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Background and purpose: Primary lateral sclerosis (PLS) is a neurodegenerative disorder that primarily affects the central motor system. In rare cases, clinical features of PLS may overlap with those of progressive supranuclear palsy (PSP). We investigate neuroimaging features that can help distinguish PLS with overlapping features of PSP (PLS‐PSP) from PSP. Methods: Six patients with PLS‐PSP were enrolled between 2019 and 2023. We compared their clinical and neuroimaging characteristics with 18 PSP–Richardson syndrome (PSP‐RS) patients and 20 healthy controls. Magnetic resonance imaging, 18F‐flortaucipir positron emission tomography (PET), quantitative susceptibility mapping, and diffusion tensor imaging tractography (DTI) were performed to evaluate eight brain regions of interest. Area under the receiver operating characteristic curve (AUROC) was calculated. Results: Five of the six PLS‐PSP patients (83.3%) were male. Median age at symptom onset was 61.5 (52.5–63) years, and all had mixed features of PLS and PSP. Volumes of the pallidum, caudate, midbrain, and cerebellar dentate were smaller in PSP‐RS than PLS‐PSP, providing good discrimination (AUROC = 0.75 for all). The susceptibilities in pallidum, midbrain, and cerebellar dentate were greater in PSP‐RS compared to PLS‐PSP, providing excellent discrimination (AUROC ≥ 0.90 for all). On DTI, fractional anisotropy (FA) in the posterior limb of the internal capsule from the corticospinal tract was lower in PLS‐PSP compared to PSP‐RS (AUROC = 0.86), but FA in the superior cerebellar peduncle was lower in PSP‐RS (AUROC = 0.95). Pallidum flortaucipir PET uptake was greater in PSP‐RS compared to PLS‐PSP (AUROC = 0.74). Conclusions: Regional brain volume, tractography, and magnetic susceptibility, but not tau‐PET, are useful in distinguishing PLS‐PSP from PSP. [ABSTRACT FROM AUTHOR]

Objective: Although astrocytic pathology is a pathological hallmark of progressive supranuclear palsy (PSP), its pathophysiological role remains unclear. This study aimed to assess astrocyte reactivity in vivo in patients with PSP. Furthermore, we investigated alterations in brain lactate levels and their relationship with astrocyte reactivity. Methods: We included 30 patients with PSP‐Richardson syndrome and 30 healthy controls; in patients, tau deposition was confirmed through 18F‐florzolotau positron emission tomography. Myo‐inositol, an astroglial marker, and lactate were quantified in the anterior cingulate cortex through magnetic resonance spectroscopy. We measured plasma biomarkers, including glial fibrillary acidic protein as another astrocytic marker. The anterior cingulate cortex was histologically assessed in postmortem samples of another 3 patients with PSP with comparable disease durations. Results: The levels of myo‐inositol and plasma glial fibrillary acidic protein were significantly higher in patients than those in healthy controls (p < 0.05); these increases were significantly associated with PSP rating scale and cognitive function scores (p < 0.05). The lactate level was high in patients, and correlated significantly with high myo‐inositol levels. Histological analysis of the anterior cingulate cortex in patients revealed reactive astrocytes, despite mild tau deposition, and no marked synaptic loss. Interpretation: We discovered high levels of astrocyte biomarkers in patients with PSP, suggesting astrocyte reactivity. The association between myo‐inositol and lactate levels suggests a link between reactive astrocytes and brain energy metabolism changes. Our results indicate that astrocyte reactivity in the anterior cingulate cortex precedes pronounced tau pathology and neurodegenerative processes in that region, and affects brain function in PSP. ANN NEUROL 2024;96:247–261 [ABSTRACT FROM AUTHOR]

Neurolymphomatosis (NL) describes an infiltration of cranial and peripheral nerves by lymphoma cells, most frequently in non-Hodgkin B-cell lymphoma. This clinical entity is rare and poses a challenging diagnosis. We describe a case of a 64-year-old female patient with NL associated with extra-nodal NK/T-cell lymphoma (ENKTL), nasal type, presenting as a painful progressive mononeuropathy multiplex with an oral cavity lesion. ENKTL is usually associated with Epstein-Barr virus (EBV) infection and rarely affects the central and peripheral nervous system. Lumbar puncture, magnetic resonance imaging (MRI), nerve biopsy, and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) help to establish the diagnosis. Thereby, NL should be considered in the differential diagnosis of painful progressive multiple neuropathies, even in patients without previous history of cancer. [ABSTRACT FROM AUTHOR]

