Guillermo J Tearney

Harvard Medical School, Boston, Massachusetts, United States

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Publications (251)1342.57 Total impact

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    ABSTRACT: A large percentage of breast cancer patients treated with breast conserving surgery need to undergo multiple surgeries due to positive margins found during post-operative margin assessment. Carcinomas could be removed completely during the initial surgery and additional surgery avoided if positive margins can be determined intraoperatively. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that has a potential to rapidly image the entire surgical margin at subcellular resolution and accurately determine margin status intraoperatively. In this study, in order to test the feasibility of using SECM for intraoperative margin assessment, we have evaluated the diagnostic accuracy of SECM for detecting various types of breast cancers. Forty-six surgically removed breast specimens were imaged with an SECM system. Side-by-side comparison between SECM and histologic images showed that SECM images can visualize key histomorphologic patterns of normal/benign and malignant breast tissues. Small (500 μm × 500 μm) spatially registered SECM and histologic images (n=124 for each) were diagnosed independently by three pathologists with expertise in breast pathology. Diagnostic accuracy of SECM for determining malignant tissues was high, average sensitivity of 0.91, specificity of 0.93, positive predictive value of 0.95, and negative predictive value of 0.87. Intra-observer agreement and inter-observer agreement for SECM were also high, 0.87 and 0.84, respectively. Results from this study suggest that SECM may be developed into an intraoperative margin assessment tool for guiding breast cancer excisions.Laboratory Investigation advance online publication, 18 January 2016; doi:10.1038/labinvest.2015.158.
    No preview · Article · Jan 2016 · Laboratory Investigation
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    ABSTRACT: Optical coherence tomography (OCT) is an optical diagnostic modality that can acquire cross-sectional images of the microscopic structure of the esophagus, including Barrett’s esophagus (BE) and associated dysplasia. We developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires high-resolution images of entire gastrointestinal (GI) tract luminal organs. This device has a potential to become a screening method that identifies patients with an abnormal esophagus that should be further referred for upper endoscopy. Currently, the characterization of the OCT-TCE esophageal wall data set is performed manually, which is time-consuming and inefficient. Additionally, since the capsule optics optimally focus light approximately 500 μm outside the capsule wall and the best quality images are obtained when the tissue is in full contact with the capsule, it is crucial to provide feedback for the operator about tissue contact during the imaging procedure. In this study, we developed a fully automated algorithm for the segmentation of in vivoOCT-TCE data sets and characterization of the esophageal wall. The algorithm provides a two-dimensional representation of both the contact map from the data collected in human clinical studies as well as a tissue map depicting areas of BE with or without dysplasia. Results suggest that these techniques can potentially improve the current TCE data acquisition procedure and provide an efficient characterization of the diseased esophageal wall. Automated segmentation and characterization of esophageal wall in vivo by tethered capsule optical coherence tomography endomicroscopy. Available from: https://www.researchgate.net/publication/289707455_Automated_segmentation_and_characterization_of_esophageal_wall_in_vivo_by_tethered_capsule_optical_coherence_tomography_endomicroscopy [accessed Jan 14, 2016].
    Full-text · Article · Jan 2016 · Biomedical Optics Express
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    ABSTRACT: Aims: Fibrin deposition and absent endothelium characterize unhealed stents that are at heightened risk of stent thrombosis. Optical coherence tomography (OCT) is increasingly used for assessing stent tissue coverage as a measure of healed stents, but cannot precisely identify whether overlying tissue represents physiological neointima. Here we assessed and compared fibrin deposition and persistence on bare metal stent (BMS) and drug-eluting stent (DES) using near-infrared fluorescence (NIRF) molecular imaging in vivo, in combination with simultaneous OCT stent coverage. Methods and results: Rabbits underwent implantation of one BMS and one DES without overlap in the infrarenal aorta (N = 20 3.5 × 12 mm). At Days 7 and/or 28, intravascular NIRF-OCT was performed following the injection of fibrin-targeted NIRF molecular imaging agent FTP11-CyAm7. Intravascular NIRF-OCT enabled high-resolution imaging of fibrin overlying stent struts in vivo, as validated by histopathology. Compared with BMS, DES showed greater fibrin deposition and fibrin persistence at Days 7 and 28 (P < 0.01 vs. BMS). Notably, for edge stent struts identified as covered by OCT on Day 7, 92.8 ± 9.5% of DES and 55.8 ± 23.6% of BMS struts were NIRF fibrin positive (P < 0.001). At Day 28, 18.6 ± 10.6% (DES) and 5.1 ± 8.7% (BMS) of OCT-covered struts remained fibrin positive (P < 0.001). Conclusion: Intravascular NIRF fibrin molecular imaging improves the detection of unhealed stents, using clinically translatable technology that complements OCT. A sizeable percentage of struts deemed covered by OCT are actually covered by fibrin, particularly in DES, and therefore such stents might remain prothrombotic. These findings have implications for the specificity of standalone clinical OCT assessments of stent healing.
    No preview · Article · Dec 2015 · European Heart Journal
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    ABSTRACT: While coronary atherosclerosis is a leading cause of mortality, evaluation of coronary lesions was previously limited to either indirect angiographic assessment of the lumen silhouette or post mortem investigations. Intracoronary (IC) imaging modalities have been developed that allow for visualization and characterization of coronary atheroma in living patients. Used alone or in combination, these modalities have enhanced our understanding of pathobiological mechanisms of atherosclerosis, identified factors responsible for disease progression, and documented the ability of various medications to reverse the processes of plaque growth and destabilization. These methodologies have established a link between in vivo plaque characteristics and subsequent coronary events, thereby improving individual risk stratification, paving the way for risk-tailored systemic therapies and raising the option for pre-emptive interventions. Moreover, IC imaging is increasingly used during coronary interventions to support therapeutic decision-making in angiographically inconclusive disease, guide and optimize procedural results in selected lesion and patient subsets, and unravel mechanisms underlying stent failure. This review aims to summarize current evidence regarding the role of IC imaging for diagnosis and risk stratification of coronary atherosclerosis, and to describe its clinical role for guiding percutaneous coronary interventions. Future perspectives for in-depth plaque characterization using novel techniques and multimodality imaging approaches are also discussed.
    Full-text · Article · Dec 2015 · European Heart Journal

