Kook-Jin Ahn

Simultaneous in vivo tracking of dendritic cells and priming of an antigen-specific immune response

We report the fabrication of a one-pot antigen system that delivers antigen to dendritic cells (DCs) and tracks their in vivo migration after injection. Multifunctional polymer nanoparticles containing ovalbumin protein, magnetic resonance imaging contrast agents (iron oxide nanoparticles), and near-infrared fluorophores (indocyanine green, ICG), MPN-OVA, were prepared using a double emulsion method. The MPN-OVA was efficiently taken up by the dendritic cells and subsequently localized in the lysosome. Flow cytometry analysis revealed an increase in the uptake of OVA antigen by MPN-OVA at 37 °C, when compared with soluble OVA protein. We found that MPN-OVA had no effect on DC surface expression of MHC class I, costimulatory (CD80, CD86) or adhesion (CD54) molecules or the ability of DCs to mature in response to LPS. Following the uptake of MPN-OVA, exogenous OVA antigen was delivered to the cytoplasm, and OVA peptides were presented on MHC class I molecules, which enhanced OVA antigen-specific cross-presentation to OT-1 T cells and CD8OVA1.3 T cell hybridoma in vitro. The immunization of mice with MPN-OVA-treated DCs induced OVA-specific CTL activity in draining lymph nodes. The presence of MPN allowed us to monitor the migration of DCs via lymphatic drainage using NIR fluorescence imaging, and the homing of DCs into the lymph nodes was imaged using MRI. This system has potential for use as a delivery system to induce T cell priming and to image DC-based immunotherapies.

Difference of the hippocampal and white matter microalterations in MCI patients according to the severity of subcortical vascular changes: neuropsychological correlates of diffusion tensor imaging.

OBJECTIVES Most imaging studies of mild cognitive impairment (MCI) have focused on gray matter alterations, although many MCI patients demonstrate subcortical vascular changes. We investigated the changes of the hippocampal area and various white matter areas in MCI patients with using diffusion tensor imaging (DTI), according to the severity of subcortical vascular changes, and we then correlated the DTI findings with the neuropsychological results. PATIENTS AND METHODS Among the 40 MCI patients, the 21 non-vascular MCI (nvMCI) and 19 vascular MCI (vMCI) patients were subdivided according to Erkinjunttis imaging criteria. The mean diffusivity (MD) and fractional anisotropy (FA) were compared in the bilateral temporal, frontal, parietal and occipital white matter regions, as well as in the bilateral hippocampi, centrum semiovale, and the midline genu and splenum of the corpus callosum among the nvMCI and vMCI patients and the 17 controls. The neuropsychological findings were also compared between the subgroups. RESULTS All the MCI patients showed decreased FA and increased MD in all the regions except the occipital areas. In the parietal regions and centrum semiovale, the vMCI patients had a greater FA decrease than the nvMCI patients and controls. In the hippocampi, the FA was lowest in the nvMCI patients. The memory function in the nvMCI patients was more impaired than that in the vMCI patients. The vMCI patients showed impairment of the visuospatial and frontal executive functions. CONCLUSION We were able to correlate the microstructural alterations with the neuropsychological findings in the MCI subgroups.

Hypoperfusion and Ischemia in Cerebral Amyloid Angiopathy Documented by 99mTc-ECD Brain Perfusion SPECT

Cerebral amyloid angiopathy (CAA) is known to be an important cause of spontaneous cortical–subcortical intracranial hemorrhage in normotensive older persons. CAA can also manifest as leukoencephalopathy, brain atrophy, and ischemia secondary to hypoperfusion. Our goal was to verify cerebral hypoperfusion in patients with CAA using 99mTc-ethylcysteinate dimer (99mTc-ECD) brain perfusion SPECT. Methods: A total of 11 patients (5 men and 6 women; age range, 58–78 y; mean age ± SD, 70.0 ± 7.0 y) with clinically and radiologically established probable CAA who underwent 99mTc-ECD SPECT were included. 99mTc-ECD SPECT scans were also obtained from 13 age-matched healthy control subjects (7 men and 6 women; age range, 60–79 y; mean age ± SD, 66.7 ± 6.4 y) for comparison. The relative regional cerebral blood flow values obtained for patients and controls were compared using software. Results: Compared with controls, patients with probable CAA showed hypoperfusion in the inferior parietal lobule of both parietal lobes (Brodmann area [BA] 40), middle temporal gyrus of the left temporal lobe (BA 39), postcentral gyrus of the right parietal lobe, superior temporal gyrus of the right temporal lobe (BA 22), superior temporal gyrus of the right frontal lobe (BA 10), inferior temporal gyrus of the left temporal lobe (BA 20), and both caudate bodies (P < 0.0001, t = 4.65). Conclusion: Patients with probable CAA had significantly decreased cerebral perfusion and may be at risk for leukoencephalopathy, atrophy, and ischemia.

