Guillermo J Tearney

Harvard Medical School, Boston, Massachusetts, United States

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Publications (244)1279.42 Total impact

  • [Show abstract] [Hide abstract]
    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.
    European Heart Journal – Cardiovascular Imaging 09/2015; DOI:10.1093/ehjci/jev229 · 4.11 Impact Factor
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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.
    Gastrointestinal endoscopy 09/2015; DOI:10.1016/j.gie.2015.08.050 · 5.37 Impact Factor
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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.
    Gastrointestinal endoscopy 05/2015; 82(4). DOI:10.1016/j.gie.2015.03.1968 · 5.37 Impact Factor

  • Gastrointestinal Endoscopy 05/2015; 81(5):AB389-AB390. DOI:10.1016/j.gie.2015.03.1566 · 5.37 Impact Factor

  • Gastrointestinal Endoscopy 05/2015; 81(5):AB387. DOI:10.1016/j.gie.2015.03.1562 · 5.37 Impact Factor

  • Gastrointestinal Endoscopy 05/2015; 81(5):AB158-AB159. DOI:10.1016/j.gie.2015.03.103 · 5.37 Impact Factor
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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.
    The international journal of cardiovascular imaging 04/2015; 31(6). DOI:10.1007/s10554-015-0668-0 · 1.81 Impact Factor
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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.
    Sovremennye Tehnologii v Medicine 04/2015; 7(7):29-33. DOI:10.17691/stm2015.7.1.04
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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.
    Biomedical Optics Express 04/2015; 6(4). DOI:10.1364/BOE.6.001363 · 3.65 Impact Factor

  • Journal of the American College of Cardiology 03/2015; 65(10):A1793. DOI:10.1016/S0735-1097(15)61793-4 · 16.50 Impact Factor
  • Guillermo J Tearney ·

    JACC. Cardiovascular imaging 01/2015; 8(1):73-5. DOI:10.1016/j.jcmg.2014.09.019 · 7.19 Impact Factor

