Development and clinical translation of a handheld imaging device for 5-ALA-induced fluorescence guided breast conserving surgery

Twenty-three percent of patients who undergo breast conserving surgery (BCS) for early stage breast cancer require reoperation within 1y to remove residual tumour cells not detected in the initial surgery. Re-excisions... [ view full abstract ]

Twenty-three percent of patients who undergo breast conserving surgery (BCS) for early stage breast cancer require reoperation within 1y to remove residual tumour cells not detected in the initial surgery. Re-excisions increase discomfort, stress, adjuvant delay, medical costs, and local recurrence. The purpose of this project is to develop a new custom-designed handheld fluorescence imaging device that allows real-time visualization of residual breast tumour within the surgical cavity. We hypothesize that fluorescence-guided resection using this device with 5-aminolevulinic acid (contrast agent) will improve BCS resection completeness compared to the standard of care.

5-aminolevulinic acid (5-ALA) is an oral prodrug that promotes tumour-specific accumulation of protoporphyrin IX (PpIX), which primarily fluoresces (glows) bright red when excited with 405 nm (violet) light. We have previously demonstrated a proof-of-concept to image breast tumour margins intraoperatively based on 5-ALA-induced PpIX fluorescence in resected tissues (clinicaltrials.gov ID NCT01837225). Clinical user feedback from this ongoing trial has informed the design of an optimized fluorescence imaging prototype device that will be tested in tissue phantoms painted with PpIX. Following initial validation of the new device, we will test our hypothesis in a recently funded Phase III Pan-Canadian multicentre randomized clinical trial (“The Canadian FIGHT Breast Cancer Surgical Trial”; PI: R. DaCosta).

We built a new proof-of-concept imaging device (RPi-Cam) which captures and streams fluorescence images wirelessly to a computer in real-time. We have successfully demonstrated detection of PpIX on pork tissue with RPi-Cam. Additionally, RPi-Cam includes white light illumination for anatomic colocalization of PpIX. Next steps include preparing RPi-Cam for trial readiness by miniaturizing into a clinically-informed housing design. In its early stages, RPi-Cam provides a number of benefits over competing technologies. We anticipate the results of this study will elucidate the clinical applicability of intraoperative fluorescence image guidance for BCS.