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Rational: To validate a population-based input function (PBIF) model that alleviates the need for scanning since injection time in dynamic whole-body (WBdyn) PET. Methods: Thirty-seven patients with suspected/known well-differentiated neuroendocrine tumors were included (GAPETNET trial NTC03576040). All WBdyn 68Ga-DOTATOC-PET/CT acquisitions were performed on a digital PET system (one heart-centered 6 min-step followed by nine WB-passes). The PBIF model was built from 20 image-derived input functions (IDIFs) obtained from a respective number of patients' WBdyn exams using an automated left-ventricle segmentation tool. All IDIF peaks were aligned to the median time-to-peak, normalized to patient weight and administrated activity, and then fitted to an exponential model function. PBIF was then applied to 17 independent patient studies by scaling it to match the respective IDIF section at 20-55 min post-injection time windows corresponding to WB-passes 3-7. The ratio of area under the curves (AUCs) of IDIFs and PBIF3-7 were compared using a Bland--Altman analysis (mean bias ± SD). The Patlakestimated mean Ki for physiological uptake (Ki-liver and Ki-spleen) and tumor lesions (Ki-tumor) using either IDIF or PBIF were also compared. Results: The mean AUC ratio (PBIF/IDIF) was 0.98 ± 0.06. The mean Ki bias between PBIF3-7 and IDIF was -2.6 ± 6.2% (confidence interval, CI: -5.8; 0.6). For Ki-spleen and Ki-tumor, low relative bias with low SD were found [4.65 ± 7.59% (CI: 0.26; 9.03) and 3.70 ± 8.29% (CI: -1.09; 8.49) respectively]. For Ki-liver analysis, relative bias and SD were slightly higher [7.43 ± 13.13% (CI: -0.15; 15.01)]. Conclusion: Our study showed that the PBIF approach allows for reduction in WBdyn DOTATOC-PET/CT acquisition times with a minimum gain of 20 min. [ABSTRACT FROM AUTHOR]

Interest and research into radiopharmaceutical extravasation concepts has risen with the increase in use of radiopharmaceutical therapies, growing access to novel molecular imaging agents, and recent regulatory controversies. This minireview will examine the literature of the last twenty years to summarize the history of radiopharmaceutical extravasations, determine key trends in imaging and therapies, and highlight critical gaps in research that currently exist. The intent of this work is to provide a summary of this complex topic that helps build awareness and promotes new innovations in this interesting aspect of theranostic radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric patients have an increased risk of radiation-induced malignancies due to their ongoing development and long remaining life span. Thus, optimization of PET protocols is an important task in pediatric nuclear medicine. Long axial field-of-view (LAFOV) PET/CT has shown a significant increase in sensitivity, which provides an ideal opportunity for reduction of injected tracer activity in the pediatric population. In this study we aim to evaluate the clinical performance of a 2-[18F]FDG-tracer reduction from 3 MBq/kg to 1.5 MBq/kg on the Biograph Vision Quadra LAFOV PET/CT. Materials and methods: The first 50 pediatric patients referred for clinical whole-body PET/CT with 1.5 MBq/kg 2-[18F]FDG, were included. A standard pediatric protocol was applied. Five reconstructions were created with various time, filter and iteration settings. Image noise was computed as coefficient-of-variance (COV = SD/mean standardized-uptake-value) calculated from a spherical 20-50 mm (diameter) liver volume-of-interest. Sets of reconstructions were reviewed by one nuclear medicine physicians, who reported image lesions on a pre-defined list of sites. Paired comparison analysis was performed with significance at PB< 0.05 (Bonferroni corrected). Results: All reconstructions, except one, achieved a COVmean (0.08-0.15) equal to or lower than current clinical acceptable values (COVref ≤ 0.15). Image noise significantly improved with increasing acquisition time, lowering iterations (i) from 6i to 4i (both with five subsets) and when applying a 2 mm Gauss filter (PB< 0.001). Significant difference in lesion detection was seen from 150s to 300s and from 150s to 600s (PB = 0.006-0.007). 99% of all lesions rated as malignant could be found on the 150s reconstruction, while 100% was found on the 300s, when compared to the 600s reconstruction. Conclusion: Injected activity and scan time can be reduced to 1.5 MBq/kg 2-[18F] FDG with 5 min acquisition time on LAFOV PET/CT, while maintaining clinical performance in the pediatric population. These results can help limit radiation exposure to patients and personnel as well as shorten total scan time, which can help increase patient comfort, lessen the need for sedation and provide individually tailored scans. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric patients have an increased risk of radiation-induced malignancies due to their ongoing development and long remaining life span. Thus, optimization of PET protocols is an important task in pediatric nuclear medicine. Long axial field-of-view (LAFOV) PET/CT has shown a significant increase in sensitivity, which provides an ideal opportunity for reduction of injected tracer activity in the pediatric population. In this study we aim to evaluate the clinical performance of a 2-[18F]FDG-tracer reduction from 3 MBq/kg to 1.5 MBq/kg on the Biograph Vision Quadra LAFOV PET/CT. Materials and methods: The first 50 pediatric patients referred for clinical whole-body PET/CT with 1.5 MBq/kg 2-[18F]FDG, were included. A standard pediatric protocol was applied. Five reconstructions were created with various time, filter and iteration settings. Image noise was computed as coefficient-ofvariance (COV = SD/mean standardized-uptake-value) calculated from a spherical 20-50 mm (diameter) liver volume-of-interest. Sets of reconstructions were reviewed by one nuclear medicine physicians, who reported image lesions on a pre-defined list of sites. Paired comparison analysis was performed with significance at PB < 0.05 (Bonferroni corrected). Results: All reconstructions, except one, achieved a COVmean (0.08-0.15) equal to or lower than current clinical acceptable values (COVref = 0.15). Image noise significantly improved with increasing acquisition time, lowering iterations (i) from 6i to 4i (both with five subsets) and when applying a 2 mm Gauss filter (PB < 0.001). Significant difference in lesion detection was seen from 150s to 300s and from 150s to 600s (PB = 0.006-0.007). 99% of all lesions rated as malignant could be found on the 150s reconstruction, while 100% was found on the 300s, when compared to the 600s reconstruction. Conclusion: Injected activity and scan time can be reduced to 1.5 MBq/kg 2-[18F] FDG with 5 min acquisition time on LAFOV PET/CT, while maintaining clinical performance in the pediatric population. These results can help limit radiation exposure to patients and personnel as well as shorten total scan time, which can help increase patient comfort, lessen the need for sedation and provide individually tailored scans. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a genetic disorder characterized by recurrent airway infections, inflammation, impaired mucociliary clearance, and progressive decline in lung function. The disease may start in the small airways; however, this is difficult to prove due to the limited accessibility of the small airways with the current single-photon mucociliary clearance assay. Here, we developed a dynamic positron emission tomography assay with high spatial and temporal resolution. We tested that mucociliary clearance is abnormal in the small airways of newborn cystic fibrosis pigs. Clearance of [68Ga]-tagged macroaggregated albumin from small airways started immediately after delivery and continued for the duration of the study. Initial clearance was fast but slowed down a few minutes after delivery. Cystic fibrosis pigs' small airways cleared significantly less than non-CF pigs' small airways (non-CF 25.1 ± 3.1% vs. CF 14.6 ± 0.1%). Stimulation of the cystic fibrosis airways with the purinergic secretagogue uridine-5′-triphosphate (UTP) further impaired clearance (non-CF with UTP 20.9 ± 0.3% vs. CF with UTP 13.0 ± 1.8%). None of the cystic fibrosis pigs treated with UTP (n = 6) cleared more than 20% of the delivered dose. These data indicate that mucociliary clearance in the small airways is fast and can easily be missed if the assay is not sensitive enough. The data also indicate that mucociliary clearance is impaired in the small airways of cystic fibrosis pigs. This defect is exacerbated by stimulation of mucus secretions with purinergic agonists. NEW & NOTEWORTHY: We developed a novel positron emission tomography scan assay with unprecedented temporal and spatial resolution to measure mucociliary clearance in the small airways. We proved a long-standing but unproven assertion that mucociliary clearance is inherently abnormal in the small airways of newborn cystic fibrosis piglets that are otherwise free of infection or inflammation. This technique can be easily extended to other airway diseases such as asthma, idiopathic pulmonary fibrosis, or chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Copper (Cu) is used as a cofactor in all organisms, and yet it can be toxic at high intracellular concentrations, causing cell death. Diethyldithiocarbamate (DDC) is a Cu ionophore that can transport Cu effectively into the cell. Copper-diethyldithiocarbamate (Cu-DDC) can treat prostate cancer (PCa) and may correlate with the cell death process. However, the specific Cu-DDC-related cell death genes in PCa are still unknown. Information about the Cu-DDC-related cell death genes was obtained from a previous study. Concurrently, the RNA expression profiles and clinical data were downloaded from public databases such as GEO, TCGA, and CPGEA. Using data from TCGA database, the logistic and lasso regression models were generated using R software. The influence of these genes in affecting PCa progression and prognosis was analyzed. Finally, the expression of these genes was verified in clinical samples. We found five Cu-DDC-related cell death genes associated with the occurrence of PCa from GSE35988, a gene dataset, namely, CDKN2A, PRC1, CDK1, SOX2, and ZNF365. CDKN2A, PRC1, and CDK1 are known to influence PCa patients' disease-free survival (DFS) status and were overexpressed, whereas SOX2 and ZNF365 were under-expressed in PCa in the different databases. Some of these genes can affect PCa progression. Consistent with the database results, the mRNA and protein expression of CDKN2A, PRC1, and CDK1 was also higher in clinical samples. In conclusion, we identified five hub genes which are important for Cu-DDC-related cell death process that can predict the development of PCa. [ABSTRACT FROM AUTHOR]

