Comparison of Blood Oxygenation Level-Dependent fMRI and Provocative DSC Perfusion MR Imaging for Monitoring Cerebrovascular Reserve in Intracranial Chronic Cerebrovascular Disease.

BACKGROUND AND PURPOSE: Loss of hemodynamic reserve in intracranial cerebrovascular disease reduces blood oxygenation level-dependent activation by fMRI and increases asymmetry in MTT measured by provocative DSC perfusion MR imaging before and after vasodilation with intravenous acetazolamide. The concordance for detecting hemodynamic reserve integrity has been compared. MATERIALS AND METHODS: Patients (n = 40) with intracranial cerebrovascular disease and technically adequate DSA, fMRI and provocative DSC perfusion studies were retrospectively grouped into single vessels proximal to and distal from the circle of Willis, multiple vessels, and Moyamoya disease. The vascular territories were classified as having compromised hemodynamic reserve if the expected fMRI blood oxygenation level-dependent activation was absent or if MTT showed increased asymmetry following vasodilation. Concordance was examined in compromised and uncompromised vascular territories of each group with the Fischer exact test and proportions of agreement. RESULTS: Extensive leptomeningeal collateral circulation was present in all cases. Decreased concordance between the methods was found in vascular territories with stenosis distal to but not proximal to the circle of Willis. Multivessel and Moyamoya diseases also showed low concordance. A model of multiple temporally displaced arterial inputs from leptomeningeal collateral flow demonstrated that the resultant lengthening MTT mimicked compromised hemodynamic reserve despite being sufficient to support blood oxygenation level-dependent contrast. CONCLUSIONS: Decreased concordance between the 2 methods for assessment of hemodynamic reserve for vascular disease distal to the circle of Willis is posited to be due to well-developed leptomeningeal collateral circulation providing multiple temporally displaced arterial input functions that bias the perfusion analysis toward hemodynamic reserve compromise while blood oxygenation level-dependent activation remains detectable.

Hot topics in functional neuroradiology.

Functional neuroradiology represents a relatively new and ever-growing subspecialty in the field of neuroradiology. Neuroradiology has evolved beyond anatomy and basic tissue signal characteristics and strives to understand the underlying physiologic processes of central nervous system disease. The American Society of Functional Neuroradiology sponsors a yearly educational and scientific meeting, and the educational committee was asked to suggest a few cutting-edge functional neuroradiology techniques (hot topics). The following is a review of several of these topics and includes "Diffusion Tensor Imaging of the Pediatric Spinal Cord"; "Diffusional Kurtosis Imaging"; "From Standardization to Quantification: Beyond Biomarkers toward Bioscales as Neuro MR Imaging Surrogates of Clinical End Points"; Resting-State Functional MR Imaging"; and "Current Use of Cerebrovascular Reserve Imaging."

In vivo evaluation of quantitative MR angiography in a canine carotid artery stenosis model.

BACKGROUND AND PURPOSE: Large-vessel cerebral blood flow quantification has emerged as a potential predictor of stroke risk. QMRA uses phase-contrast techniques to noninvasively measure vessel flows. To evaluate the in vivo accuracy of QMRA for measuring the effects of progressive arterial stenosis, we compared this technique with invasive flow measurements from a sonographic transit-time flow probe in a canine model. MATERIALS AND METHODS: A sonographic flow probe was implanted around the CCA of hound dogs (n = 4) under general anesthesia. Pulsatile blood flow and arterial pressure were continuously recorded during CCA flow measurements with QMRA. A vascular tourniquet was applied around the CCA to produce progressive stenosis and varying flow rates. Statistical comparisons were made by using the Pearson product moment correlation coefficient. RESULTS: A total of 60 paired CCA flow measurements were compared. Mean blood flows ranged between 21 and 691 mL/min during QMRA acquisition as measured by the flow probe. The correlation coefficients between flow probe and QMRA measurements for mean, maximum, and minimum volume flow rates were 0.99 (P < .0001), 0.98 (P < .0001), and 0.96 (P < .0001), respectively. The overall proportional difference between the 2 techniques was 7.8 ± 1%. Measurements at higher flow rates and in the absence of arterial stenosis had the lowest PD. CONCLUSIONS: Noninvasive CCA flow measurements by using QMRA are accurate compared with invasive flow-probe measurements in a canine arterial flow model with stenosis and may be useful for the evaluation of the hemodynamic effects of stenosis caused by cerebrovascular atherosclerosis.

