Chlamydia pneumoniae Lung Infection in Mice Induces Fatty Acid-Binding Protein 4-Dependent White Adipose Tissue Pathology.

Fatty acid-binding protein 4 (FABP4) is a critical immune-metabolic modulator, mainly expressed in adipocytes and macrophages, secreted from adipocytes in association with lipolysis, and plays essential pathogenic roles in cardiovascular and metabolic diseases. We previously reported Chlamydia pneumoniae infecting murine 3T3-L1 adipocytes and causing lipolysis and FABP4 secretion in vitro. However, it is still unknown whether C. pneumoniae intranasal lung infection targets white adipose tissues (WATs), induces lipolysis, and causes FABP4 secretion in vivo. In this study, we demonstrate that C. pneumoniae lung infection causes robust lipolysis in WAT. Infection-induced WAT lipolysis was diminished in FABP4-/- mice or FABP4 inhibitor-pretreated wild-type mice. Infection by C. pneumoniae in wild-type but not FABP4-/- mice induces the accumulation of TNF-α- and IL-6-producing M1-like adipose tissue macrophages in WAT. Infection-induced WAT pathology is augmented by endoplasmic reticulum (ER) stress/the unfolded protein response (UPR), which is abrogated by treatment with azoramide, a modulator of the UPR. C. pneumoniae lung infection is suggested to target WAT and induce lipolysis and FABP4 secretion in vivo via ER stress/UPR. FABP4 released from infected adipocytes may be taken up by other neighboring intact adipocytes or adipose tissue macrophages. This process can further induce ER stress activation and trigger lipolysis and inflammation, followed by FABP4 secretion, leading to WAT pathology. A better understanding of the role of FABP4 in C. pneumoniae infection-induced WAT pathology will provide the basis for rational intervention measures directed at C. pneumoniae infection and metabolic syndrome, such as atherosclerosis, for which robust epidemiologic evidence exists.

High performance plasma amyloid-ß biomarkers for Alzheimer's disease.

To facilitate clinical trials of disease-modifying therapies for Alzheimer's disease, which are expected to be most efficacious at the earliest and mildest stages of the disease, supportive biomarker information is necessary. The only validated methods for identifying amyloid-ß deposition in the brain-the earliest pathological signature of Alzheimer's disease-are amyloid-ß positron-emission tomography (PET) imaging or measurement of amyloid-ß in cerebrospinal fluid. Therefore, a minimally invasive, cost-effective blood-based biomarker is desirable. Despite much effort, to our knowledge, no study has validated the clinical utility of blood-based amyloid-ß markers. Here we demonstrate the measurement of high-performance plasma amyloid-ß biomarkers by immunoprecipitation coupled with mass spectrometry. The ability of amyloid-ß precursor protein (APP)669-711/amyloid-ß (Aß)1-42 and Aß1-40/Aß1-42 ratios, and their composites, to predict individual brain amyloid-ß-positive or -negative status was determined by amyloid-ß-PET imaging and tested using two independent data sets: a discovery data set (Japan, n = 121) and a validation data set (Australia, n = 252 including 111 individuals diagnosed using 11C-labelled Pittsburgh compound-B (PIB)-PET and 141 using other ligands). Both data sets included cognitively normal individuals, individuals with mild cognitive impairment and individuals with Alzheimer's disease. All test biomarkers showed high performance when predicting brain amyloid-ß burden. In particular, the composite biomarker showed very high areas under the receiver operating characteristic curves (AUCs) in both data sets (discovery, 96.7%, n = 121 and validation, 94.1%, n = 111) with an accuracy approximately equal to 90% when using PIB-PET as a standard of truth. Furthermore, test biomarkers were correlated with amyloid-ß-PET burden and levels of Aß1-42 in cerebrospinal fluid. These results demonstrate the potential clinical utility of plasma biomarkers in predicting brain amyloid-ß burden at an individual level. These plasma biomarkers also have cost-benefit and scalability advantages over current techniques, potentially enabling broader clinical access and efficient population screening.

