Fluorescence and Glioma Heterogeneity
Condition: Malignant Gliomas
MeSH terms: Glioma
Study type: Observational

Summary: 
      The investigators aim to study the heterogeneity of fluorescence within malignant gliomas by
      sampling tissues from these variable areas within the same tumor. These tissue samples will
      then be subjected to pathological and biological analysis to assess proteins related to ALA
      metabolism and correlated with the fluorescence emitted as well as levels of protoporphyrin
      IX in the tissues.
    

Detailed description: 
      Malignant gliomas are the commonest malignant brain tumors but are extremely challenging to
      treat. Neuro-oncology has seen little progress in its treatment despite extensive research.
      Extent of resection remains a very important prognostic factor in these tumors. Better the
      resection, better the outcomes. However resecting these tumors is not very easy primarily due
      to their infiltrative nature and difficulty in discerning tumor boundaries intraoperatively.
      Fluorescence guided resection (FGR) has recently been shown to be a very important and useful
      adjunct in maximizing this goal. FGR involves administration of aminolevulinic acid (ALA) to
      the patient prior to surgery. The ALA is converted to protoporphyrin IX (PPIX) in glioma
      cells. The PPIX is a fluorophore and can be visualized intraoperatively using a suitably
      modified microscope. Neurosurgeons can then resect the tumor radically guided by this
      fluorescence which is superior to the conventional microscopic resection. Selective PPIX
      accumulation in glioma cells is the key to the accuracy of this technique. The biological
      basis of selectivity of PPIX accumulation within glioma cells is however poorly understood.
      Various mechanisms could be involved starting from variable transport (related to blood-brain
      barrier properties), differential uptake (governed by active transport mechanisms) and
      differential metabolism within the cell. Understanding these mechanisms can lead to
      refinements in this strategy, overcoming its present limitations and development of methods
      to extend its scope.
    

Intervention name(s): ALA
Intervention type(s): Procedure
Intervention description(s): Prior to surgery all patients would receive freshly prepared solution of 5-ALA, 20 mg/kg bodyweight dissolved in 100 ml of potable water orally approximately 4 hours (range 4-6 hrs) before the commencement of anesthesia induction for surgery.
The surgery would then be performed with the help of navigation. After craniotomy, the navigation software would be used to identify the selected target areas based on the preoperative images (MR as well as PET when available) and directed image-guided biopsies from these representative areas will be collected for histological evaluation
Other intervention name(s): 5- ALA
Observational model: Case-Control
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        Patients with malignant glioma
      
Biospecimen description: 
      The heterogeneity of fluorescence within malignant gliomas by sampling tissues from these
      variable areas within the same tumor. These tissue samples will then be subjected to
      pathological and biological analysis to assess proteins related to ALA metabolism and
      correlated with the fluorescence emitted as well as levels of protoporphyrin IX in the
      tissues.
    
Keywords: ALA; Malignant gliomas