Numerous surgical procedures would benefit from the ability to obtain real-time intraoperative microscopic information. For example, it is common in some cancer operations to look for spread of cancer by taking biopsies. These are then processed rapidly by a pathologist to make an intraoperative diagnosis. Similarly, tumour margins also often require biopsy and microscopic assessment intra-procedurally. The surgeon uses this information to determine the surgical strategy for the remainder of the procedure. Real time microscopy could provide non-invasive histological observations and offer a time saving alternative to this approach.
Other applications include monitoring of microvascular reperfusion (for
example in organ transplant surgery), and mapping of diffuse diseases throughout
the abdomen such as endometriosis.
Optiscan has constructed prototype devices to allow testing of these applications in animals. Subsequently, sterilisable prototypes have also been built and used for human imaging pilot studies involving open and minimally invasive surgical procedures at Bankstown–Lidcombe Hospital, (Sydney, Australia), and laparoscopic liver biopsy at Johannes Gutenberg University of Mainz (Mainz, Germany).
Optiscan has also completed a 15 patient clinical trial at the Royal Women’s
Hospital (Melbourne, Australia) to assess the accuracy of a prototype rigid
confocal endoscope for detection and diagnosis of early cervical cancer (cervical
intraepithelial neoplasia; CIN). CIN is an early abnormal change in the cells
of the cervical epithelium that may be classified as CIN1 (mild), CIN2 (moderate)
or CIN3 (severe). Current methods used to detect malignant and premalignant
changes of the cervix rely on the Pap smear (www.cervicalscreen.health.gov.au)
and colposcopy (www.colposcopy.org.uk).
Both tests are subject to sampling and reading errors that may allow a lesion
to progress to advanced disease before it is detected. Confocal microscopy
may be used as an adjunct to conventional imaging techniques to view the
cells of the cervix in real time.
The confocal image data collected during the trial showed significant differences in nuclear density and size between the colposcopically normal and abnormal regions. The images showed significant correlation to the findings of conventional histology and suggest confocal microscopy could be used for the in vivo detection of pathology of the cervical epithelium. Previous in vitro studies with biopsy specimens also indicated that confocal microscopy provides useful information about the presence of precancerous changes of the cervix. The ability to assess the grade of cervical abnormality at the time of patient examination may assist to reduce or guide biopsy excision.
Several scientific papers have been published and presented in this area:
McLaren, W.J., Tan, J. and Quinn, A.M. (2003). Detection of cervical neoplasia using non-invasive fibre-optic confocal microscopy. Eurogin, SS15-08, p178, 2003.
McLaren W., Tan J., Quinn M, (2003). Detection of Cervical Neoplasia Using Non-Invasive Fibre-Optic Confocal Microscopy. Eurogin Proceedings 2003, 213-217.
McLaren, W.J., Tan, J. and Quinn, M. (2004). Fibre-optic confocal microscopy: a novel technique to enable in vivo histology of the cervical epithelium. Eurogin, RS2-4, p36, 2004.
Bott, E.M., Young, R., Jenkin, G. & McLaren, W.J. (2006). Detection of morphological changes of the ovine cervix in response to sex steroids using a fluorescence confocal endomicroscope. Am J Obstet Gynecol, 194(1): 105–112.
In collaboration with Optiscan P/L, the School of Mechanical Engineering
(University of Western Australia) has developed a novel laser scanning confocal
arthroscope (LSCA) that utilises Optiscan’s patented fibre optic technology.
The device has many potential applications in the fields of orthopaedic research
and orthopaedic surgery. The requirement for mechanical biopsy is obviated
by the ability of the LSCA to generate 2D and 3D views of tissue microstructure.
Two major studies have recently been undertaken. The first in vitro study
in sheep utilised the LSCA for the characterisation of healthy muscle, tendon,
menisci and articular cartilage. More recently, the LSCA has been used in
an in vivo longitudinal study of the progression of osteoarthritis (OA) in
ovine stifle joints. The results showed the common histological features
of these tissues and demonstrate the efficacy of the LSCA as a rapid method
for non-destructive assessment of cartilage. Using a well-established animal
model of arthritic disease, preliminary results from the osteoarthritis study
have shown noticeable changes from healthy cartilage in diseased tissue.
Chondrocyte cluster formations associated with arthritis are easily visible.
The study is unique in that it is the first time that non-destructive confocal
arthroscopy has been employed in vivo for a longitudinal study in a large
animal model.
Confocal imaging technology has been applied in the field of clinical ophthalmology
for many years in the field of scanning laser ophthalmoscopes (SLOs). These
devices are used primarily for scanning the retina at the back of the eyeball.
However, Optiscan’s unique technology offers unprecedented miniaturisation,
allowing small probes for either handheld use or integration with other ophthalmic
devices for imaging the front of the eye. Diseases such as glaucoma (the
second leading cause of blindness, afflicting 90 million people globally)
have been the subject of interest in the technology, where microscopic subsurface
changes next to the iris (the coloured part of the eye), and healing processes
from common glaucoma surgery procedures could be observed directly. Since
microscopic changes in these tissues cannot normally be observed (biopsy
of these parts of the eye is not practical), imaging in this way would offer
fundamentally new information to the ophthalmologist, and may greatly facilitate
patient management and lead to improved outcomes.
A prototype handheld device has been used in a pilot clinical trial to establish
the potential utility of the imaging technology in patients who have undergone
glaucoma surgery. The main goal in this application would be to observe inflammatory
processes, and use the information to better manage interventions and prevent
scar tissue formation (which leads to failure of the surgical procedure).
Further development is also being performed to enable imaging of deeper structures,
which would permit fundamental disease processes to be observed in patients being
monitored for Glaucoma and other ophthalmic diseases.
