Brain Tumors: Gliomas and Function-Preserving Neuro-Oncology at the INI

Brain tumors pose unique challenges for diagnosis and treatment. Unlike tumors in many other organs, the therapeutic strategy is determined not only by the biological characteristics of the tumor. Its location, its relationship to functionally critical brain regions and fiber pathways, and the individual functional organization of each patient’s brain are equally important.

This is particularly true for gliomas.

Gliomas arise from cells of the central nervous system and encompass biologically very different tumors. Some grow slowly over many years, while others exhibit distinctly more aggressive behavior. At the same time, many gliomas do not merely displace the surrounding brain but infiltrate it.

The central challenge is therefore to combine the most effective possible tumor treatment with the best possible preservation of neurological and cognitive function.

At the International Neuroscience Institute (INI), the treatment of gliomas is therefore based on a comprehensive concept combining tumor biology and molecular diagnostics, high-end imaging, functional brain mapping, neuropsychology, microsurgical expertise, intraoperative imaging, neurophysiology, neuro-oncology, and neurorehabilitation.

Gliomas – Different Tumors with Different Biology

The term glioma encompasses a group of biologically highly diverse tumors.

Modern classification increasingly incorporates the molecular characteristics of a tumor in addition to its microscopic appearance. These features allow substantially more precise classification and may have a decisive influence on prognosis and further treatment.

Important glioma groups include astrocytomas with IDH mutation, oligodendrogliomas with IDH mutation and 1p/19q codeletion, and glioblastomas, which are predominantly IDH-wildtype.

We also treat numerous rarer glial, glioneuronal, and neuronal tumors, including ependymomas, pilocytic astrocytomas, gangliogliomas, pleomorphic xanthoastrocytomas, neurocytic tumors, diffuse midline gliomas, and other rare tumor entities.

For the surgical strategy, however, the name of a tumor alone is never decisive. Its location, growth pattern, functional environment, molecular biology, and the individual situation of the patient must be considered together.

Precision Diagnostics Before Surgery

Successful brain tumor surgery begins long before the operation itself.

Together with the highly specialized Department of Neuroradiology led by Professor Heiner Lanfermann and his team, state-of-the-art neuroradiological techniques and two high-performance 3-Tesla MRI systems are available.

In addition to high-resolution structural MRI, further techniques can be used depending on the clinical question. These include perfusion and diffusion imaging, MR spectroscopy, quantitative 3D imaging, and functional MRI. Modern high-end post-processing methods and increasingly AI-based analytical approaches allow more advanced characterization of complex imaging data.

Within scientific collaborations, these methods are continuously refined and complemented by innovative techniques in quantitative and functional imaging.

The aim is to obtain as much information as possible about the tumor before surgery: Where are its true boundaries? Which regions appear biologically most active? How homogeneous or heterogeneous is the tumor? What does the imaging suggest about tumor type and biology? How does the tumor relate to the surrounding brain? And which functionally important structures are located within or immediately adjacent to the planned surgical field?

This information may influence whether, when, and above all how surgery should be performed. In biologically heterogeneous tumors, it may also help identify particularly relevant areas for targeted biopsy, multisampling, or resection.

More Than 25 Years of Functional Imaging and Brain Mapping at the INI

Functional visualization of the human brain has been a major focus of the INI since the Institute opened.

As early as 2000, the INI had one of the first clinically used 3-Tesla MRI systems in Europe.

Under the scientific leadership of Professor Hans-Jochen Freund, a pioneer in functional imaging and the study of functional networks of the human brain, functional MRI was systematically integrated into neuroscientific and clinical work at the INI at an early stage.

Today, functional brain mapping includes not only conventional task-based functional MRI but also modern techniques for visualizing functional networks, including resting-state fMRI.

Under the leadership, among others, of Professor Bahram Mohammadi, these methods were further developed and integrated into modern concepts of functional brain mapping.

Diffusion imaging and tractography represent another essential component. Modern high-end processing techniques allow important fiber pathways to be reconstructed and their relationship to the tumor to be visualized.

This creates an individualized functional map of the brain before surgery.

We do not only want to know where the tumor is located. We want to understand how this particular patient’s brain is organized around the tumor.

Cognitive Neurology and Neuropsychology – Function Means More Than Movement and Language

Preserving neurological function during brain tumor surgery means more to us than protecting motor function, sensation, or language.

Tumors and their treatment may also affect complex cognitive functions such as attention, memory, concentration, processing speed, spatial perception, executive functions, and other higher cortical abilities.

