The Clinical Efficacy of Magnetic Resonance Imaging in Neuroimaging

[Note that sections in this review are numbered so that they can be identified with cross-references as supporting evidence in the article Magnetic Resonance Imaging of the Brain and Spine: A Revised Statement, published in the Position Paper section of this issue; see pages 872-875.The Editor] 1. Magnetic resonance imaging (MRI) has revolutionized neuroimaging. Many internists now are familiar with the technology. However, strong support for a greatly expanded role of MRI for diagnosis and management of neurologic diseases is lacking because the evidence for clinical efficacy in the published literature is incomplete [1-3]. Because many more studies have appeared in the past 6 years, the American College of Physicians decided to update its 1987 report on the clinical efficacy of MRI in neuroimaging [4]. This review provides the basis for the updated assessment and accompanying suggestions for use of MRI in various clinical situations. 2. Methods 2.1 Titles and abstracts of 3125 citations from the peer-reviewed medical literature from 1987 through November 1993 were found using MEDLINE and ancillary searches. After screening out reviews, technical reports, case reports, and other publications describing fewer than 30 original case-patients, we identified 285 papers for further review. Two investigators independently read and classified each article according to the disease studied, the applicable level of clinical efficacy, and the methodologic quality of the study design. This three-part classification is summarized in Table 1 and has been described in detail previously [3]. Discrepant ratings were resolved by consensus. Table 1. Three Dimensions to Classification of Studies of a Diagnostic Test* 2.2 Because the imaging capabilities of MRI have been widely discussed in case series, we focused on the 156 articles that addressed diagnostic accuracy or diagnostic impact, therapeutic impact, or patient outcomes. For diagnostic accuracy and effect, methodologic quality was rated as A if the study had more than 35 patients with and more than 35 without the pathologic abnormality in question, drawn from a clinically relevant sample whose clinical symptoms were completely described, whose diagnoses were defined by an appropriate reference standard, and whose magnetic resonance images were technically of high quality and were evaluated independently of the reference diagnosis. Studies were rated D if they had no credible reference standard for diagnosis, or if the test result and determination of final diagnosis were not independent, or if the sample size was smaller than 35 for patients with and without the disease, or if the source of the patient cohort could not be determined or was obviously influenced by the test results (work-up bias). 2.3 Studies of therapeutic impact or changes in patient outcomes were evaluated for methodologic quality according to a similar A through D scale, adapted from Sackett [5]. For example, an A-rated study required a randomized, controlled trial using a clinically relevant, well-described sample, with adequate power to detect differences in well-characterized outcomes. The rationale and details for these ratings have been described [3, 6]. 2.4 Among 143 articles reporting on diagnostic accuracy or impact, 1 was rated A, 14 were rated B, 14 were rated C, and 113 were rated D for methodologic quality. Deficiencies included small numbers of patients, failure to describe the source of patients and their spectrum of disease, failure to maintain independence between interpretation of the MRI scan and an appropriate reference standard, or obsolescence of the magnetic resonance technology. Estimates of sensitivity and specificity were derived from the A, B, and C studies. Results from receiver-operating characteristic (ROC) curves are discussed in the text when available. Among 21 articles reporting on the therapeutic impact of MRI, none were rated A, 1 randomized trial was rated B, and 2 comparisons with computed tomography (CT) were rated C (Table 2). Five studies comparing treatment plans before and after MRI, but without comparison to an alternative test, were rated D for methodologic quality. Retrospective surveys of anecdotal experiences were not rated. No studies provided data on long-term patient outcomes. Table 2. Studies Indicating Therapeutic Impact or Changes in Patient Outcomes* 2.5 Suggestions for practice are given in the companion report from the American College of Physicians [4]. A strong strength-of-evidence rating would have been given to a suggestion supported by randomized, controlled studies of patient outcomes and by conclusive evidence about diagnostic accuracy. The one suggestion given a moderate rating was supported by studies that used comparison groups to show improved therapeutic choices and a definite impact on diagnoses. Most of the suggestions given weak ratings were supported by fair or good studies of diagnostic accuracy but had no supporting studies of therapeutic impact or patient outcomes. The suggestion given an equivocal rating was based only on prevalent expert opinion and several reports describing a predominance of clinical practice patterns. 