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Purpose: To determine the diagnostic accuracy and the clinical impact of ultrasound (US) and computed tomography (CT) in diagnosing appendicitis, and to evaluate the impact of laboratory tests on the treatment of acute appendicitis. Material and Methods: All patients who, during 2005, underwent an acute ultrasound or CT investigation due to suspected appendicitis, or were diagnosed and/or surgically treated for appendicitis at Umeå University Hospital, Umeå, were included. The type of radiological investigation, its findings, the choice of treatment, final diagnosis, C-reactive protein (CRP), leukocyte particle count (LPC), body temperature, age, and sex were recorded for each patient. The histological result from surgery was considered the gold standard. Results: The material included 305 cases with an overall appendicitis prevalence of 58%. Fifty-two percent of the patients were female. The mean age was 29 years, with a total range of 2-94 years. Twenty percent (60/305) underwent a CT investigation, 40% (123/305) underwent an US investigation, 5% (14/305) underwent both a CT and an US investigation, and 35% (108/305) of patients did not undergo any radiological investigation at all. The sensitivities and specificities were 91% and 94% for CT, and 83% and 98% for US, respectively. The positive likelihood ratio was 15.1 and 45.5 for CT and US, and the negative likelihood ratio was 0.09 and 0.18 for CT and US, respectively. It was not possible to visualize the appendix in 31% of patients examined with US. The prevalence of appendicitis in this group was the same as the prevalence among patients where it was possible to see the appendix, i.e., 35%. The mean CRP for all patients with appendicitis was 59 (95% CI 10-491) mg/l, and the mean LPC was 11.1 (95% CI 2.6-28.1) x10(-9)/l. The mean LPC level was significantly higher for the appendicitis patients. Body temperature could not significantly verify or exclude appendicitis. The overall negative appendectomy rate was 9% (16/176), and it was higher in women, i.e., 11% (9/79). The negative appendectomy rate was slightly higher in the group that was examined by CT and/or US, i.e., 12% (8/69) compared to 7% (8/107) in the group not examined radiologically. Conclusion: Diagnostic accuracy was high for US as well as for CT. US was better for diagnosing positive findings, while CT was better for excluding diagnosis of appendicitis. The diagnostic accuracy of LPC, CRP, and body temperature was low. By combining findings from the radiological examination with the results from the clinical examination and laboratory values, a low negative appendectomy rate can be achieved. [ABSTRACT FROM AUTHOR]

Three monoclonal antibodies and their Fab and Fab2′ fragments with specificity against human placental alkaline phosphatase (PLAP) were evaluated for tumour immunolocalization of human PLAP-producing Hela Hep 2 tumours in nude mice. The antibodies and their fragments were labelled with 125I and injected intraperitoneally in mice with developing Hep 2 tumours. The animals were followed individually for 14 days with repetitive computerized gamma-camera recordings, which enable quantitation of several crucial parameters, i.e. the time-dependent antibody uptake in the tumours, decrease in background activity and tumour/background ratio. Excellent radioimmunolocalization was obtained with both the intact PLAP-specific immunoglobulins and their fragments but not with the nonspecific antibodies. No background subtraction had to be used. As much as 15 % of the initially injected dose could be visualized in the tumours and for the uncleaved mab up to 80% of the radioactivity in the animals was retained in the tumours after 14 days, a considerably longer observation time than usually reported in such tumour xenograft models. The Fab and Fab2′ fragments were found to be excreted fast with less than 5 % of the injected dose remaining in the animals after 48 h, but still with positive specific localization to the tumours after an initial high uptake in the kidneys. The results are encouraging and indicate significant potentials of the PLAP-antiPLAP mab system for immunolocalization studies in patients. Copyright © 1989 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Although age differences in the dopamine system have been suggested to contribute to age-related cognitive decline based on cross-sectional data, recent large-scale cross-sectional studies reported only weak evidence for a correlation among aging, dopamine receptor availability, and cognition. Regardless, longitudinal data remain essential to make robust statements about dopamine losses as a basis for cognitive aging. We present correlations between changes in D2/3 dopamine receptor availability and changes in working memory measured over 5 yr in healthy, older adults (n = 128, ages 64 to 68 yr at baseline). Greater decline in D2/3 dopamine receptor availability in working memory-relevant regions (caudate, middle frontal cortex, hippocampus) was related to greater decline in working memory performance in individuals who exhibited working memory reductions across time (n = 43; caudate: rs = 0.494; middle frontal cortex: rs = 0.506; hippocampus; rs = 0.423), but not in individuals who maintained performance (n = 41; caudate: rs = 0.052; middle frontal cortex: rs = 0.198; hippocampus; rs = 0.076). The dopamine-working memory link in decliners was not observed in the orbitofrontal cortex, which does not belong to the core working memory network. Our longitudinal analyses support the notion that aging-related changes in the dopamine system contribute to working memory decline in aging., (© The Author(s) 2025. Published by Oxford University Press.)