Fexofenadine is a second-generation inverse agonist of H1-receptor of histamine which is highly selective with proven efficacy in relieving symptoms associated with allergic conditions. It has an additional benefit of not penetrating the blood–brain barrier and therefore do not induce sedation and not impair the cognitive function/psychomotor performance. This review aimed at providing evidence based on available controlled studies to reinforce the non-sedative property of fexofenadine for treating patients with allergic rhinitis and urticaria. We performed an electronic literature search using keywords such as fexofenadine, drowsiness, somnolence, sedation, fatigue, cognitive, impairment, psychomotor, driving performances, sleep, rapid eye movement, alertness, clinical study, in vitro study, in vivo study, and pharmacodynamics in the Embase search engine. The review included randomized controlled trials, review articles, systematic reviews, and meta-analyses, together with post-marketing analysis conducted in healthy subjects and patients with allergy and were focused on comparing the antihistaminic potential or safety of fexofenadine with other antihistamines or placebo. Positron emission tomography (PET) and proportional impairment ratio (PIR) data along with other objective tests from various studies confirmed the non-sedative property of fexofenadine. Results of brain H1-receptor occupancy (H1RO) obtained from PET showed no H1RO by fexofenadine, the receptor which is known to cause sedation of H1 antihistamines. Most studies calculating PIR value as 0 showed fexofenadine to be a non-impairing oral antihistamine regardless of dose. Clinical trials in adults and children showed fexofenadine to be well tolerated without sedative effect or impairment of cognitive/psychomotor function even at higher than recommended doses. Published literature based on various parameters and clinical trials conducted for evaluating the effect of fexofenadine on sedation and central nervous system shows fexofenadine is both clinically effective and non-sedating. [ABSTRACT FROM AUTHOR]

This article discusses a case of giant cell arteritis (GCA) with genital system involvement. GCA is a chronic inflammatory condition that primarily affects individuals over the age of 50. While GCA commonly affects the temporal arteries, it can also involve other arteries, including those in the lung, breast, and gynecological system. The article presents a case of a 61-year-old female patient who was diagnosed with GCA based on the analysis of ovarian and uterine pathology specimens. The patient's symptoms and acute phase reactants returned to normal with treatment, and her progress has been monitored for 3 years. The article emphasizes the importance of considering GCA in patients with systemic inflammatory symptoms and genital system problems. [Extracted from the article]

Background: Parkinson's disease (PD) manifests as a wide variety of clinical phenotypes and its progression varies greatly. However, the factors associated with different disease progression remain largely unknown. Methods: In this retrospective cohort study, we enrolled 113 patients who underwent 18F-FP-CIT PET scan twice. Given the negative exponential progression pattern of dopamine loss in PD, we applied the natural logarithm to the specific binding ratio (SBR) of two consecutive 18F-FP-CIT PET scans and conducted linear mixed model to calculate individual slope to define the progression rate of nigrostriatal degeneration. We investigated the clinical and dopamine transporter (DAT) availability patterns associated with the progression rate of dopamine depletion in each striatal sub-region. Results: More symmetric parkinsonism, the presence of dyslipidemia, lower K-MMSE total score, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the caudate nucleus. More symmetric parkinsonism and lower anteroposterior gradient of the mean putaminal SBR were associated with faster depletion of dopamine in the anterior putamen. Older age at onset, more symmetric parkinsonism, the presence of dyslipidemia, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the posterior putamen. Lower striatal mean SBR predicted the development of LID, while lower mean SBR in the caudate nuclei predicted the development of dementia. Discussion: Our results suggest that the evaluation of baseline clinical features and patterns of DAT availability can predict the progression of PD and its prognosis. [ABSTRACT FROM AUTHOR]

