Nambeom Kim

Quantitative analysis of the hippocampus using images obtained from 7.0 T MRI

In-vivo volumetric measurements of hippocampus have proven to be highly informative for studying various neurological diseases such as Alzheimers disease. The usefulness of volumetric imaging, however, has been limited due to the poor image resolutions obtained by currently available MRI images. In this study, a new result of volumetric image measurement of the hippocampus using 7.0 T MRI images of high contrast and resolution is described. To verify the usefulness of the proposed method, its reliability and sensitivity were examined and compared with existing imaging techniques such as 1.5 T or 3.0 T MRI imaging. The results of our study with 7.0 T MRI clearly demonstrated superior boundary detection for the hippocampal head, body, and tail compared with low field MRIs. In conclusion, robust and reproducible volumetric measurements as well as 3D images of clear contrast obtained with 7.0 T suggest the usefulness of high field MR imaging and its eventual use for the accurate diagnosis of hippocampal diseases and related research.

Observation of Glucose Metabolism in the Thalamic Nuclei by Fusion PET/MRI

The anatomy of the thalamus and its connectivity with surrounding areas are known. Localized metabolic activities at the thalamic substructural level have not been measured in vivo in human brains because of limited resolution and contrast. Methods: The energy metabolism and fine anatomic structures of the thalamus were measured simultaneously in 5 healthy subjects using a PET/MRI fusion imaging system. Measured metabolism in individual thalamic nuclei was quantified by corresponding PET/MRI images. Results: Substructures of the thalamus were clearly distinguished in 7.0-T MRI images, and the corresponding metabolic activities measured by PET were integrated by the PET/MRI system. The medial dorsal thalamic nucleus consistently showed the highest glucose uptake among the thalamic nuclei. Conclusion: These results demonstrate that substructure-specific metabolic activities in the thalamus can be measured with a PET/MRI system consisting of an ultra-high-resolution PET component and an ultra-high-field MRI component.

Analysis of Biased PET Images Caused by Inaccurate Attenuation Coefficients

PET scanners with an elongated axial field of view intended to increase overall system sensitivity, such as the high-resolution research tomograph (HRRT) scanner, have been reported to produce images with decreased signals in the brain stem and cerebellum. The cause of this negative bias of the images was analyzed, and the effects of an inaccurate linear attenuation coefficient (μ-value) of tissue and bones were separately examined. Methods: A new phantom was manufactured, and 18 human subjects were recruited for the study. 18F-FDG PET images were reconstructed using attenuation coefficient maps generated by various algorithms. The algorithms included maximum a posteriori reconstruction for transmission data (MAP-TR) with default priors, MAP-TR with adjusted priors for bone (MAP-TRadj-b), MAP-TR with adjusted priors for tissue (MAP-TRadj-t), and noise-equivalent count TR and CT-TR. Results: With the CT-TR and MAP-TRadj-t algorithms, increased intensity in the brain stem and cerebellum was seen, and negative bias was reduced. With the MAP-TRadj-t algorithm, however, positive bias increased in the central region. Inappropriate attenuation coefficients of brain tissue increased the positive or negative bias of reconstructed images, especially for the central regions of the volume. Poor representation of the skull or bone also locally increased the bias in the near regions where bone detection had failed. Conclusion: An inaccurate μ-map obtained from the MAP-TR algorithm caused the bias problem for the HRRT system. The CT-TR algorithm provided a relatively more reliable μ-map that demonstrated a small degree of intensity bias. Appropriate priors for μ-values of each tissue compartment and better classification to distinguish bone from tissue are necessary for accurate attenuation correction.

The Relationship between Sarcopenia and Systemic Inflammatory Response for Cancer Cachexia in Small Cell Lung Cancer.