Impact of respiratory gating and ECG gating on 18F-FDG PET/CT for cardiac sarcoidosis.

BACKGROUND: The aim of this study was to estimate the impact of respiratory and electrocardiogram (ECG)-gated FDG positron emission tomography (PET)/computed tomography (CT) on the diagnosis of cardiac sarcoidosis (CS). METHODS AND RESULTS: Imaging from thirty-one patients was acquired on a PET/CT scanner equipped with a respiratory- and ECG-gating system. Non-gated PET images and three kinds of gated PET/CT images were created from identical list-mode clinical PET data: respiratory-gated PET during expiration (EX), ECG-gated PET at end diastole (ED), and ECG-gated PET at end systole (ES). The maximum standardized uptake value (SUVmax) and cardiac metabolic volume (CMV) were measured, and the locations of FDG accumulation were analyzed using a polar map. The mean SUVmax of the subjects was significantly higher after application of either respiratory-gated or ECG-gated reconstruction. Conversely, the mean CMV was significantly lower following the application of respiratory-gated or ECG-gated reconstruction. The segment showing maximum accumulation was shifted to the adjacent segment in 25.8%, 38.7%, and 41.9% of cases in EX, ED, and ES images, respectively. CONCLUSION: In FDG PET/CT scanning for the diagnosis of CS, gated scanning is likely to increase quantitative accuracy, but the effect depends on the location and synchronization method.

Asymmetric diffuse thyroid uptake on 18F-FDG PET/CT in patient with subacute thyroiditis: Case report and literature review.

A 48-year-old man with an intermittent fever of 39.0oC for more than three weeks underwent computed tomography (CT) and blood testing, which revealed no clues. Antibiotics wereadministered, but his condition did not improve. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed right-lobe-dominant diffuse thyroid uptake. On technetium-99m (99mTc) pertechnetate scintigraphy, the thyroid gland could not be visualized, and he was diagnosed with subacute thyroiditis (SAT). When asymmetric 18F-FDG diffuse thyroid uptake on PET/CT is observed in a patient with a fever of unknown origin (FUO), SAT may need to be considered.

The usefulness of the total metabolic tumor volume for predicting the postoperative recurrence of thoracic esophageal squamous cell carcinoma.

BACKGROUND: Induction or adjuvant therapies are not always beneficial for thoracic esophageal squamous cell carcinoma (ESCC) patients, and it is thus important to identify patients at high risk for postoperative ESCC recurrence. We investigated the usefulness of the total metabolic tumor volume (TMTV) for predicting the postoperative recurrence of thoracic ESCC. METHODS: We retrospectively analyzed the cases of 163 thoracic ESCC patients (135 men, 28 women; median age of 66 [range 34-82] years) treated at our hospital in 2007-2012. The TMTV was calculated from the fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the primary lesion and lymph node metastases. The optimal cut-off values for relapse and non-relapse were obtained by the time-dependent receiver operating curve analyses. Relapse-free survival (RFS) was evaluated by the Kaplan-Meier method, and between-subgroup differences in survival were analyzed by log-rank test. The prognostic significance of metabolic parameters and clinicopathological variables was assessed by a Cox proportional hazard regression analysis. The difference in the failure patterns after surgical resection was evaluated using the χ2-test. RESULTS: The optimal cut-off value of TMTV for discriminating relapse from non-relapse was 3.82. The patients with a TMTV ≥3.82 showed significantly worse prognoses than those with low values (p < 0.001). The TMTV was significantly related to RFS (model 1 for preoperative risk factors: TMTV: hazard ratio [HR] =2.574, p = 0.004; model 2 for preoperative and postoperative risk factors: HR = 1.989, p = 0.044). The combination of the TMTV and cN0-1 or pN0-1 stage significantly stratified the patients into low-and high-risk recurrence groups (TMTV cN0-1, p < 0.001; TMTV pN0-1, p = 0.004). The rates of hematogenous and regional lymph node metastasis were significantly higher in the patients with TMTV ≥3.82 than those with low values (hematogenous metastasis, p < 0.001, regional lymph node metastasis, p = 0.011). CONCLUSIONS: The TMTV was a more significantly independent prognostic factor for RFS than any other PET parameter in patients with resectable thoracic ESCC. The TMTV may be useful for the identifying thoracic ESCC patients at high risk for postoperative recurrence and for deciding the patient management.

