High-Resolution Haplotyping of the PAH Gene Enables Early Gestation Noninvasive Prenatal Diagnosis of Phenylketonuria and Evolution Analysis of Recurrent Pathogenic Variations.

BACKGROUND: The clinical performance of RHDO-based NIPD for PKU during early gestation remains under-evaluated. Furthermore, studies focused on SNP loci obtained by next-generation sequencing to analyze the genetic evolution of pathogenic variations in PKU is limited. METHODS: Maternal peripheral blood, along with proband and paternal samples, was collected between 7 and 12 weeks of gestation. The PAH gene and surrounding high heterozygosity SNPs were targeted for enrichment and sequencing. Fetal genotypes were inferred using RHDO-based NIPD. High-resolution PAH haplotypes were used for the analysis of two common pathogenic variants in the Chinese population: c.728G>A and c.1238G>C. RESULTS: Sixty one PKU families participated with an average fetal fraction of 6.08%. The median gestational age was 8+6 weeks. RHDO-based NIPD successfully identified fetal genotypes in 59 cases (96.72%, 59/62). Two cases failed because of insufficient informative SNPs. In addition, a recombination event was assessed in one fetus of 59 cases. Six, and three haplotypes were identified for c.728G>A(p.Arg243Gln) and c.1238G>C(p.Arg413Pro), respectively. Hap_3 and hap_8 were identified as the ancestral haplotypes for these pathogenic variants, with other haplotypes arising from mutations or recombination based on these ancestral haplotypes. CONCLUSIONS: This study validates the feasibility of an RHDO-based assay for NIPD of PKU in early pregnancy and introduces its application in the demonstration of founder effects in recurrent pathogenic variations, offering new insights into the evolutionary analysis of PAH variations.

Comparison of the value of adipose tissues in abdomen and lumbar vertebra for predicting disease activity in Crohn's disease: A preliminary study based on CSE-MRI.

BACKGROUND: To compare the value of adipose tissues in abdomen and lumbar vertebra for predicting Crohn's disease (CD) activity based on chemical shift encoded magnetic resonance imaging (CSE-MRI). METHODS: 84 CD patients were divided into remission, mild, and moderate-severely groups based on CD activity index (CDAI). Differences in different adipose parameters [subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), mesenteric fat index (MFI), and bone marrow fat fraction (BMFF)] and blood inflammatory indicators among three groups, as well as the correlation of above parameters and CDAI were analyzed. The areas under the receiver-operating characteristic curves (AUCs) for the parameters selected by multivariate logistic regression analysis for predicting active CD were calculated. RESULTS: There were no significant differences in VAT and MFI among three groups (both P > 0.05). The cross-sectional areas of SAT in moderate-severe group were significantly lower than those in remission group (P = 0.014). BMFF values of remission group were significantly higher than those in the mild and moderate-severe groups (both P < 0.001). BMFF was negatively correlated with CDAI (r = -0.595, P < 0.001). SAT exhibited no significant correlation with CDAI. Erythrocyte sedimentation rate (ESR) and BMFF were the independent predictors of CDAI. Both combined had a higher diagnostic efficacy for active CD with an AUC of 0.895. CONCLUSIONS: BMFF is the best marker for predicting CD activity in fat parameters of abdomen and lumbar vertebra based on CSE-MRI. The model based on BMFF and ESR has a high efficiency in predicting active CD. TRIAL REGISTRATION: No. 22 K164 (Registered 18-07-2022).

Hypertension Impacts the Oscillatory Dynamics Serving the Encoding Phase of Verbal Working Memory.

BACKGROUND: Chronic hypertension is known to be a major contributor to cognitive decline, with executive function and working memory being among the domains most commonly affected. Despite the growing literature on such dysfunction in patients with hypertension, the underlying neural processes are poorly understood. METHODS: In this cross-sectional study, we examine these neural processes by having participants with controlled hypertension, uncontrolled hypertension, and healthy controls perform a verbal working memory task during magnetoencephalography. Neural oscillations associated with the encoding and maintenance components of the working memory task were imaged and statistically evaluated among the 3 groups. RESULTS: Differences related to hypertension emerged during the encoding phase, where the hypertension groups exhibited weaker α-ß oscillatory responses compared with controls in the left parietal cortices, whereas such oscillatory activity differed between the 2 hypertension groups in the right prefrontal regions. Importantly, these neural responses in the prefrontal and parietal cortices during encoding were also significantly associated with behavioral performance across all participants. CONCLUSIONS: Overall, our data suggest that hypertension is associated with neurophysiological abnormalities during working memory encoding, whereas the neural processes serving maintenance seem to be preserved. The right hemispheric neural responses likely reflected compensatory processing, which patients with controlled hypertension may use to achieve verbal working memory function at the level of controls, as opposed to the uncontrolled hypertension group where diminished resources may have limited such additional recruitment.