Objective: Half of ALS patients are cognitively and/or behaviourally impaired. As cognition/behaviour and cerebral glucose metabolism can be correlated by means of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET), we aimed to utilise FDG-PET, first, to replicate group-level differences in glucose metabolism between non-demented ALS patients separated into non-impaired (ALSni), cognitively impaired (ALSci), behaviourally impaired (ALSbi), and cognitively and behaviourally impaired (ALScbi) groups; second, to investigate glucose metabolism and performance in various cognitive domains; and third, to examine the impact of partial volume effects correction (PVEC) of the FDG-PET data on the results. Methods: We analysed neuropsychological, clinical, and imaging data from 67 ALS patients (30 ALSni, 21 ALSci, 5 ALSbi, and 11 ALScbi). Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen, and two social cognition tests. FDG-PET and structural MRI scans were acquired for each patient. Voxel-based statistical analyses were undertaken on grey matter volume (GMV) and non-corrected vs. PVE-corrected FDG-PET scans. Results: ALSci and ALScbi had lower cognitive scores than ALSni. In contrast to both ALSni and ALSci, ALScbi showed widespread hypometabolism in the superior- and middle-frontal gyri in addition to the right temporal pole. Correlations were observed between the GMV, the FDG-PET signal, and various cognitive scores. The FDG-PET results were largely unaffected by PVEC. Interpretation: Our study identified widespread differences in hypometabolism in the ALScbi-ni but not in the ALSci-ni group comparison, raising the possibility that cerebral metabolism may be more closely related to the presence of behavioural changes than to mild cognitive deficits. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate and compare the diagnostic accuracy of modalities used to aid the diagnosis of aseptic knee arthroplasty loosening. Methods: A comparative diagnostic test accuracy systematic review and meta‐analysis was conducted following the Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines. PubMed, EMBASE and Cochrane databases were searched for original articles evaluating diagnostic modalities up to March 2024. Included studies compared the modality (index test) to the intraoperative finding as reference test. The QUADAS‐C (Quality Assessment of Diagnostic Accuracy Studies‐Comparative) tool was used to assess the quality of the included studies. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to evaluate the certainty of evidence. Level of evidence was evaluated using the Oxford Levels of Evidence tool. The primary outcome was the summary of diagnostic accuracy metrics for each modality as demonstrated by a summary receiver‐operating characteristic (SROC) curve. Results: The search yielded 467 articles. Of these, 14 articles were included. These 14 articles evaluated a total of five different diagnostic modalities: bone scintigraphy (three studies, 146 cases), 18‐fluorodeoxyglucose positron emission tomography (two studies, 50 cases), single‐photon emission computed tomography combined with computed tomography (SPECT/CT) (seven studies, 371 cases), radionuclide arthrogram (three studies, 196 cases) and magnetic resonance imaging (MRI) (one study, 116 cases). Nine studies exhibited a high risk of bias in patient selection, and all studies showed a high risk of bias related to the reference test. The majority of the included studies were classified as Level III evidence, leading to an overall low level of certainty in the evidence. The most accurate tests, as demonstrated by the SROC analysis, were MRI and SPECT/CT, with sensitivities ranging from 0.00 to 1.00 and 0.33 to 1.00 and specificities between 0.31–1.00 and 0.00–1.00, respectively. Conclusions: This review and meta‐analysis evaluated available diagnostic modalities to aid the diagnosis of knee arthroplasty loosening and based on a low certainty of evidence suggests that MRI and SPECT/CT are currently the most accurate modalities available to aid the diagnosis of aseptic loosening of knee arthroplasty components. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

The article explores the need for updated and standardized definitions for assessing treatment response in clinical trials for invasive fungal diseases (IFD). The current definitions, established in 2008, may not accurately capture the complexities of evaluating antifungal efficacy in patients with mold disease. This could potentially impact the evaluation and approval of new antifungal agents. The article presents arguments for and against updating the definitions, emphasizing the importance of clear and non-subjective criteria for standardized assessment in clinical trials. The article also discusses the limitations of the current definitions and proposes potential improvements, such as incorporating new assessment methods and considering diverse patient populations. [Extracted from the article]

Background: Combined PET/CT using 18F could be very effective with minimal hazards as well as false findings compared to the use one of these components alone in assessment of lymphoma. The purpose of this study was to review the usefulness of FDG PET/CT in diagnosis and staging of lymphoma, assessment of response to therapy, follow up and assessment of remissions and relapses among patients who had extranodal lymphoma. Methods: This cross-sectional study involved 36 patients who had pathologically confirmed lymphoma who underwent PET/CT study. A PET/CT in-line system was used to collect all of the data (General Electric PET CT Discovery). Prior to conducting a diagnostic enhanced whole-body CT scan, we conducted a low-dose enhanced CT scan, then a whole-body PET study. Results: The study compared the efficacy of contrast-enhanced CT and PET/CT in detecting lymphoma manifestations in 36 patients. PET/CT showed high sensitivity (100%) in detecting lymph node involvement and other extranodal manifestations, with varying specificity. Treatment response was evaluated using International Harmonization Project (IHP) and visual assessment based on the Déauville Criteria, showing a high level of agreement between the two methods. Conclusion: One promising oncologic imaging modality that could play a significant role in lymphoma care is a PET/CT combination that using 18F-FDG. In the early interim and after treatment ended, response assessments based on the Deauville criteria seemed to agree with IHP classifications to a reasonable degree. [ABSTRACT FROM AUTHOR]

