Higher harmonic generation microscopy for instant on-site pathologic feedback of lung biopsies

Abstract

<b>Introduction:</b> Treatment for lung cancer patients requires a tissue diagnosis. To date, the absence of on-site feedback on the quality of histology samples regularly results in non-diagnostic and repeat procedures. Higher harmonic generation microscopy (HHGM) provides rapid histological images of unprocessed tissue. <b>Aim:</b> Assess the feasibility of HHGM for instant bronchoscopic and pleural biopsy pathological quality assessment. <b>Methods:</b> Fresh biopsies of patients undergoing diagnostic bronchoscopy or thoracoscopy were imaged with a mobile HHG microscope (Flash Pathology B.V.) and subsequently processed for routine diagnostics. Dedicated lung pathologists assessed independently the HHGM image quality for pathological assessment. <b>Results:</b> In 47 patients, final diagnosis: malignant (16), non-malignant (29), non-representative (2), 107 biopsies were evaluated. HHGM provided total biopsy scans within 1-2 minutes and generated a high, cellular resolution image within an additional 3 minutes (Figure1). The HHGM image quality was adequate for 89% and 94% of the biopsies according to 2 independent pathologists (inter-observer agreement of 87%). Next, at least 2 pathologists will compare both HHGM and standard histology images to set HHGM malignancy criteria for HHGM biopsy quality/diagnosis. <b>Conclusion:</b> HHGM for on-site rapid assessment of bronchoscopic and pleural biopsies is feasible. Its clinical value requires further research.