Optical diagnosis – highlighting the clinical applications of vibrational spectroscopy

Kathleen M. Gough a and Frédéric Leblond b
aDepartment of Chemistry, University of Manitoba, Winnipeg, Canada
bDepartment of Engineering Physics, Polytechnique Montréal, CP 6079, Succ. Centre-Ville, Montréal, QC H3C 3A7, Canada

This Optical Diagnosis themed issue of Analyst, guest-edited by Professor Frédéric Leblond and Professor Kathleen Gough, highlights papers and discussions from the ninth SPEC conference, SPEC 2016: Clinical Applications of Vibrational Spectroscopy, which was held at the Palais des Congrès in Montréal, Canada, 26–30 June 2016. This international conference series brings together clinicians and scientists who are developing and improving innovative pre-clinical and clinical applications of vibrational spectroscopy that can lead to health-care delivery improvements. Analyst's themed issues from this conference series began in 2009 with the successful SPEC 2008 meeting held in São José dos Campos, Brazil, and continued with SPEC 2010 in Manchester, UK, SPEC 2012 in Chiang Mai, Thailand, and SPEC 2014 in Krakow, Poland. Together, these issues constitute an extensive and detailed resource for the rapid advances in this growing field.

In a significant and auspicious step forward, the ninth meeting was the first to be held since the establishment of the International Society for Clinical Spectroscopy (CLIRSPEC), which will provide the organizational structure for future SPEC meetings. Aligned with the CLIRSPEC goals, the intent of this conference is to create an international forum that facilitates the constructive, collaborative exchange of ideas among academic, clinical and industry experts to address the challenges and opportunities in bringing vibrational spectroscopic techniques from the laboratory to the clinic. The format of the 2016 conference has evolved to meet this goal: 16 invited and 39 contributed papers chosen to fit the sub-themes of the meeting were presented in the main conference room; poster sessions with refreshments allowed for longer conversations among small groups on multiple days. Lively discussion sessions that engage the entire community are an integral part of the regular program at these meetings. Following the SPEC 2014 meeting, a special editorial ‘Spectropathology for the next generation: Quo vadis?’ (Byrne et al., c4an02036g) reviewed the main points from the daily discussion sessions. Significant progress has been made in areas of concern identified at the 2014 meeting, in particular, increased engagement with the clinical community and the development of standardized of protocols.

The goals of those active in this field are to improve health care and achieve better outcomes for patients through the development of practical, economical applications based on the techniques of vibrational spectroscopy. The SPEC 2016 program included three general discussion sessions: Monday: Practical steps forward to clinical translation; Wednesday: An overview of CLIRSPEC; and Thursday: What lies on (and over) the horizon? The Monday morning discussion was formed around a panel of clinicians, including Dr Hugh Barr, a gastrointestinal surgeon, Gloucestershire Hospitals, UK; Dr James Livermore, a neurosurgery resident, University of Oxford, UK; Dr Kevin Petrecca, a neurosurgeon with the Montréal Neurological Institute and Hospital; and Dr Josep Sulé-Suso, an oncologist at Royal Stoke University Hospital, UK; and Dr Dominique Trudel, a pathologist from CRCHUM/Institut du Cancer de Montréal; moderated by Prof. Brian Wilson, Princess Margaret Cancer Centre, University of Toronto, Canada. This forum provided a special opportunity to discuss the shared concerns of all participants, from practising clinicians and pathologists to those developing and testing new applications. Brief, high-level thoughts from each of the panel members gave the session an energetic start. The ensuing discussion so engaged both panel and audience that, by general agreement, it was extended through the lunch hour. Highlights of this thought-provoking session are summarized here.

Recurring themes addressed key steps in the clinical translation process, starting with how to ask the right question, ending with how to achieve adoption and implementation in the operating theatre, clinic or pathology lab. It was generally acknowledged that, as individual scientists, we continue to address problems that are motivated by technology pull – the serendipitous innovation or technological advance that makes a new question possible – and by technology push – the targeted, large-scale collaborations designed to meet a single major goal, such as a protocol for classification of a biopsy as cancer/non-cancer. Two essential criteria were identified: consultation with clinicians and pathologists to identify unmet needs and advise on the goals for spectroscopic analyses, and business development, particularly issues relating to intellectual property, financial models and the establishment of strategic industry partnerships leading to clinical adoption and commercialization.

