Biomedical subjects

K D Merboldt

Publications and source records attributed to K D Merboldt.

At least 19 recordsLinked to original sources

PubMed2003

Thresholding in correlation analyses of magnetic resonance functional neuroimaging.

The definition of objective and effective thresholds in MRI of human brain function is a crucial step in the analysis of paradigm-related activations. This paper introduces a user-independent and robust procedure that calculates statistical parametric maps based on correlation coefficients. Thresholds are introduced as p values and defined with respect to the physiologic noise distribution of the individual maps. Experimental examples from the human visual and motor system rely on dynamic acquisitions of gradient-echo echo-planar images (2.0 T, TR = 2,000 ms, 96 x 128 matrix) with blood oxygenation level-dependent contrast. The results demonstrate the disadvantages of thresholding with fixed correlation coefficients. In contrast, taking the individual noise into account allows for a derivation of p values and a reliable identification of highly significant activation centers. An adequate delineation of the spatial extent of activation may be achieved by adding directly neighboring pixels provided their correlation coefficients comply with a second lower p value threshold.

Brain↗

PubMed2001

Functional MRI with reduced susceptibility artifact: high-resolution mapping of episodic memory encoding.

Visual episodic memory encoding was investigated using echoplanar magnetic resonance imaging at 2.0 x 2.0 mm2 resolution and 1.0 mm section thickness, which allows for functional mapping of hippocampal, parahippocampal, and ventral occipital regions with reduced magnetic susceptibility artifact. The memory task was based on 54 image pairs each consisting of a complex visual scene and the face of one of six different photographers. A second group of subjects viewed the same set of images without memory instruction as well as a reversing checkerboard. Apart from visual activation in occipital cortical areas, episodic memory encoding revealed consistent activation in the parahippocampal gyrus but not in the hippocampus proper. This finding was most prominently evidenced in sagittal maps covering the right hippocampal formation. Mean activated volumes were 432 +/- 293 microl and 259 +/- 179 microl for intentional memory encoding and non-instructed viewing, respectively. In contrast, the checkerboard paradigm elicited pure visual activation without parahippocampal involvement.

Adult↗

PubMed2001

Functional MRI of the human amygdala?

In view of an increasing number of publications that deal with functional mapping of the human amygdala using blood oxygenation-level-dependent (BOLD) magnetic resonance imaging, we reevaluated the underlying image quality of T2*-weighted echoplanar imaging (EPI) and fast low angle shot (FLASH) sequences at 2.0-T with regard to susceptibility-induced signal losses and geometric distortions. Apart from the timing of the gradient echoes, the degree of susceptibility influences is controlled by the image voxel size. Whereas published amygdala studies report voxel sizes ranging from 22 to 125 microl, the present results suggest that reliable imaging of the amygdala with BOLD sensitivity requires voxel sizes of 4 to 8 microl or less. Preferentially, acquisitions should be performed with a coronal section orientation. Although high-resolution BOLD MRI is at the expense of temporal resolution and volume coverage, it seems to provide the only solution to this physical problem.

Amygdala↗

PubMed2000

Reducing inhomogeneity artifacts in functional MRI of human brain activation-thin sections vs gradient compensation.

We evaluated two methods for correcting inhomogeneity-induced signal losses in magnetic resonance gradient-echo imaging that either use gradient compensation or simply acquire thin sections. The strategies were tested in the human brain in terms of achievable quality of T2*-weighted images at the level of the hippocampus and of functional activation maps of the visual cortex. Experiments were performed at 2.0 T and based on single-shot echo-planar imaging at 2. 0 x 2.0 mm(2) resolution, 4 mm section thickness, and 2.0 s temporal resolution. Gradient compensation involved a sequential 16-step variation of the refocusing lobe of the slice-selection gradient (TR/TE = 125/53 ms, flip angle 15 degrees ), whereas thin sections divided the 4-mm target plane into either four 1-mm or eight 0.5-mm interleaved multislice acquisitions (TR/TE = 2000/54 ms, flip angle 70 degrees ). Both approaches were capable of alleviating the inhomogeneity problem for structures in the base of the brain. When compared to standard 4-mm EPI, functional mapping in the visual cortex was partially compromised because of a lower signal-to-noise ratio of inhomogeneity-corrected images by either method. Relative to each other, consistently better results were obtained with the use of contiguous thin sections, in particular for a thickness of 1 mm. Multislice acquisitions of thin sections require minimal technical adjustments.