Chronic pain is highly prevalent and burdensome, affecting millions of people worldwide. Although it emerges at any point in life, it often manifests in adolescence. Given that adolescence is a unique developmental period, additional strains associated with persistent and often idiopathic pain lead to significant long-term consequences. While there is no singular cause for the chronification of pain, epigenetic modifications that lead to neural reorganization may underpin central sensitization and subsequent manifestation of pain hypersensitivity. Epigenetic processes are particularly active during the prenatal and early postnatal years. We demonstrate how exposure to various traumas, such as intimate partner violence while in utero or adverse childhood experiences, can significantly influence epigenetic regulation within the brain and in turn modify pain-related processes. We provide compelling evidence that the burden of chronic pain is likely initiated early in life, often being transmitted from mother to offspring. We also highlight two promising prophylactic strategies, oxytocin administration and probiotic use, that have the potential to attenuate the epigenetic consequences of early adversity. Overall, we advance understanding of the causal relationship between trauma and adolescent chronic pain by highlighting epigenetic mechanisms that underlie this transmission of risk, ultimately informing how to prevent this rising epidemic. [ABSTRACT FROM AUTHOR]

Background: [18F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [18F]FDG PET solid tumour treatment response assessments, while comparing "standard PET" to "AI denoised half-duration PET" ("AI PET") during follow-up. Results: 110 patients referred for baseline and follow-up standard digital [18F]FDG PET/CT were prospectively included. "Standard" EORTC and, if applicable, PERCIST response classifications by 2 readers between baseline standard PET1 and follow-up standard PET2 as a "gold standard" were compared to "mixed" classifications between standard PET1 and AI PET2 (group 1; n = 64), or between AI PET1 and standard PET2 (group 2; n = 46). Separate classifications were established using either standardized uptake values from ultra-high definition PET with or without AI denoising (simplified to "UHD") or EANM research limited v2 (EARL2)-compliant values (by Gaussian filtering in standard PET and using the same filter in AI PET). Overall, pooling both study groups, in 11/110 (10%) patients at least one EORTCUHD or EARL2 or PERCISTUHD or EARL2 mixed vs. standard classification was discordant, with 369/397 (93%) concordant classifications, unweighted Cohen's kappa = 0.86 (95% CI: 0.78–0.94). These modified mixed vs. standard classifications could have impacted management in 2% of patients. Conclusions: Although comparing similar PET images is preferable for therapy response assessment, the comparison between a standard [18F]FDG PET and an AI denoised half-duration PET is feasible and seems clinically satisfactory. [ABSTRACT FROM AUTHOR]

