Yonglin Pu

Brain activation in the processing of Chinese characters and words: A functional MRI study

Functional magnetic resonance imaging was used to identify the neural correlates of Chinese character and word reading. The Chinese stimuli were presented visually, one at a time. Subjects covertly generated a word that was semantically related to each stimulus. Three sorts of Chinese items were used: single characters having precise meanings, single characters having vague meanings, and two‐character Chinese words. The results indicated that reading Chinese is characterized by extensive activity of the neural systems, with strong left lateralization of frontal (BAs 9 and 47) and temporal (BA 37) cortices and right lateralization of visual systems (BAs 17–19), parietal lobe (BA 3), and cerebellum. The location of peak activation in the left frontal regions coincided nearly completely both for vague‐ and precise‐meaning characters as well as for two‐character words, without dissociation in laterality patterns. In addition, left frontal activations were modulated by the ease of semantic retrieval. The present results constitute a challenge to the deeply ingrained belief that activations in reading single characters are right lateralized, whereas activations in reading two‐character words are left lateralized. Hum. Brain Mapping 10:16–27, 2000.

Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer.

OBJECTIVE To assess the prognostic value of metabolic tumor burden as measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT), independent of current Union Internacional Contra la Cancrum/American Joint Committee on Cancer tumor, node, and metastasis (TNM) stage; in comparison with that of standardized uptake value (SUV) in surgical patients with non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS This study retrospectively reviewed 104 consecutive surgical patients (47 males, 57 females, median age at PET/CT scan of 67.92 years) with diagnosed stage I to IV NSCLC who had baseline (18)F-FDG PET/CT scans. The (18)F-FDG PET/CT scans were performed in accordance with National Cancer Institute guidelines. The MTV of tumors in the whole body (MTV(WB)), TLG of tumors in the whole body (TLG(WB)), the maximum standardized uptake value of tumors in the whole body (SUV(maxWB)) as well as the mean standardized uptake value of tumor in the whole body (SUV(meanWB)) were measured. The median follow-up among 67 survivors was 42.07 months from the PET/CT (range 2.82-80.95 months). Statistical methods included Kaplan-Meier curves, Cox regression, and C-statistics. The interobserver variability of SUV(maxWB), SUV(meanWB), MTV(WB), and TLG(WB) between two observers was analyzed using concordance correlation coefficients (CCCs). RESULTS The interobserver variability of SUV(maxWB), SUV(meanWB), MTV(WB) and TLG(WB) was very low with CCCs greater than 0.882. There was a statistically significant association of stage with overall survival (OS). The hazard ratio (HR) of stage III and stage IV as compared with stage I was 3.60 (P = .001) and 4.00 (P = .013), respectively. The MTV(WB) was significantly associated with OS with a HR for 1-unit increase of ln(MTV(WB)) of 1.40/1.32 (P = .004/.039), before/after adjusting for stage and other prognostic factors including chemoradiation therapy, and surgical procedure, respectively. TLG(WB) had a statistically significant association with OS before and after adjusting for stage and the other prognostic factors. The HR for 1-unit increase in ln(TLG(WB)) was 1.26 (P = .011) and 1.25 (P = .031), before and after the adjustment, respectively. Subjects with conditions that led to pneumonectomy (HR = 2.82, P = .035) or segmental resection (HR = 3.44, P = .044) had significantly worse survival than those needing lobectomy. There was no statistically significant association between OS and age, gender, tumor histology, ln(SUV(maxWB)), and ln(SUV(meanWB)) (all P > .05). There were 37 deaths during follow-up. CONCLUSION Baseline whole-body metabolic tumor burden as measured with MTV(WB) and TLG(WB) on FDG PET is a prognostic measure independent of clinical stage and other prognostic factors including chemoradiation therapy and surgical procedure with low interobserver variability and may be used to further risk stratify surgical patients with NSCLC. This study also suggests that MTV and TLG are better prognostic measures than SUV(max) and SUV(mean). These results will need to be validated in larger cohorts in a prospective study.

Cerebral blood flow measurement by dynamic contrast MRI using singular value decomposition with an adaptive threshold

Singular value decomposition (SVD) is a promising deconvolution technique for use in dynamic contrast agent magnetic resonance perfusion imaging. Computer simulations, however, show that the selection of the threshold for SVD affects the accuracy of the cerebral blood flow measurements and may distort the shape of the vascular residue function. In this report, a pixel‐by‐pixel thresholding method is proposed based on the signal‐to‐noise ratio of the concentration time curve at maximum concentration (SNRC). Monte Carlo simulations were used to determine the optimal threshold for different SNRC. This technique was used to analyze data from six healthy volunteers, resulting in a mean gray to white matter cerebral blood flow ratio of 2.67 ± 0.07. This value is in excellent agreement with values published in the literature. Magn Reson Med 42:167–172, 1999.

