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Fluorescence-Guided Brain Tumour Excision In Mumbai
5-ALA Fluorescence Surgery for Maximum Malignant Glioma Resection with Real-Time Tumour Visualisation at Shree Hospitals
Fluorescence-guided tumour excision using 5-ALA (5-aminolevulinic acid) is one of the most significant advances in brain tumour surgery of the past two decades. After the patient drinks a solution of 5-ALA three to four hours before surgery, malignant brain tumour cells selectively accumulate a fluorescent compound (protoporphyrin IX - PpIX), which glows vivid pink-red under a specialised violet-blue light filter on the operating microscope. Normal brain tissue does not accumulate PpIX and appears dark blue-grey. This real-time, colour-coded tumour-normal tissue boundary allows the neurosurgeon to see and remove tumour tissue that would be indistinguishable from normal brain under conventional white light, dramatically improving the completeness of tumour removal and patient survival. At Shree Hospitals, our specialist neurosurgeons use 5-ALA fluorescence-guided resection alongside neuronavigation and intraoperative ultrasound as the complete technology platform for high-grade glioma surgery.
High-Grade Brain Tumour? Consult Our Specialist Neurosurgeons at Shree Hospitals
Quick facts
Technique : 5-ALA Fluorescence-Guided Resection (FGR)
Primary Indication : High-Grade Glioma (GBM Grade IV, Anaplastic Astrocytoma Grade III)
Also Used For : Recurrent High-Grade Glioma, Selected Metastases, High-Grade Areas in Low-Grade Glioma
5-ALA Dose : 20mg/kg oral solution 3 to 4 hours before anaesthesia induction
Microscope : Modified Zeiss KINEVO 900 or equivalent with BLUE 400 fluorescence filter
Key Benefit : Doubles the rate of complete tumour resection vs white light surgery
What is 5-ALA Fluorescence-Guided Brain Tumour Surgery?
5-aminolevulinic acid (5-ALA) is a naturally occurring precursor of haem (the oxygen-carrying compound in red blood cells). When taken orally approximately 3 to 4 hours before surgery, 5-ALA is selectively taken up and metabolised by malignant brain tumour cells (particularly high-grade gliomas) into protoporphyrin IX (PpIX), a fluorescent compound that accumulates within the tumour cells. Under standard white light, the operating microscope shows brain tissue in its natural colours - the tumour surface often looks similar to normal brain, making it extremely difficult to identify the precise tumour-brain boundary. Under a blue-violet light filter (405nm wavelength - the BLUE 400 mode), the PpIX-containing tumour cells fluoresce a characteristic vivid pink-red while normal brain tissue appears dark. This colour difference is visible in real-time, allowing the neurosurgeon to see exactly where tumour ends and normal brain begins throughout the resection.
The landmark clinical trial of 5-ALA fluorescence-guided surgery - the Stummer et al. Phase III trial (New England Journal of Medicine, 2006) - demonstrated that patients with glioblastoma (GBM) who underwent 5-ALA guided surgery had complete tumour resection (as defined by the absence of any enhancing tumour on the post-operative MRI) in 65% of cases, compared with only 36% of patients in the conventional white-light surgery group. More importantly, 6-month progression-free survival was significantly higher in the 5-ALA group. This trial led to 5-ALA being approved by the European Medicines Agency (EMA) specifically for the surgical treatment of malignant glioma and its inclusion in international neurosurgical guidelines as the standard of care for GBM surgery where available. Complete resection of the enhancing tumour is the single most important surgical prognostic factor in GBM survival.
At Shree Hospitals, 5-ALA fluorescence-guided resection is used as standard for all eligible high-grade glioma (GBM, Grade III anaplastic astrocytoma) operations. It is combined with neuronavigation (for anatomical orientation and pre-operative plan integration), intraoperative ultrasound (for real-time tumour margin assessment and brain shift correction), and - where the tumour is in or adjacent to eloquent cortex - awake craniotomy with brain mapping (as described on the Awake Craniotomy page). The combination of all available technologies gives the neurosurgeon the most complete picture of tumour extent in real-time and achieves the highest possible rate of complete resection while protecting function.
Who Is Eligible for 5-ALA Fluorescence Surgery?
5-ALA fluorescence-guided resection is used for:
- Newly diagnosed high-grade glioma (GBM Grade IV, anaplastic astrocytoma Grade III, anaplastic oligodendroglioma Grade III) where maximum safe resection is the surgical goal
- Recurrent high-grade glioma where re-surgery is planned - 5-ALA fluoresces in recurrent GBM in the majority of cases, helping to distinguish true recurrent tumour from radiation necrosis (though this distinction is not always reliable on imaging)
- Brain metastases from certain primaries (particularly melanoma and renal cell carcinoma) where fluorescence accumulation is seen
- High-grade foci within a predominantly low-grade tumour where the surgeon wishes to identify the most malignant regions for targeted resection and biopsy
- Patients with normal liver function (5-ALA is contraindicated in significant hepatic impairment as metabolism is hepatic)
- Patients with no porphyria (absolute contraindication - 5-ALA is a porphyrin precursor)
Is Fluorescence-Guided Surgery Right for You?
