ABSTRACT
PURPOSE: Physical activity has been known to improve survival and quality of life of patients with breast cancer. To find factors associated with physical activity, we analyzed the dataset of the multicenter controlled trial of exercise intervention. METHODS: Three hundred fifty-six participants were assigned to two groups: "Smart After-Care" (smartphone application and pedometer were provided) or exercise education only. Physical activity was measured by International Physical Activity Questionnaire-Short Form (IPAQ-SF) at baseline and after 12 weeks. The association between physical activity and other clinical characteristics was analyzed. RESULTS: At baseline, physical activity amount was 2315.5 ± 3513.2 MET min/week: 33.0% inactive, 49.6% minimally active, and 17.4% health-enhancing physical activity (HEPA) active. Factors associated with HEPA include cancer stage and grip strength. A significantly lower proportion was HEPA active among those with advanced stage than among those with stage 0. After intervention, physical activity was increased to 3466.2 ± 4712.5 MET min/week: 15.3% inactive, 50.4% minimally active, and 34.2% HEPA active. Physical activity was increased in 63.4% of the participants. Factors associated with physical activity increase include cancer stage, diarrhea, and type of exercise intervention. Participants with advanced stage have a 3.3 times higher chance of increasing physical activity. Participants who received "Smart After-Care" have a 64% higher chance of increasing physical activity. CONCLUSION: Before the intervention, participants with advanced stage are less likely to be HEPA active. Exercise intervention was more beneficial for those with advanced stage or physical symptoms. "Smart After-Care" was more effective than education only in increasing physical activity.
Subject(s)
Breast Neoplasms, Male/physiopathology , Breast Neoplasms, Male/rehabilitation , Breast Neoplasms/physiopathology , Breast Neoplasms/rehabilitation , Exercise Therapy/methods , Actigraphy , Adult , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Breast Neoplasms, Male/pathology , Breast Neoplasms, Male/therapy , Exercise , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Quality of Life , SmartphoneABSTRACT
Dysregulation of cellular energy metabolism is closely linked to cancer development and progression. Calorie or glucose restriction (CR or GR) inhibits energy-dependent pathways, including IGF-1/PI3K/Akt/mTOR, in cancer cells. However, alterations in proton dynamics and reversal of the pH gradient across the cell membrane, which results in intracellular alkalinization and extracellular acidification in cancer tissues, have emerged as important etiopathogenic factors. We measured glucose, lactate, and ATP production after GR, plant-derived CR-mimetic curcumin treatment, and curcumin plus GR in human hepatoma cells. Intracellular pH regulatory effects, in particular, protein-protein interactions within mTOR complex-1 and its structural change, were investigated. Curcumin treatment or GR mildly inhibited Na+/H+ exchanger-1 (NHE1). vATPase, monocarboxylate transporter (MCT)-1, and MCT4 level. Combination treatment with curcumin and GR further enhanced the inhibitory effects on these transporters and proton-extruding enzymes, with intracellular pH reduction. ATP and lactate production decreased according to pH change. Modeling of mTOR protein revealed structural changes upon treatments, and curcumin plus GR decreased binding of Raptor and GßL to mTOR, as well as of Rag A and Rag B to Raptor. Consequently, 4EBP1 phosphorylation was decreased and cell migration and proliferation were inhibited in a pH-dependent manner. Autophagy was increased by curcumin plus GR. In conclusion, curcumin treatment combined with GR may be a useful supportive approach for preventing intracellular alkalinization and cancer progression.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/metabolism , Curcumin/pharmacology , Glucose/deficiency , Liver Neoplasms/metabolism , Alkalies/metabolism , Cell Line , Cell Proliferation/drug effects , Glucose/metabolism , Hep G2 Cells , Humans , Monocarboxylic Acid Transporters/metabolism , Regulatory-Associated Protein of mTOR/metabolism , Vacuolar Proton-Translocating ATPases/metabolismABSTRACT
Manifestation of the functionalities from the structural brain network is becoming increasingly important to understand a brain disease. With the aim of investigating the differential structure-function couplings according to network systems, we investigated the structural and functional brain networks of patients with spastic diplegic cerebral palsy with periventricular leukomalacia compared to healthy controls. The structural and functional networks of the whole brain and motor system, constructed using deterministic and probabilistic tractography of diffusion tensor magnetic resonance images and Pearson and partial correlation analyses of resting-state functional magnetic resonance images, showed differential embedding of functional networks in the structural networks in patients. In the whole-brain network of patients, significantly reduced global network efficiency compared to healthy controls were found in the structural networks but not in the functional networks, resulting in reduced structural-functional coupling. On the contrary, the motor network of patients had a significantly lower functional network efficiency over the intact structural network and a lower structure-function coupling than the control group. This reduced coupling but reverse directionality in the whole-brain and motor networks of patients was prominent particularly between the probabilistic structural and partial correlation-based functional networks. Intact (or less deficient) functional network over impaired structural networks of the whole brain and highly impaired functional network topology over the intact structural motor network might subserve relatively preserved cognitions and impaired motor functions in cerebral palsy. This study suggests that the structure-function relationship, evaluated specifically using sparse functional connectivity, may reveal important clues to functional reorganization in cerebral palsy. Hum Brain Mapp 38:5292-5306, 2017. © 2017 Wiley Periodicals, Inc.
