Head & neck optical diagnostics: vision of the future of surgery.

Abstract

Review paper and Proceedings of the Inaugural Meeting of the Head and Neck Optical Diagnostics Society (HNODS) on March 14th 2009 at University College London. The aim of our research must be to provide breakthrough translational research which can be applied clinically in the immediate rather than the near future. We are fortunate that this is indeed a possibility and may fundamentally change current clinical and surgical practice to improve our patients' lives.

Full text

Page 1

BioMed Central
Page 1 of 9
(page number not for citation purposes)
Head & Neck Oncology
Open Access
Meeting report
Head & neck optical diagnostics: vision of the future of surgery
Tahwinder Upile1,2,3, Waseem Jerjes1,2,3,4, Henricus JCM Sterenborg1,5,
Adel K El-Naggar1,6, Ann Sandison1,7, Max JH Witjes1,8, Merrill A Biel1,9,
Irving Bigio1,10, Brian JF Wong1,11, Ann Gillenwater1,12,
Alexander J MacRobert1,13, Dominic J Robinson1,14, Christian S Betz1,15,
Herbert Stepp1,16, Lina Bolotine1,17, Gordon McKenzie1,2,18,
Charles Alexander Mosse1,13, Hugh Barr1,19, Zhongping Chen1,20,
Kristian Berg1,21, Anil K D'Cruz1,22, Nicholas Stone1,19, Catherine Kendall1,19,
Sheila Fisher1,23, Andreas Leunig1,15, Malini Olivo1,24, Rebecca Richards-
Kortum1,25, Khee Chee Soo1,26, Vanderlei Bagnato1,27, Lin-Ping Choo-
Smith1,28, Katarina Svanberg1,29, I Bing Tan1,30, Brian C Wilson1,31,32,
Herbert Wolfsen1,32,33, Arjun G Yodh1,34 and Colin Hopper*1,2,3,4
Address: 1The "Head and Neck Optical Diagnostics Society" Council, Head & Neck Centre, University College Hospital, 250 Euston Road, London,
NW1 2PG, UK, 2UCLH Head and Neck Centre, London, UK, 3Department of Surgery, University College London Medical School, London, UK,
4Unit of Oral & Maxillofacial Surgery, Division of Maxillofacial, Diagnostic, Medical and Surgical Sciences, UCL Eastman Dental Institute, London,
UK, 5Center for Optical Diagnostics and Therapy, Erasmus University Medical Center, Rotterdam, the Netherlands, 6Department of Pathology, The
University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA, 7Department of Histopathology, Imperial College and The Hammersmith
Hospitals, London, UK, 8Department of Oral & Maxilofacial Surgery, University Medical Center Groningen, the Netherlands, 9Virginia Piper
Cancer Institute-Abbott Northwestern Hospital, Minnesota, USA, 10Department of Biomedical Engineering, Electrical & Computer Engineering,
Physics, Boston University, Boston, USA, 11The Beckman Laser Institute and Medical Clinic, The University of California Irvine, Irvine, CA, USA,
12Department of Head and Neck Surgery, Division of Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA,
13National Medical Laser Centre, University College London, London, UK, 14Center for Optical Diagnostics and Therapy, Department of Radiation
Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands, 15Department of Otorhinolaryngology, Head & Neck Surgery, Ludwig
Maximilian University, Munich, Germany, 16LIFE Center, University Clinic Munich, Munich, Germany, 17Research Centre for Automatic Control