Adult↗

PubMed1999

Does stimulus quality affect the physiologic MRI responses to brief visual activation?

We studied the effect of stimulus quality on the basic physiological response characteristics of oxygenation-sensitive MRI signals. Paradigms comprised a contrast-reversing checkerboard vs. darkness or vs. gray light as well as gray light vs. darkness in a 2 s/52 s protocol (nine subjects). MRI was performed at 2.0 T using single-shot gradient-echo EPI (TR/TE = 500/54 ms, flip angle 30 degrees). All paradigms elicited almost identical signal intensity time courses comprising a latency period (1-2s), an activation-induced signal increase (4-4.5% at about 6-7 s after stimulus onset) and a post-stimulus signal undershoot (-1%) that slowly recovered to baseline (about 50 s). Thus, in contrast to findings for sustained stimulation, brief presentations of distinct visual stimuli exhibit similar physiological response characteristics that support the use of a uniform response profile for the evaluation of event related paradigms.

Adult↗

PubMed1999

Effects of sedation, stimulation, and placebo on cerebral blood oxygenation: a magnetic resonance neuroimaging study of psychotropic drug action.

The effects of pharmacologic depression and stimulation of cerebral activity were investigated in seven healthy young volunteers using blood oxygenation-sensitive MRI at 2.0 T. Dynamic gradient-echo imaging (7 min) was performed before, during and after the intravenous application of 10 mg diazepam and 15 mg metamphetamine as well as of the corresponding drug placebos (isotonic saline) in a brain section covering frontotemporal gray matter, subcortical gray matter structures, and cerebellum. The MRI responses were significantly different for the two drugs applied (p = 0.01). Relative to signal strength during injection, metamphetamine elicited a signal increase of 0.97 +/- 0.03% (mean +/- SD, p = 0.02) within the whole section 4-5 min after injection. Similarly, both placebo conditions led to a small signal increase, i.e. 0.50 +/- 0. 03% (n.s.) for the metamphetamine placebo and 0.40 +/- 0.07% (p = 0. 03) for the diazepam placebo. Diazepam abolished this signal increase. A topographic analysis revealed the metamphetamine-induced signal increase to be more pronounced in subcortical gray matter structures (p = 0.01) and cerebellum (p = 0.02) than in frontotemporal cortical gray matter (p = 0.04). This finding is in agreement with the hypothesis that pertinent responses not only reflect global cerebral hemodynamic adjustments, but also localized perfusion changes coupled to alterations in synaptic activity. The occurrence of a placebo response is best explained by expectancy and may provide a confounding factor in the design of functional activation experiments.

Adult↗

PubMed1999

MRI of functional deactivation: temporal and spatial characteristics of oxygenation-sensitive responses in human visual cortex.

Magnetic resonance imaging (MRI) of neuronal "activation" relies on the elevation of blood flow and oxygenation and a related increase of the blood oxygenation level-dependent (BOLD) MRI signal. Because most cognitive paradigms involve both switches from a low degree of activity to a high degree of activity and vice versa, we have undertaken a baseline study of the temporal and spatial characteristics of positive and negative BOLD MRI responses in human visual cortex. Experiments were performed at 2.0 T using a multislice gradient-echo EPI sequence (TR = 1 s, mean TE = 54 ms, flip angle 50 degrees) at 2x2-mm2 spatial resolution. Activation and "deactivation" processes were accomplished by reversing the order of stimulus presentations in paradigms using homogeneous gray light and an alternating checkerboard as distinct functional states. For sustained stimulation (> or = 60 s) the two conditions resulted in markedly different steady-state BOLD MRI signal strengths. The transient responses to brief stimulation (< or = 18 s) differed insofar as activation processes temporally separate positive BOLD and negative undershoot effects by about 10 s, whereas negative BOLD effects and undershoot contributions overlap for deactivation processes. Apart from differences in stimulus features (e.g., motion) the used activation and deactivation protocols revealed similar maps of neuronal activity changes.

Adult↗

PubMed1999

Temporal and spatial MRI responses to subsecond visual activation.