Dural venous sinus thrombosis in a patient with sickle cell disease: case report and literature review.

We report a case of dural venous sinus thrombosis (DVST) in a patient who developed seizures following exchange transfusion for treatment of acute chest syndrome associated with sickle cell disease. Evaluation with magnetic resonance imaging and magnetic resonance venography of the brain indicated left sigmoid sinus thrombosis. The history and laboratory evaluation did not reveal any other inherited or acquired hypercoagulable states. This is the fourth case of dural venous sinus thrombosis associated with sickle cell disease reported in literature. The patient had a favorable outcome with early treatment of unfractionated heparin.

Direct visualization of the human subthalamic nucleus with 3T MR imaging.

BACKGROUND AND PURPOSE: Electrical stimulation of the subthalamic nucleus (STN) is an accepted treatment for advanced Parkinson disease (PD). Although procedural details are well established, targeting STN remains problematic because of its variable location and relatively small size (20-30 mm(3)). A combination of anatomic imaging with a stereotactic frame, atlas coordinates, and intraoperative neurophysiology is currently considered the most reliable approach for STN targeting. CT imaging is dependent on atlas coordinates, because the STN is not visualized. The STN is also difficult to visualize directly by using MR imaging at 1.5 T. METHODS: We performed preoperative stereotactic MR imaging at 3T to visualize the STN in 13 patients undergoing deep-brain stimulation for PD. With the patient positioned within a standard Leksell type G stereotactic frame localizer, rapidly acquired scout images are used to prescribe volumes of contiguous high-resolution T2-weighted fast spin-echo images in the axial, sagittal, and coronal planes through the midbrain and basal ganglia. The STN is identified in all 3 planes by cross-referencing in a 3-plane viewer. These coordinates are used for surgical targeting. RESULTS: At 3T, the STN was visualized as a small, hypointense, almond-shaped structure in 3 planes located immediately lateral to the anterior edge of the red nucleus, medial to the internal capsule, about 5 mm inferior, 1-2 mm posterior, and 9-12 mm lateral to the midcommissural point. Intraoperative microelectrode recordings confirmed these coordinates in all cases from the first microelectrode pass, thereby eliminating prolonged intraoperative electrophysiological STN searching and tissue disruption that may occur from multiple passes. CONCLUSION: 3T MR imaging appears to be an excellent tool for reliable and accurate direct visualization of the human STN, necessary for precise surgical targeting.

Investigating the neurobiological basis of cognitive rehabilitation therapy with fMRI.

The neurobiological changes occurring during cognitive rehabilitation therapy (CRT) have yet to be systematically studied. In the present study, functional magnetic resonance imaging (fMRI) was used to demonstrate brain plasticity in response to CRT (n = 5) following mild traumatic brain injury. Neuropsychological tests and two fMRI activation tasks, a visually guided saccades and a reading comprehension task, were employed pre- and post-CRT. CRT was used to systematically address the identified deficits in visual scanning and language processing. As hypothesized, changes in the pattern and extent of activation within expected neuroanatomical areas occurred post-CRT. Changes in fMRI activation are discussed for each subject and related to changes on neuropsychological measures. This study demonstrates how fMRI can illustrate the neurobiological mechanisms of recovery in individual subjects. The variability in subject responses to CRT supports the notion of tailoring rehabilitation strategies to each subject in order to optimize recovery following brain injury.

Neocortical system abnormalities in autism: an fMRI study of spatial working memory.

