Radiology Section - Magnetoencephalography/Magnetic Source Imaging (MSI)

IMPORTANT REMINDER

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PLEASE NOTE: Contracts exclude from coverage, among other things, services or procedures that are considered investigational or cosmetic. Providers may bill members for services or procedures that are considered investigational or cosmetic. Providers are encouraged to inform members before rendering such services that the members are likely to be financially responsible for the cost of these services.

DESCRIPTION

Magnetoencephalography (MEG) is a noninvasive functional imaging technique in which the weak magnetic forces associated with the electrical activity of the brain are recorded externally on the scalp. Using mathematical modeling, the recorded data are then analyzed to provide an estimated location of the electrical activity. This information can be superimposed on an anatomic image of the brain, typically a magnetic resonance imaging scan (MRI), to produce a functional/anatomic image of the brain, referred to as magnetic source imaging or MSI. The primary advantage of MSI is that while the conductivity and thus measurement of electrical activity as recorded by the electro-encephalogram (EEG) is altered by surrounding brain structures, the magnetic fields are not.  This results, for instance, in better spatial localization of epileptic foci detected by MEG as compared with surface EEG, which can produce distorted signals.  However, MEG has some limitations as well, since magnetic fields generated deep within brain tissues decay rapidly over distance and may be less likely to be detected at the surface compared with electrical fields.  Therefore, surface EEG and MEG are often considered complimentary technologies.

The technique itself is extremely sophisticated. Detection of the weak magnetic fields depends on gradiometer detection coils coupled to a superconducting quantum interference device (SQUID), which in turn requires a specialized room, shielded from other magnetic sources. Mathematical modeling programs based on idealized assumptions are then used to translate the detected signals into functional images. In its early evolution, clinical applications were limited by the use of only one detection coil requiring lengthy imaging times, which, because of body movement, were also difficult to coordinate with the MRI. However, more recently the technique has evolved to multiple detection coils arranged in an array that can provide data more efficiently over a wide extracranial region.

One clinical application is localization of the pre- and postcentral gyri as a guide to surgical planning in patients scheduled to undergo neurosurgery for epilepsy, brain neoplasms, arteriovenous malformations, or other brain disorders.  These gyri contain the “eloquent” sensorimotor areas of the brain involved in sensory, motor or language function.  The preservation of these areas is considered critical during any type of brain surgery. In normal situations, these areas can be identified anatomically by MRI, but frequently the anatomy is distorted by underlying disease processes. In addition, the location of eloquent functions is variable even among healthy patients. Therefore, localization of eloquent cortex often requires such intraoperative invasive functional techniques as cortical stimulation under local anesthesia or somatosensory-evoked responses on electrocorticography (ECoG). While these techniques can be done at the same time as the planned resection, they are cumbersome and can add up to 45 minutes of anesthesia time. Furthermore, sometimes these techniques can be limited by the small surgical field.  An additional presurgical test that is often used to localize the eloquent hemisphere is the intracarotid amobarbital test (Wada test),   MEG/MSI has been proposed as a substitute for the invasive Wada test.

Another related clinical application of MEG/MSI is localization of epileptic foci, particularly for screening of surgical candidates and surgical planning. Alternative techniques include MRI, positron emission tomography (PET), or single photon emission computed tomography (SPECT) scanning. Anatomic imaging (i.e., MRI) is effective when epilepsy is associated with a mass lesion, such as a tumor, vascular malformations, or hippocampal atrophy. If an anatomic abnormality is not detected, patients may undergo a PET scan. In a small subset of patients, extended electrocorticography (ECoG) or stereotactic electroencephalography (SEEG) with implanted electrodes are considered the gold standards for localizing epileptogenic foci. MEG/MSI was principally investigated as an alternative to invasive monitoring.

MSI has also been used as a research tool in the investigation of dyslexia, psychiatric disorders, functional evaluation of the gastrointestinal tract, diagnosis of mesenteric ischemia, and evaluation of uterine contractions in pregnancy.

POLICY/CRITERIA

1. Magnetoencephalography and magnetic source imaging for the purpose of determining the laterality of language function, as a substitute for the Wada test, in patients being prepared for surgery for epilepsy, brain tumors, and other indications requiring brain resection, may be considered medically necessary.
   
   
2. Magnetoencephalography and magnetic source imaging are considered investigational for all other indications, including but not limited to localization of seizure focus for patients undergoing evaluation for surgical treatment of intractable seizures.

POSITION STATEMENT

Ideally, randomized trials comparing the outcomes of patients who received magnetoencephalography (MEG) as part of their diagnostic workup compared to patients who did not receive MEG could determine whether MEG improves patient outcomes. However, almost all of the studies evaluating MEG have been retrospective studies, where MEG, other tests, and surgery have been selectively applied to patients. Since patients often drop out of the diagnostic process before having intra-cranial electroencephalogram (IC-EEG), and many patients ultimately do not undergo surgery, most studies of associations between diagnostic tests and between diagnostic tests and outcomes are irreparably biased by selection and ascertainment biases. For example, studies evaluating the correlation between MEG and IC-EEG invariably did not account for the fact that MEG information was used to deselect a patient from undergoing IC-EEG. In addition, IC-EEG findings only imperfectly correlated with surgical outcomes, meaning that it was an imperfect reference standard.