Introduction: Data acquisition and image reconstruction protocols affect image quality and quantification accuracy in PET imaging. We aimed to standardize and optimize image acquisition, and reconstruction parameter sets using a simultaneous quantitative and qualitative assessment framework for a lutetium oxyorthosilicate (LSO)-based PET/CT scanner. Methods: The NEMA IEC Body Phantom acquisition was performed in list mode for 10 minutes with four spheres to background ratios (SBRs). Raw PET data were reconstructed using 60 different protocols. Image quality was evaluated for standardization using contrast, CNR, and noise. Recovery coefficient (RC) measurements were performed for different common VOI definitions. Results: No significant differences were observed between RCs for various acquisition durations. The contrast to noise ratio (CNR) increased at all SBRs by expanding the acquisition duration from 60 to 600 seconds. PET scan time was reduced to 90 seconds per bed position while preserving image quality. Up to 50% improvement in CNR for the highest sub-iteration with a high level of smoothing was observed. PSF-based reconstruction produced a positive bias of RCmax in high SBRs (8 and 10) using higher sub-iterations (30 to 60) with Gaussian filters less than 6 mm FWHM. Moreover, a Sub-iteration of more than 32 with a 4-6 mm FWHM Gaussian filter provides optimized reconstruction sets. Conclusion: Our study demonstrates it would be feasible for PET image acquisition and reconstruction settings to simultaneously allow optimal lesion detection with high image quality while providing accurate quantification. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric patients have an increased risk of radiation-induced malignancies due to their ongoing development and long remaining life span. Thus, optimization of PET protocols is an important task in pediatric nuclear medicine. Long axial field-of-view (LAFOV) PET/CT has shown a significant increase in sensitivity, which provides an ideal opportunity for reduction of injected tracer activity in the pediatric population. In this study we aim to evaluate the clinical performance of a 2-[18F]FDG-tracer reduction from 3 MBq/kg to 1.5 MBq/kg on the Biograph Vision Quadra LAFOV PET/CT. Materials and methods: The first 50 pediatric patients referred for clinical whole-body PET/CT with 1.5 MBq/kg 2-[18F]FDG, were included. A standard pediatric protocol was applied. Five reconstructions were created with various time, filter and iteration settings. Image noise was computed as coefficient-ofvariance (COV = SD/mean standardized-uptake-value) calculated from a spherical 20--50 mm (diameter) liver volume-of-interest. Sets of reconstructions were reviewed by one nuclear medicine physicians, who reported image lesions on a pre-defined list of sites. Paired comparison analysis was performed with significance at PB < 0.05 (Bonferroni corrected). Results: All reconstructions, except one, achieved a COVmean (0.08--0.15) equal to or lower than current clinical acceptable values (COVref ≤ 0.15). Image noise significantly improved with increasing acquisition time, lowering iterations (i) from 6i to 4i (both with five subsets) and when applying a 2 mm Gauss filter (PB < 0.001). Significant difference in lesion detection was seen from 150s to 300s and from 150s to 600s (PB = 0.006--0.007). 99% of all lesions rated as malignant could be found on the 150s reconstruction, while 100% was found on the 300s, when compared to the 600s reconstruction. Conclusion: Injected activity and scan time can be reduced to 1.5 MBq/kg 2-[18F] FDG with 5 min acquisition time on LAFOV PET/CT, while maintaining clinical performance in the pediatric population. These results can help limit radiation exposure to patients and personnel as well as shorten total scan time, which can help increase patient comfort, lessen the need for sedation and provide individually tailored scans. [ABSTRACT FROM AUTHOR]

Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted. [ABSTRACT FROM AUTHOR]

Background: Pancreatic neuroendocrine tumors (P-NETs) constitute a subset of pancreatic mass lesions characterized by diverse clinical presentations. Despite their inherent malignant potential, the timely identification and treatment of these tumors are critical for achieving favorable clinical outcomes. This study aims to shed light on the heterogeneous tumor biology of P-NETs and the management strategies employed at a tertiary care center in Pakistan. Method: A retrospective study encompassing all patients with a biopsy-confirmed diagnosis of P-NETs at Shifa International Hospital between January 1st, 2016, and June 30th, 2021, was conducted. Meticulous data extraction from pathology records and thorough searches of medical records were performed to gather relevant demographic and clinical information. Results: A total of 24 patients were retrieved from our database, with 13 (54%) female patients. The mean age was 49.5 ± 16.3 years. Eight out of the 24 patients presented with abdominal pain. Most patients (14 out of 24) had lesions in the pancreatic head region. In three cases, lesions exhibited multicentricity. The mean lesion size measured 4.4 ± 2.3 cm. Three of the 24 patients displayed distant liver metastasis at the presentation time. 19 out of the 24 patients underwent surgical resections, while endoscopic ultrasound (EUS)-guided biopsy was performed in 4 out of 24 cases. EUS-guided tissue biopsy yielded accurate diagnoses in all four cases. Conclusion: Most P-NETs are non-functional, and there is an almost equal distribution between male and female patients. Solitary lesions predominate, and metastasis is uncommon at initial presentation. EUS-guided fine needle biopsy stands out as a dependable diagnostic modality for P-NETs. [ABSTRACT FROM AUTHOR]

Background: Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases. Methods: For this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified by the most commonly used PET parameter, the maximum tumor voxel normalized by dose and body weight (SUVmax) and also by the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals for SUVmax and SULpeak were used to determine the limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment. Results: The mean relative difference of SUVmax and SULpeak in 38 bone tumors of the first cohort were 4.3% and 6.7%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and − 16.3% for SUVmax, and 21.2% and − 17.5% for SULpeak. 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification using SULpeak for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria for SULpeak changed the status of 3 patients compared to the standard Positron Emission Tomography Response Criteria in Solid Tumors of ± 30% SULpeak. Conclusion: In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG SUVmax, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions in these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response. [ABSTRACT FROM AUTHOR]

Objective approaches to treatment. [ABSTRACT FROM AUTHOR]

Background: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. Methods: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). Results: In 20,887 screened references, 79 articles (82.5% in 2017–2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5–52,000, median 21) and large-span sample size (range 80–3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. Conclusion: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field. [ABSTRACT FROM AUTHOR]

