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.
Near-infrared spectroscopy (NIRS) based techniques in brain monitoring utilize the spectrum range approximately between 650 nm and 950 nm, where light attenuation is low enough to enable reaching the cerebral cortex of the brain. In these studies, particularly oxygenation changes in the cerebral cortex are of great interest since the concentrations of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) change due to coupling of hemodynamics to cortical neural activity. There are numerous simulation and phantom studies that show near-infrared (NIR) light can penetrate in the human head to a depth of approximately 1–2 cm, reaching the brain cortex. However, NIR propagation and light attenuation is also dependent on anatomy and size of the subject’s head. This related, we studied experimentally the effect of layer thicknesses of dura and cerebrospinal fluid (CSF), skull and skin to detected light intensity when measured in vivo from human heads with different layer thicknesses. We studied anatomy of 15 human heads in magnetic resonance imaging (MRI), particularly the thickness and morphology of the tissue layers of CSF, skull and skin. At the same time, we measured intensity and absorbance spectrum, at range of 600 nm to 1100 nm, from the forehead of these subjects when fibre detector was placed at distances of 1 cm and 3 cm from the fibre source. Our results show that each layer affects the detected NIR spectrum when layer thickness changes, particularly at 3 cm source-detector distance. However, these small spectral variations, caused by changes head anatomy, most likely do not have significant influence in quantifying cerebral hemodynamics.
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.
Radiotherapy is already well-established and an effective form of treatment for many cancers, especially for brain tumors. Currently, the clinical efficacy of a treatment, however, can only be established based on clinical or radiological responses observed after a significant period of time following the single irradiations during radiotherapy course. On the other hand, the radiotherapy dose is limited by its toxicity to surrounding healthy tissues. Particularly, radiation to brain tumors may sub-acutely or chronically affect cognition and cause fatigue even with conventional doses. However, there is currently no on-line and safe method to monitor the effects of radiation to the brain during the irradiation. In our project, we aim to develop an on-line method to monitor effects in brain tissue that correlate with the radiation dose in radiotherapy. In this case study, we use functional near-infrared spectroscopy (fNIRS) and study possible temporal effects in cerebral haemodynamics during irradiations of whole-brain radiotherapy (WBRT). fNIRS is safe for the patient, it can be used noninvasively and also in demanding environments, such as in radiotherapy treatment rooms during irradiation, and thus could be in future potential technique to be utilized for monitoring tailored radiotherapy.
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