Young-Bo Kim

Seven‐tesla magnetic resonance images of the substantia nigra in Parkinson disease

To investigate anatomical changes in the substantia nigra (SN) of Parkinson disease (PD) patients with age‐matched controls by using ultra‐high field magnetic resonance imaging (MRI).

Neural substrates, experimental evidences and functional hypothesis of acupuncture mechanisms.

Objectives –  Athough acupuncture therapy has demonstrated itself to be effective in several clinical areas, the underlying mechanisms of acupuncture in general and the analgesic effect in particular are, however, still not clearly delineated. We, therefore, have studied acupuncture analgesic effect through fMRI and proposed a hypothesis, based on the obtained result, which will enlighten the central role of the brain in acupuncture therapy.

Observation of the Lenticulostriate Arteries in the Human Brain In Vivo Using 7.0T MR Angiography

Background and Purpose— We sought to examine the feasibility of observing the lenticulostriate arteries (LSAs) noninvasively by ultrahigh-field MRI with 7.0T. Methods— We used 3-dimensional time-of-flight MR angiography with a radiofrequency coil optimized for 7.0T MRI. We examined the LSAs of 6 healthy subjects and compared 7.0T MR angiography images with 1.5T ones to examine the potentials of ultrahigh-field MRI for angiography. Results— The results show clear details of LSAs and their distribution in the normal healthy subjects with large variations in the shapes, the number of branches and the sites of origin. We also observed substantial differences between the left and right sides within each subject. Although we studied only 6 subjects, we found no age- or gender-related differences in the LSAs. Conclusions— The visualization of microvasculature of the brain, such as LSAs, using 7.0T MR angiography, is possible in in vivo human studies noninvasively. We, therefore, believe that it could play a major role in the study of small vascular abnormalities, such as the early stages of cerebral strokes.

Multitracer PET imaging of amyloid plaques and neurofibrillary tangles in Alzheimer's disease

Recently developed positron emission tomography (PET) tracers, such as PIB and FDDNP, help to visualize amyloid plaques and neurofibrillary tangles in living subjects. FDDNP binds to both amyloid plaques and tangles, whereas PIB selectively labels amyloid plaques. Therefore, it will be interesting to see a direct comparison of the regional binding of the two radiotracers for plaques (PIB) and plaques and tangles (FDDNP) using multitracer PET imaging for both PIB and FDDNP in the same subjects with and without Alzheimers disease. Here we report that multitracer PET images of PIB and FDDNP in the same Alzheimer subjects show negligible PIB but strong FDDNP binding in the medial temporal cortex (hippocampus, amygdala, and parahippocampal gyrus), whereas there are significant quantities of both PIB and FDDNP binding in neocortical areas. These results suggest that tangles rather than amyloid plaques are the dominant pathology in the medial temporal cortex of living Alzheimer patients. In nondemented elderly normal subjects, PIB binding shows a significant increase in the posterior cingulate cortex compared with other brain regions, whereas in the same normal subjects we found significant FDDNP binding in the medial temporal cortex. Interestingly, the medial temporal FDDNP uptake values in normal elderly subjects were inversely correlated with long delay recall scores in the California Verbal Learning Test, a measure of episodic memory performance. We conclude that multitracer PET imaging of amyloid plaques and tangles using FDDNP and PIB in both nondemented and demented subjects provides important insight into these complicated pathological processes in living subjects.

Involvement of the anterior thalamic radiation in boys with high functioning autism spectrum disorders: A Diffusion Tensor Imaging study

BACKGROUND Autism has been hypothesized to reflect neuronal disconnection. Several recent reports implicate the key thalamic relay nuclei and cortico-thalamic connectivity in the pathophysiology of autism. Accordingly, we aimed to focus on evaluating the integrity of the thalamic radiation and sought to replicate prior white matter findings in Korean boys with high-functioning autism spectrum disorders (ASD) using Diffusion Tensor Imaging (DTI). METHODS We compared fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in 17 boys with ASD and 17 typically developing controls in the anterior thalamic radiation (ATR), superior thalamic radiation (STR), posterior thalamic radiation (PTR), corpus callosum (CC), uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF). RESULTS The two groups were group-matched on age, IQ, handedness and head circumference. In whole-brain voxel-wise analyses, FA was significantly reduced and MD was significantly increased in the right ATR, CC, and left UF in subjects with ASD (p<0.05, corrected). We found significantly lower FA in right and left ATR, CC, left UF and right and left ILF and significantly higher MD values of the CC in the ASD group in region of interest-based analyses. We also observed significantly higher RD values of right and left ATR, CC, left UF, left ILF in subjects with ASD compared to typically developing boys and significantly lower AD values of both ILF. Right ATR and right UF FA was significantly negatively correlated with total SRS score within the ASD group (r=-.56, p=.02). CONCLUSIONS Our preliminary findings support evidence implicating disturbances in the thalamo-frontal connections in autism. These findings highlight the role of hypoconnectivity between the frontal cortex and thalamus in ASD.

A fusion PET-MRI system with a high-resolution research tomograph-PET and ultra-high field 7.0 T-MRI for the molecular-genetic imaging of the brain.

