Assessment of whole-body and regional body fat using abdominal quantitative computed tomography in Chinese women and men.

BACKGROUND: Being overweight or obese has become a serious public health concern, and accurate assessment of body composition is particularly important. More precise indicators of body fat composition include visceral adipose tissue (VAT) mass and total body fat percentage (TBF%). Study objectives included examining the relationships between abdominal fat mass, measured by quantitative computed tomography (QCT), and the whole-body and regional fat masses, measured by dual energy X-ray absorptiometry (DXA), as well as to derive equations for the prediction of TBF% using data obtained from multiple QCT slices. METHODS: Whole-body and regional fat percentage were quantified using DXA in Chinese males (n = 68) and females (n = 71) between the ages of 24 and 88. All the participants also underwent abdominal QCT measurement, and their VAT mass and visceral fat volume (VFV) were assessed using QCT and DXA, respectively. RESULTS: DXA-derived TBF% closely correlated with QCT abdominal fat percentage (r = 0.89-0.93 in men and 0.76-0.88 in women). Stepwise regression showed that single-slice QCT data were the best predictors of DXA-derived TBF%, DXA android fat percentage and DXA gynoid fat percentage. Cross-validation analysis showed that TBF% and android fat percentage could be accurately predicted using QCT data in both sexes. There were close correlations between QCT-derived and DXA-derived VFV (r = 0.97 in men and 0.93 in women). CONCLUSION: Clinicians can assess the TBF% and android and gynoid fat percentages of Chinese women and men by analysing existing abdominal CT-derived data using the QCT technique.

Risk factors and clinical prediction models for osteoporosis in pre-dialysis chronic kidney disease patients.

BACKGROUND: Osteoporosis in pre-dialysis chronic kidney disease (CKD) patients has been overlooked, and the risk factors of osteoporosis in these patients have not been adequately studied. OBJECTIVE: To identify risk factors for osteoporosis in pre-dialysis CKD patients and develop predictive models to estimate the likelihood of osteoporosis. METHODS: Dual-energy X-ray absorptiometry was used to measure bone mineral density, and clinical examination results were collected from 326 pre-dialysis CKD patients. Binary logistic regression was employed to explore the risk factors associated with osteoporosis and develop predictive models. RESULTS: In this cohort, 53.4% (n = 174) were male, 46.6% (n = 152) were female, and 21.8% (n = 71) were diagnosed with osteoporosis. Among those diagnosed with osteoporosis, 67.6% (n = 48) were female and 32.4% (n = 23) were male. Older age and low 25-(OH)-Vitamin D levels were identified as risk factors for osteoporosis in males. For females, older age, being underweight, higher bone alkaline phosphatase (NBAP), and advanced CKD (G5) were significant risk factors, while higher iPTH was protective. Older age, being underweight, and higher NBAP were risk factors for osteoporosis in the G1-4 subgroup. In the G5 subgroup, older age and higher NBAP increased the risk, while high 25-(OH)-Vitamin D or iPTH had protective effects. Nomogram models were developed to assess osteoporosis risk in pre-dialysis patients based on gender and renal function stage. CONCLUSION: Risk factors for osteoporosis vary by gender and renal function stages. The nomogram clinical prediction models we constructed may aid in the rapid screening of patients at high risk of osteoporosis.

Deep-learning-based estimation of attenuation map improves attenuation correction performance over direct attenuation estimation for myocardial perfusion SPECT.

BACKGROUND: Deep learning (DL)-based attenuation correction (AC) is promising to improve myocardial perfusion (MP) SPECT. We aimed to optimize and compare the DL-based direct and indirect AC methods, with and without SPECT and CT mismatch. METHODS: One hundred patients with different 99mTc-sestamibi activity distributions and anatomical variations were simulated by a population of XCAT phantoms. Additionally, 34 patients 99mTc-sestamibi stress/rest SPECT/CT scans were retrospectively recruited. Projections were reconstructed by OS-EM method with or without AC. Mismatch between SPECT and CT images was modeled. A 3D conditional generative adversarial network (cGAN) was optimized for two DL-based AC methods: (i) indirect approach, i.e., non-attenuation corrected (NAC) SPECT paired with the corresponding attenuation map for training. The projections were reconstructed with the DL-generated attenuation map for AC; (ii) direct approach, i.e., NAC SPECT paired with the corresponding AC SPECT for training to perform direct AC. RESULTS: Mismatch between SPECT and CT degraded DL-based AC performance. The indirect approach is superior to direct approach for various physical and clinical indices, even with mismatch modeled. CONCLUSION: DL-based estimation of attenuation map for AC is superior and more robust to direct generation of AC SPECT.

