BOLD Imaginge Applications for Patients with
Memory Deficitys and Temporal Lobe Epiliepsy
Figure 1. fMRI statistical activation map from a control subject being shown
a scene encoding paradigm. Brain activation is seen in the (A) right anterior hippocampus/
parahippocampal region (p<.005) (arrow), and (B) left anterior hippocampus and fusiform gyrus (p<.005)
(arrow). Activation is seen in other language areas of the brain.
Epilepsy affects an estimated 1% of the U.S. population; consequently about 1.5 million Americans have active epilepsy. In approximately 60% of these patients, seizures arise in the region of the brain known as the temporal lobe. Since the medial temporal lobe is mainly involved in memory processing, memory dysfunction is the most significant neurocognitive morbidity in patients with temporal lobe epilepsy (TLE). Currently, anterior temporal lobectomy is the best neurosurgical procedure for refractory complex partial seizures; however, the procedure itself may further compromise memory function. There are approximately 100,000 potential candidates in the U.S. who would benefit from epilepsy surgery each year. Assessment of medial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. Patients are routinely evaluated preoperatively by a battery of neuropsychological tests and by the intracarotid amobarbitol test (IAT) to assess memory status. However, neither of these tests is reliable in its ability to predict postoperative memory decline.
Functional MRI (fMRI) is proving to be a valid noninvasive tool for assessing brain function. Unlike structural MRI, which measures differences between tissues, fMRI measures changes in blood oxygenation in the brain over time. This technique maps changes in brain hemodynamics corresponding to various perceptual, motor, or cognitive processes, while providing anatomical images to display maps of human brain function (FIGURE 1). This newfound ability to directly observe brain function opens an array of opportunities that advance our understanding of brain organization and reorganization (plasticity). fMRI is being used at NYU to predict the postoperative functional memory status in patients with TLE.
MRI: STRUCTURAL/ANATOMIC EVALUATION OF THE BRAIN IN TEMPORAL LOBE EPILEPSY
The primary role of MRI in the evaluation of patients with epilepsy is to identify and characterize a structural abnormality in the brain which represents the epileptogenic focus. Such a focus, however, can only be found in up to 25% of patients. A dedicated MR seizure protocol including high-resolution coronal imaging of the frontal and temporal lobes is utilized at NYU to evaluate these patients (FIGURE 2). Common pathologic entities found on MRI include medial temporal sclerosis, brain tumors, vascular malformations, gliosis, and developmental abnormalities.
Structural images allow for volumetric measurements of the medial temporal lobe structures (particularly the hippocampus). MRI studies have shown correlation between medial temporal lobe volume loss and memory dysfuntion. Evidence indicates, however, that identifying structural abnormalities on MRI alone does not adequately reflect functional status. Direct relationships between structural metrics and neuropsychological measures are modest at best and leave a significant proportion of variance unexplained. The combination of structural, functional fluorodeoxyglucose (FDG) positron emission tomography (PET), and demographic and disease variables (age of onset of seizures, chronological age, duration of epilepsy) allows associations to be made between hippocampal volume and memory measures.
BOLD FUNCTIONAL MRI: FUNCTIONAL EVALUATION OF THE BRAIN IN PATIENTS WITH TEMPORAL LOBE EPILEPSY
Blood oxygen level-dependent (BOLD) contrast is a noninvasive fMRI technique for localizing brain signal intensity changes in response to task performance. This technique measures metabolic correlates (blood oxygenation level) of neuronal activity (but not neuronal activity itself). fMRI uses no intravenous contrast agents and depends mainly on regional changes in endogenous intravascular paramagnetic deoxyhemoglobin. Signal intensity changes in BOLD fMRI are attributed to the documented mismatch in response to regional activation between increases in regional cerebral blood flow and cerebral blood volume, and the much less profound increase in actual oxygen utilization in the area. As opposed to contrast-bolus MR imaging techniques and PET, the performance of BOLD fMRI measurements is not limited by contrast dose or radiation limits; therefore, several activation experiments can be performed.
With recent technologic advances, fMRI can be acquired within ultrashort acquisition times using echo planar imaging. fMRI demonstrates brain function with neuroanatomic localization on a real-time basis. BOLD contrast requires the detection of small signal intensity changes of 0–3% at 1.5T, and up to 6% at 3T. Since BOLD contrast originates from the intravoxel magnetic field inhomogeneity induced by paramagnetic deoxyhemoglobin, higher field strength imaging results in improved sensitivity related primarily to BOLD changes in capillary beds in response to neural activity. Recent fMRI studies comparing cognitive processing at 1.5T and 3T have shown that at 3T there were increased volumes of activation as compared to 1.5T, and significant activation of neuroanatomically distinct brain regions were detected at 3T that were not activated at 1.5T.
fMRI provides several other advantages over other functional imaging techniques in the evaluation of memory function. fMRI has spatial and temporal resolution which greatly exceeds IAT or PET, particularly with high field strengths. Patients can be studied longitudinally, allowing for the impact of surgery to be assessed. Another major advantage of fMRI over IAT is that it is a test of activation during specific tasks, whereas the IAT is based on performance failure during brain inactivation.
Figure 2. MRI. T2W and FLAIR images. Coronal MR images of the frontal and temporal
regions demonstrate atrophy and abnormal high signal intensity within the left hippocampus in a patient
with medial temporal sclerosis (arrow).
FUNCTIONAL MRI IN TEMPORAL LOBE EPILEPSY AT NYU
Funded research at NYU includes the application of fMRI methods to quantify areas of brain activation in patients with memory deficits and TLE. fMRI has been shown to be useful in mapping memory functions in the medial temporal and frontal lobes in patients with TLE. Our MR evaluation provides both an anatomic and functional assessment of the temporal lobes as well as detecting collateral compensatory function which can occur within other regions of the brain in both the preoperative and postoperative states. Understanding the distribution of temporal lobe memory circuits, as defined by fMRI, has the potential to significantly impact not only the preoperative decision as to whether or not to defer surgery in patients with TLE, but also to determine the extent of temporal lobe resection when indicated. The ultimate goals of our research are to improve the current understanding and accuracy of the diagnosis of memory dysfunction in TLE, and to help predict further memory decline postoperatively.