The temporal and spatial characteristics of oxygenation-sensitive MRI responses to very brief visual stimuli (five Hz reversing black and white checkerboard pattern versus darkness) were investigated (nine subjects) by means of serial single-shot gradient-echo echo-planar imaging (2.0 T, TR=400 ms, mean TE=54 ms, flip angle 30 degrees). The use of a 0.2-s stimulus and a 90-s control phase resulted in an initial latency phase (about 2 s, no signal change), a positive MRI response (2.5% signal increase peaking at 5 s after stimulus onset), and a post-stimulus undershoot (1% signal decrease peaking at 15 s after stimulus onset) lasting for about 50-60 s. The finding that a subsecond visual stimulus elicits both a strong positive MRI response and a long-lasting undershoot provides further evidence for the neuronal origin of slow signal fluctuations seen in the absence of functional challenge and their utility for mapping functional connectivity. The additional observation that a reduction of the inter-stimulus control phase from 90 s to 9.8 s does not seem to affect the spatial extent of cortical activation in pertinent maps is of major relevance for the design and analysis of "event-related" MRI studies.

Adult↗

PubMed1998

Physiologic aspects of event related paradigms in magnetic resonance functional neuroimaging.

In order to substantiate event related paradigms in magnetic resonance functional neuroimaging, we assessed the temporal and spatial characteristics of oxygenation-sensitive MRI responses to 1 s periods of visual activation in repetitive protocols. A main finding is a reduction of the functional contrast between conditions (reversing checkerboard vs. darkness) for decreasing interstimulus intervals yielding 4.5% signal change for 89 s, 4% for 9 s, 3% for 6 s, and 1% for 3 s, respectively. Although rapid repetitions of identical stimuli preclude the development of the full positive and negative MRI signal deflections, pertinent responses leave the spatial pattern of activated brain regions unaffected and result in identical maps. These findings suggest the use of interstimulus intervals of the order of the response time from stimulus onset to maximum signal strength (5-6 s in the visual system). The resulting distinction in time will allow for separate mapping of stimulus-related responses with spatially overlapping cortical representations.

Adult↗

PubMed1998

Temporal characteristics of oxygenation-sensitive MRI responses to visual activation in humans.

Series of single-shot blipped echo-planar images with spin-density weighting and T2* sensitivity (2.0 T, TR = 400 ms, TE = 54 ms, flip angle = 30 degrees) were used to study the temporal response profiles to repetitive visual activation (5 Hz, reversing black and white checkerboard versus darkness) for protocols comprising multiple cycles of a 1.6-s stimulus in conjunction with a 8.4-s or 90-s recovery phase and a 10-s stimulus with a 20-s or 90-s recovery phase. Analysis of the real-time data from all activated pixels resulted in a strong positive MRI response (mean values 3-6%) as well as a marked poststimulus undershoot (mean values 1-2%, duration 60-90 s) for all paradigms. Repetitive protocols with insufficient recovery periods of 8.4 s or 20 s gave rise to a wraparound effect when analyzing time-locked averages from multiple activation cycles. This problem may lead to an early signal decrease that originates from the ongoing undershoot of preceding activations folded back into the initial latency phase of a subsequent activation. When ensuring complete decoupling of responses to successive stimuli by using a 90-s recovery period, the wraparound effect vanished and an initial dip was observed in one of seven subjects for a 10-s/90-s protocol.

Adult↗

PubMed1997

Equivalent responses to lexical and nonlexical visual stimuli in occipital cortex: a functional magnetic resonance imaging study.

Stimulus-related changes in cerebral blood oxygenation were measured using high-resolution functional magnetic resonance imaging sequentially covering visual occipital areas in contiguous sections. During dynamic imaging, healthy subjects silently viewed pseudowords, single false fonts, or length-matched strings of the same false fonts. The paradigm consisted of a sixfold alternation of an activation and a control task. With pseudowords as activation vs single false fonts as control, responses were seen mainly in medial occipital cortex. These responses disappeared when pseudowords were alternated with false font strings as the control and reappeared when false font strings instead of pseudowords served as activation and were alternated with single false fonts. The string-length contrast alone, therefore, is sufficient to account for the activation pattern observed in medial visual cortex when word-like stimuli are contrasted with single characters.

Adult↗

PubMed1997

Dynamic NMR studies of perfusion and oxidative metabolism during focal brain activation.