Noninvasive twin genotyping for recessive monogenic disorders by relative haplotype dosage.

OBJECTIVE: To establish a haplotype-based noninvasive prenatal testing (NIPT) workflow for single-gene recessive disorders that adapt to dizygotic (DZ) twin pregnancies. METHOD: Twin pregnancies at risk of Duchenne muscular dystrophy, Becker muscular dystrophy, hemophilia B, spinal muscular atrophy, phenylketonuria, and nonsyndromic hearing loss were recruited. For subsequent analysis, capture sequencing targeting highly heterozygotic single nucleotide polymorphism sites was conducted. Paternal-specific alleles were used to calculate the total and individual fetal fractions and determine zygosity. A two-step Bayes Factor model was applied to clarify the complex genomic landscape in the maternal plasma: the first step involved determining whether the twins inherited the same haplotype, and the second step involved estimating their individual genotypes. NIPT results were subsequently confirmed by invasive diagnosis. RESULTS: Nine twin pregnancies were recruited, including five DZ and four monozygotic (MZ) twins. The earliest gestational age was 8+0 weeks, and the minimum fetal fraction was 4.6%. Three twin pregnancies were reported with one affected fetus, while the remaining six were reported without affected fetuses. Two dichorionic diamniotic twin pregnancies were confirmed to be MZ twins. The NIPT results were 100% consistent with those of invasive procedures or diagnostic genetic testing after birth. CONCLUSION: This study is the first to perform NIPT for single-gene disorders in twin pregnancies and preliminarily confirm its clinical feasibility. Acknowledging the twins' genotypes in the first trimester is valuable as it empowers obstetric care providers and parents to have adequate time for pregnancy management and decision-making.

Exploring factors impacting haplotype-based noninvasive prenatal diagnosis for single-gene recessive disorders.

Haplotype-based noninvasive prenatal diagnosis (NIPD) is applicable for various recessive single-gene disorders in proband families. However, a comprehensive exploration of critical factors influencing the assay performance, such as fetal fraction, informative single nucleotide polymorphism (SNP) count, and recombination events, has yet to be performed. It is critical to identify key factors affecting NIPD performance, including its accuracy and success rate, and their impact on clinical diagnostics to guide clinical practice. We conducted a prospective study, recruiting 219 proband families with singleton pregnancies at risk for eight recessive single-gene disorders (Duchenne muscular dystrophy, spinal muscular atrophy, phenylketonuria, methylmalonic acidemia, hemophilia A, hemophilia B, non-syndromic hearing loss, and congenital adrenal hyperplasia) at 7-14 weeks of gestation. Haplotype-based NIPD was performed by evaluating the relative haplotype dosage (RHDO) in maternal circulation, and the results were validated via invasive prenatal diagnosis or newborn follow-ups. Among the 219 families, the median gestational age at first blood draw was 8+5 weeks. Initial testing succeeded for 190 families and failed for 29 due to low fetal fraction (16), insufficient informative SNPs (9), and homologous recombination near pathogenic variation (4). Among low fetal fraction families, successful testing was achieved for 11 cases after a redraw, while 5 remained inconclusive. Test failures linked to insufficient informative SNPs correlated with linkage disequilibrium near the genes, with F8 and MMUT exhibiting the highest associated failure rates (14.3% and 25%, respectively). Homologous recombination was relatively frequent around the DMD and SMN1 genes (8.8% and 4.8%, respectively) but led to detection failure in only 44.4% (4/9) of such cases. All NIPD results from the 201 successful families were consistent with invasive diagnostic findings or newborn follow-up. Fetal fraction, informative SNPs count, and homologous recombination are pivotal to NIPD performance. Redrawing blood effectively improves the success rate for low fetal fraction samples. However, informative SNPs count and homologous recombination rates vary significantly across genes, necessitating careful consideration in clinical practice. We have designed an in silico method based on linkage disequilibrium data to predict the number of informative SNPs. This can identify genomic regions where there might be an insufficient number of SNPs, thereby guiding panel design. With these factors properly accounted for, NIPD is highly accurate and reliable.

