ABSTRACT
Optical neuroimaging provides an effective neuroscience tool for multi-scale investigation of the neural structures and functions, ranging from molecular, cellular activities to the inter-regional connectivity assessment. Amongst experimental preparations, the implementation of an artificial window to the central nervous system (CNS) is primarily required for optical visualization of the CNS and associated brain activities through the opaque skin and bone. Either thinning down or removing portions of the skull or spine is necessary for unobstructed long-term in vivo observations, for which types of the cranial and spinal window and applied materials vary depending on the study objectives. As diversely useful, a window can be designed to accommodate other experimental methods such as electrophysiology or optogenetics. Moreover, auxiliary apparatuses would allow the recording in synchrony with behavior of large-scale brain connectivity signals across the CNS, such as olfactory bulb, cerebral cortex, cerebellum, and spinal cord. Such advancements in the cranial and spinal window have resulted in a paradigm shift in neuroscience, enabling in vivo investigation of the brain function and dysfunction at the microscopic, cellular level. This Review addresses the types and classifications of windows used in optical neuroimaging while describing how to perform in vivo studies using rodent models in combination with other experimental modalities during behavioral tests. The cranial and spinal window has enabled longitudinal examination of evolving neural mechanisms via in situ visualization of the brain. We expect transformable and multi-functional cranial and spinal windows to become commonplace in neuroscience laboratories, further facilitating advances in optical neuroimaging systems.
ABSTRACT
OBJECTIVE: To determine the reliable perfusion parameters in dynamic contrast-enhanced MRI (DCE-MRI) for the monitoring antiangiogenic treatment in mice. MATERIALS AND METHODS: Mice, with U-118 MG tumor, were treated with either saline (n = 3) or antiangiogenic agent (sunitinib, n = 8). Before (day 0) and after (days 2, 8, 15, 25) treatment, DCE examinations using correlations of perfusion parameters (Kep, Kel, and AH from two compartment model; time to peak, initial slope and % enhancement from time-intensity curve analysis) were evaluated. RESULTS: Tumor growth rate was found to be 129% +/- 28 in control group, -33% +/- 11 in four mice with sunitinib-treatment (tumor regression) and 47% +/- 15 in four with sunitinib-treatment (growth retardation). Kep (r = 0.80) and initial slope (r = 0.84) showed strong positive correlation to the initial tumor volume (p < 0.05). In control mice, tumor regression group and growth retardation group animals, Kep (r : 0.75, 0.78, 0.81, 0.69) and initial slope (r : 0.79, 0.65, 0.67, 0.84) showed significant correlation with tumor volume (p < 0.01). In four mice with tumor re-growth, Kep and initial slope increased 20% or greater at earlier (n = 2) than or same periods (n = 2) to when the tumor started to re-grow with 20% or greater growth rate. CONCLUSION: Kep and initial slope may a reliable parameters for monitoring the response of antiangiogenic treatment.