Technological innovations in genomics and related fields have facilitated large sequencing efforts, supported new biological discoveries in cancer, and spawned an era of liquid biopsy biomarkers. Despite these advances, precision oncology has practical constraints, partly related to cancer's biological diversity and spatial and temporal complexity. Advanced imaging technologies are being developed to address some of the current limitations in early detection, treatment selection and planning, drug delivery, and therapeutic response, as well as difficulties posed by drug resistance, drug toxicity, disease monitoring, and metastatic evolution. We discuss key areas of advanced imaging for improving cancer outcomes and survival. Finally, we discuss practical challenges to the broader adoption of precision imaging in the clinic and the need for a robust translational infrastructure., Competing Interests: Declaration of interests HH serves on the board of directors for Ion Beam Applications; the external advisory board of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University; the international advisory board of the University of Vienna; the scientific committee and board of trustees of the DKFZ (German Cancer Research Center); the board of directors of iCAD; the advisory board of The Lancet Oncology; and receives stock options from iCAD. KH receives grants from Novartis and Sofie Biosciences; has consulted for Advanced Accelerator Applications, Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien München, Janssen Pharmaceuticals, Merck, Molecular Partners, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, Theragnostics, and Y-mAbs Therapeutics; has stock options in Sofie Biosciences, Pharma15, Vision, Convergent, Aktis Oncology, AdvanCell; is an advisory board member of Fusion and GE Healthcare; receives honoraria from PeerView; and has received travel support from Janssen Pharmaceuticals. JSL reports research support from Clarity Pharmaceuticals and Avid Radiopharmaceuticals; has acted as an advisor for Alpha-9 Theranostics, Boxer, Clarity Pharmaceuticals, Earli, Curie Therapeutics, Evergreen Theragnostics, West Street Life Sciences, Inhibrx, Luminance Biosciences, NexTech Venture, Sanofi US Services, Solve Therapeutics, Suba Therapeutics, TPG Capital, Telix Pharmaceuticals, pHLIP, and Precirix; is a co-inventor on technologies licensed to Diaprost, Elucida Oncology, Theragnostics, CheMatech, Daiichi Sankyo, and Samus Therapeutics; is the co-founder of pHLIP; holds equity in Summit Biomedical Imaging, Telix Pharmaceuticals, Clarity Pharmaceuticals, and Evergreen Theragnostics; and is supported by National Institutes of Health grant R35 CA232130. MGP has consulted for CraniUS, UCLA Cancer Center, Ventyx, Einseca, and ModeX; receives royalties from Lantheus Holdings, Novartis, Intuitive Surgical and Cyclotek; has 70 patents issued or filed related to imaging or informatics; and has stock options in D&D Pharmatech, PlenaryAI, Earli, and Immunosity. AMS reports trial funding from EMD Serono, ITM, Telix Pharmaceuticals, AVID Radiopharmaceuticals, Fusion Pharmaceuticals, and Cyclotek; research funding from Medimmune, AVID Radiopharmaceuticals, Adalta, Antengene, Humanigen, Telix Pharmaceuticals, and Theramyc; and payment for participation in advisory boards of Imagion and Immunos. RW has consulted for ModeRNA, Boston Scientific, Lumicell, Seer Biosciences, Earli, and Accure Health. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background and Purpose: Dose escalation in external radiotherapy of prostate cancer shows promising results in terms of biochemical disease-free survival. Boost volume delineation guidelines are sparse which may cause high interobserver variability. The aim of this research was to characterize gross tumor volume (GTV) delineations based on multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen-positron emission tomography (PSMA-PET) in relation to histopathology-validated Gleason grade 4 and 5 regions., Material and Methods: The study participants were examined with [ 68 Ga]PSMA-PET/mpMRI prior to radical prostatectomy. Four radiation oncologists