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Effects of cerebral ischemia on evoked cerebral blood oxygenation responses and BOLD contrast functional MRI in stroke patients.

BACKGROUND AND PURPOSE: To evaluate the mechanisms of failure of blood oxygenation level-dependent (BOLD) imaging in stroke, we compared the evoked cerebral blood oxygenation (CBO) responses and activation volumes (AVs) of BOLD functional MRI (fMRI) in chronic stroke patients with moderate and severe cerebral ischemia. METHODS: We measured the evoked CBO responses in the primary sensorimotor cortex (PSMC) by means of near-infrared spectroscopy during contralateral motor tasks. We compared the AV of BOLD-functional MRI in the PSMC on the nonlesion and lesion sides. Single-photon emission computed tomography was used to classify ischemic status as moderate (slight reduction of regional cerebral blood flow and cerebrovascular reserve capacity [CVRC]) or severe (marked reduction of regional cerebral blood flow and CVRC; ie, misery perfusion). RESULTS: In age-matched controls, deoxyhemoglobin concentration decreased with concomitant increases in oxyhemoglobin and total hemoglobin concentrations during activation. The PSMC on the nonlesion side exhibited a normal CBO response pattern. On the lesion side, moderate cerebral ischemia did not affect the CBO response pattern, but severe cerebral ischemia caused an increase of deoxyhemoglobin during the task, associated with increases of oxyhemoglobin and total hemoglobin. Moderate cerebral ischemia induced only a slight reduction of the AV on the lesion side; however, severe cerebral ischemia markedly reduced the AV on the lesion side. The BOLD signal did not change in some areas of the PSMC on the lesion side in severe cerebral ischemia, whereas it tended to decrease in other areas during the tasks. CONCLUSIONS: Misery perfusion caused a marked reduction of the AV on BOLD imaging, associated with an increase of deoxyhemoglobin concentration during activation. BOLD-fMRI investigations of stroke patients should be performed while giving consideration to baseline circulatory status. Functional near-infrared spectroscopy could be an alternative means to assess the CVRC.

Adult↗

Evoked-cerebral blood oxygenation changes in false-negative activations in BOLD contrast functional MRI of patients with brain tumors.

Blood oxygenation level dependent contrast functional MRI (BOLD-fMRI) has been used to define the functional cortices of the brain in preoperative planning for tumor removal. However, some studies have demonstrated false-negative activations in such patients. We compared the evoked-cerebral blood oxygenation (CBO) changes measured by near-infrared spectroscopy (NIRS) and activation mapping of BOLD-fMRI in 12 patients with brain tumors who had no paresis of the upper extremities. On the nonlesion side, NIRS demonstrated a decrease in deoxyhemoglobin (Deoxy-Hb) with increases in oxyhemoglobin (Oxy-Hb) and total hemoglobin (Total-Hb) during a contralateral hand grasping task in the primary sensorimotor cortex (PSMC) of all patients. On the lesion side, NIRS revealed a decrease in Deoxy-Hb in five patients (Deoxy-decrease group), and an increase in Deoxy-Hb in seven patients (Deoxy-increase group); the Oxy-Hb and Total-Hb were increased during activation in both groups, indicating the occurrence of rCBF increases in response to neuronal activation. BOLD-fMRI demonstrated clear activation areas in the PSMC on the nonlesion side of all patients and on the lesion side of the Deoxy-decrease group. However, in the Deoxy-increase group, BOLD-fMRI revealed only a small activation area or no activation on the lesion side. Intraoperative brain mapping identified the PSMC on the lesion side that was not demonstrated by BOLD-fMRI. The false-negative activations might have been caused by the atypical evoked-CBO changes (i.e. increases in Deoxy-Hb) and the software employed to calculate the activation maps, which does not regard an increase of Deoxy-Hb (i.e., a decrease in BOLD-fMRI signal) as neuronal activation.

Adult↗

[Brain functional MRI of the visual cortex with echo planar imaging].

