Researching the Effects of Brain Tumor Removal on Language

Study Used fMRI to Identify Tasks Activated By Language

In the study, a database of right-handed patients with left brain gliomas was collected, including subjects who performed preoperative task-based fMRI and underwent awake surgery with direct cortical stimulation.

“In about 95% of right-handed patients (majority of the population), the left cerebral hemisphere is dominant for language. This means that the language cortex, the brain area that sustains the capability of speaking, is in the left hemisphere,” Dr. Pasquini said. “Selecting left-hemispheric tumors in right-handed patients allows us to infer the presence of language reorganization by looking at the language dominance: a deviation from the normal percentage of left dominance in right-handed patients (95%) may suggest recruitment of the right hemisphere for language function reorganization.”

The patients were classified according to task-based fMRI results from phonemic fluency tasks plus clinical data regarding the patient (demographic info, clinical speech deficits) and tumor (location, pathology and grade, size, tumor genetics).

fMRI was used to depict the areas of the brain that were activated by the patient performing a specific function, in this case a phonemic fluency task.  According to Dr. Pasquini, fMRI can image distortions in the magnetic field caused by the iron content of the blood supplying the areas of the brain that are activated by the task.

The functional language networks were developed from the fMRI time signal of active clusters labeled on fMRI maps, by means of statistical inference techniques. Then, a novel graph theoretical framework was developed by the researchers to identify and analyze the most influential nodes in the brain based on optimal percolation, which is the problem of finding the minimal set of nodes whose removal from the whole would fragment the system into disconnection. 

Dr. Pasquini and colleagues showed that language reorganization is influenced by age, sex and tumor location near eloquent areas, such as Broca’s and Wernicke’s areas, which are cortical areas specialized for production and comprehension of human language.

Language reorganization can also be influenced by certain molecular features of the tumor such as methylation of O6-methylguanine-DNA methyltransferase (MGMT)— a DNA repair enzyme that rescues tumor cells from alkylating agent-induced damage—in high-grade gliomas. Another example is the lack of fibroblast growth factor receptors (FGFR) mutation, which, if present, can be implicated in a wide variety of cancers.

A possible explanation, according to Dr. Pasquini, resides in the longer survival and less aggressive behavior of neoplasms harboring these molecular changes. Tumors of different location produce different effects on brain connectivity, both locally and in distant regions. Furthermore, brain connectivity analyses showed that language reorganization develops over a time frame of six months to 1 ½ years after surgery, and is characterized by the progressive recruitment of the right hemisphere in language function. Such connectivity changes correlate with the results of intra-operative stimulation and carry clinical relevance, helping the patients to compensate speech deficits.

“To reconstruct the language network, we look at the interdependence of the fMRI signal in the specific areas of the cortex that serve language function. This is achieved with graph theory—a mathematical model which describes the architecture of networks,” Dr. Pasquini said.

The researchers discovered that adding information about language areas connectivity and functional reorganization to the gold-standard fMRI tasks can help a neurosurgeon with a hierarchy of language areas to guide surgical resection and help identify candidate patients for language reorganization.

“Language reorganization may signify that the surgeon can safely remove a brain tumor growing in the dominant cerebral hemisphere for language without causing any speech deficit. Cancer patients can therefore have a better quality of life, and maintain the ability               to communicate and understand others,” Dr. Pasquini said. “This can also help with surgical planning, where multiple surgeries might be required to remove the tumor and to allow the brain to develop reorganization in between. After surgery, reorganization is the key for recovery. Widening our understanding of plastic phenomena may lead to uncountable applications in clinical care.”

R&E Foundation Grant Helped Expand Opportunities

The protected research time provided by the R&E Foundation grant has made a difference for Dr. Pasquini, who decided to develop his career as a neuroradiologist and neuroscientist in the U.S.

This grant allowed Dr. Pasquini to lay the foundation of his work focused on brain cancer and neuroplasticity, with the intention of expanding his achievements nurturing international collaborations and future grant applications.

“I completed my training as a radiologist specialized in diagnostic neuroradiology in Italy, and I am currently completing radiology and nuclear medicine accreditation in the U.S.,” Dr. Pasquini said. “The R&E Foundation grant gave me the exceptional opportunity of expanding my neuroradiology fellowship with an additional year of research. The work developed through the grant was also used to complete my PhD in neuroscience.”

For More Information

Learn more about R&E Foundation grants at RSNA.org/Research/Funding-Opportunities.

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