Radiosynthesis and preliminary evaluation of 11C-labeled 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e] [1,2,4] thiadiazine 1,1-dioxide for PET imaging AMPA receptors.

The α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) belong to the family of ionotropic transmembrane receptors for glutamate (iGluRs) that are implicated in the pathology of neurological disorders and neurodegenerative diseases. Inspired by a recently developed positive allosteric modulator of AMPARs, 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[ e ][1,2,4]thiadiazine 1,1-dioxide (16; EC50 = 2.0 nM), we designed a new synthetic route for N-protected phenolic precursor 13 and efficiently radiolabeled a PET ligand [11C]AMPA-1905 ([11C]16) using a modified one-pot two-step strategy in high radiochemical yield and high molar activity. Preliminary in vivo evaluation was carried out to investigate the suitability of [11C]16 as a potential PET probe for AMPAR imaging.

A population stereotaxic positron emission tomography brain template for the macaque and its application to ischemic model.

PURPOSE: Positron emission tomography (PET) is a non-invasive imaging tool for the evaluation of brain function and neuronal activity in normal and diseased conditions with high sensitivity. The macaque monkey serves as a valuable model system in the field of translational medicine, for its phylogenetic proximity to man. To translation of non-human primate neuro-PET studies, an effective and objective data analysis platform for neuro-PET studies is needed. MATERIALS AND METHODS: A set of stereotaxic templates of macaque brain, namely the Institute of High Energy Physics & Jinan University Macaque Template (HJT), was constructed by iteratively registration and averaging, based on 30 healthy rhesus monkeys. A brain atlas image was created in HJT space by combining sub-anatomical regions and defining new 88 bilateral functional regions, in which a unique integer was assigned for each sub-anatomical region. RESULTS: The HJT comprised a structural MRI T1 weighted image (T1WI) template image, a functional FDG-PET template image, intracranial tissue segmentations accompanied with a digital macaque brain atlas image. It is compatible with various commercially available software tools, such as SPM and PMOD. Data analysis was performed on a stroke model compared with a group of healthy controls to demonstrate the usage of HJT. CONCLUSION: We have constructed a stereotaxic template set of macaque brain named HJT, which standardizes macaque neuroimaging data analysis, supports novel radiotracer development and facilitates translational neuro-disorders research.

Sex- and age-specific percentiles of body composition indices for Chinese adults using dual-energy X-ray absorptiometry.

PURPOSE: The aims of the study were to develop sex- and age-specific percentiles for lean mass index (LMI), appendicular LMI (aLMI), fat mass index (FMI), and body fat distribution indices in Chinese adults using dual-energy X-ray absorptiometry (DXA), and to compare those indices with those of other ethnicities using the US NHANES data. METHODS: Whole-body and regional lean mass and fat mass (FM) were measured using DXA in 5688 healthy males (n = 1693) and females (n = 3995) aged 20-90 years. Body fat distribution indices were expressed as % fat trunk/% fat legs, trunk/appendicular FM ratio (FMR), and android/gynoid FMR. Percentile curves of LMI, aLMI, FMI, and body fat distribution indices were obtained by the Lambda-Mu-Sigma method. RESULTS: The aLMI and LMI were negatively associated with age, decreasing from the fifth decade for males, but were not associated with age in females. Females had more total FM than males, whereas males had greater central adiposity (% fat trunk/% fat legs ratio, trunk/appendicular FMR, and android/gynoid FMR) than females. Moreover, FMI and body fat distribution indices consistently increased with age in both sexes, especially in women. In comparison with white, black, and Mexican populations in the USA, Chinese adults had lower total FM, but had greater central adiposity (% fat trunk/% fat legs ratio and trunk/appendicular FMR). Additionally, older white and Mexican populations showed greater decreases for aLMI and LMI than their Chinese counterparts. CONCLUSIONS: We present the sex- and age-specific percentiles for aLMI, LMI, FMI, and body fat distribution indices by DXA in Chinese adults, which may refine the individual assessment of the nutritional status of Chinese adults.

