Coverage Policy Manual
Policy #: 2007001
Category: Radiology
Initiated:
Last Review: July 2018
  Magnetic Resonance Imaging (MRI), Functional

Description:
Before neurologic surgery for seizure disorders or resection of brain tumors, localization of certain areas of the brain, such as speech centers, is important. For example, from 25% to 60% of patients who undergo left anterior temporal lobectomy develop dysnomia (language/naming difficulties). Most often these “eloquent” areas are assessed using the Wada test and direct electrical stimulation. Both of these tests are invasive and require involvement of various specialists. Direct intracortical electrical stimulation involves functional mapping of the exposed cortex with electrodes, which may elicit a motor or verbal response including arrest of speech, random answering, or perseveration to stimulation. The Wada test is an inactivating method that blocks the function of one hemisphere by injection of amobarbital into the carotid artery, allowing functional testing of the reserve capacity of the nonanesthetized hemisphere.
 
fMRI is an activation method that uses sequences based on T2-weighted blood oxygen level-dependent (BOLD) response. These studies are often done on MR scanners with field strengths of 1.5 Tesla or greater. The interhemispheric difference between activated volumes in the left and right hemispheric regions of interest is calculated as the laterality index (LI), which ranges from -1 to 1. A positive LI is considered left-dominant, while a negative LI is right-dominant. FMRI-determined LIs may be derived for several different functional areas (regions of interest) that include either Broca area (language production) or Wernicke area (language comprehension). Various thresholds (eg, -0.1 to +0.1, or -0.5 to +0.5) have been proposed to differentiate laterality from bilaterality. Bilateral activation patterns can result from the
detection of language-associated, but not language-essential cortex. Therefore, bilateral activation is not necessarily indicative of a bilateral distribution of language-essential cortex and may be task-dependent. In addition, sensitivity and specificity may change with the application of different statistical thresholds. Simultaneous EEG-fMRI is being investigated for the localization of seizures. EEG-fMRI combines the temporal resolution of EEG and the spatial resolution of fMRI. Simultaneous EEG-fMRI may allow the detection of cerebral hemodynamic changes associated with seizures and interictal epileptiform discharges that are identified on scalp EEG. Another potential use of EEG-fMRI is to facilitate the implantation strategy of invasive subdural electrodes.
 
Regulatory Status
There are several fMRI hardware (eg, fMRI Hardware System, NordicNeuroLab AS) and fMRI software packages (eg, BrainAcquireRx™/ BrainProcessRx™ Data Suite, Kyron Clinical Imaging, Inc.) with 510(k) marketing clearance from the U.S. Food and Drug Administration for use in conjunction with a magnetic resonance imaging scanner to perform fMRI. FDA Product Code: LNH
 
Coding
There is CPT coding specific to functional MRI.  The codes differentiate between circumstances when a physician or psychologist does all of the functional testing and when the testing is done by other professionals.
 
70554: Magnetic resonance imaging, brain, functional MRI; including test selection and administration of repetitive body part movement and/or visual stimulation, not requiring physician or psychologist administration
 
70555: Magnetic resonance imaging, brain, functional MRI; requiring physician or psychologist administration of entire neurofunctional testing
 
The physician or psychologist who administers the testing would use the following CPT code:
 
96020: Neurofunctional testing selection and administration during noninvasive imaging functional brain mapping, with test administered entirely by a physician or psychologist, with review of test results and report.
 

Policy/
Coverage:
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Functional MRI meets primary coverage criteria for effectiveness and is covered in the preoperative evaluation of patients with seizures or brain tumors who are candidates for neurosurgical therapy when the results of the functional MRI will obviate the need for either the Wada test or direct electrical stimulation.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
  
The use of functional MRI in any other circumstance than what is listed above, including but not limited to the evaluation of dementia, Alzheimer’s disease and mental disease, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For contracts without primary coverage criteria, the use of functional MRI in any other circumstance than what is listed above, including but not limited to the evaluation of dementia, Alzheimer’s disease and mental disease,  is considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:
Studies ( Medina) have summarized the high degree of concordance of language lateralization of functional MR imaging and either Wada test or direct electrical stimulation.  In this summary, functional MRI was concordant with the Wada test in 78 of 83 (94%) cases and with direct electrical stimulation in 23 of 26 (88%) cases.
 
Sabsevitz and colleagues reported on a series of 24 consecutive patients who underwent both functional MRI and Wada testing before left anterior temporal lobectomy for seizure disorders. While both tests were predictive of language changes, in this study functional MRI had a sensitivity of 100% and specificity of 57% while results for the Wada test were 100% and 43% respectively.
 