Together, the present results on oxygenation, flow, and metabolism indicate that the prevalence of nonoxidative glycolysis and associated lactate production during the initial phase of activation is replaced by the upregulation of oxidative glucose consumption (see sketches in Fig. 5). Following rapid circulatory changes the gap between oxygen availability and oxygen consumption gradually closes until a recoupling of perfusion and oxidative metabolism is achieved a few minutes after switching the state of neural activity. While brain glucose and lactate concentrations reflect an initial prevalence of anaerobic glycolysis, the changes in blood oxygenation suggest that the rapid adjustment of blood flow (enhanced oxygen delivery) is followed by a slower upregulation of oxidative metabolism (enhanced oxygen consumption). The physiological uncoupling of perfusion and oxidative metabolism emerges as a transient phenomenon in response to both onset and end of stimulation. Recoupling at enhanced cerebral metabolic rates of oxygen (CMRO2) and glucose occurs a few minutes after switching the state of neural activity. Since glycolysis takes place primarily in astrocytes, the stimulus-related increase and decrease of lactate seen here may reflect a transfer of astrocytic lactate to neurons where it is converted into pyruvate and channelled into oxidative phosphorylation. This model of metabolic responses to functional activation is supported by a recently detected pathway for glutamate-stimulated glycolysis in astrocytes that provides a simple mechanism linking astrocytic glucose utilization to neuronal activity (Pellerin and Magistretti, 1994). In summary, evidence has accumulated that the physiological uncoupling of perfusion and oxidative metabolism associated with the onset of functional activation is a transient phenomenon leading to an only temporal mismatch of oxygen delivery and consumption. Recoupling at enhanced though balanced levels of glucose and oxygen consumption is most remarkably documented by the pronounced "negative" uncoupling at the end of stimulation.

Blood Flow Velocity↗

PubMed1996

Dynamic uncoupling and recoupling of perfusion and oxidative metabolism during focal brain activation in man.

Changes in glucose consumption, lactate production, and blood oxygenation were measured during prolonged neuronal activation (4-6 min) in human primary visual cortex using dynamic magnetic resonance spectroscopy and imaging. A decrease of steady-state glucose by 40% because of enhanced use by 21% was accompanied by a transient accumulation of lactate with a peak value of 170% 2.5 min after stimulation onset. Rapid blood hyperoxygenation indicating "uncoupling" of blood flow and oxidative metabolism was followed by a return to basal levels over 3 min. Thus, initial nonoxidative glucose consumption during functional activation is gradually complemented by a slower adjustment of oxidative phosphorylation that "recouples" perfusion and oxygen consumption at a new equilibrium.

Adult↗

PubMed1996

Simultaneous recording of cerebral blood oxygenation changes during human brain activation by magnetic resonance imaging and near-infrared spectroscopy.

Changes in cerebral blood oxygenation due to functional activation of the primary sensorimotor cortex during a unilateral finger opposition task were simultaneously mapped by deoxyhemoglobin-sensitive magnetic resonance imaging (MRI) and monitored by near-infrared spectroscopy (NIRS). Activation foci along the contralateral central sulcus displayed task-associated increases in MRI signal intensity, indicating a concomitant decrease of the focal concentration of deoxyhemoglobin. This interpretation was confirmed by simultaneous reductions in deoxyhemoglobin measured optically. Since observation of the latter effect required exact spatial matching of the MRI-detected activation foci and position of the fiber optic bundles ("optodes") used for transmitting and receiving light, it may be concluded that optical recordings of changes in deoxyhemoglobin during functional challenge probe only a restricted brain tissue region. While deoxyhemoglobin responses seen by NIRS were smaller for ipsi- than for contralateral finger movements, task-related increases in oxyhemoglobin were rather similar between both conditions and, thus, seem to be less specific. Furthermore, no consistent changes were obtained for total hemoglobin during task performance, possibly due to the short timing of the repetitive protocol. In general, results underline, in humans, the hitherto assumed signal physiology for functional brain mapping by oxygenation-sensitive MRI and allow assessment of both constraints and practicability of functional studies by NIRS.

Adult↗

PubMed1995

Functional MRI of human brain activation combining high spatial and temporal resolution by a CINE FLASH technique.

