Blood Oxygen Level-dependent Functional Imaging Research Articles

Multimodal 18F-AV-1451 and MRI Findings in Nonfluent Variant of Primary Progressive Aphasia: Possible Insights on Nodal Propagation of Tau Protein Across the Syntactic Network.

Although abnormally folded tau protein has been found to self-propagate from neuron to connected neuron, similar propagation through human brain networks has not been fully documented. We studied tau propagation in the left hemispheric syntactic network, which comprises an anterior frontal node and a posterior temporal node connected by the white matter of the left arcuate fasciculus. This network is affected in the nonfluent variant of primary progressive aphasia, a neurodegenerative disorder with tau accumulation. Methods: Eight patients with the nonfluent variant of primary progressive aphasia (age, 67.0 ± 7.4 y; 4 women) and 8 healthy controls (age, 69.6 ± 7.0 y; 4 women) were scanned with 18F-AV-1451 tau PET to determine tau deposition in the brain and with MRI to determine the fractional anisotropy of the arcuate fasciculus. Normal syntactic network characteristics were confirmed with structural MRI diffusion imaging in our healthy controls and with blood oxygenation level-dependent functional imaging in 35 healthy participants from the Alzheimer Disease Neuroimaging Initiative database. Results: Language scores in patients indicated dysfunction of the anterior node. 18F-AV-1451 deposition was greatest in the 2 nodes of the syntactic network. The left arcuate fasciculus had decreased fractional anisotropy, particularly near the anterior node. Normal MRI structural connectivity from an area similar to the one containing tau in the anterior frontal node projected to an area similar to the one containing tau in the patients in the posterior temporal node. Conclusion: Tau accumulation likely started in the more affected anterior node and, at the disease stage at which we studied these patients, appeared as well in the brain region (in the temporal lobe) spatially separate from but most connected with it. The arcuate fasciculus, connecting both of them, was most severely affected anteriorly, as would correspond to a loss of axons from the anterior node. These findings are suggestive of tau propagation from node to connected node in a natural human brain network and support the idea that neurons that wire together die together.

Visual cortex and auditory cortex activation in early binocularly blind macaques: A BOLD-fMRI study using auditory stimuli

Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A (p < 0.05). In conclusion, the bilateral visual cortices of binocularly blind macaques can be reorganized to process auditory stimuli after visual deprivation, and this effect is more obvious in the right than the left visual cortex. These results indicate the establishment of cross-modal plasticity within the visual and auditory cortices.

Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles.

Active neurons increase their energy supply by dilating nearby arterioles and capillaries. This neurovascular coupling underlies BOLD functional imaging signals, but its mechanism is controversial. Canonically, neurons release glutamate to activate metabotropic glutamate receptors (mGluR5) on astrocytes, evoking Ca2+ release from internal stores, activating phospholipase A2 and generating vasodilatory arachidonic acid derivatives. However, adult astrocytes lack mGluR5, and knock-out of the IP3 receptors that release Ca2+ from stores does not affect neurovascular coupling. We now show that buffering astrocyte Ca2+ inhibits neuronally-evoked capillary dilation, that astrocyte [Ca2+]i is raised not by release from stores but by entry through ATP-gated channels, and that Ca2+ generates arachidonic acid via phospholipase D2 and diacylglycerol kinase rather than phospholipase A2. In contrast, dilation of arterioles depends on NMDA receptor activation and Ca2+-dependent NO generation by interneurons. These results reveal that different signalling cascades regulate cerebral blood flow at the capillary and arteriole levels.

Comment on “The physiology of developmental changes in BOLD functional imaging signals” by Harris, Reynell, and Attwell

Comment on “The physiology of developmental changes in BOLD functional imaging signals” by Harris, Reynell, and Attwell

Component structure of event-related fMRI responses in the different neurovascular compartments

In most functional magnetic resonance imaging (fMRI) studies, brain activity is localized by observing changes in the blood oxygenation level-dependent (BOLD) signal that are believed to arise from capillaries, venules and veins in and around the active neuronal population. However, the contribution from veins can be relatively far downstream from active neurons, thereby limiting the ability of BOLD imaging methods to precisely pinpoint neural generators. Hemodynamic measures based on apparent diffusion coefficients (ADCs) have recently been used to identify more upstream functional blood flow changes in the capillaries, arterioles and arteries. In particular, we recently showed that, due to the complementary vascular sensitivities of ADC and BOLD signals, the voxels conjointly activated by both measures may identify the capillary networks of the active neuronal areas. In this study, we first used simultaneously acquired ADC and BOLD functional imaging signals to identify brain voxels activated by ADC only, by both ADC and BOLD and by BOLD only, thereby delineating voxels relatively dominated by the arterial, capillary, and draining venous neurovascular compartments, respectively. We then examined the event-related fMRI BOLD responses in each of these delineated neurovascular compartments, hypothesizing that their event-related responses would show different temporal componentries. In the regions activated by both the BOLD and ADC contrasts, but not in the BOLD-only areas, we observed an initial transient signal reduction (an initial dip), consistent with the local production of deoxyhemoglobin by the active neuronal population. In addition, the BOLD-ADC overlap areas and the BOLD-only areas showed a clear poststimulus undershoot, whereas the compartment activated by only ADC did not show this component. These results indicate that using ADC contrast in conjunction with BOLD imaging can help delineate the various neurovascular compartments, improve the localization of active neural populations, and provide insight into the physiological mechanisms underlying the hemodynamic signals.

Perfusion‐based functional magnetic resonance imaging

AbstractThe measurement of cerebral blood flow (CBF) is a very important way of assessing tissue viability, metabolism, and function. CBF can be measured noninvasively with magnetic resonance imaging (MRI) by using arterial water as a perfusion tracer. Because of the tight coupling between neural activity and CBF, functional MRI (fMRI) techniques are having a large impact in defining regions of the brain that are activated due to specific stimuli. Among the different fMRI techniques, CBF‐based fMRI has the advantages of being specific to tissue signal change, a critical feature for quantitative measurements within and across subjects, and for high‐resolution functional mapping. Unlike the conventional blood oxygenation level dependent (BOLD) technique, the CBF change is an excellent index of the magnitude of neural activity change. Thus, CBF‐based fMRI is the tool of choice for longitudinal functional imaging studies. A review of the principles and theoretical backgrounds of both continuous and pulsed arterial spin labeling methods for measuring CBF is presented, and a general overview of their current applications in the field of functional brain mapping is provided. In particular, examples of the use of CBF‐based fMRI to investigate the fundamental hemodynamic responses induced by neural activity and to determine the signal source of the most commonly used BOLD functional imaging are reviewed. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson 16A: 16–27, 2003