Hang-Keun Kim

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.

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.

Association of harm avoidance with dopamine D2/3 receptor availability in striatal subdivisions: a high resolution PET study.

We examined the relationship between the personality trait of harm avoidance (HA) and the dopamine D(2/3) receptor availability in striatal subdivisions using high resolution positron emission tomography (PET) with [(11)C]raclopride. Twenty-one healthy subjects completed 3T magnetic resonance imaging and high resolution PET scans with [(11)C]raclopride in order to measure D(2/3) receptor availability in subregions of the striatum. The D(2/3) receptor availability was obtained on the basis of the Logan graphical method. The Temperament and Character Inventory was used to measure the biogenetic temperament of HA. The analysis revealed that the HA score had significant negative correlations with D(2/3) receptor availability in the pre-commissural dorsal caudate and post-commissural putamen, suggesting that HA is associated with D(2/3) receptor availability in the associative and sensorimotor subdivisions of the striatum, which are mainly involved in cognition and locomotion. Further research is required to determine if pathological states have similar dopaminergic mechanisms in specific striatal subdivisions.

Substructural Hippocampal Glucose Metabolism Observed on PET/MRI

The hippocampus is one of the best-known neural structures in the brain and has been of interest in observing the substructures and their metabolic functions. However, it has been difficult to distinguish its substructures and functions in vivo because of its small size. Methods: 18F-FDG PET and high-resolution MRI of the hippocampus were performed on 5 healthy subjects using a PET/MRI system. The metabolism of each hippocampal substructure was measured in vivo on the basis of the MR images. Results: The dentate gyrus and cornu ammonis 4 showed the highest glucose uptake in the healthy subjects. Conclusion: Measuring glucose metabolism in the substructures of the hippocampus could provide a new tool for the future investigation of related brain diseases or functional studies, such as Alzheimer disease or memory and learning studies.

Effects of age on dopamine D2 receptor availability in striatal subdivisions: a high-resolution positron emission tomography study.

The purpose of the present study was to examine the relationship between age and dopamine D(2) receptor availability in striatal subdivisions of young and middle-aged healthy subjects using high-resolution positron emission tomography (PET) with [(11)C]raclopride to better characterize the nature of age-related decrements in striatal D(2) receptor availability. Twenty-four healthy volunteers completed 3-Tesla magnetic resonance imaging and high-resolution [(11)C]raclopride PET scans. The analyses using linear and exponential models revealed that age had a significant negative correlation with D(2) receptor availability in the post-commissural putamen (postPU) and that D(2) receptor binding in the postPU decreased significantly more with age than in the ventral striatum, suggesting subregional differences in age-related changes in D(2) receptor binding. The postPU, which belongs to the sensorimotor striatum, may be particularly vulnerable to the effects of age in young and middle-aged subjects.

Glucose metabolism of the midline nuclei raphe in the brainstem observed by PET-MRI fusion imaging.

UNLABELLED The brainstem contains various important monoaminergic neuronal centers, including the raphe nuclei which contain serotonergic neurons. The raphe nuclei, however, are not easily identifiable and located by conventional neuroimaging. METHODS Fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) were performed in seven healthy subjects using a new PET-MRI, which consists of a high-resolution research tomograph (HRRT) PET and 7.0 T-MRI. Glucose metabolism of raphe nuclei was semiquantitatively measured and identified along the midline brainstem region in vivo. RESULTS Midline nuclei clustered in four groups appeared to be the raphe nuclei and could be clearly visualized; specifically, we identified the groups as the dorsal raphe, raphe reticularis centralis superior, raphe pontis, and raphe magnus group. CONCLUSION FDG imaging of the midline raphe nuclei in vivo could potentially be an important tool for investigating brain diseases as well as conducting functional brain studies in the context of sleep disorders, depression, and neurodegenerative disease.