Numerous studies have shown associations between MEG findings and other noninvasive and invasive diagnostic tests including IC-EEG, and between MEG findings and surgical outcomes. However, such studies do not allow any conclusions regarding whether MEG added incremental information to aid the management of such patients, and whether patients’ outcomes were improved as a result of the additional diagnostic information.

Localization of Seizure Focus

This section is based on a 2008 TEC Special Report reviewing the evidence regarding MEG for localization of epileptic lesions. (2) MEG has been proposed as a method for localizing seizure foci for patients with normal or equivocal MRI and negative video-EEG examinations, so-called “nonlesional” epilepsy. Such patients often undergo MEG, positron emission tomography (PET), or ictal-SPECT (single photon emission computed tomography) tests to attempt to localize the seizure focus. They then often undergo invasive IC-EEG, a surgical procedure in which electrodes are inserted next to the brain. MEG would be considered useful if, when compared to not using MEG, it improved patient outcomes. Such improvement in outcomes would include more patients being rendered seizure-free, use of a less invasive and morbid diagnostic workup, and increased surgical success rates. This is a complicated array of outcomes that has not thoroughly been evaluated in a comprehensive manner.

A representative study of MEG by Knowlton and colleagues demonstrated many of the problematic issues of evaluating MEG. (3) In this study of 160 patients with nonlesional epilepsy, all had MEG, but only 72 proceeded to IC-EEG. The calculations of diagnostic characteristics of MEG were biased by incomplete ascertainment of the reference standard. However, even examining the diagnostic characteristics of MEG using the 72 patients who underwent IC-EEG, sensitivities and specificities were well below 90%, indicating the likelihood of both false-positive and false-negative studies. Predictive values based on these sensitivities and specificities mean that MEG can neither rule in nor rule out a positive IC-EEG, meaning that MEG cannot be used as a triage test before IC-EEG to avoid the potential morbidity in a subset of patients.

Several studies correlated MEG findings to surgical outcomes. Lau and colleagues performed a meta-analysis of 17 such studies. In this meta-analysis, sensitivity and specificity had unorthodox definitions. (4) Sensitivity was defined as the proportion of patients cured with surgery in whom the MEG-defined epileptic region was resected, and specificity was the proportion of patients not cured with surgery in whom the MEG-defined epileptic region was not resected. The pooled sensitivity was 0.84, meaning that among the total number of cured patients, 14% occurred despite the MEG-defined region not being resected. Pooled specificity was 0.52, meaning that among 48% of patients not cured, the MEG-localized region was resected. These results are consistent with an association between resection of the MEG-defined region and surgical cure, but it is an imperfect predictor of surgical success. The analysis did not address the question of whether MEG contributed original information to improve the probability of cure.

In summary, the use of MEG in studies to select and deselect patients in the diagnostic pathway resulted in deficiencies in the literature, primarily ascertainment and selection biases.  These deficiencies make it difficult to determine whether use of MEG for the purpose of seizure localization improves patient outcomes.

Localization of Eloquent and Sensorimotor Areas

The determination of the laterality of the language function is important to know to determine the suitability of a patient for surgery and what types of additional functional testing might be needed prior to or during surgery. There are two ways to analyze the potential utility of MEG for this indication. MEG could potentially be a noninvasive substitute for the Wada test, which is a standard method of determining hemispheric dominance for language. The Wada test requires catheterization of the internal carotid arteries, which carries the risk of complications. If MEG provided concordant information with the Wada test, then such information would be obtained in a noninvasive manner.

In a 2003 TEC Assessment of MEG, the evidence for this indication concluded that the evidence was insufficient to demonstrate efficacy. (5) At that time, the studies reviewed had relatively weak study methods and very limited numbers of subjects. Since the 2003 TEC assessment, several studies have shown high concordance between the Wada test and MEG. In the largest study by Papanicolaou and co-workers among 85 patients, there was concordance between the MEG and Wada tests in 74 (87%). (6) In no cases were the tests discordant in a way that the findings were completely opposite. The discordant cases occurred mostly where the Wada test indicated left dominance and the MEG indicated bilateral language function. In an alternative type of analysis where the test was being used to evaluate the absence or presence of language function in the side in which surgical treatment was being planned, using the Wada procedure as the gold standard, MEG was 98% sensitive and 83% specific. Thus, if the presence of language function in the surgical site required intraoperative mapping and/or a tailored surgical approach, use of MEG rather than Wada would have “missed” one case where such an approach would be needed, and resulted in five cases in which such an approach was unnecessary (false-positive MEG). It should be noted, however, that the Wada test is not a perfect reference standard, and some discordance may reflect inaccuracy of the reference standard. In another study by Hirata and colleagues MEG and the Wada test agreed in 19/20 (95%) of cases. (7)

