Chronic Cranial Window For High Resolution Photoacoustic Microscopy

With the continuous improvement of life quality,health issues have attracted increasing attention over the past decades.As the main technique of disease diagnosis,biomedical imaging systems have also been rapidly developed.The new imaging technologies,including but not limited to optical imaging,ultrasound imaging and photoacoustic imaging,provide new us with diagnostic approaches for basic brain research,allowing us comprehensively understand the structural and functional information of the brain.Especially with the development of long-term cranial window,we can monitor the development of brain diseases for an extended period of time,which better guide the diagnosis and treatment strategy.Among them,photoacoustic imaging,as a non-invasive imaging technique,possesses the characteristics of rich contrast of optical imaging and high penetration depth of ultrasound imaging.In addition,photoacoustic imaging is ultrasensitive to hemoglobin,leading to the unique dominance in visualizing microcirculation of brain cortex.Hence,photoacoustic imaging has widespread applications in diagnosis and analysis of cerebral vascular diseases.However,the existing chronic cranial windows are usually designed for pure optical imaging,which can not meet the demand of ultrasound detection in photoacoustic imaging,which greatly limits the extensive application of photoacoustic imaging in the investigation of chronic cerebrovascular diseases.To better apply the photoacoustic imaging to chronic cerebrovascular disease research,this paper introduces a unique cranial window implant based on Polydimethylsiloxane film,which is bonded with a ring glass through the plasma cleaning.Such a design not only ensures the effective transmission of ultrasound wave,but also maintains the smooth surface of the cranial window implant,effectively avoiding the optical refraction and scattering caused by surface folds,which allows high quality long-term photoacoustic microscopic imaging.Based on this concept,we firstly designed and fabricated the type 1 cranial window,which can be integrated with previously reported portable optical resolution photoacoustic microscopy,allowing a large imaging area of 5mm×5mm.Subsequently,we applied the cranial window for long-term monitoring of cortical cerebrovascular in anesthetized rats.Furthermore,in order to apply the cranial window to longitudinal brain imaging in freely moving rats,we introduced a 3D printed resin frame,which allows us to integrate the new designed type 2 cranial window with wearable optical resolution photoacoustic microscopy.Finally,we successfully performed brain imaging in freely moving rats for 12 days.These results prove that the proposed cranial window has great application in long-term brain imaging of both anesthetized and free-moving rats.In addition,we further applied this cranial window to long-term monitoring of the growth of brain tumor in rat,successfully revealing the changes of vascular network and brain inflammation in tumor region,which has positive guiding significance for the diagnosis and treatment of tumor.