Fluorescence Guided Resection of Brain Tumors

The first phase of study (Stage I) will use FI coregistered with pMR, iUS and iSV images to test the overall hypothesis that there is a high degree of spatial correlation between local tissue FI signal and coregistered conventional imaging and corresponding histopathology. Additionally, coregistered probe measurements and biopsy specimens will be acquired intraoperatively. Biopsy specimens will be processed post-operatively (via fluorescence microscopy and chemical spectrofluorimetry) to assess PpIX concentration which will allow direct comparisons of FI signal strength with PpIX production (based on both in vivo probe data and ex vivo histological quantification) as a function of histological grade. The study protocol is outlined below. Because of the overall interest and importance of relating this data to the existing body of literature and the excellent safety record of oral administration of ALA reported in these trials [1, 33-36], we will use the same dose/time schedule described in [1, 33]. The operative procedures will follow existing practice at Dartmouth for image-guided resection of meningiomas, pituitary adenomas and metastases with additional acquisition of FI and biopsy data at predefined time points that are related to the expected volume of tumor tissue. In this first phase of the study, resection decisions will not be made based on FI data alone. Should residual fluorescence remain after the intended resection volume has been removed further excisions will require biopsy confirmation in the OR. It is anticipated that 234 patients will be enrolled in Stage I.

Inclusion criteria

• Preoperative diagnosis of either presumed low or high grade glioma (astrocytoma, oligodendroglioma, mixed oligo-astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme) or meningioma, pituitary adenoma or metastasis.
• Tumor judged to be suitable for open cranial resection based on preoperative imaging studies.
• Patient able to provide written informed consent.
• Age ≥ 21 years old.

Exclusion criteria

• Pregnant women or women who are breast feeding
• History of cutaneous photosensitivity, porphyria, hypersensitivity to porphyrins, photodermatosis, exfoliative dermatitis
• History of liver disease within the last 12 months,
• AST, ALT, ALP or bilirubin levels greater than 2.5 times the normal limit at any time during the previous 2 months
• Plasma creatinine in excess of 180 mol/L.
• Inability to comply with the photosensitivity precautions associated with the study
• Patients with an existing DSM-IV Axis 1diagnosis
• Inability to give informed consent