Subject(s)
Brain/diagnostic imaging , Brain/physiopathology , Cerebral Palsy/diagnostic imaging , Cerebral Palsy/physiopathology , Adolescent , Adult , Brain/pathology , Brain Mapping , Cerebral Palsy/pathology , Child , Diffusion Tensor Imaging , Female , Humans , Magnetic Resonance Imaging , Male , Neural Pathways/diagnostic imaging , Neural Pathways/pathology , Neural Pathways/physiopathology , Rest , Young AdultABSTRACT
PURPOSE: To investigate and compare the effects of mobile health (mHealth) and pedometer with conventional exercise program using a brochure on physical function and quality of life (QOL). METHODS: The study was a prospective, quasi-randomized multicenter trial where 356 patients whose cancer treatment had been terminated were enrolled. All patients were instructed to perform a 12-week regimen of aerobic and resistance exercise. The mHealth group received a pedometer and a newly developed smartphone application to provide information and monitor the prescribed exercises. Those in the conventional group received an exercise brochure. Physical measurements were conducted at baseline, 6 weeks, and 12 weeks. Self-reported physical activity (international physical activity questionnaire-short form), general QOL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30), and breast cancer-specific QOL (Quality of Life Questionnaire Breast Cancer Module 23) were assessed at baseline and 12 weeks. A user satisfaction survey was assessed in the mHealth group. RESULTS: Basic characteristics were not different between the two groups except for age and previous radiotherapy. Physical function, physical activity, and QOL scores were significantly improved regardless of the intervention method, and changes were not significantly different between the two groups. Additionally, the mean Likert scale response for overall satisfaction with the service was 4.27/5 in the mHealth group. CONCLUSIONS: Overall, both the mHealth coupled with pedometer and conventional exercise education using a brochure were effective in improving physical function, physical activity, and QOL. This study provides a basis of mHealth research in breast cancer patients for progressing further developing field, although superiority of the mHealth over the conventional program was not definitely evident.
Subject(s)
Breast Neoplasms/therapy , Exercise Therapy , Actigraphy , Adult , Breast Neoplasms/diagnosis , Combined Modality Therapy , Comorbidity , Exercise , Exercise Therapy/instrumentation , Exercise Therapy/methods , Female , Humans , Middle Aged , Neoplasm Staging , Physical Fitness , Quality of Life , Self Report , Telemedicine/instrumentation , Telemedicine/methods , Treatment OutcomeABSTRACT
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide; however, the genetic mechanisms underlying its pathogenesis are incompletely understood. Genetically engineered mouse (GEM) models of HCC have been developed to elucidate the role of individual cancer-related genes in hepatocarcinogenesis. However, the expensive and time-consuming processes related to generating a GEM model discourage the development of diverse genotype models. Recently, a simple and inexpensive liver-specific transgenic approach was developed, in which a hydrodynamics-based transfection (HT) method was coupled with the Sleeping Beauty transposase system. Various HT models in which different oncogenic pathways are activated and/or tumor-suppressing pathways inactivated have been developed in recent years. The applicability of HT models in liver cancer research is expected to broaden and ultimately elucidate the cooperation between oncogenic signaling pathways and aid in designing molecular therapy to target altered pathways.
Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms, Experimental/genetics , Transfection/methods , Animals , Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Hydrodynamics , Liver Neoplasms, Experimental/drug therapy , Mice , Mice, Transgenic , Molecular Targeted TherapyABSTRACT
OBJECTIVES: To evaluate the clinical implications of lymph node (LN) density on 18F-FDG PET/CT for mediastinal LN characterization in non-small cell lung cancer (NSCLC). METHODS: One hundred and fifty-two patients with 271 mediastinal LNs who underwent PET/CT and endobronchial ultrasound-guided transbronchial needle aspiration for staging were enrolled. Maximum standardized uptake value (SUVmax), short axis diameter, LN-to-primary cancer ratio of SUVmax, and median Hounsfield unit (HU) based on CT histogram were correlated to histopathology. RESULTS: Of 271 nodes, 162 (59.8 %) were malignant. SUVmax, short axis diameter, and LPR of malignant LNs were higher than those of benign nodes. Among malignant LNs, 71.0 % had median HU between 25 and 45, while 78.9 % of benign LNs had values <25 HU or >45 HU. Using a cutoff value of 4.0, SUVmax showed the highest diagnostic ability for detecting malignant LNs with a specificity of 94.5 %, but showing a sensitivity of 70.4 %. Using additional density criteria (median HU 25-45) in LNs with 2.0< SUVmax ≤4.0, the sensitivity increased to 88.3 % with the specificity of 82.6 %. CONCLUSIONS: LN density is useful for the characterization of LNs with mild 18F-FDG uptake. The risk of mediastinal LN metastasis in NSCLC patients could be further stratified using both 18F-FDG uptake and LN density. KEY POINTS: ⢠SUVmax showed the highest diagnostic ability for detecting malignant LNs. ⢠LN density was useful in characterization of LNs with mild FDG uptake. ⢠SUVmax and LN density together could stratify the risk of LN metastasis.
Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Cone-Beam Computed Tomography/methods , Fluorodeoxyglucose F18/metabolism , Lung Neoplasms/diagnostic imaging , Lymph Nodes/diagnostic imaging , Neoplasm Staging/methods , Positron Emission Tomography Computed Tomography/methods , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/pathology , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Male , Mediastinum/pathology , Middle Aged , Multimodal Imaging , Radiopharmaceuticals , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray ComputedABSTRACT
PURPOSE: The purpose of this study was to investigate the prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with ampullary adenocarcinoma (AAC) after curative surgical resection. METHODS: Fifty-two patients with AAC who had undergone (18)F-FDG PET/CT and subsequent curative resections were retrospectively enrolled. The maximum standardized uptake value (SUVmax) and tumor to background ratio (TBR) were measured on (18)F-FDG PET/CT in all patients. The prognostic significances of PET/CT parameters and clinicopathologic factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. RESULTS: Of the 52 patients, 19 (36.5%) experienced tumor recurrence during the follow-up period and 18 (35.8%) died. The 3-year RFS and OS were 62.3 and 61.5%, respectively. Preoperative CA19-9 level, tumor differentiation, presence of lymph node metastasis, SUVmax, and TBR were significant prognostic factors for both RFS and OS (p < 0.05) on univariate analyses, and patient age showed significance only for predicting RFS (p < 0.05). On multivariate analyses, SUVmax and TBR were independent prognostic factors for RFS, and tumor differentiation, SUVmax, and TBR were independent prognostic factors for OS. CONCLUSION: SUVmax and TBR on preoperative (18)F-FDG PET/CT are independent prognostic factors for predicting RFS and OS in patients with AAC; patients with high SUVmax (>4.80) or TBR (>1.75) had poor survival outcomes. The role of and indications for adjuvant therapy after curative resection of AAC are still unclear. (18)F-FDG uptake in the primary tumor could provide additive prognostic information for the decision-making process regarding adjuvant therapy.
Subject(s)
Adenocarcinoma/diagnostic imaging , Ear Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Positron-Emission Tomography , Radiopharmaceuticals , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Multimodal Imaging , Predictive Value of Tests , Preoperative Period , Prognosis , Tomography, X-Ray ComputedABSTRACT
OBJECTIVES: We aimed to assess the usefulness of F-fluorodeoxyglucose (F-FDG) positron emission tomography-computed tomography (PET/CT) in the monitoring of adhesive capsulitis (AC), a joint problem commonly observed in the upper arm after breast cancer treatment. METHODS: This retrospective study included 230 patients who underwent F-FDG PET/CT before and after modified radical mastectomy of whom 22 patients were identified as having AC and categorized into 2 groups: with severely and mildly limited range of motion in the shoulder joint. The F-FDG uptake patterns and mean and maximum standardized uptake values (SUVs) were analyzed. RESULTS: The overall incidence of AC after MRM was 9.57%. The SUVs were significantly higher in patients with severely limited range of motion compared with the other group. There was no association between the SUV and radiotherapy. The F-FDG uptake pattern differed between the groups. CONCLUSIONS: F-fluorodeoxyglucose PET/CT is useful in evaluating AC after breast cancer treatment.