Temporal dissociation of parallel processing in the human subcortical outputs

Many tasks require rapid and fine-tuned adjustment of motor performance based on incoming sensory information. This process of sensorimotor adaptation engages two parallel subcortico–cortical neural circuits, involving the cerebellum and basal ganglia, respectively. How these distributed circuits are functionally coordinated has not been shown in humans. The cerebellum and basal ganglia show very similar convergence of input–output organization,, which presents an ideal neuroimaging model for the study of parallel processing at a systems level. Here we used functional magnetic resonance imaging to measure the temporal coherence of brain activity during a tactile discrimination task. We found that, whereas the prefrontal cortex maintained a high level of activation, output activities in the cerebellum and basal ganglia showed different phasic patterns. Moreover, cerebellar activity significantly correlated with the activity of the supplementary motor area but not with that of the primary motor cortex; in contrast, basal ganglia activity was more strongly associated with the activity of the primary motor cortex than with that of the supplementary motor area. These results demonstrate temporally partitioned activity in the cerebellum and basal ganglia, implicating functional independence in the parallel subcortical outputs. This further supports the idea of task-related dynamic reconfiguration of large-scale neural networks,.

Prognostic Value of the Quantitative Metabolic Volumetric Measurement on 18F-FDG PET/CT in Stage IV Nonsurgical Small-cell Lung Cancer

RATIONALE AND OBJECTIVES Stage IV non-small-cell lung cancer (NSCLC) consists of a heterogeneous group of patients with different prognoses. We assessed the prognostic value of baseline whole body tumor burden as measured by metabolic tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake values (SUV(max) and SUV(mean)) of all tumors in nonsurgical patients with Stage IV NSCLC. MATERIALS AND METHODS Ninety-two consecutive patients with newly diagnosed Stage IV NSCLC who had a pretreatment F-18 fludeoxyglucose positron emission tomography/computed tomography scan were retrospectively reviewed. The MTV, TLG, SUV(mean), and SUV(max) of whole-body (WB) tumors were measured with the MIMvista workstation with manual adjustment. RESULTS There was a statistically significant association between overall survival (OS) and ln(MTV)/ln(TLG) at the level of WB tumor burden (MTV(WB)) and of primary tumor (MTV(T)). The hazard ratio (HR) for a 1-unit increase of ln(MTV(WB)) and ln(MTV(T)) before and after adjusting for age and gender was 1.48/1.48 (both P < .001) and 1.25/1.25 (P = .006, .007), respectively. The HR for a 1-unit increase of ln(TLG(WB)) and ln(TLG(T)) before and after adjusting for age and gender was 1.37/1.37 (both P = .001) and 1.19/1.19 (P = .001, .017), respectively. There was no statistically significant association between OS and ln(SUV(max)) and ln(SUV(mean)) at WB tumor burden, primary tumor, nodal metastasis, or distant metastasis (P > .05). There was low interobserver variability between two radiologists with concordance correlation coefficients of 0.90 for ln(MTV(WB)) and greater than 0.90 for SUV(maxWB), SUV(meanWB), and ln(TLG(WB)). CONCLUSION Baseline WB metabolic tumor burden, as measured with MTV and TLG, is a prognostic measurement in patients within Stage IV NSCLC with low interobserver variability. This study also suggests pretreatment MTV and TLG measurements may be used to further stratify patients with Stage IV NSCLC and are better prognostic measures than SUV(max) and SUV(mean) measurements.

The human red nucleus and lateral cerebellum in supporting roles for sensory information processing

A functional MRI study compared activation in the red nucleus to that in the lateral cerebellar dentate nucleus during passive and active tactile discrimination tasks. The study pursued recent neuroimaging results suggesting that the cerebellum may be more associated with sensory processing than with the control of movement for its own sake. Because the red nucleus interacts closely with the cerebellum, the possibility was examined that activity in red nucleus might also be driven by the requirement for tactile sensory processing with the fingers rather than by finger movement alone. The red and dentate nuclei were about 300% more active (a combination of activation areas and intensities) during passive (non‐motor) tactile stimulation when discrimination was required than when it was not. Thus, the red nucleus was activated by purely sensory stimuli even in the absence of the opportunity to coordinate finger movements or to use the sensory cues to guide movement. The red and dentate nuclei were about 70% more active during active tactile tasks when discrimination was required than when it was not (i.e., for simple finger movements alone). Thus, the red nucleus was most active when the fingers were being used for tactile sensory discrimination. In both the passive and active tactile tasks, the observed activation had a contralateralized pattern, with stronger activation in the left red nucleus and right dentate nucleus. Significant covariation was observed between activity in the red nucleus and the contralateral dentate during the discrimination tasks and no significant correlation between the red nucleus and the contralateral dentate activity was detected during the two non‐discrimination tasks. The observed interregional covariance and contralateralized activation patterns suggest strong functional connectivity during tactile discrimination tasks. Overall, the pattern of findings suggests that the activity in the red nucleus, as in the lateral cerebellum, is more driven by the requirements for sensory processing than by motor coordination per se. Hum. Brain Mapping 10:147–159, 2000.

