Functional Magnetic Resonance Imaging to Determine Hemispheric Language Dominance Prior to Carotid Endarterectomy M. Smits, MD, PhD, R. G. Wieberdink, MD, S. L. M. Bakker, MD, PhD, D. W. J. Dippel, MD, PhD From the Departments of Radiology (MS), Epidemiology & Biostatistics (RGW), and Neurology (DWJD), Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Neurology, St. Franciscus General Hospital, Rotterdam, The Netherlands (RGW, SLMB). ABSTRACT BACKGROUND AND PURPOSE We describe a left-handed patient with transient aphasia and bilateral carotid stenosis. Computed tomography (CT) arteriography showed a 90% stenosis of the right and 30% stenosis of the left internal carotid artery. Head CT and magnetic resonance imaging (MRI) of the brain showed no recent ischemic changes. As only the symptomatic side would require surgical intervention, and because hemispheric dominance for language in left-handed patients may be either left or right sided, a preoperative assessment of hemispheric dominance was required. METHODS We used functional MRI to determine hemispheric dominance for language and hence to establish the indication for carotid endarterectomy surgery. RESULTS Functional MRI demonstrated right hemispheric dominance for language and right-sided carotid endarterectomy was performed. Keywords: Language, functional laterality, endarterectomy, fMRI. Acceptance: Received September 4, 2009, and in revised form December 18, 2009. Accepted for publication January 7, 2010. Correspondence: Address correspondence to M. Smits, MD, PhD, Department of Radiology (Hs-224), Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands. E-mail: marion.smits@erasmusmc.nl. J Neuroimaging 2011;21:e162-e165. DOI: 10.1111/j.1552-6569.2010.00479.x CONCLUSIONS We propose that the clinical use of functional MRI as a noninvasive imaging technique for the assessment of hemispheric language dominance may be extended to the assessment of hemispheric language dominance prior to carotid endarterectomy. Introduction Functional magnetic resonance imaging (fMRI) is increasingly used as a noninvasive alternative for the Wada test in the assessment of hemispheric language dominance.1 The clinical use of fMRI for language mapping has been described in the presurgical evaluation of epilepsy2 and tumor surgery,3 and in neuropsychiatric disorders such as schizophrenia.4 The use of fMRI in language lateralization before carotid endarterectomy surgery has as yet not been described. In this case report we describe a left-handed patient with transient aphasia and bilateral carotid stenosis. As only the symptomatic side would require surgical intervention, and because hemispheric dominance for language in left-handed patients may be either left or right sided, a preoperative assessment of hemispheric dominance was required. We used fMRI to determine hemispheric dominance for language in this left-handed patient with bilateral carotid stenosis to establish the indication for carotid endarterectomy. Case Report Clinical Presentation A 91-year-old left-handed (Edinburgh handedness inventory5 score = −0.8) man was admitted to our hospital after 7 short episodes of aphasia that same day. Each episode lasted 2-3 e162 ◦ minutes, consisted of fluent aphasia with neologisms, and was followed by complete recovery. Aphasia was not accompanied by other symptoms. Relevant comorbidity included diabetes mellitus and hypertension. On physical and neurological examination no abnormalities were found, except for discrete signs of polyneuropathy of the lower extremities. A clinical diagnosis of recurrent transient ischemic attacks with aphasia was made. Laboratory and Conventional Imaging Findings Routine laboratory findings were within normal limits. Computed tomography (CT) showed no signs of recent focal ischemia. Carotid ultrasound studies demonstrated a high-grade stenosis of the right internal carotid artery and a nonsignificant stenosis of the left internal carotid artery. CT arteriography confirmed these findings and showed a 90% stenosis of the right and 30% stenosis of the left internal carotid artery. Magnetic Resonance Imaging (MRI) Informed consent was obtained from the patient prior to MRI scanning, which was performed on a 3T system (GE Healthcare, Milwaukee, IL). No recent ischemic lesions in either hemisphere were seen on the mean diffusivity (MD) or apparent diffusion coefficient (ADC) maps, which were acquired with diffusion tensor imaging (2-dimensional single-shot echo planar imaging [EPI] with a maximum b value of 1,000 s/mm2 acquired in 25 noncollinear directions; repetition time [TR]/echo Copyright C 2010 by the American Society of Neuroimaging time [TE]/inversion time [TI] 8,000/120/2,000 ms; voxel size 0.8 × 1.6 × 2.5 mm3 ). For anatomical detail a high-resolution 3-dimensional T1 weighted image was acquired (TR/TE/TI 10.7/2.2/300 ms; voxel size 0.6 × 0.7 × 0.8 mm3 ). For functional MRI, a T2∗ weighted EPI sequence, sensitive to blood oxygenation level dependent (BOLD) contrast, and covering the entire brain was used (TR/TE 3,000/30 ms; voxel size 3.8 × 2.5 × 3.5 mm3 ). We used a verbal fluency/verb generation task with a blocked design to assess functional hemispheric language lateralization.6 The task consisted of 10 alternating blocks of 30 second each (total duration 5:00 minutes), in which both the active and the control condition stimuli were presented binaurally through the scanner headphone system. A stimulus was presented every 3 seconds and generated automatically with Presentation v9.81 software (Neurobehavioral Systems, Albany, CA), which was synchronized with the image acquisition. Stimuli in the control condition consisted of high (2,000 Hz) and low (400 Hz) tones to engage auditory processing and attention. The patient was instructed to listen to the tones attentively. During the active condition, a noun was presented every 3 second. The patient was instructed to covertly produce a verb that was semantically related to the presented noun. The patient performed the task twice and data from the two tasks were pooled. Statistical analysis of the fMRI data was performed using Statistical Parametric Mapping version 2 (SPM2; Wellcome Department