Clinical evaluation of smartphone-based fluorescence imaging for guidance and monitoring of ALA-PDT treatment of early oral cancer

Abstract

Clinical evaluation of smartphone-based fluorescence imaging for guidance and monitoring of ALA-PDT treatment of early oral cancer," J. AbstractSignificance: India has one of the highest rates of oral cancer incidence in the world, accounting for 30% of reported cancers. In rural areas, a lack of adequate medical infrastructure contributes to unchecked disease progression and dismal mortality rates. Photodynamic therapy (PDT) has emerged as an effective modality with potential for treating early stage disease in resourcelimited settings, while photosensitizer fluorescence can be leveraged for treatment guidance.Aim: Our aim was to assess the capability of a simple smartphone-based device for imaging 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence for treatment guidance and monitoring as part of an ongoing clinical study evaluating low-cost technology for ALA-based PDT treatment of early oral cancer.Approach: A total of 29 subjects with <2 cm diameter moderately/well-differentiated microinvasive (< 5 mm depth) oral squamous cell carcinoma lesions (33 lesions total, mean area ∼1.23 cm 2 ) were administered 60 mg∕kg ALA in oral solution and imaged before and after delivery of 100 J∕cm 2 total light dose to the lesion surface. Smartphone-based fluorescence and white light (WL) images were analyzed and compared with ultrasound (US) imaging of the same lesions.Results: We present a comparative analysis of pre-and post-treatment fluorescence, WL, and US images of oral lesions. There was no significant difference in the distribution of lesion widths measured by fluorescence and US (mean widths of 14.5 and 15.3 mm, respectively) and linear regression shows good agreement (R 2 ¼ 0.91). In general, PpIX fluorescence images obtained prior to therapeutic light delivery are able to resolve lesion margins while dramatic photobleaching (∼42%) is visible post-treatment. Segmentation of the photobleached area confirms the boundaries of the irradiated zone. Conclusions:A simple smartphone-based approach for imaging oral lesions is shown to agree in most cases with US, suggesting that this approach may be a useful tool to aid in PDT treatment guidance and monitoring photobleaching as part of a low-cost platform for intraoral PDT.

Photodynamic therapy, priming and optical imaging: Potential co-conspirators in treatment design and optimization — a Thomas Dougherty Award for Excellence in PDT paper

“…Additional studies have used PpIX photobleaching in clinical settings in e.g. basal cell carcinoma [227], and most recently in monitoring ALA-PDT in oral cancers [228]. These observations are consistent with the earlier reports by Van Der Veen et al, in which photobleaching of PpIX was utilized as a method to study the benefits of a second illumination in ALA-PDT [229].…”

Smartphone-based imaging systems for medical applications: a critical review

“…Treatment guidance imaging systems may have many overlapping requirements with diagnostic applications but primarily differ in that they have more stringent requirements for real-time visualization and analysis to provide active procedural guidance and support more rapid clinical decision making. Recent reports for SBI systems and applications that involve treatment guidance include image-guided surgery, 18 – 20 , 22 , 37 , 38 , 41 management of severe burn injuries, 40 , 95 PDT, 6 – 9 and venipuncture. 63 , 136 …”

“…A clinical evaluation of another SBI system for photodynamic therapy of oral lesions at a medical center was recently reported by Khan et al. 9 to assess low-cost technological treatments for this disease. Twenty-nine patients with confirmed oral squamous cell carcinoma lesions and who were undergoing PDT were imaged using white light, ultrasound, autofluorescence, and PpIX fluorescence imaging pre- and post-treatment.…”

“… 1 – 4 SBI is also frequently proposed for noninvasive monitoring and diagnosis of externally accessible tissues, particularly in dermatological applications. 5 More recently, SBI for minimally invasive procedures and treatment guidance has also been reported, including photodynamic therapy (PDT), 6 – 9 endoscopy, 10 – 13 in vivo microscopy, 14 – 17 and surgery. 18 – 22 As ex vivo diagnostic applications have been extensively reviewed elsewhere, 1 – 4 this review focuses on SBI systems for real-time tissue imaging applications (i.e., in vivo monitoring, diagnosis, and treatment guidance).…”

Perspectives on interstitial photodynamic therapy for malignant tumors

“…[75][76][77][78] Building on the positive patient responses, relative simplicity, and low cost of this approach, PDT is also showing great promise for treating early stage oral cancers as a primary modality in developing countries with high incidence. [79][80][81] On the other hand, 60% of the patients present with already advanced HNSCCs (stage III/ IV). Recurrent and metastatic cases often exhibit the additional challenge of acquired cytostatic drug resistance.…”