(CRAN), Nancy-University, UMR CNRS, France, 18Michelson Diagnostics, 11A Grays Farm Production Village, Grays Farm Road, Orpington, Kent,
BR5 3BD, UK, 19Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK, 20Department of Biomedical Engineering, Beckman Laser
Institute, University of California, Irvine, USA, 21Dept. of Radiation Biology, The Norwegian Radium Hospital, Montebello, Norway, 22Department
of Oral & Maxillofacial Surgery, Tata Memorial Hospital, Mumbai, India, 23Department of Oral & Maxillofacial Surgery, Leeds Dental Institute,
Leeds, UK, 24Photodynamic Therapy and Diagnosis Laboratory, Division of Medical Sciences, National Cancer Centre, Singapore, 25Department
of Bioengineering, Rice University, Houston, USA, 26National Cancer Centre, Singapore 169610, Singapore, 27Univiersity of Sao Paulo, Sao Carlos,
SP, Brazil, 28National Research Council Canada-Institute for Biodiagnostics, Winnipeg, Manitoba, Canada, 29Division of Oncology, Lund
University Hospital, Lund, Sweden, 30Department of Head & Neck Oncology & Surgery, The Netherlands Cancer Institute – Antoni van
Leeuwenhoek Hospital, Amsterdam, the Netherlands, 31Division of BioPhysics and BioImaging, Ontario Cancer Institute, Ontario, Canada,
32Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Canada, 33Division of Gastroenterology and
Hepatology, Mayo Clinic, Florida, USA and 34Physics and Astronomy, University of Pennsylvania, Philadelphia, USA
Email: Tahwinder Upile - mrtupile@yahoo.com; Waseem Jerjes - waseem_wk1@yahoo.co.uk;
Henricus JCM Sterenborg - h.j.c.m.sterenborg@erasmusmc.nl; Adel K El-Naggar - anaggar@mdanderson.org;
Ann Sandison - ann_sandison@hotmail.com; Max JH Witjes - m.j.h.witjes@kchir.umcg.nl; Merrill A Biel - Bielx001@umn.edu;
Irving Bigio - bigio@bu.edu; Brian JF Wong - bjwong@uci.edu; Ann Gillenwater - agillenw@mdanderson.org;
Alexander J MacRobert - a.macrobert@ucl.ac.uk; Dominic J Robinson - d.robinson@erasmusmc.nl; Christian S Betz - christian.betz@med.uni-
muenchen.de; Herbert Stepp - Herbert.Stepp@med.uni-muenchen.de; Lina Bolotine - l.bolotine@nancy.fnclcc.fr;
Gordon McKenzie - gordon.mckenzie@md-ltd.co.uk; Charles Alexander Mosse - smosse@medphys.ucl.ac.uk;
Hugh Barr - hugh.barr@glos.nhs.uk; Zhongping Chen - z2chen@uci.edu; Kristian Berg - kristian.berg@rr-research.no;
Anil K D'Cruz - docdcruz@gmail.com; Nicholas Stone - n.stone@medical-research-centre.com; Catherine Kendall - c.kendall@medical-research-
centre.com; Sheila Fisher - s.e.fisher@doctors.org.uk; Andreas Leunig - andreas.leunig@med.uni-muenchen.de;
Malini Olivo - dmsmcd@nccs.com.sg; Rebecca Richards-Kortum - rkortum@rice.edu; Khee Chee Soo - admskc@nccs.com.sg;
Vanderlei Bagnato - vander@ifsc.usp.br; Lin-Ping Choo-Smith - Lin-P'ing.Choo-Smith@nrc-cnrc.gc.ca;
Katarina Svanberg - katarina.svanberg@med.lu.se; I Bing Tan - i.tan@nki.nl; Brian C Wilson - wilson@uhnresearch.ca;
Herbert Wolfsen - wolfsen.herbert@mayo.edu; Arjun G Yodh - yodh@physics.upenn.edu; Colin Hopper* - c.hopper@ucl.ac.uk