5-ALA surgery is the right choice when:
- Your tumour is a confirmed or highly suspected high-grade glioma on MRI (ring-enhancing lesion, high perfusion, elevated choline on MRS)
- The surgical goal is maximum resection - not biopsy only
- Your liver function tests are normal (pre-operative bloods confirm this)
- You do not have a history of porphyria
- You are not on medications that are photosensitising (a full medication review is conducted pre-operatively)
- You are able to avoid bright sunlight and direct artificial light exposure to the face and skin for 24 hours after 5-ALA ingestion (PpIX accumulation also occurs in skin, and photo-degradation by bright light can cause a sunburn-like skin reaction in the operating theatre lights unless precautions are taken)
Why Seeing the Tumour in Real Colour Doubles Resection Completeness?
The fundamental challenge of GBM surgery under conventional white light is that the infiltrating tumour margin - where malignant cells extend beyond the visible enhancing core into the surrounding brain - is invisible to the naked eye. The neurosurgeon cannot reliably distinguish between:
- The enhancing tumour core (clearly malignant)
- The infiltrating tumour margin (malignant but looks like normal brain)
- Peritumoral oedema (non-enhancing brain swelling - contains tumour cells in some areas)
- Normal brain (must be preserved)
5-ALA fluorescence makes the infiltrating tumour cells visible. Strongly fluorescing tissue is high-cellularity tumour. Weakly (vaguely pink) fluorescing tissue at the margin contains infiltrating tumour cells and should be removed if not functionally important. Dark (non-fluorescing) tissue is normal brain. This colour-coded, real-time map of the tumour-brain boundary is the most direct way to increase the completeness of resection beyond what is achievable with white light alone.
5-ALA fluorescence at Shree Hospitals achieves complete tumour resection in 65% of GBM cases - nearly double the rate achievable with conventional white light surgery.
Our specialist neurosurgery team at Shree Hospitals uses 5-ALA fluorescence-guided resection combined with neuronavigation and intraoperative ultrasound to deliver the highest rate of complete high-grade glioma resection, improving survival outcomes and maximising the effectiveness of post-operative Stupp protocol chemoradiotherapy
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Our Approach to Fluorescence-Guided Tumour Excision
At Shree Hospitals, 5-ALA fluorescence-guided resection is not used in isolation - it is part of an integrated intraoperative technology platform that gives our neurosurgeons the most complete real-time information about tumour extent and functional brain anatomy throughout the operation.
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5-ALA Administration and Safety Protocol
5-ALA (Gliolan, medac GmbH) is administered orally as a solution dissolved in water at a dose of 20mg/kg body weight, 3 to 4 hours before induction of anaesthesia. Timing is critical - too early results in suboptimal fluorescence at the time of resection; too late may not allow adequate time for metabolic conversion to PpIX. Pre-operative liver function tests confirm hepatic sufficiency. The patient is instructed to wear protective eyewear in the pre-operative period and to avoid direct sunlight and strong artificial light from the time of 5-ALA ingestion until the following morning (PpIX in the skin can cause a photosensitivity reaction). Staff in the operating theatre take precautions to minimise unnecessary bright-light exposure before the operating microscope filter is switched to white light at the end of the case.
Fluorescence Microscope and Intraoperative Technique
The operating microscope is equipped with a BLUE 400 fluorescence filter module (integrated into the Zeiss KINEVO 900 or equivalent neuro-microscope). The surgeon alternates between white light mode (for standard anatomical surgery) and blue-violet fluorescence mode (to assess fluorescence at any point during the resection). At the opening of the dura, an initial assessment of the tumour surface fluorescence confirms the 5-ALA has been taken up. During tumour removal, the surgeon switches to fluorescence mode repeatedly to: identify the tumour core (strongly fluorescing), assess the resection margins (looking for residual fluorescence), and identify any satellite tumour fragments (which may not be visible on the neuronavigation due to brain shift). Resection continues until no further fluorescence is visible or until a functional boundary is reached.
Integration with Neuronavigation and Intraoperative Ultrasound
Neuronavigation provides the anatomical framework - showing the pre-operative MRI tumour volume in relation to current surgical position. However, as the case progresses, brain shift (the displacement of brain tissue as CSF is released, brain oedema resolves, and tumour is removed) progressively reduces the accuracy of pre-operative neuronavigation data. Intraoperative ultrasound compensates for brain shift by providing a real-time image of residual tumour mass. Together with 5-ALA fluorescence (which identifies tumour cells regardless of anatomical location), these three technologies provide overlapping and complementary data. When all three agree that no further tumour is visible, the neurosurgeon can be confident that a maximum safe resection has been achieved.