Circulating tumor DNA (ctDNA), which circulates in the blood after being shed from cancer cells in the body, has recently gained attention as an excellent tumor marker. The purpose of this study was to evaluate whether ct human papillomavirus (HPV) 16 DNA (ctHPV16DNA) levels were associated with quantitative PET parameters in patients with HPV-positive head and neck (HN) squamous cell carcinoma (SCC). Fifty patients with oropharyngeal SCC (OPSCC) and 5 with SCC of unknown primary (SCCUP) before treatment were included. They all underwent blood sampling to test ctHPV16DNA levels and FDG PET-CT examinations. Quantitative PET parameters included SUVmax, metabolic tumor volume (MTV), MTV of whole-body lesions (wbMTV), and 56 texture features. ctHPV16DNA levels were compared to texture features of primary tumors in OPSCC patients (Group A) or the largest primary or metastatic lymph node lesions in OPSCC and SCCUP patients (Group B) and to other PET parameters. Spearman rank correlation test and multiple regression analysis were used to confirm the associations between ctHPV16DNA levels and PET parameters. ctHPV16DNA levels moderately correlated with wbMTV, but not with SUVmax or MTV in Groups A and B. ctHPV16DNA levels exhibited a weak negative correlation with low gray-level zone emphasis in Groups A and B. Multiple regression analysis revealed that wbMTV and high gray-level zone emphasis were the significant factors for ctHPV16DNA levels in Group B. These results were not observed in Group A. This study demonstrated that ctHPV16DNA levels correlated with the whole-body tumor burden and tumor heterogeneity visualized on FDG PET-CT in patients with HPV-positive HNSCC. [ABSTRACT FROM AUTHOR]

Background: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. Methods: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). Results: In 20,887 screened references, 79 articles (82.5% in 2017–2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5–52,000, median 21) and large-span sample size (range 80–3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. Conclusion: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field. [ABSTRACT FROM AUTHOR]

Introduction: Functional informaton is introduced as the mechanism to adapt cancer therapies uniquely to individual patients based on changes defined by qualified tumor biomarkers. Methods: To demonstrate the methodology, a tumor volume biomarker model, characterized by a tumor volume reduction rate coefficient, is used to adapt a tumor cell survival bioresponse radiotherapy model in terms of therapeutic radiation dose. Tumor volume, acquired from imaging data, serves as a surrogate measurement for tumor cell death, but the biomarker model derived from this data cannot be used to calculate the radiation dose absorbed by the target tumor. However, functional information does provide a mathematical connection between the tumor volume biomarker model and the tumor cell survival bioresponse model by quantifying both data sets in the units of information, thus creating an analytic conduit from bioresponse to biomarker. Results: The information guided process for individualized dose adaptations using information values acquired from the tumor cell survival bioresponse model and the tumor volume biomarker model are presented in detailed form by flowchart and tabular data. Clinical data are used to generate a presentation that assists investigator application of the information guided methodology to adaptive cancer therapy research. Conclusions: Information guided adaptation of bioresponse using surrogate data is extensible across multiple research fields because functional information mathematically connects disparate bioresponse and biomarker data sets. Thus, functional information offers adaptive cancer therapy by mathematically connecting immunotherapy, chemotherapy, and radiotherapy cancer treatment processes to implement individualized treatment plans. [ABSTRACT FROM AUTHOR]

Background: Chronic postsurgical pain (CPP) markedly impairs patients' quality of life. Research has shown that chronic stress may extend incisional nociception in male mice. Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) are integral to stress-related mental disorders (including major depressive disorder, anxiety disorders, and PTSD) and pain. However, the impact of chronic social defeat stress (CSDS) on mesolimbic dopamine (DA) transmission in the development of CPP is yet to be established. It remains uncertain whether the dopamine signals in the rostral anterior cingulate cortex (rACC), which regulate pain, derive from the VTA. This study aims to explore the role of VTA-rACC dopaminergic circuits in a mouse model of CPP induced by CSDS. Methods: We conducted CSDS on C57BL/6 J wild-type male mice (n = 12–16 mice/group) and DAT-cre male mice (n = 10–12 mice/group). After 10 days of CSDS, a left posterior plantar incision was made to establish a mouse model of CPP. Paw withdrawal thresholds (PWTs) were evaluated using Von-Frey fibre stimulation. The open field test (OFT) and elevated plus maze test (EPM) were used to assess pain-related negative emotions. We used immunofluorescence staining and Western Blot to analyse D1, D2, c-Fos, and TH expression. DAergic fibre projections in the VTA-rACC neural pathway were traced using retrograde tracing and immunofluorescence staining. Optogenetics and Chemogenetics were employed to manipulate DAergic neurons in the VTA and their axons in the rACC. Results: The ipsilateral PWTs in male C57BL/6 J mice significantly decreased after surgery, returning to baseline after seven days. Conversely, in CSDS mice, ipsilateral PWTs remained reduced for at least 30 days post-incision. A significant reduction in TH-positive neurons expressing c-Fos in the VTA of CPP mice was observed 15 days post-incision. Activating DAergic neurons significantly improved ipsilateral PWTs and locomotor performance in the OFT and EPM in CPP mice post-incision. Additionally, D1 expression in the rACC was found to decrease in CPP mice, and this reduction counteracted the increase in PWTs caused by activating DAergic neuron axon terminals in the rACC. Conclusion: CSDS results in chronicity of postsurgical nociception and anxiety-like negative emotions, with alterations in DA transmission playing a role in CPP. Specific activation of DAergic neurons mitigates nociceptive responses and anxiety-like bahaviors, possibly mediated by D1 receptors in the rACC. [ABSTRACT FROM AUTHOR]