University College London, UK) implemented in Matlab version 6.5.1 (The Mathworks, Natick, MA). After realignment, registration, and smoothing (6 × 6 × 6 mm3 fullwidth half maximum) of the functional imaging data, an activation map was generated using the general linear model contrasting the active with the rest condition. The activation map was thresholded at P < .001 (not corrected for multiple comparisons) and visually assessed for hemispheric dominance by a Neuroradiologist (M.S.) with ample experience in clinical fMRI. Hemispheric Dominance for Language Significant activation was observed in the inferior frontal cortex bilaterally (expressive language areas; Fig 1A), the superior, and middle temporal gyrus as well as the supramarginal gyrus bilaterally (receptive and associative language areas; Fig 1B), and the left cerebellum (Fig 1C). The latter finding indicated a right-hemispheric dominance for language.7 Treatment and Follow-Up Right internal carotid endarterectomy was performed without complications. On the sixth day postoperatively the patient was discharged in good condition to return to his residential home for the elderly. He died of bowel cancer at the age of 92 years after a stroke-free period of 17 months. Discussion Carotid endarterectomy reduces the incidence of ipsilateral hemispherical strokes when significant and symptomatic carotid artery stenosis is present.8,9 In the case reported here, we could not be certain that the severe right carotid artery steno- sis was indeed symptomatic. Neither neurological examination nor MRI indicated the symptomatic hemisphere. Although the patient was strongly left-handed, right hemispheric dominance is found in only 10% of left-handed subjects.10 Assessment of hemispheric dominance for language prior to surgery was therefore required. The use of fMRI to determine language lateralization as a noninvasive alternative for the Wada test has first been described independently by Desmond (1995)11 and Binder (1996).12 In our institution, fMRI is fully implemented in clinical practice for the presurgical assessment of hemispheric language dominance in brain tumor patients.13 Extending the application of language fMRI, we performed fMRI to assess hemispheric language lateralization to identify the symptomatic hemisphere and hence establish the indication for carotid endarterectomy. In our patient, language-related brain activation was symmetrical in the frontal expressive and posterior parietotemporal receptive language areas, while activation was clearly lateralized toward the left cerebellar hemisphere. Crossed laterality of cerebral and cerebellar language dominance has been shown with fMRI by Jansen et al in 14 healthy subjects, 7 with left- and 7 with right-hemispheric dominance.7 Anatomically, crossed reciprocal connections between the cerebellum and the Brodmann areas 6, 44, and 45 exist, further supporting the idea of cerebellar contribution being contralateral to the side of cerebral dominance.14 We postulated that the lack of cerebral lateralization resulted from the severe right internal carotid stenosis, which presumably led to compensatory hemodynamic changes in the brain also affecting the BOLD response in the ipsilateral hemisphere.15,16 The signal change in BOLD fMRI depends on local changes of blood flow, cerebral metabolic rate of oxygen consumption, and cerebral blood volume in response to neuronal activity. Loss of vasoreactivity in functioning brain tissue due to severe cerebrovascular occlusive disease may lead to an inability of the local vasculature to respond to such neuronal activity and consequently to reduced or even absent BOLD sensitivity.15 In our patient, reduced activation in the right hemisphere may therefore be explained by the severe ipsilateral carotid stenosis, falsely indicating symmetrical rather than right-lateralized language representation. An alternative explanation would be that language representation in our patient was in fact not lateralized but symmetrical, which is also seen in left handers. Cerebellar activation, however, would then also be expected to be symmetrical. In our patient cerebellar activation was strongly lateralized favoring lateralized rather than symmetrical language representation in this case. Given the fact that the cerebellum is not dependent on the anterior, but on the unaffected posterior circulation, the BOLD response would not be affected in cerebellar regions. This would explain why such a strong lateralization in the cerebellum could still be observed in our patient. Unfortunately we were unable to test this hypothesis with repeat MR imaging after the surgery due to logistical reasons. The predominantly left-lateralized activation in the cerebellum, however, made assessment of hemispheric dominance for language possible, as the cerebellar contribution to language processing is found to be contralateral to the side of cerebral Smits et al: fMRI of Language Prior to Carotid Endarterectomy e163 Fig 1. Activation maps overlaid on T1 weighted images in the sagittal (upper row), coronal (middle row), and axial (bottom row) planes. Symmetrical activation in the frontal expressive (A) and posterior parietotemporal receptive (B) language areas. Lateralized activation in the left cerebellar hemisphere (C). language dominance,7 while the cerebellum is not affected by hemodynamic changes induced by carotid artery stenosis. Conclusion The clinical use of fMRI as a noninvasive imaging technique for the assessment of hemispheric language dominance does not need to be limited for patients prior to brain surgery. We present the new potential use of fMRI in the assessment of hemispheric language dominance prior to carotid endarterectomy. References 1. Lurito JT, Dzemidzic M. Determination of cerebral hemisphere language dominance with functional magnetic resonance imaging. Neuroimaging Clin N Am 2001;11(2):355-363, x. 2. Medina LS, Bernal B, Dunoyer C, et al. Seizure disorders: functional MR imaging for diagnostic evaluation and surgical treatment–prospective study. Radiology. 2005;236(1):247-253. 3. Sunaert S. Presurgical planning for tumor resectioning. 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