Non-invasive treatment of ischemia/reperfusion injury: Effective transmission of therapeutic near-infrared light into the human brain through soft skin-conforming silicone waveguides.
Paul T MorseSamuel TuckMike KernsDennis J GoebelJunmei WanTom WaddellJoseph M WiderCharlotte L HüttemannMoh H MalekIcksoo LeeThomas H SandersonMaik HüttemannPublished in: Bioengineering & translational medicine (2023)
Noninvasive delivery of near-infrared light (IRL) to human tissues has been researched as a treatment for several acute and chronic disease conditions. We recently showed that use of specific IRL wavelengths, which inhibit the mitochondrial enzyme cytochrome c oxidase (COX), leads to robust neuroprotection in animal models of focal and global brain ischemia/reperfusion injury. These life-threatening conditions can be caused by an ischemic stroke or cardiac arrest, respectively, two leading causes of death. To translate IRL therapy into the clinic an effective technology must be developed that allows efficient delivery of IRL to the brain while addressing potential safety concerns. Here, we introduce IRL delivery waveguides (IDWs) which meet these demands. We employ a low-durometer silicone that comfortably conforms to the shape of the head, avoiding pressure points. Furthermore, instead of using focal IRL delivery points via fiberoptic cables, lasers, or light-emitting diodes, the distribution of the IRL across the entire area of the IDW allows uniform IRL delivery through the skin and into the brain, preventing "hot spots" and thus skin burns. The IRL delivery waveguides have unique design features, including optimized IRL extraction step numbers and angles and a protective housing. The design can be scaled to fit various treatment areas, providing a novel IRL delivery interface platform. Using fresh (unfixed) human cadavers and isolated cadaver tissues, we tested transmission of IRL via IDWs in comparison to laser beam application with fiberoptic cables. Using the same IRL output energies IDWs performed superior in comparison to the fiberoptic delivery, leading to an up to 95% and 81% increased IRL transmission for 750 and 940 nm IRL, respectively, analyzed at a depth of 4 cm into the human head. We discuss the unique safety features and potential further improvements of the IDWs for future clinical implementation.
Keyphrases
- ischemia reperfusion injury
- endothelial cells
- cardiac arrest
- oxidative stress
- primary care
- white matter
- multiple sclerosis
- blood brain barrier
- intensive care unit
- cerebral ischemia
- respiratory failure
- photodynamic therapy
- molecular dynamics
- optic nerve
- high throughput
- brain injury
- wound healing
- current status
- hepatitis b virus
- extracorporeal membrane oxygenation
- subarachnoid hemorrhage