Comparison of RECIST, EORTC criteria and PERCIST for evaluation of early response to chemotherapy in patients with non-small-cell lung cancer.

PURPOSE: To compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the European Organization for Research and Treatment of Cancer (EORTC) criteria and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 using PET volume computer-assisted reading (PET VCAR) for response evaluation in patients with advanced non-small-cell lung cancer (NSCLC) treated with chemotherapy. METHODS: A total of 35 patients with NSCLC were included in this prospective study. All patients received standard chemotherapy and underwent (18)F-FDG PET/CT scans before and after treatment. With the assistance of PET VCAR, the chemotherapeutic responses were evaluated according to the RECIST 1.1, EORTC criteria and PERCIST 1.0. Concordance among these protocols was assessed using Cohen's κ coefficient and Wilcoxon's signed-ranks test. Progression-free survival (PFS) was calculated using the Kaplan-Meier test. RESULTS: RECIST 1.1 and EORTC response classifications were discordant in 20 patients (57.1 %; κ = 0.194, P < 0.05), and RECIST 1.1 and PERCIST 1.0 classifications were discordant in 22 patients (62.9 %; κ = 0.139, P < 0.05). EORTC and PERCIST 1.0 classifications were discordant in only 4 patients (11.4 %), resulting in better concordance (κ = 0.804, P > 0.05). Patients with a partial remission according to RECIST 1.1 had significantly longer PFS (P < 0.001) than patients with progressive disease, but not significantly longer than patients with stable disease (P = 0.855). According to both the EORTC criteria and PERCIST 1.0, patients with a partial metabolic response had a significantly longer PFS than those with stable metabolic disease and those with progressive metabolic disease (P = 0.020 and P < 0.001, respectively, for EORTC; both P < 0.001 for PERCIST 1.0). CONCLUSION: EORTC criteria and PERCIST 1.0 are more sensitive and accurate than RECIST 1.1 for the detection of an early therapeutic response to chemotherapy in patients with NSCLC. Although EORTC criteria and PERCIST 1.0 showed similar results, PERCIST 1.0 is preferred because detailed and unambiguous definitions are given. We also found that response evaluations with PERCIST 1.0 using a single lesion and multiple lesions gave similar response classifications.

Relationships between the lean mass index and bone mass and reference values of muscular status in healthy Chinese children and adolescents.

This study aimed to analyze the relationships between the lean mass index (LMI) and bone outcomes in Chinese children and adolescents using dual-energy X-ray absorptiometry (DXA) and to establish sex-specific reference percentile curves for the assessment of muscle status. A total of 1541 Chinese children and adolescents between the ages of 5 and 19 years were recruited from southern China. Body composition was measured by DXA (Lunar Prodigy) to acquire total body and total body less head (TBLH) measures. LMI was calculated as the LM (kg) divided by the height in meters squared. Strong sex gaps were observed after age 14 in total body LMI and appendicular LMI (p < 0.001). LM and LMI values continued to increase for boys up to age 14 compared to girls who plateaued after age 12. For each sex group, total body bone mineral content (BMC) and TBLH BMC were highly correlated with total body LMI and appendicular LMI (r = 0.856-0.916 in boys, and r = 0.651-0.804 in girls, p < 0.001). The appendicular LMI was more strongly associated with total body BMC and TBLH BMC than was total body LMI. The correlations between the BMC values and the LM measures were stronger than the fat mass results. We also present sex-specific percentile curves for LM-age and LMI-age relationships, which could be useful for identifying the LM deficits in this population.

Reference data and percentile curves of body composition measured with dual energy X-ray absorptiometry in healthy Chinese children and adolescents.

