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BACKGROUND: In modern positron emission tomography (PET) with multi-modality imaging (e.g., PET/CT and PET/MR), the attenuation correction (AC) is the single largest correction factor for image reconstruction. One way to assess AC methods and other reconstruction parameters is to utilize software-based simulation tools, such as a lesion insertion tool. Extensive validation of these simulation tools is required to ensure results of the study are clinically meaningful. PURPOSE: To evaluate different PET AC methods using a synthetic lesion insertion tool that simulates lesions in a patient cohort that has both PET/MR and PET/CT images. To further demonstrate how lesion insertion tool may be used to extend knowledge of PET reconstruction parameters, including but not limited to AC. METHODS: Lesion quantitation is compared using conventional Dixon-based MR-based AC (MRAC) to that of using CT-based AC (CTAC, a ground truth). First, the pre-existing lesions were simulated in a similar environment; a total of 71 lesions were identified in 18 pelvic PET/MR patient images acquired with a time-of-flight simultaneous PET/MR scanner, and matched lesions were inserted contralaterally on the same axial slice. Second, synthetic lesions were inserted into four anatomic target locations in a cohort of four patients who didnt have any observed clinical lesions in the pelvis. RESULTS: The matched lesion insertions resulted in unity between the lesion error ratios (mean SUVs), demonstrating that the inserted lesions successfully simulated the original lesions. In the second study, the inserted lesions had distinct characteristics by target locations and demonstrated negative max-SUV%diff trends for bone-dominant sites across the patient cohort. CONCLUSIONS: The current work demonstrates that the applied lesion insertion tool can simulate uptake in pelvic lesions and their expected SUV values, and that the lesion insertion tool can be extended to evaluate further PET reconstruction corrections and algorithms and their impact on quantitation accuracy and precision.

Introduction ATRX protein is a chromatin remodeler involved in multiple cellular processes including maintenance of chromatin status and DNA structure and regulation of gene expression (1-3). Playing essential roles in [...], ATP-dependent chromatin remodeling protein ATRX is an essential regulator involved in maintenance of DNA structure and chromatin state and regulation of gene expression during development. ATRX was originally identified as the monogenic cause of X-linked a-thalassemia mental retardation (ATR-X) syndrome. Affected individuals display a variety of developmental abnormalities and skeletal deformities. Studies from others investigated the role of ATRX in skeletal development by tissue-specific Atrx knockout. However, the impact of ATRX during early skeletal development has not been examined. Using preosteoblast-specific Atrx conditional knockout mice, we observed increased trabecular bone mass and decreased osteoclast number in bone. In vitro coculture of Atrx conditional knockout bone marrow stromal cells (BMSCs) with WT splenocytes showed impaired osteoclast differentiation. Additionally, Atrx deletion was associated with decreased receptor activator of nuclear factor [kappa]-B ligand (Rank!)/ osteoprotegerin (Opg) expression ratio in BMSCs. Notably, Atrx-deficient osteolineage cells expressed high levels of the neuropeptide cocaine- and amphetamine-regulated transcript prepropeptide (Cartpt). Mechanistically, ATRX suppresses Cartpt transcription by binding to the promoter, which is otherwise poised for Cartpt expression by RUNX2 binding to the distal enhancer. Finally, Cartpt silencing in Atrx conditional knockout BMSCs rescued the molecular phenotype by increasing the Rankl/Opg expression ratio. Together, our data show a potent repressor function of ATRX in restricting Cartpt expression during skeletal development.