Page 2

Head & Neck Oncology 2009, 1:25http://www.headandneckoncology.org/content/1/1/25
Page 2 of 9
(page number not for citation purposes)
* Corresponding author
Abstract
Review paper and Proceedings of the Inaugural Meeting of the Head and Neck Optical Diagnostics
Society (HNODS) on March 14th 2009 at University College London.
The aim of our research must be to provide breakthrough translational research which can be
applied clinically in the immediate rather than the near future. We are fortunate that this is indeed
a possibility and may fundamentally change current clinical and surgical practice to improve our
patients' lives.
Introduction
Upper aero-digestive tract (UADT) carcinomas continue
to be the 6th most common cancer worldwide with
approximately 270,000 new oral cavity tumours per year
[1]. Unfortunately, the majority of these tumours present
in late stage with the attendant functional, psychological
and economic costs to their victims. Early diagnosis is
often delayed as tumour precursors or early cancers are
hardly visible and not picked up by common imaging
methods. It's clearly evident that screening and early
detection of the cancer and its early precursors have the
potential to reduce the morbidity and mortality of this
disease. In that context, current oral examination methods
including incandescent light or toluidine blue, reflectance
visualization and illumination with chemi-luminescent
light source, are largely subjective, dependent on the expe-
rience of the examiner and are considered in-effective
tools in primary care settings [2].
The true or important surgical margin of these lesions is
still not defined [3]. In the treatment of cancer the funda-
mental surgical goal is to remove all local malignant dis-
ease and leave no residual malignant cells. Studies have
demonstrated the benefit of achieving negative resection
margins in terms of disease free local recurrence and over-
all survival. The surgical margins for head & neck cancer
may vary widely depending on the site of disease. This var-
iation reflects the biological and anatomical environment
of the tumour site at macroscopic and microscopic levels.
There is no accepted standard for the quantity of normal
tissue to be removed and the effect of positive margins on
recurrence rate appears to be considerably dependent on
the site of the tumour. The extent of tumour volume resec-
tion is determined by the need for cancer control and the
peri-operative, functional and aesthetic morbidity of the
surgery.
Resection margins are currently assessed intra-operatively
by frozen section and retrospectively after definitive histo-
logical analysis of the resection specimen. There are limi-
tations to this assessment. The margin may not be
consistent in three dimensions and may be susceptible to
errors in sampling and histological interpretation. Assign-
ing the true excision margin may be difficult due to post-
excision changes secondary to shrinkage and fixation [3].
Local recurrence occurs even among tumours with exten-
sive histological demonstration of adequate resection
margins. Sites with significant recurrence rates after nega-
tive resection margins are oral cavity, sub-mandibular
region, tonsil and pharynx. Therefore, it is accepted that
cancers at these sites require larger margins of excision
than tumours elsewhere in the head and neck [3].
The development of optical techniques for non-invasive
diagnosis of disease is an ongoing challenge to biomedi-
cal optics. Optical diagnostics have proved to be a reliable
resource that can be used to give an instant diagnosis of
soft and, more recently, hard tissue diseases. In the field of
head and neck malignancy, most of the experimental
spectroscopy work has been performed using fluorescence
spectroscopy, Raman spectroscopy, elastic scattering spec-
troscopy, microendoscopy and optical coherence tomog-
raphy [4]. Furthermore, the exponential rise in computer
Published: 13 July 2009
Head & Neck Oncology 2009, 1:25doi:10.1186/1758-3284-1-25
Received: 2 July 2009
Accepted: 13 July 2009
This article is available from: http://www.headandneckoncology.org/content/1/1/25
© 2009 Upile et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Page 3

Head & Neck Oncology 2009, 1:25http://www.headandneckoncology.org/content/1/1/25
Page 3 of 9
(page number not for citation purposes)
processing power, adaptive statistical software packages
and the development of nanofilament and refined fibre
optics has lead to quantum leaps in our ability to define
the edge of pathology. The search for the optimum imag-
ing modality to refine this "disease edge" is occurring
along several often mutually complementary optical tech-
nological pathways which were outlined at the meeting
and are critically summarised below (Figure 1).
Tumour margin detection in real-time without the use of
additional molecular stain would be desirable. Surgical
use of a microscopy tool would be ideal, but most systems
focus on microscopic disease evaluation, whereas tools
for macroscopic scanning of tissue such as enhanced
endoscopy imaging are less well developed.
For head and neck cancer there are two immediate fields
of potential application
1) Screening for second primaries in patients with a his-
tory of cancer. This requires imaging techniques or an
approach where a larger area can be scanned quickly.
2) Distinguishing potentially malignant visible primary
lesions from benign ones. Here fibre-optic point measure-
ments can be used as the location of the lesion is known.
Macroscopic view of laser resected tumour orientated by suture and clinical diagram
Figure 1
Macroscopic view of laser resected tumour orientated by suture and clinical diagram. This shows the complexity
of pathological interpretation which can be liable to sampling error. A whole mount view of H&E stained section of transverse
slice through the tumour and tonsil show the close margin of excision. It is reasonable to assume that high quality 'real-time'
pathological data would aid surgical incision and ensure a more complete excision. Retrospective analysis paraffin section H&E
appears less useful since it cannot immediately inform surgery only later therapy. Optical diagnostics technology may provide a
means to improve surgical treatment and eventual outcome by informing the surgeon in 'real-time' and improving the margin;
(Courtesy of Dr A Sandison, Imperial College, London).