delineated GTVs in 15 study participants, on four different image types; T2-weighted (T2w), diffusion weighted imaging (DWI), dynamic contrast enhanced (DCE) and PSMA-PET scans separately. The simultaneous truth and performance level estimation (STAPLE) algorithm was used to generate combined GTVs. GTVs were subsequently compared to histopathology. We analysed how Dice similarity coefficient (DSC) and lesion coverage are affected by using single versus multiple image types as well as by adding a clinical target volume (CTV) margin., Results: Median DSC (STAPLE) for different GTVs varied between 0.33 and 0.52. GTV PSMA-PET/mpMRI generated the highest median lesion coverage at 0.66. Combining different image types achieved similar lesion coverage as adding a CTV margin to contours from a single image type, while reducing non-malignant tissue inclusion within the target volume., Conclusion: The combined use of mpMRI or PSMA-PET/mpMRI shows promise, achieving higher DSC and lesion coverage while minimizing non-malignant tissue inclusion, in comparison to the use of a single image type with an added CTV margin., Competing Interests: This work was funded by Swedish Cancer Society, Cancer research foundation of Northen Sweden, Prostatacancerförbundet and Västerbotten County. Furthermore, Joakim Jonsson and Tufve Nyholm are part-owner in Hero Imaging AB which produces the software HERO that were used in the analysis., (© 2024 The Author(s).)

Losses in dopamine (DA) functioning may contribute to aging-related decline in cognition. Hippocampal DA is necessary for successful episodic memory formation. Previously, we reported that higher DA D2 receptor (D2DR) availability in hippocampus is beneficial for episodic memory only in older carriers of more advantageous genotypes of well-established plasticity-related genetic variations, the brain-derived neurotrophic factor (BDNF, rs6265) and the kidney and brain expressed protein (KIBRA, rs17070145) polymorphisms. Extending our observations to the longitudinal level, the current data show that individuals with one or no beneficial BDNF and KIBRA genotype (n = 80) decline more in episodic memory across five years, without any contribution of losses in hippocampal D2DR availability to memory decline. Although carriers of two beneficial genotypes (n = 39) did not decline overall in episodic memory, losses of hippocampal D2DR availability were predictive of episodic-memory decline among these individuals. Our findings have implications for interventions targeting DA modulation to enhance episodic memory in aging, which may not benefit all older individuals., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology., Materials and Methods: The study population consisted of 15 patients with confirmed high-risk PC intended for prostatectomy. [68Ga]-PSMA-PET/MR was performed prior to surgery. Prostate lesions identified in histopathology were transferred to the in vivo [68Ga]-PSMA-PET/MR coordinate system. Four radiation oncologists manually delineated intraprostatic lesions based on PET data. Various semi-automatic segmentation methods were employed, including absolute and relative thresholds, adaptive threshold, and multi-level Otsu threshold., Results: The gross tumour volumes (GTVs) delineated by the oncologists showed a moderate level of interobserver agreement with Dice similarity coefficient (DSC) of 0.68. In comparison with histopathology, manual delineations exhibited the highest median DSC and the lowest false discovery rate (FDR) among all approaches. Among semi-automatic approaches, GTVs generated using standardized uptake value (SUV) thresholds above 4 (SUV > 4) demonstrated the highest median DSC (0.41), with 0.51 median lesion coverage ratio, FDR of 0.66 and the 95th percentile of the Hausdorff distance (HD95%) of 8.22 mm., Interpretation: Manual delineations showed a moderate level of interobserver agreement. Compared to histopathology, manual delineations and SUV > 4 exhibited the highest DSC and the lowest HD95% values. The methods that resulted in a high lesion coverage were associated with a large overestimation of the size of the lesions.

