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Neuroradiology |
1 From the Department of Radiology (L.S.M., B.B., L.C., M.R., E.P., N.R.A.), Health Outcomes, Policy and Economics (HOPE) Center (L.S.M., L.C., M.R., N.R.A.), Brain Institute (L.S.M., B.B., C.D., E.P., P.J., G.M., J.R., N.R.A.), and Departments of Neurology (C.D., P.J.) and Neurological Surgery (G.M., J.R.), Miami Children's Hospital, 3100 SW 62 Ave, Miami, FL 33155. Received April 16, 2004; revision requested June 25; revision received August 12; accepted September 8. Supported in part by a grant from the American Society of Pediatric Neuroradiology. Address correspondence to L.S.M. (e-mail: smedina{at}post.harvard.edu).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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MATERIALS AND METHODS: Institutional review board approval was obtained; informed consent was obtained either from the patient or the parent or guardian in all patients. This study was conducted with Health Insurance Portability and Accountability Act compliance. Sixty consecutively enrolled patients (33 males, 27 females; mean age, 15.8 years ± 8.7 [standard deviation]; range, 6.8–44.2 years) were prospectively examined. Forty-five (75%) patients were right handed, nine (15%) were left handed, and six (10%) had indeterminate hand dominance. Prospective questionnaires were used to evaluate diagnostic work-up, counseling, and treatment plans of the seizure team before and after functional MR imaging. Confidence level scales were used to determine effect of functional MR imaging on diagnostic and therapeutic thinking. Paired t test and 95% confidence interval analyses were performed.
RESULTS: In 53 patients, language mapping was performed; in 33, motor mapping; and in seven, visual mapping. The study revealed change in anatomic location or lateralization of language-receptive (Wernicke) (28% of patients) and language-expressive (Broca) (21% of patients) areas. Statistically significant increases were found in confidence levels after functional MR imaging in regard to motor and visual cortical function evaluation. In 35 (58%) of 60 patients, the seizure team thought that functional MR imaging results altered patient and family counseling. In 38 (63%) of 60 patients, functional MR imaging results helped to avoid further studies, including Wada test. In 31 (52%) and 25 (42%) of 60 patients, intraoperative mapping and surgical plans, respectively, were altered because of functional MR imaging results. In five (8%) patients, two-stage surgery with extraoperative direct electrical stimulation mapping was averted, and resection was accomplished in one stage. In four (7%) patients, extent of surgical resection was altered because eloquent areas were identified close to seizure focus.
CONCLUSION: Functional MR imaging results influenced diagnostic and therapeutic decision making of the seizure team; results indicated language dominance changed, confidence level in identification of critical brain function areas increased, patient and family counseling were altered, and intraoperative mapping and surgical approach were altered.
© RSNA, 2005
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Functional magnetic resonance (MR) imaging, which does not require the use of exogenous contrast material or catheterization, is a noninvasive alternative method for evaluation of eloquent areas of the brain. Functional MR imaging is less time-consuming than the Wada test and requires no postprocedural recovery time. Many studies have been reported in which the results of functional MR imaging for language lateralization have been compared with those of the Wada test and of direct electrical stimulation. These results are summarized in Table 1. Overall, excellent agreement has been found between the results obtained with these procedures (1,7–15). Despite the excellent diagnostic performance and noninvasiveness of functional MR imaging, it is not used more widely because of limited data about outcome. The purpose of our study, therefore, was to prospectively evaluate the effect that functional MR imaging has on diagnostic work-up and treatment planning in patients with seizure disorders who are candidates for surgical treatment.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Imaging
After the procedure was explained to the patient and parent or guardian, the patient was positioned in a 1.5-T MR imager (LX MRI; GE Medical Systems, Milwaukee, Wis), and the audiovisual system was tested. The auditory stimulus was delivered from a personal computer that used prerecorded sound files. A transducer located inside the room provided the sound to be transmitted to the patient's ears via tubes and MR imaging–compatible earphones. The visual paradigm was delivered through MR imaging–compatible goggles (model S10VSB; Gragg Instruments, West Warwick, RI) having a 3 x 3 light-emitting array. A frequency of 8 Hz was used. Anatomic landmark images of the entire head were obtained with a three-dimensional spoiled gradient-recalled acquisition in the steady state sequence (repetition time msec/echo time msec, 17.3/3.6; flip angle, 25°). Functional MR imaging sequences based on the blood oxygenation level–dependent effect, with 3750/60 and a flip angle of 90°, were applied. Ten transverse sections were obtained, each with a section thickness of 6 mm and a gap of 2 mm between sections.