BackgroundVasculopathy is a hallmark of systemic sclerosis (SSc) putting patients at an increased risk of cardiovascular disease. Approximately 20–25% of all SSc patients show prolonged elevated C-reactive protein (CRP) levels and thus signs of chronic low-grade inflammation. While CRP−positivity is an independent predictor of cardiovascular disease in non-SSc populations, the relationship between CRP−positivity and cardiovascular health/atherosclerosis in SSc patients is only incompletely understood. Here, we aimed to assess (1) which general, SSc disease-specific and cardiovascular parameters are associated with CRP−positivity in a cohort of SSc patients with prolonged CRP elevations (CRP+ SSc group) relative to SSc patients without CRP elevations (CRP− SSc group). In addition (2), we aimed to investigate whether prolonged CRP−positivity in SSc patients is associated with a higher cardiovascular risk and an increased atherosclerotic burden. We also aimed to (3) identify via random forest classification modeling which combined cardiovascular and/or SSc-specific parameters could differentiate best between SSc patients with elevated CRP levels (the so-called “inflammatory SSc subtype”) and SSc patients without increased CRP levels.MethodsSixty-five SSc patients were recruited and assigned to the CRP+ SSc group (n = 20) if their CRP levels were > 5 mg/L in at least three half-yearly visits within 2 years before enrolment or to the CRP− SSc group (n = 45), respectively. All patients underwent an anamnesis, physical examination, blood draw, and bilateral carotid ultrasound in order to assess arteriosclerotic burden including the presence, number and height of plaques, and carotid intima–media thickness (CIMT) as well as lipid profiles. 10-year ASCVD risk was estimated via the ASCVD risk estimator plus. Statistical evaluation included Spearman’s correlations, logistic regression and random forest modeling under 5-fold cross-validation, and permutation testing to determine combinations of cardiovascular variables highly discriminatory for CRP−positivity.ResultsSSc groups showed comparable mean age, height, and extent of SSc organ involvement. Regarding cardiovascular health, CRP+ SSc patients exhibited a significantly altered HDL-, LDL-, and triglyceride profile (0.001 ≤ p ≤ 0.017) and a significantly higher 10-year ASCVD risk (p = 0.047), relative to CRP− SSc patients. Additionally, within the subgroup of CRP+ SSc patients, positive correlations between CRP levels and CIMT right (ρ = 0.657, p = 0.002) and mean CIMT left and right (ρ = 0.497, p = 0.026) were seen. Combined ROC models identified the four lipid components (HDL, LDL, total cholesterol, and triglycerides) or the SSc duration and ASCVD category to differentiate with high cross-validated ROC-AUCs (AUC: 0.83 ± 0.15, and AUC: 0.86 ± 0.09, p

A major remaining challenge for magnetic resonance-based attenuation correction methods (MRAC) is their susceptibility to sources of magnetic resonance imaging (MRI) artifacts (e.g., implants and motion) and uncertainties due to the limitations of MRI contrast (e.g., accurate bone delineation and density, and separation of air/bone). We propose using a Bayesian deep convolutional neural network that in addition to generating an initial pseudo-CT from MR data, it also produces uncertainty estimates of the pseudo-CT to quantify the limitations of the MR data. These outputs are combined with the maximum-likelihood estimation of activity and attenuation (MLAA) reconstruction that uses the PET emission data to improve the attenuation maps. With the proposed approach uncertainty estimation and pseudo-CT prior for robust MLAA (UpCT-MLAA), we demonstrate accurate estimation of PET uptake in pelvic lesions and show recovery of metal implants. In patients without implants, UpCT-MLAA had acceptable but slightly higher root-mean-squared-error (RMSE) than Zero-echotime and Dixon Deep pseudo-CT when compared to CTAC. In patients with metal implants, MLAA recovered the metal implant; however, anatomy outside the implant region was obscured by noise and crosstalk artifacts. Attenuation coefficients from the pseudo-CT from Dixon MRI were accurate in normal anatomy; however, the metal implant region was estimated to have attenuation coefficients of air. UpCT-MLAA estimated attenuation coefficients of metal implants alongside accurate anatomic depiction outside of implant regions.

Introduction Osteogenesis imperfecta (OI) is an inherited multi-systemic disorder characterized by low bone mass, recurrent fractures, growth deficiency, and skeletal deformities (1-3). Extraskeletal manifestations may include muscle weakness, dentinogenesis imperfecta, [...], Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes, in addition to the bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in interferon-induced transmembrane protein 5 (IFITM5). Here, we generated a conditional Roso26-knockin mouse model to study the mechanistic consequences of the recurrent mutation. Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with the pathology reported in patients with OI type V. Surprisingly, expression of mutant Ifitm5 in mature osteoblasts caused no obvious skeletal abnormalities. In contrast, earlier expression in osteo-chondroprogenitors was associated with an increase in the skeletal progenitor cell population within the periosteum. Lineage tracing showed that chondrogenic cells expressing the mutant Ifitm5 had decreased differentiation into osteoblastic cells in diaphyseal bone. Moreover, mutant IFITM5 disrupted early skeletal homeostasis in part by activating ERK signaling and downstream SOX9 protein, and inhibition of these pathways partially rescued the phenotype in mutant animals. These data identify the contribution of a signaling defect altering osteo-chondroprogenitor differentiation as a driver in the pathogenesis of OI type V.