Subject(s)
Breast Neoplasms/surgery , Bursitis/diagnosis , Bursitis/etiology , Fluorodeoxyglucose F18 , Mastectomy, Radical/adverse effects , Positron-Emission Tomography/methods , Tomography, X-Ray Computed/methods , Breast Neoplasms/complications , Breast Neoplasms/diagnosis , Humans , Middle Aged , Multimodal Imaging/methods , Observer Variation , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity , Treatment OutcomeABSTRACT
PURPOSE: This study assessed the prognostic value of pre-operative 2-[(18)F] fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) volumetric parameters, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in patients with epithelial ovarian cancer. METHODS: A total of 175 patients with epithelial ovarian cancer who underwent (18) F-FDG PET/CT and subsequent cytoreductive surgery were retrospectively enrolled. Maximum standardized uptake value (SUVmax) on (18)F-FDG PET/CT was measured for all patients. Because nine patients showed low tumor-to-background uptake ratios, MTV and TLG were measured in 166 patients. Univariate and multivariate analyses were performed to evaluate the prognostic significance of SUVmax, MTV, TLG, and clinicopathological factors for disease progression-free survival. RESULTS: Disease progressed in 78 (44.6 %) of the 175 patients, and the 2-year disease progression-free survival rate was 57.5 %. Univariate analysis showed that tumor stage, histopathological type, presence of regional lymph node metastasis, residual tumor after cytoreductive surgery, pre-operative serum carbohydrate antigen 125 (CA125) level, SUVmax, MTV, and TLG were significant prognostic factors (p < 0.05). Among these variables, tumor stage (p = 0.0006) and TLG (p = 0.008) independently correlated with disease progression-free survival on multivariate analysis. The disease progression rate was only 2.3 % in stage I-II patients with low TLG (≤100.0), compared to 80.0 % in stage III-IV patients with high TLG (>100.0). CONCLUSION: Along with tumor stage, TLG is an independent prognostic factor for disease progression after cytoreductive surgery in patients with epithelial ovarian cancer. By combining tumor stage and TLG, one can further stratify the risk of disease progression for patients undergoing cytoreductive surgery.
Subject(s)
Carcinoma/diagnostic imaging , Glycolysis , Multimodal Imaging , Ovarian Neoplasms/diagnostic imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , Adult , Aged , Carcinoma/metabolism , Female , Fluorodeoxyglucose F18 , Humans , Middle Aged , Ovarian Neoplasms/metabolism , Prognosis , RadiopharmaceuticalsABSTRACT
Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.
Subject(s)
Antitubercular Agents/administration & dosage , Antitubercular Agents/therapeutic use , Metronidazole/administration & dosage , Metronidazole/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Adult , Antitubercular Agents/adverse effects , Antitubercular Agents/pharmacokinetics , Area Under Curve , Confidence Intervals , Double-Blind Method , Female , Humans , Lung/microbiology , Lung/pathology , Male , Metronidazole/adverse effects , Metronidazole/pharmacokinetics , Mycobacterium tuberculosis/isolation & purification , Peripheral Nervous System Diseases/chemically induced , Severity of Illness Index , Sputum/microbiology , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: Neuroprotective or regenerative strategies are invaluable in multiple system atrophy (MSA) due to its rapid progression with fatal prognosis. We evaluated the efficacy of autologous mesenchymal stem cells (MSC) in patients with MSA-cerebellar type (MSA-C). METHODS: Thirty-three patients with probable MSA-C and baseline unified MSA rating scale (UMSARS) scores ranging from 30 to 50 were randomly assigned to receive MSC (4 × 10(7) /injection) via intra-arterial and intravenous routes or placebo. The primary outcome was change in the total UMSARS scores from baseline throughout a 360-day follow-up period between groups. Secondary outcomes were changes in the UMSARS part II scores, cerebral glucose metabolism, gray matter density, and cognitive performance over a 360-day period. RESULTS: The mixed model analysis of neurological deficits revealed a significant interaction effect between treatment group and time, suggesting that the MSC group had a smaller increase in total and part II UMSARS scores compared with the placebo group (p = 0.047 and p = 0.008, respectively). Cerebral glucose metabolism and gray matter density at 360 days relative to the baseline were more extensively decreased in the cerebellum and the cerebral cortical areas, along with greater deterioration of frontal cognition in the placebo group compared with the MSC group. We found no serious adverse effects that were directly related to MSC treatment. However, intra-arterial infusion resulted in small ischemic lesions on magnetic resonance imaging. INTERPRETATION: MSC therapy could delay the progression of neurological deficits in patients with MSA-C, suggesting the potential of MSC therapy as a treatment candidate of MSA.