Haplotype-based noninvasive prenatal diagnosis of methylmalonic acidemia and the discovery of a recurrent pathogenic haplotype associated with c.609G>A.

BACKGROUND: Early diagnosis and intervention are crucial for the prognosis of methylmalonic acidemia (MMA). However, research focused on early prenatal diagnosis of MMA is limited. METHODS: A 161.89kb capture panel was designed for selectively enriching highly heterozygous SNPs. Fetal genotypes were inferred using relative haplotype dosage (RHDO) and Bayes factor, followed by invasive prenatal diagnosis (IPD) for validation. A core pathogenic haplotype associated with c.609G>A was identified based on the frequency differences between pathogenic and normal haplotypes. RESULTS: We recruited 41 pregnancies at risk of MMA with a median gestational age of 8+2  weeks. The assay success rate of NIPD-MMA for maternal variants was 92.7% (38/41), and after incorporating the paternal result, the overall assay success rate reached 100% (41/41). All NIPD results were concordant with IPD. Notably, a core haplotype (hap_2), comprising 28 SNPs, demonstrates significant enrichment within pathogenic haplotypes bearing the c.609G>A variation. On average, c.609G>A carriers had 22.38 heterozygous loci within these 28 SNPs. CONCLUSION: NIPD-MMA presents a viable choice for early, accurate, and safe prenatal diagnosis. Furthermore, the discovery of the recurrent core pathogenic haplotype provides a novel approach for haplotype phasing and has the potential for realizing proband-independent NIPD in the future.

Air bronchogram on chest CT in radiological pure-solid appearance lung cancer: Correlation analysis with genetic pathological features and survival outcomes.

PURPOSE: To investigate the correlation of air bronchogram sign with clinicopathological characteristics and prognosis in patients with clinical stage (c-stage) I non-small cell lung cancer (NSCLC) with radiological pure-solid appearance. METHOD: We retrospectively evaluated 276 patients with pure-solid c-stage I NSCLC and assessed the correlation between the air bronchogram and clinicopathological characteristics. A Cox proportional hazards model was performed to identify the effect of air bronchogram and clinicopathological variables on oncological outcomes. Recurrence-free survival (RFS) and overall survival (OS) were calculated by Kaplan-Meier curves and were compared using log-rank tests. RESULTS: Presence of air bronchogram was associated with a well differentiated degree (P =.026), higher incidence of EGFR mutation (P <.001) and lower recurrence(P =.021). Kaplan-Meier survival curves showed that air bronchogram group was associated with favorable RFS(67.0% vs. 50.2%; P =.015). A multivariable analysis revealed that air bronchogram and EGFR mutation were independent significant prognostic factors associated with RFS (hazard ratio [HR] = 0.495, 95% confidence interval [CI]: 0.322-0.761, P =.001; HR = 1.625, 95% CI: 1.074-2.457, P =.021; respectively), but not with OS. Additionally, we found that pathological lymph node metastasis was identified as an independent prognostic factor associated with poor RFS and OS(HR = 2.808, 95% CI: 1.913-4.123, P <.001 for RFS; HR = 1.983, 95% CI: 1.185-3.318, P =.009 for OS). CONCLUSIONS: Presence of air bronchogram was associated with well differentiated degree, higher incidence of EGFR mutation and had additional positive prognostic value for RFS in c-stage I NSCLC with a radiological pure-solid appearance.

mDIXON-Quant technique diagnostic accuracy for assessing bone mineral density in male adult population.

BACKGROUND: To investigate the diagnostic efficacy of mDIXON-Quant technique for prediction of bone loss in male adults. METHODS: One hundred thirty-eight male adults were divided into normal, osteopenia, and osteoporosis groups based on DXA and QCT for the lumbar spine. Differences in mDIXON-Quant parameters [fat fraction (FF) and T2* value] among three groups, as well as the correlation of mDIXON-Quant parameters and bone mineral density (BMD) were analyzed. The areas under the curves (AUCs) for mDIXON-Quant parameters for prediction of low bone mass were calculated. RESULTS: According to DXA standard, FF and T2* value were significantly increased in osteoporosis group compared with normal group (P = 0.012 and P < 0.001). According to QCT standard, FF was significantly increased in osteopenia and osteoporosis groups compared with normal group (both P < 0.001). T2* values were significantly different among three groups (all P < 0.05). After correction for age and body mass index, FF was negatively correlated with areal BMD and volumetric BMD (r = -0.205 and -0.604, respectively; both P < 0.05), and so was T2* value (r = -0.324 and -0.444, respectively; both P < 0.05). The AUCs for predicting low bone mass according to DXA and QCT standards were 0.642 and 0.898 for FF, 0.648 and 0.740 for T2* value, and 0.677 and 0.920 for both combined, respectively. CONCLUSIONS: FF combined with T2* value has a better diagnostic efficacy than FF or T2* value alone in prediction of low bone mass in male adults, which is expected to be a promising MRI method for the screening of bone quality. TRIAL REGISTRATION: ChiCTR1900024511 (Registered 13-07-2019).