  • No preview · Article · Oct 2015 · Pediatric Pulmonology
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    ABSTRACT: Aims: The aim of this study was to investigate the reproducibility of intravascular optical coherence tomography (IVOCT) assessments, including a comparison to intravascular ultrasound (IVUS). Intra-observer and inter-observer variabilities of IVOCT have been previously described, whereas inter-institute reliability in multiple laboratories has never been systematically studied. Methods and results: In 2 independent laboratories with intravascular imaging expertise, 100 randomized matched data sets of IVOCT and IVUS images were analysed by 4 independent observers according to published consensus document definitions. Intra-observer, inter-observer, and inter-institute variabilities of IVOCT qualitative and quantitative measurements vs. IVUS measurements were assessed. Minor inter- and intra-observer variability of both imaging techniques was observed for detailed qualitative and geometric analysis, except for inter-observer mixed plaque identification on IVUS (κ = 0.70) and for inter-observer fibrous cap thickness measurement reproducibility on IVOCT (ICC = 0.48). The magnitude of inter-institute measurement differences for IVOCT was statistically significantly less than that for IVUS concerning lumen cross-sectional area (CSA), maximum and minimum lumen diameters, stent CSA, and maximum and minimum stent diameters (P < 0.001, P < 0.001, P < 0.001, P = 0.02, P < 0.001, and P = 0.01, respectively). Minor inter-institute measurement variabilities using both techniques were also found for plaque identification. Conclusion: In the measurement of lumen CSA, maximum and minimum lumen diameters, stent CSA, and maximum and minimum stent diameters by analysts from two different laboratories, reproducibility of IVOCT was more consistent than that of IVUS.
    No preview · Article · Sep 2015 · European Heart Journal – Cardiovascular Imaging
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    ABSTRACT: Fibrinolytic therapy of venous thromboembolism (VTE) is increasingly utilized, yet limited knowledge is available regarding in vivo mechanisms that govern fibrinolytic efficacy. In particular, it is unknown how age-dependent thrombus organization limits direct blood contact with fibrin, the target of blood-based fibrinolytic agents. Utilizing high-resolution in vivo optical molecular imaging with FTP11, a near-infrared fluorescence (NIRF) fibrin-specific reporter, here we investigated the in vivo interrelationships of blood accessibility to fibrin, thrombus age, thrombus neoendothelialization, and fibrinolysis in murine venous thrombosis (VT). In both stasis VT and non-stasis VT, NIRF microscopy showed that FTP11 fibrin binding was thrombus age-dependent. FTP11 localized to the luminal surface of early-stage VT, but only minimally to subacute VT (p<0.001). Transmission electron microscopy of early stage VT revealed direct blood cell contact with luminal fibrin-rich surfaces. In contrast, subacute VT exhibited an encasing CD31+ neoendothelial layer that limited blood cell contact with thrombus fibrin in both VT models. Next we developed a theranostic strategy to predict fibrinolytic efficacy based on the in vivo fibrin accessibility to blood NIRF signal. Mice with variably aged VT underwent FTP11 injection and intravital microscopy (IVM), followed by tissue plasminogen activator infusion to induce VT fibrinolysis. Fibrin molecular IVM revealed that early stage VT, but not subacute VT, bound FTP11 (p<0.05), and experienced higher rates of fibrinolysis and total fibrinolysis (p<0.05 vs. subacute VT). Before fibrinolysis, the baseline FTP11 NIRF signal predicted the net fibrinolysis at 60 minutes (p<0.001). Taken together, these data provide novel insights into the temporal evolution of VT and its susceptibility to therapeutic fibrinolysis. Fibrin molecular imaging may provide a theranostic strategy to identify venous thrombi amenable to fibrinolytic therapies.
    No preview · Article · Sep 2015 · Theranostics