Page 4

Head & Neck Oncology 2009, 1:25http://www.headandneckoncology.org/content/1/1/25
Page 4 of 9
(page number not for citation purposes)
Techniques
Elastic Scattering Spectroscopy
Optical spectroscopy mediated by fibre-optic probes can
be used to perform non-invasive, or minimally-invasive,
real-time assessment of tissue pathology in situ. The
method of elastic scattering spectroscopy (ESS) is sensitive
to the sub-cellular architectural changes, such as nuclear
grade and nuclear to cytoplasm ratio, mitochondrial size
and density...etc., which correlates with features often
used by pathologists when performing histological assess-
ment. ESS is also sensitive to ultrastructural changes that
are beyond the Abbe resolution limit for optical micros-
copy, and thus conveys information that may not be avail-
able from conventional histology. ESS has proved to be a
promising method for detecting premalignant and malig-
nant changes in a variety of organ areas, including oral tis-
sues, with high sensitivity and specificity. Several head
and neck tissues, including lymph nodes, archival bones,
skin and resection margins, have been interrogated using
ESS with very promising results [4,5].
It should be noted that the ESS method senses micromor-
phology changes without actually imaging the micro-
scopic structure. Consequently, diagnosis is provided by
objective statistical and analytical methods, rather than
subjective interpretation of images. Clinical studies of ESS
have been conducted in a variety of organ sites, and larger-
scale clinical studies are now ongoing. Further develop-
ments include an analytical model that extracts, from the
ESS spectra, the underlying physical correlates of the tis-
sue relating to disease, such as mean size of scattering cen-
tres, blood perfusion and haemoglobin oxygen saturation
(Figure 2).
Differential path-length spectroscopy (DPS)
Various techniques for point measurements have been
developed and investigated clinically for different applica-
tions. Differential path-length spectroscopy is a recently
developed fibre-optic point measurement technique that
measures scattered light in a broad spectrum. Due to the
specific fibre-optic geometry, only scattered photons that
have travelled a predetermined path length are measured.
The spectrum is analyzed mathematically and the meas-
ured curve is translated into a set of parameters that are
related to the microvasculature and to the intracellular
morphology. DPS has been extensively evaluated on opti-
cal phantoms and tested clinically in various clinical
applications (Figure 3) [6].
The first measurements in biopsy proven squamous cell
carcinoma showed significant changes in both vascular
and morphological parameters. Measurements on thick
keratinized lesions however failed to generate any vascu-
lar signatures. This is related to the sampling depth of the
standard optical fibres used. Recently the group devel-
oped a fibre-optic probe with a ~1 mm sampling depth.
Measurements on several leukoplakias have shown that
with this new probe one may now sample just below the
keratin layer to obtain vascular signatures. This enables
clinically significant diagnostic measurements [6].
Spectral scatter scanning system
A novel technique showing great translational utility is a
recent raster scanning scatter spectroscopy system that has
been evaluated for imaging the spectral signature remitted
from tissue, with real-time classification algorithm, which
maximizes the ability to identify regions of tumour from
regions of normal tissue. The system uses a wide band of
wavelengths from 400 nm up to 700 nm, and recovers the
scatter power, scatter amplitude, and absorption species,
from the reflectance from a 100 micron spot, allowing
imaging of tissue a high frame rate. The system uses dark
field illumination and spectrometer detection in the emis-
sion channel together with a scanning mirror. The early
prototypes of the system were tested on pancreas tumours
and prostate tumour margin detection, and current work
is ongoing in breast cancer margin delineation [7].
Raman Spectroscopy
Raman spectroscopy is a spectroscopic technique used in
physics and chemistry to study vibrational and other low-
frequency modes in a system. Raman spectroscopy is
laser-based technique that enables chemical characteriza-
tion and structure of molecules in sample. Raman spec-
troscopy methods are being considered as techniques
which could be complementary or even alternative to
biopsy, pathology and clinical assays in many medical
technologies (Figure 4).
The applications of Raman spectroscopy in the life sci-
ences are still in the early stages of development. Raman
spectroscopy is being investigated in a broad spectrum of
biological and toxicological sciences. In oncology Raman
is being investigated as a diagnostic tool for characterising
cancer cells and early malignant changes and distinguish-
ing these from normal cells. Raman spectroscopy has the
distinct advantage over other optical techniques that it
provides information on molecular composition and
structure of living tissue. There is a strong rationale for
using Raman spectroscopy in epithelial cancer. Although
Raman spectroscopy has been investigated for several dec-
ades, clinical head & neck studies are scarce [8].
A significant problem associated with Raman applications
arises from inherently weak signal produced by the
Raman Effect. Biomedical samples are extremely intricate
systems which reflect complex Raman spectra. Raman
bands due to biological constitutes are generally over-
lapped, making it difficult to identify individual compo-
nents correctly. Furthermore, due to the minimal sample