Diagnostic utility of fusion 18F-fluorodeoxyglucose positron emission tomography/cardiac magnetic resonance imaging in cardiac sarcoidosis.

BACKGROUND: Although each 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) has been used to diagnose cardiac sarcoidosis (CS), active CS is still misdiagnosed. METHODS: Active CS, diagnosed by PET alone, was defined as focal or focal on diffuse FDG uptake pattern. In fusion PET/CMR imaging, using a regional analysis with AHA 17-segment model, the patients were categorized into four groups: (1) PET-/LGE-, (2) PET+/LGE-, (3) PET+/LGE+, and (4) PET-/LGE+. PET+/LGE+ was defined as active CS. RESULTS: 74 Patients with suspected CS were enrolled. Between PET alone and fusion PET/CMR imaging, 20 cases had mismatch evaluations of active CS, and most had diffuse or focal on diffuse FDG uptake pattern on PET alone imaging. 40 Patients fulfilled the 2016 the Japanese Circulation Society diagnostic criteria for CS. The interobserver diagnostic agreement was excellent (κ statistics 0.89) and the overall accuracy for diagnosing CS was 87.8% in fusion PET/CMR imaging, which were superior to those in PET alone imaging (0.57 and 82.4%, respectively). In a sub-analysis of diffuse and focal on diffuse patterns, the agreement (κ statistics 0.86) and overall accuracy (81.8%) in fusion PET/CMR imaging were still better. CONCLUSIONS: Fusion PET/CMR imaging with regional analysis offered reliable and accurate diagnosis of CS, covering low diagnostic area by FDG-PET alone.

Spontaneous closure of non-cavernous sinus dural arteriovenous fistulas: A case series and systematic review of the literature.

BACKGROUND AND PURPOSE: To report 9 new cases of non-cavernous sinus dural arteriovenous fistulas (NCS-DAVFs) that closed spontaneously and systematically review reports of other cases in the literature. MATERIAL AND METHODS: We performed a retrospective analysis of 9 cases from 2 institutions of NCS-DAVFs that closed spontaneously. Using PubMed and Scopus in accordance with the PRISMA guidelines, we systematically reviewed English language articles about NCS-DAVFs showing spontaneous closure. RESULTS: Review of the cases from 2 institutions identified 9 cases of NCS-DAVFs showing spontaneous closure in follow-up magnetic resonance angiography (MRA), and the systematic review of the literature yielded an additional 38 cases, which had been diagnosed by repeated arteriography. Collectively, the patients included 23 men and 24 women with a mean age of 54 years. The shunts were located in the transverse-sigmoid sinus in 24 cases (51%), anterior condylar confluence in 11, and other locations in 12. Based on the venous drainage pattern on arteriography, 27 cases (57%) were classified as low-risk NCS-DAVF (without cortical venous reflux) and 17 were classified as high-risk NCS-DAVF (with cortical venous reflux). Shunt closure was observed within 3 months in 17 cases (36%). Extrinsic predisposing factors for shunt closure were detected in 14 cases (30%). These included angiography in 7 cases, sinus recanalization in 4, development of sinus occlusion in 2, and sinus compression by a newly developed hematoma in 1. CONCLUSION: Spontaneous closures of NCS-DAVFs can occur for both high- and low-risk types. One-third of these closures occur within 3 months.

Chlamydia pneumoniae infection-induced endoplasmic reticulum stress causes fatty acid-binding protein 4 secretion in murine adipocytes.

