Chronic regional impairments of the lymphatic circulation often lead to striking architectural abnormalities in the lymphedematous tissues. Lymphedema is a common, disabling disease that currently lacks a cure. Vascular endothelial growth factors C and D mediate lymphangiogenesis through the VEGFR-3 receptor on lymphatic endothelia. The purpose of this study was to investigate the therapeutic potential for lymphangiogenesis with VEGF-C. We developed a rabbit ear model to simulate human chronic postsurgical lymphatic insufficiency. Successful, sustained surgical ablation of the ear lymphatics was confirmed by water displacement volumetry. After complete healing, the experimental animals (n=8) received a single, s.c. 100 microg dose of VEGF-C in the operated ear; controls (n=8) received normal saline. Radionuclide lymphoscintigraphy was performed to quantitate lymphatic function. Immunohistochemistry (IHC) was performed 7-8 days following treatment. After VEGF-C, there was a quantifiable amelioration of lymphatic function. IHC confirmed a significant increase in lymphatic vascularity, along with reversal of the intense tissue hypercellularity of untreated lymphedema. This study confirms the capacity of a single dose of VEGF-C to induce therapeutic lymphangiogenesis in acquired lymphedema. In addition to improving lymphatic function and vascularity, VEGF-C can apparently reverse the abnormalities in tissue architecture that accompany chronic lymphatic insufficiency.

Conventional brain imaging modalities are limited in that they image only secondary physical manifestations of brain injury, which may occur well after the actual insult to the brain and represent irreversible structural changes. A real-time continuous bedside monitor that images functional changes in cerebral blood flow or oxygenation might allow for recognition of brain tissue ischemia or hypoxia before the development of irreversible injury. Visible and near infrared light pass through human bone and tissue in small amounts, and the emerging light can be used to form images of the interior structure of the tissue and measure tissue blood flow and oxygen utilization based on light absorbance and scattering. We developed a portable time-of-flight and absorbance system which emits pulses of near infrared light into tissue and measures the transit time of photons through the tissue. Images can then be reconstructed mathematically using either absorbance or scattering information. Pathologic brain specimens from adult sheep and human newborns were studied with this device using rotational optical tomography. Images generated from these optical scans show that neonatal brain injuries such as subependymal and intraventricular hemorrhages can be successfully identified and localized. Resolution of this system appears to be better than 1 cm at a tissue depth of 5 cm, which should be sufficient for imaging some brain lesions as well as for detection of regional changes in cerebral blood flow and oxygenation. We conclude that light-based imaging of cerebral structure and function is feasible and may permit identification of patients with impending brain injury as well as monitoring of the efficacy of intervention. Construction of real-time images of brain structure and function is now underway using a fiber optic headband and nonmechanical rotational scanner allowing comfortable, unintrusive monitoring over extended periods of time.