A preliminary study on degenerate characteristics of lumbar and abdominal muscles in middle-aged and elderly people with varying bone mass.

BACKGROUND: With the wide application of QCT in the clinical assessment of osteoporosis and sarcopenia, the characteristics of musculoskeletal degeneration in middle-aged and elderly people need to be further revealed. We aimed to investigate the degenerate characteristics of lumbar and abdominal muscles in middle-aged and elderly people with varying bone mass. METHODS: A total of 430 patients aged 40-88 years were divided into normal, osteopenia, and osteoporosis groups according to quantitative computed tomography (QCT) criteria. The skeletal muscular mass indexes (SMIs) of five muscles [abdominal wall muscles (AWM), rectus abdominis (RA), psoas major muscle (PMM), posterior vertebral muscles (PVM), and paravertebral muscles (PM)] included in lumbar and abdominal muscles were measured by QCT. Differences in SMIs among three groups, as well as the correlation between SMIs and volumetric bone mineral density (vBMD) were analyzed. The areas under the curves (AUCs) for SMIs for prediction of low bone mass and osteoporosis were calculated. RESULTS: In male group, SMIs of RA and PM in osteopenia group were significantly lower than those in the normal group (P = 0.001 and 0.023, respectively). In female group, only SMI of RA in osteopenia group was significantly lower than that in the normal group (P = 0.007). SMI of RA was positively correlated with vBMD with the highest coefficients in male and female groups (r = 0.309 and 0.444, respectively). SMIs of AWM and RA had higher AUCs varying from 0.613 to 0.737 for prediction of low bone mass and osteoporosis in both genders. CONCLUSIONS: The changes of SMIs of the lumbar and abdominal muscles in patients with varying bone mass are asynchronous. SMI of RA is expected to be a promising imaging marker for predicting abnormal bone mass. TRIAL REGISTRATION: ChiCTR1900024511 (Registered 13-07-2019).

Correlation between musculoskeletal mass and perfusion in patients with gastrointestinal malignancy: a preliminary study based on quantitative CT and CT perfusion.

BACKGROUND: To investigate the correlation between musculoskeletal mass and perfusion using quantitative computer tomography (QCT) and CT perfusion (CTP) in patients with gastrointestinal malignancy. METHODS: In this prospective study, 96 patients (mean age 66 years, range 25-90; 63.5% male) with gastrointestinal malignancy underwent QCT and CTP between May 2019 and February 2021. Bone mineral density (BMD) and body composition [perivertebral muscular mass index (PMI), skeletal muscular mass index (SMI) and muscular fat fraction] were evaluated through QCT. Musculoskeletal perfusion parameters were measured by CTP. Differences in these parameters between (or among) two (or three) groups (grouped by BMD, SMI, and TNM staging) were analyzed. RESULTS: There were significant differences in PMI and muscular fat fraction among normal (n = 30), osteopenia (n = 43), and osteoporosis (n = 23) groups (both P < 0.001). Blood flow (r = 0.336, P = 0.001; adjusted for age and gender, r = 0.383, P < 0.001), blood volume (r = 0.238, P = 0.011; adjusted for age and gender, r = 0.329, P = 0.001), and flow extraction product (r = 0.217, P = 0.034; adjusted for age and gender, r = 0.320, P = 0.002) vaules of vertebral perfusion showed positive correlation with BMD. However, the relationships between PMI and perfusion parameters of perivertebral muscle were not significant. No significant differences were found in musculoskeletal mass and perfusion parameters between different TNM staging. CONCLUSIONS: The changes of bone mass and perivertebral muscular mass in patients with gastrointestinal malignancy are synchronous. Decreased vertebral bone mass is accompanied with reduced perivertebral muscular mass, increased muscular fat, and decreased bone perfusion. However, the changes of perfusion in vertebra and perivertebral muscles are asynchronous. Musculoskeletal mass and perfusion have no correlation with TNM staging of the patients with gastrointestinal malignancy. TRIAL REGISTRATION: SHSY-IEC-4.1/20-242/01 (Registered 09-12-2020, Retrospectively registered).

