Functional near infrared spectroscopy (fNIRS) is a non-invasive and safe method to measure hemodynamics of the cerebral cortex. The use fNIRS in combination with brain radiotherapy is currently of our high interest since it provides a method to measure tissue oxygenation levels during irradiation. This can potentially help to advance the field of personalized cancer treatment. However, one limitation of the fNIRS technique is associated with penetration depth into tissues. Tissue optical clearing (TOC) could potentially improve the efficiency of fNIRS and for this use of radiopaque solutions, such as Omnipaque™ (iohexol), Visipaque™ (iodixanol), etc., are proposed as effective optical clearing agents (OCA). The presented study experiments the feasibility of using TOC for fNIRS measurements in radiotherapy. The effectiveness of isosmotic Visipaque™ and an OCA with a high osmolarity, a solution of 70% glycerol with 10% DMSO, was evaluated when using chicken samples.
SignificanceCancer therapy treatments produce extensive changes in the physiological and morphological properties of tissues, which are also individual dependent. Currently, a key challenge involves developing more tailored cancer therapy, and consequently, individual biological response measurement during therapy, such as tumor hypoxia, is of high interest. This is the first time human cerebral haemodynamics and cerebral tissue oxygenation index (TOI) changes were measured during the irradiation in clinical radiotherapy and functional near-infrared spectroscopy (fNIRS) technique was demonstrated as a feasible technique for clinical use in radiotherapy, based on 34 online patient measurements.AimOur aim is to develop predictive biomarkers and noninvasive real-time methods to establish the effect of radiotherapy during treatment as well as to optimize radiotherapy dose planning for individual patients. In particular, fNIRS-based technique could offer an effective and clinically feasible online technique for continuous monitoring of brain tissue hypoxia and responses to chemo- and radiotherapy, which involves modulating tumor oxygenation to increase or decrease tumor hypoxia. We aim to show that fNIRS is feasible for repeatability measuring in patient radiotherapy, the temporal alterations of tissue oxygenation induced by radiation.ApproachFiber optics setup using multiwavelength fNIRS was built and combined with a medical linear accelerator to measure cerebral tissue oxygenation changes during the whole-brain radiotherapy treatment, where the radiation dose is given in whole brain area only preventing dosage to eyes. Correlation of temporal alterations in cerebral haemodynamics and TOI response to brain irradiation was quantified.ResultsOnline fNIRS patient measurement of cerebral haemodynamics during clinical brain radiotherapy is feasible in clinical environment, and results based on 34 patient measurements show strong temporal alterations in cerebral haemodynamics and decrease in TOI during brain irradiation and confirmed the repeatability. Our proof-of-concept study shows evidently that irradiation causes characteristic immediate changes in brain tissue oxygenation.ConclusionsIn particular, TOI seems to be a sensitive parameter to observe the tissue effects of radiotherapy. Monitoring the real-time interactions between the subjected radiation dose and corresponding haemodynamic effects may provide important tool for the researchers and clinicians in the field of radiotherapy. Eventually, presented fNIRS technique could be used for improving dose planning and safety control for individual patients.
Radiotherapy is one of the well-established and effective methods for many cancer treatments especially for brain tumors. Despite remarkable advancements, the dose tolerances of normal tissues continue being the main limitation in radiotherapy. Consequently, there is a high unmet medical need to develop predictive biomarkers, and particularly noninvasive real-time methods to establish the radiotherapy effect during the treatment, as well as to optimize radiotherapy dose planning to avoid severe short and long-term toxicities. Optical techniques are well suited for in vivo clinical tissue imaging as they are non-ionizing and can be label-free. In particular, near-infrared (NIR) spectroscopy technology is easy to exploit in online monitoring clinical treatments in demanding clinical environments. In this paper, we study its potential to utilize it in radiotherapy for measuring immediate effects of irradiation on skin tissue. Skin is sensitive to acute side effects of irradiation in radiotherapy and to reduce these unwanted effects is of high interest. We used diffuse reflectance spectroscopy, at spectral range of 650 nm – 1100 nm, and continuously measured human skin in radiotherapy before, during and after irradiation, and compared the response with ex vivo chicken sample measurements. In our results we show that irradiation causes dynamical changes in the detected NIR light when measured in vivo from human skin. These spectral responses could be potentially exploited in development of methods to perceive skin toxicity risks in radiotherapy.
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