Measurements of body composition by dual-energy X-ray absorptiometry (DXA) have evident value in evaluating skeletal and muscular status in growing children and adolescents. This study aimed to generate age-related trends for body composition in Chinese children and adolescents, and to establish gender-specific reference percentile curves for the assessment of muscle-bone status. A total of 1541 Chinese children and adolescents aged from 5 to 19 years were recruited from southern China. Bone mineral content (BMC), lean mass (LM) and fat mass (FM) were measured for total body and total body less head (TBLH). After 14 years, total body LM was significantly higher in boys than girls (p < 0.001). However, total body FM was significantly higher in girls than boys in age groups 13-19 years (p < 0.01). Both LM and FM were consistent independent predictors of total body and subcranial bone mass in both sexes, even after adjustment for the well-known predictors of BMC. The results of multiple linear regression identified LM as the stronger predictor of total body and subcranial skeleton BMC while the fat mass contributed less. For all the subjects, significant positive correlations were observed between total body LM, height, total body BMC and subcranial BMC (p < 0.01). Subcranial BMC had a better correlation with LM than total body BMC. We have also presented gender-specific percentile curves for LM-for-height and BMC-for-LM which could be used to evaluate and follow various pediatric disorders with skeletal manifestations in this population.

The value of the first postoperative diagnostic I-131 scan in patients with papillary thyroid carcinoma.

OBJECTIVE: To explore the feasibility of the postoperative diagnostic 131I whole-body planar scans (Dx-WBS) in papillary thyroid cancer (PTC) patients, and to clarify its value for accurate staging, risk stratification, and postoperative radioactive iodine (RAI) treatment management. DESIGN: Retrospective study from 2015 to 2021. SETTING: A total of 1294 PTC patients in the tertiary referral hospital. PARTICIPANTS: Patients with differentiated thyroid cancer who underwent total/subtotal thyroidectomy were included. Patients with non-PTC pathological type, non-first RAI treatment, and incomplete data such as Dx-WBS and postablation WBS (Rx-WBS) were excluded. METHODS: The diagnostic efficacy of Dx-WBS was calculated with Rx-WBS as the reference. All patients were initially staged by the 8th edition of TNM staging, and risk stratification was performed based on clinical and pathological information. After Dx-WBS, the risk stratification was re-evaluated, and management was reconfirmed. RESULTS: The detection rates of Dx-WBS for residual thyroid, cervical lymph nodes, upper mediastinal lymph nodes, lung, and bone distant metastasis were 97.6%, 78.3%, 82.1%, 66.7%, and 61.2%, respectively. The risk stratification of 113 patients (8.7%) changed after Dx-WBS, of which 107 patients changed from low to intermediate risk, 2 from low to high risk, and 4 from medium to high risk. A total of 241 patients (18.6%) adjusted the RAI regimen after Dx-WBS. CONCLUSION: This study confirms the diagnostic efficacy of the postoperative Dx-WBS in PTC patients and the value of Dx-WBS in accurately assessing risk stratification, as well as assisting in determining RAI treatment.

Development and validation of nomograms for predicting survival in differentiated thyroid cancer patients with or without radioiodine therapy.

Objective: This study aimed to establish and validate the nomograms for predicting overall survival (OS) probabilities in differentiated thyroid cancer (DTC) patients who received and did not receive radioiodine therapy (RAI), respectively. Methods: In this study, 11, 099 patients diagnosed with DTC in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 were selected. Whether they have RAI, they are divided into RAI (n=6427) and non-RAI (n=4672) groups. They were randomly assigned to either a training cohort (RAI: n=4498, non-RAI: n=3263) or a validation cohort (RAI: n=1929, non-RAI: n=1399) using R software to divide the patients in a 7-to-3 ratio randomly. Variables were selected using a backward stepwise method in a Cox regression model to determine the independent prognostic factors, which were then utilized to build two nomograms to predict the 5-, 8-, and 10-year OS probabilities in DTC patients with or without RAI. The concordance index (C-index), the area under the time-dependent receiver operating characteristics curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA) were used to evaluate the performance of our models. Results: The multivariate analyses demonstrated that birth of the year, race, histological type, tumor size, grade, TNM stage, lymph node dissections, surgery, and chemotherapy were risk factors for OS. Compared to the AJCC stage, the C-index (RAI: training group: 0.911 vs. 0.810, validation group: 0.873 vs. 0.761; non-RAI: training group: 0.903 vs. 0.846, validation group: 0.892 vs. 0.808). The AUC values for the training cohort (RAI: 0.940, 0.933, and 0.942; non-RAI: 0.891, 0.884, and 0.852 for the 5-, 8-, and 10-year OS, respectively) and validation cohort (RAI: 0.855, 0.825, and 0.900, non-RAI: 0.867, 0.896, and 0.899), and the calibration plots of both two models all exhibited better performance. Additionally, the NRI and IDI further showed that they exhibited good 5-, 8-, and 10-year net benefits. Conclusion: We have established the prediction models of DTC patients with or without RAI respectively through various variables. The nomogram may be more targeted to guide clinical decisions in the future.