Subject(s)
Disease Progression , Mesenchymal Stem Cell Transplantation/methods , Multiple System Atrophy/therapy , Adult , Aged , Brain/metabolism , Brain/pathology , Cognition , Double-Blind Method , Female , Humans , Infusions, Intra-Arterial , Male , Middle Aged , Multiple System Atrophy/metabolism , Multiple System Atrophy/pathology , Multiple System Atrophy/psychology , Neuropsychological Tests , Transplantation, Autologous , Treatment OutcomeABSTRACT
OBJECTIVES: The major role of herpes simplex virus (HSV) type 1 infection in Behçet's disease (BD) immunopathogenesis has been demonstrated and inoculating the earlobes of ICR mice with HSV produced a BD-like mouse model. (18)Ffluorodeoxyglucose positron emission tomography (FDG PET) is widely used for diagnosing numerous human diseases other than malignancies. The aim of our study was to evaluate the inflammatory activities of BD-like symptoms in a HSV type 1-induced BD-like mouse model by small-animal FDG PET. METHODS: Five HSV-infected ICR mice with BD-like lesions, two asymptomatic HSV-infected mice, and two untreated mice were scanned with microPET, and autopsy specimens were histopathologically assessed to evaluate for infiltration by mixed inflammatory cells. RESULTS: The histopathological evaluation of the inflammatory process in knee and elbow joints significantly correlated with the quantitative assessment of FDG accumulation in the same joints in BD-like ICR mice, HSV-infected asymptomatic mice, and untreated control mice. Small-animal FDG PET clearly detected asymptomatic joint inflammatory processes in both BD-like mice and HSV-infected asymptomatic mice. In addition, genital ulcers and skin ulcers with associated perilesional lymphadenopathies in BD-like models were detected by microPET. However, biodistributed PET-positive images from the stasis of secreted FDG into the bowel lumen could not be distinguished from the inflammatory bowel lesions of BD when compared to FDG uptake in control mice. CONCLUSIONS: Our data indicate that FDG PET can non-invasively and quantitatively detect the inflammatory process in an HSV-induced BD-like mouse model.
Subject(s)
Behcet Syndrome/diagnostic imaging , Fluorodeoxyglucose F18 , Herpes Simplex/diagnostic imaging , Inflammation/diagnostic imaging , Joints/diagnostic imaging , Positron-Emission Tomography , Radiopharmaceuticals , Animals , Behcet Syndrome/immunology , Behcet Syndrome/pathology , Behcet Syndrome/virology , Disease Models, Animal , Herpes Simplex/immunology , Herpes Simplex/pathology , Herpes Simplex/virology , Herpesvirus 1, Human/immunology , Herpesvirus 1, Human/pathogenicity , Inflammation/immunology , Inflammation/pathology , Inflammation/virology , Joints/immunology , Joints/pathology , Joints/virology , Male , Mice , Mice, Inbred ICR , Predictive Value of TestsABSTRACT
OBJECTIVE: The assessment of disease activity in Takayasu arteritis (TA) is difficult in clinical situations because clinical symptoms and laboratory parameters do not always reflect the actual inflammation of the arterial wall. We undertook this study to comprehensively investigate the role of (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of disease activity in patients with TA. METHODS: We performed a retrospective chart review of 53 FDG-PET scans in 38 patients with TA. We measured (18) F-fluorodeoxyglucose ((18) F-FDG) accumulation in the vascular wall of the large vessel using semiquantitative (visual grade) and quantitative (standard uptake value intensity) analyses. Clinical disease activity was evaluated based on the National Institutes of Health criteria for active TA, and erythrocyte sedimentation rates (ESRs) and C-reactive protein (CRP) levels were measured. RESULTS: At baseline, active vascular (18) F-FDG uptake (visual grade ≥2) was observed in 18 of 24 patients with active disease and in 5 of 14 patients with inactive disease. There was a significant association between clinical disease activity and disease activity judged by FDG-PET (P = 0.008). Visual grade, standard uptake value intensity, and the number of vascular lesions with active (18) F-FDG uptake were significantly higher in patients with active disease and correlated well with the ESR and CRP levels. In 15 followup FDG-PET scans, the changes in visual grade, areas of active vascular (18) F-FDG uptake, and standard uptake value intensity reflected changes in clinical disease activity. CONCLUSION: (18) F-FDG uptake was associated with clinical disease activity and markers of inflammation, and FDG-PET reflected changes in clinical disease activity in patients with TA. FDG-PET may be a useful tool for aiding in the assessment of disease activity in patients with TA.