Omentin­1 induces osteoblast viability and differentiation via the TGF­ß/Smad signaling pathway in osteoporosis.

Osteoporosis is a bone­related disease that results from impaired bone formation and excessive bone resorption. The potential value of adipokines has been investigated previously, due to their influence on osteogenesis. However, the osteogenic effects induced by omentin­1 remain unclear. The aim of the present study was to determine the regulatory effects of omentin­1 on osteoblast viability and differentiation, as well as to explore the underlying molecular mechanism. The present study investigated the effects of omentin­1 on the viability and differentiation of mouse pre­osteoblast cells (MC3T3­E1) using quantitative and qualitative measures. A Cell Counting Kit­8 assay was used to assess the viability of MC3T3­E1 cells following treatment with different doses of omentin­1. Omentin­1 and bone morphogenetic protein (BMP) inhibitor were added to osteogenic induction mediums in different ways to assess their effect. The alkaline phosphatase (ALP) activity and Alizarin Red S (ARS) staining of MC3T3­E1 cells treated with omentin­1 and/or BMP inhibitor were used to examine the effects of omentin­1 on differentiation and mineralization. Western blotting was used to further explore its potential mechanism, and to study the role of omentin­1 on the viability and differentiation of osteoblasts. The results showed that omentin­1 altered the viability of MC3T3­E1 cells in a dose­dependent manner. Omentin­1 treatment significantly increased the expression of members of the TGF­ß/Smad signaling pathway. In the omentin­1 group, the ALP activity of the MC3T3­E1 cells was increased, and the ARS staining area was also increased. The mRNA and protein expression levels of BMP2, Runt­related transcription factor 2, collagen1, osteopontin, osteocalcin and osterix in the omentin­1 group were also significantly upregulated. All these effects were reversed following treatment with SIS3 HCl. These results demonstrated that omentin­1 can significantly promote osteoblast viability and differentiation via the TGF­ß/Smad signaling pathway, thereby promoting bone formation and preventing osteoporosis.

Association of Periaortic Fat and Abdominal Visceral Fat with Coronary Artery Atherosclerosis in Chinese Middle Aged and Elderly Patients Undergoing Computed Tomography Coronary Angiography.

Background and Aims: Coronary artery disease (CAD) is usually caused by atherosclerosis, which is associated with general obesity and stronger associations with localized ectopic fat depots have been reported. We measured body ectopic fat distribution in Chinese patients to determine the association with coronary artery atherosclerosis (CA). Methods: Patients undergoing coronary computed tomography angiography (CCTA) who agreed to participate in the study (n = 750, 50.4% men, mean age 64.8 years) had cardiovascular disease and risk assessment. Body ectopic fat depots were measured from CT and their association with CA, determined from CCTA, was evaluated by univariate and multivariate logistic regression models. Results: CAD with CA (CAD-CA) was present in 57.2% of participants with CAD of moderate/severe CA (CAD-msCA) present in 23.5% and both were significantly more frequent in men than in women. Overall, men had greater body mass index (BMI) but there was no difference in waist circumference (WC) between genders. However, significantly higher visceral adipose tissue (VAT) and periaortic fat volume (PAFV) were observed in men, whereas women had significantly higher abdominal subcutaneous adipose tissue (SAT). With increasing age, there was a significant decline in BMI, WC and SAT in men, but a significant increase of WC and VAT, PAFV and epicardial fat volume (EFV) in women. A high proportion of non-calcified plaques was observed in CAD-CA, 55.3% in CAD of minimal/mild CA (CAD-mmCA) with 38.7% exclusively non-calcified plaques, and 59.7% in CAD-msCA with multiple type plaques containing non-calcified ones. Multivariate logistic regression showed a significant association of PAFV with CAD-CA and CAD-msCA that was independent of general obesity and clinical risk factors, and independent of abdominal obesity in the highest PAFV quartile patients. VATA was associated with an increased prevalence of CAD-msCA in the patients in the upper 2 VATA quartiles that was independent of clinical risk factors and both general and abdominal obesity. Conclusions: We found age and gender differences of body ectopic fat distribution in Chinese patients with higher VAT and PAFV in men and higher SAT in women. With increased age, there was a decline of WC and SAT in men but not in women and an increase in WC, VAT and PAFV in women but not in men. PAFV was significantly associated with overall CAD-CA and CAD-msCA, while VAT was associated with CAD-msCA.

