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Diffusion-weighted (DW) functional magnetic resonance imaging (fMRI) signal changes have been noted as a promising marker of neural activity. Although there is no agreement on the signal origin, the blood oxygen level dependent (BOLD) effect has figured as one of the most likely sources. In order to investigate possible BOLD and non-BOLD contributions to the signal, DW fMRI was performed on normal volunteers using a sequence with two echo-planar acquisitions after pulsed-gradient spin-echo. Along with the changes to the signal amplitude (ΔS/S) measured at both echo-times, this sequence allowed changes to the transverse relaxation rate (ΔR2) to be estimated for multiple b-values during hypercapnia (HC) and visual stimulation (VS). ΔS/S and ΔR2 observed during HC were relatively insensitive to increasing b-value. On the other hand, ΔS/S demonstrated a clear dependence on b-value at both echo-times for VS. In addition, ΔR2 during the latter half of VS was significantly more negative at b=1400s/mm(2) than for the time-courses at lower b-value, but ΔR2 during the post-stimulus undershoot was independent of b-value. The results have been discussed in terms of two models: the standard intravascular-extravascular model for fMRI and a three-compartment model (one intra- and two extravascular compartments). Within these interpretations the results suggest that the majority of the response is linked to changes in transverse relaxation, but possible contributions from other sources may not be ruled out., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

As the oscillating gradient spin-echo sequence has shown promise as a means to probe tissue microstructure, it was applied here to diffusion-tensor imaging of in vivo rat brain. The apparent diffusion tensor (ADT) was estimated for motion-probing gradient (MPG) frequencies in the range 33.3-133.3 Hz, and regions-of-interest (ROIs) in the corpus callosum (CC), visual cortex (VC), cerebellar white matter (CBWM) and cerebellar grey matter (CBGM) were selected for detailed analysis. There were substantial, approximately linear changes to the ADT with increasing MPG frequency for all four ROIs. All ROIs showed clear increases in mean diffusivity. CBWM had a substantial decrease in fractional anisotropy, whereas the CC and VC had minor increases of the same parameter. All eigenvalues of the ADT tended to increase with frequency for the CBWM, CBGM and VC, but only the principal eigenvalue increased strongly for the CC. On the other hand, there was no evidence that the orientation of the principal eigenvector varied systematically with MPG frequency for any of the ROIs. The relationship between the behaviour of the eigenvalues and the behaviours of the mean diffusivity and fractional anisotropy is investigated in detail. Pixelwise linear fits to the MD from individual animals found elevated changes across the cerebellum. The data acquired for this work encompassed a range of effective diffusion-times from 7.5 ms down to 1.875 ms, and some ideas on how the results might be used to extract quantitative information about brain tissue microstructure are discussed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Spin-echo diffusion-weighted functional MRI (DW-fMRI) was performed on a rat forepaw electrostimulation model at 7 T. This small animal model used electric (rather than visual) stimulation and allowed DW-fMRI experiments to be performed over a broader range of acquisition parameters than previous work on humans and cats. Resting state experiments with injections of ultra-small superparamagnetic iron oxide (USPIO) were also used to investigate the effects of gradient coupling on the signal change. The experiments were performed over five b-values (0, 200, 800, 1400 and 2000s/mm(2)) and three echo-times (30, 60 and 90 ms). Alterations to the stimulation-induced response with respect to TE and b-value were evaluated in two intervals: the positive stimulus-correlated response (5-20s after stimulus onset) and the post-stimulus undershoot (27-40s). There was no strong dependence of the signal change on b-value for any of the intervals or TEs. Similarly, changes to the apparent transverse relaxation rate showed no clear dependence on b-value. In contrast to previous DW-fMRI studies, the simplest explanation for the observed data is a single-compartment signal model with the functional signal changes probably corresponding to extravascular SE-BOLD. Experiments with USPIO suggested that at 7 T and within the range of parameters used, the influence of gradient coupling may be sufficient to explain minor DW-fMRI signal changes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Positron Emission Tomography (PET) has the unique capability of measuring brain function but its clinical potential is affected by low resolution and lack of morphological detail. Here we propose and evaluate a wavelet synergistic approach that combines functional and structural information from a number of sources (CT, MRI and anatomical probabilistic atlases) for the accurate quantitative recovery of radioactivity concentration in PET images. When the method is combined with anatomical probabilistic atlases, the outcome is a functional volume corrected for partial volume effects., Methods: The proposed method is based on the multiresolution property of the wavelet transform. First, the target PET image and the corresponding anatomical image (CT/MRI/atlas-based segmented MRI) are decomposed into several resolution elements. Secondly, high-resolution components of the PET image are replaced, in part, with those of the anatomical image after appropriate scaling. The amount of structural input is weighted by the relative high frequency signal content of the two modalities. The method was validated on a digital Zubal phantom and clinical data to evaluate its quantitative potential., Results: Simulation studies showed the expected relationship between functional recovery and the amount of correct structural detail provided, with perfect recovery achieved when true images were used as anatomical reference. The use of T1-MRI images brought significant improvements in PET image resolution. However improvements were maximized when atlas-based segmented images as anatomical references were used; these results were replicated in clinical data sets., Conclusion: The synergistic use of functional and structural data, and the incorporation of anatomical probabilistic information in particular, generates morphologically corrected PET images of exquisite quality.