Intramural Hematoma Detection by Susceptibility-Weighted Imaging in Intracranial Vertebral Artery Dissection

Background: The radiologic diagnosis of vertebral artery dissection (VAD) depends on characteristic intraluminal findings on angiography and intramural hematoma or a double-lumen sign on high-resolution vessel wall imaging. We aimed to evaluate the accuracy of intramural hematoma sign on susceptibility-weighted imaging (SWI) in VAD. Methods: We retrospectively analyzed SWI, phase map images and brain computed tomography (CT) of the consecutive patients who suffered an ischemic stroke in the vertebral artery territory from August 2010 to July 2012. We divided the patients into 2 groups: the VAD group and the nondissection group. VAD was diagnosed by conventional catheter angiographic findings (aneurysmal dilatation, pearl-and-string or tapered steno-occlusion) and pathognomonic findings such as intramural hematoma or a double-lumen sign on the source images of TOF-MRA, high-resolution T1-weighted MRI or high-resolution T2-weighted MRI. Intramural hematoma sign was considered positive if the patient had an eccentric or concentric hypointense signal lesion in the vertebral artery on SWI, a corresponding hyperintense signal on phase map and no evidence of calcification on the brain CT, suggesting blood products other than calcification. Two experienced neuroradiologists blinded to clinical information and angiographic findings were asked to judge for the presence of intramural hematoma sign on SWI. The accuracy of intramural hematoma sign on SWI was evaluated. Phase value, demographic and clinical data were compared between the VAD and the nondissection groups. Results: Thirty-nine patients were included: 10 in the VAD group and 29 in the non-dissection group. Among the VAD group cases, intramural hematoma sign on SWI was positive in 9 of the 10 VAD cases and in 1 out of the 29 cases in the nondissection group. The intramural hematoma sign on SWI was significantly associated with VAD (p < 0.001), and showed sensitivity of 90% and specificity of 96.6%. Mean phase values of intramural hematomas (n = 9) were all positive and those of calcified lesions (n = 13) were all negative (0.45 radian vs. -0.42 radian, p < 0.001). Conclusions: The intramural hematoma sign on SWI was significantly associated with VAD and the phase map values were higher in intramural hematomas when compared with atherosclerotic calcifications.

Potential role of advanced MRI techniques for the peritumoural region in differentiating glioblastoma multiforme and solitary metastatic lesions

Differentiation between solitary metastatic lesions and glioblastomas, two of the most common malignant brain neoplasms, is often a diagnostic challenge. The purpose of this review is to emphasize the potential roles of advanced magnetic resonance imaging (MRI) techniques, including diffusion-based techniques, such as diffusion-weighted imaging (DWI), exponential DWI, and diffusion tensor imaging, MR perfusion, and MR spectroscopy, as well as conventional MRI, in making a distinction between glioblastomas and solitary metastases in peritumoural regions. Integration of advanced MRI features with conventional MRI, may provide valuable information for differentiating glioblastoma from solitary metastatic lesions.

DCE and DSC MR perfusion imaging in the differentiation of recurrent tumour from treatment-related changes in patients with glioma.

AIM To retrospectively compare the utility of perfusion magnetic resonance imaging (MRI) in distinguishing treatment-related changes from recurrent disease in glioma patients. MATERIALS AND METHODS Thirty-one patients with histologically diagnosed gliomas and increased enhancement after or during concurrent (chemo-) radiation therapy were enrolled. They underwent dynamic contrast-enhanced (DCE) permeability MRI followed by dynamic susceptibility contrast (DSC) perfusion MRI. The vascular transfer constant (rK(trans)) and initial areas under the concentration curve (riAUC) were obtained from DCE MRI, and cerebral blood volume (rCBV) was obtained from DSC MRI. Patients were classified as having treatment-related changes or recurrent tumours based on clinicoradiological results or pathological results from surgery. RESULTS Nineteen patients were diagnosed as having recurrences and 12 patients as having treatment-related changes. The rK(trans), riAUC, and rCBV values in the recurrent group were significantly higher than the values in the group with treatment-related changes (p < 0.05). For all 31 patients, there was no significant difference between DSC MRI and DCE MRI for the differentiating power between recurrence and treatment-related changes (p = 0.7227). However, when including only the 24 patients with concordant values of rK(trans) and riAUC, DCE MRI showed a significant AUC value of 0.786 in the receiver operating characteristic (ROC) curve analysis (p = 0.003), whereas DSC MRI did not (AUC = 0.643, p = 0.229). CONCLUSION MRI perfusion images appear to show promise in distinguishing treatment-related changes from recurrent tumours. When both rK(trans) and riAUC show concordant values, DCE MRI seems to be more powerful than DSC MRI in the differentiation of recurrence from treatment-related changes.

