The feasibility of real-time in vivo optical detection of blood–brain barrier disruption with indocyanine green

Abstract

Osmotic disruption of the blood-brain barrier (BBB) by intraarterial mannitol injection is sometimes required for the delivery of chemotherapeutic drugs to brain tissue. Osmotic disruption is affected by a number of factors, and there is a significant variability in the degree and distribution of BBB disruption in clinical and experimental settings. Brain tissue concentrations of indocyanine green (ICG) can be measured by optical techniques. The aim of this experiment was to determine whether the disruption of the BBB significantly altered the regional pharmacokinetics of ICG. We were able to track in vivo brain tissue concentrations of ICG in 13 New Zealand white rabbits by employing a novel optical approach. Evan's blue was used to assess the distribution of BBB disruption on post mortem examination. BBB disruption by intraarterial mannitol injection was found to be highly variable, and only five of the 13 animals demonstrated the disruption at the site of optical measurements. In these animals, we observed a ninefold increase in ICG concentrations and fourfold increase in the area under the concentration-time curve, compared to those without BBB disruption at the site of measurement. This study shows the feasibility of optical monitoring of BBB disruption with intravenous (IV) ICG injections. Virtual real-time optical monitoring of the BBB disruption could help improve intraarterial delivery of chemotherapeutic drugs.

Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery

“…This effect explains delivery in that small molecules may pass through a disrupted tumor blood brain barrier and be retained due a relative lack of drainage (by lymphatics, for example). 14 Prior work has demonstrated that accumulation within may occur due to the relatively hypoxic microenvironment. 15 As a molecule, ICG is amphiphilic; it has 2 ringed groups (1 with positive charge) and 2 negatively charged sulfonate groups.…”

In Vivo Imaging of a New Indocyanine Green Micelle Formulation in an Animal Model of Laser-Induced Choroidal Neovascularization

“…4 Common medical applications include visualization of blood flow in different organs and screening of inflammation in rheumatoid arthritis. [5][6][7][8][9][10][11][12] In ophthalmology, ICG has been used for both diagnostic purposes and surgical interventions. [13][14][15][16] For the former, intravenous injection of ICG into the blood enables retinal and choroidal angiography.…”

Low-Dose Evans Blue Dye for Near-Infrared Fluorescence Imaging in Photothrombotic Stroke Model

“…Moreover, the NIR fluorescence imaging eliminates autofluorescence from the body, which can increase accuracy of imaging data from animals 11 - 17 . However, the number of approaches demonstrating the feasibility of assessment BBB impairment with NIR fluorescence techniques is limited 1 , 18 , 19 . EBD has the optical property that it becomes a moderate-strength fluorophore emitting at 680 nm when diluted to levels that are almost undetectable to the human eye.…”