Port wine stain (PWS) birthmarks are one class of benign congenital vascular malformation. Laser therapy is the most successful treatment modality of PWS. Unfortunately, this approach has limited efficacy, with only 10% of patients experiencing complete blanching of the PWS. To address this problem, several research groups have developed technologies and methods designed to study treatment outcome and improve treatment efficacy. This paper reviews seven optical imaging techniques currently in use or under development to assess treatment efficacy, focusing on: Reflectance spectrophotometers/tristimulus colorimeters, Laser Doppler flowmetry (LDF) and Laser Doppler imaging (LDI), Cross-polarized diffuse reflectance color imaging system (CDR), Reflectance Confocal Microscopy (RCM), Optical Coherence Tomography (OCT), Spatial Frequency Domain Imaging (SFDI), and Laser Speckle Imaging (LSI).

Alzheimer’s disease (AD) and cerebrovascular disease are often comorbid conditions, but the relationship between amyloid-β and in vivo vascular pathophysiology is poorly understood. We utilized a multimodal, multiscale optical imaging approach, including spatial frequency domain imaging, Doppler optical coherence tomography, and confocal microscopy, to quantify AD-dependent changes in a triple transgenic mouse model (3xTg-AD) and age-matched controls. From three months of age (naïve) to 20 months (severe AD), the brain tissue concentration of total and oxy-hemoglobin (Total Hb, ctO2Hb) decreased 50 and 70%, respectively, in 3xTg-AD mice. Compared to age-matched controls, significant differences in brain hemoglobin concentrations occurred as early as eight months (Total Hb: 126 ± 5 μM versus 108 ± 4 μM; ctO2Hb: 86 ± 5 μM versus 70 ± 3 μM; for control and AD, respectively). These changes were linked to a 29% vascular volume fraction decrease and 35% vessel density reduction in the 20-month-old 3xTg-AD versus age-matched controls. Vascular reduction coincided with increased brain concentration of amyloid-β protein, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS) at eight and 20 months compared to the three-month baseline. Our results suggest that amyloid-β blocks the normally reparative effects of upregulated VEGF and eNOS, and may accelerate in vivo vascular pathophysiology in AD.

No abstract

The incidence of Alzheimer’s disease increases in people who have had an ischemic episode. Furthermore, APP expression is increased following ischemic or hypoxic conditions, as is the production of the Aβ peptide. To address the question of why APP and Aβ are increased in hypoxic and ischemic conditions we induced an ischemic episode in APP knockout mice (APP−/−) and BACE1 knockout mice (BACE−/−). We find that both APP−/− and BACE−/− mice have a dramatically increased risk of mortality as a result of cerebral ischemia. Furthermore, APP knockout mice have reduced cerebral blood flow in response to hypoxia, while wild-type mice maintain or increase cerebral blood flow to the same conditions. The transcription factor, serum response factor (SRF), and calcium-binding molecule, calsequestrin, both involved in vascular regulation, are significantly altered in the brains of APP−/− mice compared to wild type controls. These results show that APP regulates cerebral blood flow in response to hypoxia, and that it, and its cleavage fragments, are crucial for rapid adaptation to ischemic conditions.