  • Theranostics 01/2015; 5(12):1317-1327. DOI:10.7150/thno.12494 · 8.02 Impact Factor
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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.
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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.
    Analytical cellular pathology (Amsterdam) 12/2014; 2014:1-1. DOI:10.1155/2014/797108 · 0.85 Impact Factor
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    ABSTRACT: Spectrally encoded confocal microscopy (SECM) is a reflectance confocal microscopy technology that can rapidly image large areas of luminal organs at microscopic resolution. One of the main challenges for large-area SECM imaging in vivo is maintaining the same imaging depth within the tissue when patient motion and tissue surface irregularity are present. In this paper, we report the development of a miniature vari-focal objective lens that can be used in an SECM endoscopic probe to conduct adaptive focusing and to maintain the same imaging depth during in vivo imaging. The vari-focal objective lens is composed of an aspheric singlet with an NA of 0.5, a miniature water chamber, and a thin elastic membrane. The water volume within the chamber was changed to control curvature of the elastic membrane, which subsequently altered the position of the SECM focus. The vari-focal objective lens has a diameter of 5 mm and thickness of 4 mm. A vari-focal range of 240 μm was achieved while maintaining lateral resolution better than 2.6 μm and axial resolution better than 26 μm. Volumetric SECM images of swine esophageal tissues were obtained over the vari-focal range of 260 μm. SECM images clearly visualized cellular features of the swine esophagus at all focal depths, including basal cell nuclei, papillae, and lamina propria.
    Biomedical Optics Express 12/2014; 5(12). DOI:10.1364/BOE.5.004350 · 3.65 Impact Factor
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    Elena F. Brachtel · Barbara L. Smith · Guillermo J. Tearney · Dongkyun Kang ·
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    ABSTRACT: Complete removal of breast cancer during a single breast-conserving lumpectomy procedure is often challenging due to the lack of adequate intraoperative tools to accurately determine the margin status. About one-third of lumpectomy patients are found to have positive margins upon final histologic analysis, which usually is reported within a week after surgery. These patients are then required to undergo additional surgeries, which increases the patient morbidity, cosmetic challenges, and healthcare cost. Spectrally encoded confocal microscopy (SECM) is a high-speed confocal microscopy technique [1] that can visualize cellular and subcellular features of an unstained fresh tissue. SECM is 10–100 times faster than conventional confocal microscopes and has been demonstrated to image an entire endoscopic mucosal resection (EMR) esophageal tissue (10 mm by 10 mm) within 15 seconds [2]. The high imaging speed of SECM may make it possible to rapidly image the margins of entire lumpectomy specimens to comprehensively determine margin status without sampling error. Real-time feedback regarding the margin status could enable the surgeon to achieve more thorough tumor removal in a single surgery and will significantly reduce the need for additional surgeries. The aim of this preliminary study was to test SECM for visualizing breast cancers with various morphologic features.
    Analytical cellular pathology (Amsterdam) 11/2014; 2014:1-2. DOI:10.1155/2014/573851 · 0.85 Impact Factor
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    ABSTRACT: We present portable preclinical low-coherence interference (LCI) instrumentation for aiding fine needle aspiration biopsies featuring the second-generation LCI-based biopsy probe and an improved scoring algorithm for tissue differentiation. Our instrument and algorithm were tested on 38 mice with cultured tumor mass and we show the specificity, sensitivity, and positive predictive value of tumor detection of over 0.89, 0.88, and 0.96, respectively.
    Journal of Biomedical Optics 11/2014; 19(11):116005. DOI:10.1117/1.JBO.19.11.116005 · 2.86 Impact Factor
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    ABSTRACT: Intravascular optical coherence tomography (IVOCT) is a well-established method for the high-resolution investigation of atherosclerosis in vivo. Intravascular near-infrared fluorescence (NIRF) imaging is a novel technique for the assessment of molecular processes associated with coronary artery disease. Integration of NIRF and IVOCT technology in a single catheter provides the capability to simultaneously obtain co-localized anatomical and molecular information from the artery wall. Since NIRF signal intensity attenuates as a function of imaging catheter distance to the vessel wall, the generation of quantitative NIRF data requires an accurate measurement of the vessel wall in IVOCT images. Given that dual modality, intravascular OCT-NIRF systems acquire data at a very high frame-rate (>100 frames/s), a high number of images per pullback need to be analyzed, making manual processing of OCT-NIRF data extremely time consuming. To overcome this limitation, we developed an algorithm for the automatic distance-correction of dual-modality OCT-NIRF images. We validated this method by comparing automatic to manual segmentation results in 180 in vivo images from six New Zealand White rabbit atherosclerotic after indocyanine-green injection. A high Dice similarity coefficient was found (0.97 ± 0.03) together with an average individual A-line error of 22 µm (i.e., approximately twice the axial resolution of IVOCT) and a processing time of 44 ms per image. In a similar manner, the algorithm was validated using 120 IVOCT clinical images from eight different in vivo pullbacks in human coronary arteries. The results suggest that the proposed algorithm enables fully automatic visualization of dual modality OCT-NIRF pullbacks, and provides an accurate and efficient calibration of NIRF data for quantification of the molecular agent in the atherosclerotic vessel wall.
    The International Journal of Cardiovascular Imaging 10/2014; DOI:10.1007/s10554-014-0556-z · 1.81 Impact Factor
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    Kengyeh K. Chu · Giovanni J. Ughi · Linbo Liu · Guillermo J. Tearney ·
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    ABSTRACT: Intravascular optical coherence tomography (IVOCT) has made significant clinical impact, providing a method of visualizing coronary plaques, optimizing percutaneous coronary intervention, and monitoring treatment results. Achieving cellular resolution in cardiovascular optical coherence tomography (OCT) adds even greater utility; thin-cap fibroatheromas (TCFA) that include microcalcifications, cholesterol crystals, and macrophages are hypothesized to correlate with rupture potential, yet are too small to be imaged by conventional OCT. In this review, we survey new developments in the optical technology that may contribute to the advancement of IVOCT into the microscopic domain, including new light sources and optical configurations. We also describe recent progress in micro-OCT (μOCT), a high-resolution OCT implementation developed in our laboratory that utilizes many of these advances to achieve 1-μm resolution.
    Current Cardiovascular Imaging Reports 10/2014; 7(12):9308. DOI:10.1007/s12410-014-9308-7
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    ABSTRACT: Mucociliary clearance (MCC) and submucosal glands (SMGs) are major components of airway innate immunity that have impaired function in cystic fibrosis (CF). Although both of these defense systems develop post-natally in the ferret, the lungs of newborn ferrets remain sterile in the presence of a functioning cystic fibrosis transmembrane conductance regulator (CFTR) gene. We evaluated several components of airway innate immunity and inflammation in the early CF ferret lung. At birth, the rates of MCC did not differ between CF and non-CF animals, but the height of the airway surface liquid was significantly reduced in CF newborn ferrets. CF ferrets had impaired MCC after 7 days of age, despite normal rates of ciliogenesis. Only non-CF ferrets eradicated Pseudomonas directly introduced into the lung after birth, while both genotypes could eradicate Staphylococcus. CF bronchioalveolar lavage fluid (BALF) had significantly lower and selective antimicrobial activity against Pseudomonas than non-CF, which was insensitive to changes in pH and bicarbonate. LC-MS-MS and cytokine analysis of BALF from sterile C-sectioned and non-sterile naturally-born animals demonstrated CF-associated disturbances in IL-8, TNFα, and IL-β, and pathways that control immunity and inflammation including the complement system, macrophage functions, mTOR signaling, and eIF2 signaling. Interestingly, during the birth transition, IL-8 was selectively induced in CF BALF, despite no genotypic difference in bacterial load shortly after birth. These results suggest that newborn CF ferrets have defects in both innate immunity and inflammatory signaling that may be important in the early onset and progression of lung disease in these animals.
    American Journal of Respiratory Cell and Molecular Biology 10/2014; DOI:10.1165/rcmb.2014-0250OC · 3.99 Impact Factor

Publication Stats

10k Citations
1,279.42 Total Impact Points


  • 2001-2015
    • Harvard Medical School
      • • Department of Pathology
      • • Department of Radiology
      • • Department of Dermatology
      Boston, Massachusetts, United States
    • Beverly Hospital, Boston MA
      BVY, Massachusetts, United States
  • 2000-2015
    • Massachusetts General Hospital
      • • Department of Pathology
      • • Wellman Center for Photomedicine
      • • Division of Cardiology
      Boston, Massachusetts, United States
  • 2014
    • Mayo Clinic - Rochester
      • Department of Gastroenterology and Hepatology
      Рочестер, Minnesota, United States
  • 1997-2014
    • Harvard University
      • School of Engineering and Applied Sciences
      Cambridge, Massachusetts, United States
  • 2011
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 2010
    • Lahey Hospital and Medical Center
      Burlington, Massachusetts, United States
  • 1996-2009
    • Massachusetts Institute of Technology
      • • Division of Health Sciences and Technology
      • • Department of Electrical Engineering and Computer Science
      Cambridge, 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