Page 5

Head & Neck Oncology 2009, 1:25http://www.headandneckoncology.org/content/1/1/25
Page 5 of 9
(page number not for citation purposes)
ESS spectra obtained from bivalved cervical lymph nodes showing spectra acquired from histopathologicaly negative nodes (top) and positive ones (bottom); (Courtesy of Dr W Jerjes, University College London, London)
Figure 2
ESS spectra obtained from bivalved cervical lymph nodes showing spectra acquired from histopathologicaly
negative nodes (top) and positive ones (bottom); (Courtesy of Dr W Jerjes, University College London, Lon-
don).

Page 6

Head & Neck Oncology 2009, 1:25http://www.headandneckoncology.org/content/1/1/25
Page 6 of 9
(page number not for citation purposes)
preparation encountered in the clinical environment, bio-
medical sample samples usually produce a strong fluores-
cent background which may completely obscure the true
Raman signals [8].
Fluorescence Techniques
In an attempt to improve intra-operative tissue diagnosis,
tools and methods for an "optical biopsy" have been pro-
posed, some of them exploiting fluorescent properties of
endogenous or exogenous fluorochromes [9,10].
Fluorescence spectroscopy tries to capture characteristic
spectral features of fluorochromes and correlate these
with the disease state. Several mathematical methods have
been proposed to evaluate recorded spectra to maximize
the discrimination between "normal" and "malignant".
Fluorescence imaging aims at highlighting malignant tis-
sue, especially where it is not evident under white light in
a large field of view. Autofluorescence as well as drug-
induced fluorescence can be detected and displayed with
commercial equipment. They usually rely on capturing
fluorescence in one or two colour channels and remission
in another channel. Sophisticated image processing to
quantify fluorescence or eliminate disturbing signal is
only slowly becoming available.
Auto-fluorescence imaging has recently been shown to
improve the detection of premalignant and malignant
oral lesions. This method is based on the illumination in
the absorption of tissue fluorophore molecules (NADH
and FAD in the epithelial layer and collagen, and elastin
in the stroma) in ultraviolet visible spectrum leading to
the emission of lower energy photon that can be detected
as fluorescence from the oral surface mucosa. Studies of
these methods in normal oral mucosa have shown
increased green fluorescence in comparison to neoplastic
lesions upon ultraviolet (UV) or near UV light source. The
histopathological manifestations and heterogeneity of
oral squamous lesions and the confounding factors for
DPS spectrum of normal oral mucosa with a fit of the descriptive model
Figure 3
DPS spectrum of normal oral mucosa with a fit of the descriptive model. The graph indicates that the fit residues are
in the order of the measurement noise. With the parameters derived we can classify a measurement site where the overall
amplitude of scattering, the Mie amplitude, the saturation, the vessel diameter and the blood vessel to blood volume ratio con-
tribute significantly to the classification; (Courtesy of Prof HJCM Sterenborg, Erasmus Medical Center, Rotterdam).