Brain functional MR imaging (fMRI) is a non invasive imaging method for detecting neural activity. We performed functional MRI of the visual cortex with gradient-echo echo planar imaging (GE-EPI) and spin-echo EPI (SE-EPI) using 1.5T MRI system. Visual stimuli was performed with a checkerboard patterns. Magnitude and temporal phase of correlation between each pixel's time-course and sine functions at the frequency of the stimulus was calculated. In all subjects, the activation area in visual cortex obtained from SE-EPI was smaller than that from GE-EPI. Temporal phase delay images from both GE-EPI and SE-EPI showed signal spread from the primary visual cortex to peripheral supplementary areas. Temporal phase analysis is important to discriminate the source of the hemodynamic response to neural activation in fMRI.

Echo-Planar Imaging↗

Navigated transcranial magnetic stimulation for presurgical planning--correlation with functional MRI.

PURPOSE: This paper describes the potential of navigated transcranial magnetic stimulation to map the motor cortex in patients with mass lesions near the primary motor cortex by comparing the results of this technique to those of functional MRI. MATERIAL AND METHODS: Ten patients with mass lesions near the central sulcus were studied preoperatively using a figure-of-eight transcranial magnetic stimulator attached to a neuronavigation system to allow for direct visualization of the stimulated brain region. Subsequently, in all patients a blood oxygenation level dependent 2D multislice multishot T2*-weighted gradient echo EPI sequence on a 1.5 T Philips Gyroscan during motor activation was performed. Results of both methods were coregistered and compared. RESULTS: The distances between the peak parenchymal fMRI activation and the cortical area where TMS elicited the maximum MEPs ranged between 0 and 1.2 cm (mean 0.6 cm, SD 0.4 cm). CONCLUSION: We conclude that navigated TMS is a reliable alternative for localizing the motor-related areas in the human brain preoperatively and therefore may be a useful adjunct or, in selected patients, even a helpful alternative to functional MRI.

Adult↗

Increased cerebral blood volume in HIV-positive patients detected by functional MRI.

OBJECTIVE: To study changes in cerebral hemodynamics related to HIV infection. BACKGROUND: Cerebral injury is a well-known manifestation of HIV infection. Physiologic changes in the HIV brain may precede structural changes and may be detected by functional MRI (fMRI). METHODS: Dynamic contrast fMRI was used to measure the cerebral blood volume (CBV) in 13 patients infected with HIV and in 7 healthy control subjects. RESULTS: Significant increases in dynamic CBV were found in the deep (p < 0.001) and cortical gray matter (p < 0.05) of HIV-positive (HIV+) patients. Patients with definite cognitive impairment showed significantly greater increases in CBV in the deep gray matter (DGM) compared with those without impairment. In one patient with rapidly progressive cognitive impairment, these abnormalities reversed and paralleled clinical improvement after initiation of zidovudine monotherapy. CONCLUSIONS: This study supports the hypothesis that HIV infection is associated with significant cerebral hemodynamic changes, particularly in the DGM, that may contribute to cognitive dysfunction in AIDS. Functional MRI may be useful for early detection of cerebral injury and for the assessment of novel therapies.

Adult↗

A functional MRI case study of acquired cerebral dyschromatopsia.