The right question should be accompanied by a response plan that may be implemented once the question has been answered. In cancer research, much effort has gone into the spectroscopic identification and characterization of tumor margins. Real-time identification of tumor type can dramatically affect the next surgical step in other ways, including a decision to increase the volume of resected tissue or to halt the resection procedure if a non-surgical treatment will offer a greater chance for recovery. For example, certain lymphoma may respond well to chemotherapy; cancer at the surface of the esophagus can now be treated with surface ablation.

Automated screening can reduce the burden on pathologists by providing support, in the form of a spectroscopy-based method for removing confirmed normal samples from the workflow, allowing the pathologists to spend more time on cells that are suspicious for cancer. Final decisions will continue to be made by the medical experts. Rather than drive for a fully automated system for the objective classification of a sample as cancer/non-cancer, it was urged that the goal should be to assist the surgeon and pathologist in decision-making, a philosophy of “guide, don't decide”.

Many of the applications presented at the meeting were directed towards unmet needs in the areas of infectious disease, chronic degenerative diseases and pathogen identification. Personalized medicine is on the horizon; genetic and immunotherapies for presently incurable diseases will alter the demands for diagnoses in the Western world. Other applications focus on the need for simple, low-cost diagnostics in remote or economically-challenged regions.

After 20 years of development, the question persists: what it will take for techniques based on vibrational spectroscopy to be adopted into mainstream clinical workflow? The scientific and economic challenges remain the same: to demonstrate improved patient outcomes, with lower costs and reduced burden on the health-care system. The steadily increasing participation of clinicians at SPEC meetings must now be matched by similar inclusion of business developers. The classic examples of breast and prostate cancer screening represent a huge burden on the pathologist, hence, a much larger market. Developing the spectroscopic tools is more difficult, given that the spectral differences are subtle and may be expected to change with tumor stage. Whether developing tools for a small market with clearly identifiable problems, or targeting a much larger market with a much more difficult problem, significant financial investment and validation through large-scale clinical trials will be required to bring these methods to the market.

Proof-of-concept has been demonstrated in many individual laboratories, on disparate targets from biofluids and cells to biopsies, ex vivo and in vivo, with infrared- and Raman-based implementations in many forms. The establishment of internationally-accepted standard protocols, built on the combined expertise of clinicians, academics and industry, are essential to the creation of clinical applications. In a very positive step forward, CLIRSPEC and Raman4Clinics are conducting multi-lab, round-robin measurements, collecting data from the same samples at different sites, on different instruments. These activities are a measure of the growing maturity of this field as well as the collaboration within the community, and carry the promise of future success.

The papers in this themed issue are organized to follow the flow of the meeting, from examples of tools currently being studied for surgical guidance and in vivo applications, to the next steps in translational medical research, histopathology and clinical applications (Raman and infrared), diagnostics and disease studies with biopsies, body fluids and cytological samples, cell cultures and 3D models for medical research applications, data calibration, pre-processing and analysis, and concluding with emerging technologies.

The distribution of papers and posters reflected the interests and focus of the participants. Clinical translation and adoption into mainstream practice are the ultimate goals of this community; a growing number of researchers are engaged in the development, testing and optimizing stages of research. SPEC 2016 included reports on prototype tools providing in-vivo surgical guidance; however, most presentations involved work still moving towards clinical translation. Of the more than 200 abstracts, the majority were self-identified as belonging to diagnostics and disease studies with biopsies, body fluids and cytological samples (78), emerging technologies leading to clinical applications (47) and applications in infrared and Raman histopathology (45). The frank and helpful discussions among this diverse community are key to developing and maintaining collaborative, constructive interactions. Networking at the SPEC meeting allowed for a thorough airing of concerns, exchange of ideas, stimulating conversations throughout the week and beyond. The papers in this themed issue represent some of the best of the science presented and serve as a snapshot of the current state of the field.

This journal is © The Royal Society of Chemistry 2017