Page 7

Head & Neck Oncology 2009, 1:25 http://www.headandneckoncology.org/content/1/1/25
Page 7 of 9
(page number not for citation purposes)
the validation and the clinical applications of auto-fluo-
rescence imaging are hurdles to overcome [9,10] (Figure
5).
The fluorescence contrast is even slightly enhanced by
using exogenously applied fluorescent markers or their
precursors (e.g., 5-aminolevulinic acid induced Protopor-
phyrin IX). Recent advances include the possibility to
extract true spectra of single fluorophores ("intrinsic spec-
tra") by mathematically eliminating the undesired influ-
ences of scattering and absorption. As well, tumour-
specific enzymes are about to be specifically targeted by
fluorescent markers "smart probes" in order to improve
both sensitivity and specificity.
Optical Coherence Tomography
Optical coherence tomography is an imaging modality
that uses light to determine cross-sectional anatomy in
turbid media such as living tissues. Optical coherence
tomography (OCT) is based on coherence-domain optical
technology. OCT takes advantage of the short coherence
length of broadband light sources to perform micrometer-
scale, cross-sectional imaging of biological tissue. OCT is
analogous to ultrasound imaging except that it uses light
rather than sound. The high spatial resolution of OCT
enables non-invasive in vivo "optical biopsy" and provides
immediate and localized diagnostic information (Figure
6).
Despite the recent development of Fourier domain OCT
that significantly increases imaging speed and sensitivity,
the OCT system that achieves both high speed and high
sensitivity simultaneously at 1.3 m is not currently avail-
able. The recent development of a Fourier-domain-mode-
lock (FDML) swept source based OCT system can now
achieve high speed (>100 kHz A-scan rate) and high spa-
tial resolution (<4 m) simultaneously. In addition, the
development of various miniature scanning probes that
allow high-speed 3-D OCT imaging will be reported. This
has been augmented by the development of a non-itera-
tive digital focusing method to alleviate the compromise
between lateral resolution and depth measurement range,
which allows high lateral resolution over the full depth
measurement range [11].
The major clinical applications of OCT in head and neck
surgery that have been explored recently are: examination
of the true vocal folds with the aim of identifying and
characterizing pre-cancerous and early stage malignancy
and examination of the paediatric/neonatal sub-glottis.
OCT imaging can discern subtle differences in the sub-
glottic mucosa and hopefully provide a means to identify
patients at risk for extubation failure, and ideally in the
future be used in the neonatal ICU to optimize endotra-
cheal tube management [12].
This technology still as yet gives the unfulfilled promise of
the basement membrane recognition which is all impor-
tant in defining the extent of malignant spread and dis-
ease prognosis. Its resolution is still clearly just below the
tissue level but rapidly approaching the cellular scale. Fur-
ther developments in hardware (i.e. optics, probe design
Examples of molecules and their Raman spectrum; (Courtesy of Dr GW Puppels, Erasmus Medical Center, Rotterdam)
Figure 4
Examples of molecules and their Raman spectrum;
(Courtesy of Dr GW Puppels, Erasmus Medical
Center, Rotterdam).
Representative enhanced fluorescence image of a T1 SCC of the vocal cords; (Courtesy of Dr CS Betz, Ludwig Maximilian University, Munich)
Figure 5
Representative enhanced fluorescence image of a T1
SCC of the vocal cords; (Courtesy of Dr CS Betz,
Ludwig Maximilian University, Munich).

Page 8

Head & Neck Oncology 2009, 1:25http://www.headandneckoncology.org/content/1/1/25
Page 8 of 9
(page number not for citation purposes)
and laser scanning) and software processing (including
pattern recognition and rendering) continue to improve
resolution and clinical utility.
Other techniques
Several other optically based systems for tissue interroga-
tion are described as well as their current ex-vivo and prac-
tical applications
Infrared Spectroscopy
The potential role of infrared spectroscopy in biomedical
science has been described to distinguish different bio-
molecules by probing chemical bond vibrations and using
these molecular and sub-molecular patterns to define and
differentiate pathological from healthy samples. Several
protocols have been described to exploit the potential of
infrared spectroscopy in defining spectral profiles in sali-
vary gland disease attributable to various kinds of cancer
and the corresponding healthy tissues. Researchers sug-
gest the potential of infrared micro-spectroscopy imaging,
in combination with multivariate data analysis, to high-
light even subtle biochemical and morphological
changes, distinguishing various kinds and grades of neo-
plasia in human tissues [13].
An inverted OCT image of the lateral border of the tongue
Figure 6
An inverted OCT image of the lateral border of the tongue. There are processing artefacts running across the image.
The surface differentiation is evident as visible tongue papillae poorly. 'Rete Ridges/pegs' can be seen projecting into the under-
lying mucosa. The various forms of tongue papillae are also visible. Histologically this area was found to represent multifocal
squamous cell carcinoma; (Courtesy of Drs W Jerjes and Z Hamdoon, University College London, London)

