Disruption of the blood brain barrier following ALA mediated photodynamic therapy

Henry Hirschberg M.D.; Qian Peng; Francisco A. Uzal; David Chighvinadze; Michelle J. Zhang; Steen J. Madsen

doi:10.1117/12.767323

8 February 2008 Disruption of the blood brain barrier following ALA mediated photodynamic therapy

Henry Hirschberg M.D., Qian Peng, Francisco A. Uzal, David Chighvinadze, Michelle J. Zhang, Steen J. Madsen

Proceedings Volume 6842, Photonic Therapeutics and Diagnostics IV; 68422O (2008) https://doi.org/10.1117/12.767323
Event: SPIE BiOS, 2008, San Jose, California, United States

Abstract

Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to tumor cells as well as degradation of the blood brain barrier (BBB). We have evaluated the ability of ALA mediated PDT to open the BBB in rats. This will permit access of chemotherapeutic agents to brain tumor cells remaining in the resection cavity wall, but limit their penetration into normal brain remote from the site of illumination. Materials and Methods: ALA-PDT was performed on non tumor bearing inbred Fisher rats at increasing fluence levels. T2 weighted MRI scans were used to evaluate edema formation and post-contrast T₁ MRI scans were used to monitor the degree BBB disruption which could be inferred from the intensity and volume of the contrast agent visualized. Results. PDT at increasing fluence levels between 9J and 26J demonstrated an increasing contrast flow rate. No effect on the BBB was observed if 26J of light were given in the absence of ALA. A similar increased contrast volume was observed with increasing fluence rates. The BBB was found to be disrupted 2hrs. following PDT and 80-100% restored 72hrs later. Conclusion: PDT was highly effective in opening the BBB in a limited region of the brain. The degradation of the BBB was temporary in nature, opening rapidly following treatment and significantly restored during the next 72 hrs.

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Henry Hirschberg M.D., Qian Peng, Francisco A. Uzal, David Chighvinadze, Michelle J. Zhang, and Steen J. Madsen "Disruption of the blood brain barrier following ALA mediated photodynamic therapy", Proc. SPIE 6842, Photonic Therapeutics and Diagnostics IV, 68422O (8 February 2008); https://doi.org/10.1117/12.767323

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KEYWORDS

Blood brain barrier

Photodynamic therapy

Brain

Tumors

Magnetic resonance imaging

Tissues

Neuroimaging

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