For selected patients, we therefore incorporate detailed neuropsychological and cognitive-neurological assessment into treatment planning before surgery.

For this purpose, we work closely with a specialized team in Cognitive Neurology and Neuropsychology at University Hospital Magdeburg.

Neuropsychological assessment allows the patient’s individual cognitive baseline to be documented systematically before surgery and may identify changes already caused by the tumor.

Of particular importance is the integration of these findings with preoperative functional brain mapping.

Functional MRI, resting-state fMRI, tractography, and modern network and post-processing methods demonstrate the individual functional organization of the brain. Neuropsychological testing complements these maps by documenting the patient’s actual cognitive performance.

We do not only want to know where a tumor is located; we want to understand how the individual patient’s brain functions and which networks are particularly important for that person’s abilities.

This information can influence planning of the surgical approach, the resection strategy, and – in suitable patients – the selection of functions to be tested during awake surgery.

Surgical Experience – Particularly Where Tumors Are Most Difficult to Reach

Modern technology is an essential component of brain tumor surgery. It cannot, however, replace the personal operative experience of the neurosurgeon.

The neurosurgeons at the INI have exceptionally extensive operative experience in the treatment of complex brain tumors, including tumors located in deep, functionally critical, or anatomically particularly challenging regions of the brain.

This includes tumors immediately adjacent to eloquent cortical areas and fiber pathways, as well as tumors of the insula, basal ganglia, thalamus, deep midline, ventricular system, and other difficult-to-access regions.

Because of this particular expertise, patients from Germany, throughout Europe, and many other countries are referred to the INI for assessment and treatment of complex brain tumors. This also includes patients specifically referred by other neurosurgical centers or colleagues for a second opinion or surgical treatment because tumor location, extent, functional relationships, or previous treatment make the case particularly challenging.

These referrals also include patients with tumors initially considered only partially operable or inoperable because of their location or complexity, as well as patients following previous surgery, with recurrent tumors, or with residual tumor.

Such a previous assessment does not automatically mean that surgery is possible or appropriate. Every case is reassessed individually at the INI on the basis of current imaging, tumor biology, functional anatomy, and the patient’s personal situation.

In such tumors, success is determined not only by the ability to remove the lesion. Equally important is the choice of the least disruptive and functionally most favorable microsurgical route.

The surgical tradition of the INI and its associated neurosurgical school has been shaped substantially by the development and continuous refinement of such microsurgical approaches. Several techniques and surgical routes used today were developed, modified, or further refined through large personal operative series by neurosurgeons of the INI and its surgical school.

The objective is to plan the route to the tumor in a way that minimizes disturbance of healthy and, in particular, functionally relevant brain tissue.

The anatomically shortest route is not necessarily the safest route.

The decisive question is which approach, taking into account individual anatomy, functional networks and fiber pathways, and tumor location, offers the lowest functional cost for the most effective possible tumor removal.

Especially in difficult brain tumors, a particular strength of the INI therefore lies in combining exceptional personal operative experience, differentiated microsurgical approach strategies, and state-of-the-art imaging and functional technology.

The Brain Suite – Intraoperative High-Field MRI Since 2007

Since 2007, the INI has operated a hybrid operating room specifically designed for image-guided neurosurgery – the Brain Suite.

The Brain Suite was conceived and established at the INI by Professor Rudolf Fahlbusch, who is among the international pioneers of intraoperative MRI in neurosurgery. He began the clinical development and application of this technology in the mid-1990s.

When Professor Fahlbusch joined the INI in 2006, he brought with him more than ten years of personal experience with intraoperative MRI. On this basis, he developed and implemented the INI Brain Suite, which opened in 2007 and integrated intraoperative high-field MRI directly into the neurosurgical workflow.

The key advantage is that repeat MRI can be obtained within a short period during an operation.

This allows the surgeon to assess how much of the tumor has actually been removed and whether relevant residual tumor remains that can be safely resected further.

This is particularly important for infiltrating and low-grade gliomas, whose boundaries are often not clearly visible under the operating microscope.

At the same time, anatomy changes during surgery. Tumor removal, loss of cerebrospinal fluid, and tissue displacement produce the so-called brain shift. Preoperative navigation data therefore become progressively less representative of the actual intraoperative anatomy.

Intraoperative MRI allows these anatomical data – and consequently navigation – to be updated.