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    ABSTRACT: Background & aims: Probe-based confocal laser endomicroscopy (pCLE) and volumetric laser endomicroscopy (VLE) are advanced endoscopic imaging modalities that may be useful in the diagnosis of dysplasia associated with Barrett's esophagus (BE). We performed pCLE examination in ex-vivo endoscopic mucosal resection (EMR) specimens and compared the diagnostic performance of using the current VLE scoring index (OCT-SI) and a novel VLE diagnostic algorithm (VLE-DA) for the detection of dysplasia. Methods: 27 patients with BE enrolled in a surveillance program at a tertiary center underwent 50 clinically indicated EMRs that were imaged with VLE and pCLE and classified into neoplastic (N=34; high-grade dysplasia, intramucosal adenocarcinoma) and non-neoplastic (N=16; low-grade dysplasia, non-dysplastic BE) based on histology. Image datasets (VLE, N=50; pCLE, N=50) were rated by 3 gastroenterologists trained in the established diagnostic criteria for each imaging modality as well as a new diagnostic algorithm for VLE derived from a training set that demonstrated association of specific VLE features with neoplasia. Sensitivity, specificity, and diagnostic accuracy were assessed for each imaging modality and diagnostic criteria. Results: The sensitivity, specificity and diagnostic accuracy of pCLE for detection of BE dysplasia was 76% (95% CI, 59-88), 79% (95% CI, 53-92) and 77% (95% CI, 72-82), respectively. The optimal diagnostic performance of OCT-SI showed a sensitivity of 70% (95% CI, 52-84), specificity of 60% (95% CI, 36-79) and diagnostic accuracy of 67%; (95% CI, 58-78). The use of the novel VLE-DA showed a sensitivity of 86% (95% CI, 69-96), specificity of 88% (95% CI, 60-99) and diagnostic accuracy of 87% (95% CI, 86-88). The diagnostic accuracy of using the new VLE-DA criteria was significantly superior to the current OCT-SI (p<0.01). Conclusions: The use of a new VLE-DA showed enhanced diagnostic performance for detecting BE dysplasia ex vivo compared with the current OCT-SI. Further validation of this algorithm in vivo is warranted.
    Full-text · Article · Sep 2015 · Gastrointestinal endoscopy
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    ABSTRACT: Volumetric laser endomicroscopy (VLE) produces high-resolution, cross-sectional surface, and subsurface images for detecting neoplasia, targeting biopsies, and guiding real-time treatment. To evaluate the safety and feasibility of the Nvision VLE system. Prospective, multicenter study. Tertiary-care medical centers. One hundred patients with suspected Barrett's esophagus, including 52 patients with prior endotherapy. The first-generation Nvision VLE Imaging System, a balloon-centered, rotating optical probe provided images of the mucosa and submucosa through a 6-cm segment length and 360° scan of the distal esophagus. Acquisition of a complete, 6-cm scan from the distal esophagus, demographic and procedural data, and final histologic diagnosis. VLE imaging was successfully performed in 87 cases. After VLE imaging, biopsy specimens were obtained in 77 patients and mucosal resection was performed in 20 patients. The final pathologic diagnoses of the patients studied were adenocarcinoma (4 patients), high-grade dysplasia (10 patients), low-grade dysplasia (11 patients), indefinite (5 patients), intestinal metaplasia (29 patients), and normal squamous cells (18 patients). VLE was not completed in 13 of 100 (13%) because of optical probe and console issues. There were 2 minor adverse events (mucosal lacerations not requiring therapy). This was a feasibility study with a first-generation device. There was no direct histopathologic correlation with the VLE images or any comparative analysis with white-light endoscopy or narrow-band imaging findings. VLE is a safe procedure for patients with suspected or confirmed Barrett's esophagus. Real-time VLE images enabled visualization of the mucosa and submucosa in 87% of cases. Further studies are needed to evaluate the in vivo diagnostic accuracy and clinical utility of VLE. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.
    No preview · Article · May 2015 · Gastrointestinal endoscopy