Fatty acid-binding protein 4 (FABP4) is predominantly expressed in adipocytes and macrophages and regulates metabolic and inflammatory pathways. FABP4 is secreted from adipocytes during lipolysis, and elevated circulating FABP4 levels are associated with obesity, metabolic disease, and cardiac dysfunction. We previously reported that the bacterial respiratory pathogen Chlamydia pneumoniae infects murine adipocytes and exploits host FABP4 to mobilize fat and replicate within adipocytes. However, whether C. pneumoniae induces FABP4 secretion from adipocytes has not been determined. Here, we show that FABP4 is actively secreted by murine adipocytes upon C. pneumoniae infection. Chemical inhibition of lipase activity and genetic deficiency of hormone-sensitive lipase blocked FABP4 secretion from C. pneumoniae-infected adipocytes. Mechanistically, C. pneumoniae infection induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), resulting in elevated levels of mitochondrial reactive oxygen species and cytosolic Ca2+ Of note, exposure to a mitochondrial reactive oxygen species-specific scavenger, MitoTEMPO, reduced FABP4 release from C. pneumoniae-infected adipocytes. Furthermore, treatment with azoramide, which protects cells against ER stress, decreased FABP4 release from C. pneumoniae-infected adipocytes. Using gene silencing of CHOP (C/EBP homologous protein), a central regulator of ER stress, we further validated the role of C. pneumoniae infection-induced ER stress/UPR in promoting FABP4 secretion. Overall, these results indicate that C. pneumoniae infection robustly induces FABP4 secretion from adipocytes by stimulating ER stress/UPR. Our findings shed additional light on the etiological link between C. pneumoniae infection and metabolic syndrome.

Predicting tumor response and prognosis to neoadjuvant chemotherapy in esophageal squamous cell carcinoma patients using PERCIST: a multicenter study in Japan.

PURPOSE: To investigate the usefulness of the positron emission tomography response criteria in solid tumors 1.0 (PERCIST1.0) for predicting tumor response to neoadjuvant chemotherapy and prognosis and determine whether PERCIST improvements are necessary for esophageal squamous cell carcinoma (ESCC) patients. PATIENTS AND METHODS: We analyzed the cases of 177 ESCC patients and examined the association between PERCIST and their pathological responses. Associations of whole-PERCIST with progression-free survival (PFS) and overall survival (OS) were evaluated by a Kaplan-Meier analysis and Cox proportional hazards model. To investigate potential PERCIST improvements, we used the survival tree technique to understand patients' prognoses. RESULTS: There were significant correlations between the pathologic response and PERCIST of primary tumor (p < 0.001). The optimal cutoff value of the primary tumors' SULpeak response to classify pathologic responses was -50.0%. The diagnostic accuracy of SULpeak response was 87.3% sensitivity, 54.1% specificity, 68.9% accuracy, positive predictive value 60.5%, and negative predictive value 84.1%. Whole-PERCIST was significantly associated with PFS and OS. The survival tree results indicated that a high reduction of the whole SULpeak response was significantly correlated with the patients' prognoses. The cutoff values for the separation of prognoses were - 52.5 for PFS and - 47.1% for OS. CONCLUSION: PERCIST1.0 can help predict tumor responses and prognoses. However, 18F-FDG-PET/CT tends to underestimate residual tumors in histopathological response evaluations. Modified PERCIST, in which the partial metabolic response is further classified by the SULpeak response (-50%), might be more appropriate than PERCIST1.0 for evaluating tumor responses and stratifying high-risk patients for recurrence and poor prognosis.

Chlamydia trachomatis targets mitochondrial dynamics to promote intracellular survival and proliferation.