Comparison of pathological, radiological, and prognostic features between cellular schwannoma and non-cellular schwannoma.

PURPOSE: To investigate the differences of pathological, radiological, and prognostic features between cellular schwannoma (CS) and non-cellular schwannoma (NCS). METHODS: CT and MRI images of 24 patients with CSs and 30 patients with NCSs were reviewed retrospectively. Clinico-pathological characteristics of CSs and NCSs and tumor radiological features including location, shape, size, border, cystic-solid components, hemorrhage, calcification, bone remodeling, pattern of CT/MRI precontrast scan, degree of enhancement, target sign, and tumor vessels were recorded. Statistical analyses were performed with Chi square or Fisher's exact test, independent sample t test, and logistic regression analysis to compare the differences between CSs and NCSs. RESULTS: Four CSs showed mitotic activity, which was not found in the NCS group (P = 0.034). The CS group showed higher MIB-1 index than that in the NCS group (P = 0.002). Two patients with CS presented with tumor recurrence. Compared to NCSs, CSs were often located in spinal area (P = 0.028) and irregular (P = 0.013) with larger size (P = 0.005). Target sign, a common finding in NCSs (7/22, 31.8 %), was not seen in CSs (P = 0.014). The tumor vessels were only seen in CS group (4/22, 18.2 %; P = 0.027). Regression analysis revealed that location (P = 0.048) and size (P = 0.012) were independent indicators in differentiating CSs from NCSs. CONCLUSIONS: CS is a rare subtype of schwannoma with some significant radiological features including a predilection for the spinal area, irregular shape, large tumor size, absent target sign, tumor vessels, and potential risk of recurrence. Location and size of the schwannomas were the most useful indicators in differentiating CSs from NCSs.

A Stronger Association of Epicardial Fat Volume with Non-Valvular Atrial Fibrillation Than Measures of General Obesity in Chinese Patients Undergoing Computed Tomography Coronary Angiography.

OBJECTIVE: An association of atrial fibrillation (AF) with epicardial fat volume (EFV) varied in different ethnic groups. We evaluated the AF-related risk factors and its association with pericardial fat in Chinese patients. METHODS: Patients referred for coronary computed tomography angiography (CCTA) in Shanghai East Hospital during 2012 to 2014 (n=2042, 43.8% women, mean age 65.0 years) had AF and cardiovascular risk assessment. Pericardial fat depots were measured from CT and the association of EFV with non-valvular AF risk factors was evaluated by multivariate logistic regression models. RESULTS: AF was present in 8.5% of patients with 11.6% of AF patients having rheumatic heart disease (RHD) and 8.7% having other valvular diseases. With increasing age, the proportion of RHD-related AF decreased and the risk factors for non-valvular AF increased. There was a significantly higher proportion of risk factors for non-valvular AF in men than in women (p=0.008), but RHD-related AF was more prevalent in women than men (p=0.013). The patients with non-valvular AF had significantly higher BMI and EFV with more pronounced elevation of EFV (p<0.001). Multivariate logistic regression showed a significant association of EFV with AF after adjustment for BMI and clinical risk factors, and the highest EFV quartile was associated with AF independent of left atrial size and obstructive coronary artery disease. CONCLUSION: The association of EFV with non-valvular AF in Chinese patients was independent of generalized adiposity and clinical risk factors especially in highest EFV quartile. These findings support the growing appreciation of the association of EFV with AF.

Differentiation of borderline tumors from type I ovarian epithelial cancers on CT and MR imaging.