  • No preview · Article · May 2015 · Gastrointestinal Endoscopy

  • No preview · Article · May 2015 · Gastrointestinal Endoscopy

  • No preview · Article · May 2015 · Gastrointestinal Endoscopy

  • No preview · Article · May 2015 · Arteriosclerosis Thrombosis and Vascular Biology
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    ABSTRACT: Intracoronary optical frequency domain imaging (OFDI), requires the displacement of blood for clear visualization of the artery wall. Radiographic contrast agents are highly effective at displacing blood however, may increase the risk of contrast-induced nephropathy. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. The aim of this work was to determine the optimal flushing parameters necessary to reliably perform intracoronary OFDI while reducing the volume of administered radiographic contrast, and assess the influence of flushing media choice on vessel wall measurements. 144 OFDI pullbacks were acquired together with synchronized EKG and intracoronary pressure wire recordings in three swine. OFDI images were graded on diagnostic quality and quantitative comparisons of flushing efficiency and intracoronary cross-sectional area with and without precise refractive index calibration were performed. Flushing media with higher viscosities resulted in rapid and efficient blood displacement. Media with lower viscosities resulted in increased blood-media transition zones, reducing the pullback length of diagnostic quality images obtained. Flushing efficiency was found to increase with increases in flow rate and duration. Calculations of lumen area using different flushing media were significantly different, varying up to 23 % (p < 0.0001). This error was eliminated with careful refractive index calibration. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. For patients with sensitivity to contrast, to reduce the risk of contrast induced nephrotoxicity we recommend that intracoronary OFDI be conducted with flushing solutions containing little or no radiographic contrast. In addition, our findings show that careful refractive index compensation should be performed, taking into account the specific contrast agent used, in order to obtain accurate intravascular OFDI measurements.
    No preview · Article · Apr 2015 · The international journal of cardiovascular imaging
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    Kanwarpal Singh · Daisuke Yamada · Guillermo Tearney
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    ABSTRACT: Common path probes are highly desirable for optical coherence tomography as they reduce system complexity and cost by eliminating the need of dispersion compensation and polarization controlling optics. In this work, we demonstrate a monolithic ball lens based, common path, side viewing probe that is suitable for Fourier domain optical coherence tomography. The probe design parameters were simulated in Zemax modeling software and the simulated performance parameters were compared with experimental results. We characterized the performance of the probe by measuring its collection efficiency, resolution, and sensitivity. Our results demonstrated that with a source input power of 25 mW, we could achieve sensitivity of 100.5 dB, which is within 7 dB of the maximum possible sensitivity that could be achieved using a separate reference arm. The axial resolution of the system was found to be 15.6 µm in air and the lateral resolution (full width half maximum) was approximately 49 µm. The probe optics were assembled in a 1 mm diameter hypotube with a 500 µm inner diameter. Images of finger skin acquired using this probe demonstrated clear visualization of the stratum corneum, epidermis, and papillary dermis, along with sweat ducts.
    Full-text · Article · Apr 2015 · Sovremennye Tehnologii v Medicine
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    ABSTRACT: While optical coherence tomography (OCT) has been shown to be capable of imaging coronary plaque microstructure, additional chemical/molecular information may be needed in order to determine which lesions are at risk of causing an acute coronary event. In this study, we used a recently developed imaging system and double-clad fiber (DCF) catheter capable of simultaneously acquiring both OCT and red excited near-infrared autofluorescence (NIRAF) images (excitation: 633 nm, emission: 680nm to 900nm). We found that NIRAF is elevated in lesions that contain necrotic core – a feature that is critical for vulnerable plaque diagnosis and that is not readily discriminated by OCT alone. We first utilized a DCF ball lens probe and a bench top setup to acquire en face NIRAF images of aortic plaques ex vivo (n = 20). In addition, we used the OCT-NIRAF system and fully assembled catheters to acquire multimodality images from human coronary arteries (n = 15) prosected from human cadaver hearts (n = 5). Comparison of these images with corresponding histology demonstrated that necrotic core plaques exhibited significantly higher NIRAF intensity than other plaque types. These results suggest that multimodality intracoronary OCT-NIRAF imaging technology may be used in the future to provide improved characterization of coronary artery disease in human patients.
    Full-text · Article · Apr 2015 · Biomedical Optics Express