Page 9

Publish with BioMed Central and every
scientist can read your work free of charge
"BioMed Central will be the most significant development for
disseminating the results of biomedical research in our lifetime."
Sir Paul Nurse, Cancer Research UK
Your research papers will be:
available free of charge to the entire biomedical community
peer reviewed and published immediately upon acceptance
cited in PubMed and archived on PubMed Central
yours — you keep the copyright
Submit your manuscript here:
http://www.biomedcentral.com/info/publishing_adv.asp
BioMedcentral
Head & Neck Oncology 2009, 1:25 http://www.headandneckoncology.org/content/1/1/25
Page 9 of 9
(page number not for citation purposes)
Con-focal endo-microscopy
Confocal Endomicroscopy (CEM) is a non invasive imag-
ing tool enabling "optical biopsies" of tissues at cellular
level. Clinical studies have successfully reported the accu-
racy of CEM for the characterization of gastrointestinal,
dermatologic and ocular diseases. Researchers have
assessesed the potential use of endomicroscopy in combi-
nation with clinically approved fluorophores to character-
ize premalignant and malignant lesions in human larynx.
Imaging of squamous cell carcinoma provided clear infor-
mation on the heterogeneous distribution of tumour cells
surrounded by stroma. Cellular anomalies and disorders
of keratinisation such as dyskeratosis and keratin pearls
were also discerned by CEM and the images corroborated
with histological data [14].
Conclusion
Optical diagnosis of the head and neck is a rapidly devel-
oping area of clinical research that can be readily trans-
lated to inform patient treatment and overall quality of
life. Much still needs to be achieved and granting organi-
sations are directed to pay attention to this specialty where
relatively small investments may lead to enormous divi-
dends in terms of improvements in treatments through-
out the fields of medicine and surgery.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
TU, WJ, HJCMS, AKE, AS, MJHW, MAB, IB, BJFW, AG,
AJM, DJR,CSB, HS, LB, GM, CAM, HB, ZC, KB, AKD, NS,
CK, SF, AL, MO, RR, KCS, VB, LC, KS, IBT, BCW, HW,
AGY,CH: contributed to conception and design, designed
the review, carried out the literature research, and manu-
script preparation, editing and manuscript review. All
authors read and approved the final manuscript.
Acknowledgements
To the organisers, speakers and delegates who provided a powerful and
rich forum to critically discuss the latest developments in their fields.
References
1.El-Naggar AK: Role of histopathologic and phenotypic assess-
ment in the development and validation of optical diagnostic
devices for head and neck mucosal lesions. Head & Neck Oncol-
ogy 2009, 1(Suppl 1):O9.
2. Gillenwater A: Optical technologies for detection and diagno-
sis of oral neoplasia. Head & Neck Oncology 2009, 1(Suppl
1):O11.
3. Sandison A: The surgical resection margin. Head & Neck Oncol-
ogy 2009, 1(Suppl 1):I1.
4.Hopper C: The clinical application of elastic scattering spec-
troscopy in the head and neck. Head & Neck Oncology 2009,
1(Suppl 1):O2.
5.Bigio IJ: Elastic light scattering spectroscopy for the detection
of pre-cancer: an overview. Head & Neck Oncology 2009, 1(Suppl
1):O1.
6. Sterenborg HJCM, Witjes MJH, De Visscher S, Amelink A: Differen-
tial pathlength spectroscopy for diagnosis of head and neck
cancer. Head & Neck Oncology 2009, 1(Suppl 1):O7.
Pogue BW, Krishnaswamy V, Laughney A, Paulsen KD, Hoopes PJ,
Allende PBG: Spectral scatter scanning system for surgical
margin detection. Head & Neck Oncology 2009, 1(Suppl 1):O12.
Witjes MJH: Raman spectroscopy in clinical diagnosis of head
& neck pathology. Head & Neck Oncology 2009, 1(Suppl 1):O8.
Betz CS, Makriniotis T, Stepp H, Jerjes W, Upile T, Hopper C, Leunig
A: Diagnosis of head & neck malignancy using fluorescence
spectroscopy and imaging. Head & Neck Oncology 2009, 1(Suppl
1):O4.
Stepp H, Johansson A, Betz CS, Leunig A: Fluorescence spectros-
copy and fluorescence imaging for tissue diagnostics – prin-
ciples and methods. Head & Neck Oncology 2009, 1(Suppl 1):O3.
Chen Z: Optical coherence tomography: challenge and
opportunity. Head & Neck Oncology 2009, 1(Suppl 1):O5.
Wong BJF: The clinical application of optical coherence tom-
ography in the head and neck. Head & Neck Oncology 2009,
1(Suppl 1):O6.
Conti C, Ferraris P, Giorgini E, Rubini C, Sabbatini S, Tosi G: Micro-
imaging FT-IR of Head and Neck Tumours. The case of sali-
vary glands. Head & Neck Oncology 2009, 1(Suppl 1):O13.
Abbaci M, Temam S, Casiraghi O, Vielh P, Bosq J, Fouret P, Laplace-
Builhé C: Characterization of laryngeal carcinoma by confocal
endomicroscopy. Head & Neck Oncology 2009, 1(Suppl 1):O14.
7.
8.
9.
10.
11.
12.
13.
14.