As in conventional 1H MRI, T1 and T2 relaxation times of hyperpolarized (HP) 13C nuclei can provide important biomedical information. Two new approaches were developed for simultaneous T1 and T2 mapping of HP 13C probes based on balanced steady state free precession (bSSFP) acquisitions: a method based on sequential T1 and T2 mapping modules, and a model-based joint T1/T2 approach analogous to MR fingerprinting. These new methods were tested in simulations, HP 13C phantoms, and in vivo in normal Sprague-Dawley rats. Non-localized T1 values, low flip angle EPI T1 maps, bSSFP T2 maps, and Bloch-Siegert B1 maps were also acquired for comparison. T1 and T2 maps acquired using both approaches were in good agreement with both literature values and data from comparative acquisitions. Multiple HP 13C compounds were successfully mapped, with their relaxation time parameters measured within heart, liver, kidneys, and vasculature in one acquisition for the first time.

Accurate quantification of uptake on PET images depends on accurate attenuation correction in reconstruction. Current MR-based attenuation correction methods for body PET use a fat and water map derived from a 2-echo Dixon MRI sequence in which bone is neglected. Ultrashort-echo-time or zero-echo-time (ZTE) pulse sequences can capture bone information. We propose the use of patient-specific multiparametric MRI consisting of Dixon MRI and proton-density-weighted ZTE MRI to directly synthesize pseudo-CT images with a deep learning model: we call this method ZTE and Dixon deep pseudo-CT (ZeDD CT). Methods: Twenty-six patients were scanned using an integrated 3-T time-of-flight PET/MRI system. Helical CT images of the patients were acquired separately. A deep convolutional neural network was trained to transform ZTE and Dixon MR images into pseudo-CT images. Ten patients were used for model training, and 16 patients were used for evaluation. Bone and soft-tissue lesions were identified, and the SUVmax was measured. The root-mean-squared error (RMSE) was used to compare the MR-based attenuation correction with the ground-truth CT attenuation correction. Results: In total, 30 bone lesions and 60 soft-tissue lesions were evaluated. The RMSE in PET quantification was reduced by a factor of 4 for bone lesions (10.24% for Dixon PET and 2.68% for ZeDD PET) and by a factor of 1.5 for soft-tissue lesions (6.24% for Dixon PET and 4.07% for ZeDD PET). Conclusion: ZeDD CT produces natural-looking and quantitatively accurate pseudo-CT images and reduces error in pelvic PET/MRI attenuation correction compared with standard methods.

Simultaneous positron emission tomography and MRI (PET/MRI) is a technology that combines the anatomic and quantitative strengths of MR imaging with physiologic information obtained from PET. PET and computed tomography (PET/CT) performed in a single scanning session is an established technology already in widespread and accepted use worldwide. Given the higher cost and complexity of operating and interpreting the studies obtained on a PET/MRI system, there has been question as to which patients would benefit most from imaging with PET/MRI versus PET/CT. In this article, we compare PET/MRI with PET/CT, detail the applications for which PET/MRI has shown promise and discuss impediments to future adoption. It is our hope that future work will prove the benefit of PET/MRI to specific groups of patients, initially those in which PET/CT and MRI are already performed, leveraging simultaneity and allowing for greater degrees of multiparametric evaluation.Level of evidence5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1247-1262.

Aim: Adolescent mental ill‐health is a common international challenge affecting both high‐ and lower‐middle‐income countries. The Republic of the Philippines enacted its first mental health law in 2019, underlining the importance of the promotion of adolescent mental health education in schools. In Japan, course instructions about mental ill‐health were formulated in a Course of Study that reflects governmental curriculum guidelines. Embedded since 2022, the Course of Study aimed to promote an understanding of current issues of adolescent health. The National Center for Global Health and Medicine in Japan has been sharing experience of promoting public health practices and advancing medical technology in low‐ and middle‐income countries, especially in the Western Pacific region. This paper describes the development process and content of these resources by an interdisciplinary team from Japan and the Philippines. Methods: The interdisciplinary team created an embedded mental health education programme using animated videos for the Philippine school curriculum to improve mental health literacy in adolescents. Results: Two six‐minute animated videos of age‐relevant stories were created. The animation scenarios illustrate: 1) mental health problems and recovery; and 2) major symptoms of mental illnesses, including depression, anxiety, and schizophrenia. Each animated video presents several items for discussion among students and/or teachers, both in class and online for students unable to attend school. Conclusion: Our efforts may provide good opportunities for enhancing adolescents' mental health activities in the Philippines. In the following steps, we should investigate the effectiveness of school‐based MHL using these animated videos with rigorous evaluation methods. [ABSTRACT FROM AUTHOR]