High prevalence of pineal cysts in healthy adults demonstrated by high-resolution, noncontrast brain MR imaging

BACKGROUND AND PURPOSE: Although the prevalence of pineal cysts in autopsy series has been reported as being between 25% and 40%, MR studies have documented their frequency to range between 1.5% and 10.8%. The purpose of this high-resolution brain MR imaging study at 1.9T was to determine the prevalence of pineal cysts in healthy adults. MATERIALS AND METHODS: Brain MR images of 100 healthy young volunteers were randomly selected from our International Consortium for Brain Mapping project data base. Cysts were detected as circular areas of isointensity relative to CSF on both 3D gradient-echo T1-weighted and 2D fast spin-echo T2-weighted images. The inner diameters of all visualized pineal cysts were measured, and a criterion of 2.0 mm of the largest inner cross-sectional diameter was used to categorize cysts as being either small cystic changes (<2.0-mm diameter) or pineal cysts (>2.0-mm diameter). RESULTS: Twenty-three percent (23/100) of the volunteers had pineal cysts with a mean largest inner cross-sectional diameter of 4.3 mm (range, 2–14 mm); 13% (13/100) demonstrated cystic changes involving the pineal gland with the largest inner cross-sectional diameter of less than 2.0 mm. There was a slight female predominance. Two subjects with long-term follow-up scans showed no symptoms or changes in the size of their pineal cysts. CONCLUSION: On high-resolution MR imaging, the prevalence of pineal cysts was 23% in our healthy group of adults, which is consistent with previous autopsy studies. Long-term follow-up studies of 2 cases demonstrated the stability of the cysts.

Cerebral hemodynamic response in Chinese (first) and English (second) language processing revealed by event-related functional MRI

Comparative functional neuroimaging studies using the block design paradigm have previously demonstrated that there are no significant differences in the location of areas of cerebral activation when native Chinese speakers independently process single words or sentences in both the Chinese (first) and English (second) languages. While it has also been documented that significant domains of brain response include the inferior to middle left frontal lobe, the latency, amplitude and duration of the associated hemodynamic changes during isolated neural processing of Chinese and English languages still remain unknown. The aim of this study, therefore, was to examine the characteristics of the hemodynamic alterations in the above-mentioned regions with event-related functional MRI (ER-fMRI) when native Chinese speakers performed verb generation tasks in both the Chinese (first) and English (second) languages. Our results demonstrate the presence of a similar neural activity-induced hemodynamic response in the inferior to middle left frontal lobe during both tasks. Further, there were also no statistically significant differences among the variables that described the hemodynamic response curves. These findings strongly imply that the underlying neural mechanism for Chinese (first) and English (second) language processing may be similar in native Chinese speakers.

Children's Brain Activations While Viewing Televised Violence Revealed by fMRI

Though social and behavioral effects of TV violence have been studied extensively, the brain systems involved in TV violence viewing in children are, at present, not known. In this study, 8 children viewed televised violent and nonviolent video sequences while brain activity was measured with functional magnetic resonance imaging. Both violent and nonviolent viewing activated regions involved in visual motion, visual object and scenes, and auditory listening. However, viewing TV violence selectively recruited a network of right hemisphere regions including precuneus, posterior cingulate, amygdala, inferior parietal, and prefrontal and premotor cortex. Bilateral activations were apparent in hippocampus, parahippocampus, and pulvinar. TV violence viewing transiently recruits a network of brain regions involved in the regulation of emotion, arousal and attention, episodic memory encoding and retrieval, and motor programming. This pattern of brain activations may explain the behavioral effects observed in many studies, especially the finding that children who are frequent viewers of TV violence are more likely to behave aggressively. Such extensive viewing may result in a large number of aggressive scripts stored in long-term memory in the posterior cingulate, which facilitates rapid recall of aggressive scenes that serve as a guide for overt social behavior.

Comparison of the temporal response in perfusion and BOLD-based event- related functional MRI

Event‐related functional MRI (ER‐fMRI) based on both blood oxygen level‐dependent (BOLD) contrast and perfusion contrast has been recently developed to study human brain activation due to brief stimulation. In this report, both BOLD‐ and perfusion‐based ER‐fMRI were directly compared using repeated single‐trial, short visual stimulation (1 sec) in six human volunteers. The results show that the cerebral blood flow change reached a maximum approximately 1 sec earlier than the BOLD signal change (4.2 ± 0.2 sec vs. 5.1 ± 0.2 sec after the stimulation, P < 0.05). The full width at half maximum of the hemodynamic response measured by perfusion was not significantly different from that measured with BOLD (5.1 ± 0.6 sec vs. 5.9 ± 0.6 sec). A positive linear correlation was found between the maximum perfusion and maximum BOLD signal changes (r = 0.77, P = 0.07). Magn Reson Med 43:768–772, 2000.