Evidence from imaging studies suggests that primary visual cortex and multiple areas in ventral occipitotemporal cortex subserve color perception in humans. To learn more about the organization of these areas, we used structural and functional MRI (fMRI) to examine a patient with damage to ventral cortex. An art professor, KG, suffered a cerebrovascular accident during heart surgery that impaired his ability to perceive color. The Farnsworth-Munsell 100-Hue test was used to assess the extent of his deficit. When tested 12 months after the lesion, KG performed worse than 95% of age-matched normals on the 100-Hue test, but well above chance. Structural and functional MRI studies were conducted 3 years after the lesion to investigate the neuroanatomical correlates of KG'ss remaining color ability. Structural MRI revealed bilateral damage to ventral occipitotemporal cortex. In young and age-matched normal controls, an fMRI version of the 100-Hue reliably activated bilateral, color-selective regions in primary visual cortex and anterior and posterior ventral cortex. In subject KG, color-selective cortex was found in bilateral primary visual cortex. In ventral cortex, no color-selective activity was observed in right ventral cortex, and only a small area of activity was observed in left anterior ventral cortex. However, significant color-selective activity was observed in posterior left ventral cortex spared by the lesion. This posterior left ventral activation was similar in extent, position, and degree of color-selectivity to the posterior left posterior activation observed in normal controls, suggesting that this focus may be the cortical substrate underlying KG's remaining color perception.

Adult↗

Functional MRI BOLD signal coincides with electrical activity in the rat whisker barrels.

Functional MRI (fMRI) provides a noninvasive method for mapping brain functional activity based on blood oxygenation level dependent (BOLD) image contrast that is primarily due to localized increases in perfusion. Recently, Malonek and Grinvald (Science 272:551-554, 1996) suggested that during sustained functional activation, the increases in perfusion were spread over a much larger area than the localized electrical activity. In this study, it is demonstrated that the spatial distribution of the BOLD fMRI signal during sustained stimulation of rat whiskers has the same spatial pattern and dimension as that of neuronal electrical activity in the rat whisker barrels.

Animals↗

Altered hemodynamic responses in patients after subcortical stroke measured by functional MRI.

BACKGROUND AND PURPOSE: Blood oxygenation level-dependent (BOLD) functional MRI (fMRI) is a promising method for defining brain recovery after stroke quantitatively. Applications thus far have assumed that the BOLD hemodynamic response in patients after stroke is identical to that in healthy controls. However, because of local vascular compromise or more diffuse vascular disease predisposing to infarction, this assumption may not be justified after stroke. We sought to test whether patients who have suffered a lacunar stroke show BOLD fMRI response characteristics identical to those of healthy controls. METHODS: We measured the BOLD fMRI signal time course in the sensorimotor cortex contralateral to the affected hand with finger- or hand-tapping tasks for minimally or mildly impaired right-handed patients (n=12) after lacunar strokes causing limb weakness and for healthy controls (n=20). RESULTS: With a right-handed sequential finger-tapping task, the rate of rise and maximum increase of the BOLD signal in the contralateral sensorimotor cortex were > 30% lower (P< or =0.01) in the stroke patients. Similar relative decreases were found for the same task performed with the left hand. These changes were found in patients both in the hemisphere affected by stroke and in the unaffected hemisphere, suggesting that the BOLD fMRI time course differences observed arise from a diffuse functional pathology. The difference between patients and controls is not a result of age alone, since differences were not found between the younger (n=10; aged 22 to 38 years) and the older (n=10; aged 56 to 83 years) healthy controls. The effect also does not seem to be dependent on the specific hand movement task used. CONCLUSIONS: The magnitude of the BOLD fMRI response can be reduced in stroke patients even if infarcts do not involve the cortex. This may be a consequence of the stroke, but the observation that the BOLD signal time course is similar in the affected and unaffected hemispheres suggests that it also could result from preexisting pathophysiological changes in the cerebral microvasculature.

Adult↗

Hidden Markov event sequence models: toward unsupervised functional MRI brain mapping.