Dopamine D 2/3 receptor availability and human cognitive impulsivity: a high-resolution positron emission tomography imaging study with [ 11 C]raclopride

Objective Human impulsivity is a complex multidimensional construct encompassing cognitive, emotional, and behavioural aspects. Previous animal studies have suggested that striatal dopamine receptors play a critical role in impulsivity. In this study, we investigated the relationship between self-reported impulsiveness and dopamine D2/3 receptor availability in striatal subdivisions in healthy subjects using high-resolution positron emission tomography (PET) with [11C]raclopride. Methods Twenty-one participants completed 3-T magnetic resonance imaging and high-resolution PET scans with [11C]raclopride. The trait of impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11). Partial correlation analysis was performed between BIS-11 scores and D2/3 receptor availability in striatal subregions, controlling for the confounding effects of temperament characteristics that are conceptually or empirically related to dopamine, which were measured by the Temperament and Character Inventory. Results The analysis revealed that the non-planning (p = 0.004) and attentional (p = 0.007) impulsiveness subscale scores on the BIS-11 had significant positive correlations with D2/3 receptor availability in the pre-commissural dorsal caudate. There was a tendency towards positive correlation between non-planning impulsiveness score and D2/3 receptor availability in the post-commissural caudate. Conclusion These results suggest that cognitive subtrait of impulsivity is associated with D2/3 receptor availability in the associative striatum that plays a critical role in cognitive processes involving attention to detail, judgement of alternative outcomes, and inhibitory control.

Individually Differentiated Serotonergic Raphe Nuclei Measured with Brain PET/MR Imaging

PURPOSE To measure the activity of individual raphe nuclei with fluorine 18 fluorodeoxyglucose (FDG) and carbon 11 ((11)C) 3-amino-4-(2-dimethylaminomethylphenylthio) benzonitrile (DASB) imaging using a brain positron emission tomography(PET)/magnetic resonance (MR) imaging fusion system. MATERIALS AND METHODS The study was approved by the Institutional Review Board of Gil Medical Center, and all volunteers provided written informed consent. FDG PET, (11)C-DASB PET, and T2*-weighted MR images from seven healthy volunteers were acquired by using a PET/MR imaging fusion system. The standard uptake value ratio (SUVR) of FDG (FDG-SUVR) and nondisplaceable binding potential (BPnd) of (11)C-DASB (DASB-BPnd) were determined for each raphe nucleus. A Pearson correlation analysis was performed to show the correlation between FDG-SUVR and DASB-BPnd for the raphe nuclei. RESULTS Each raphe nucleus could be distinguished in both FDG (identifiability ratio, 0.86; κ = 0.77) and (11)C-DASB (identifiability ratio, 0.89; κ = 0.72) images. The mean values of DASB-BPnd for each raphe nucleus from dorsal to caudal direction were 6.08 (raphe nucleus 1), 5.93 (raphe nucleus 2), 3.86 (raphe nucleus 3), 3.18 (raphe nucleus 4), and 2.74 (raphe nucleus 5); the mean FDG-SUVR values were 1.00 (raphe nucleus 1), 1.00 (raphe nucleus 2), 0.87 (raphe nucleus 3), 0.94 (raphe nucleus 4), and 0.90 (raphe nucleus 5). FDG-SUVR and DASB-BPnd for the raphe nuclei were significantly correlated (r = 0.506, P = .002). CONCLUSION Serotonergic activity, both glucose metabolism and transporter binding potential of raphe nuclei, were measured with a brain-dedicated PET/MR imaging system and showed a significant correlation.

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.

Fast forward projection and backward projection algorithm using SIMD

Recent developments in PET scanners such as the HRRT (High Resolution Research Tomograph) developed by Siemens greatly enhanced their resolution as well as sensitivity, but they increased coincidence lines of response more than 4.5 times 10 generated by as many nuclear detectors as 120,000. This formidable amount of data poses a real problem in the image reconstruction and its applications. It also has been the major bottleneck in further developments of the higher resolution PET scanners. To remedy this problem in the image reconstruction, we developed a new algorithm based on the SIMD (Single Instruction Multiple Data) technique incorporated with the symmetry properties of the projection and backprojection processes, especially in the 3D OSEM algorithm. We refer to this technique as the SSP (Symmetry and SIMD based Projection-backprojection) algorithm. As a demonstration, the algorithm was applied to the OSEM (Ordered Subset Expectation Maximization) 3D algorithm with HRRT data and it effectively reduced the total image reconstruction time to 80 folds.