CoreView and FIBI for rapid-onsite evaluation and molecular profiling of core-needle breast biopsies.

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Abstract Patients with concerning breast masses require diagnosis, triage, and management. This proposal seeks to combine three recently developed technologies to provide rapid diagnostic support for patient breast tumor evaluation. Currently, this process consists of biopsy, standard histology, phenotype determination via im- munohistochemistry, and increasingly, molecular assays. In well-served areas, the challenges involve obtain- ing appropriate and representative biopsies, waiting for slide preparation, review by a pathologist, then im- munostaining (IHC), and optionally, submission for nucleic-acid based studies. We propose a simple tissue-direct-to-digital slide-free imaging solution (FIBI, fluorescence imitating brightfield imaging, UC Davis) coupled with a virtually hands-off millifluidic specimen handling device (CoreView, UW). Images, intrinsically digital, are of diagnostic quality, and can be interpreted locally by trained pathology per- sonnel, or streamed anywhere in the world for real-time evaluation. Eventually, on-site or cloud-based com- puter-assisted tools will be available. An additional goal is to achieve same-session multiplexed immunostain- ing and imaging, based on rapid-quench click chemistry approaches developed by Dr. Ko (Univ. Penn.) We will build and test versions of the combined imaging and automated sample handling of needle-derived specimens initially using excess fresh or recently fixed human breast tissue, and subsequently clinically ac- quired core-needle biopsies. Tasks involve optimization of staining, imaging, image display, reproducibility demonstration, and sample integrity assessments. Incorporation of single-step immunostaining with far-red la- bels will be included, and methods for rapid probe cycling (for multiplexing—ER, PR, HER2) will be applied and tested. Subspecialty pathology review will ensure that the FIBI images and immunostains are reliable and of diagnostic quality. The goal is to implement a context-appropriate, automated instrument that can capture his- topathology images from core-needle biopsies, while retaining their integrity for downstream processing as needed. Results will be available within minutes and allow for informed patient triage or even immediate on-site treatment, especially valuable if the patient has had to travel long distances to reach the clinic. Statement of Potential Impact: Current biopsy evaluation interposes at least 1-3 days delay, and involves consuming some or all of small tissue specimens. Immunostaining contributes additional delay. The situation is more challenging in poorly served areas, as histology laboratories and the pathologists capable of interpreting the results are rare outside major urban centers. The CoreView-FIBI approach could dramatically improve pa- tient-level care velocity, but also enterprise-level efficiency, allowing for same-day disease treatment planning. For biospecimen applications, preanalytical variables will be under complete control, the non-destructive nature of the imaging means that more tissue is available for storage and research, and imaging of the specimen prior to banking provide assurance of tissue content and abundance estimates of relevant components.