, Volume 189, Issue 2, pp 111–119 | Cite as

Progress Toward Optical Biopsy: Bringing the Microscope to the Patient

  • Richard C. NewtonEmail author
  • Samuel V. Kemp
  • Pallav L. Shah
  • Daniel Elson
  • Ara Darzi
  • Kiyoshi Shibuya
  • Stephen Mulgrew
  • Guang-Zhong Yang


The investigation of many lung diseases currently requires bronchoscopic or surgical histopathological tissue biopsy. This creates risks for patients and entails processing costs and delays in diagnosis. However, several mainly probe-based biophotonic techniques that can image solitary lesions and diffuse lung diseases are fuelling a paradigm shift toward real-time in vivo diagnosis. Optical coherence tomography (OCT) uses near-infrared light in a process analogous to ultrasonography to image the mucosal and submucosal tissue boundaries of the bronchial tree. With 15-μm resolution, early work suggests it can differentiate between neoplasia, carcinoma in situ, dysplasia, and metaplasia based around epithelial thickness and breaches in the basement membrane. Probe-based confocal laser endomicroscopy (pCLE) has superior resolution but less penetration than OCT and employs blue argon laser light to fluoresce the endogenous elastin of (1) the acinar scaffold of the peripheral lung and (2) the basement membrane lying under bronchial mucosa. Initial studies suggest that the regular fibre arrangement of the basement membrane is altered in the presence of overlying malignant epithelium. pCLE produces detailed representations of the alveolar septal walls, microvessels, and some inflammatory cells. A third device, the endocytoscope, is a contact microscope requiring contrast agent to provide subcellular resolution of bronchial mucosa. Further development of these “optical biopsy” techniques and evaluation of diagnostic sensitivity and specificity of the acquired images are needed before they can be considered effective methods for eliminating the need for, and thus risks of, pinch biopsy to enable real-time diagnosis to streamline management.


Optical biopsy Confocal endomicroscopy Optical coherence tomography Endocytoscopy Lung cancer Diffuse lung disease 



Imperial College’s pCLE hardware was partially funded by its RT-ISIS grant from the EPSRC.


Olympus kindly provided the RBH with a free endocytoscope system. Dr. S. Kemp is partly supported by an unconditional grant from Olympus for an unrelated research project.

Supplementary material

pCLE imaging - fluorescent macrophages are specific to smokers (MPG 818 kb)

pCLE imaging – healthy basement membrane of right main bronchus (MPG 926 kb)

pCLE imaging – healthy lobule (MPG 3950 kb)

408_2011_9282_MOESM4_ESM.mpg (2.1 mb)
pCLE imaging of a microvessel – mosaicing increases field of view (MPG 2102 kb)


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Richard C. Newton
    • 1
    Email author
  • Samuel V. Kemp
    • 2
  • Pallav L. Shah
    • 2
  • Daniel Elson
    • 3
  • Ara Darzi
    • 1
  • Kiyoshi Shibuya
    • 4
  • Stephen Mulgrew
    • 5
  • Guang-Zhong Yang
    • 3
  1. 1.Department of Surgery and CancerImperial College, St Mary’s HospitalLondonUK
  2. 2.Department of Respiratory MedicineRoyal Brompton HospitalLondonUK
  3. 3.The Hamlyn Centre for Robotic SurgeryImperial CollegeLondonUK
  4. 4.Department of Chest SurgeryMatsudo City HospitalMatsudo CityJapan
  5. 5.Department of SurgeryLister HospitalStevenageUK

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