Researchers from Vancouver have developed a novel way to selectively close single blood vessels within tissue, using a highly targeted laser therapy called multiphoton photothermolysis. The technique could be used to treat a variety of vascular diseases and dysregulated blood vessels in conditions ranging from cancers to macular degeneration to port wine birthmarks (Sci. Adv. 5 eaan9388).
The treatment uses multiphoton absorption to selectively close targeted blood vessels. A focused beam from a near-infrared femtosecond laser is aimed at the centre of the targeted vessel, generating localized heating that spreads to the wall of the blood vessel and causes it to collapse. Multiphoton absorption is only induced at the focal point, where the power density from the laser is extremely high. Outside of this site, the power density is low, thus nearby vessels remain unaffected.
“The process of two-photon absorption has the advantage of absorption at the focal point only,” explains corresponding author Haishan Zeng from the BC Cancer Agency. “If you align the focal point with a microstructure you can treat the microstructure very precisely without generating any adverse effect to the surrounding tissues.”
Zeng and colleagues created an optical system that images, targets and closes a single blood vessel. The system employs a 785 nm diode laser to image the targeted blood vessel via reflectance confocal microscopy, and to confirm blood vessel closure after treatment. Treatment is delivered using a high-power Ti:sapphire femtosecond laser tuned to 830 nm. The researchers note that the use of near-infrared light enables deeper penetration than the visible wavelengths employed for single-photon absorption-based approaches.
Using a mouse ear model, the team demonstrated closure of single vessels of varying sizes ranging from capillaries to venules. They showed that the technique can close blood vessels deep within a tissue while preserving overlying superficial blood vessels. This would allow selective denaturation of certain vessels while sparing other vessels to preserve normal tissue physiology once the disease is healed.
The researchers also showed that vessels could be partially blocked instead of completely closed. In vivo confocal Raman spectroscopy of the treated sites revealed that the vessel closure was mediated by local coagulation of blood cells.
“We are the first to use the multiphoton process for therapeutic applications,” says Zeng. “We made the system very fast so that we can image at a video rate in real time, which is the key to enable clinical application.”
The authors state that this precise microsurgical anti-vascular method holds particular promise for treating diseases in complex organs such as the eye (non-invasively) or brain, where high spatial selectivity is critical to prevent collateral effects on vision or central nervous system function.
“In this publication we’ve used [multiphoton photothermolysis] to close off blood vessels one at a time, but I can see a range of different targets and structures in the body that this would be very applicable to,” says co-author Harvey Lui. “Not only to blood vessels but any other type of cell or tissue structure.”
