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October 9, 2006

Treating Brain Tumors: fMRI Impacts Neurosurgical Planning
By Dan Harvey
Radiology Today
Vol. 7 No. 20 P. 21

Surgical treatment for brain tumors involves notoriously complex preoperative and intraoperative issues. Neurosurgeons have been forced to tread a fine line to avoid postoperative problems for patients.

“Resecting too little tissue risks tumor recurrence, while resecting too much may create neurological deficits,” says Jeffrey R. Petrella, MD, associate professor of radiology in the neuroradiology division at Duke University in Durham, N.C. “A neurosurgeon might resect a vital area next to the tumor that controls a patient’s speech or physical activity.” Obviously well-intended, aggressive resection, as Petrella suggests, could potentially damage the motor and cognitive areas of the brain, leading to problems with limb function and language processing.

Functional MRI (fMRI) can help neurosurgeons better navigate that fine line. That is one of the conclusions of a study conducted by Petrella and fellow researchers. The study, which was reported in the September issue of Radiology (“Preoperative Functional MR Imaging Localization of Language and Motor Areas: Effect on Therapeutic Decision Making in Patients with Potentially Resectable Brain Tumors”), demonstrates that fMRI helps neurosurgeons avoid neurological damage by enabling them to preoperatively identify and, in turn, spare vital brain areas—specifically the motor and language regions—during a tumor excision, thus reducing the risk of damage to speech and motor processes.

Equally notable, as well as logically consequent, the information provided by fMRI significantly impacted treatment decisions for the neurosurgeons involved in the study, according to the researchers. For one half of the participating brain tumor patients, the physicians revised their treatment strategies because fMRI could identify the important brain regions before surgery. “[fMRI] has a significant effect on therapeutic planning in patients with potentially resectable brain tumors by facilitating the selection of therapeutic options that might otherwise not have been considered because of functional risk,” reports lead author Petrella and coauthors Lubdha M. Shah, MD; Katy M. Harris, BS; Allen H. Friedman, MD; Timothy M. George, MD; John H. Sampson, MD, PhD; Joseph S. Pekala, MD; and James T. Voyvodic, PhD.

Further, Petrella and colleagues report that, in patients undergoing fMRI, neurosurgeons removed more tumor tissue. Further, the fMRI information led to reduced intraoperative time and smaller skull incisions.

Shedding Light
As fMRI reveals metabolic changes during brain activity (during an exam, specific areas “light up” when activated), the modality can be particularly useful in preoperative planning for excision of tumors because the tumors can cause brain areas to shift.

“Particular brain areas light up when a subject does a particular activity. With speech, there’s increased activity in the frontal and temporal lobes. Similarly, if someone squeezes a hand or wiggles a foot, we can see increased activity in the motor areas of the brain that control the hand or foot,” says Petrella.

If a tumor does cause a brain area to shift, the visual recognition afforded by fMRI enables surgeons to perceive such a shift, thus reducing the potential damage to these vital regions during surgical procedures.

“Functional MR imaging can be used to identify eloquent cortical regions, particularly when these cortical regions are displaced or reorganized secondary to pathologic processes and can facilitate the assessment of potential neurosurgical risks,” the coauthors write.

Petrella reports that fMRI has been viewed as an effective alternative to intraoperative cortical stimulation craniotomy, the gold standard technique surgeons use to indicate whether they are taking too much or too little tissue when performing brain tumor surgery. The complex technique involves performing part of the surgery while the patient is under local anesthesia. “The surgeons test the patient’s language and motor skills while they resect the tumor to make sure they’re not invading a critical area. That is, while the patient is awake, they resect some tissue, perform some testing, then resect a little bit more, and do some more testing,” he explains.

Alternatively, fMRI, when employed preoperatively, gives surgeons a better idea of where the important language and motor areas are, relative to the tumor, much more quickly and without the tediously methodical steps. “The modality provides surgeons with a preoperative map that reveals exactly where those areas are located,” says Petrella. “Otherwise, it may take a surgeon a while to try and probe around to identify different areas. With the map, they can go right to the ‘money area,’ so to speak.”

This speeds up surgery, Petrella adds. Also, fMRI provides the neurosurgeons with a better idea about the feasibility of surgery. “For some patients, surgery would just be too dangerous, as the tumor would be too close to a critical area,” he says. “Without fMRI, a surgeon may think, ‘Yes, I think this patient is a good candidate.’ But with fMRI, the modality might say to the surgeon, ‘No, you better think twice.’”

Conversely, fMRI findings may provide reason to revise for a surgeon inclined to err on the side of caution. For example, before fMRI, a surgeon may have believed a tumor in the motor area was too large to resect, as it would have left the patient with a deficit. But now, fMRI may show that the motor area is separate from the tumor, which means there’s a chance that the entire tumor can be resected. “Even with fMRI, surgical planning is tricky, but because it provides more information, fMRI provides surgeon a better edge,” says Petrella.