  • No preview · Article · Mar 2015 · Journal of the American College of Cardiology
  • Guillermo J Tearney

    No preview · Article · Jan 2015 · JACC. Cardiovascular imaging
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    ABSTRACT: Calcific aortic valve disease (CAVD) is still an unsolved medical problem, because the pathogenesis of CAVD is poorly understood and early calcification is hard to identify. The lack of high-resolution imaging tools to study early stage disease further hampers the search for therapeutic targets. Micro-optical coherence tomography (μOCT), which is a new form of OCT, is the highest-resolution cross-sectional OCT technology available today with 1 μm resolution. We used μOCT to visualize detailed cellular and subcellular structure associated with early calcific changes in diseased human and murine aortic valves. The results suggest that μOCT imaging has the potential to provide new insights into underlying mechanisms of CAVD.
    Full-text · Article · Jan 2015
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    Guillermo J. Tearney
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    ABSTRACT: Today's gold standard for medical diagnosis is histology of excised biopsies or surgical specimens where tissue is taken out of the body, processed, sectioned, stained, and looked at under a light microscope by a pathologist. There are many limitations of this technique, including the fact that it is inherently invasive, time consuming, costly, and dangerous for some organs. Furthermore, oftentimes the diseased tissue is not readily seen by visual inspection and as a result the tissue is sampled at a random location, which can be highly inaccurate. If we could instead conduct microscopy inside the body, then we could provide tools for screening, targeting biopsies, making primary disease diagnosis, and guiding intervention on the cellular basis. This promise has motivated the development of a new field, termed in vivo microscopy, the goal of which is to obtain microscopic images from living human patients. Two in vivo microscopy technologies, confocal microscopy and optical coherence tomography, are currently available and in clinical use. Upcoming developments, including whole organ microscopy, swallowable microscopy capsules, molecular imaging, and very high resolution microscopic devices, are in the pipeline and will likely revolutionize how disease is diagnosed and how medicine is practiced in the future.
    Preview · Article · Dec 2014 · Analytical cellular pathology (Amsterdam)

Publication Stats

11k Citations
1,342.57 Total Impact Points

Institutions

  • 2001-2015
    • Harvard Medical School
      • • Department of Radiology
      • • Department of Dermatology
      • • Department of Pathology
      Boston, Massachusetts, United States
    • Beverly Hospital, Boston MA
      BVY, Massachusetts, United States
  • 2000-2015
    • Massachusetts General Hospital
      • • Wellman Center for Photomedicine
      • • Division of Cardiology
      Boston, Massachusetts, United States
  • 1997-2015
    • Harvard University
      • School of Engineering and Applied Sciences
      Cambridge, Massachusetts, United States
  • 2014
    • Mayo Clinic - Rochester
      • Department of Gastroenterology and Hepatology
      Рочестер, Minnesota, United States
  • 2011
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 2010
    • Lahey Hospital and Medical Center
      Burlington, Massachusetts, United States
  • 2007
    • Duke University
      Durham, North Carolina, United States
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2004
    • Tufts Medical Center
      Boston, Massachusetts, United States
  • 2003
    • Kinki University
      Ōsaka, Ōsaka, Japan
  • 1996-1997
    • Massachusetts Institute of Technology
      • Department of Electrical Engineering and Computer Science
      Cambridge, Massachusetts, United States