Navigation, Microscopy, Intraoperative Ultrasound, and Fluorescence

The Brain Suite and the neurosurgical operating rooms are equipped with modern neuronavigation systems, navigation-linked operating microscopes, navigated intraoperative ultrasound, and fluorescence-guided surgical techniques, particularly using 5-aminolevulinic acid (5-ALA). This technological spectrum is complemented by stereotactic and robot-assisted procedures as well as MRI-guided Laser Interstitial Thermal Therapy (LITT) for selected indications.

These technologies provide different and complementary perspectives on the same tumor.

Navigation supports spatial orientation within the individual anatomy. The operating microscope enables high-resolution microsurgical dissection. In appropriate tumors, fluorescence can help visualize biologically relevant tumor tissue.

Intraoperative ultrasound can provide additional real-time information about tumor boundaries, the resection cavity, and potentially remaining tumor tissue during surgery. When linked to neuronavigation, ultrasound information can be incorporated directly into the surgeon’s spatial orientation.

We do not regard intraoperative ultrasound as an alternative to intraoperative MRI. The two modalities have different strengths and – depending on tumor type, location, and the intraoperative situation – can complement one another effectively.

Intraoperative MRI ultimately provides a high-resolution update of the anatomical situation, assessment of the extent of resection, and updating of navigation after brain shift has occurred.

Imaging, Neurophysiology, and Awake Surgery – Complementary Rather Than Competing

No single technology can answer every decisive question during glioma surgery.

Intraoperative MRI, intraoperative ultrasound, neuronavigation, fluorescence, neurophysiological monitoring, direct electrical stimulation, and awake surgery are therefore not competing techniques. They provide different and complementary information.

Imaging shows where residual tumor may remain. Navigation shows where the surgeon is within the individual anatomy. Fluorescence may help visualize biologically relevant tumor tissue. Neurophysiological monitoring continuously assesses the integrity of important functional systems. Direct electrical stimulation identifies functionally indispensable cortical areas and subcortical fiber pathways. In selected tumors, awake surgery allows complex functions – particularly language, but depending on the individual situation also other higher cortical functions – to be tested directly during resection.

The combination of these techniques makes it possible to define the limits of surgery not solely anatomically, but anatomically, radiologically, and functionally.

The decisive boundary is function.

The objective is therefore an individualized maximum safe resection: the greatest oncologically meaningful tumor removal while consistently preserving neurological and cognitive function.

Which of these methods are used and how they are combined is decided individually for each patient.

The quality of an operation is not determined by the maximum number of technologies employed, but by their purposeful combination in the hands of an experienced neurosurgical team.

When a Biopsy Is Required

Primary resection is not the correct strategy for every brain tumor.

In selected situations, a targeted biopsy may first be required to establish a reliable histological and molecular diagnosis.

Different techniques are available at the INI, ranging from conventional stereotactic biopsy to robot-assisted procedures using the Cirq® system and the combination of intraoperative MRI with VarioGuide®.

Preoperative high-end imaging can help identify particularly informative target regions for tissue sampling within biologically heterogeneous tumors.

Here too, the focus is not on a particular technology, but on determining which technique provides the safest and diagnostically most effective solution for the individual patient.

Minimally Invasive Procedures – Laser Interstitial Thermal Therapy (LITT)

Conventional microsurgical resection is not possible or appropriate for every brain tumor. This may be particularly relevant for deeply located or difficult-to-access tumors, in selected recurrent disease settings, or after previous surgery and other treatments.

For carefully selected patients, Laser Interstitial Thermal Therapy (LITT) may provide an additional minimally invasive treatment option. A thin laser probe is placed stereotactically or under navigational guidance into the target tissue. The target tissue can then be thermally ablated under MRI-based real-time temperature monitoring.

We do not regard LITT as a replacement for microsurgical tumor resection. When safe microsurgical removal is feasible and oncologically appropriate, microsurgery remains a fundamental treatment option. LITT may, however, provide an important additional option when a conventional microsurgical approach is not, or is no longer, reasonably feasible because of tumor location, previous treatments, or the individual risk profile.

Whether LITT is suitable in an individual case depends, among other factors, on tumor type, size and geometry, location and accessibility, the relationship to functionally relevant structures, and previous treatment. As with all brain tumor treatments at the INI, the indication is therefore determined individually and on an interdisciplinary basis.

Neuropathology, Molecular Biology, and Tumor Heterogeneity

Today, the definitive diagnosis of a brain tumor is based on the combination of histology and molecular tumor characterization.

For this purpose, there is close cooperation with the Department of Neuropathology at Hannover Medical School (MHH).

