Abstract

Advances in optical designs are enabling the development of miniature microscopes that can examine tissue in situ for early anatomic and molecular indicators of disease, in real time, and at cellular resolution. These new devices will lead to major changes in how diseases are detected and managed, driving a shift from today's diagnostic paradigm of biopsy followed by histopathology and recommended therapy, to non-invasive point-of-care diagnosis with possible same-session definitive treatment. This shift may have major implications for the training requirements of future physicians to enable them to interpret real-timein vivomicroscopic data, and will also shape the emerging fields of telepathology and telemedicine. Implementation of new technologies into clinical practice is a complex process that requires bridging gaps between clinicians, engineers and scientists. This article provides a forward-looking discussion of these issues, with a focus on malignant and pre-malignant lesions, by first highlighting some of the clinical areas where point-of-carein vivomicroscopy could address unmet needs, and then by reviewing the technological challenges that are being addressed, or need to be addressed, forin vivomicroscopy to become a standard clinical tool.

Highlights

  • Rationale for in vivo microscopyMicroscopic observation of tissue specimens— prepared according to established protocols in histology for fixation, embedding, sectioning and staining— is regarded by the medical community as a highly reliable method for the diagnosis of disease and is

  • Liu et al / Point-of-care pathology with miniature microscopes human tissue will continue as the clinical standard for diagnosis of cancer and pre-cancerous conditions for the foreseeable future

  • The simplest view of in vivo pathology is that the proceduralist obtains diagnostic morphologic information in real time and relies only on the in vivo morphologic findings to make on-the-spot decisions about patient management and intervention

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Summary

Rationale for in vivo microscopy

Microscopic observation of tissue specimens— prepared according to established protocols in histology for fixation, embedding, sectioning and staining— is regarded by the medical community as a highly reliable method for the diagnosis of disease and is. While in situ sampling error remains a potential problem, and in vivo molecular imaging has its own set of challenges, POCP has the potential to provide immediate assessment of disease status, improve diagnostic accuracy, guide tissue biopsies, and accelerate diagnostic and therapeutic processes. This development may even permit identification of new molecular and functional signatures of cancer. Optical imaging is ideally suited for the simultaneous detection of multiple probes, each emitting and/or absorbing light at a different wavelength [15] These advanced agents can provide optical contrast and report on both the molecular content and environment of living tissue, and have the unique potential to advance the field of point-ofcare pathology. Given the enormous scope of this specific topic, including the challenges posed by obtaining regulatory approval, and the fact that such reagents have recently been reviewed elsewhere [7,8,9,10,11,12,13], we will not discuss them further

Clinical paradigms
Bridging the gap between technology and practice
Specific clinical applications
Technical advances
Approaches towards miniaturization
Achromatic designs
Clinical deployment
Translational considerations
Summary

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