PET/CT and radioisotope therapy are diagnostic and therapeutic arms of Nuclear Medicine, respectively. With the emergence of better technology, PET/CT has become an accessible modality. Diagnostic tracers exploring diseasespecific targets has led the clinicians to look beyond FDG PET. Moreover, with the emergence of theranostic pairs of radiopharmaceuticals, radioisotope therapy is gradually making it's way into treatment algorithm of common cancers in India. We therefore would like to discuss in detail the updates in PET/CT imaging and radionuclide therapy and generate a consensus-driven evidence based document which would guide the practitioners of Oncology. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The standardized uptake value ratio (SUVR) is used to measure amyloid beta–positron emission tomography (Aβ‐PET) uptake in the brainDifferences in PET scanner technologies and image reconstruction techniques can lead to variability in PET images across scanners. This poses a challenge for Aβ‐PET studies conducted in multiple centers. The aim of harmonization is to achieve consistent Aβ‐PET measurements across different scanners. In this study, we propose an Aβ‐PET harmonization method of matching spatial resolution, as measured via a barrel phantom, across PET scanners. Our approach was validated using paired subject data, for which patients were imaged on multiple scanners. METHODS: In this study, three different PET scanners were evaluated: the Siemens Biograph Vision 600, Siemens Biograph molecular computed tomography (mCT), and Philips Gemini TF64. A total of five, eight, and five subjects were each scanned twice with [18F]‐NAV4694 across Vision‐mCT, mCT‐Philips, and Vision‐Philips scanner pairs. The Vision and mCT scans were reconstructed using various iterations, subsets, and post‐reconstruction Gaussian smoothing, whereas only one reconstruction configuration was used for the Philips scans. The full‐width at half‐maximum (FWHM) of each reconstruction configuration was calculated using [18F]‐filled barrel phantom scans with the Society of Nuclear Medicine and Molecular Imaging (SNMMI) phantom analysis toolkit. Regional SUVRs were calculated from 72 brain regions using the automated anatomical labelling atlas 3 (AAL3) atlas for each subject and reconstruction configuration. Statistical similarity between SUVRs was assessed using paired (within subject) t‐tests for each pair of reconstructions across scanners; the higher the p‐value, the greater the similarity between the SUVRs. RESULTS: Vision‐mCT harmonization: Vision reconstruction with FWHM = 4.10 mm and mCT reconstruction with FWHM = 4.30 mm gave the maximal statistical similarity (maximum p‐value) between regional SUVRs. Philips‐mCT harmonization: The FWHM of the Philips reconstruction was 8.2 mm and the mCT reconstruction with the FWHM of 9.35 mm, which gave the maximal statistical similarity between regional SUVRs. Philips–Vision harmonization: The Vision reconstruction with an FWHM of 9.1 mm gave the maximal statistical similarity between regional SUVRs when compared with the Philips reconstruction of 8.2 mm and were selected as the harmonized for each scanner pair. CONCLUSION: Based on data obtained from three sets of participants, each scanned on a pair of PET scanners, it has been verified that using reconstruction configurations that produce matched‐barrel, phantom spatial resolutions results in maximally harmonized Aβ‐PET quantitation between scanner pairs. This finding is encouraging for the use of PET scanners in multi‐center trials or updates during longitudinal studies. Highlights: Question: Does the process of matching the barrel phantom‐derived spatial resolution between scanners harmonize amyloid beta–standardized uptake value ratio (Aβ‐SUVR) quantitation?Pertinent findings: It has been validated that reconstruction pairs with matched barrel phantom‐derived spatial resolution maximize the similarity between subjects paired Aβ‐PET (positron emission tomography) SUVR values recorded on two scanners.Implications for patient care: Harmonization between scanners in multi‐center trials and PET camera updates in longitudinal studies can be achieved using a simple and efficient phantom measurement procedure, beneficial for the validity of Aβ‐PET quantitation measurements. [ABSTRACT FROM AUTHOR]

Attenuation correction (AC) is essential for quantitative positron emission tomography (PET) images. Attenuation coefficient maps (μ-maps) are usually generated from computed tomography (CT) images when PET-CT combined systems are used. If CT has been performed prior to PET imaging, pre-acquired CT can be used for brain PET AC, because the human head is almost rigid. This pre-acquired CT-based AC approach is suitable for stand-alone brain-dedicated PET, such as VRAIN (ATOX Co. Ltd., Tokyo, Japan). However, the headrest of PET is different from the headrest in pre-acquired CT images, which may degrade the PET image quality. In this study, we prepared three different types of μ-maps: (1) based on the pre-acquired CT, where namely the headrest is different from the PET system (μ-map-diffHr); (2) manually removing the headrest from the pre-acquired CT (μ-map-noHr); and (3) artificially replacing the headrest region with the headrest of the PET system (μ-map-sameHr). Phantom images by VRAIN using each μ-map were investigated for uniformity, noise, and quantitative accuracy. Consequently, only the uniformity of the images using μ-map-diffHr was out of the acceptance criteria. We then proposed an automated method for removing the headrest from pre-acquired CT images. In comparisons of standardized uptake values in nine major brain regions from the 18F-fluoro-2-deoxy-D-glucose-PET of 10 healthy volunteers, no significant differences were found between the μ-map-noHr and the μ-map-sameHr. In conclusion, pre-acquired CT-based AC with automated headrest removal is useful for brain-dedicated PET such as VRAIN. [ABSTRACT FROM AUTHOR]

Background: The calculation of the net administered activity (Aadmin) in patients undergoing 90Y‐radioembolization is essential for dosimetry and radiation safety, yet current methods for measuring residual 90Y activity are often associated with high uncertainty. Therefore, an accurate, robust, and clinically viable method for the determination of Aadmin across approved 90Y microsphere devices is desirable. Purpose: We report on a novel method to determine Aadmin by leveraging the quantitative capabilities of SPECT/CT to measure 90Y‐emission in vivo from patients following 90Y‐radioembolization with glass or resin microspheres. Methods: 90Y‐SPECT/CT attenuation‐corrected count data from 147 sequential 90Y‐radioembolization patients was used for this analysis. Aadmin was calculated as part of routine clinical practice via the exposure rate differences between the initial 90Y‐vial and the 90Y‐residual jar. This served as our gold standard measure of Aadmin. Patient data for each microsphere device were separated into training and testing cohorts to first develop regression models and then to independently assess model performance. The training cohorts were divided into four groups: first, based on the microsphere device (glass or resin), and second, based on the SPECT volume used to calculate counts (the full SPECT field of view (FOV) or liver only (VOIliver)). Univariate linear regression models were generated for each group to predict Aadmin based on 90Y‐SPECT data from the training cohorts. Leave‐one‐out cross validation was implemented to estimate variability in model parameters. To assess performance, linear models derived from the training cohort were applied to 90Y‐SPECT data from the testing cohort. A comparison of the models between microspheres devices was also performed. Results: Linear models derived from the glass and resin training cohorts demonstrated a strong, positive correlation between 90Y‐SPECT image counts and Aadmin for VOIliver and FOV with R2 > 0.98 in all cases. In the glass training cohort, model accuracy (100%—absolute mean prediction error) and precision (95% prediction intervals of mean prediction error) were 99.0% and 15.4% for the VOIliver and 99.7% and 17.5% for the FOV models, respectively. In the resin training cohort, the corresponding values were 98.6% and 16.7% for VOIliver and > 99.9% and 11.4% for the FOV models, respectively. The application of these linear models to 90Y‐SPECT data from the testing cohort showed Aadmin prediction errors to have high accuracy and precision for both microsphere devices. For the glass testing cohort, accuracy (precision) was 96.9% (19.6%) and 98.8% (21.1%) for the VOIliver and FOV models, respectively. The corresponding values for the resin training cohort were 97.3% (26.2%) and 98.5% (25.7%) for the VOIliver and FOV models, respectively. The slope of the linear models between the two microsphere devices was observed to be significantly different with resin microspheres generating 48%–49% more SPECT counts for equivalent 90Y activity based on each device manufacturer's activity calibration process. Conclusion: 90Y‐SPECT image counts can reliably predict (accuracy > 95% and precision < 18%) Aadmin after 90Y‐radioembolization, with performance characteristics essentially equivalent for both glass and resin microspheres. There is a clear indication that activity calibrations are fundamentally different between the two microsphere devices. [ABSTRACT FROM AUTHOR]