Petrella and fellow researchers conducted their study at Duke University Medical Center between May 2004 and February 2005. Their aim was to prospectively assess how preoperative fMRI localization of the brain’s language and motor areas would affect surgeons’ decisions regarding how they treated patients with potentially resectable brain tumors.

Study Protocol
The study involved 39 patients (19 males and 20 females with an average age of 42.2). They were referred for fMRI by surgeons involved in the study. All subjects underwent a preoperative fMRI diagnosis of the brain. Ten minutes before examination, the patients were trained in verbal and motor tasks, which they then performed during the imaging. These sentence-completion tasks and bilateral hand-squeezing tasks were designed to respectively map areas of the brain involved in language processing and motor skills. According to the researchers, the time involved in performing an entire preoperative fMRI session was less than an hour. This included the complete patient training and image acquisition. Researchers performed the imaging with GE Medical System’s Horizon, a 1.5-Tesla MRI system equipped with echo-planar imaging capabilities.

Also as part of the study, the participating neurosurgeons completed before-and-after imaging questionnaires that would help the researchers determine the impact fMRI had on treatment-planning decisions. The neurosurgeons also completed a postoperative questionnaire to indicate their confidence in the fMRI results and determine whether those results impacted their surgical approach, the time they spent in surgery, and the extent of resection. According to the study, the surgeons were, on average, “fairly confident” about speech and motor function localization and “very confident” in speech-function lateralization to the left or right side of the brain.

Altered Approaches
Petrella and colleagues reported that, because of the fMRI findings, treatment was significantly altered in 49% of cases (19 of the 39 patients)—that is, the surgeons were compelled to change their treatment plans after a review of the fMRI results. More specifically, neurosurgeons adopted a more aggressive surgical approach in 18 of those 19 cases.

Also, because of the fMRI findings:

• surgery time was reduced by a range of 15 to 60 minutes in 22 patients;

• more complete tumor resection was accomplished in six cases; and

• craniotomy incisions were smaller in two cases.

Originally, no surgical intervention was planned for nine patients. But after imaging, treatment for five of those patients was changed to craniotomy with mapping. Two other patients subsequently underwent biopsy. Treatment for the remaining two patients remained unchanged; they didn’t undergo surgery. Of the 30 patients scheduled to undergo surgical intervention, seven had their treatments changed from biopsy to craniotomy with mapping, while one was changed from biopsy to craniotomy with general anesthesia and three more were changed from craniotomy with mapping to craniotomy with general anesthesia, the researchers report. For the patients whose treatment plans remained unchanged, the researchers indicate that the neurosurgeons’ decisions were most likely influenced by their confidence in fMRI.

Further, no patients experienced any neurological deficits following tumor removal surgery. Commenting on the findings, Petrella says the results suggest that fMRI may make it possible to safely perform surgery in patients previously considered ineligible for surgery due to the location of their tumor. He also says the study clearly demonstrates that fMRI can influence how neurosurgeons preoperatively plan surgery.

He also indicates that fMRI findings can help determine how aggressive a surgeon wants to be when attacking a tumor. “The fMRI information tends to lead neurosurgeons to take a slightly more aggressive approach,” he says. “Essentially, it makes them a little more confident. With that confidence, they would do things they otherwise might not have done. In certain cases, they may resect a little more tumor than they would have without the information.”

Follow-up
Petrella says the next logical step in this direction would be to conduct a multicenter, randomized control trial involving a larger number of patients to determine the impact on patient outcomes. Such a study could lead to fMRI becoming a new standard of care: “Yes, we’ve shown that fMRI does influence how neurosurgeons treat their patients in a significant number of cases, but how does it influence outcome? Will it offer patients a better quality of life? Will it increase their survival? Those are the big questions.”

However, developing such a study would involve substantial problems, he points out. For one thing, any outcome-based study would take a long time, for obvious reasons. “You have to follow the natural history of the disease,” says Petrella. “It would be an ideal next step if we did a study like that, where you compare patients with access to fMRI to a control group without access.”

But that step would involve theoretical, ethical problems. “If a neurosurgeon has access to fMRI, and they believe in the benefits of the modality in guiding treatment, it would be very difficult, from an ethical standpoint, to convince that neurosurgeon to randomize a patient to the non-fMRI wing of the study,” says Petrella. “Many neurosurgeons would have trouble with that, from an ethical standpoint. No surgeon would want to deny a patient information that would be helpful.”

In the meantime, the researchers have added a valuable section to the literature on fMRI. “The gist of this study is that fMRI does make a difference in how neurosurgeons go about caring for their patients,” says Petrella.

— Dan Harvey is a freelance writer based in Wilmington, Del., and a regular contributor to Radiology Today.