Lida P. Hariri

Post-Doctoral Fellow (Translational Biomedical Optics) at Massachusetts General Hospital / Harvard Medical School

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Division of Pulmonary and Critical Care Medicine / Department of Pathology Employer: Massachusetts General Hospital / Harvard Medical School The Hariri Optical Imaging Laboratory is a multidisciplinary research group at Massachusetts General Hospital and Harvard Medical School. The focus of the laboratory is on the design, development and clinical translation of endoscopic optical coherence tomography (OCT)-based imaging devices for microscopic detection, diagnosis and monitoring of pulmonary diseases, including lung fibrosis, smoking and vaping-related lung diseases, post-COVID lung disease and interstitial lung abnormalities. A highly motivated, independent, innovative, and organized individual with an interest in translational optical/diagnostic imaging and biomedicine is sought for a Post-Doctoral Research Fellow position. The appropriate candidate will work in a highly collaborative multidisciplinary research environment consisting of engineers, physicians and technici...

Reply to: Endobronchial Optical Coherence Tomography: Shining New Light on Diagnosing UIP?

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From the Authors: We thank Kalverda and colleagues for their letter regarding our recently published paper [1], and appreciate the opportunity to provide additional clarity on the points that they raise about the work. Below we address the questions asked by Kalverda and colleagues: Enrollment criteria Our primary objective was to conduct a blinded, prospective study to evaluate the diagnostic accuracy of endobronchial OCT (EB-OCT) for microscopic ILD diagnosis as compared to concurrent surgical lung biopsy (SLB) and clinical follow-up diagnosis. Our inclusion criteria were: a) age >21 years, b) fibrotic ILD based on high-resolution computed tomography (HRCT) with unclear diagnosis, c) SLB required for ILD diagnosis based on the clinical decision of the treating pulmonologist, and d) ability to give informed consent. Therefore, in our patient cohort, there was no high-confidence clinical-radiologic diagnosis prior to SLB. Our institution does not routinely use bronchoalveolar lav...

Rapid non-destructive volumetric tumor yield assessment in fresh lung core needle biopsies using polarization sensitive optical coherence tomography

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Adequate tumor yield in core-needle biopsy (CNB) specimens is essential in lung cancer for accurate histological diagnosis, molecular testing for therapeutic decision-making, and tumor biobanking for research. Insufficient tumor sampling in CNB is common, primarily due to inadvertent sampling of tumor-associated fibrosis or atelectatic lung, leading to repeat procedures and delayed diagnosis. Currently, there is no method for rapid, non-destructive intraprocedural assessment of CNBs. Polarization-sensitive optical coherence tomography (PS-OCT) is a high-resolution, volumetric imaging technique that has the potential to meet this clinical need. PS-OCT detects endogenous tissue properties, including birefringence from collagen, and degree of polarization uniformity (DOPU) indicative of tissue depolarization. Here, PS-OCT birefringence and DOPU measurements were used to quantify the amount of tumor, fibrosis, and normal lung parenchyma in 42 fresh, intact lung CNB specimens. PS-OCT res...

Diagnostic Accuracy of Endobronchial Optical Coherence Tomography for the Microscopic Diagnosis of Usual Interstitial Pneumonia

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Rationale: Early, accurate diagnosis of interstitial lung disease (ILD) informs prognosis and therapy, especially in idiopathic pulmonary fibrosis (IPF). Current diagnostic methods are imperfect. HRCT resolution is limited while surgical lung biopsy (SLB) carries risks of morbidity/mortality. Endobronchial optical coherence tomography (EB-OCT) is a low-risk, bronchoscope-compatible modality that images large lung volumes in vivo with microscopic resolution, including subpleural lung, and has the potential to improve the diagnostic accuracy of bronchoscopy for ILD diagnosis. Objectives: We performed a prospective diagnostic accuracy study of EB-OCT in ILD patients with a low-confidence diagnosis undergoing SLB. Primary endpoints were EB-OCT sensitivity/specificity for diagnosis of the histopathologic pattern of usual interstitial pneumonia (UIP) and clinical IPF. The secondary endpoint was agreement between EB-OCT and SLB for diagnosis of the ILD fibrosis pattern. Methods: EB-OCT was...

