Peter Fransson

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.

Modulation of cerebral blood oxygenation by indomethacin: MRI at rest and functional brain activation

The modulation of blood oxygenation level‐dependent (BOLD) cerebral MRI contrast by the vasoconstrictive drug indomethacin (i.v. 0.2 mg/kg b.w.) was investigated in 10 healthy young adults without and with functional challenge (repetitive and sustained visual activation). For comparison, isotonic saline (placebo, 20 mL) and acetylsalicylate (i.v. 500 mg) were investigated as well, each in separate sessions using identical protocols. After indomethacin, dynamic T2*‐weighted echo‐planar MRI at 2.0 T revealed a rapid decrease in MRI signal intensity by 2.1%–2.6% in different gray matter regions (P ≤ 0.001 compared to placebo), which was not observed for acetylsalicylate and the placebo condition. Regional signal differences were not significant within gray matter, but all gray matter regions differed significantly from the signal decrease of only 1.2% ± 0.7% observed in white matter (P = 0.001). For the experimental parameters used, a 1% MRI signal decrease in response to indomethacin was estimated to correlate with a decrease of the cerebral blood flow by about 12 ml/100 g/minute, and an increase of the oxygen extraction fraction by about 15%. Responses to visual activation were not affected by saline or acetylsalicylate, and yielded 5.0%–5.5% BOLD MRI signal increases both before and after drug application. In contrast, indomethacin reduced the initial response strength to 82%–85% of that obtained without the drug. The steady‐state response during sustained activation reached only 47% of the corresponding pre‐drug level (P < 0.01). During repetitive activation the BOLD contrast was reduced to 66% of that observed for control conditions (P < 0.001). In conclusion, indomethacin attenuates the vasodilatory force at functional brain activation, indicating different mechanisms governing neurovascular coupling. J. Magn. Reson. Imaging 2001;13:325–334.

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.

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

Visual episodic memory encoding was investigated using echo-planar magnetic resonance imaging at 2.0 × 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 occipi- tal 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 μl and 259 ± 179 μl for intentional memory encoding and non-instructed viewing, respectively. In contrast, the checkerboard paradigm elicited pure visual activation without parahippocampal involvement.

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.

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.

A comparative FLASH and EPI study of repetitive and sustained visual activation

Functional responses to either brief repetitive or sustained activation of the human visual cortex (movie presentation) were monitored using both fast low angle shot and echo planar imaging sequences. To allow for proper comparisons, native image contrasts were equally sensitized to changes in cerebral blood oxygenation with other experimental conditions matched as much as possible. Putative influences of receiver bandwidth and absolute voxel size were specifically addressed. In all cases resulting correlation maps and regional signal intensity time courses showed excellent spatial and temporal congruence, respectively. In particular, for a 6u2009min protocol of sustained activation, both FLASH and EPI yielded an initial signal increase (oxygenation overshoot), a subsequent signal decrease during ongoing stimulation, and a marked signal drop (oxygenation undershoot) after the end of stimulation. These findings exclude technical differences between FLASH and EPI as the source of previous contradictory observations more likely to be explained by differences in stimulus design.

Magnetic resonance imaging of human brain function.

Noninvasive methods for studying metabolic and functional properties of the central nervous system provide new tools for understanding the human brain at the system level. As a bridging technology between basic neurobiologic research in (transgenic) animals, system-oriented studies in humans, and medical applications to patients with neurologic disease, magnetic resonance is expected to gain further importance in linking advances in molecular neurobiology and neurogenetics to cerebral metabolism and physiology and even beyond to human brain function.