Subject(s)
Aorta/diagnostic imaging , Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Radiopharmaceuticals , Takayasu Arteritis/diagnostic imaging , Adult , Aged , Aorta/pathology , Blood Sedimentation , C-Reactive Protein/metabolism , Female , Humans , Male , Middle Aged , Retrospective Studies , Takayasu Arteritis/pathology , Young AdultABSTRACT
The aim of this study was to develop a highly reliable radiofluorination method for the preparation of N-{2-[4-(2-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4-(18) F-fluoromethylcyclohexane)carboxamide ([(18) F]Mefway) by using a fully automated system. The optimal condition is composed of two parts. The extraction system of the trapped F-18 in the anion exchange resin (i.e., quaternary methylamine cartridge) is a complex of Kryptofix 2.2.2. (K222, 4 mg/0.9 mL methanol) and K2 CO3 (1 mg/0.1 mL H2 O). After removing the solvents, the trans-tosylated Mefway precursor (1 mg/0.5 mL acetonitrile) was reacted with dried K222-K[(18) F] at 100°C for 5 min. After purification and formulation, [(18) F]Mefway was obtained with 38 ± 2.4% (decay corrected, n = 34) radiochemical yield, a total synthesis time of 52 ± 3.4 min, specific activity was 120.6 ± 8.7 GBq/µmol at the end of synthesis and a radiochemical purity of 99%. According to the quality control tests, formulated [(18) F]Mefway is suitable to apply parenteral clinical application.
Subject(s)
Fluorine Radioisotopes/chemistry , Isotope Labeling/methods , Piperazines/chemical synthesis , Pyridines/chemical synthesis , Radiopharmaceuticals/chemical synthesisABSTRACT
Despite the widespread view of the brain as a large complex network, the dynamicity of the brain network over the course of a day has yet to be explored. To investigate whether the spontaneous human brain network maintains long-term stability throughout a day, we evaluated the intra-class correlation coefficient (ICC) of results from an independent component analysis (ICA), seed correlation analysis, and graph-theoretical analysis of resting state functional MRI, acquired from 12 young adults at three-hour intervals over 24 consecutive hours. According to the ICC of the usage strength of the independent network component defined by the root mean square of the temporal weights of the network components, the default mode network centered at the posterior cingulate cortex and precuneus, the superior parietal, and secondary motor networks showed a high temporal stability throughout the day (ICC>0.5). However, high intra-individual dynamicity was observed in the default mode network, including the anterior cingulate cortex and medial prefrontal cortex or posterior-anterior cingulate cortex, the hippocampal network, and the parietal and temporal networks. Seed correlation analysis showed a highly stable (ICC>0.5) extent of functionally connected regions from the posterior cingulate cortex, but poor stability from the hippocampus throughout the day. Graph-theoretical analysis using local and global network efficiency suggested that local brain networks are temporally stable but that long-range integration behaves dynamically in the course of a day. These results imply that dynamic network properties are a nature of the resting state brain network, which remains to be further researched.
Subject(s)
Brain Mapping , Brain/physiology , Nerve Net/physiology , Adult , Female , Humans , Image Interpretation, Computer-Assisted , Magnetic Resonance Imaging , Male , TimeABSTRACT
OBJECTIVE: The purposes of this study were to assess the diagnostic accuracy of 18F-FDG PET (FDG PET) for the detection of metastatic supraclavicular lymph nodes (LNs) and to propose an optimal diagnostic strategy with additional sonography, contrast-enhanced CT (CECT), or both. MATERIALS AND METHODS: One hundred supraclavicular LNs initially detected using FDG PET were examined using sonography. Regardless of the imaging findings, all 100 supraclavicular LNs underwent sonography-guided fine-needle aspiration biopsy. The maximum standardized uptake values (SUVsmax) of the supraclavicular LNs were measured, and a receiver operating characteristic (ROC) analysis was performed to determine the cutoff SUVmax. Then we evaluated the diagnostic performance of FDG PET and figured out the optimal combination of FDG PET and sonography or CECT to improve the diagnostic accuracy of the imaging studies and minimize procedures. RESULTS: In total, 86 of 100 PET-detected supraclavicular LNs were malignant. With application of the cutoff value obtained by ROC analysis (SUVmax=3.0), the diagnostic accuracy of FDG PET was 75.0% with a sensitivity of 74.4% and specificity of 78.6%. For supraclavicular LNs with an SUVmax of more than 3.0, FDG PET showed a positive predictive value of 95.5%; for supraclavicular LNs with an SUVmax of 3.0 or less, sonography excluded all false-negative FDG PET cases and showed a high negative predictive value of 100%. When sonography was selectively applied to cases with an SUVmax of 3.0 or less, the overall diagnostic accuracy increased to 92%. CONCLUSION: Our study revealed a high incidence rate of metastasis in PET-detected supraclavicular LNs in cancer patients. We believe that our proposed diagnostic workflow could decrease unnecessary diagnostic procedures in the evaluation of PET-positive supraclavicular LNs in cancer patients with reliability.