Establishing age-adjusted trabecular bone score curves using dual-energy X-ray absorptiometry in Chinese women and men: a cross-sectional study.

Background: Trabecular bone score (TBS) is a relatively new gray-level textural parameter that provides information on bone microarchitecture. TBS has been shown to be a good predictor of fragility fractures independent of bone density and clinical risk factors. Estimating the normal reference values of TBS in both sexes among the Chinese population is necessary to improve the clinical fracture risk assessment. Methods: This retrospective study enrolled healthy Chinese participants living in Guangzhou, China, including 1,018 men and 3,061 women (aged 20-74 years). Bone mineral density images were obtained with dual-energy X-ray absorptiometry (DXA) scanning of the lumbar region (L1-4). Lumbar spine TBS values were calculated. The correlations between the scores and bone mineral density, age, height, and weight were calculated for men and women. A TBS reference plot was established in relation to age (20-74 years). Values 2 standard deviations below the mean score for each sex were used as the cutoff values for low-quality bone. Results: The TBS (L1-4) was significantly higher in Chinese men than in Chinese women. The scores peaked at 25-29 years (1.47±0.08 years) in men and at 20-24 years (1.43±0.08 years) in women. According to the statistical confidence interval, in Chinese males, a TBS ≥1.39 is considered normal, a TBS between 1.31 and 1.39 indicates partially degraded microarchitecture, and a TBS ≤1.31 indicates degraded microarchitecture. In Chinese females, a TBS ≥1.35 is considered normal, a TBS between 1.27 and 1.35 indicates partially degraded microarchitecture, and a TBS ≤1.27 indicates degraded microarchitecture. Conclusions: This study provides normative reference ranges for the TBS in Chinese men and women. Chinese men with a TBS score ≤1.31 and Chinese women with a TBS score ≤1.27 are can be considered to have reduced bone microarchitecture and may be at higher risk of having osteoporosis fractures.

Precision of quantitative parameters of 18F-FDG PET/CT in a rabbit VX2 tumor model.

Background: The precision reflecting repeated measurement error of quantitative parameters of flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for evaluating the therapeutic effect of solid tumor can help observe whether a real biologic change in glucose metabolism occurred, or if the change was caused by errors before and after the treatment. Methods: A total of 18 VX2 tumor-bearing male New Zealand rabbits confirmed by pathology were used, three of which were used for determining the best scanning time point after injection and 15 for a precision experiment by repeating PET/CT scans for three consecutive days. The PET volume computer-assisted reading (PET VCAR) software (GE Healthcare) was used to analyze the standardized uptake value (SUV) and total lesion glycolysis (TLG) parameters. The lean body mass (LBM) to calculate the SUV corrected for lean body mass (SUL) parameters was measured using dual energy X-ray absorptiometry (DXA). The precision was represented as the coefficient of variation of root mean square (RMS-CV) and standard deviation of root mean square (RMS-SD). The least significant change (LSC) was also calculated when considering precision. Results: The precision of SUV parameters, including SUVmax, SUVmean and SUVpeak ranged from 18.3% to 18.8%, which was similar to that of the SUL parameters (18.0-18.4%). Using 80% confidence interval (CI), the LSC of SUVmax and SULpeak were 33.1% and 33.3%, respectively; using 95% CI, the LSC of SUVmax and SULpeak were 50.1% and 51.0%, respectively. Conclusions: This research established the method of precision in a rabbit VX2 tumor model, which can be used for monitoring changes to assess the effects of drug treatment on solid tumors in experimental studies with 18F-FDG PET/CT imaging.

