Synthesis and Isolation of a Homochiral Nanohoop Composed of a Tröger's Base and Hexaparaphenylene.

Invited for the cover of this issue are Yusuke Yoshigoe, Hirotaka Shimada, and Shinichi Saito at the Tokyo University of Science, and Takuya Takaki and Yoshitane Imai at Kindai University. The image depicts a witch with a racemic pair of our nanohoops, TB[6]CPPs, chanting words shown in the font of a magical world. Read the full text of the article at 10.1002/chem.202304059.

Synthesis and Isolation of a Homochiral Nanohoop Composed of a Tröger's Base and Hexaparaphenylene.

The synthesis of a new nanohoop containing a stereogenic Tröger's base skeleton tethered to a curved hexaparaphenylene ([6]CPP) is reported. The TB[6]CPP nanohoop possesses a stable C2 symmetrical structure, which promotes the allowed transition that gives rise to pale blue emission with a quantum yield of ~0.69, surpassing the value of the more symmetrical [8]CPP. Moreover, TB[6]CPP shows chiroptical properties including circular dichroism and circularly polarized luminescence with a moderate dissymmetry factor (|glum|) of ~2.1×10-3.

Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease.

Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aß) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aß1-42, Aß1-40, Aß1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by 99mTc-ethyl cysteinate dimer single photon emission computerized tomography (99mTc ECD-SPECT), as well as the mean cortical standard uptake value ratio by 11C-labeled Pittsburgh Compound B-positron emission tomography (11C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aß1-38, Aß1-40, Aß1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant.

γ-Aminobutyric acid type A receptor binding affinity in the right inferior frontal gyrus at resting state predicts the performance of healthy elderly people in the visual sustained attention test.

ABSTRACTBackground:Although recent studies have suggested that the γ-aminobutyric acid type A (GABAA) receptor binding affinity can be a more sensitive marker of age-related neuronal loss than regional gray matter (GM) volume, knowledge about the relationship between decreased GABAA receptor binding affinity and cognitive decline during normal aging is still limited. METHODS: Thirty-seven healthy elderly individuals (aged 50-77 years (mean, 64.5 ± 7.3 years); 15 males and 22 females) were enrolled in this study. We investigated the association of the performance of the healthy elderly in the attentional function test with regional GM volume, regional cerebral bold flow (rCBF), and GABAA receptor binding affinity in the resting state by structural magnetic resonance imaging (MRI), arterial spin labeling (ASL), and 123I-iomazenil (IMZ) SPECT, with the analysis focusing on the bilateral inferior frontal gyri. RESULTS: The score of the rapid visual information processing (RVP) test, which is used to assess visual sustained attention, showed a positive correlation with GABAA receptor binding affinity in the right inferior frontal gyrus. No significant correlation was found between RVP test score and regional GM volume or rCBF. CONCLUSION: The findings of 123I-IMZ SPECT, but not those of structural MRI or ASL, suggest that a decreased GABAA receptor binding affinity can be a sensitive marker of cognitive impairment.

Evaluation of bone scan index change over time on automated calculation in bone scintigraphy.

OBJECTIVE: Bone scintigraphy (bone scan) is useful in detecting metastatic bone lesions through visual assessment of hot spots. A semi-quantitative analysis method that evaluates bone scan images has been eagerly anticipated. BONENAVI is software that enables automatic assessment of bone scan index (BSI). BSI is useful for stratifying cancer patients and monitoring their therapeutic response. The purpose of this study was to evaluate the BONENAVI reading in determining BSI and hot spots at different time intervals after radioisotope injection. METHODS: We evaluated 32 patients, including 22 males and 10 females. Ten patients had breast cancer, 20 patients had prostate cancer, and 2 had malignant pheochromocytoma. Patients were injected with 740 MBq of (99m)Tc-methylene diphosphonate and bone scintigraphy was performed at 2, 4, and 6 h after injection on each patient. The BSI and the number of hot spots were obtained from BONENAVI software. Bone scan images were also visually assessed to exclude false positives due to artifacts. Analyses were performed in all lesions, selected true lesions, segment based and cancer type based. Non-parametric statistical analyses for pairwise multiple group comparison were performed using Friedman test followed with post hoc analysis. RESULTS: The BSIs and the number of hot spots were significantly increased with time, with significant differences between each of time points (P < 0.001). Analysis of regional BSI (rBSI) and hot spot number changes of selected 15 true lesions also showed similar increase (P < 0.001). In general, the pelvic segment was the most prone to rBSI changes and the chest segment was the most prone to hot spot number changes. Visual assessment showed that BONENAVI diagnosed some typical artifacts as metastases (hot spots). CONCLUSION: BONENAVI reading of BSIs and hot spot numbers was highly affected by acquisition time. In serial or follow-up examinations (in particular, for monitoring therapeutic efficacy), acquisition time should be fixed for each patient. Cautious interpretation should be made on segments with high physiological uptake. BONENAVI reading was prone to misinterpretation of artifacts. Visual assessment is necessary to rule out this possibility.

CSF levels of Aß1-38/Aß1-40/Aß1-42 and (11)C PiB-PET studies in three clinical variants of primary progressive aphasia and Alzheimer's disease.