Dopamine D(2) receptor occupancy by antipsychotic drugs has been measured with positron emission tomography (PET) by comparing the binding potential (BP) values before and after drug administration. This occupancy has been found to be related to clinical effects and side effects. In this study, we evaluated the uncertainty of the quantitative analysis for estimating the dopamine D(2) receptor occupancy by antipsychotics in simulation and human studies of [(11)C]raclopride and for the high affinity ligand [(11)C]FLB 457. Time-activity curves of [(11)C]raclopride and [(11)C]FLB 457 were simulated, and the reliability of BP estimated by a simplified reference tissue model and the calculated occupancy were investigated for various noise levels, BP values, and scan durations. Then, in the human PET study with and without antipsychotics, the uncertainty of BP and occupancy estimates and the scan duration required for a reliable estimation were investigated by a bootstrap approach. Reliable and unbiased estimates of [(11)C]raclopride BP(ND) could be obtained with recording as short as 32 min, with the relative standard deviation (SD) of the striatal occupancy remaining less than 10%. Conversely, in [(11)C]FLB 457 studies, the mean value increased and SD of the temporal cortex and thalamus exceeded 10% when the scan duration was shorter than 60 min. These results demonstrated that dopamine D(2) receptor occupancy by antipsychotics can be estimated precisely with an optimal scan duration with [(11)C]raclopride and [(11)C]FLB 457.

When we cannot recall the name of a well-known person despite preserved access to his/her semantic knowledge, a phonological hint such as his/her initials sometimes helps us to recall the name. This type of recall failure appeared to occur by the transmission deficit from the lexical-semantic stage to the lexical-phonological stage in name recall processes, and the phonological cue appeared to activate this transmission, which leads to successful recall. We hypothesized that the brain regions responsible for the transmission would respond to the phonological cue that facilitates name recall, and would also respond to successful recall. A famous face image was presented with a phonological cue, and the subjects were required to recall and overtly pronounce the name during fMRI scanning. The behavioral results showed that the first syllable cue induced greater number of successful recall trials than both the non-verbal sound of the chime and the non-first syllable cue, suggesting that the first syllable facilitated name recall. The fMRI results demonstrated that two regions in the left superior temporal gyrus responded more strongly to the first syllable than both to the non-verbal sound of the chime and to the non-first syllable. In addition, these two regions were activated when the name recall was successful. These results suggest that two regions in the left superior temporal gyrus may play a crucial role in the transmission from the lexical-semantic to the lexical-phonological stage in the name recall processes.

Cerebral vascular mean transit time (MTT) characterizes the cerebral circulation. MTT has been measured in humans by carotid angiography, x-ray computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). However, regional distribution of MTT has not been investigated in detail. Thus, we investigated regional distribution of normal human MTT. Regional cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured by PET with H(2)(15)O and (11)CO, respectively, in each of 10 normal subjects. MTT was calculated as MTT = CBV/CBF. MTT for cerebral cortical regions was 3.2 to 4.4 s. These values were in accord with MTT measured by carotid angiography, CT, and MRI. Considered regionally, MTT was longest in the temporooccipital cortex, and shorter in the cerebellum, thalamus, and putamen, than in all other regions. These regional differences in MTT that are inversely proportional to cerebral perfusion pressure might relate to regional differences in cerebral vascular tone. Simulation studies showed that errors in CBF and thus MTT caused by regional differences in regional tracer appearance time, distribution volume, and gray-white matter mixing were negligible.

We have created images of z value, error, and variation components for a PET activation study using various ANOVA designs and anatomical standardization methods. Data were acquired in four PET centers. In each center, CBF was measured on six normal male subjects under resting and covert verb generation, three times for each. The images were anatomically standardized with LINEAR transformation, SPM (Ver. 95), HBA (Karolinska/Tohoku), or MICHIGAN (Minoshima). ANOVA was performed pixel by pixel to compute t (and z) for the task main effect (Verb vs Rest) in four different designs: (i) two way (subject and task) (2W), (ii) two-way with interaction (2WI), (iii) subject considered a random factor (2WI-MX), and (iv) three-way (subject, task, and replication) (3W). A large area extending from the Broca to the left premotor cortex was activated. The localization of the highest peak depended both on the anatomical standardization and on the ANOVA design, the variation ranging 3-4 cm. Smoothing reduced the variation while erasing possible subfoci. The z images of 2W, 2WI, and 3W looked alike, whereas 2WI-MX presented lower peak z values. SPM tended to present higher z values than the other methods. The error was high in the gray and low in the white matter. The root mean square for the subject effect was high on the border of gray matter especially in LINEAR and HBA, revealing intersubject mismatch in the gray matter distribution. The root mean square for the subject-by-task interaction effect revealed individual variation in activation., (Copyright 1998 Academic Press.)