Predictive value of metabolic parameters derived from preoperative 18F-FDG positron emission tomography/computed tomography for brain metastases in patients with surgically resected non-small cell lung cancer.

Background: Brain metastases (BMs) are common complications in patients with non-small cell lung cancer (NSCLC). The purpose of this study was to investigate whether the metabolic parameters derived from preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) can predict BM development in patients with surgically resected NSCLC. Methods: We retrospectively reviewed 128 consecutive patients with stage I-IIIA NSCLC who underwent 18F-FDG PET/CT before curative surgery at The First Affiliated Hospital of Jinan University between November 2012 and October 2021. By drawing a volume of interest (VOI), the maximum standardized uptake values (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor as well as the mean SUV (SUVmean) of the liver and arterial blood were measured. The tumor-to-liver SUV ratio (TLR) and tumor-to-blood SUV ratio (TBR) were also calculated. Receiver operating characteristic curve analysis was used to determine the best cut-off values for positron emission tomography (PET) parameters to predict BM-free survival, and Cox proportional hazards regression analysis was used to assess the predictive value of clinical variables and PET parameters. Results: The median follow-up duration for survival patients was 23.4 months, and 15 patients (11.7%) experienced BM as the initial relapse site. The cumulative rates of BM over the course of 1, 2, and 5 years were 4.5%, 10.5%, and 17.5%, respectively. The optimal cut-off values for the prediction of BM-free survival were 7.7, 4.9, and 4.5 for SUVmax, TLR, and TBR, and 5.5 mL and 16.1 for MTV and TLG, respectively. In the Cox proportional hazards model, the risk of BM was significantly associated with TLR [hazard ratio (HR) =10.712; 95% confidence interval (CI): 2.958-38.801; P<0.001] and MTV (HR =3.150; 95% CI: 0.964-10.293; P=0.020) after adjusting for tumor stage, clinicopathological factors, and other PET parameters. Conclusions: Preoperative TLR and MTV of the primary tumor may be helpful in predicting BM development in patients with surgically resected NSCLC. Tumor metabolic parameters may potentially be used to stratify the risk of BM and determine individualized surveillance strategies.

Recent developments on the application of molecular probes in multiple myeloma: Beyond [18F]FDG.

Multiple myeloma (MM) is a neoplastic plasma cell proliferative disorder characterized by various osteolytic bone destruction as a radiological morphological marker. Functional imaging, particularly nuclear medicine imaging, is a promising method to visualize disease processes before the appearance of structural changes by targeting specific biomarkers related to metabolism ability, tumor microenvironment as well as neoplastic receptors. In addition, by targeting particular antigens with therapeutic antibodies, immuno-PET imaging can support the development of personalized theranostics. At present, various imaging agents have been prepared and evaluated in MM at preclinical and clinical levels. A summary overview of molecular functional imaging in MM is provided, and commonly used radiotracers are characterized.

Predictive value of baseline metabolic tumor burden on 18F-FDG PET/CT for brain metastases in patients with locally advanced non-small-cell lung cancer.

Objectives: Brain metastases (BMs) are a major cause leading to the failure of treatment management for non-small-cell lung cancer (NSCLC) patients. The purpose of this study was to evaluate the predictive value of baseline metabolic tumor burden on 18F-FDG PET/CT measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for brain metastases (BMs) development in patients with locally advanced non-small-cell lung cancer (NSCLC) after treatment. Methods: Forty-seven patients with stage IIB-IIIC NSCLC who underwent baseline 18F-FDG PET/CT examinations were retrospectively reviewed. The maximum standardized uptake value (SUVmax), MTV, and TLG of the primary tumor (SUVmaxT, MTVT, and TLGT), metastatic lymph nodes (SUVmaxN, MTVN, and TLGN), and whole-body tumors (SUVmaxWB, MTVWB, and TLGWB) were measured. The optimal cut-off values of PET parameters to predict brain metastasis-free survival were obtained using Receiver operating characteristic (ROC) analysis, and the predictive value of clinical variables and PET parameters were evaluated using Cox proportional hazards regression analysis. Results: The median follow-up duration was 25.0 months for surviving patients, and 13 patients (27.7%) developed BM. The optimal cut-off values were 21.1 mL and 150.0 g for MTVT and TLGT, 20.0, 10.9 mL and 55.6 g for SUVmaxN, MTVN and TLGN, and 27.9, 27.4 mL and 161.0 g for SUVmaxWB, MTVWB and TLGWB, respectively. In the Cox proportional hazards models, the risk of BM was significantly associated with MTVN and MTVWB or TLGN and TLGWB after adjusting for histological cell type, N stage, SUVmaxN, and SUVmaxWB. Conclusions: Baseline metabolic tumor burden (MTV and TLG) evaluated from the level of metastatic lymph nodes and whole-body tumors are significant predictive factors for BM development in patients with locally advanced NSCLC.