OBJECTIVE: To test the hypothesis that deficits in spatial working memory in autism are due to abnormalities in prefrontal circuitry. METHODS: Functional MRI (fMRI) at 3 T was performed in 11 rigorously diagnosed non-mentally retarded autistic and six healthy volunteers while they performed an oculomotor spatial working memory task and a visually guided saccade task. RESULTS: Autistic subjects demonstrated significantly less task-related activation in dorsolateral prefrontal cortex (Brodmann area [BA] 9/46) and posterior cingulate cortex (BA 23) in comparison with healthy subjects during a spatial working memory task. In contrast, activation of autistic individuals was not reduced in other regions comprising the neural circuitry for spatial working memory including the cortical eye fields, anterior cingulate cortex, insula, basal ganglia, thalamus, and lateral cerebellum. Autistic subjects also did not demonstrate reduced activation in any brain regions while performing visually guided saccades. CONCLUSION: Impairments in executive cognitive processes in autism may be subserved by abnormalities in neocortical circuitry as evidenced by decreased activation in prefrontal and posterior cingulate circuitry during a spatial working memory task.

Specified-resolution wavelet analysis of activation patterns from BOLD contrast fMRI.

Functional magnetic resonance (MR) MR imaging (fMRI) with blood-oxygenation-level-dependent (BOLD) contrast localizes neuronal processing of cognitive paradigms. As magnetic resonance signal responses are small, functional mapping requires statistical analysis of temporally averaged image data. Although voxels activating at the paradigm frequency can be identified from the Fourier power spectrum, such analyses collapse the temporal information that is useful to establish consistency of responses during the paradigm. The design of a set of nonorthogonal wavelets of specified frequency resolution within the power spectrum was investigated for extracting desired frequency responses from the noisy signal intensity of individual voxels. These wavelets separate the low-frequency cognitive response to the paradigm from the respiratory and cardiac responses at higher frequencies. The retention of the temporal information, possible by wavelet analysis, allows the MR signal changes to be compared to changes in behavioral responses over the duration of an entire paradigm. The amplitude and time delay of the wavelet specified by the paradigm identify quantitatively the size of the MR signal change and the temporal delay of the hemodynamic BOLD response, respectively. This specified-resolution wavelet analysis was demonstrated for individual voxels and maps through the frontal eye fields using a visually guided saccade paradigm.

Serial [18F] fluorodeoxyglucose positron emission tomography after human neuronal implantation for stroke.

OBJECTIVE: There is no known effective treatment for chronic stroke. In this report, we used positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) to map the metabolic brain response to neuronal cell implantation in the first human neuroimplantation trial for stroke. METHODS: Twelve patients (nine men, three women; mean age +/- standard deviation, 60.8+/-8.3 yr) with chronic basal ganglia infarction and persistent motor deficit underwent FDG PET within 1 week before and 6 and 12 months after stereotactic implantation of human neuronal cells. Serial neurological evaluations during a 52-week postoperative period included the National Institutes of Health stroke scale and the European stroke scale. RESULTS: Alterations in glucose metabolic activity in the stroke and surrounding tissue at 6 and 12 months after implantation correlated positively with motor performance measures. CONCLUSION: FDG PET performed as part of an initial open-label human trial of implanted LBS-Neurons (Layton BioScience, Sunnyvale, CA) for chronic stroke demonstrates a relationship between relative regional metabolic changes and clinical performance measures. These preliminary findings suggest improved local cellular function or engraftment of implanted cells in some patients.

Interdependence of nonoverlapping cortical systems in dual cognitive tasks.

One of the classic questions about human thinking concerns the limited ability to perform two cognitive tasks concurrently, such as a novice driver's difficulty in simultaneously driving and conversing. Limitations on the concurrent performance of two unrelated tasks challenge the tacitly assumed independence of two brain systems that seemingly have little overlap. The current study used fMRI (functional magnetic resonance imaging) to measure cortical activation during the concurrent performance of two high-level cognitive tasks that involve different sensory modalities and activate largely nonoverlapping areas of sensory and association cortex. One task was auditory sentence comprehension, and the other was the mental rotation of visually depicted 3-D objects. If the neural systems underlying the two tasks functioned independently, then in the dual task the brain activation in the main areas supporting the cognitive processing should be approximately the conjunction of the activation for each of the two tasks performed alone. We found instead that in the dual task, the activation in association areas (primarily temporal and parietal areas of cortex) was substantially less than the sum of the activation when the two tasks were performed alone, suggesting some mutual constraint among association areas. A similar result was obtained for sensory areas as well.

Maturation of widely distributed brain function subserves cognitive development.