Chlamydia trachomatis is an obligate intracellular bacterium that scavenges host metabolic products for its replication. Mitochondria are the power plants of eukaryotic cells and provide most of the cellular ATP via oxidative phosphorylation. Several intracellular pathogens target mitochondria as part of their obligatory cellular reprogramming. This study was designed to analyse the mitochondrial morphological changes in response to C. trachomatis infection in HeLa cells. Mitochondrial elongation and fragmentation were found at the early stages and late stages of C. trachomatis infection, respectively. C. trachomatis infection-induced mitochondrial elongation was associated with the increase of mitochondrial respiratory activity, ATP production, and intracellular growth of C. trachomatis. Silencing mitochondrial fusion mediator proteins abrogated the C. trachomatis infection-induced elevation in the oxygen consumption rate and attenuated chlamydial proliferation. Mechanistically, C. trachomatis induced the elevation of intracellular cAMP at the early phase of infection, followed by the phosphorylation of fission-inactive serine residue 637 (S637) of Drp1, resulting in mitochondrial elongation. Accordingly, treatment with adenylate cyclase inhibitor diminished mitochondrial elongation and bacterial growth in infected cells. Collectively, these results strongly indicate that C. trachomatis promotes its intracellular growth by targeting mitochondrial dynamics to regulate ATP synthesis via inhibition of the fission mediator Drp1.

Association between the Onset of Idiopathic Normal Pressure Hydrocephalus Symptoms and Reduced Default Mode Network Connectivity.

OBJECTIVE: The aim was to examine the association between connectivity changes in the default mode network (DMN) and the progression of idiopathic normal pressure hydrocephalus (iNPH). METHODS: We retrospectively recruited cases of preclinical and clinical iNPH from 2,196 patients who had received whole-body 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scanning. We included 31 cases with asymptomatic ventriculomegaly with features of iNPH on MRI (AVIM; reported as preclinical iNPH) and 12 with iNPH. We performed a voxel-based analysis of the brain FDG-PET images of the AVIM and iNPH groups as well as for each background-matched normal control (NC) group, using Statistical Parametric Mapping 12. Volume of interest (VOI)-based analysis was also performed. We set the VOI as the region from the precuneus to the posterior cingulate cortices (PCC), and compared the mean regional standardized uptake value ratio (SUVR) between the AVIM and iNPH group FDG-PET/CT images and each corresponding NC group. RESULTS: The voxel-based analysis showed a greater decreased FDG uptake in the PCC in the iNPH group than in the AVIM group. The VOI-based analysis revealed no significant difference in the mean SUVR of the AVIM group and the corresponding NC group, but that of the iNPH group was significantly lower than that of its corresponding NC group. CONCLUSIONS: DMN connectivity was reduced in the clinical iNPH group but not in the preclinical group. These data suggest that alterations in the functional connectivity of the DMN are related to the onset of iNPH symptoms.

Magnetic Resonance Imaging of Recurrent Adult Granulosa Cell Tumor of the Ovary: A Retrospective Analysis of 11 Cases.

OBJECTIVE: The aim of the study was to characterize magnetic resonance imaging findings in patients with recurrent ovarian adult granulosa cell tumors (AGCTs). METHODS: Clinical and magnetic resonance imaging manifestations of recurrent AGCTs were evaluated in 11 patients. RESULTS: Initial recurrences of AGCT were diagnosed between 13 months and 30 years (mean, 11.3 years). Recurrent tumors were located in the pelvic peritoneum, the abdominal peritoneum, the retroperitoneum, and bone. The number of recurrent tumors varied from 1 to 5. Tumors varied in morphology and all margins were well circumscribed. The internal structures noted were as follows: multilocular cystic and solid and cystic. Furthermore, internal hemorrhage and sponge-like multicystic components were identified. CONCLUSIONS: Ovarian AGCTs recurred in the pelvic peritoneum, abdominal peritoneum, and the retroperitoneal lymph nodes. Large recurrent AGCTs were commonly well circumscribed, round or lobulated, and multilocular cystic or solid and cystic. Moreover, they frequently included internal hemorrhage and sponge-like multicystic components.

A strategy to account for noise in the X-variable to reduce underestimation in Logan graphical analysis for quantifying receptor density in positron emission tomography.