Medina and colleagues evaluated 60 consecutive patients prior to surgery.  In 53 patients language mapping was performed, in 33 motor mapping, and in 7 visual mapping. The functional MRI study revealed change in anatomic location or lateralization of language-receptive (Wernicke) in 28% of patients and in language-expressive (Broca) in 21%. In 38 (63%) patients, functional MRI helped to avoid further studies, including Wada test. In 31 (52%) and 25 (42%) of the patients, intraoperative mapping and surgical plans were altered because of functional MRI results.
 
Petrella and colleagues reported on the impact of functional MRI preoperatively on 39 consecutive patients with brain tumors.   In four patients, additional tests, e.g. the Wada test, were not ordered because of the functional MRI result. Treatment plans differed in 19 patients after functional MRI with a more aggressive approach recommended after imaging in 18 patients. However, the impact of the altered treatment plans on patient outcome was not assessed. Functional MRI resulted in reduced surgical time for 22 patients; it also led to decisions to perform crainiotomy in 13 patients where less invasive approaches had been initially planned.
 
Thus, studies show that functional MRI is comparable to the Wada test and direct electrical stimulation in localizing certain eloquent functions; although there are less data for direct electrical stimulation. In patients who are to undergo neurosurgery for seizures or brain tumors, functional MRI may obviate the need for these tests. However, the impact of function MRI on other outcomes in these patients is uncertain.
 
2007-2008 Update
A search of the MEDLINE database was performed for the period of December 2006 through January 2008. Current research appears to focus on improving and establishing standardized protocols for  presurgical evaluation of the eloquent cortex. One report described a routine preoperative functional MRI protocol in 81 consecutive patients(70 with tumors on the left side and11 with tumors on the right side and language deficits) (Stippich et al, 2007).  Patients were trained to recall simple sentences (picture cues) or to generate words in a category (word cues). Although 11 patients were not able to complete the more cognitively demanding word generation task, the combination of tasks allowed localization of both the Broca and Wernicke areas and determination of hemispheric language dominance in 79 (98%) patients.  Surgical plans were modified in 9 patients based on the functional MRI findings (7 patients underwent radiation therapy instead of surgery and 2 patients had partial resection of large malignant gliomas). Results of the surgeries were not described. The authors noted that although functional MRI is capable of localizing the center of a functional area, resection borders cannot be reliably determined by this technique.
 
In another report the preoperative localization of epileptic focus was assessed in 29 complex cases (unclear focus and/or multifocality) that had been rejected for epilepsy surgery. (Ziijlmans et al, 2007) Patients were included in the study if they had no contraindications for MRI, had more than 10 interictal discharges in 40 minutes of previously recorded electroencephalogram (EEG), and if the reason for rejection was the inability to localize a single source with EEG. Functional MRI (fMRI) results were considered robust if a consensus-defined interictal electrical discharge was associated with a significant positive blood oxygen level-dependent (BOLD) response. In 8 (28%) patients, a robust functional MRI response was considered to be topographically related to interictal electrical discharges. The EEG-functional MRI findings improved localization in 4 of 6 unclear foci and advocated one of multiple foci in another patient; in 4 other patients multiple foci were confirmed. As a result of the testing, 4 patients (14%) were considered to be surgical candidates and 1 of the 4 had undergone surgery at the time of the publication.  The authors of the European-based study describe this as the first report of the clinical use of EEG-functional MRI.  Although promising, the use of functional MRI to localize epileptic foci requires additional study.
 
2009 Update
A literature update for the period of February 2008 through April 2009 was performed using the MEDLINE database. Several studies were identified that assessed language lateralization with fMRI in comparison with the Wada test or intraoperative electrocortical mapping.
 
Bizzi and colleagues assessed the sensitivity and specificity of fMRI for mapping language and motor functions using intraoperative intracortical mapping as the reference standard (Bizzi et al, 2008).  Thirty-four consecutive patients with a focal mass adjacent to eloquent cortex were included in the study. A site-by-site comparison between fMRI and intracortical mapping was performed with verb generation or finger tapping of the contralateral hand. A total of 251 sites were tested; 141 in patients evaluated with verb generation and 110 in patients evaluated with finger tapping. For hand motor function alone, sensitivity and specificity were 88% and 87%, respectively. For language, sensitivity and specificity were 80% and 78%, respectively. Functional MRI for Broca’s area showed 100% sensitivity and 68% specificity, while Wernicke’s area showed 64% sensitivity and 85% specificity. Functional MR imaging sensitivity decreased from 93% for World Health Organization grade II gliomas to 65% for grade IV gliomas. Other authors reported that successful pre-operative fMRI decreased intracortical mapping time from about 50 minutes to 30 minutes, and total operative time from an average 8.5 hours to about 7 hours (Xie et al, 2008).
 