Subject(s)
Lymphatic Metastasis/diagnostic imaging , Multimodal Imaging/methods , Neoplasms/pathology , Positron-Emission Tomography , Tomography, X-Ray Computed , Adult , Aged , Biopsy, Fine-Needle , Clavicle , Contrast Media , Diagnosis, Differential , Female , Fluorodeoxyglucose F18 , Humans , Iohexol/analogs & derivatives , Male , Middle Aged , Predictive Value of Tests , ROC Curve , Radiopharmaceuticals , Retrospective Studies , Ultrasonography, InterventionalABSTRACT
Periventricular leucomalacia has long been investigated as a leading cause of motor and cognitive dysfunction in patients with spastic diplegic cerebral palsy. However, patients with periventricular leucomalacia on conventional magnetic resonance imaging do not always have motor dysfunction and preterm children without neurological abnormalities may have periventricular leucomalacia. In addition, it is uncertain whether descending motor tract or overlying cortical injury is related to motor impairment. To investigate the relationship between motor pathway injury and motor impairment, we conducted voxelwise correlation analysis using tract-based spatial statistics of white matter diffusion anisotropy and voxel-based-morphometry of grey matter injury in patients with periventricular leucomalacia and spastic diplegia (n = 43, mean 12.86 ± 4.79 years, median 12 years). We also evaluated motor cortical and thalamocortical connectivity at resting state in 11 patients using functional magnetic resonance imaging. The functional connectivity results of patients with spastic diplegic cerebral palsy were compared with those of age-matched normal controls. Since γ-aminobutyric acid(A) receptors play an important role in the remodelling process, we measured neuronal γ-aminobutyric acid(A) receptor binding potential with dynamic positron emission tomography scans (n = 27) and compared the binding potential map of the patient group with controls (n = 20). In the current study, white matter volume reduction did not show significant correlation with motor dysfunction. Although fractional anisotropy within most of the major white matter tracts were significantly lower than that of age-matched healthy controls (P < 0.05, family wise error corrected), fractional anisotropy mainly within the bilateral corticospinal tracts and posterior body and isthmus of the corpus callosum showed more significant correlation with motor dysfunction (P < 0.03) than thalamocortical pathways (P < 0.05, family-wise error corrected). Cortical volume of the pre- and post-central gyri and the paracentral lobule tended to be negatively correlated with motor function. The motor cortical connectivity was diminished mainly within the bilateral somatosensory cortex, paracentral lobule, cingulate motor area and visual cortex in the patient group. Thalamovisual connectivity was not diminished despite severe optic radiation injury. γ-Aminobutyric acid(A) receptor binding potential was focally increased within the lower extremity homunculus, cingulate cortex, visual cortex and cerebellum in the patient group (P < 0.05, false discovery rate corrected). In conclusion, descending motor tract injury along with overlying cortical volume reduction and reduced functional connectivity appears to be a leading pathophysiological mechanism of motor dysfunction in patients with periventricular leucomalacia. Increased regional γ-aminobutyric acid(A) receptor binding potential appears to result from a compensatory plasticity response after prenatal brain injury.