Paradigms of eloquent areas were tailored according to brain region of suspected seizure focus. Motor and visual areas also were explored when needed, according to the clinical particularities of each case. Functional MR imaging language paradigms included listening to a story, semantic fluency tasks, and verb generation. In the part of the evaluation concerned with the task of listening to a story, during the on epoch, the patient listened passively to three story fragments, each of which lasted 30 seconds. In the task concerned with semantic fluency, the patient had to think of as many nouns as possible in each of three categories (animals, vegetables, and fruits). In the verb generation task, the patient had to generate one or more verbs related to a list of nouns that was orally presented. During the off epoch, the patient thought about a blue sky and, hence, tried to avoid thinking of words. Motor paradigms included finger tapping contrasted with rest. The visual paradigm included observing flashing lights during the on epoch and observing nothing during the off epoch.
The paradigm for each task included three on and three off conditions distributed at 48 time points, for a total duration of 3 minutes. The patient was briefly trained and tested with similar exercises before the procedure to ensure comprehension and good performance of the tasks. Subsequent image data were analyzed for motion and were spatially smoothed with a Gaussian kernel of full width at half maximum of 10 mm to reduce the noise in the images. Signal normalization was performed by using dedicated software (MEDx, version 3.4.1; Sensor Systems, Sterling, Va). Motion analysis was performed by an author (B.B., who had 5 years of experience with functional MR imaging) by using Automatic Image Registration, a module of the software. Parametric statistical (z score) maps were obtained by using the unpaired Student t test. The z score maps were registered and fused with the three-dimensional image volumes. The z score maps were threshold for values of signal intensity with P 
.05 and corrected for multiple comparisons.
Study Analysis
The seizure team consisted of two pediatric neurologists and clinical neurophysiologists (P.J., C.D.) and two neurosurgeons (J.R., G.M.). The seizure team members were aware of the ongoing study about the evaluation of the role of functional MR imaging in diagnostic work-up and surgical planning in patients with seizure disorders but were not aware of the functional MR imaging results during the pretest questionnaire evaluation. Primary data consisted of prospective questionnaires for evaluation of the diagnostic work-up and treatment plans of the seizure team (P.J., C.D) at two stages: before and after viewing functional MR imaging data. Questionnaires were answered by the members of the seizure team independently, without direct input from radiologists (Fig 1).
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The posttest questionnaire was completed after the functional MR imaging findings were reviewed in detail. The same questions about the predicted anatomic location and extent of critical areas of the brain were answered. Change in functional location or lateralization of language was defined as no overlap of anatomic maps or Brodmann areas or differences in functional dominance, respectively, between the questionnaires completed before and after functional MR imaging. Changes in diagnostic work-up and surgical strategies that occurred as a result of the functional MR imaging input were recorded by using four questions: (a) Was intraoperative electrocortical mapping changed because of functional MR imaging results? (b) Was the intended surgical approach altered because of functional MR imaging results? (c) Were further tests, including the Wada test, avoided because of functional MR imaging results? (d) Were patient counseling and family counseling altered because of functional MR imaging results? The answers to the four questions, which denoted the usefulness of functional MR imaging, were quantified by using a modified Likert scale from 1 (low) to 6 (high). This scale range was as follows: 1, absolutely no; 2, probably no; 3, maybe no; 4, maybe yes; 5, probably yes; and 6, absolutely yes. Scores of 4 or greater were considered to denote significant usefulness of functional MR imaging.
Statistical Analysis
The confidence level and Likert scale questionnaire results were analyzed and compared by using the paired t test with a two-tailed P value (Instat, 2000; GraphPad, San Diego Calif). A P value of less than .05 was considered statistically significant; 95% confidence intervals were derived for the confidence level means of the different critical brain areas (16).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Effect on Diagnostic and Therapeutic Strategies
In 35 (58%) of 60 patients, the seizure team thought that functional MR imaging results altered patient counseling and family counseling (Table 5). In 38 (63%) of 60 patients, the Wada test was avoided because of functional MR imaging results. In 31 (52%) and 25 (42%) of 60 patients, intraoperative mapping and surgical plans, respectively, were altered because of functional MR imaging results. In five (8%) patients, two-stage surgery with extraoperative direct electrical stimulation mapping was averted, and resection was accomplished at one-stage surgery. In four (7%) patients, the extent of surgical resection was altered because eloquent areas were identified close to the seizure focus. During functional MR imaging performed in patients in this study, we found no major localization problems because of mass effects or regional hemodynamic alterations from the neoplasms or other focal lesions.