BACKGROUND: The Logan graphical analysis (LGA) algorithm is widely used to quantify receptor density for parametric imaging in positron emission tomography (PET). Estimating receptor density, in terms of the non-displaceable binding potential (BPND), from the LGA using the ordinary least-squares (OLS) method has been found to be negatively biased owing to noise in PET data. This is because OLS does not consider errors in the X-variable (predictor variable). Existing bias reduction methods can either only reduce the bias slightly or reduce the bias accompanied by increased variation in the estimates. In this study, we addressed the bias reduction problem by applying a different regression method. METHODS: We employed least-squares cubic (LSC) linear regression, which accounts for errors in both variables as well as the correlation of these errors. Noise-free PET data were simulated, for 11C-carfentanil kinetics, with known BPND values. Statistical noise was added to these data and the BPNDs were re-estimated from the noisy data by three methods, conventional LGA, multilinear reference tissue model 2 (MRTM2), and LSC-based LGA; the results were compared. The three methods were also compared in terms of beta amyloid (A ß) quantification of 11C-Pittsburgh compound B brain PET data for two patients with Alzheimer's disease and differing A ß depositions. RESULTS: Amongst the three methods, for both synthetic and actual data, LSC was the least biased, followed by MRTM2, and then the conventional LGA, which was the most biased. Variations in the LSC estimates were smaller than those in the MRTM2 estimates. LSC also required a shorter computational time than MRTM2. CONCLUSIONS: The results suggest that LSC provides a better trade-off between the bias and variability than the other two methods. In particular, LSC performed better than MRTM2 in all aspects; bias, variability, and computational time. This makes LSC a promising method for BPND parametric imaging in PET studies.

Regional dissociation between the cerebral blood flow and gray matter density alterations in idiopathic normal pressure hydrocephalous: results from SINPHONI-2 study.

PURPOSE: The purpose of this study was to elucidate the specific regional cerebral blood flow (rCBF) alterations for idiopathic normal pressure hydrocephalus (iNPH) by comparing the proportional rCBF and gray matter change from those of a normal database at the same point of SPECT and MRI examinations. METHODS: Thirty subjects with iNPH underwent both CBF SPECT and MRI. After normalization, voxel-wise two-sample t tests between patients and 11 normal controls were conducted to compare the regional alteration in the gray matter density and rCBF. RESULTS: The rCBF reduction and the gray matter decrease were seen in almost similar regions surrounding Sylvian fissure, the left parietotemporal region and frontal lobes, whereas we did not find rCBF increase at the top of the high convexity, where the increase of the gray matter density was the highest (p < 0.05). CONCLUSION: Our study showed regional associations and dissociations between the relative gray matter density and rCBF in patients with iNPH.

Changes in brain morphology in patients in the preclinical stage of idiopathic normal pressure hydrocephalus.

BACKGROUND: Specific ventriculomegaly features, including tight high-convexity and medial subarachnoid spaces, are found on magnetic resonance images in patients with idiopathic normal pressure hydrocephalus (iNPH). However, some healthy elderly individuals with no typical triad symptoms of iNPH also exhibit specific magnetic resonance image features of iNPH. Therefore, this study quantitatively clarified the brain morphology of suspected iNPH patients with no objective triad symptoms (iNPH-NOS). METHODS: We recruited patients with suspected iNPH and divided them into two groups based on their iNPH grading scale scores: the iNPH-NOS group and the iNPH with apparent objective triad symptoms (iNPH-AOS) group. Data for normal controls (NC) were taken from the database used in our previous study. We compared the relative volumes of ventricle systems (VS), Sylvian fissures (SF), and sulci at high convexity and the midline (SHM), adjusted by the intracranial volume, of the iNPH-NOS, iNPH-AOS, and NC groups. Additionally, we compared the relative volumes of VS, SF, and SHM in iNPH-NOS patients between their first visit and follow-up 1 year later. RESULTS: Fifteen iNPH-NOS patients and 45 iNPH-AOS patients were recruited, and 24 NCs were found in the database. The relative volumes of VS and SF were significantly smaller than in NCs than in the iNPH-NOS and iNPH-AOS groups, and the relative volume of SHM was significantly larger in NCs. The relative volume of SHM was significantly larger in the iNPH-NOS group than in the iNPH-AOS group, but there were no significant differences in the relative volumes of VS and SF between these groups. In the iNPH-NOS group, the relative volumes of VS and SF were significantly smaller at the first visit than 1 year later, whereas the relative volume of SHM was significantly larger. In 6 of 15 iNPH-NOS patients, objective symptoms appeared during the observation period. CONCLUSIONS: Our results indicate that iNPH-NOS patients were in the transitional stage between normal and iNPH-AOS, both morphologically and clinically.