Functional mapping of human brain activation has been accomplished at high spatial and temporal resolution (voxel size 4.9 microliter, temporal increment 100 ms). The approach was based on oxygenation-sensitive long-echo time FLASH MRI sequences synchronized to multiply repeated cycles of visual stimulation in a CINE acquisition mode. This high temporal resolution revealed that stimulus-related signal intensity changes in human visual cortex display an initial latency followed by increases extending over several seconds. Furthermore, the temporal characteristics of the complete CINE MRI signal time course depended on the absolute and relative durations of activation and control periods and, for example, caused an apparent absence of a poststimulation "under-shoot" phenomenon. Complementing hyperoxygenation due to rapid hemodynamic adjustments, these results suggest signal intensity modulation by enhanced oxygen consumption and concomitant deoxygenation during prolonged and/or repetitive stimulation.

Artifacts↗

PubMed1995

Hemimegalencephaly: localized proton magnetic resonance spectroscopy in vivo.

Two children with hemimegalencephaly were examined by magnetic resonance imaging (MRI) and localized proton MR spectroscopy (MRS). In both cases, structural changes in the enlarged hemisphere included pachy- or polymicrogyria and gliosis of white matter. Associated metabolic disturbances included a dramatic reduction of glutamate and N-acetylaspartate (NAA) in white matter. Less severe or no alterations were noted in cortical gray matter, basal ganglia, and cerebellum. The older child (13 years) showed increased myoinositol in both gray and white matter as well as markedly increased choline-containing compounds in gray matter. Both children also had mildly decreased NAA levels in the white matter of the contralateral hemisphere. The spectroscopic findings indicate loss of vital neuroaxonal tissue and glial cell proliferation. Metabolic disturbances were more pronounced in the older child. The normal-appearing hemisphere was mildly affected in both cases.

Brain↗

PubMed1995

Magnetic resonance imaging of regional cerebral blood oxygenation changes under acetazolamide in carotid occlusive disease.

BACKGROUND: Gradient-echo magnetic resonance imaging can demonstrate changes in cerebral blood oxygenation with high spatiotemporal resolution. We have previously shown that this technique allows monitoring of autoregulatory responses under vasodilatory stress in the healthy human brain. Here the approach has been extended to assess impairment of the autoregulatory reserve capacity in patients with carotid occlusive disease. SUMMARY OF REPORT: We studied four patients with unilateral occlusion of the internal carotid artery on a 2.0-T clinical high-field magnetic resonance system. Oxygenation-sensitive imaging was based on long-echo-time, gradient-echo sequences (repetition time, 62.5 milliseconds; echo time, 30 milliseconds) with low flip angles (10 degrees) to emphasize changes in blood oxygenation rather than flow velocity. Dynamic recording monitored signal intensities before and after injecting 1 g of acetazolamide. In sections covering the hand area of the primary sensorimotor cortex, acetazolamide-induced magnetic resonance signal increases were attenuated in the vascular territories of occluded arteries. Lateralization of responses in the left and right hemispheric parts of the section corresponded to decreased hemodynamic reserve capacity as measured globally by transcranial Doppler ultrasonography. CONCLUSIONS: The present findings indicate that magnetic resonance imaging can demonstrate exhaustion of the autoregulatory reserve capacity when monitoring cerebral blood oxygenation changes during vasodilatory stress. We suggest that this method can help to evaluate regional cerebral hemodynamics in patients with carotid occlusive disease.

Acetazolamide↗

PubMed1995

[Strategies for data analysis of brain activation studies with functional MR tomography].

The sensitivity of gradient-echo magnetic resonance imaging (MRI) to changes in cerebral blood oxygenation has been introduced for mapping functional brain activation. To benefit from the high spatial and temporal resolution of the respective dynamic MRI data sets, their analysis requires algorithms that are capable of both precisely delineating task-related activation patterns and demonstrating functional connectivity of interacting areas. Here, we present various strategies for data evaluation by means of correlational analyses that surpass the quality of subtraction-based activation maps by improving both sensitivity and robustness. On a pixel-by-pixel basis the approach correlates signal time courses with a reference function, reflecting the temporal sequence of activated and control states. Extended versions employ the calculation of auto- or cross-correlation functions that increase sensitivity, but require periodic stimulations. Following individual correction for non-specific but correlated signal fluctuations, mapping of task-related coherent activation can be improved using neighborhood principles. Such refined strategies are expected to enhance the usefulness of oxygenation-sensitive MRI for studying the functional anatomy of the human brain under both physiological and pathological conditions.

Algorithms↗