PURPOSE: To investigate the value of CT and MR imaging features in differentiating borderline ovarian tumor (BOT) from type I ovarian epithelial cancer (OEC), which could be significant for suitable clinical treatment and assessment of the prognosis of the patient. METHODS: Thirty-three patients with BOTs and 35 patients with type I OECs proven by pathology were retrospectively evaluated. The clinico-pathological information (age, premenopausal status, CA-125, and Ki-67) and imaging characteristics were compared between two groups of ovarian tumors. The diagnostic performance of the imaging features was evaluated using receiver operating characteristic analysis. The best predictor variables for type I EOCs were recognized via multivariate analyses. RESULTS: BOTs are more likely to involve younger patients and frequently show lower CA-125 values and lower proliferation indices (Ki-67 < 15%) than type I OECs. Compared with type I OECs, BOTs were more often purely cystic (15/33, 45.45% vs. 1/35, 2.86%; p < 0.001) and displayed less frequent mural nodules (16/33, 48.48% vs. 28/35, 80.00%; p = 0.007), less frequently unclear margin (3/33, 9.09% vs. 11/35, 31.43%; p = 0.023), smaller solid portion (0.56 ± 2.66 vs. 4.51 ± 3.88; p < 0.001), and thinner walls (0.3 ± 0.17 vs. 0.55 ± 0.24; p < 0.001). The maximum wall thickness presented the largest area under the curve (AUC, 0.848). Multivariate analysis revealed that the solid portion size (OR 10.822, p = 0.002) and maximum wall thickness (OR 9.130, p = 0.001) were independent indicators for the differential diagnosis between the two groups of lesions. CONCLUSION: The solid portion size and maximum wall thickness significantly influenced the classification of the two groups of ovarian tumors.

Bone microarchitectural parameters can detect oxytocin induced changes prior to bone density on mitigating bone deterioration in rabbit osteoporosis model using micro-CT.

BACKGROUND: This study is aimed to determine the efficacy of X-Ray Microtomography (micro-CT) in predicting oxytocin (OT) treatment response in rabbit osteoporosis(OP) model. METHODS: Sixty-five rabbits were randomly divided into three groups: control group, ovariectomy (OVX) -vehicle and OVX-oxytocin group. The controls underwent sham surgery. OVX-vehicle and OVX-oxytocin groups were subjected to bilateral OVX. The rabbits in OVX-oxytocin group were injected with oxytocin. In the 0th, 4th, 8th, 10th and 12th weeks post OVX operation, bone mineral density (BMD) and bone micro-architectural parameters were measured in three groups. RESULTS: Bone mineral density (BMD), bone volume fraction (BV/TV), Trabecular Number (Tb.N), and Trabecular Thickness (Tb.Th) decreased, while Trabecular Spacing (Tb.Sp) and Structure Model Index (SMI) increased overtime in all the three groups. In OVX-oxytocin group, the bone deterioration tendency is slowing down compared with that of the OVX-vehicle group. The BMD of the OVX-oxytocin group was significantly lower than those in the OVX-vehicle group at 12th week (P = 0.017). BV/TV and Tb.Sp in OVX-oxytocin group changed significantly from 8th week (P = 0.043) and 12th week (P = 0.014), which is earlier than that of BMD and other bone micro-architectural parameters. CONCLUSION: BV/TV and Tb.Sp changed prior to BMD and other bone micro-architectural parameters with oxytocin intervention, which indicate that they are more sensitive markers for predicting early osteoporosis and treatment monitoring when using micro-CT to evaluate osteoporosis rabbit model.

Body compositions differently contribute to BMD in different age and gender: a pilot study by QCT.

The study was to investigate the correlation between body compositions and bone mineral density (BMD) and to evaluate the body composition contribution to BMD. In male, LM showed positive effect on BMD. In female, SAT showed positive, and FM and F/L showed negative effect on BMD. PURPOSE: The purpose of the study was to investigate the correlation between body compositions and bone mineral density (BMD) performed by quantitative computed tomography (QCT), and to evaluate the body composition contribution to BMD. METHODS: Three hundred ninety-four participants, including 122 male (31%) and 272 female (69%), were divided into groups by gender, age, and BMD. BMD and body compositions [including fat mass (FM), lean mass (LM), bone mass/lean mass ratio (B/L), fat mass/lean mass ratio (F/L), total adipose tissue (TAT), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT)] were retrospectively compared among groups using one-way ANOVA or t test. A stepwise multivariate analysis was used to evaluate the body composition contribution to BMD and produced models. RESULTS: In male, BMD got decreased with age (P < 0.05). LM increased before 30-49 years, then decreased (P < 0.05). TAT and SAT decreased with age (P < 0.05). LM in OP group was lower than those in the other two groups (P < 0.05). Through stepwise multivariate analysis, LM firstly got into model 1 (M1, ß = 0.589). In female, BMD, LM TAT, and VAT were increased before 30-49 years, then decreased (P < 0.05). FM and F/L increased with age (P < 0.05). SAT decreased with age (P < 0.05). FM and F/L in OP group were higher than those in other groups. LM, B/L, TAT, and SAT in the OP group were lower than those in the other groups (P < 0.05). SAT entered the M1 with a maximum ß value (ß = 0.584). CONCLUSIONS: BMD and body compositions displayed different characteristics with age. In male, LM showed positive effect on BMD. In female, SAT showed positive, and FM and F/L showed negative effect on BMD.