In vivo assessment of changes to canine airway smooth muscle volume following bronchial thermoplasty with OR-OCT

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The inability to assess and measure changes to the airway smooth muscle (ASM) in vivo is a major challenge to evaluating asthma and its clinical outcomes. Bronchial thermoplasty (BT) is a therapy for asthma that aims to reduce the severity of excessive bronchoconstriction by ablating ASM. While multiple long-term clinical studies of BT have produced encouraging results, the outcomes of BT treatment in practice have been variable, and questions remain regarding the selection of patients. Previously we have demonstrated an imaging platform called orientation-resolved optical coherence tomography that can assess ASM endoscopically using an imaging catheter compatible with bronchoscopy. In this work, we present results obtained from a longitudinal BT study performed using a canine model (n = 8) and with the goal of investigating the use of OR-OCT for measuring the effects of BT on ASM. We demonstrate that we are capable of accurately assessing ASM both before and in the weeks following ...

Toward the Guidance of Transbronchial Biopsy Identifying Pulmonary Nodules With Optical Coherence Tomography

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Background Solitary pulmonary nodules (SPNs) frequently require transbronchial needle aspiration (TBNA) or biopsy to determine malignant potential, but have variable diagnostic yields. Confirming needle placement within SPNs during TBNA could significantly increase diagnostic yield. Optical coherence tomography (OCT) provides nondestructive, high-resolution, microstructural imaging with potential to distinguish SPN from parenchyma. We have developed needle-based OCT probes compatible with TBNA. Before OCT can play any significant role in guiding clinical TBNA, OCT interpretation criteria for differentiating SPN from lung parenchyma must be developed and validated. Methods OCT of SPN and parenchyma was performed on 111 ex vivo resection specimens. OCT criteria for parenchyma and SPN were developed and validated in a blinded assessment. Six blinded readers (two pulmonologists, two pathologists, and two OCT experts) were trained on imaging criteria in a 15-min training session prior to...

Distinguishing Tumor from Associated Fibrosis to Increase Diagnostic Biopsy Yield with Polarization-Sensitive Optical Coherence Tomography

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Purpose: With recent advancements in personalized medicine, biopsies must contain sufficient tumor for histologic diagnosis and molecular testing. However, inadvertent biopsy of tumor-associated fibrosis compromises tumor yield, resulting in delayed diagnoses and/or repeat procedures when additional tumor is needed. The ability to differentiate tumor from fibrosis intraprocedurally during biopsy could significantly increase tumor yield. Polarization-sensitive optical coherence tomography (PS-OCT) is an imaging modality that is endoscope- and/or needle-compatible, and provides large volumetric views of tissue microstructure with high resolution (∼10 μm) while simultaneously measuring birefringence of organized tissues such as collagen. We aim to determine whether PS-OCT can accurately detect and distinguish tumor-associated fibrosis from tumor. Experimental Design: PS-OCT was obtained ex vivo in 64 lung nodule samples. PS-OCT birefringence was measured and correlated to collag...

In Vivo and Ex Vivo Microscopy: Moving Toward the Integration of Optical Imaging Technologies Into Pathology Practice

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The traditional surgical pathology assessment requires tissue to be removed from the patient, then processed, sectioned, stained, and interpreted by a pathologist using a light microscope. Today, an array of alternate optical imaging technologies allow tissue to be viewed at high resolution, in real time, without the need for processing, fixation, freezing, or staining. Optical imaging can be done in living patients without tissue removal, termed in vivo microscopy, or also in freshly excised tissue, termed ex vivo microscopy. Both in vivo and ex vivo microscopy have tremendous potential for clinical impact in a wide variety of applications. However, in order for these technologies to enter mainstream clinical care, an expert will be required to assess and interpret the imaging data. The optical images generated from these imaging techniques are often similar to the light microscopic images that pathologists already have expertise in interpreting. Other clinical specialists do not h...

