In 2006, the Medical Advisory Secretariat received an application to review magnetoencephalography (MEG).  Soon after this request, the Medical Advisory Secretariat received an application to review magnetic resonance spectroscopy (MRS).  Rather than review these technologies discretely, the Medical Advisory Secretariat and the Ontario Health Technology Advisory Committee decided to review a spectrum of functional brain imaging technologies to identify whether there are imaging modalities that are more effective than others for various brain pathology conditions. This health technology policy assessment reviews MEG, MRS, positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions:  Alzheimer’s disease (AD), brain tumours, epilepsy, multiple sclerosis (MS) and Parkinson’s disease (PD).

AD is a progressive degenerative neurologic condition, which is characterized by cognitive impairments and memory loss.  The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (~60,000 women) of dementia (including AD) in Canada in 2006.

In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatment for brain tumours may include surgery and/or radiation therapy.  Radiation therapy damages tissue though necrosis and scarring.  Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging.

Epilepsy is a chronic disorder that provokes repetitive seizures.  In Ontario, the rate of epilepsy is estimated to be 5 cases per 1000. The majority of people with epilepsy are effectively managed with drug therapy, while approximately 30% of people with epilepsy do not respond to drug therapy. Surgical resection of the seizure foci may be considered in the refractory patients and functional brain imaging may play a role in localizing the seizure foci.

MS is a progressive inflammatory demyelinating disease of the central nervous system.  The cause of MS is unknown. It is expected to have a combination of aetiologies including both genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000.

Parkinson’s disease is the most prevalent movement disorder and affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes and response to therapy.

Functional brain imaging technologies measure blood flow and/or metabolism.  The results are often used in conjunction with structural imaging (i.e. MRI or CT).  PET and MRS identify abnormalities in brain tissues.  PET measures abnormalities through uptake of radiotracers in the brain, while MRS measures chemical shifts in metabolite ratios to identify abnormalities.  The potential role of fMRI is to identify the areas of language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. MEG measures magnetic fields of the electric currents in the brain, identifying aberrant activity. MEG may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex, language and auditory cortex.

In terms of regulatory status, MEG and PET are both licensed by Health Canada.  Both MRS and fMRI use a MRI platform, thus they do not have a separate licence from Health Canada.  The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application.

The literature published up to September 2006 was searched in the following databases:  MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and INAHTA.  The database search was supplemented with a search of relevant Web sites, and a review of the bibliographies of selected papers. 

General inclusion criteria were applied to all conditions.  Those criteria included:

• Full reports of systematic reviews, randomized controlled trials , cohort-control studies, prospective cohort studies, retrospective studies
• Sample sizes of at least 20 patients (>10 with condition being reviewed)
• English
• Human studies
• Any age
• Studying at least one of the following functional brain imaging modalities:  fMRI, PET, MRS, MEG
• Functional brain imaging modality must be compared with a clearly defined reference standard
• At least level 2 on the Fryback & Thornbury hierarchy
• Must report at least 1 of the following outcomes:  sensitivity, specificity, accuracy, positive predictive value, receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health or cost.

There is evidence to indicate that PET can accurately diagnose AD. However, at this time there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients.

The addition of MRS or O-(2-18F-Fluoroethyl)-L-Tyrosine (FET)-PET to Gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis, may provide a higher specificity than Gd-enhanced MRI alone.  The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results. 

The addition of MRS, FET-PET or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone.  The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of patients.  Based on the evidence available, it is unclear if one of the imaging modalities (MRS, FET-PET or MRI T2) offers significantly improved specificity over another.

There may be a role for fMRI in the identification of surgical candidates for tumour resection, but this requires further research.

Based on the studies available, it is unclear if MEG has similar accuracy in localizing seizure foci as ICEEG.  More high-quality research is needed to establish whether there is a difference in accuracy between MEG and ICEEG.

The results of the studies comparing PET to noninvasive EEG did not demonstrate that PET was more accurate at localizing seizure foci. However, there may be some specific conditions such as tuberous sclerosis, where PET may be more accurate than noninvasive EEG. (Personal communication, clinical expert, December 12, 2006) 

There may be some clinical utility for MEG or fMRI in presurgical functional mapping, but this needs further investigation involving comparisons with other modalities.  The clinical utility of MRS has yet to be established for patients with epilepsy.

PET has high sensitivity and specificity in the diagnosis of PD and the differential diagnosis of parkinsonian syndromes. It is unclear at this time if the addition of PET in the diagnosis of these conditions contributes to the treatment and clinical outcomes of patients.

There is limited clinical utility of functional brain imaging in the management of patients with MS at this time.  Diagnosis of MS is established through clinical history, evoked potentials and MRI.  MRI can identify the multifocal white lesions and other structural characteristics of MS.