Comparison of semi-quantitative and quantitative dynamic contrast-enhanced MRI evaluations of vertebral marrow perfusion in a rat osteoporosis model.

BACKGROUND: This study aims to investigate the technical feasibility of semi-quantitative and quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the assessment of longitudinal changes of marrow perfusion in a rat osteoporosis model, using bone mineral density (BMD) measured by micro-computed tomography (micro-CT) and histopathology as the gold standards. METHODS: Fifty rats were randomly assigned to the control group (n=25) and ovariectomy (OVX) group whose bilateral ovaries were excised (n=25). Semi-quantitative and quantitative DCE-MRI, micro-CT, and histopathological examinations were performed on lumbar vertebrae at baseline and 3, 6, 9, and 12 weeks after operation. The differences between the two groups in terms of semi-quantitative DCE-MRI parameter (maximum enhancement, Emax), quantitative DCE-MRI parameters (volume transfer constant, Ktrans; interstitial volume, Ve; and efflux rate constant, Kep), micro-CT parameter (BMD), and histopathological parameter (microvessel density, MVD) were compared at each of the time points using an independent-sample t test. The differences in these parameters between baseline and other time points in each group were assessed via Bonferroni's multiple comparison test. A Pearson correlation analysis was applied to assess the relationships between DCE-MRI, micro-CT, and histopathological parameters. RESULTS: In the OVX group, the Emax values decreased significantly compared with those of the control group at weeks 6 and 9 (p=0.003 and 0.004, respectively). The Ktrans values decreased significantly compared with those of the control group from week 3 (p<0.05). However, the Ve values decreased significantly only at week 9 (p=0.032), and no difference in the Kep was found between two groups. The BMD values of the OVX group decreased significantly compared with those of the control group from week 3 (p<0.05). Transmission electron microscopy showed tighter gaps between vascular endothelial cells with swollen mitochondria in the OVX group from week 3. The MVD values of the OVX group decreased significantly compared with those of the control group only at week 12 (p=0.023). A weak positive correlation of Emax and a strong positive correlation of Ktrans with MVD were found. CONCLUSIONS: Compared with semi-quantitative DCE-MRI, the quantitative DCE-MRI parameter Ktrans is a more sensitive and accurate index for detecting early reduced perfusion in osteoporotic bone.

Reduction of Longitudinal Vertebral Blood Perfusion and Its Likely Causes: A Quantitative Dynamic Contrast-enhanced MR Imaging Study of a Rat Osteoporosis Model.

Purpose To determine the longitudinal relationships among lumbar vertebral blood perfusion, bone mass, and marrow adipose tissue in a rat osteoporosis model after ovariectomy by using quantitative dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging, microcomputed tomography (micro-CT), and proton MR spectroscopy. Materials and Methods In this animal review committee-approved study, lumbar vertebrae were evaluated through MR spectroscopy, quantitative DCE MR imaging, micro-CT, and histopathologic analysis, and blood was examined at 0, 2, 6, 10, 14, 18, and 24 weeks after ovariectomy consisting of exposure of the ovaries but no excision (n = 35) or sham operation, defined as exposure of the ovaries but no excision (n = 35). Differences in the parameters of these examinations between two groups at the same time point were analyzed by an independent-sample t test. Results Significantly reduced volume transfer constant (Ktrans) and volume of extravascular extracellular space per unit volume of tissue (week 2 and 10, respectively; P = .036 and P = .014, respectively), decreased bone mineral density (week 2; P = .014), and increased fat fraction (week 6; P = .036) in the ovariectomy group were observed, compared with those in the sham group. Vascular endothelial growth factor and microvessel density values of the ovariectomy group decreased significantly compared with those of the sham group from weeks 18 (P = .005) and 14 (P = .018), respectively. Transmission electron microscopy revealed tighter gaps among vascular endothelial cells and more marrow fibrosis in the ovariectomy group. Conclusion Quantitative DCE MR imaging can directly reflect marrow perfusion. Ktrans is a promising parameter to demonstrate early reduced marrow perfusion. Enhanced vasoconstriction and tightened gaps among vascular endothelial cells may be the likely causes in the initial stage of osteoporosis. Increased marrow adipose tissue, decreased microvessel density, and increased marrow fibrosis may aggravate marrow ischemia in the late stage of osteoporosis. © RSNA, 2016 Online supplemental material is available for this article.