Nano-optic endoscope for high-resolution optical coherence tomography in vivo

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Acquisition of high-resolution images from within internal organs using endoscopic optical imaging has numerous clinical applications. However, difficulties associated with optical aberrations and the trade-off between transverse resolution and depth of focus significantly limit the scope of applications. Here, we integrate a metalens, with the ability to modify the phase of incident light at subwavelength level, into the design of an endoscopic optical coherence tomography catheter (termed nano-optic endoscope) to achieve near diffraction-limited imaging through negating non-chromatic aberrations. Remarkably, the tailored chromatic dispersion of the metalens in the context of spectral interferometry is utilized to maintain high-resolution imaging beyond the input field Rayleigh range, easing the trade-off between transverse resolution and depth of focus. We demonstrate endoscopic imaging in resected human lung specimens and in sheep airways in vivo. The combination of the superior ...

Needle-based Optical Coherence Tomography to Guide Transbronchial Lymph Node Biopsy

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Background: Transbronchial needle aspiration (TBNA), often used to sample lymph nodes for lung cancer staging , is subject to sampling error even when performed with endobronchial ultrasound. Optical coherence tomography (OCT) is a high-resolution imaging modality that rapidly generates helical cross-sectional images. We aim to determine if needle-based OCT can provide microstructural information in lymph nodes that may be used to guide TBNA, and improve sampling error. Methods: We performed ex vivo needle-based OCT on thoracic lymph nodes from patients with and without known lung cancer. OCT imaging features were compared against matched histology. Results: OCT imaging was performed in 26 thoracic lymph nodes, including 6 lymph nodes containing metastatic carcinoma. OCT visualized lymphoid follicles, adipose tissue, pigment-laden histiocytes, and blood vessels. OCT features of metastatic carcinoma were distinct from benign lymph nodes, with microarchitectural features that reflecte...

Optical coherence tomography (OCT) imaging of dynamic airway behavior in an asthma model

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To better understand bronchoconstriction in asthma, it is critical to dynamically visualize airway behavior in vivo. However, currently available imaging techniques do not have sufficient temporal and spatial resolution to investigate airway dynamics. We propose to use endobronchial Optical Coherence Tomography (OCT) to provide real-time cross-sectional images of airway dynamics with a high spatial resolution. Our aim was to study the structure and function of spatially distinct airways during tidal breathing (TB), breath-holds (BH) at end inspiration, and in a response to single deep inspiration (DI) and multiple DI (MDI) in a preclinical sheep asthma model. Anesthetized and mechanically ventilated sheep (n=3) were imaged with OCT in 4 dependent and 4 non-dependent airways at baseline and in methacholine constricted airways. We assessed airway morphology during TB, BH, DI and MDI maneuvers. The change in airway lumen area was found to be greater in the dependent airways compared to...

Birefringence microscopy platform for assessing airway smooth muscle structure and function in vivo

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The inability to visualize airway smooth muscle (ASM) cells in vivo is a major obstacle in understanding their role in normal physiology and diseases. At present, there is no imaging modality available to assess ASM in vivo. Confocal endomicroscopy lacks the penetration depth and field of view, and conventional optical coherence tomography (OCT) does not have sufficient contrast to differentiate ASM from surrounding tissues. We have developed a birefringence microscopy platform that leverages the micro-organization of tissue to add further dimension to traditional OCT. We have used this technology to validate ASM measurements in ex vivo swine and canine studies, visualize and characterize volumetric representations of ASM in vivo, and quantify and predict ASM contractile force as a function of optical retardation. We provide in vivo images and volumetric assessments of ASM in living humans and document structural disease variations in subjects with mild asthma. The opportunity to li...

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