Chlamydia pneumoniae exploits adipocyte lipid chaperone FABP4 to facilitate fat mobilization and intracellular growth in murine adipocytes.

Fatty acid-binding protein 4 (FABP4), a cytosolic lipid chaperone predominantly expressed in adipocytes and macrophages, modulates lipid fluxes, trafficking, signaling, and metabolism. Recent studies have demonstrated that FABP4 regulates metabolic and inflammatory pathways, and in mouse models its inhibition can improve type 2 diabetes mellitus and atherosclerosis. However, the role of FABP4 in bacterial infection, metabolic crosstalk between host and pathogen, and bacterial pathogenesis have not been studied. As an obligate intracellular pathogen, Chlamydia pneumoniae needs to obtain nutrients such as ATP and lipids from host cells. Here, we show that C. pneumoniae successfully infects and proliferates in murine adipocytes by inducing hormone sensitive lipase (HSL)-mediated lipolysis. Chemical inhibition or genetic manipulation of HSL significantly abrogated the intracellular growth of C. pneumoniae in adipocytes. Liberated free fatty acids were utilized to generate ATP via ß-oxidation, which C. pneumoniae usurped for its replication. Strikingly, chemical inhibition or genetic silencing of FABP4 significantly abrogated C. pneumoniae infection-induced lipolysis and mobilization of liberated FFAs, resulting in reduced bacterial growth in adipocytes. Collectively, these results demonstrate that C. pneumoniae exploits host FABP4 to facilitate fat mobilization and intracellular replication in adipocytes. This work uncovers a novel strategy used by intracellular pathogens for acquiring energy via hijacking of the host lipid metabolism pathway.

Semi-quantitative dopamine transporter standardized uptake value in comparison with conventional specific binding ratio in [123I] FP-CIT single-photon emission computed tomography (DaTscan).

PURPOSE: We developed a new analytical method to quantify the dopamine transporter (DAT) radiation dose in the striatum on [123I] FP-CIT single-photon emission computed tomography (SPECT). This method is based on the dopamine transporter standardized uptake value (DaTSUV). The purpose of this study was to compare DaTSUV with the classical specific binding ratio (SBR) in the discrimination of dopaminergic neurodegenerative diseases (dNDD) from non-dNDD. METHOD: Seventy-seven consecutive patients who underwent DaTscan were included. Patients were divided into a dNDD group (n = 44; 24 men, 20 women; median age 73 years) and a non-dNDD group (n = 33; 14 men, 19 women; median age 75 years) based on their clinical diagnoses. The relationship between each method was evaluated by Pearson's correlation coefficient. Differences in SBR and DaTSUV in each group were evaluated by t test. Pairwise comparison of receiver operating characteristic (ROC) curve analysis was performed to compare the discriminating abilities of each method according to the standard error of the area under the curve (AUC). A value of p < 0.05 was considered statistically significant. RESULT: There was a significant strong correlation between DaTSUV and SBR (r = 0.910 [95% CI = 0.862-0.942], p < 0.001). The dNDD group showed significantly lower SBR (3.48 [1.25-7.91] vs 6.58 [3.81-11.1], p < 0.001) and DaTSUV (4.91 [1.59-13.6] vs 8.61 [2.29-15.6], p < 0.001) than the non-dNDD group. The discriminating ability of SBR (AUC = 0.918) was significantly higher than that of DaTSUV (AUC = 0.838, p = 0.0176). CONCLUSION: DaTSUV has a good correlation with SBR, but it could not exceed SBR for discriminating dNDD from non-dNDD.

