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Intra-operative Imaging Techniques During Surgical Management of Gliomas

light, emits a red fluorescence which can be viewed through a 455 nm long-pass filter. In effect, it makes glioma cells directly visible under the operating microscope (see Figure 5). 5-ALA is administered as an oral solution from six to 24 hours prior to surgery. Intra-operatively, the tumor is resected using standard techniques. As the pseudo-margins of the tumor are approached, fluorescence within cells may be used as one indicator that further resection is warranted.

Thus far, results with 5-ALA have been promising. It improves the extent of resection.32,33

In one study, it increased the rate of complete

resection of the enhancing portion of glioblastoma multiforme from 36 to 65 %; the 5-ALA patients also doubled their progression-free survival.34

In another study, patients receiving 5-ALA had median

residual tumor volumes of 0 cm compared with 0.5 cm in the conventional group.35

were more likely to have short-term neurologic deficits than control patients. This increased temporary morbidity is likely a result of the extended resections: 5-ALA does not differentiate between eloquent and non-eloquent tissue, so the resection must not be extended to the limits of fluorescence without consideration of functional pathways. Again, in this trial patients with complete resections had longer survival and time to neurologic progression.

Pre-operative Imaging—Integration with Intra-operative Navigation

Since its advent in 1991, fMRI has become the dominant technique for functional brain imaging. It uses the blood-oxygen-level dependence (BOLD) signal, which is a reflection of the changing levels of oxyhemoglobin and deoxyhemoglobin in functionally active brain regions. fMRI is limited by relatively poor temporal resolution (several seconds). It is a safe, non-invasive method that allows for whole-brain coverage, including the ability to examine activity in deep structures. Importantly, the widespread availability of MR scanners has made the technique easy to adopt across the medical field. In patients with brain tumors, fMRI has been used to identify sensorimotorcortex (see Figure 6), but other modalities such as DTI and TMS (see below) are proving to be more accurate for this purpose. Currently, the use of fMRI to delineate regions associated with specific language tasks (i.e. word repetition, word reading, and object naming) is in the experimental stage. Similarly, language lateralization with fMRI is a subject of continuing research and is rapidly reaching equivalent sensitivity and specificity to Wada testing.36

DTI is another MR-based technique used to measure the diffusion of water molecules in tissue. Because water molecules tend to diffuse preferentially along densely myelinated white-matter tracts, DTI can accurately trace white-matter tracts, a process known as tractography. In this modality, regions of interest that are presumed to be functionally connected are selected (i.e. primary motor cortex and cerebral peduncle). The algorithm then calculates the most likely pathway connecting those

1. Smith JS, Chang EF, Lamborn KR, et al., Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas, J Clin Oncol, 2008;26:1338–45.

2. Claus EB, Horlacher A, Hsu L, et al., Survival rates in patients with low-grade glioma after intraoperative magnetic resonance image guidance, Cancer, 2005;103:1227–33.

3. Ahmadi R, Dictus C, Hartmann C, et al., Long-term outcome In that study, however, patients receiving 5-ALA

regions (see Figure 7). DTI can be performed on most modern MRI scanners. DTI-based tractography is commonly used to define the pyramidal tract10,37–39 pathways41,42

and, to a lesser extent, language40 and subcortical areas.

MEG measures tiny magnetic fields outside of the head that are generated by neural activity. Because it measures these fields directly, MEG offers excellent temporal resolution (<1 ms). Furthermore, magnetic fields are unimpeded by biological tissue, so MEG recordings offer an undistorted signature of underlying neural activity. MEG scanners, however, are expensive and relatively rare, so MEG is less widespread than MR-based techniques. MEG studies are useful for localization of sensory, motor43

(see Figure 8), and language regions (see Figure 9).44 They are also used to localize seizure foci, which is often helpful in the management of epileptogenic tumors such as oligodendrogliomas.

TMS is a technique that uses an externally applied, highly focused, brief magnetic pulse that is of sufficient strength to induce a depolarization in the underlying neuronal units. Depending on the frequency and location of the pulse, it can either cause neuronal excitability or have a temporary lesion effect. Navigated TMS, in which the magnetic pulses are guided by a co-registered, pre-operative MRI scan, allows for highly accurate mapping of the motor system (see Figure 10). TMS is frequently used in the management of peri-Rolandic tumors, where the pyramidal tract is at highest risk of disruption from surgical resection.

Each of these four modalities can offer valuable information in the pre-operative period, assisting in planning of the surgical approach, delineating the location of the tumor with respect to eloquent brain regions, and informing pre-operative discussions with patients regarding expected risks and post-operative course. However, they are highly valuable intra-operatively as well. Each of these modalities can be co-registered to a structural MRI scan and uploaded to a frameless stereotactical intra-operative neuronavigational system. With the functional imaging data thus integrated into the intra-operative navigation, it becomes a powerful tool for identifying in real time those regions that have been pre-operatively identified with a given functional study. While these techniques lack the accuracy of direct electrocortical stimulation mapping (see Figure 9c–d), they are increasingly useful adjuncts in the operative management of gliomas.


Intra-operative imaging is playing an increasing role in the surgical management of gliomas. Current techniques allow the surgeon to define functional brain regions, navigate accurately during the surgical resection, identify critical structures, and maximize the extent of resection while preserving function. As these modalities become increasingly refined and complex, a thorough understanding of their advantages and limitations will lead to better outcomes for patients. n

and survival of surgically treated supratentorial low-grade glioma in adult patients, Acta Neurochir (Wien), 2009;151:1359–65.

4. Chaichana KL, McGirt MJ, Laterra J, et al., Recurrence and malignant degeneration after resection of adult hemispheric low-grade gliomas, J Neurosurg, 2010;112:10–7.

5. Sanai N, Polley MY, McDermott MW, et al., An extent of resection threshold for newly diagnosed glioblastomas,

J Neurosurg, 2011;115:3–8.

6. Warnke PC, Stereotactic volumetric resection of gliomas, Acta Neurochir Suppl, 2003;88:5–8.

7. Krishnan R, Raabe A, Hattingen E, et al., Functional magnetic resonance imaging-integrated neuronavigation: correlation between lesion-to-motor cortex distance and outcome, Neurosurgery, 2004;55:904–14; discussion 914–5.

and visual in patients with lesions in proximity to eloquent cortical



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