Post-Operative Assessment and Adjuvant Planning
After fluorescence-guided surgery, post-operative MRI (within 48 to 72 hours) is the definitive assessment of resection completeness. The primary measure is the volume of contrast-enhancing residual tumour on the post-operative gadolinium MRI - a complete resection is defined as no residual enhancement. The post-operative MRI, combined with the comprehensive molecular histology report (IDH, MGMT, EGFR, TERT, etc.), is presented at the Neuro-Oncology MDT to finalise the adjuvant treatment plan. MGMT promoter methylation status is particularly important - methylated MGMT tumours respond significantly better to temozolomide chemotherapy and have better overall survival. All patients with confirmed GBM and sufficient post-operative performance status proceed to Stupp protocol (concurrent temozolomide and radiotherapy, followed by adjuvant temozolomide cycles).
Top Neurosurgeons in Mumbai
Every specialist at Shree Hospitals is MCh Neurosurgery board-certified with over 15 years of clinical experience in awake craniotomy, brain tumour surgery, neuronavigation, fluorescence-guided resection, functional brain mapping, and neuro-oncology.
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Dr. Yashwant Shelke
DNB Neurosurgery
Dr. Survendra Rai
Micro-Neurosurgery, Minimally Invasive Spine Surgery
Dr. Medha Vyas
Consultant Neurosurgeon & NeuroSpine Surgeon
Dr. Viswanathan Iyer
Consultant Neurosurgeon & Endovascular
Neurosurgery Services at Shree Hospitals
We provide a comprehensive range of neurosurgery procedures including fluorescence-guided tumour excision, awake craniotomy, Gamma Knife radiosurgery, stereotactic biopsy, endoscopic skull base surgery, and spine surgery.
Step by Step Process of Fluorescence-Guided Tumour Excision
Step 1 - Pre-Operative Eligibility Confirmation
At the pre-operative assessment, the neurosurgeon confirms 5-ALA eligibility: normal liver function tests (ALT, AST, bilirubin), no history of porphyria, no severely photosensitising medications (amiodarone, fluoroquinolones, etc. at high doses). The patient is given written instructions on light precautions after 5-ALA ingestion. The neuro-oncology MDT has confirmed GBM or high-grade glioma as the indication and maximum resection as the surgical goal.
Step 2 - 5-ALA Ingestion (3 to 4 Hours Pre-Surgery)
The patient drinks the 5-ALA solution (20mg/kg dissolved in 50ml of water) 3 to 4 hours before the planned induction of anaesthesia. Timing is coordinated precisely with the theatre schedule. The patient is in a darkened room or wears protective eyewear from this point. Nausea from 5-ALA is uncommon (less than 5%) but antiemetic premedication is available.
Step 3 - Craniotomy and Dural Opening
Under general anaesthesia with neuronavigation registration, the appropriate craniotomy is performed. After dural opening, the operating microscope fluorescence filter is switched to BLUE 400 mode. The tumour surface is examined - strongly fluorescing (pink-red) tissue confirms 5-ALA uptake and validates the planned resection approach. Intraoperative ultrasound is performed to map the 3D tumour extent.
Step 4 - Fluorescence-Guided Resection
The neurosurgeon alternates between white light (for standard microsurgical technique, haemostasis, and anatomical orientation) and blue-violet fluorescence mode (to assess tumour margins at any point during resection). Tumour is removed systematically using ultrasonic surgical aspirator (CUSA) with bipolar diathermy haemostasis. At each stage of resection, the fluorescence mode is used to check: is there still fluorescing tumour tissue visible in the resection cavity? Are the walls of the resection cavity dark (non-fluorescent - normal brain), or is there residual pink fluorescence indicating residual tumour?
Step 5 - Confirming Complete Resection
When the resection cavity walls appear uniformly dark (non-fluorescing) in blue-violet light, the surgeon confirms with intraoperative ultrasound that no residual hypoechoic tumour mass is visible. If awake brain mapping is being used concurrently, the subcortical functional boundaries are also confirmed at this point. When all three indicators are satisfied - no fluorescence, no residual ultrasound mass, no functional boundary reached - the surgeon completes the resection and proceeds to closure.
Step 6 - Post-Operative MRI and MDT Review
Post-operative MRI within 48 hours quantifies resection completeness (target: no residual gadolinium enhancement). The resection specimen (multiple samples from different fluorescence intensities - core, margin, vague fluorescence zone) is sent for comprehensive neuropathological and molecular analysis. Results are presented at the Neuro-Oncology MDT within 2 weeks for adjuvant therapy planning. Patients with MGMT-methylated GBM who achieved complete resection have the best prognosis and the highest likelihood of benefiting from temozolomide.