3. Safety, Technical Issues, and Costs 3.1 Safety evaluations indicate that noncontrast MRI is safe for most patients, including pregnant women [7-9]. Pacemakers, many cerebral aneurysm clips, intraocular metal, and cochlear implants are definite contraindications to MRI. Other vascular clips, vena cava filters, and most metallic implants require individual patient consultation [10]. Incomplete or technically inadequate studies occur because of patient or equipment problems in 3% to 10% of attempted scans [11-13]. By comparison, safety concerns about CT are focused on iodinated contrast dye reactions. Some acute reaction occurs in 3% to 12% of patients, with severe reactions in 0.02% to 0.2% of patients [14, 15]. Newer nonionic contrast agents are associated with lower reaction risks. 3.2 Paramagnetic contrast agents improve confidence in diagnosis in 45% to 75% of scans and actually change the apparent diagnosis in up to 30% of patients [12, 16-22]. None of these studies could report diagnostic accuracy statistics because the comparisons were done without any independent reference standards. The larger multicenter evaluations of contrast agents probably contain case-selection biases that skew statistical analysis [21]. Paramagnetic contrast agents cross the placenta and typically are contraindicated during pregnancy [9], but all are otherwise safe [23, 24]. Minor adverse reactions to the agents occur in 2% to 3% of patients, and anaphylaxis occurs in about 1 in 100 000 patients [25]. 3.3 Diagnostic specificity for MRI has been studied only infrequently [3]. Although specificity has been used to mean that an imaging test can determine specific tissue composition, specificity as used in this paper is one minus the false-positive rate [26, 27]. Classically, a false-positive result is a positive test result when no disease is present. However, MRI often shows incidental anatomic abnormalities that are real and technically are not false-positive images (examples in Table 3). If any incidental abnormality of the cerebral white matter is called a false-positive result, the apparent diagnostic specificity can be low (0.28 to 0.58 [28-31]). The specificity is much higher if a more stringent test interpretation, such as one requiring multiple abnormalities to indicate disease, is used (0.80 to 0.90 [28]). The reliability of readings about white matter abnormalities is low [32]. No studies have reported investigations into the incidence of therapeutic misadventures caused by overinterpretation of white matter findings or by other asymptomatic abnormalities. Table 3. Diagnostic Accuracy of Magnetic Resonance Imaging for Various Conditions 3.4 Costs of MRI historically have been high compared with competing technologies. Facility and professional charges for MRI are 30% to 100% higher than for CT (Table 4). Some payers reimburse MRI only at a rate equivalent to CT (for example, Medi-Cal). If MRI obviates further tests but CT does not, using MRI as the initial test may be less expensive than using CT. Similarly, if MRI replaces an invasive test associated with inpatient facility charges (such as a myelogram, cisternogram, or cerebral arteriogram), then the MRI cost is less than the total cost of the alternative. New fast-imaging sequences, contrast agents, and studies focused only on high-yield views for particular diagnoses can shorten examination times and improve efficiency at imaging centers. Table 4. Recent Charges for Magnetic Resonance Imaging and Competing Technologies* 4. Stroke and Transient Ischemic Attacks 4.1 The clinical diagnosis of the cause of a stroke is erroneous in 10% to 20% of patients [33], so most patients have imaging. Because spatial resolution of MRI has improved, smaller infarctions have been seen, often on the first day after onset of illness [34-36]. Among several studies with small sample sizes [13, 34, 37-39], the sensitivity of MRI for the infarction ranged from 0.86 to 0.95, whereas the sensitivity of CT ranged from 0.50 to 0.68. One study of posterior circulation infarctions also reported a specificity of 0.88 [38]. 4.2 No studies rated as using grade C or better methods have compared MRI with either noncontrast or contrast-enhanced CT. Further, the impact of MRI on final diagnosis or therapeutic choices for patients with stroke has been reported only once [40]. In that study, MRI reportedly led to a change in diagnosis of the cause of stroke for 16% of patients and to changes in anticoagulation management for 19%. Treatment changes were not tabulated or evaluated for appropriateness; biasing of case selection through the influence of referral or nonreferral for imaging by treating clinicians also was not considered. No studies have investigated changes in patient outcomes attributable to