Yau Yau Wai

Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent - a pilot study

PURPOSEnThe compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([(18)F]AV-45) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid (A beta) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [(18)F]AV-45 in human subjects.nnnMETHODSnIn vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimers disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0+/-5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7+/-13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information.nnnRESULTSnIn vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12+/-0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7+/-78.6 microGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq, respectively.nnnCONCLUSIONn[(18)F]AV-45 binds specifically to A beta in vitro, and is a safe PET tracer for studying A beta distribution in human brain. The dosimetry is suitable for clinical and research application.

Study-specific EPI template improves group analysis in functional MRI of young and older adults

Spatial normalization to a common coordinate space, e.g. via the Montreal Neurological Institute (MNI) brain template, is an essential step of analyzing multi-subject functional MRI (fMRI) datasets. The imperfect compensation for individual regional discrepancies during spatial transformation, which could potentially introduce localization errors of the activation foci and/or reduce the detection sensitivity, may be minimized if a template specifically designed for the subjects of a study is applied. In this fMRI study, we proposed and evaluated the use of a study-specific template (SST) based on the mean of individually normalized echo-planar images for group data analysis. A hand flexion and a word generation tasks were performed on young volunteers in experiment 1. Comparing with the MNI template approach, greater t-values of local maxima and activated voxels were detected within volume-of-interests (VOIs) with the SST approach in both tasks. Moreover, the SST approach reduced Euclidean distances between activation foci of individuals and group by 1.52 mm in motor fMRI and 5.84 mm in language fMRI. Similar results were obtained with or without spatial smoothing of the echo-planar images. Experiment 2 further examined these two approaches in older adults, in which volumetric differences between subjects are of great concerns. With a working memory task, the SST approach showed greater t-values of local maxima and activated voxels within the VOI of prefrontal gyrus. This study demonstrated that the SST resulted in more focused activation patterns and effectively improved the fMRI sensitivity, which suggested potentials of reducing number of subjects required for group analysis.

Functional MRI of amblyopia before and after levodopa

Functional magnetic resonance imaging (fMRI) was applied to five older amblyopes with monocular amblyopia before and after levodopa treatment. During the experiment, images were acquired in two runs with visual stimulation delivered through the sound and the amblyopic eyes, respectively. The experiment was performed on each of the subjects, before and after their oral administration of levodopa/carbidopa (0.5/0.12 mg/kg) three times per day for 7 weeks. Our study demonstrated that there was no effect on the spatial extent of the visual cortical activation during the sound eye stimulation (P=0.17), but some improvement during the amblyopic eye stimulation (P=0.06). The volume ratio between the amblyopic and sound eye stimulation significantly increased after the treatment (P<0.05). This finding supports the previous studies of levodopa effect on amblyopia at the visual cortical level, and suggests that fMRI can be a useful tool in assessing changes of visual cortical activity after the treatment

Vascular space occupancy-dependent functional MRI by tissue suppression†

To measure the cerebral blood volume (CBV) dynamics during neural activation, a novel technique named vascular space occupancy (VASO)‐based functional MRI (fMRI) was recently introduced for noninvasive CBV detection. However, its application is limited because of its low contrast‐to‐noise ratio (CNR) due to small signal change from the inverted blood.

Inflow effects on hemodynamic responses characterized by event-related fMRI using gradient-echo EPI sequences.

The purpose of this study is to determine whether blood inflow impacts the temporal behavior of BOLD-contrast fMRI signal changes in a typical event-related paradigm. The inflow contributions in the hemodynamic response to repeated single trials of short visual stimulation were assessed with a gradient-echo EPI sequence by altering the flip angle (FA) from 30 degrees to 90 degrees at a repetition time of 1 s. For each FA condition (30 degrees, 60 degrees, and 90 degrees), 30 trials were performed on 15 healthy volunteers on a 3T MRI scanner. Comparing the percent BOLD contrast, prominent inflow effects were found with statistical significance between the 90 degrees- and 30 degrees-FA conditions (0.73 +/- 0.15 versus 0.67 +/- 0.12%, p=0.028). BOLD responses with FA=30 degrees exhibited latencies significantly slower than those with FA=90 degrees (3.69 +/- 0.39 s versus 3.37 +/- 0.28 s, p=0.001). The falling time of the 30 degrees-FA responses was earlier but not statistically different from that of the 90 degrees-FA (8.17 +/- 1.04 s versus 8.03 +/- 1.15 s, p=0.3). Using a voxelwise analysis, the latency variations of the activated visual areas were determined at several contrast-to-noise ratio (CNR) levels (controlled by averaging different numbers of randomly selected trials). The latency variations from the 90 degrees-FA responses were greater at lower CNR but similar at higher CNR levels when comparing to the 30 degrees-FA ones. This study suggests that inflow effects contribute to the BOLD signal, resulting in hemodynamic response with shorter latency.

False-Positive Analysis of Functional MRI During Simulated Deep Brain Stimulation: A Phantom Study

To investigate the false‐positive activations/deactivations in functional MRI (fMRI) of deep brain stimulation (DBS) using a phantom.