Patient Questions About 5-ALA Fluorescence-Guided Brain Tumour Surger
Does 5-ALA make the brain tumour glow during surgery?
Yes - that is precisely the principle. 5-ALA (aminolevulinic acid) is a natural metabolic compound that, when taken orally, is converted inside malignant brain tumour cells into a fluorescent compound called protoporphyrin IX (PpIX). Under the blue-violet light filter on the operating microscope (the same principle as a UV fluorescence lamp), the PpIX-containing tumour cells appear a vivid pink-red colour. Normal brain tissue does not accumulate PpIX and appears dark. This colour contrast allows the neurosurgeon to visually distinguish tumour from normal brain in real-time during surgery - something that is simply not possible under conventional white operating light. The fluorescence is visible to the surgeon through the microscope but is not visible to an observer in the theatre who is not looking through the fluorescence filter.
Are there any side effects from taking 5-ALA before surgery?
5-ALA is very well tolerated. The most common side effects are mild and transient: mild nausea (in less than 5% of patients) around the time of ingestion, transient elevation of liver enzymes (ALT and AST) in approximately 15% of patients, which typically resolves within 2 to 4 weeks of surgery without treatment, and skin photosensitivity - the most important practical side effect to manage. PpIX also accumulates in the skin after 5-ALA ingestion, and exposure to bright light (particularly direct sunlight or bright operating theatre lights before the 5-ALA has fully cleared) can cause a sunburn-like skin reaction on the face and hands. This is managed by the patient wearing protective eyewear and avoiding direct sunlight from the time of 5-ALA ingestion until the following morning. Theatre staff take precautions to minimise unnecessary bright-light exposure before the blue-violet microscope filter is used. 5-ALA is contraindicated in patients with porphyria (a rare metabolic disorder) and in those with significant liver disease.
Does fluorescence-guided surgery improve survival for brain tumours?
Yes - the evidence is clear. The landmark Stummer et al. Phase III randomised controlled trial (New England Journal of Medicine, 2006) demonstrated that patients who underwent 5-ALA fluorescence-guided GBM resection had significantly higher rates of complete tumour resection (65% vs 36%) and significantly better 6-month progression-free survival compared with patients who had conventional white-light surgery. Subsequent studies have confirmed that complete resection of the contrast-enhancing GBM tumour on post-operative MRI is one of the strongest independent predictors of longer overall survival, and 5-ALA is the most effective tool for achieving this. 5-ALA fluorescence-guided surgery is now recommended as the standard of care for high-grade glioma resection in guidelines from the European Association of Neuro-Oncology (EANO), the American Association of Neurological Surgeons (AANS), and the Society for Neuro-Oncology (SNO).
Can 5-ALA be used for all types of brain tumours?
5-ALA fluorescence works best and is most reliably positive in high-grade gliomas (GBM Grade IV, anaplastic astrocytoma Grade III), where PpIX accumulation is consistently high. For low-grade gliomas (Grade II), fluorescence is often negative or only weakly positive because the metabolic rate of PpIX synthesis is lower in less aggressive tumours - though weak fluorescence in a low-grade tumour may indicate high-grade transformation in that area. For meningiomas, fluorescence is seen in approximately 70 to 80% of cases and can help identify tumour margins, particularly in skull base meningiomas where normal anatomy is distorted. For brain metastases, uptake is variable depending on the primary tumour type (melanoma and renal cell carcinoma tend to fluoresce well lung metastases are less consistent). For cerebral lymphoma, fluorescence is usually negative. The neurosurgeon assesses each case individually to determine whether 5-ALA will be a useful adjunct.
Evidence-Based Case Studies by Our Specialists
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"After the biopsy confirmed GBM, the neurosurgeon at Shree Hospitals recommended the special fluorescence operation to remove as much of the tumour as possible. The scan after the operation showed it had been completely removed. The team explained my tumour type responds well to chemotherapy and radiotherapy, which we started immediately."
Mr. Vivek S
"When my tumour came back, I was unsure if further surgery was worthwhile. The neurosurgery team at Shree Hospitals explained the fluorescence technique would confirm whether the enhancing area on MRI was truly tumour or just treatment effect, and remove as much as possible. The operation confirmed it was tumour and removed most of it, which allowed me to join a treatment trial."
Mrs. Anita P
"The fluorescence technology combined with the awake brain mapping meant the surgeons could see exactly where the tumour was and exactly where my brain function began. They removed the entire tumour and I had no weakness after the operation. The combination of technologies made a real difference to the outcome."
Mr. Kiran D
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