Background The prognostic significance of sarcopenia, an important component of cancer cachexia, has been demonstrated in oncologic patients. Catabolic drivers have been suggested to be key features of cancer cachexia. Objective To determine the relationship between systemic inflammatory markers and CT-determined muscle mass in patients with SCLC. Methods Cross-sectional muscle areas were evaluated at the level of the third lumbar vertebra (L3) using baseline CT images in 186 SCLC patients. Sarcopenia was defined as a L3 muscle index (L3MI, muscle area at L3/height2) of < 55 cm2/m2 for men and of < 39 cm2/m2 for women. Systemic inflammatory markers investigated included serum white blood cell count (WBC), neutrophil: lymphocyte ratio (NLR), C-reactive protein (CRP), and albumin. Results Mean L3MI was 47.9 ± 9.7 cm2/m2 for men and 41.6 ± 7.0 cm2/m2 for women. Sarcopenia was present in 128 patients (68.8%), and sarcopenic patients had significant serum lymphocyte counts and albumin levels (p = 0.002 and 0.041, respectively), and higher NLRs and CRP levels (p = 0.011 and 0.026) than non-sarcopenic patients. Multivariable analysis revealed that CRP independently predicted L3MI (β = -0.208; 95% CI, -0.415 to -0.002; p = 0.048), along with gender and BMI (p values < 0.001) and performance status (p = 0.010). Conclusion The present study confirms a significant linear relationship exists between CT-determined muscle mass and CRP in SCLC patients. This association might provide a better understanding of the mechanism of cancer cachexia.

Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI) in Patients with Small Cell Lung Cancer_ Comparison with Original ALI.

Background Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR]) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI) using CT-determined L3 muscle index (L3MI, muscle area at L3/height2) beyond original ALI. Methods L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the prognostic values of low ALI and low mALI were tested using Kaplan-Meier method and Cox proportional hazards analysis. Finally, deviance statistics was used to test whether the goodness of fit of the prognostic model is improved by adding mALI as an extra variable. Results Patients with low ALI (cut-off, 31.1, n = 94) had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p < 0.001), and patients with low mALI (cut-off 67.7, n = 94) had shorter OS than patients with high mALI (median, 6.8 months vs. 16.5 months; p < 0.001). There was no significant difference in estimates of median survival time between low ALI and low mALI (z = 0.000, p = 1.000) and between high ALI and high mALI (z = 0.330, p = 0.740). Multivariable analysis showed that low ALI was an independent prognostic factor for shorter OS (HR, 1.67, p = 0.004), along with advanced age (HR, 1.49, p = 0.045), extensive disease (HR, 2.27, p < 0.001), supportive care only (HR, 7.86, p < 0.001), and elevated LDH (HR, 1.45, p = 0.037). Furthermore, goodness of fit of this prognostic model was not significantly increased by adding mALI as an extra variable (LR difference = 2.220, p = 0.136). Conclusion The present study confirms mALI using CT-determined L3MI has no additional prognostic value beyond original ALI using BMI. ALI is a simple and useful prognostic indicator in SCLC.

Ambulatory balance monitoring using a wireless attachable three-axis accelerometer

BACKGROUND AND OBJECTIVES The ability of conventional diagnostic equipment to monitor feelings of dizziness experienced during daily activities is limited. Our goal is to develop an ambulatory multipurpose device for monitoring balance to prevent falling in daily life. MATERIALS AND METHODS A three-axis accelerometers and gyroscope sensors were attached to the head, pelvis, and legs of vestibular neuritis (VN) patients or age-, height-, and body weight-matched healthy volunteers. The sum of the deviations for the scalar value of acceleration [signal vector magnitude, SVM (g)] and angular velocity (°/s) was measured using the modified Romberg test. RESULTS The repeated measure ANOVA model with acceleration showed a greater group difference (p < 0.001) than that with angular velocity (p < 0.01). There was no significant interaction effect within-subjects factor between replication and groups (p < 0.178). SVM within the VN group significantly increased for all sensor locations compared to the control group (p < 0.01). Strong correlations between measurements taken at head and pelvis as sensor location were observed for both groups (VN/control, r=0.68/r=072). CONCLUS ION The SVM appears to accurately assess balance while standing, even repetitive measurement or any location in body.

Neural substrates of Hanja (Logogram) and Hangul (Phonogram) character readings by functional magnetic resonance imaging.