Of the 60 patients enrolled, 28 underwent surgery for seizures, and 32 were not surgical candidates or refused surgery. Of the 28 patients who underwent surgery, 17 were seizure free; eight patients had seizure reduction between 50% and 90%, and three patients had less than 50% seizure reduction at 6-month follow-up. Immediate postoperative complications included four cases of stroke and one case of hematoma that required drainage. No patient had postoperative aphasia or speech problems.
Three patients illustrated some examples of the importance of functional MR imaging. The first was an 8-year-old left-handed female patient with left hippocampal sclerosis. The pretest questionnaire denoted uncertainty about the hemispheric language dominance and attributed a confidence level with a score of 5 for either side. Functional MR imaging demonstrated left hemispheric language dominance (receptive and expressive) and bilateral auditory representation (Fig 2). The posttest questionnaire reflected a change in language lateralization, with a confidence level with a score of 9 for the left side. Functional MR imaging results were important for patient and family counseling and surgical planning. The family did not opt for surgery at the moment. The second was a 9-year-old left-handed male patient with intractable seizures and diffuse left cerebral hemisphere cortical dysplasia (Fig 3). Functional MR imaging revealed right hemispheric language (receptive and expressive) dominance. Functional MR imaging results were important for surgical planning and patient and family counseling. The third was a 10-year-old male child with intractable seizures (Fig 4). MR imaging revealed bilateral occipital lobe cortical dysplasia and right occipital lobe subependymal gray matter heterotopia. Functional MR imaging visual activation showed substantial visual cortex activation on the left side, with only minimal activation on the right side. Functional MR imaging results were important for surgical planning and family and patient counseling. The patient underwent right occipital lobectomy.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Brain surgery has proved to be an effective treatment for individuals with medically intractable epilepsy, particularly for those patients with a single seizure focus (1,3). It is important to map lesions that are located in close proximity to critical areas of the brain because of the proximity of the pathologic condition to functional regions (1) and because reorganization of the brain functions may be transferred to other areas in the ipsilateral or contralateral hemispheres (18,19). Surgical resection of such epileptogenic lesions requires knowledge of the location of the brain functions of bordering areas to provide a better outcome, preferably without neurologic deficit (2).
The determination of language lateralization in the preoperative evaluation of epileptic patients has been traditionally performed with the Wada test with injection of amobarbital into a carotid artery (1,3,5). Neuropsychological evaluation is conducted during and after the transient period of hemispheric anesthesia. The procedure is invasive, expensive, and nonlocalizing (1,5,20). Direct electrical stimulation mapping is performed with cortical stimulation after surgical implantation of subdural electroencephalographic grids or strips (4). It can be performed as a separate procedure in advance of the surgery (ie, two-stage procedure) or during the definitive surgical resection (ie, one-stage procedure). This is an invasive study, with important limitations; the most important limitation is that usually only one hemisphere can be evaluated (5), and intraoperative cortical stimulation usually helps to identify only those eloquent and critical brain regions that are on the surface of the brain (5).
Noninvasive functional MR imaging that relies on the blood oxygen level–dependent effect has been used to depict functional brain tissue (1,2,7–15). The blood oxygen level–dependent effect mechanism relies on the fact that an increase in regional cortical blood flow occurs in response to task performance from stimulation but that this is not accompanied by a concomitant increase in local tissue oxygen extraction (6). The increased cerebral perfusion causes a paradoxical decrease in concentration of deoxyhemoglobin (1). Oxyhemoglobin is diamagnetic, whereas deoxyhemoglobin is paramagnetic (1). The paramagnetic properties of deoxyhemoglobin create local field inhomogeneities, which decrease the signal intensity on T2- and T2*-weighted images (1,21,22). An increase in the level of venous blood oxygenation, therefore, is associated with a decrease in deoxyhemoglobin levels and an increase in MR imaging signal intensity (1). This change in signal intensity can be detected with magnetic susceptibility-sensitive imaging sequences, such as gradient-echo and echo-planar imaging (1).
Since its introduction, functional MR imaging has been investigated for presurgical mapping as an alternative for the invasive tests—Wada testing and direct electrical stimulation mapping. Investigators in several studies have compared mapping with functional MR imaging with Wada testing and direct electrical stimulation mapping. Functional MR imaging has been reported not only to be successful in mapping the main brain functions—including motor, sensory, and language functions—but also to correlate well with both Wada testing and electrocortical mapping (1,7–15).
