Cerebral tissue oxygenation response to brain irradiation measured during clinical radiotherapy.

Significance: Cancer 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. Aim: Our 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. Approach: Fiber 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. Results: Online 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. Conclusions: In 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.

No adverse effects on periarticular tissue by intra-articular vitamin D analogue calcipotriol in a reduced-dose zymosan-induced arthritis model in rats.

Calcipotriol, a vitamin D analogue, is an antiproliferative and anti-inflammatory drug currently used in psoriasis. Here, our aim was to analyse the safety of calcipotriol for cartilage and bone in alleviated-dose (0.1 mg instead of usual ≥1mg dose) zymosan-induced arthritis in rats. Theoretically, high doses of vitamin D or analogues could have detrimental effects on bone or cartilage. The rats were divided into four groups: vehicle (n = 9), dexamethasone 0.1 mg/kg (n = 9), calcipotriol 0.1 mg/kg (n = 8) and negative control (n = 10) with no injections. Arthritic rats were given phosphate-buffered saline (PBS) injections to left knees as a control. After euthanasia on day 8, all knees were imaged with micro-computed tomography for surface lesions and decalcified for histological analyses. Contrary to our expectations, no significant changes could be observed in the tomography data and histological scores among the three treatment groups or between the vehicle-treated and non-arthritic group. Calcipotriol did not cause adverse effects on cartilage or subchondral bone within a week, suggesting that it could be safely used in local treatment of arthritis. The alleviated model caused synovitis with local and systemic inflammatory response without cartilage erosions, which might be useful in studying self-limiting synovitis where cartilage or bone effects are not of primary interest.