The two basic scripts of the Korean writing system, Hanja (the logography of the traditional Korean character) and Hangul (the more newer Korean alphabet), have been used together since the 14th century. While Hanja character has its own morphemic base, Hangul being purely phonemic without morphemic base. These two, therefore, have substantially different outcomes as a language as well as different neural responses. Based on these linguistic differences between Hanja and Hangul, we have launched two studies; first was to find differences in cortical activation when it is stimulated by Hanja and Hangul reading to support the much discussed dual-route hypothesis of logographic and phonological routes in the brain by fMRI (Experiment 1). The second objective was to evaluate how Hanja and Hangul affect comprehension, therefore, recognition memory, specifically the effects of semantic transparency and morphemic clarity on memory consolidation and then related cortical activations, using functional magnetic resonance imaging (fMRI) (Experiment 2). The first fMRI experiment indicated relatively large areas of the brain are activated by Hanja reading compared to Hangul reading. The second experiment, the recognition memory study, revealed two findings, that is there is only a small difference in recognition memory for semantic transparency, while for the morphemic clarity was much larger between Hanja and Hangul. That is the morphemic clarity has significantly more effect than semantic transparency on recognition memory when studies by fMRI in correlation with behavioral study. Graphical Abstract

Behavioral changes of zebrafish according to cisplatin-induced toxicity of the balance system

Background and objectives: Zebrafish are commonly used as experimental animals in otolaryngology studies. However, the behavioral characteristics of these fish are not well known, especially those related to the vestibular system. The goal of this study was to evaluate behavioral changes in zebrafish due to toxicity in the balance system. Materials and methods: Zebrafish were exposed to 1000 μM cisplatin for 6 h. We, then, periodically monitored swimming depth, total swimming distance, peak swimming velocity, and mean swimming velocity of the fish for approximately 21 days. Results: Total swimming distance (p < 0.0001), peak swimming velocity (p = 0.0063), and mean swimming velocity (p < 0.0001) in the cisplatin-administered group were significantly decreased when compared with control fish. Conclusion: Our findings demonstrate that cisplatin can alter the locomotion behavior of zebrafish.

Intermixed structure of voxels with different hemispheric characteristics in the fusiform face area.

The fusiform face area, a high-level visual area, is pivotal in processing facial information. This area receives inputs from the left and right visual fields unlike the primary visual area, which only receives inputs from its contralateral visual field. Response of the fusiform face area to ipsilateral stimulation depends on the signals crossing over at the corpus callosum. We investigated the distribution of voxel-wise activation to determine whether ipsilateral-dominant voxels exist in the fusiform face area using high spatial resolution functional MRI at 7 T. We further examined the possible functional differences between ipsilateral-dominant and contralateral-dominant voxels. By unilateral visual field stimulation, we detected ipsilateral-dominant voxels in the right fusiform face area. Their distribution was spatially heterogeneous. We tested upright and inverted facial stimulation confined to unilateral visual fields and found that these ipsilateral-dominant voxels had a different functional nature from contralateral-dominant voxels.

Changes in subcortical resting-state functional connectivity in patients with psychophysiological insomnia after cognitive–behavioral therapy

Study objectives To examine the resting-state functional connectivity (FC) between subcortical regions in relation to whole-brain activity in patients with psychophysiological insomnia (PI) and changes following cognitive–behavioral therapy for insomnia (CBTi). Methods The FC between subcortical seed regions (caudate, putamen, pallidum, amygdala, thalamus, and hippocampus) and whole-brain voxels were compared between the PI group (n = 13, mean age: 51.0 ± 10.2 years) and good sleepers (GS, n = 18, mean age: 42.7 ± 12.3 years). Also, in the PI group, FC was compared before and after 5 weeks of CBTi. Results Compared to the GS group, the PI group exhibited stronger FC between the thalamus and prefrontal cortex and between the pallidum and precuneus but weaker FC between the pallidum and angular gyrus, the caudate and orbitofrontal cortex, and the hippocampus and fusiform gyrus. After CBTi, the PI group exhibited decreased FC between the thalamus and parietal cortex, the putamen and motor cortices, and the amygdala and lingual gyrus, but increased FC between the caudate and supramarginal gyrus, the pallidum and orbitofrontal cortex, and the hippocampus and frontal/parietal gyri. Conclusions The present findings demonstrate different FC in PI patients compared to GS and provide insight into the neurobiological rationale for CBTi.