Jun 15, 2009
Lasers make their mark in medicine
This week, Munich in Germany plays host to one of the optics industry's signature events: the biennial LASER World of Photonics congress and tradeshow. The congress includes a two-day symposium - Medical Laser Applications 2009 - dedicated to the use of optical techniques for diagnosis and treatment of disease. Today's agenda, dubbed Science Day, sees researchers present in-vitro and in-vivo studies, clinical trials and technical developments in the field of laser medicine.
One technology receiving much attention is optical coherence tomography (OCT) - a non-invasive interferometric imaging technique. Having made its mark in ophthalmology, OCT is now being studied for a wide range of medical applications, and was the subject of many of the Science Day presentations. For example, Gereon Hüttmann, from the University of Lübeck, told delegates about the use of OCT for three-dimensional intraoperative imaging of tissue structures.
OCT offers non-contact tissue analysis with a penetration depth of 2-3 mm and a spatial resolution of 4-15 µm - compatible with the resolution of modern operating microscopes. As such, Hüttmann and colleagues adapted a high-speed spectral-domain OCT system to a camera port on a motorized operating microscope, via a specially designed two-axis scanner.
The combined OCT-microscope system enables visualization of 840 nm OCT images during surgical procedures, displayed via a dedicated video ocular in the microscope. Hüttmann suggests that the device, which has proved successful in preclinical tests, could be used during surgery for brain- or vocal-cord-tumours, placement of cochlear transplants and bone surgery in the middle ear.
OCT may also be of value for differentiating healthy skin from various skin lesions, explained Maria Ziolkowska, from the Elisabeth Klinik in Berlin. Ziolkowska and co-workers obtained two-dimensional OCT images of healthy skin, actinic skin lesions with different degrees of dysplasia, and basal cell carcinoma lesions from 10 patients.
Comparing the OCT images with images of histological samples revealed a strong correlation between histological and OCT images for the upper layers of the dermis. In unhealthy skin, equivalents of typical histological features of epithelial dysplasia and changes in dermal layers could be seen in the OCT images.
Laser light also plays an important role in many therapeutic techniques, such as photodynamic therapy (PDT), for example, which uses a light-activated drug to kill cancer cells. Herbert Stepp from Ludwig Maximilian University in Munich described PDT treatment of bladder cancer using hexyl-aminolevulinate (h-ALA), a photosensitizer that's already approved in Europe for fluorescence detection of bladder cancer.
The prospective study assessed the feasibility of h-ALA PDT using whole-bladder-wall irradiation with white light and a newly developed catheter. The research team performed PDT on 17 patients with bladder cancer, applied in three sessions separated by six-week intervals. Light was delivered from a high-power white-light source via a quartz fibre with a spherically diffusing tip, fixed in a flexible irrigation catheter.
PDT was achieved without any technical complications. The main side effects were postoperative urgency and bladder pain. The researchers conclude that white-light PDT with the flexible catheter system is technically feasible and safe. They note that nine of 12 patients assessed three months after the third PDT session showed complete response, with two of these patients free of recurrence at the final follow-up of 84 weeks.
In another presentation from Ludwig Maximilian University, Florian Bergmann described a preliminary evaluation of PDT for treating hepatoblastoma and neuroblastoma, cancers that occur in early childhood. The study, undertaken in collaboration with the University of Leipzig, examined cell cultures incubated with 5-aminolevulinic acid (5-ALA), a precursor of the fluorescent photosensitizer PpIX.
PpIX fluorescence approached saturation at a drug concentration of 150 μg/ml, with hepatoblastoma and neuroblastoma cells showing comparable fluorescence intensities and control (human fibroblast) cells exhibiting low fluorescence. Following PDT, cell survival was lowest for the hepatoblastoma cells (median lethal dose, LD50: 1.5 J/cm2) compared to neuroblastoma (LD50: 6 J/cm2) and control (human fibroblast) cells (LD50: >20 J/cm2).
The team also studied hepatoblastoma cells implanted between the peritoneum and abdominal wall of nude rats. In vivo tumour fluorescence was highest around 200 minutes post-injection, with a maximum contrast to the surrounding peritoneum at around 150 minutes. Following PDT, the peritoneum remained unaffected, while the liver exhibited superficial necrosis and sensitized tumour showed deep necrosis.
Optical techniques can also be used to monitor therapeutic response, as explained by Michael Peller from the University Hospital of Munich. Peller described the use of a backscattered light detector (BLD) for visualizing tissue coagulation during MRI-assisted interstitial laser thermotherapy (ILTT).
The BLD uses a single fibre to transmit a 632 nm test signal and detect the diffusely backscattered light. The underlying premise is that thermally altered tissue will exhibit different optical parameters to native tissue. The researchers determined ILTT-induced necrosis in muscle and liver tissue samples using macroscopic examination and 1.5 T MRI, and correlated these results with the position- and time-dependent BLD signal.
The backscatter intensity showed a reproducible sigmoidal time course during the appearance of tissue whitening. The researchers conclude that the BLD provides additional, online information regarding local changes in tissue state that, when combined with MR-parameters, may improve thermotherapy monitoring and could be used to define a local switch-off criterion for ILTT.
• These studies are being presented on 15 June at Medical Laser Applications 2009, organized by the German Society for Laser Medicine (DGLM). Accompanying papers are published in the journal Medical Laser Application, volume 24, issue 2 (May 2009).