Multimodal Optical Imaging to Investigate Spatiotemporal Changes in Cerebrovascular Function in AUDA Treatment of Acute Ischemic Stroke

Administration of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) has been demonstrated to alleviate infarction following ischemic stroke. Reportedly, the main effect of AUDA is exerting anti-inflammation and neovascularization via the inhibition of soluble epoxide hydrolase. However, the major contribution of this anti-inflammation and neovascularization effect in the acute phase of stroke is not completely elucidated. To investigate the neuroprotective effects of AUDA in acute ischemic stroke, we combined laser speckle contrast imaging and optical intrinsic signal imaging techniques with the implantation of a lab-designed cranial window. Forepaw stimulation was applied to assess the functional changes via measuring cerebral metabolic rate of oxygen (CMRO2) that accompany neural activity. The rats that received AUDA in the acute phase of photothrombotic ischemia stroke showed a 30.5 ± 8.1% reduction in the ischemic core, 42.3 ± 15.1% reduction in the ischemic penumbra (p < 0.05), and 42.1 ± 4.6% increase of CMRO2 in response to forepaw stimulation at post-stroke day 1 (p < 0.05) compared with the control group (N = 10 for each group). Moreover, at post-stroke day 3, increased functional vascular density was observed in AUDA-treated rats (35.9 ± 1.9% higher than that in the control group, p < 0.05). At post-stroke day 7, a 105.4% ± 16.4% increase of astrocytes (p < 0.01), 30.0 ± 10.9% increase of neurons (p < 0.01), and 65.5 ± 15.0% decrease of microglia (p < 0.01) were observed in the penumbra region in AUDA-treated rats (N = 5 for each group). These results suggested that AUDA affects the anti-inflammation at the beginning of ischemic injury and restores neuronal metabolic rate of O2 and tissue viability. The neovascularization triggered by AUDA restored CBF and may contribute to ischemic infarction reduction at post-stroke day 3. Moreover, for long-term neuroprotection, astrocytes in the penumbra region may play an important role in protecting neurons from apoptotic injury.

An Empirical Model for Describing the Small Field Penumbra in Radiation Therapy

Purpose. We developed a mathematic empirical model for describing the small field penumbra in order to analyze the potential dose perturbation caused by overlapping field to avoid the dose calculation errors in linear accelerator-based radiosurgery. Materials and methods. A ball phantom was fabricated for measuring penumbra at 4 different gantry angles in the coplanar plane. A least square root estimation (LSRE) Model was created to fit the measured penumbra dose profile and to predict the penumbra dose profile at any gantry angles. The Sum of Squared Errors (SSE) was used for finding the parameters n and t for the best fitting of the LSRE model. Geometric and mathematical methods were used to derive the model parameters. Results. The results showed that the larger the gantry angle of the field, the more the expansion of the penumbra dose profile. The least square root estimation model for describing small field penumbra is as follows: PenumbraDš=T⋅1/2⋅1−š/n+š2+t where PenumbraDš denotes the dose profile D(š) at the penumbra region, T is the penumbra height (usually in scalar 100), n is the parameter for curvature, š = x − Wd/2 (x and š are the values in cm on x-axis), and t is the radiation transmission of the collimator. Geometric analysis establishes the correlation between the penetration depth of the exposure and its effect on the penumbra region in ball phantom. The penumbra caused by an exposure at any arbitrary angles can be geometrically derived by using a one-variable quadratic equation. Conclusion. The dose distribution in penumbra region of small field can be created by the LSRE model and the potential overdosage or underdosage owing to overlapping field perturbation can be estimated.