Objective: Non-blinded image deblurring with deep learning was performed on blurred numerical brain images without point spread function (PSF) reconstruction to obtain edge artifacts (EA)-free images. This study uses numerical simulation to investigate the mechanism of EA in PSF reconstruction based on the spatial frequency characteristics of EA-free images. Methods: In 256 × 256 matrix brain images, the signal values of gray matter (GM), white matter, and cerebrospinal fluid were set to 1, 0.25, and 0.05, respectively. We assumed ideal projection data of a two-dimensional (2D) parallel beam with no degradation factors other than detector response blur to precisely grasp EA using the PSF reconstruction algorithm from blurred projection data. The detector response was assumed to be a shift-invariant and one-dimensional (1D) Gaussian function with 2–5 mm full width at half maximum (FWHM). Images without PSF reconstruction (non-PSF), PSF reconstruction without regularization (PSF) and with regularization of relative difference function (PSF-RD) were generated by ordered subset expectation maximization (OSEM). For non-PSF, the image deblurring with a deep image prior (DIP) was applied using a 2D Gaussian function with 2–5 mm FWHM. The 1D object-specific modulation transfer function (1D-OMTF), which is the ratio of 1D amplitude spectrum of the original and reconstructed images, was used as the index of spatial frequency characteristics. Results: When the detector response was greater than 3 mm FWHM, EA in PSF was observed in GM borders and narrow GM. No remarkable EA was observed in the DIP, and the FWHM estimated from the recovery coefficient for the deblurred image of non-PSF at 5 mm FWHM was reduced to 3 mm or less. PSF of 5 mm FWHM showed higher spatial frequency characteristics than that of DIP up to around 2.2 cycles/cm but was lower than the latter after 3 cycles/cm. PSF-RD showed almost the same spatial frequency characteristics as that of DIP above 3 cycles/cm but was inferior below 3 cycles/cm. PSF-RD has a lower spatial resolution than DIP. Conclusions: Unlike DIP, PSF lacks high-frequency components around the Nyquist frequency, generating EA. PSF-RD mitigates EA while simultaneously suppressing the signal, diminishing spatial resolution. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of a clinical-MRI radiomics model based on clinical characteristics and T2-weighted imaging (T2WI) for preoperatively evaluating lymph node (LN) metastasis in patients with MRI-predicted low tumor (T) staging rectal cancer (mrT1, mrT2, and mrT3a with extramural spread ≤ 5 mm). Methods: This retrospective study enrolled 303 patients with low T-staging rectal cancer (training cohort, n = 213, testing cohort n = 90). A total of 960 radiomics features were extracted from T2WI. Minimum redundancy and maximum relevance (mRMR) and support vector machine were performed to select the best performed radiomics features for predicting LN metastasis. Multivariate logistic regression analysis was then used to construct the clinical and clinical-radiomics combined models. The model performance for predicting LN metastasis was assessed by receiver operator characteristic curve (ROC) and clinical utility implementing a nomogram and decision curve analysis (DCA). The predictive performance for LN metastasis was also compared between the combined model and human readers (2 seniors). Results: Fourteen radiomics features and 2 clinical characteristics were selected for predicting LN metastasis. In the testing cohort, a higher positive predictive value of 75.9% for the combined model was achieved than those of the clinical model (44.8%) and two readers (reader 1: 54.9%, reader 2: 56.3%) in identifying LN metastasis. The interobserver agreement between 2 readers was moderate with a kappa value of 0.416. A clinical-radiomics nomogram and decision curve analysis demonstrated that the combined model was clinically useful. Conclusion: T2WI-based radiomics combined with clinical data could improve the efficacy in noninvasively evaluating LN metastasis for the low T-staging rectal cancer and aid in tailoring treatment strategies. [ABSTRACT FROM AUTHOR]

In radiomics research, the issue of different instruments being used is significant. In this study, we compared three correction methods to reduce the batch effects in radiogenomic data from fluorodeoxyglucose (FDG) PET/CT images of lung cancer patients. Texture features of the FDG PET/CT images and genomic data were retrospectively obtained. The features were corrected with different methods: phantom correction, ComBat method, and Limma method. Batch effects were estimated using three analytic tools: principal component analysis (PCA), the k-nearest neighbor batch effect test (kBET), and the silhouette score. Finally, the associations of features and gene mutations were compared between each correction method. Although the kBET rejection rate and silhouette score were lower in the phantom-corrected data than in the uncorrected data, a PCA plot showed a similar variance. ComBat and Limma methods provided correction with low batch effects, and there was no significant difference in the results of the two methods. In ComBat- and Limma-corrected data, more texture features exhibited a significant association with the TP53 mutation than in those in the phantom-corrected data. This study suggests that correction with ComBat or Limma methods can be more effective or equally as effective as the phantom method in reducing batch effects. [ABSTRACT FROM AUTHOR]

Background: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are common in Veterans and linked to behavioral disturbances, increased risk of cognitive decline, and Alzheimer's disease. Objective: We studied the synergistic effects of PTSD and TBI on behavioral, cognitive, and neuroimaging measures in Vietnam war Veterans. Methods: Data were acquired at baseline and after about one-year from male Veterans categorized into: PTSD, TBI, PTSD+TBI, and Veteran controls without PTSD or TBI. We applied manual tractography to examine white matter microstructure of three fiber tracts: uncinate fasciculus (N = 91), cingulum (N = 87), and inferior longitudinal fasciculus (N = 95). ANCOVAs were used to compare Veterans' baseline behavioral and cognitive functioning (N = 285), white matter microstructure, amyloid-β (N = 230), and tau PET (N = 120). Additional ANCOVAs examined scores' differences from baseline to follow-up. Results: Veterans with PTSD and PTSD+TBI, but not Veterans with TBI only, exhibited poorer behavioral and cognitive functioning at baseline than controls. The groups did not differ in baseline white matter, amyloid-β, or tau, nor in behavioral and cognitive functioning, and tau accumulation change. Progression of white matter abnormalities of the uncinate fasciculus in Veterans with PTSD compared to controls was observed; analyses in TBI and PTSD+TBI were not run due to insufficient sample size. Conclusions: PTSD and PTSD+TBI negatively affect behavioral and cognitive functioning, while TBI does not contribute independently. Whether progressive decline in uncinate fasciculus microstructure in Veterans with PTSD might account for cognitive decline should be further studied. Findings did not support an association between PTSD, TBI, and Alzheimer's disease pathology based on amyloid and tau PET. [ABSTRACT FROM AUTHOR]

