SignificanceOptical tissue phantoms serve as inanimate and stable reference materials used to calibrate, characterize, standardize, and test biomedical imaging instruments. Although various types of solid tissue phantoms have been described in the literature, current phantom models are limited in that they do not have a depth feature that can be adjusted in real-time, they cannot be adapted to other applications, and their fabrication can be laborious and costly.AimOur goal was to develop an optical phantom that could assess the imaging performance of fluorescence imaging devices and be customizable for different applications.ApproachWe developed a phantom with three distinct components, each of which can be customized.ResultsWe present a method for fabricating a solid optical tissue that contains (1) an adjustable depth capability using thin film phantoms, (2) a refillable chip loaded with fluorophores of the user’s choice in various desired quantities, and (3) phantom materials representative of different tissue types.ConclusionsThis article describes the development of phantom models that are customizable, adaptable, and easy to design and fabricate.
Re-excision due to inability to visualize positive margins following breast-conserving surgery is a significant clinical challenge. 5-aminolevulinic acid (5-ALA), a non-fluorescent prodrug, leads to intracellular accumulation of fluorescent porphyrins in tumor cells. This single-centre Phase II randomized controlled trial evaluated the clinical safety, feasibility and diagnostic performance of a new handheld fluorescence imaging device (PRODIGI) combined with 5-ALA hydrochloride (HCl) for intraoperative visualization of invasive breast carcinomas. Fifty-four patients were enrolled in the study and randomized to receive no 5-ALA HCl or orally administered 5-ALA HCl (15 mg/kg or 30 mg/kg BW). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed and biopsies were collected from within and outside the clinically-demarcated tumor border for blinded histopathological analysis. In the absence of 5-ALA HCl, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Administration of 5-ALA HCl resulted in tumors that fluoresced bright red with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA dose group the positive predictive value (PPV) for detecting tumor inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively and 100.0% and 50.0% respectively in the 30 mg/kg dose group. No drug or device-related adverse events were observed and technical feasibility and clinical integration of this intraoperative tumor visualization approach were confirmed. This is the first known clinical report of visualization of 5-ALA HCl-induced fluorescence in invasive lobular and ductal breast carcinoma using a real-time handheld intraoperative fluorescence imaging device.
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