The other potential use of MEG would be for the purpose of mapping the sensorimotor area of the brain, again to avoid such areas in the surgical resection area. Intraoperative mapping just before resection is generally done as the reference standard. Preoperative mapping as potentially done by MEG might aid in determining the suitability of the patient for surgery, or for assisting in the planning of other invasive testing. Similar to the situation for localization of epilepsy focus, the literature is problematic in terms of evaluating the comprehensive outcomes of patients due to ascertainment and selection biases. Studies tended to be limited to correlations between MEG and intraoperative mapping. The intraoperative mapping would be performed anyway in most resection patients. Several of the studies evaluated in the 2003 TEC Assessment showed good to high concordance between MEG findings and intraoperative mapping. A technology assessment on functional brain imaging performed by the Ontario Ministry of Health reviewed ten studies of MEG and invasive functional mapping and showed good to high correspondence between the two tests. (8) However, these studies did not demonstrate that MEG would replace intraoperative mapping or reduce the morbidity of such mapping by allowing a more focused procedure.

Practice Guidelines

American College of Neurology

At this time, the AAN’s 2003 clinical practice guidelines are being updated and are not available. In 2009, the Medical Economics and Management Committee (MEM) of the American Academy of Neurology (AAN) published a model medical policy for MEG. (9) This model policy reported the results of a number of clinical trials but did not provide a critical analysis of the quality of the studies. Nor did the model policy describe the process by which the evidence was used to reach conclusions. For example, the AAN concluded that the Knowlton and colleagues article (3) demonstrated the value of MEG for localization of seizure foci in spite of the low sensitivity, specificity, positive- and negative-predictive values (72%, 70%, 78% and 64%, respectively).

American College of Radiology

In a 2006 update of their epilepsy practice guidelines, the ACR made the following conclusion: “Available data indicate that interictal MEG can be an effective tool for localization of seizure foci in patients with medical refractory partial epilepsy. Significant shortcomings include limited availability, high cost, and assessment limited to relatively superficial and tangential sources. Nonetheless, MSI does provide unique, accurate, and useful information about epileptogenic regions in the brain, and where available, has a potential role in the diagnostic workup of most patients with epilepsy. does provide unique, accurate, and useful information about epileptogenic regions in the brain, and where available, has a potential role in the diagnostic workup of most patients with epilepsy”. (10)

REFERENCES

1. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 6.01.21
2. BlueCross BlueShield Association Technology Evaluation Center 2008 Special Report.  Magnetoencephalography and Magnetic Source Imaging for the Purpose of Presurgical Localization of Epileptic Lesions—A Challenge for Technology Evaluation. Available online at http://www.bcbs.com/blueresources/tec/vols/23/special-report-meg-and-msi.html (Verified 6/29/09)
3. Knowlton RC, Elgavish RA, Limdi N et al. Functional imaging: I. Relative predictive value of intracranial electroencephalography. Ann Neurol 2008;64(1):25-34
4. Lau M, Yam D, Burneo JG. A systematic review on MEG and its use in the presurgical evaluation of localization-related epilepsy. Epilepsy Res 2008;79(2-3):97-104
5. BlueCross BlueShield Association Technology Evaluation Center TEC Assessment. MEG and MSI: Presurgical localization of epileptic lesions and presurgical functional mapping. 2003; Vol 18, Tab 6
6. Papanicolaou AC, Simos PG, Castillo EM et al. Magnetoencephalography: a noninvasive alternative to the Wada procedure. J Neurosurg 2004;100(5):867-76
7. Hirata M, Kato A, Taniguchi M, et al.  Determination of language dominance with synthetic aperture magnetometry: comparison with the Wada test.  Neuroimage 2004;23(1):46-53
8. Ontario Ministry of Health, Medical Advisory Secretariat (MAS). Functional brain imaging. Health Technology Policy Assessment. Toronto, ON: MAS; December 2006. Available online at: http://www.health.gov.on.ca/english/ providers/program/mas/tech/reviews/sum_fbi_012507.html (Verified 6/29/09)
9. American Academy of Neurology. Magnetoencephalography (MEG) Policy, 2009. Available online at: http://www.aan.com/globals/axon/assets/5641.pdf (Verified 6/29/09)
10. Karis JP, Seidenwurm DJ, Davis PC, et al. American College of Radiology. ACR Appropriateness Criteria® epilepsy. 2006. Available online at: http://www.guideline.gov/summary/summary.aspx?doc_id=10604&nbr= 005546&string=magnetoencephalography (Verified 6/29/09)

Cross References

None

Radiology Section Table of Contents