Background: In order to support the ongoing research across Europe to facilitate access to novel radionuclides, the PRISMAP consortium (European medical radionuclides programme) was established to offer the broadest catalog of non-conventional radionuclides for medical and translational research. The aim of this article is to introduce readers with current status of novel radionuclides in Europe. Main body: A consortium questionnaire was disseminated through the PRISMAP consortium and user community, professional associations and preclinical/clinical end users in Europe and the current status of clinical end-users in nuclear medicine were identified. A total of 40 preclinical/clinical users institutions took part in the survey. Clinical end users currently use the following radionuclides in their studies: 177Lu, 68 Ga, 111In, 90Y, other alpha emitters, 225Ac, 64Cu and Terbium isotopes. Radionuclides that would be of interest for users within the next 2–5 years are 64Cu, Terbium radionuclide "family" and alpha emitters, such as 225Ac. Conclusions: Thanks to a questionnaire distributed by the PRISMAP consortium, the current status and needs of clinical end-users in nuclear medicine were identified. [ABSTRACT FROM AUTHOR]

Background: Despite reports of gross motor problems in mild cognitive impairment (MCI) and Alzheimer's disease (AD), fine motor function has been relatively understudied. Objective: We examined if finger tapping is affected in AD, related to AD biomarkers, and able to classify MCI or AD. Methods: Forty-seven cognitively normal, 27 amnestic MCI, and 26 AD subjects completed unimanual and bimanual computerized tapping tests. We tested 1) group differences in tapping with permutation models; 2) associations between tapping and biomarkers (PET amyloid-β, hippocampal volume, and APOEɛ4 alleles) with linear regression; and 3) the predictive value of tapping for group classification using machine learning. Results: AD subjects had slower reaction time and larger speed variability than controls during all tapping conditions, except for dual tapping. MCI subjects performed worse than controls on reaction time and speed variability for dual and non-dominant hand tapping. Tapping speed and variability were related to hippocampal volume, but not to amyloid-β deposition or APOEɛ4 alleles. Random forest classification (overall accuracy = 70%) discriminated control and AD subjects, but poorly discriminated MCI from controls or AD. Conclusions: MCI and AD are linked to more variable finger tapping with slower reaction time. Associations between finger tapping and hippocampal volume, but not amyloidosis, suggest that tapping deficits are related to neuropathology that presents later during the disease. Considering that tapping performance is able to differentiate between control and AD subjects, it can offer a cost-efficient tool for augmenting existing AD biomarkers. [ABSTRACT FROM AUTHOR]

Despite being thirteen years since the installation of the first PET-MR system, the scanners constitute a very small proportion of the total hybrid PET systems installed. This is in stark contrast to the rapid expansion of the PET-CT scanner, which quickly established its importance in patient diagnosis within a similar timeframe. One of the main hurdles is the development of an accurate, reproducible and easy-to-use method for attenuation correction. Quantitative discrepancies in PET images between the manufacturer-provided MR methods and the more established CT- or transmission-based attenuation correction methods have led the scientific community in a continuous effort to develop a robust and accurate alternative. These can be divided into four broad categories: (i) MR-based, (ii) emission-based, (iii) atlas-based and the (iv) machine learning-based attenuation correction, which is rapidly gaining momentum. The first is based on segmenting the MR images in various tissues and allocating a predefined attenuation coefficient for each tissue. Emission-based attenuation correction methods aim in utilising the PET emission data by simultaneously reconstructing the radioactivity distribution and the attenuation image. Atlas-based attenuation correction methods aim to predict a CT or transmission image given an MR image of a new patient, by using databases containing CT or transmission images from the general population. Finally, in machine learning methods, a model that could predict the required image given the acquired MR or non-attenuation-corrected PET image is developed by exploiting the underlying features of the images. Deep learning methods are the dominant approach in this category. Compared to the more traditional machine learning, which uses structured data for building a model, deep learning makes direct use of the acquired images to identify underlying features. This up-to-date review goes through the literature of attenuation correction approaches in PET-MR after categorising them. The various approaches in each category are described and discussed. After exploring each category separately, a general overview is given of the current status and potential future approaches along with a comparison of the four outlined categories. [ABSTRACT FROM AUTHOR]

Background: Several software tools have been developed for gated PET imaging that use distinct algorithms to analyze tracer uptake, myocardial perfusion, and left ventricle volumes and function. Studies suggest that different software tools cannot be used interchangeably in humans. In this study, we sought to compare the left ventricular parameters in gated 18F-FDG PET/CT imaging in mice by three commercially available software tools: PMOD, MIM, and QGS. Methods and results: Healthy mice underwent ECG-gated 18F-FDG imaging using a small-animal nanoPET/CT (Mediso) under isoflurane narcosis. Reconstructed gates PET images were subsequently analyzed in three different software tools, and cardiac volume and function (end-diastolic (EDV), end-systolic volumes (ESV), stroke volume (SV), and ejection fraction (EF)) were evaluated. While cardiac volumes correlated well between PMOD, MIM, and QGS, the left ventricular parameters and cardiac function differed in agreement using Bland–Altman analysis. EDV in PMOD vs. QGS: r = 0.85; p < 0.001, MIM vs. QGS: r = 0.92; p < 0.001, and MIM vs. PMOD: r = 0.88; p < 0.001, showed good correlations. Correlation was also found in ESV: PMOD vs. QGS: r = 0.48; p = 0.07, MIM vs QGS: r = 0.79; p < 0.001, and MIM vs. PMOD: r = 0.69; p < 0.01. SV showed good correlations in: PMOD vs. QGS: r = 0.73; p < 0.01, MIM vs. QGS: r = 0.86; p < 0.001, and MIM vs. PMOD: r = 0.92; p < 0.001. However, EF among correlated poorly: PMOD vs. QGS: r = −0.31; p = 0.26, MIM vs. QGS: r = 0.48; p = 0.07, and MIM vs. PMOD: r = 0.23; p = 0.41. Inter-class and intra-class correlation coefficient were > 0.9 underlining repeatability in using PMOD, MIM, and QGS for cardiac volume and function assessment. Conclusions: All three commercially available software tools are feasible in small animal cardiac volume assessment in gated 18F-FDG PET/CT imaging. However, due to software-related differences in agreement analysis for cardiac volumes and function, PMOD, MIM, and QGS cannot be used interchangeably in murine research. [ABSTRACT FROM AUTHOR]