Cognitive and brain maturational changes continue throughout late childhood and adolescence. During this time, increasing cognitive control over behavior enhances the voluntary suppression of reflexive/impulsive response tendencies. Recently, with the advent of functional MRI, it has become possible to characterize changes in brain activity during cognitive development. In order to investigate the cognitive and brain maturation subserving the ability to voluntarily suppress context-inappropriate behavior, we tested 8-30 year olds in an oculomotor response-suppression task. Behavioral results indicated that adult-like ability to inhibit prepotent responses matured gradually through childhood and adolescence. Functional MRI results indicated that brain activation in frontal, parietal, striatal, and thalamic regions increased progressively from childhood to adulthood. Prefrontal cortex was more active in adolescents than in children or adults; adults demonstrated greater activation in the lateral cerebellum than younger subjects. These results suggest that efficient top-down modulation of reflexive acts may not be fully developed until adulthood and provide evidence that maturation of function across widely distributed brain regions lays the groundwork for enhanced voluntary control of behavior during cognitive development.

Stimulus-response incompatibility activates cortex proximate to three eye fields.

We used functional magnetic resonance imaging (fMRI) to investigate cortical activation during the performance of three oculomotor tasks that impose increasing levels of cognitive demand. (1) In a visually guided saccade (VGS) task, subjects made saccades to flashed targets. (2) In a compatible task, subjects made leftward and rightward saccades in response to foveal presentation of the uppercase words "LEFT" or "RIGHT." (3) In a mixed task, subjects made rightward saccades in response to the lowercase word "left" and leftward saccades in response to the lowercase word "right" on incompatible trials (60%). The remaining 40% of trials required compatible responses to uppercase words. The VGS and compatible tasks, when compared to fixation, activated the three cortical eye fields: the supplementary eye field (SEF), the frontal eye field (FEF), and the parietal eye field (PEF). The mixed task, when compared to the compatible task, activated three additional cortical regions proximate to the three eye fields: (1) rostral to the SEF in medial frontal cortex; (2) rostral to the FEF in dorsolateral prefrontal cortex (DLPFC); (3) rostral and lateral to the PEF in posterior parietal cortex. These areas may contribute to the suppression of prepotent responses and in holding novel visuomotor associations in working memory.

Transplantation of cultured human neuronal cells for patients with stroke.

Transplantation of cultured neuronal cells is safe in animal models and improves motor and cognitive deficits in rats with stroke. The authors studied the safety and feasibility of human neuronal cellular transplantation in patients with basal ganglia stroke and fixed motor deficits, including 12 patients (aged 44 to 75 years) with an infarct 6 months to 6 years previously (stable for at least 2 months). Serial evaluations (12 to 18 months) showed no adverse cell-related serologic or imaging-defined effects. The total European Stroke Scale score improved in six patients (3 to 10 points), with a mean improvement 2.9 points in all patients (p = 0. 046). Six of 11 PET scans at 6 months showed improved fluorodeoxyglucose uptake at the implant site. Neuronal transplantation is feasible in patients with motor infarction.

Functional MR imaging using a visually guided saccade paradigm for comparing activation patterns in patients with probable Alzheimer's disease and in cognitively able elderly volunteers.

BACKGROUND AND PURPOSE: Alzheimer's disease is associated with progressive visuospatial dysfunction. This study used functional MR (fMR) imaging with an eye movement paradigm to investigate differences in visuospatial cognition between patients with probable Alzheimer's disease (pAD) and cognitively able elderly volunteers. METHODS: Using established, although imperfect, clinical criteria, patients with pAD (n = 18) and cognitively able elderly volunteers (n = 10) were selected for study. All patients underwent echo-planar fMR imaging at 1.5 T. The visually guided saccade paradigm consisted of alternating periods (30 s) of central fixation and visually guided saccades to a target appearing randomly along the horizontal meridian. Activation maps were derived using a voxelwise t test, comparing the signal intensities between the two steady-state conditions. The activation patterns were characterized by Talairach coordinates, activation volumes, and laterality ratios (LRs). RESULTS: Statistically significant differences existed between the activation patterns of the patients with pAD and those of the volunteers. In contrast to the control group, a left-dominant parietal activation pattern and enhanced prefrontal cortical activation were observed in most patients with pAD. CONCLUSION: Within the limitations of the imperfect clinical standard of reference, the reduction in right parietal activation producing the left-dominant LR for the intraparietal sulcus may reflect the progressive dysfunction in spatial attention associated with Alzheimer's disease, considering the known parietal lobe involvement in this function and the disease. The high specificity of a positive intraparietal sulcal LR measured by fMR imaging may have a role in detecting and monitoring Alzheimer's disease.