RATIONALE AND OBJECTIVES: Most methods used in functional MRI (fMRI) brain mapping require restrictive assumptions about the shape and timing of the fMRI signal in activated voxels. Consequently, fMRI data may be partially and misleadingly characterized, leading to suboptimal or invalid inference. To limit these assumptions and to capture the broad range of possible activation patterns, a novel statistical fMRI brain mapping method is proposed. It relies on hidden semi-Markov event sequence models (HSMESMs), a special class of hidden Markov models (HMMs) dedicated to the modeling and analysis of event-based random processes. MATERIALS AND METHODS: Activation detection is formulated in terms of time coupling between (1) the observed sequence of hemodynamic response onset (HRO) events detected in the voxel's fMRI signal and (2) the "hidden" sequence of task-induced neural activation onset (NAO) events underlying the HROs. Both event sequences are modeled within a single HSMESM. The resulting brain activation model is trained to automatically detect neural activity embedded in the input fMRI data set under analysis. The data sets considered in this article are threefold: synthetic epoch-related, real epoch-related (auditory lexical processing task), and real event-related (oddball detection task) fMRI data sets. RESULTS: Synthetic data: Activation detection results demonstrate the superiority of the HSMESM mapping method with respect to a standard implementation of the statistical parametric mapping (SPM) approach. They are also very close, sometimes equivalent, to those obtained with an "ideal" implementation of SPM in which the activation patterns synthesized are reused for analysis. The HSMESM method appears clearly insensitive to timing variations of the hemodynamic response and exhibits low sensitivity to fluctuations of its shape (unsustained activation during task). Real epoch-related data: HSMESM activation detection results compete with those obtained with SPM, without requiring any prior definition of the expected activation patterns thanks to the unsupervised character of the HSMESM mapping approach. Along with activation maps, the method offers a wide range of additional fMRI analysis functionalities, including activation lag mapping, activation mode visualization, and hemodynamic response function analysis. Real event-related data: Activation detection results confirm and validate the overall strategy that consists in focusing the analysis on the transients, time-localized events that are the HROs. CONCLUSION: All the experiments performed on synthetic and real fMRI data demonstrate the relevance of HSMESMs in fMRI brain mapping. In particular, the statistical character of these models, along with their learning and generalizing abilities are of particular interest when dealing with strong variabilities of the active fMRI signal across time, space, experiments, and subjects.

Adolescent↗

Functional MRI studies in awake rhesus monkeys: methodological and analytical strategies.

Functional imaging of the non-human primate brain in awake animals is now feasible because of recent methodological advances. Here we detail our procedures for conducting functional MRI (fMRI) studies in rhesus monkeys. Our emphasis has been on analyzing drug-evoked responses within and across test groups, meaning that techniques have had to be developed for training and testing relatively large groups of animals. Group size is important as unbiased estimates are best derived from analyzing responses in multiple animals with replicate scans per animal due to partial volume errors in evaluating small brain regions and motion artifacts during scanning. While the procedures presented here were developed for mapping responses obtained from stimulating dopaminergic systems, much of the methodology is generally applicable for non-human primate fMRI studies and addresses specific problems encountered in imaging awake animals. These are (1) adapting animals to an MRI environment, (2) minimizing head movements, (3) reducing ambient scanning noise levels, and (4) developing multivariate methods of image data analysis suitable for eliciting the dynamic brain response while (5) detecting and deleting outlying observations due to motion artifacts. Procedures are demonstrated for first pre-processing and analyzing responses in a voxel-based approach in a single animal and then proceeding to analyze responses across animals and replicate scans for regions of interest. Collectively, the procedures described provide an approach for fMRI mapping of elicited responses using conventional 1.5T MR scanners.

Animals↗

Functional MRI of human olfaction.

