**2. fMRI and DTI methodology and limitations**

Depiction of the classic surface anatomy of the brain has proven to be useful in native (non-lesional) cases, where anatomy is undistorted by pathological processes. High-resolution, thin-cut T2-weighted, FLAIR, and MPRAGE sequences provide a detailed morphological map to establish eloquent regions of the brain. Eloquent regions specifically refer to primary areas of the cerebral cortex which carry a distinct function which cannot be simply substituted by other areas or neuronal circuitry, including: a) Primary sensorimotor cortex; b) Primary auditory cortex; c) Primary visual cortex; and d) Primary expressive language area (Broca's Area). Distortion of these regions by space-occupying lesions can pose challenges for even the most skilled surgeon to safely navigate the resection safely based on gross anatomical landmarks alone. In these situations, presurgical fMRI superimposed on MPRAGE sequences can help the surgeon to achieve three goals:


Limitations of BOLD fMRI are related to dependence of the technique to neurovascular coupling, hence any delays in hemodynamic response following neuronal activation leads to poor temporal resolution on fMRI with alterations

#### *Pre-Surgical and Surgical Planning in Neurosurgical Oncology - A Case-Based Approach… DOI: http://dx.doi.org/10.5772/intechopen.99155*

of BOLD signal in regions of the brain with altered blood flow [10]. BOLD fMRI is task-related imaging and hence is subject to statistical rules and interpretation of data. Another use of BOLD signal application is resting-state fMRI (rs-fMRI), which does not require a stimulus or task and acquires spontaneous BOLD signal alterations [11]. Data acquisition occurs while the patient is at rest or by inferring resting-state data from periods of rest embedded within a series of tasks [12]. The lack of a need for a patient to perform tasks may overcome the limitations of BOLD fMRI in patients with neurologic, neurosurgical, and psychiatric conditions hence the growing popularity of the rs-fMRI for use in the clinical setting.

From early fMRI studies by Yetkin and colleagues, a now historic rule had been established that *the minimal safe distance between a lesion margin and the resection border should measure about 10 mm* [13]. This paradigm was established based on the observation that the rate of neurological deficits significantly increase when the distance between the margin and resection border falls below 10 mm [2]. It needs to be noted though, that this much quoted study result was significantly underpowered, thus not allowing to draw strong conclusions since these observations were obtained in a very small sized single center cohort with only a handful of patients entered in each group. Another criticism of the golden rule of a "must-respect minimal distance" comes from the fact that the observed BOLD signal in any given fMRI study represents the display of a **statistical threshold signal value** that can be arbitrarily set and adjusted by the fMRI analyst/investigator and that the underlying signal to noise ratio is profoundly dependent on a variety of technical factors as well as intraoperative scenarios (i.e., brain relaxation and progressive shift with resection). Vascular re-routing of blood by a lesion (commonly called "venous contamination") can also generate false signals that need to be accounted for. These can be assessed by a matching CTA/CTV scan.

One further aspect that was criticized in the past by fMRI skeptics is the lack of connectivity information in primary fMRI data which points to the fact that BOLD fMRI signal is a surface related signal of oxygen brain metabolism, not taking into account subcortical structures such as fiber tracts. As detailed above, the latter aspect can be remedied by simultaneous integration of modern DTI data. Once uploaded and fused on a single modern intraoperative neuronavigation platform (e.g., BrainLab; Stryker/Synaptiv) this adds the fiber tract component to the surgical planning step. This capability is especially valuable for deep seated intraaxial lesions such as gliomas which may be infiltrative to those tracts or in close topography to these essential structures. Another use of this imaging technology is the scenario, where surgical access to deep seated lesions is required and traversing the white matter is best accomplished via a route that minimizes damage to fibers running towards essential cortical regions.

A recent survey across American neurosurgical departments with a residency program assessing the surgeons' uses and experience with preoperative fMRI in surgical planning for neuro-oncology patients [14]. Indications and surgeons' preferences for using fMRI in pre-surgical planning were dominant hemisphere and functionally eloquent location of lesions, motor symptoms, and aphasia. Most common reasons for fMRI amongst surgeons surveyed included identifying language laterality (which yielded the highest interrater reliability), planning the extent of resection, and discussing surgical planning with patients. The majority of surgeons ordered fMRIs in patients with low- and high-grade gliomas (94% and 82%, respectively). However, 77% of surgeons resected an fMRI-positive functional site if it was "cleared" by cortical stimulation, and 98% of responders reported that if there was a discrepancy between fMRI and intraoperative mapping that they would rely on intraoperative mapping. There have been concerns about the sensitivity and specificity of fMRI, especially for language mapping, with sensitivity ranging from

59–100% and specificity ranging from 0–97% when compared across 9 published studies [15]. Tumors of oligodendroglioma subtype, tumor relative cerebral blood volume (CBV) > 1.5 on MR perfusion imaging, lower cortical CBV, and distance to tumor have also been shown to cause higher false-positive fMRI signals [16]. Southwell and colleagues presented another limitation of using pre-surgical fMRI planning in its inability to offer surgeons the ability to account for compensable areas that can be resected and critical areas that need to be preserved, leading to underselection of patients for surgery and increase the likelihood for achieving subtotal resections due to miscalculation of needing to preserve seeming critical areas [17]. They also achieved an average 90% resection with no new postoperative neurological deficits in a series of 58 glioma patient resections, further pointing out the limitations of fMRI [17].