Effects of stereotactic radiosurgery on an animal model of hippocampal epilepsy.

OBJECTIVE: Stereotactic radiosurgery has been shown in small clinical series to reduce or abolish seizures in patients with lesion-related or idiopathic epilepsy. The radiation dose necessary to eliminate epileptogenesis is unknown, and the histological and metabolic effects of radiosurgery remain undefined. We hypothesized that in a rat model of kainic acid-induced hippocampal epilepsy, radiosurgery could provide a significant reduction in seizure frequency while limiting biochemical and structural histological damage to the brain. METHODS: Kainic acid (8 g) was injected into the rat hippocampus using stereotactic targeting. Focal seizures so generated were identified with scalp and depth electroencephalography (EEG). Epileptic rats were randomized to a control group (n = 20) and to radiosurgery groups in which maximum doses of 20, 40, 60, or 100 Gy (8-9 animals per group) were administered. Over a 42-day period, seizure frequency was determined by direct observation for 8 hours per week. Scalp EEG was performed weekly in all animals. Magnetic resonance imaging (MRI) studies (T1- and T2-weighted water-proton and quantitative sodium images) were obtained on Days 7, 21, and 42. RESULTS: As compared with the control group, treated animals showed significant reductions in the number of seizures during each successive week after 20-Gy radiosurgery (P = 0.01-0.002). When we combined the number of seizures observed in the latter half of the study (Weeks 4-6), we found a significant reduction in seizures after 20-Gy (P = 0.007), 40-Gy (P = 0.03), 60-Gy (P = 0.03), and 100-Gy (P = 0.03) radiosurgery as compared with control animals. Increasing doses of radiosurgery correlated with higher percentages of rats that became seizure-free by EEG criteria. MRI-determined total sodium concentration in the injected hippocampus was 49.8+/-3 mmol/L, compared with 42.8 mmol/L on the contralateral side (within normal limits). This significant increase in sodium concentration was present in control rats (because of the kainic acid) and did not change with increasing radiosurgery dose. No parenchymal effects from radiosurgery were identified after 20, 40, and 60 Gy, and only two rats had necrosis at 100 Gy. All animals showed hippocampal injury from kainic acid by proton MRI and histological examination. CONCLUSION: In this rat hippocampal epilepsy model, stereotactic radiosurgery was followed by a significant dose-dependent reduction in the frequency of observed and EEG-defined seizures. These effects were not accompanied by increased radiation-induced structural or metabolic brain injury as assessed by proton and sodium MRI or histological examination. The role of radiosurgery as a new, nondestructive surgical therapy for idiopathic epilepsy warrants further investigation.

Developmental and lesion effects in brain activation during sentence comprehension and mental rotation.

The development of neurocognitive networks was examined in 2 cognitive paradigms: auditory sentence comprehension and mental rotation of alphanumeric stimuli. Patterns of brain activation were measured with whole brain echoplanar functional magnetic resonance imaging at 3 Tesla in 5 adults (20-28 years old), 7 children (9-12 years old), and 6 pediatric patients (9-12 years old) with perinatal strokes or periventricular hemorrhages. Healthy children and adults activated similar neurocognitive networks, but there were developmental differences in the distribution of activity across these networks. In the sentence task, children showed more activation in the inferior visual area suggesting an imagery strategy rather than a linguistic strategy for sentence processing. Furthermore, consistent use of a sentence comprehension strategy, whether correct or incorrect as compared to chance performance, was associated with greater activation in the inferior frontal area (Broca's) in both children and pediatric patients. In the mental rotation task, healthy adults showed more activation in the superior parietal and middle frontal areas and less activation in the supramarginal gyrus, suggesting adults were primarily engaged in visual-spatial manipulation and less engaged in the recognition of noncanonical views of stimuli. The pediatric patients showed patterns of activation consistent with organization of cognitive processing into homologous areas of the contralateral hemisphere.