Primary progressive aphasia (PPA) is a cognitive syndrome characterized by progressive and isolated language impairments due to neurodegenerative diseases. Recently, an international group of experts published a Consensus Classification of the three PPA clinical variants (naPPA, svPPA and lvPPA). We analyzed 24 patients with PPA by cognitive functions, neuroimaging (MRI, (99 m)Tc ECD-SPECT, (11)C PiB-PET and FDG-PET) and cerebrospinal fluid (CSF) analysis (ptau-181, Aß1-42, Aß1-40 and Aß1-38), to elucidate relationships between neuroimaging studies and biochemical findings in the three PPA clinical variants. Cognitive and speech functions were measured by mini-mental state examination and standard language test of aphasia. The patients with lvPPA showed significant decreases in CSF Aß1-42 and ratios of Aß1-42/Aß1-40 and Aß1-42/Aß1-38, and significant increases in CSF ptau-181 and ratios of ptau-181/Aß1-42 and ptau-181/Aß1-38; these findings were similar to those of patients with Alzheimer's disease (AD). We observed a higher frequency of the ApoE ε4 allele in the lvPPA patients relative to the two other PPA variants. In (11)C PiB-PET of lvPPA patients, PiB positive findings were detected in cortices of frontal, temporal and parietal lobes and the posterior cingulate, where massive Aß may accumulate due to AD. Our results of AD-CSF markers including Aß1-38 and (11)C PiB-PET in the lvPPA patients demonstrate a common pathological mechanism with the occurrence of AD.

[Normal database (NDB) of 123I-IMP brain perfusion SPECT examination is affected by statistical image analysis in the presence or absence of scatter correction and attenuation correction].

PURPOSE: The purpose of our study is the establishment of normal database (NDB) from persons (aged 50-80 years) for 3D-SSP analysis of 123I-IMP brain perfusion SPECT image, and we analyzed whether the presence or absence of image correction methods, scatter correction (SC) and attenuation correction (AC), affects the created NDB and 3D-SSP analysis. MATERIALS AND METHODS: We created NDB from 63 healthy volunteers (32 males and 31 females, aged 50-80 years), and calculated the coefficient of variation for each pixel from the mean value and standard deviation. Next, we compared the visual assessments of the standard deviation images by each image correction method, and the coefficient of variation of SEE analysis in each part of the brain. Furthermore, we examined frontotemporal dementia and healthy volunteers by 3D-SSP analysis, and evaluated the differences of Z-score in the presence or absence of image correction methods. RESULTS: In NDB, the coefficient of variation was the minimum when SC and AC were not applied and the maximum in periventricular and cerebellum when SC and AC were applied. In Z-score image of 3D-SSP analysis, Z-score of the low value was the maximum when SC and AC were not applied. CONCLUSION: It was shown that the results from NDB coefficient of variation and 3D-SSP analysis were affected by the differences of image correction methods. It is important to understand the feature of imaging reconstruction conditions in your own facilities, and evaluate 3D-SSP analysis.

Improvement of image resolution of brain SPECT by use of the wide-angle offset acquisition method.

OBJECTIVE: Cerebral SPECT images require high spatial and contrast resolution for precise evaluation of the abnormal tracer distribution in the brain. A shorter data acquisition time is preferable so that artifacts due to patient movement are avoided. We tried to shorten data acquisition time applying larger sampling angle and offset acquisition method, in which half degree of the step angle was shifted in the opposite gamma camera of the dual-detector SPECT system. METHODS: A simulation study was performed with a 3-dimensional mathematical phantom. The phantom studies were performed with a hot-rod phantom and a brain phantom. A clinical study with 99(m)Tc-ECD SPECT was also performed on a patient who had a cerebral infarction. Reconstruction of images was done for the normal 6° and 12° onset and 12° offset. Data for the 12° offset were acquired by shifting of sampling angles of the opposite detector by half (6°) of the sampling angles of 12°. The MLEM algorithm was used for image reconstruction. Image qualities in the simulation study, the phantom studies, and the clinical study were compared for the 6° and 12° onset, and for the 12° offset by quantitative analysis with use of profile curves. RESULTS: Analysis of the profile curves revealed that the image quality of the 12° offset was better than that of the 12° onset and compared to that of the 6° onset in the simulation study, the phantom studies, and the clinical study. CONCLUSIONS: The present study indicates that wide-angle offset data acquisition improves the image resolution of brain SPECT compared to onset data acquisition with the same sampling time.

[Evaluation of Radio-activated Compounds Produced in the Walls and Adjacent Areas of a Small Medical Cyclotron].

According to the (18)O(p, n) (18)F reaction, fast neutrons produced in the target will cause residual radioactivity in a cyclotron itself and in the concrete walls mainly after thermalization of neutrons.As exploratory work prior to decommissioning of a medical cyclotron facility, surface and core samples of the facility's concrete walls were collected after confirming the external radiation was at a low level based on hollow ionization chamber-type survey meter and glass dosimeter measurements. The residual radioactivity in these samples was measured by gamma-spectrometry. Residual radioactivity was detected in all of the components of the cyclotron. In the concrete, eight residual radioactive nuclides were identified. However, radioactivity concentrations of these radionuclides were less than that of (40)K which may exist generally in a natural environment. A clearance level for radioactive solid waste has not been defined nor implemented at present in Japan, and reliable evaluation will be required to minimize radioactive waste at the time of decommissioning. The present results provide basic data for establishment of regulatory guidelines for decommissioning of medical cyclotrons.