Similarly, a study incorporating 96 individual surgical planning cases using DTI of ground-truth white matter tracts from 20 research groups found a high falsepositive rate with many of the tractograms representing more invalid than valid bundles [18]. This was further corroborated by a study by Mandelli and colleagues demonstrating relatively poor performance in differentiating lateral vs. medial projections [19]. Leclercq and colleagues compared DTI to intraoperative subcortical language mapping and found that while 17 out of 21 positive cortical stimulation sites corresponded to DTI tractograms, negative tractograms did not rule out the presence of white matter tracts [20]. Another study reported intraoperative image distortion in over one-third of cases, negating the use of DTI whilst favoring the use of cortical stimulation as the superior intraoperative mapping modality [21]. Finally, a prospective study randomizing 328 glioma patients to either DTI, 3D MRI, or routine neuronavigation reported a higher rate of GTR in higher-grade glioma patients, however, the increase in GTR was only reported in high-grade tumors whilst the neuronavigation in the control arm did not utilize cortical stimulation and the authors only reported outcomes for motor function [22]. These above studies serve to indicate that functional imaging modalities such as fMRI and DTI are still in their infancy and should be used as an adjunct along with more established tools such as neuronavigation and cortical stimulation.

### **3. Case illustrations**

#### **3.1 Case 1: 36 year-old male with a recurrent atypical parasagittal meningioma**

A 36 year-old male who had undergone a prior resection for a parasagittal meningioma 4 years ago at an outside institution was referred to our neurosurgical outpatient tumor clinic by radiation oncology with minimal gait abnormalities and a recurrent tumor in the same location. Pre-surgical post-contrast T1WI and CT demonstrated a large parasagittal contrast-enhancing lesion spanning the anterior to middle sections of the superior sagittal sinus (SSS, **Figure 1A**–**C**, yellow arrows). CT angiography reconstruction scans demonstrated significant occlusion of the SSS (**Figure 1D and E**, yellow arrows). fMRI scan localized the primary motor area (yellow) and the sensory area (green) just posterior to the lesion (**Figure 1F**–**I**), predicting likely success of resection as long as we remained anterior to these eloquent areas, only expecting a temporary supplementary motor area (SMA) syndrome. Surrounding venous anatomy was also taken into consideration during pre-surgical planning.

Thorough discussions with the patient regarding the spatial and anatomical relationships of his recurrent tumor to the functional eloquent regions of the brain, as shown on fMRI, were taken with an explanation of the risks of the surgery,

*Pre-Surgical and Surgical Planning in Neurosurgical Oncology - A Case-Based Approach… DOI: http://dx.doi.org/10.5772/intechopen.99155*

#### **Figure 1.**

*Recurrent atypical meningioma. Pre-op MRI A) sagittal, B) coronal, and C) axial T1WI post-contrast scans showing a large, en plaque, recurrent parasagittal meningioma. Pre-op CTA D) coronal and E) sagittal views showing occlusion of the anterior third of the superior sagittal sinus. Pre-op fMRI showing F) sagittal, G) coronal views of the primary sensorimotor cortex (yellow) and H) axial, and I) sagittal views of the left primary motor cortex innervating the right leg (green). Post-op MRI J) sagittal, K) coronal, and L) axial TWI post-contrast scans showing resection of the meningioma.*

including vascular injury to the sinus, and a post-operative SMA syndrome which would likely recover over the course of weeks. Surgery was recommended and the patient was taken to the operating room. A bilateral craniotomy was performed with intraoperative neuronavigation and the osseous midline bridge was dissected off. The SSS was tied off just anterior and posterior to the lesion, leaving the next surface draining veins intact. Surface mapping was used to confirm the motor strip location. A near gross total resection (GTR) was accomplished (**Figure 1J**–**L**) with a minimal 5 mm tumor cuff remaining which was encasing a draining vein in the posterior left SSS.

#### *Frontiers in Clinical Neurosurgery*

The patient woke up from surgery with a dense bilateral leg plegia, suggestive of a predicted SMA syndrome which recovered after 8 weeks requiring rehabilitation and physical therapy. He has since regained complete lower leg function and mobility at 6-months follow-up. Pathology came back WHO Grade II atypical meningioma. The patient was referred back to radiation oncology for post-operative stereotactic radiosurgery (SRS) to the tumor bed and the remaining cuff of tumor.