We have developed a positron emission tomography (PET) and magnetic resonance imaging (MRI) fusion system for the molecular‐genetic imaging (MGI) of the in vivo human brain using two high‐end imaging devices: the HRRT‐PET, a high‐resolution research tomograph dedicated to brain imaging on the molecular level, and the 7.0 T‐MRI, an ultra‐high field version used for morphological imaging. HRRT‐PET delivers high‐resolution molecular imaging with a resolution down to 2.5 mm full width at half maximum (FWHM), which allows us to observe the brains molecular changes using the specific reporter genes and probes. On the other front, the 7.0 T‐MRI, with submillimeter resolution images of the cortical areas down to 250 μm, allows us to visualize the fine details of the brainstem areas as well as the many cortical and subcortical areas. The new PET–MRI fusion imaging system will provide many answers to the questions on neurological diseases as well as cognitive neurosciences. Some examples of the answers are the quantitative visualization of neuronal functions by clear molecular and genetic bases, as well as diagnoses of many neurological diseases such as Parkinsons and Alzheimers. The salient point of molecular‐genetic imaging and diagnosis is the fact that they precede the morphological manifestations, and hence, the early and specific diagnosis of certain diseases, such as cancers.

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.

Voxel-based analysis of Alzheimer's disease PET imaging using a triplet of radiotracers: PIB, FDDNP, and FDG

Beta amyloid plaques, neurofibrillary tangles, and impaired glucose metabolism are among the most prevalent pathological characteristics of Alzheimers disease (AD). However, separate visualization of these three AD-related pathologies in living humans has not been conducted. Here, we show that positron emission tomography (PET) imaging using the three radiotracers (11)C-Pittsburgh compound B (PIB), 2-(1-{6-[(2-(18)F-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile (FDDNP), and 2-[18F]fluoro-2-deoxy-d-glucose (FDG), in the same subjects, with and without AD, can provide valuable information on the pathological patterns of the distribution of tracers for amyloid plaque, neurofibrillary tangle, and glucose hypometabolism in AD. Voxel-based analysis of PIB-PET in patients with AD compared with normal control subjects showed that patients with AD have highly significant PIB retention in brain regions known to have high amyloid plaque deposition (e.g., frontal, parietal, temporal, and posterior cingulate/precuneus cortices). In contrast, voxel-based analysis of FDDNP-PET showed significantly high FDDNP binding in some brain regions known to have high tangle accumulation in patients with AD compared with age-matched normal subjects (e.g., entorhinal cortex, inferior temporal gyrus, and secondary visual cortex). In addition, because FDDNP binds both plaques and tangles but PIB binds plaques specifically, we examined subtracted PET data (FDDNP minus PIB) acquired from the same patients with AD using an SPM analysis. We found that the hippocampal formation was the most significant brain region in the voxel mapping of FDDNP minus PIB in the same patients with AD. Voxel-based analysis of FDG-PET in the same subjects revealed that brain regions with glucose hypometabolism in patients with AD overlap with regions of high PIB binding. In conclusion, PET imaging using these three radiotracers in the same subjects may contribute toward developing and testing disease-modifying drugs targeting amyloid pathology, tau pathology, and/or energy metabolism.

Hypertension Correlates With Lenticulostriate Arteries Visualized by 7T Magnetic Resonance Angiography

Hypertension, a major risk factor for stroke, is associated with altered arterial anatomy and function; however, the limited resolution of current imaging techniques has restricted the in vivo study of microvascular changes in the brain. In this report, we quantitatively examined the lenticulostriate arteries in hypertensive patients using ultrahigh-field 7T MRI. We compared the number of stems and branches, curvature, and tortuosity of the lenticulostriate arteries by 3D time-of-flight magnetic resonance angiography among 20 hypertensive patients (mean age: 46.6±9.1 years) and 20 age-matched healthy subjects (mean age: 47.7±8.1 years). The average numbers of stems and branches in hypertensive patients were significantly less than those of healthy subjects (P<0.002). However, this difference was abolished in older volunteers (>45 years old), whereas the difference between young hypertensive patients (≤45 years old) and age-matched healthy controls was augmented by 55% for stems and 91% for branches (P=0.001). In comparison, there were no differences in the average curvature and tortuosity of the lenticulostriate arteries and no significant difference when corrected for smoking (P=0.064). In conclusion, our results showed that there was a substantial difference in the lenticulostriate arteries of hypertensive patients compared with healthy individuals when observed in vivo by ultrahigh-resolution 7T magnetic resonance angiography, and the difference was considerable in young subjects.

Neural responses in rat brain during acute immobilization stress: A [F-18]FDG micro PET imaging study

We used the [F-18]FDG micro PET neuroimaging technique to investigate changes in brain activity induced by acute stress in rats. Animals were given immobilization stress for 1 or 2 h, or 1-h stress followed by 1-h recovery, after which their brains were scanned. Plasma corticosterone levels measured at various time points in separate groups of rats showed a rapid increase during stress and slower decrease after termination of the stress. Immobilization stress given for an hour activated the hypothalamus, entorhinal and insular/piriform cortices, and raphe pallidus nucleus. At the same time, the dorsal hippocampus, thalamus, other cortical areas (motor, somatosensory and barrel field), striatum, superior colliculus and cerebellum were deactivated. With 2-h immobilization stress, the activity of the hypothalamus, various cortical areas and dorsal hippocampus habituated during the second hour while that of the thalamus and cerebellum did not. During 1-h recovery, the hypothalamic activation and widespread cortical deactivation disappeared, but the dorsal hippocampus, thalamus and cerebellum still remained significantly deactivated. Additional brain areas such as the septum and prelimbic cortex now showed deactivation during recovery. Changes in glucose metabolism in the dorsal hippocampus and hypothalamus exhibited a highly significant negative correlation, supporting the view that the hippocampus is involved in regulating the stress response of the hypothalamo-pituitary-adrenal axis. The advantages and limitations of the [F-18]FDG micro PET used in this study are discussed.