RESUMEN
Prostate cancer continues to be the most diagnosed non-skin malignancy in men. While up to one in eight men will be diagnosed in their lifetimes, most diagnoses are not fatal. Better lesion location accuracy combined with emerging localized treatment methods are increasingly being utilized as a treatment option to preserve healthy function in eligible patients. In locating lesions which are generally <2cc within a prostate (average size 45cc), small variance in MRI-determined boundaries, tumoral heterogeneity, patient characteristics including location of lesion and prostatic calcifications, and patient motion during the procedure can inhibit accurate sampling for diagnosis. The locations of biopsies are recorded and are then fully processed by histology and diagnosed via pathology, often days to weeks later. Utilization of real-time feedback could improve accuracy, potentially prevent repeat procedures, and allow patients to undergo treatment of clinically localized disease at earlier stages. Unfortunately, there is currently no reliable real-time feedback process for confirming diagnosis of biopsy samples. We examined the feasibility of implementing structured illumination microscopy (SIM) as a method for on-site diagnostic biopsy imaging to potentially combine the diagnostic and treatment appointments for prostate cancer patients, or to confirm tumoral margins for localized ablation procedures. We imaged biopsies from 39 patients undergoing image-guided diagnostic biopsy using a customized SIM system and a dual-color fluorescent hematoxylin & eosin (H&E) analog. The biopsy images had an average size of 342 megapixels (minimum 78.1, maximum 842) and an average imaging duration of 145 s (minimum 56, maximum 322). Comparison of urologist's suspicion of malignancy based on MRI, to pathologist diagnosis of biopsy images obtained in real time, reveals that real-time biopsy imaging could significantly improve confirmation of malignancy or tumoral margins over medical imaging alone.
RESUMEN
Optical sensors have numerous positive attributes such as low invasiveness, miniaturizability, biocompatibility, and ease of signal transduction. Recently, there has been a strong research focus on using phosphorescent readout mechanisms, specifically from long-lifetime phosphorescent or 'persistent luminescence' particles, for in vitro and in vivo sensors. Persistent luminescence readouts can avoid cellular autofluorescence during biological monitoring, leading to an improved signal-to-noise ratio over a more traditional fluorescence readout. In this study, we show for the first time an ionophore-based optical bulk optode sensor that utilizes persistent luminescence microparticles for ion detection. To achieve this, we combined long-lifetime strontium aluminate-based 'glow-in-the-dark' microparticles with a non-fluorescent pH-responsive dye in a hydrophobic plasticized polymer membrane along with traditional ionophore-based optical sensor components to create a phosphorescent 'Glow Sensor'. The non-fluorescent pH indicator dye gates the strontium aluminate luminescence signal so that it decreases in magnitude with increasing sodium concentration. We characterized the Glow Sensor in terms of emission lifetime, dynamic range, response time, reversibility, selectivity, and stability.