PURPOSE: Our goal was to use functional MRI (fMRI) to measure brain activation in response to olfactory stimuli. METHOD: fMRI brain scans were obtained in 17 normal subjects (9 men, 8 women) using-multislice FLASH MRI in response to three olfactory stimuli (pyridine, menthone, amyl acetate) in three coronal brain sections selected from anterior to posterior temporal brain regions. Activation images were derived using correlation analysis, and ratios of areas of brain activated to total brain areas were calculated. RESULTS: Activation was present in each section in all subjects. Subjective estimation of vapor intensity followed relative vapor pressure of stimuli presented (pyridine > amyl acetate > menthone) and were similar for both men and women. However, brain activation did not follow subjective responsiveness order but rather pyridine > menthone > amyl acetate, a pattern demonstrated by both men and women. Brain activation in women was consistently lower than in men for all vapors in all brain sections, although regions of activation did not differ. Activation occurred in regions previously recognized as associated with olfactory stimulation, including orbitofrontal and entorhinal cortex; however, extensive regions within frontal cortex including cingulate gyrus were also activated. Brain regions activated to odors considered pleasant or unpleasant did not differ. CONCLUSION: The techniques used in this study demonstrated that brain activation to olfactory stimuli could be measured quantitatively such that differences between groups of subjects (in this case men and women) could be compared. Although localization of brain activation was not the major thrust of this study, activation to olfactory stimuli was found not only in brain regions previously associated with processing of olfactory information but also in several other areas of frontal cortex, in cingulate gyrus, and in several components of the limbic system. This is the first study in which activation in human brain parenchyma of normal humans to olfactory stimuli has been quantitated by fMRI.

Adult↗

Evaluation of renovascular hypertension: comparison of functional MRI and contrast-enhanced MRA with a routinely performed renal scintigraphy and DSA.

OBJECTIVE: The main objective of this study was to evaluate a clinically suspected renovascular hypertension (RVH) by means of MRI. It was to find out if functional MRI (fMRI) is able to provide adequate results with regard to MAG3 captopril scintigraphy and if contrast-enhanced MR angiography (MRA) is able to provide adequate results in the stenosis grading compared with the nonselective digital subtraction angiography (DSA). METHODS: This open, monocentric, prospective, phase 3 study included patients with a clinically suspected RVH. For fMRI a dynamic TurboFLASH sequence and for MRA a single-shot breath-hold flash 3D sequence was performed. Gadodiamide was injected as contrast medium. RESULTS: Sixty patients were included in the study. The correlation between fMRI and scintigraphy had an accuracy, a sensitivity, and a specificity of 69%, 5%, and 92%, respectively, and correlations between MRA and DSA of 95%, 92%, and 96%. CONCLUSION: The noninvasive MRA can replace DSA in the diagnosis of renal artery stenosis. However, fMRI can not replace renal scintigraphy.

Angiography, Digital Subtraction↗

Odor maps of aldehydes and esters revealed by functional MRI in the glomerular layer of the mouse olfactory bulb.

Odorant identity is believed to be encoded in the olfactory bulb (OB) by glomerular activity patterns. It has not yet been possible to visualize and compare entire patterns for different odorants in the same animal because of technical limitations. For this purpose we used high-resolution functional MRI at 7 T, combined with glomerular-layer flat maps, to reveal responses to aliphatic homologues in the mouse OB. These odorants elicited reproducible patterns in the OB, with the medial and lateral regions containing the most intense signals. Unexpectedly, in view of the symmetrical projections of olfactory receptor neurons to medial and lateral glomeruli, the activity patterns in these regions were asymmetrical. The highly activated medial and lateral areas were shared by homologous members, generating a conserved "family signature" for a homologous series. The moderately active areas, including the dorsal region that has been extensively studied by optical imaging, were more sensitive to the length of the carbon chain, producing more subtle features of individual members and different changing trends among homologues. The global mapping with functional MRI not only extended previous studies but also revealed additional rules for representation of homologues in the OB. Insights into possible relations between the functional patterns, molecular projections, and odor perception may now be obtained based on the global from the olfactory epithelium to the OB glomerular activity patterns.

Aldehydes↗

Brain or vein--oxygenation or flow? On signal physiology in functional MRI of human brain activation.

Stimulus-related signal changes in functional MRI of human brain activation not only reflect associated adjustments of cerebral blood flow and oxygen consumption, but strongly depend on the MRI technique chosen and the actual experimental setting. A list of relevant parameters includes static field homogeneity of the magnet, MR pulse sequence and signal type, TE, TR, flip angle, gradient strengths, gradient waveforms, receiver bandwidth and voxel size. In principle, a local signal increase during functional activation may reflect a regional change in cerebral blood flow or deoxyhemoglobin concentration or both. This ambiguity was demonstrated using long TE FLASH MRI at high spatial resolution. Subsequently, experimental strategies were evaluated that either discriminate MRI effects in large vessels from those in the cortical microvasculature or separate changes in blood flow velocity from those in blood oxygenation. Examples comprise studies of the human visual and motor cortex.

