Enabling point of care optical diagnostics and treatment of oral lesions in resource-limited settings: Preclinical development and evaluation of a low-cost theranostic intraoral device for image-guided photodynamic therapy

在资源匮乏地区实现口腔病变即时光学诊断和治疗:低成本口腔内诊疗一体化设备在图像引导光动力疗法中的临床前开发和评估

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Abstract

SIGNIFICANCE: Oral squamous cell carcinoma (OSCC) is exceedingly prevalent and deadly in South Asia, especially the Indian subcontinent, affecting 15 out of every 100,000 people and claiming over 70,000 lives annually. This problem is further compounded by inadequate medical infrastructure for screening and cancer care, especially in rural areas. AIM: This study evaluates the design and assessment of a theranostic, low-cost, intraoral device to enable simultaneous multichannel optical imaging and photodynamic therapy (PDT) for detection and treatment of early oral cancer. APPROACH: The system's performance was assessed using buccal mucosal tissue phantoms containing protoporphyrin IX (PpIX), as well as OSCC phantoms photosensitized with 5-aminolevulinic acid (ALA)-induced PpIX. A murine xenograft model (Swiss nu/nu mice) implanted with TR146 OSCC cells was used to test the device's performance before and after ALA administration, as well as to evaluate photobleaching following light delivery (630nm, 100J/cm(2)). RESULT: The PpIX fluorescence signal demonstrated a linear correlation up to 50μM PpIX concentration. The degree of photobleaching increased with higher light doses up to 100J/cm(2) in both the tissue phantoms and the murine xenografts. Tumor volume decreased significantly, with histological analysis showing necrosis extending to a depth of 3.0-3.5 mm after PDT and consistent with monte carlo modeling of light delivery. CONCLUSION: A compact, handheld and low-cost intraoral device with dental camera form factor is able to carry out simultaneous multichannel white light and fluorescence imaging and image-guided PDT light delivery. The ability to quantify the extent of photobleaching as a dosimetry surrigate points to potential for real-time treatment monitoring with the same hardware.

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