Analysis of serum bone turnover markers in female cynomolgus monkeys of different ages.

Objective: The purpose of this study was to examine bone turnover markers, estradiol, parathyroid hormone, and 25 hydroxyvitamin D, in cynomolgus monkeys at different ages to improve our understanding of the changes in bone turnover markers throughout the life cycle of cynomolgus monkeys and to provide a basis for the establishment of a non-human primate model of osteoporosis. Methods: Total Body Bone Mineral Density and Total Body Bone Mineral Content were measured using Dual-Energy X-Ray Absorptiometry in cynomolgus monkeys at different ages. Serum bone turnover marker' levels were measured using enzyme immunoassays at each age group, and the relationship between bone turnover markers and age was assessed by Spearman rank correlation analysis to investigate the relationship between bone turnover markers and age in female cynomolgus monkeys. Results: Total Body Bone Mineral Density in female cynomolgus monkeys peaked at 10 years of age and then formed a plateau that was maintained until old age. Procollagen I Aminoterminal Propeptide, Bone Alkaline Phosphatase, Osteocalcin, and C-Terminal Telopeptide Of Type I Collagen peaked at 1 to 3 years of age and gradually decreased with age, leveling off by 10 years of age. Estradiol, parathyroid hormone, and 25 hydroxyvitamin D, follicle-stimulating hormone, luteinizing hormone, were not significantly different among age groups. Conclusion: This paper provides data on trends in bone turnover markers throughout the life cycle of female cynomolgus monkeys, which are similar to human changes.

The precision study of dual energy X-ray absorptiometry for bone mineral density and body composition measurements in female cynomolgus monkeys.

Background: Dual-energy X-ray absorptiometry (DXA) is a well-accepted tool for monitoring skeletal and body composition changes in biomedical studies. The nonhuman primate model is suitable for studies exploring the pathogenesis of and novel treatments for osteoporosis. Our objectives are to determine the precision of DXA detection in cynomolgus monkeys and to identify the difference in precision in lumbar bone mineral density (BMD) with various segment selections. Methods: Thirty adult female cynomolgus monkeys underwent duplicate total body DXA scans. Total body bone mineral density (BMDTB) and body composition, including bone mineral content (BMCTB), lean mass (LMTB), and fat mass (FMTB), were analyzed by enCORE software, while lumbar BMD was obtained by manual region-of-interest analysis. The precision was represented as the root-mean-square standard deviation (RMS-SD) and coefficient of variation (RMS-CV%), and least significant changes (LSCs) were reported. Results: The RMS-SD (RMS-CV%) of the repeated DXA analyses for BMDTB, BMCTB, LMTB and FMTB were 0.002 g/cm2 (0.50%), 0.90 g (0.42%), 0.015 kg (0.49%), and 0.031 kg (2.71%), respectively. The regional BMD precision (RMS-CV%) of the lumbar spine with various combinations ranged from 0.70% to 1.09%, The LSCs with 80% statistical confidence (LSC80) ranged from 1.27% to 1.97%, and LSC95 ranged from 1.94% to 3.01%. Conclusions: DXA provided excellent reproducibility in the measurements of BMD and body composition in nonhuman primates. We find DXA reliable for total and regional measurement in skeletal research and the evaluation of osteoporosis treatment with monkeys as animal models.

A method for evaluation of patient-specific lean body mass from limited-coverage CT images and its application in PERCIST: comparison with predictive equation.

