Hariri Lab - Lida P. Hariri, MD, PhD

My overall research interests include: 1) the development and clinical application of highresolution optical imaging for early detection and diagnosis of pulmonary diseases, including interstitial lung disease and lung cancer, and 2) the implementation and validation of optical imaging in the practice of pathology and clinical medicine.

Idiopathic Pulmonary Fibrosis (IPF)

IPF is a chronic, progressive, and ultimately fatal form of interstitial lung disease (ILD) with an abysmal median survival of 3 years. Both accurate diagnosis of IPF and the ability to monitor disease progression over time are essential to inform patient prognosis, direct selection of appropriate therapies, and assess disease progression and therapeutic responsiveness. Highresolution CT (HRCT) is a cornerstone in ILD/IPF assessment, but has inherent resolution limitations that impede detection of subtle microscopic changes, such as those required for early diagnosis or occurring over the course of anti-fibrotic therapy. Surgical lung biopsy provides tissue for microscopic diagnosis, but has known risks of morbidity and mortality in ILD patients. There is currently no method for microscopic assessment in IPF that is low-risk, does not require physical tissue removal, and is repeatable. The goal of this research is to develop a novel, minimallyinvasive, non-surgical paradigm using endobronchial optical imaging for early microscopic diagnosis, and assessment of disease progression and therapeutic response in IPF and other ILDs.

Optical coherence tomography (OCT) provides rapid 3D imaging with microscopic resolution (<10 μm) well beyond HRCT capabilities, and tissue volumes orders of magnitude larger than that assessed with surgical lung biopsies. OCT can image many more distinct sites than can be sampled with wedge biopsies. Due to its non-destructive nature, OCT can also be repeated for longitudinal assessments over time. We have developed thin endobronchial OCT catheters that are compatible with standard bronchoscopy, are able to reach the peripheral subpleural lung, and enable volumetric assessment of multiple spatially distinct locations in the lung within 5-10 minutes. We are conducting clinical in vivo endobronchial OCT imaging studies in ILD patients undergoing biopsy for diagnosis. Our preliminary studies have shown that in vivo endobronchial OCT can visualize microscopic features, including honeycombing not visible on HRCT, required to distinguish IPF and non-IPF diagnoses in ILD patients with non-diagnostic HRCTs. Our ongoing OCT studies include: 1) Clinical studies to determine the sensitivity and specificity of OCT for IPF diagnosis in patients with non-diagnostic HRCTs, and 2) A longitudinal study to investigate changes in disease progression and response to therapy at a microscopic level over time.

Selected Publications:

 

Hariri LP, Adams DC, Applegate MB, Miller AJ, Roop BW, Villiger M, Bouma BE, Suter MJ. Distinguishing tumor from associated fibrosis to increase diagnostic biopsy yield with polarization-sensitive optical coherence tomography. Clinical Cancer Research 25(17):5242-5249, 2019.

Hariri LP, Adams DC, Wain JC, Lanuti M, Muniappan A, Sharma A, Colby TV, Mino-Kenudson M, Mark EJ, Kradin RL, Goulart H, Tager AM, Suter MJ. Endobronchial optical coherence tomography for low-risk microscopic assessment and diagnosis of idiopathic pulmonary fibrosis in vivo. American Journal of Respiratory and Critical Care Medicine 197(7):949-952, 2018.

Désogère P*, Tapias LF*, Hariri LP, Rotile NJ, Rietz TA, Probst CK, Blasi F, Day H, Mino-Kenudson M, Weinreb P, Violette SM, Fuchs BC, Tager AM, Lanuti M, Caravan P. Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Science Translational Medicine 9(384), 2017.

Hariri LP, Mino-Kenudson M, Lanuti M, Miller AJ, Mark EJ, Suter MJ. Diagnosing lung carcinomas with optical coherence tomography. Annals of the American Thoracic Society 12(2):193-201, 2015.

Hariri LP, Mino-Kenudson M, Applegate MB, Mark EJ, Tearney GJ, Lanuti M, Channick CL, Chee A, Suter MJ. Towards the guidance of transbronchial biopsy: Identifying pulmonary nodules with optical coherence tomography. Chest 144(4):1261-8, 2013.

Hariri LP, Villiger, M, Applegate MB, Mino-Kenudson M, Mark EJ, Bouma BE, Suter MJ. Seeing beyond the bronchoscope to increase the diagnostic yield of bronchoscopic biopsy. American Journal of Respiratory and Critical Care Medicine 187(2): 125-9, 2013.