Modern molecular pathological techniques allow increasingly precise biological classification of brain tumors. Depending on the tumor entity, genetic and molecular alterations, expression profiles, and other biomarkers may be relevant to diagnosis, prognosis, and therapeutic decision-making.

Intratumoral heterogeneity is of particular scientific interest. Different regions of the same glioma may differ at the molecular level.

In selected tumors, image-guided and neuronavigated multisampling from different tumor regions may therefore be valuable. Combining precise spatial assignment with modern DNA- and RNA-based analysis, including transcriptomic and gene-fusion analyses, allows the biological complexity of a tumor to be characterized in greater detail.

In this way, the precision of neurosurgical tissue sampling is directly linked to modern molecular neuropathology and translational neuro-oncology.

The Interdisciplinary Tumor Board

Treatment of a glioma does not end with surgery.

Once the neuropathological and molecular findings are available, the further strategy is determined on an interdisciplinary basis.

At the neuro-oncology tumor board, all relevant findings are jointly reviewed by specialists in neurosurgery, neuroradiology, neuropathology, neurology, oncology, and radiation oncology.

The operative findings, postoperative imaging, histology and molecular tumor profile are considered together with the patient’s neurological and cognitive status, comorbidities, and individual life situation.

The tumor board is therefore not merely a formal meeting after completion of surgical treatment. It is an integral part of a continuous treatment concept.

Further Neuro-Oncological Treatment – Outpatient and Inpatient Care at the INI

Subsequent medical neuro-oncological treatment can also be provided at the INI.

Depending on tumor entity, molecular profile, and the individual clinical situation, this includes the indicated systemic and medical treatment concepts as well as clinical and imaging follow-up.

These treatments can be delivered at the INI on both an outpatient and inpatient basis, allowing our patients to receive substantial parts of their neuro-oncological care continuously within the same specialized treatment team.

When radiation therapy is required, it is provided in close coordination with our specialized local radiation oncology partners. Planning, timing, and follow-up are integrated into the joint neuro-oncological treatment concept.

In the event of suspected recurrence, tumor progression, or an equivocal radiological finding, the situation is reassessed interdisciplinarily. Options may include repeat surgery or biopsy, radiation therapy, medical treatment, and other individualized therapeutic concepts.

From Preservation of Function to Functional Recovery

Our treatment concept does not end functionally with the operation.

After surgery, neuropsychological follow-up can help objectively document changes and guide further treatment.

The human brain has a substantial capacity for neuroplasticity and functional reorganization. Particularly in slowly growing tumors, functional networks may already have shifted or reorganized before surgery. After surgery, such adaptive processes may also contribute to functional recovery and can be therapeutically supported.

In collaboration with our partners in Cognitive Neurology, Neuropsychology, and Neurorehabilitation, individualized therapeutic concepts can be developed to restore or compensate for impaired functions and to support neuroplastic reorganization.

Precision diagnostics → functional and neuropsychological brain mapping → individualized surgery or biopsy → molecular neuropathology → interdisciplinary tumor board → outpatient or inpatient neuro-oncological treatment → radiation therapy in close cooperation → functional rehabilitation and long-term clinical, neuropsychological, and imaging follow-up.

The INI Concept of Brain Tumor Treatment

Modern brain tumor treatment means substantially more to us than a technically successful operation.

It combines tumor biology and molecular diagnostics, high-end neuroradiology and modern image analysis, functional brain mapping and neuropsychology, microsurgical expertise and differentiated surgical approaches, intraoperative high-field MRI and navigated ultrasound, neurophysiology and awake surgery, modern neuro-oncology, and targeted support of functional recovery and neuroplasticity.

Not every method is required for every patient.

The true quality of treatment lies in determining, for each individual patient, which diagnostic, surgical, functional, and oncological techniques – and which combination of them – offer the greatest benefit.

Technology supports surgical experience; it does not replace it.

Our objective is therefore not merely the maximum safe removal of a tumor.

Our goal is long-term, individualized neuro-oncological care that considers tumor control and survival together with neurological and cognitive function, independence, and quality of life.

From precise diagnosis to maximum safe resection – and from preservation of function to comprehensive neuro-oncological care.

Selected Scientific Publications

Relevant publications from the INI era on gliomas and brain tumors, intraoperative MRI, neuronavigation, intraoperative ultrasound, DTI/tractography, functional imaging and brain mapping, as well as molecular neuropathology, genetics, and transcriptomics. Listed in reverse chronological order.