Comprehensive MR imaging protocol for stroke management: tissue sodium concentration as a measure of tissue viability in nonhuman primate studies and in clinical studies.

PURPOSE: To investigate sodium magnetic resonance (MR) imaging for monitoring tissue viability in stroke. MATERIALS AND METHODS: A comprehensive MR imaging protocol used to measure apparent diffusion coefficient and perfusion parameters was extended to include sodium imaging. Tissue sodium concentration was estimated by using a two-compartment model. This protocol lasted less than 45 minutes. These parameters were followed over the first 6 hours in a nonhuman primate model (n = 2) of acute embolic stroke without or with thrombolytic therapy. This protocol was used in patients in whom acute (< 24 hours, n = 11) or nonacute (> or = 24 hours, n = 31) stroke was ultimately confirmed. RESULTS: The animal model showed abnormal diffusion and perfusion parameters in the lesion immediately after embolization, and these remained abnormal for over 6 hours. Tissue sodium concentration increased with time (5.7 mmol/L/h) unless halted with thrombolytic therapy. Regions with sodium concentrations over 70 mmol/L were histochemically verified as being infarcted. In patients in whom stroke older than 6 hours was clinically confirmed, sodium concentrations over 70 mmol/L were found in the appropriate brain regions. CONCLUSION: Tissue sodium concentration provides a sensitive measure of tissue viability that is complementary to the diagnostic role of diffusion and perfusion imaging for ischemic insult.

Time course of fMRI-activation in language and spatial networks during sentence comprehension.

Functional neuroimaging previously has been considered to provide inadequate temporal resolution to study changes of brain states as a function of cognitive computations; however, we have obtained evidence of differential amounts of brain activity related to high-level cognition (sentence processing) within 1.5 s of stimulus onset. The study used an event-related paradigm with high-speed echoplanar functional magnetic resonance imaging (fMRI) to trace the time course of the brain activation in the temporal and parietal regions as participants comprehended single sentences describing a spatial configuration. Within the first set of images, on average 1 s from when the participant begins to read a sentence, there was significant activation in a key cortical area involved in language comprehension (the left posterior temporal gyrus) and visuospatial processing (the left and right parietal regions). In all three areas, the amount of activation during sentence comprehension was higher for negative sentences than for their affirmative counterparts, which are linguistically less complex. The effect of negation indicates that the activation in these areas is modulated by the difficulty of the linguistic processing. These results suggest a relatively rapid coactivation in both linguistic and spatial cortical regions to support the integration of information from multiple processing streams.

An integrated head immobilization system and high-performance RF coil for fMRI of visual paradigms at 1.5 T.

A flexible quadrature radiofrequency coil that maximizes the signal-to-noise ratio over the field of view of the human brain has been integrated into a head immobilization and visor system for fMRI at 1.5 T. Head motion is reduced by the visor that incorporates a head clamp and a simple visual sighting system that provides feedback on head position. This system is demonstrated in serial images by correction of deliberate head motions. The sensitivity at the cortical surface of fMRI using blood oxygenation level dependent contrast is increased significantly above that of the commercial rigid volume RF coil under the same acquisition conditions. This improved performance is demonstrated using visual activation and eye movement paradigms.

Functional organization of activation patterns in children: whole brain fMRI imaging during three different cognitive tasks.

1. Patterns of brain activation were measured with whole brain echo-planar functional magnetic resonance imaging (fMRI) at 3.0 Tesla in healthy children (N = 6) and in one child with a left-hemisphere encephalomalacic lesion as sequellae from early stroke. 2. Three cognitive tasks were used: auditory sentence comprehension, verb generation to line drawings, and mental rotation of alphanumeric stimuli. 3. There was evidence for significant bilateral activation in all three cognitive tasks for the healthy children. Their patterns of activation were consistent with previous functional imaging studies with adults. 4. The child with a left-hemisphere stroke showed evidence of homologous organization in the non-damaged hemisphere.