Wellmer et al. assessed whether currently recommended thresholds for the fMRI-lateralization index (LI) allowed identification of atypical dominant patients (i.e., not left-dominant) with sufficient safety for presurgical settings (We;,er et a. 2008). Out of 65 patients who had presurgical workup for epilepsy surgery, 22 were identified as atypical dominant by the Wada test. Lateralization indices were calculated for 3 functionally determined regions of interest comprising Broca’s area, a prefrontal area outside Broca’s, and temporoparietal cortex overlapping with the Wernicke area. In patients in whom the Wada  test results were compatible with typical left dominance, the fMRI-LI ranged from 1 to -0.61. Among patients with atypical language dominance according to the Wada test, fMRI-LI of the frontal and temporo-parietal regions of interest ranged from 1 to -1. Depending on the chosen LI-threshold for unilateral language dominance, between 2 and 5 patients (9% and 23%) out of this sample of atypical dominant patients would have been misclassified as typical dominant. Another study compared presurgical mapping by fMRI with either verb generation or semantic decision/tone decision and the Wada test in 28 patients with epilepsy (Szaflarski et al, 2008).  The  study found moderate correlation between the 2 tasks and between the language tasks and the Wada test.  It was estimated that the
language tasks explained approximately 58% of the variability of the Wada test with moderate convergent validity. With a LI threshold of + 0.25, 8 of the 28 patients (29%) may have been misclassified based on fMRI alone.
 
Another study assessed the language laterality index across different statistical thresholds in 13 patients with brain tumor and 7 controls; results were not compared with the Wada test (Ruff et al, 2008).  In both groups, the language LI varied as a result of statistical thresholding, presence of tumor, prior surgery, and language task. Three patients demonstrated a shift in the LI between hemispheres as a function of statistical threshold. The study found no optimal threshold for reliably determining the LI.
 
Overall, the literature indicates that fMRI is complementary to the Wada test and direct electrical stimulation in localizing certain eloquent functions. Evidence suggests that although bilateral activation patterns in fMRI cannot be conclusively interpreted, fMRI in patients who are to undergo neurosurgery for seizures or brain tumors may help to define eloquent areas, reduce surgical time and alter treatment decisions.
 
2012 Update
A literature search was conducted using the MEDLINE database through June 2012.  There was no new literature identified that would prompt a change in the coverage status. The following is a summary of the identified relevant publications.
 
In 2011, Dym et al. reported a meta-analysis of fMRI determined lateralization of language function compared to the Wada test (Dym, 2011). Inclusion criteria were examination of the same patients with both fMRI and the Wada test; preoperative examination of at least 4 patients; and reporting of the concordance in individual patients. Twenty-three studies with a total of 442 patients were included in the meta-analysis. Language dominance for each patient was classified as typical (left hemispheric language dominance) or atypical (right hemispheric language dominance or bilateral language representation), with most studies using a lateralization index threshold of 0.2. Sensitivity was defined as the ability of functional MRI (fMRI) to depict atypical language representation, and specificity was the ability of fMRI to depict typical language representation. Most of the studies did not specify whether the evaluators were blinded to the results of the other test. With the Wada test as the reference standard, fMRI had a sensitivity of 83.5% and specificity of 88.1%. Specificity was significantly higher with use of a word generation task (95.6%) than with a semantic decision task (69.5%). This analysis may oversimplify the role of fMRI, which in addition to providing information on hemispheric dominance, provides information on the localization of language and motor areas in relation to the tumor or lesion. It is also unlikely that current fMRI protocols utilize a single task (e.g., word generation) to evaluate the eloquent cortex.
 
Moeller et al. reported an EEG-fMRI study for the work-up of 9 patients with refractory frontal lobe epilepsy who did not have a clear lesion or seizure focus (Moeller, 2009). A minimum of 10 interictal discharges in 60 minutes in previously recorded scalp EEGs was required to be in the study, and the number of interictal discharges recorded during the fMRI session ranged from 9 to 744. There was concordance between spike localization and positive BOLD response in 8 of the patients and positron emission tomography (PET) and single-photon emission computed tomography (SPECT) results corresponded with BOLD signal changes in 6 of 7 studies. Surgery was subsequently performed on 2 patients, one of whom was seizure-free at the time of publication.
 
A 2011 multicenter study compared presurgical interictal discharge-related BOLD signal changes with intracranial EEG and postoperative outcome in 23 patients with refractory epilepsy (Thornton, 2011). The 23 patients were selected for analysis based on a diagnosis of focal cortical dysplasia from structural MRI or histology out of 65 patients who were undergoing presurgical evaluation for refractory focal epilepsy. The EEG-fMRI results were not used in the planning of intracranial EEG or surgical resections. Twelve of the 23 patients (52%) had interictal discharges during EEG-fMRI recording, and 11 of the 12 (92%) had significant interictal discharge-related hemodynamic changes. In the 11 patients with a BOLD response, fMRI results were concordant with the intracranial EEG-determined seizure onset zone in 5 patients (45%), and the majority (4 of the 5) had a 50% or greater reduction in seizure frequency following resective surgery. The other 6 of 11 patients had widespread or discordant regions of fMRI signal change, and the majority (n=5) had either a poor surgical outcome or a widespread seizure onset zone that precluded surgery. This study is described as the first prospective systematic evaluation of the potential role of EEG-fMRI in the presurgical evaluation of patients with focal cortical dysplasia. It should be considered exploratory.
 