Researchers in prior studies focused on evaluation of the diagnostic accuracy of functional MR imaging by comparing it with other techniques such as the Wada test and electrocortical stimulation (Table 1); these estimated the clinical efficacy of functional MR imaging. There is limited information, however, about how the seizure team uses the information provided by functional MR imaging and, hence, how this information affects diagnostic thinking and decision making. The latter question is important in determining the value of the imaging study because the goal of any imaging study is to guide the seizure team in the treatment of the patient and ultimately to acquire better patient-based outcomes (17).
Technology assessment has become increasingly important in the evaluation of imaging technology (17). A major goal of technology assessment is to determine the effect of diagnostic technology on patient health. Studies of effects of treatment are difficult because they require observation of both the seizure team and patient responses in a complex clinical environment (17). A patient will not usually receive any direct benefit from an imaging study, except when the seizure team can use the information obtained from the imaging study to guide patient treatment. Such information can be used to benefit the decision-making process in patient care. The purpose of our study was to determine whether functional MR imaging results are used to change diagnostic work-up and treatment plans in patients with seizure disorders who are considered for neurosurgical treatment.
Our study revealed that in 28% and 21% of the patients, anatomic location or lateralization of language-receptive (Wernicke) and language-expressive (Broca) areas, respectively, changed as a result of functional MR imaging findings. Statistically significant increases in the confidence levels determined before and after functional MR imaging for motor and visual cortical function evaluation were found. In 35 (58%) of 60 patients, the seizure team thought that functional MR imaging results altered patient and family counseling. In 38 (63%) of 60 patients, functional MR imaging results were used to avoid further studies, including the Wada test. In 31 (52%) and 25 (42%) of 60 patients, functional MR imaging results altered intraoperative mapping and surgical plans, respectively. In five (8%) patients, two-stage surgery with extraoperative direct electrical stimulation mapping was averted, and resection was accomplished at one surgery. In four (7%) patients, the extent of surgical resection was altered because eloquent areas were identified close to the seizure focus. Since the conclusion of this study, at our institution, noninvasive functional MR imaging is frequently performed in patients who are considered for surgery for seizures, and few clinicians are currently requiring the invasive Wada test.
Studies with the same methods as were used in our study have been published in Radiology (17,23). Test bias was controlled; the seizure team answered the same questions about anatomic location, dominance of eloquent areas, and confidence levels (score of 1 [low] to 10 [high]) before and after disclosure of functional MR imaging findings. Enrollment bias was minimized with examination of 60 consecutive patients with seizure disorders who were considered for surgery. Referral bias from the seizure team may be a factor in this type of study design. Referral bias, however, is probably against the use of functional MR imaging (performed entirely by the members of the Department of Radiology, with images read by the same members), because pediatric neurologists and clinical neurophysiologists who answered the questionnaires were involved in the performance and interpretation of the Wada test results and in the performance of intraoperative electrocortical stimulation and, hence, probably favored the latter tests. This functional MR imaging study did not depend on surgical proof as the standard, but it relied on the final diagnostic assessment of the referring seizure team. We believe that this evaluation is practical and that it provides a realistic measurement of the contribution of functional MR imaging results in all patients, not just those in whom surgical and pathologic results are available. Therefore, the strength of this study lies in the evaluation of the overall value of functional MR imaging results in the decision making of the seizure team.
Additional research studies are required. The effect of functional MR imaging memory paradigms in diagnostic work-up and treatment plans needs to be studied. Detailed cost savings of functional MR imaging in the evaluation of patients with seizures also is required, although initial studies have shown that the Wada test is 3.7 times more expensive than is functional MR imaging (20).
In summary, our study demonstrated that functional MR imaging results influence the diagnostic and therapeutic decision making of the seizure team. Functional MR imaging results frequently suggest a change in the location of language dominance, increase the confidence level in the identification of critical brain function areas, alter patient and family counseling, and alter intraoperative mapping and the surgical approach.
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FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, L.S.M., B.B., C.D., L.C.; study concepts and design, all authors; literature research, L.S.M., B.B., C.D., L.C., M.R., E.P., P.J., N.R.A.; clinical studies, all authors; data acquisition, all authors; data analysis/interpretation, L.S.M., B.B., C.D., L.C., M.R., P.J., N.R.A.; statistical analysis, L.S.M., B.B., M.R.; manuscript preparation and definition of intellectual content, L.S.M., B.B., C.D., L.C., M.R., P.J., N.R.A.; manuscript editing, L.S.M., B.B., C.D., L.C., P.J.; manuscript revision/review and final version approval, all authors
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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