Judicious selection of constituents for concrete composite can minimize the concentration of induced radio-isotopes in the shielding components around the beam loss points of an accelerator. In the present work, 18 concrete composites were prepared using different rock aggregates and cements. Samples were irradiated in the fast neutron environment to estimate the induced short-lived isotopes. Study identified least production of 24Na, 56Mn isotopes in the composite prepared using calcitic marble and white Portland cement. Utilization of this concrete composite mixture can minimize the induced isotope production, specifically at high neutron fluence regions to reduce the occupational exposures during maintenance operations. Article highlights: • Selection of potentially low induced activity generating raw materials are recommended. • Rock aggregates and cements depending on radiation type and energy can generate 24Na and 56Mn. • Composites with calcitic marble and white Portland cement can be used as strippable shielding layer. [ABSTRACT FROM AUTHOR]

The ability to adaptively guide behaviour requires the integration of external information with internal motivational factors. Decision-making capabilities can be impaired by acute stress and is often exacerbated by chronic pain. Chronic neuropathic pain patients often present with cognitive dysfunction, including impaired decision-making. The mechanisms underlying these changes are not well understood but may include altered monoaminergic transmission in the brain. In this study we investigated the relationships between dopamine, serotonin, and their metabolites in key brain regions that regulate motivated behaviour and decision-making. The neurochemical profiles of the medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens were analysed using HPLC in rats that received a chronic constriction injury (CCI) of the right sciatic nerve and an acute stress (15-min restraint), prior to an outcome devaluation task. CCI alone significantly decreased dopamine but not serotonin concentrations in the medial prefrontal cortex. By contrast, restraint stress acutely increased dopamine in the medial prefrontal cortex, and the nucleus accumbens; and increased serotonin in the medial prefrontal cortex 2 h later. The sustained dopaminergic and serotonergic responses to acute stress highlight the importance of an animal's ability to mount an effective coping response. In addition, these data suggest that the impact of nerve injury and acute stress on outcome-devaluation occurs independently of dopaminergic and serotonergic transmission in the medial prefrontal cortex, orbital prefrontal cortex and nucleus accumbens of rats. [ABSTRACT FROM AUTHOR]

Purpose: This review aims to provide a comprehensive overview of the latest literature on personalized lung cancer management using different ligands and radionuclide-based tumor-targeting agents. Background: Lung cancer is the leading cause of cancer-related deaths worldwide. Due to the heterogeneity of lung cancer, advances in precision medicine may enhance the disease management landscape. More recently, theranostics using the same molecule labeled with two different radionuclides for imaging and treatment has emerged as a promising strategy for systemic cancer management. In radionuclide-based theranostics, the target, ligand, and radionuclide should all be carefully considered to achieve an accurate diagnosis and optimal therapeutic effects for lung cancer. Methods: We summarize the latest radiotracers and radioligand therapeutic agents used in diagnosing and treating lung cancer. In addition, we discuss the potential clinical applications and limitations associated with target-dependent radiotracers as well as therapeutic radionuclides. Finally, we provide our views on the perspectives for future development in this field. Conclusions: Radionuclide-based theranostics show great potential in tailored medical care. We expect that this review can provide an understanding of the latest advances in radionuclide therapy for lung cancer and promote the application of radioligand theranostics in personalized medicine. [ABSTRACT FROM AUTHOR]

Background: Differentiating atypical lipomatous tumors (ALTs) and well-differentiated liposarcomas (WDLs) from benign lipomatous lesions is important for guiding clinical management, though conventional visual analysis of these lesions is challenging due to overlap of imaging features. Radiomics-based approaches may serve as a promising alternative and/or supplementary diagnostic approach to conventional imaging. Purpose: The purpose of this study is to review the practice of radiomics-based imaging and systematically evaluate the literature available for studies evaluating radiomics applied to differentiating ALTs/WDLs from benign lipomas. Review: A background review of the radiomic workflow is provided, outlining the steps of image acquisition, segmentation, feature extraction, and model development. Subsequently, a systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the grey literature was performed from inception to June 2022 to identify size studies using radiomics for differentiating ALTs/WDLs from benign lipomas. Radiomic models were shown to outperform conventional analysis in all but one model with a sensitivity ranging from 68 to 100% and a specificity ranging from 84 to 100%. However, current approaches rely on user input and no studies used a fully automated method for segmentation, contributing to interobserver variability and decreasing time efficiency. Conclusion: Radiomic models may show improved performance for differentiating ALTs/WDLs from benign lipomas compared to conventional analysis. However, considerable variability between radiomic approaches exists and future studies evaluating a standardized radiomic model with a multi-institutional study design and preferably fully automated segmentation software are needed before clinical application can be more broadly considered. [ABSTRACT FROM AUTHOR]

Background: The Quick Dementia Rating System (QDRS) is a brief, informant-reported dementia staging tool that approximates scores on the Clinical Dementia Rating Scale in patients with Alzheimer's disease (AD). Objective: The current study sought to examine change in the QDRS across time, which is necessary for clinical and research efforts. Methods: One-hundred ten older adults (intact, mild cognitive impairment [MCI], mild AD, classified with Alzheimer's Disease Neuroimaging Initiative criteria) were rated on the QDRS by an informant and had an amyloid positron emission tomography scan at baseline. The informant re-rated each participant on the QDRS after one year. Dependent t-tests compared the entire sample and various subgroups (e.g., cognitive status, amyloid status) on baseline and follow-up QDRS scores. Results: In the entire sample, the Total score on the QDRS significantly increased (i.e., worsened) on follow-up (p < 0.001). When subgroups were analyzed, the MCI and mild AD subjects showed increasing (i.e., worsening) QDRS Total scores (both p < 0.001), but the intact subjects remained stable over time (p = 0.28). Additionally, those classified as being amyloid positive at baseline showed significantly increased QDRS Total scores at follow-up (p < 0.001) compared to those who were amyloid negative at baseline, whose QDRS Total scores remained stable over time (p = 0.63). Conclusion: The QDRS can potentially demonstrate worsening functioning status across one year, especially in those who have MCI or mild AD and those who are amyloid positive. Therefore, the current results preliminarily suggest that the QDRS may provide an efficient tool for tracking progression in clinical trials in AD. [ABSTRACT FROM AUTHOR]