Until recently, visualizing the architectural and cellular morphology of human tissue has required histopathological examination. Samples would be excised from the patient, processed, sectioned, stained and viewed under a microscope. In addition to being invasive, time consuming and costly, the static nature of conventional pathology prohibits the study of biological dynamics and function. The Tearney Laboratory at Massachusetts General Hospital has led the way in transforming the current diagnostic paradigm through the invention and translation of new noninvasive, high-resolution optical imaging modalities that enable disease diagnosis from living patients without excising tissues from the body.
Led by Guillermo (Gary) Tearney, MD, PhD, the lab’s 40-person multidisciplinary team invents, validates and translates novel devices that use light to conduct microscopy in living patients. Light is uniquely well suited for noninvasively interrogating the microscopic structure, molecular composition and biomechanical properties of biological tissues. The goal of the laboratory’s research is to improve understanding and diagnosis of disease by imaging the human body at the highest possible level of detail in vivo.
The location of the Tearney Laboratory at Mass General, which has the largest hospital-based biomedical research program in the world, fosters collaboration among experts in physics, engineering, material science and biology.
Advancing Clinical Care
Early detection of precancerous lesions and intramucosal cancer of the esophagus Facilitated by the high speed of optical frequency domain imaging (OFDI), a recent advance from optical coherence tomography, scientists can now image the entire distal esophagus in patients with microscopic resolution, achieving comprehensive screening for focal disease. The lab has also developed a targeted biopsy platform that uses this volumetric microscopic dataset and automatically marks areas on the esophagus that correspond to the most severe disease so that these sites may be subsequently biopsied.
Detection, characterization and monitoring of coronary atherosclerosis The Tearney team is investigating OFDI, Raman spectroscopy, NIRS, and fluorescence for investigating coronary atherosclerosis. This work spans from technology development and feasibility testing through multi-center clinical studies. Researchers are also developing a newer 1-μm resolution imaging technology for coronary imaging termed micro optical coherence tomography (μOCT). This will enable the visualization of cells and subcellular structures in the coronary wall of patients.
Discovering the root cause of Cystic Fibrosis Dr. Tearney’s high resolution μOCT technology is also being brought to bear on cystic fibrosis (CF). μOCT can directly image the basic mucus clearance mechanism of the airway lining in action, including most importantly the microscopic cilia responsible for driving mucus flow, helping to answer previously unanswerable questions about cystic fibrosis, and also providing a tool to find and evaluate treatment methods meant to restore mucus clearance in CF patients.
Developing Innovative Technologies
Advanced microscopy Novel advanced microscopes, including fluorescence coherence tomography, differential near-field scanning optical microscopy, and full-field optical coherence microscopy have been developed in the Tearney Laboratory. These techniques are used to investigate human disease as well as to study small animal models, such as drosophila, zebrafish and xenopus laevis.
Optical Coherence Tomography (OCT) and Optical Frequency-Domain Imaging (OFDI) Advanced forms of OCT and OFDI are used in clinical studies of the colon, liver, biliary tract, pancreas, pulmonary tract and skin. These experiments set the foundation for additional clinical applications for OCT. Optical frequency-domain imaging was developed to overcome the limitations of optical coherence tomography and achieves a more than 50-fold improvement in image acquisition speed. The lab’s work focuses on developing advanced OFDI methods for solving clinical dilemmas surrounding early detection of atherosclerosis and cancer.
Confocal microscopy The Tearney Laboratory has developed a new form of confocal microscopy, termed spectrally encoded confocal microscopy (SECM), that does not require high speed scanning, yet is capable of obtaining cellular-level resolution images at hundreds of frames per second through an endoscope. The team is also fabricating optical probes capable of scanning entire luminal organs with this technology.
Laser speckle imaging and ultraminiature endoscopy Dr. Tearney’s team is exploring the use of laser speckle for diagnosis, including depth-dependent tissue blood perfusion determination and identification of patients with compartment syndrome. In addition the team has invented a new technology called spectrally encoded endoscopy. This technology provides high resolution three-dimensional endoscopic images through a single optical fiber, resulting in the smallest ever endoscope.
Photoacoustic imaging Photoacoustic imaging detects light-generated sound and forms high-resolution images that reveal the anatomical, functional and molecular composition of tissue. In recent investigations on animals and ex-vivo tissue, photoacoustic imaging has showed promise in detecting early-stage cancer, assessing hemodynamic and metabolic functions and identifying vulnerable atherosclerotic plaques. The Tearney Laboratory is working on advancing photoacoustic techniques toward real-world clinical applications in cardiology and emergency medicine.
Exploring New Frontiers with Human Nanoimaging
Perhaps even more exciting is the potential of human nanoimaging. Developing minimally-invasive technologies that can image cellular, subcellular and genetic processes in living patients would help accelerate a transition to an era where the occurrence of disease and response to therapies can be predicted on an individual patient basis, using genetic and molecular information obtained in vivo. One of the lab’s objectives is to create new in vivo nanoscale imaging technologies and demonstrate them in patients.
The capability to image living human subjects on the nanoscale will:
Enable unprecedented investigation of prevalent human diseases, such as atherosclerosis and cancer, in vivo at the cellular, organelle, macromolecular, dynamic and functional levels
Provide population-based screening/diagnostic tools that can localize precursor lesions and predict occurrence and progression of disease based on molecular-scale information
Guide pharmacologic and surgical therapy on an individual patient basis, based on whole organ assessment of cellular/organelle/macromolecular phenotype
The promise of this research will result in devices that image living human tissue down to the 10-nm resolution scale. Dr. Tearney’s team has made great strides toward advancing clinical in vivo microscopy and these next- generation breakthroughs in human nanoscale imaging are well within reach and will transform medicine.