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Minimally invasive monitoring of brain activity is essential not only to gain understanding on the working principles of the brain, but also for the development of new diagnostic tools. In this perspective we describe how brain thermometry could be an alternative to conventional methods (e.g., magnetic resonance or nuclear medicine) for the acquisition of thermal images of the brain with enough spatial and temperature resolution to track brain activity in minimally perturbed animals. We focus on the latest advances in transcranial luminescence thermometry introducing a critical discussion on its advantages and shortcomings. We also anticipate the main challenges that the application of luminescent nanoparticles for brain thermometry will face in next years. With this work we aim to promote the development of near infrared luminescence for brain activity monitoring, which could also benefit other research areas dealing with the brain and its illnesses.

Fe2O3 nanoparticles (NPs) have been synthesized and functionalized with SiO2 and -NH2 group, respectively. Conjugation to fluorescently-labeled poly-caspase inhibitor (SR-FLIVO) has been carried out for better cellular uptake studies of apoptosis arising from brain focal cerebral ischemia. Highest conjugation affinity to SR-FLIVO was found to be ca. 80% for Fe2O3-SiO-NH2 functionalized nanoparticles (FNPs). Tracking of SR-FLIVO conjugated functionalized nanoparticles (SR-FLIVO-FNPs) in vivo and in vitro has been carried out and detected using microscopic techniques after histochemical staining methods. Experimental results revealed that SR-FLIVO-FNPs probe could passively cross the blood brain barrier (BBB) and accumulated within the apoptotic cell. Optimization of SR-FLIVO-FNPs probe can effectively promise to open a new era for intracellular drug delivery and brain diagnosis.