2013 Update
A literature search conducted using the MEDLINE database through June 2013 did not reveal any new information that would prompt a change in the coverage statement.
 
 
2015 Update
A literature search conducted using the MEDLINE database did not reveal any new information that would prompt a change in the coverage statement.
 
2017 Update
A literature search conducted using the MEDLINE database did not reveal any new literature that would prompt a change in the coverage statement.
 
2018 Update
A literature search was conducted through June 2018.  There was no new information identified that would prompt a change in the coverage statement.

CPT/HCPCS:
70554Magnetic resonance imaging, brain, functional MRI; including test selection and administration of repetitive body part movement and/or visual stimulation, not requiring physician or psychologist administration
70555Magnetic resonance imaging, brain, functional MRI; requiring physician or psychologist administration of entire neurofunctional testing
96020Neurofunctional testing selection and administration during noninvasive imaging functional brain mapping, with test administered entirely by a physician or other qualified health care professional (ie, psychologist), with review of test results and report

References: Ruff IM, Petrovich Brennan NM et al.(2008) Assessment of the language laterality index in patients with brain tumor using functional MR imaging: effects of thresholding, task selection, and prior surgery. AJNR Am J Neuroradiol 2008; 29(3):528-35.

Zijlmans M, Huiskamp G, Hersevoort M et al.(2007) EEG-fMRI in the preoperative work-up for epilepsy surgery. Brain 2007; 130(Pt 9):2343-53.

American College of Radiology.(2007) Practice guideline for the performance of functional magnetic resonance imaging of the brain (fMRI). Available at: http://www.acr.org/SecondaryMainMenuCategories/quality_safety/guidelines/dx/head-neck/fmri.aspx. Last viewed May 2009.

Bizzi A, Blasi V, Falini A et al.(2008) Presurgical functional MR imaging of language and motor functions: validation with intraoperative electrocortical mapping. Radiology 2008; 248(2):579-89.

Dym RJ, Burns J, Freeman K et al.(2011) Is functional MR imaging assessment of hemispheric language dominance as good as the Wada test?: a meta-analysis. Radiology 2011; 261(2):446-55.

Medina LS, Pernal B, et al.(2005) Seizure disorders: Functional MRI imaging for diagnostic evaluation and surgical treatment - prospective study. Radiology, 2005, 236:247-53.

Moeller F, Tyvaert L, Nguyen DK et al.(2009) EEG-fMRI: adding to standard evaluations of patients with nonlesional frontal lobe epilepsy. Neurology 2009; 73(23):2023-30.

Petrella JR, Shah LM, et al.(2006) Preoperative functional MRI imaging localization of language and motor areas: Effect on therapeutic decision making in patients with potentially resectable brain tumors. Radiology, 2006; 240:793-802.

Sabsevitz DX, Swanson SJ, et al.(2003) Use of preoperative functional neuroimaging to predict language deficits from epilepsy surgery. Neurology, 2003; 60:1788-92.

Stippich C, Rapps N, Dreyhaupt J et al.(2007) Localizing and lateralizing language in patients with brain tumors: feasibility of routine preoperative functional MR imaging in 81 consecutive patients. Radiology 2007; 243(3):828-36.

Szaflarski JP, Holland Sk, Jacol LM et al.(2008) Comprehensive presurgical funcitonal MRI language evaluation in adult patients with epilepsy. Epilepsy Behav 2008; 12(1):74-83.

Thornton R, Vulliemoz S, Rodionov R et al.(2011) Epileptic networks in focal cortical dysplasia revealed using electroencephalography-functional magnetic resonance imaging. Ann Neurol 2011; 70(5):822-37.

Wellmer J, Weber B, Weis S et al.(2008) Strongly lateralized activation in language fMRI of atypical dominant patients-implications for presurgical work-up. Epilepsy Res 2008; 80(1):67-76.

Whiting P, Gupta R, Purch J, et al.(2006) A systematic review of the effectiveness and cost-effectiveness of neuroimaging assessments used to visualize the seizure focus in people with refractory epilepsy being considered for surgery. c

Xie J, Chen XZ, Jiang T et al.(2008) Preoperative blood oxygen level-dependent functional magnetic resonance imaging in patients with gliomas involving the motor cortical areas. Chin Med J (Engl) 2008; 121(7):631-5.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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