-905.
Yun, SH, Tearney GJ, Vakoc BJ, Shishkov M, Oh WY, Desjardins AE, Suter MJ, Chan RC, Evans JA, Jang IK, Nishioka NS, de Boer JF, Bouma BE. Comprehensive volumetric optical microscopy in vivo. Nature Medicine, 2006; 12(12): 1429-33.
Suter M, Reinhardt JM, Riker, D, Higgins W, Hoffman EA, McLennan G. Macro-optical color assessment of the pulmonary airways with subsequent 3D MDCT assisted display. J Biomed Opt 2005; 10(5):034013.
Suter M, Reinhardt JM, Zabner J, Montague P, Taft P, Lee J, McLennan G. Bronchoscopic imaging of pulmonary mucosal vasculature responses to inflammatory mediators. J Biomed Opt 2005; 10(3):034013.
Suter M, Tschirren J, Reinhardt J, Sonka M, Hoffman E, Higgins W, McLennan G. Evaluation of the human airway with multidetector X-ray computed tomography and optical imaging. Physiological Measurement 2004; 25(4):837-47.
Rooney CP, Suter M, McLennan G, Donnelley M, Reinhardt JM, Delsing A, Hoffman EA, Zabner J. Laser Fluorescence bronchoscopy for detection of fluorescent reporter genes in airway epithelia. Gene Therapy 2002; 9(23):1639-44.