BACKGROUND: Standardized uptake value (SUV) normalized by lean body mass ([LBM] SUL) is recommended as metric by PERCIST 1.0. The James predictive equation (PE) is a frequently used formula for LBM estimation, but may cause substantial error for an individual. The purpose of this study was to introduce a novel and reliable method for estimating LBM by limited-coverage (LC) CT images from PET/CT examinations and test its validity, then to analyse whether SUV normalised by LC-based LBM could change the PERCIST 1.0 response classifications, based on LBM estimated by the James PE. METHODS: First, 199 patients who received whole-body PET/CT examinations were retrospectively retrieved. A patient-specific LBM equation was developed based on the relationship between LC fat volumes (FVLC) and whole-body fat mass (FMWB). This equation was cross-validated with an independent sample of 97 patients who also received whole-body PET/CT examinations. Its results were compared with the measurement of LBM from whole-body CT (reference standard) and the results of the James PE. Then, 241 patients with solid tumours who underwent PET/CT examinations before and after treatment were retrospectively retrieved. The treatment responses were evaluated according to the PE-based and LC-based PERCIST 1.0. Concordance between them was assessed using Cohen's κ coefficient and Wilcoxon's signed-ranks test. The impact of differing LBM algorithms on PERCIST 1.0 classification was evaluated. RESULTS: The FVLC were significantly correlated with the FMWB (r=0.977). Furthermore, the results of LBM measurement evaluated with LC images were much closer to the reference standard than those obtained by the James PE. The PE-based and LC-based PERCIST 1.0 classifications were discordant in 27 patients (11.2%; κ = 0.823, P=0.837). These discordant patients' percentage changes of peak SUL (SULpeak) were all in the interval above or below 10% from the threshold (±30%), accounting for 43.5% (27/62) of total patients in this region. The degree of variability is related to changes in LBM before and after treatment. CONCLUSIONS: LBM algorithm-dependent variability in PERCIST 1.0 classification is a notable issue. SUV normalised by LC-based LBM could change PERCIST 1.0 response classifications based on LBM estimated by the James PE, especially for patients with a percentage variation of SULpeak close to the threshold.

Sequential PET/diffusion-weighted imaging in the evaluation of myocardial perfusion and viability in coronary artery disease: a preliminary study.

OBJECTIVES: To evaluate the utility of sequential F-18 fluorodeoxyglucose PET/diffusion-weighted imaging in assessing myocardial perfusion and viability in coronary artery disease. METHODS: Fourteen coronary artery disease patients and five non-coronary artery disease subjects underwent sequential cardiac F-18 fluorodeoxyglucose PET/diffusion-weighted imaging using a trimodality PET/computed tomography-MRI system. The perfusion data were acquired by measuring low b-values apparent diffusion coefficient using diffusion-weighted imaging. Regional myocardial viability was determined by perfusion/metabolism patterns. The perfusion/metabolism patterns obtained by low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake were analyzed and compared with the results from the combination of rest methoxyisobutylisonitrile (Tc-MIBI) myocardial perfusion single-photon emission computed tomography with F-18 fluorodeoxyglucose PET/computed tomography. RESULTS: Ten coronary artery disease patients and five non-coronary artery disease subjects were included in the final analysis. Low b-values apparent diffusion coefficient defects involved with 25 myocardial regions were demonstrated in nine coronary artery disease patients, while Tc-MIBI defects involved with 21 myocardial regions were shown in the same patients. The agreement between low b-values apparent diffusion coefficient and MIBI uptake was good in coronary artery disease patients (κ = 0.627, P < 0.001) and was better still in the whole subjects (κ = 0.733, P < 0.001). Low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake demonstrated mismatch patterns in six coronary artery disease patients and MIBI/fluorodeoxyglucose uptake revealed mismatch patterns in seven coronary artery disease patients. Agreement in the evaluation of regional myocardial viability between low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake and MIBI/fluorodeoxyglucose uptake was high in coronary artery disease patients (κ = 0.627, P < 0.001) and all subjects (κ = 0.728, P < 0.001). CONCLUSIONS: Low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake is comparable to MIBI/fluorodeoxyglucose uptake in assessing perfusion/metabolism patterns, indicating that microperfusion might dominate the diffusion signal at low b-values and sequential PET/diffusion-weighted imaging might be useful to evaluate myocardial viability in coronary artery disease patients.