Dopamine decline is suggested to underlie aging-related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5-year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64-68 years; 5-year follow-up: n = 129) who underwent positron emission tomography with 11 C-raclopride to assess dopamine D2-like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A data-driven approach (k-means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age-sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide-ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5-year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET) are widely used for the management of prostate cancer (PCa). However, how these modalities complement each other in PCa risk stratification is still largely unknown. We aim to provide insights into the potential of mpMRI and PET for PCa risk stratification., Methods: We analyzed data from 55 consecutive patients with elevated prostate-specific antigen and biopsy-proven PCa enrolled in a prospective study between December 2016 and December 2019. [ 68 Ga]PSMA-11 PET (PSMA-PET), [ 11 C]Acetate PET (Acetate-PET) and mpMRI were co-registered with whole-mount histopathology. Lower- and higher-grade lesions were defined by International Society of Urological Pathology (ISUP) grade groups (IGG). We used PET and mpMRI data to differentiate between grades in two cases: IGG 3 vs. IGG 2 (case 1) and IGG ≥ 3 vs. IGG ≤ 2 (case 2). The performance was evaluated by receiver operating characteristic (ROC) analysis., Results: We find that the maximum standardized uptake value (SUV max ) for PSMA-PET achieves the highest area under the ROC curve (AUC), with AUCs of 0.72 (case 1) and 0.79 (case 2). Combining the volume transfer constant, apparent diffusion coefficient and T2-weighted images (each normalized to non-malignant prostatic tissue) results in AUCs of 0.70 (case 1) and 0.70 (case 2). Adding PSMA-SUV max increases the AUCs by 0.09 (p < 0.01) and 0.12 (p < 0.01), respectively., Conclusions: By co-registering whole-mount histopathology and in-vivo imaging we show that mpMRI and PET can distinguish between lower- and higher-grade prostate cancer, using partially discriminative cut-off values., (© 2023. The Author(s).)

Objective: PET/CT and multiparametric MRI (mpMRI) are important diagnostic tools in clinically significant prostate cancer (csPC). The aim of this study was to compare csPC detection rates with [ 68 Ga]PSMA-11-PET (PSMA)-PET, [ 11 C]Acetate (ACE)-PET, and mpMRI with histopathology as reference, to identify the most suitable imaging modalities for subsequent hybrid imaging. An additional aim was to compare inter-reader variability to assess reproducibility., Methods: During 2016-2019, all study participants were examined with PSMA-PET/mpMRI and ACE-PET/CT prior to radical prostatectomy. PSMA-PET, ACE-PET and mpMRI were evaluated separately by two observers, and were compared with histopathology-defined csPC. Statistical analyses included two-sided McNemar test and index of specific agreement., Results: Fifty-five study participants were included, with 130 histopathological intraprostatic lesions >0.05 cc. Of these, 32% (42/130) were classified as csPC with ISUP grade ≥2 and volume >0.5 cc. PSMA-PET and mpMRI showed no difference in performance ( P  = 0.48), with mean csPC detection rate of 70% (29.5/42) and 74% (31/42), respectively, while with ACE-PET the mean csPC detection rate was 37% (15.5/42). Interobserver agreement was higher with PSMA-PET compared to mpMRI [79% (26/33) vs 67% (24/38)]. Including all detected lesions from each pair of observers, the detection rate increased to 90% (38/42) with mpMRI, and 79% (33/42) with PSMA-PET., Conclusion: PSMA-PET and mpMRI showed high csPC detection rates and superior performance compared to ACE-PET. The interobserver agreement indicates higher reproducibility with PSMA-PET. The combined result of all observers in both PSMA-PET and mpMRI showed the highest detection rate, suggesting an added value of a hybrid imaging approach., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)