Tau accumulation in two patients with frontotemporal lobe degeneration showing different types of aphasia using 18F-THK-5351 positron emission tomography: a case report.

ABSTRACTTau deposits in Alzheimer's disease and corticobasal syndrome have been reported using 18F-THK-5351 positron emission tomography (PET). To our knowledge, our study is the first to demonstrate tau deposits in patients with frontotemporal lobe degeneration (FTLD), using 18F-THK-5351 PET. This case report presents two patients, both of whom showed positive Tau deposition using 18F-THK-5351 PET. One patient was diagnosed with semantic variant primary progressive aphasia (PPA) and the other diagnosed with logopenic variant PPA. Our results suggest an association in the pathology of Alzheimer's disease, corticobasal syndrome, and FTLD, and could plan more effective clinical care in advance.

[Impact to Z-score Mapping of Hyperacute Stroke Images by Computed Tomography in Adaptive Statistical Iterative Reconstruction].

The purpose of this study was to evaluate the effect of a hybrid-type iterative reconstruction method on Z-score mapping of hyperacute stroke in unenhanced computed tomography (CT) images. We used a hybrid-type iterative reconstruction [adaptive statistical iterative reconstruction (ASiR)] implemented in a CT system (Optima CT660 Pro advance, GE Healthcare). With 15 normal brain cases, we reconstructed CT images with a filtered back projection (FBP) and ASiR with a blending factor of 100% (ASiR100%). Two standardized normal brain data were created from normal databases of FBP images (FBP-NDB) and ASiR100% images (ASiR-NDB), and standard deviation (SD) values in basal ganglia were measured. The Z-score mapping was performed for 12 hyperacute stroke cases by using FBP-NDB and ASiR-NDB, and compared Z-score value on hyperacute stroke area and normal area between FBP-NDB and ASiR-NDB. By using ASiR-NDB, the SD value of standardized brain was decreased by 16%. The Z-score value of ASiR-NDB on hyperacute stroke area was significantly higher than FBP-NDB (p<0.05). Therefore, the use of images reconstructed with ASiR100% for Z-score mapping had potential to improve the accuracy of Z-score mapping.

Inter-rater variability of visual interpretation and comparison with quantitative evaluation of 11C-PiB PET amyloid images of the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) multicenter study.

PURPOSE: The aim of this study was to assess the inter-rater variability of the visual interpretation of 11C-PiB PET images regarding the positivity/negativity of amyloid deposition that were obtained in a multicenter clinical research project, Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI). The results of visual interpretation were also compared with a semi-automatic quantitative analysis using mean cortical standardized uptake value ratio to the cerebellar cortex (mcSUVR). METHODS: A total of 162 11C-PiB PET scans, including 45 mild Alzheimer's disease, 60 mild cognitive impairment, and 57 normal cognitive control cases that had been acquired as J-ADNI baseline scans were analyzed. Based on visual interpretation by three independent raters followed by consensus read, each case was classified into positive, equivocal, and negative deposition (ternary criteria) and further dichotomized by merging the former two (binary criteria). RESULTS: Complete agreement of visual interpretation by the three raters was observed for 91.3% of the cases (Cohen κ = 0.88 on average) in ternary criteria and for 92.3% (κ = 0.89) in binary criteria. Cases that were interpreted as visually positive in the consensus read showed significantly higher mcSUVR than those visually negative (2.21 ± 0.37 vs. 1.27 ± 0.09, p < 0.001), and positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. Significant positive/negative associations were observed between mcSUVR and the number of raters who evaluated as positive (ρ = 0.87, p < 0.0001) and negative (ρ = -0.85, p < 0.0001) interpretation. Cases of disagreement among raters showed generally low mcSUVR. CONCLUSIONS: Inter-rater agreement was almost perfect in 11C-PiB PET scans. Positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. As some cases of disagreement among raters tended to show low mcSUVR, referring to quantitative method may facilitate correct diagnosis when evaluating images of low amyloid deposition.