PurposeThis study introduces a new hybrid ZTE/Dixon MR-based attenuation correction (MRAC) method including bone density estimation for PET/MRI and quantifies the effects of bone attenuation on metastatic lesion uptake in the pelvis.MethodsSix patients with pelvic lesions were scanned using fluorodeoxyglucose (18F-FDG) in an integrated time-of-flight (TOF) PET/MRI system. For PET attenuation correction, MR imaging consisted of two-point Dixon and zero echo-time (ZTE) pulse sequences. A continuous-value fat and water pseudoCT was generated from a two-point Dixon MRI. Bone was segmented from the ZTE images and converted to Hounsfield units (HU) using a continuous two-segment piecewise linear model based on ZTE MRI intensity. The HU values were converted to linear attenuation coefficients (LAC) using a bilinear model. The bone voxels of the Dixon-based pseudoCT were replaced by the ZTE-derived bone to produce the hybrid ZTE/Dixon pseudoCT. The three different AC maps (Dixon, hybrid ZTE/Dixon, CTAC) were used to reconstruct PET images using a TOF-ordered subset expectation maximization algorithm with a point-spread function model. Metastatic lesions were separated into two classes, bone lesions and soft tissue lesions, and analyzed. The MRAC methods were compared using a root-mean-squared error (RMSE), where the registered CTAC was taken as ground truth.ResultsThe RMSE of the maximum standardized uptake values (SUVmax ) is 11.02% and 7.79% for bone (N = 6) and soft tissue lesions (N = 8), respectively, using Dixon MRAC. The RMSE of SUVmax for these lesions is significantly reduced to 3.28% and 3.94% when using the new hybrid ZTE/Dixon MRAC. Additionally, the RMSE for PET SUVs across the entire pelvis and all patients are 8.76% and 4.18%, for the Dixon and hybrid ZTE/Dixon MRAC methods, respectively.ConclusionA hybrid ZTE/Dixon MRAC method was developed and applied to pelvic regions in an integrated TOF PET/MRI, demonstrating improved MRAC. This new method included bone density estimation, through which PET quantification is improved.

Abstract Background and purpose Mental health has emerged as an important public health concern in recent years. With a high proportion of children and adolescents affected by mental disorders, it is important to ensure that they are provided with proper care and treatment. With the goal of sharing the activities and good practices on child and adolescent mental health promotion, care, and treatment in Japan and the Philippines, the National Center for Global Health and Medicine conducted a training program on the promotion of mental health focused on treatment and care in Japan and the Philippines in September and November 2019. Key highlights The training program comprised of a series of lectures, site visits, and round table discussions in Japan and the Philippines. The lectures and site visits focused on the current situation of child and adolescent psychiatry, diagnosis of childhood mental disorders, abuse, health financing for mental disorders, pharmacotherapy, psychotherapy, and disaster child psychiatry in both countries. Round table discussions provided an opportunity to explore the similarities and differences between the two countries in terms of the themes discussed during the lectures. The training program identified the need to collaborate with other professionals to improve the diagnosis of mental disorders in children and adolescents and to increase the workforce capable of addressing mental health issues among children and adolescents. It also emphasized the importance of cooperation between government efforts during and after disasters to ensure that affected children and their families are provided with the care and support that they need.

Abstract Background Mental disorders contribute substantial burden to the society due to their widespread occurrence and debilitating effects. A quarter of the world’s population are children and adolescents, a significant number of whom experience mental disorders as early as the age of 14. Some interventions have been found to effectively reduce the risk factors and reinforce protective or preventive factors. However, there is still a need to put emphasis on mental health promotion strategies such as religious education. This paper aims to discuss the importance of religious education in promoting mental health. Discussion Religious education can be instrumental to improving adolescent mental health. Specifically, it can: (1) help develop healthier reaction to stimuli through the internalization of religious morality; (2) reinforce religious coping mechanisms which reduce the impact of stresses, enhance coping skills, and promote a less risky lifestyle; (3) increase awareness regarding religious beliefs and practices and their influence on the individual, the family, and the community; and finally, (4) promote connectedness which can enhance self-esteem and well-being. However, negative health outcomes such as discrimination and social isolation can also develop, especially among religious or gender minority groups. Conclusion It is important to reflect on the crucial role of religious education on adolescent mental health. School-based mental health education and promotion strategies can maximize the benefits of religious education by putting emphasis on effective implementation of religious education to positively influence adolescent mental health.