Diffusion weighted MR imaging of acute Wernicke's encephalopathy

We report a case of Wernickes encephalopathy in which diffusion-weighted MR images demonstrated symmetrical hyperintense lesions in the paraventricular area of the third ventricles and medial thalami. Apparent diffusion coefficient mapping showed isointensity in the aforementioned areas. Diffusion-weighted MR images may provide evidence of vasogenic edema associated with thiamine deficiency, proven in the histopathology of experimental animals. In addition, diffusion-weighted MRI has many advantages over T2 or FLARE-weighted brain MRI in detecting structural and functional abnormalities in Wernickes encephalopathy.

White matter hyperintensities (WMH) are associated with intracranial atherosclerosis rather than extracranial atherosclerosis

There is increasing evidence for an association between WMH and large-artery atherosclerosis. We evaluated 268 patients with acute ischemic stroke to assess the relationship between intracranial (IC) atherosclerosis and WMH. The patients were classified into three groups according to the location of the stenosis; IC, extracranial (EC), and non-stenosis (NS) group. WMH were rated using the semiquantitative method of Scheltens and coworkers. The IC group had significantly more WMH score in comparison with the other groups after controlling age. The linear regression analysis showed that age was the factor most strongly associated with the total score of WMH; and the location of stenosis was positively related to WMH, especially in deep white matter. Our data show that IC stenosis is associated with WMH, indicating that IC stenosis, rather than EC stenosis, is likely to cause white matter lesions. These findings raise the possibility that occlusion of penetrating arteries, embolism to border-zone areas and a hemodynamic mechanism associated with IC stenosis leads to the formation of white matter lesions.

A serial study of regional cerebral blood flow deficits in patients with left anterior thalamic infarction : Anatomical and neuropsychological correlates

Thalamic damage is associated with a variety of neuropsychological dysfunctions, as well as strategic infarct dementia. However, only a limited number of reports in the medical literature have discussed the correlation between the clinical findings and the specific functional changes observed on images. We investigated the neuropsychological correlation of the regional cerebral blood flow (rCBF) deficits in four patients with left anterior thalamic infarction within two days after their stroke. All of the patients showed anterograde amnesia on the verbal memory test. Some dysexecutive features were present such as decreased word fluency and an impaired performance on the Stroop test. A decreased rCBF was observed in the left supramarginal gyrus, the superior temporal gyrus, the middle and inferior frontal gyri, and the medial dorsal and anterior nuclei of the left thalamus. The changes of rCBF may have been due to remote suppression by the interruption of the thalamo-cortical circuit that connects the anterior thalamic nucleus and various cortical areas. These initial findings remained unchanged even on the follow-up studies.

Temporal Changes in Functional Magnetic Resonance Imaging Activation of Heterosexual Couples for Visual Stimuli of Loved Partners

Objective Previous neuroimaging studies on romantic love have focused on determining how the visual stimuli that serve as a representation of loved ones induce the neural activation patterns of romantic love. The purpose of this study was to investigate the temporal changes in romantic love over a period of 6 months and their correlated neurophysiological changes. Methods Five heterosexual couples (n=10, mean age 21.1±1.97) who started dating not less than 100 days previously were recruited to measure their blood oxygen level dependent (BOLD) signals using functional magnetic resonance imaging (fMRI) while showing them pictures of their loved ones and their previously identified, opposite-sex friends. Subsequently, the subjects were scanned under the same experimental conditions to assess possible changes in their brain activities after 180 days. Results We found that their Passionate Love Score (PLS) values (M: 118.6±9.1, F: 120.2±7.0) were significantly reduced after 6 months (M: 110.8±4.0, F: 106.2±3.0). Furthermore, significantly increased activations were found in the cingulate gyri, inferior frontal gyri, supramarginal gyri, etc., after 6 months, whereas the head and tail of the right caudate nucleus were deactivated, which is indicative of the inhibition of expression and sensory neglect. Conclusion These findings suggest that dynamic neural processes in the cortical-subcortical regions are involved in temporal changes in romantic love.