Subject(s)
Brain/pathology , Cerebral Palsy/pathology , Efferent Pathways/pathology , Leukomalacia, Periventricular/pathology , Nerve Fibers, Myelinated/pathology , Adolescent , Adult , Anisotropy , Brain/physiopathology , Cerebral Palsy/physiopathology , Child , Diffusion Tensor Imaging , Efferent Pathways/physiopathology , Female , Humans , Image Processing, Computer-Assisted , Infant, Newborn , Leukomalacia, Periventricular/physiopathology , Magnetic Resonance Imaging , Male , Organ SizeABSTRACT
It has been suggested that somatoform disorders are related to both the brain and the immune system, and that immune functions may be influenced by cerebral asymmetry. However, few studies have examined the relationship between brain activity and immune function in somatoform disorders. Thirty-two patients with non-medicated undifferentiated somatoform disorder were enrolled in this study. Blastogenic responses to phytohemagglutinin (PHA) were used to measure immunity. Regional cerebral perfusion was measured by 99m-Tc-ethyl cysteinate dimer single photon emission computed tomography (SPECT). Significant hypoperfusion was found at the left inferior parietal lobule and the left supramarginal gyrus in the more immune-suppressed (MIS) subgroup compared with the less immune-suppressed (LIS) subgroup. However, no regions of significant hyperperfusion were found in the MIS subgroup compared with the LIS subgroup. Decreased cerebral blood flow in the left inferior parietal lobule and the left supramarginal gyrus in the patient group was also significantly associated with reduced blastogenic responses to PHA regardless of sex and age. These results suggest that the left inferior parietal lobule and the left supramarginal gyrus might play an immunomodulating role in patients with undifferentiated somatoform disorder. In addition, these results suggest the role of cerebral asymmetry in altered immunity in the patients.
Subject(s)
Brain Mapping , Brain/pathology , Immunity/physiology , Somatoform Disorders/immunology , Somatoform Disorders/pathology , Adult , Brain/diagnostic imaging , Case-Control Studies , Chi-Square Distribution , Cysteine/analogs & derivatives , Female , Functional Laterality , Humans , Immunity/drug effects , Linear Models , Lymphocyte Activation/drug effects , Lymphocyte Activation/physiology , Male , Middle Aged , Organotechnetium Compounds , Phytohemagglutinins/pharmacology , Psychometrics , Somatoform Disorders/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Young AdultABSTRACT
AIM: Attention deficit has been reported in both schizophrenia patients and patients with major depressive disorder (MDD). The aim of this study was to elucidate the deficits in sustained attention and associated neural network dysfunctions in schizophrenia patients and MDD patients, and to investigate the difference between the two patient groups. METHODS: Twelve schizophrenia patients, 12 patients with non-psychotic MDD, and 12 healthy control subjects participated in this study. A sustained attention to response task (SART) was used to measure attention capacity. Cerebral blood flow (CBF) during attention tasks was measured using H(2) (15) O positron emission tomography. Statistical parametric mapping and analysis of covariance were performed to compare the behavioral performance and CBF changes during SART among three groups. RESULTS: Behavioral performances were not significantly different among the three groups except for an increased commission error rate in the schizophrenia group. Regional CBF during SART was significantly reduced in the left inferior frontal gyrus, the left cuneus, and the right superior parietal lobule and increased in the right superior frontal gyrus and the right cuneus in the schizophrenia group compared to the healthy control group. In the MDD group, neither significant regional CBF difference nor behavioral deficit was found compared to the healthy control group. CONCLUSION: Behavioral performance deficit and perfusion changes in the prefrontal and parietal cortices during SART were observed only in the schizophrenia group. Prefrontal and parietal network dysfunction for sustained attention may be involved in the pathophysiology of schizophrenia.
Subject(s)
Attention/physiology , Brain/physiopathology , Cerebrovascular Circulation/physiology , Nerve Net/physiopathology , Schizophrenia/physiopathology , Adult , Brain/diagnostic imaging , Brain Mapping , Depression/diagnostic imaging , Depression/physiopathology , Depression/psychology , Female , Humans , Male , Nerve Net/diagnostic imaging , Neuropsychological Tests , Psychomotor Performance/physiology , Radionuclide Imaging , Schizophrenia/diagnostic imaging , Schizophrenic PsychologyABSTRACT
Zinc-glutarate (ZnGA) is a promising catalyst that can form polymers from CO2 and epoxides, thereby contributing to the development of CO2 utilization technologies and future sustainability. One of the obstacles to commercializing ZnGA in polymer industries is its low catalytic activity. In this study, we introduced activated two-dimensional (2D) ZnGA to improve its catalytic activity in polymerization. The morphology-controlled 2D ZnGA was treated with H3Co(CN)6, and a porous granular-type Co-modified ZnGA (Co-ZnGA) was prepared. The morphology of 2D ZnGA is a prerequisite for the activation by H3Co(CN)6. The catalytic properties of Co-ZnGA were evaluated by copolymerization of various epoxides and CO2, and exhibited catalytic activity of 855, 1540, 1190, and 148 g g-cat-1 with propylene oxide, 1,2-epoxyhexane, 1,2-epoxybutane, and styrene oxide, respectively. This study provided a new strategy using 2D ZnGA instead of conventional ZnGA for increasing the catalytic activity in CO2 polymerization.