Temporal resolving power of perfusion- and BOLD-based event-related functional MRI

Functional magnetic resonance imaging (fMRI) based on both perfusion and blood oxygenation level-dependent (BOLD) contrasts has been widely applied in spatiotemporal mapping of the human brain function. Temporal resolving power of fMRI is limited by the smoothed hemodynamic response function dispersed from the neuronal activity. In this study, temporal modulation transfer functions were utilized to quantify the resolving powers of perfusion and BOLD fMR signals in time domain. The impulse response function was determined using brief visual stimulations and event-related image acquisition schemes. An important feature of arterial spin labeling techniques is that quantitative perfusion and BOLD signals could be simultaneously acquired. This simultaneous BOLD response may arise from signals that are more proximal to capillary beds, and its temporal resolution may be different from that of the typical BOLD response. Therefore, we assessed and compared the temporal resolving capabilities of perfusion, simultaneous BOLD, and the typical BOLD response obtained from the gradient echo EPI pulse sequence. Full-width-at-half-maximums of perfusion and simultaneous BOLD measurements were significantly smaller than that of BOLD ones (4.3+/- 0.6 s vs 5.5 +/- 0.9 s, p<0.02 and 4.7 +/- 1.3 s vs 5.5 +/- 0.9 s, p<0.01, respectively). The corresponding temporal resolving powers of perfusion and simultaneous BOLD signals were statistically better than that of BOLD signals (0.23 +/- 0.03 Hz vs 0.17 +/- 0.02 Hz, p<0.01 and 0.21 +/- 0.04 Hz vs 0.17 +/- 0.02 Hz, p<0.01, respectively). Our results showed that the typical BOLD response was significantly smoothed from the perfusion response, thus resulting in a degraded temporal resolving power. However, results from the simultaneous BOLD and perfusion measurements were not significantly different. Biophysical implications of the experimental outcomes were further investigated using a computer simulation based on the Balloon model. By fitting the measured data into the model, an apparently longer transit time was obtained for the typical BOLD signal (1.7 s), comparing to that for the simultaneous BOLD one (1.2 s). Therefore, the simultaneous BOLD signal was regarded as less susceptible to the variations from local draining veins. Combining the simulation result with the significantly discrepant resolving powers between the two BOLD signals, we speculated that the blurred effects from large vessels played a predominant role that further reduced the temporal resolution of the BOLD-based fMRI from the perfusion response.

Implementations of clinical functional magnetic resonance imaging using character-based paradigms for the prediction of Chinese language dominance

Purpose Recently, functional MRI (fMRI) using word generation (WG) tasks has been shown to be effective for mapping the Chinese language–related brain areas. In clinical applications, however, patients performance cannot be easily monitored during WG tasks. In this study, we evaluated the feasibility of a word choice (WC) paradigm in the clinical setting and compared the results with those from WG tasks. Method Intrasubject comparisons of fMRI with both WG and WC paradigms were performed on six normal human subjects and two tumor patients. Subject responses in the WC paradigm, based on semantic judgments, were recorded. Activation strength, extent, and laterality were evaluated and compared. Results Our results showed that fMRI with the WC paradigm evoked weaker neuronal activation than that with the WG paradigm in Chinese language–related brain areas. It was sufficient to reveal language laterality for clinical use, however. In addition, it resulted in less nonlanguage-specific brain activation. Conclusion Results from the patient data demonstrated strong evidence for the necessity of incorporating response monitoring during fMRI studies, which suggested that fMRI with the WC paradigm is more appropriate to be implemented for the prediction of Chinese language dominance in clinical environments.

Variations in BOLD response latency estimated from event-related fMRI at 3T: Comparisons between gradient-echo and Spin-echo

Functional magnetic resonance imaging (fMRI) commonly uses gradient‐recalled echo (GRE) signals to detect regional hemodynamic variations originating from neural activities. While the spatial localization of activation shows promising applications, indexing temporal response remains a poor mechanism for detecting the timing of neural activity. Particularly, the hemodynamic response may fail to resolve sub‐second temporal differences between brain regions because of its signal origin or noise in data, or both. This study aimed at evaluating the performance of latency estimation using different fMRI techniques, with two event‐related experiments at 3T. Experiment I evaluated latency variations within the visual cortex and their relationship with contrast‐to‐noise ratios (CNRs) for GRE, spin echo (SE), and diffusion‐weighted SE (DWSE). Experiment II used delayed visual stimuli between two hemifields (delay timeu2009=u20090, 250, and 500 ms, respectively) to assess the temporal resolving power of three protocols: GRETR1000, GRETR500, and SETR1000. The results of experiment I showed the earliest latency with DWSE, followed by SE, and then GRE. Latency variations decreased as CNR increased. However, similar variations were found between GRE and SE, when the latter had lower CNR. In experiment II, measured stimulus delays from all conditions were significantly correlated with preset stimulus delays. Inter‐subject variation in the measured delay was found to be greatest with GRETR1000, followed by GRETR500, and the least with SETR1000. Conclusively, blood oxygenation level‐dependent responses obtained from GRE exhibit greater CNR but no compromised latency variations in the visual cortex. SE is potentially capable of improving the performance of latency estimation, especially for group analysis.

The relationships between brain structural changes and perceived loneliness in older adults suffering from late-life depression

Late‐life depression is a significant health risk factor for older adults, part of which is perceived loneliness. In this voxel‐based morphometry study, we examined the relationships between perceived loneliness and depression recurrence.