Brain↗

Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI.

Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST). Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i.e. the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRI (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other. We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere. This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function. Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST. The transient signals in the go/no-go task peaked 5 s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms. These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i.e. the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.

Adaptation, Physiological↗

[Detection of angiogenesis-dependent parameters by functional MRI: correlation with histomorphology and evaluation of clinical relevance as prognostic factor using cervix carcinoma as an example].

PURPOSE: Purpose of this study is to compare functional MRI parameters with histomorphological markers of tumor microvessel density (MVD) and permeability (vascular endothelial growth factor) and to determine the ultimate value of both approaches by correlation with disease outcome in patients with primary cancer of the uterine cervix. METHOD: Pharmacokinetic parameters were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the operative whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using logrank statistics. RESULTS: Significant (p < 0.05-0.01) associations were found between MVD and dynamic MRI parameters. No significant relationships were observed between VEGF expression and dynamic MRI parameters. Disease outcome was better assessed with dynamic MRI parameters than with the histomorphological approach. CONCLUSIONS: It is concluded that 1) the pathophysiological basis for the amplitude A in dynamic MRI is MVD but not VEGF expression; and 2) a functional, dynamic MRI approach may be more suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis.

Adult↗

Acquiring simultaneous EEG and functional MRI.

OBJECTIVE: Electroencephalography (EEG) is a challenge to record simultaneously with functional MRI (fMRI), for it is prone to large artifacts induced by both the static and the time-variant fields of the MR scanner. However, truly concurrent EEG/fMRI recording has great potential for clinical and scientific neurological applications. We have devised a method for acquiring EEG simultaneously with fMRI that minimizes contamination of the EEG signals. METHODS: We recorded EEG differentially during fMRI using special twisted dual-lead electrodes in a bipolar montage, and a combination of analog pre-processing and digital post-processing of the EEG data. We implemented a functional scan protocol that typically yields artifact-free EEG over 87% of the MR scanning period. RESULTS: Our approach greatly reduced gradient, radio frequency, motion and ballistocardiographic artifact in the EEG, and allowed continuous monitoring of the EEG during functional scanning. To illustrate the quality of the EEG following post-processing, we demonstrated that EEG recorded during fMRI retains useful spectral information. CONCLUSIONS: Quality EEG may be recorded simultaneously with fMRI. With this union, activation maps could be made of any relevant changes in the EEG, such as inter-ictal spikes or spectral variations, or of evoked response potentials (ERPs).

Brain↗

Functional MRI of basal ganglia responsiveness to levodopa in parkinsonian rhesus monkeys.

Functional MRI (fMRI) was used to study striatal sensitivity to levodopa in hemiparkinsonian rhesus monkeys. Responses consistent with increased neuronal activity were seen in areas whose normal dopaminergic input from the substantia nigra pars compacta had been ablated by MPTP. Sites of increased activity following levodopa included the lateral putamen, the ventral region of the caudate head, septal areas, and midlateral amygdala in the MPTP-lesioned hemisphere. Increased activity was also observed in the same areas in the nonlesioned hemisphere, but was less pronounced in spatial extent and magnitude, suggesting either subclinical contralateral damage and/or functional adaptations in the contralateral dopamine systems. The increases in neuronal activity following levodopa treatment were temporally correlated with increases in striatal dopamine levels. Chronic levodopa treatment reduced behavioral responsiveness to levodopa and abolished the fMRI response. These results suggest that fMRI can detect changes in dopamine receptor-mediated neuronal sensitivity to dopaminergic agents.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