Delta-like ligand 3 (DLL3) is aberrantly expressed on the surface of small-cell lung cancer (SCLC) and neuroendocrine prostate cancer cells. We assessed the safety and feasibility of the DLL3-targeted imaging tracer [89Zr]Zr-DFO-SC16.56 (composed of the anti-DLL3 antibody SC16.56 conjugated to p-SCN-Bn-deferoxamine [DFO] serving as a chelator for zirconium-89) in patients with neuroendocrine-derived cancer. We conducted an open-label, first-in-human study of immunoPET-CT imaging with [89Zr]Zr-DFO-SC16.56. The study was done at Memorial Sloan Kettering Cancer Center, New York, NY, USA. Patients aged 18 years or older with a histologically verified neuroendocrine-derived malignancy and an Eastern Cooperative Oncology Group performance status of 0–2 were eligible. An initial cohort of patients with SCLC (cohort 1) received 37–74 MBq [89Zr]Zr-DFO-SC16.56 as a single intravenous infusion at a total mass dose of 2·5 mg and had serial PET-CT scans at 1 h, day 1, day 3, and day 7 post-injection. The primary outcomes of phase 1 of the study (cohort 1) were to estimate terminal clearance half-time, determine whole organ time-integrated activity coefficients, and assess the safety of [89Zr]Zr-DFO-SC16.56. An expansion cohort of additional patients (with SCLC, neuroendocrine prostate cancer, atypical carcinoid tumours, and non-small-cell lung cancer; cohort 2) received a single infusion of [89Zr]Zr-DFO-SC16.56 at the same activity and mass dose as in the initial cohort followed by a single PET-CT scan 3–6 days later. Retrospectively collected tumour biopsy samples were assessed for DLL3 by immunohistochemistry. The primary outcome of phase 2 of the study in cohort 2 was to determine the potential association between tumour uptake of the tracer and intratumoural DLL3 protein expression, as determined by immunohistochemistry. This study is ongoing and is registered with ClinicalTrials.gov , NCT04199741. Between Feb 11, 2020, and Jan 30, 2023, 12 (67%) men and six (33%) women were enrolled, with a median age of 64 years (range 23–81). Cohort 1 included three patients and cohort 2 included 15 additional patients. Imaging of the three patients with SCLC in cohort 1 showed strong tumour-specific uptake of [89Zr]Zr-DFO-SC16.56 at day 3 and day 7 post-injection. Serum clearance was biphasic with an estimated terminal clearance half-time of 119 h (SD 31). The highest mean absorbed dose was observed in the liver (1·83 mGy/MBq [SD 0·36]), and the mean effective dose was 0·49 mSv/MBq (SD 0·10). In cohort 2, a single immunoPET-CT scan on day 3–6 post-administration could delineate DLL3-avid tumours in 12 (80%) of 15 patients. Tumoural uptake varied between and within patients, and across anatomical sites, with a wide range in maximum standardised uptake value (from 3·3 to 66·7). Tumour uptake by [89Zr]Zr-DFO-SC16.56 was congruent with DLL3 immunohistochemistry in 15 (94%) of 16 patients with evaluable tissue. Two patients with non-avid DLL3 SCLC and neuroendocrine prostate cancer by PET scan showed the lowest DLL3 expression by tumour immunohistochemistry. One (6%) of 18 patients had a grade 1 allergic reaction; no grade 2 or worse adverse events were noted in either cohort. DLL3 PET-CT imaging of patients with neuroendocrine cancers is safe and feasible. These results show the potential utility of [89Zr]Zr-DFO-SC16.56 for non-invasive in-vivo detection of DLL3-expressing malignancies. National Institutes of Health, Prostate Cancer Foundation, and Scannell Foundation. [ABSTRACT FROM AUTHOR]

Purpose: Therapeutic hypothermia (TH) is widely acknowledged as one of the interventions for preventing hypoxic ischemic brain injury in comatose patients following cardiac arrest (CA). Despite its recognized efficacy, recent debates have questioned its effectiveness. This preclinical study evaluated the impact of TH on brain glucose metabolism, utilizing fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in a rat model of CA. Methods: Asphyxia CA was induced in Sprague-Dawley rats using vecuronium. Brain PET images using 18F-FDG were obtained from 21 CA rats, who were randomized to receive either TH or no intervention. Of these, 9 rats in the TH group received hypothermia under general anesthesia and mechanical ventilation for eight hours, while the remaining 12 rats in the non-TH group were observed without intervention. We conducted regional and voxel-based analyses of standardized uptake values relative to the pons (SUVRpons) to compare the two groups. Results: Survival rates were identical in both the TH and non-TH groups (67%). There was no discernible difference in the SUVRpons across the brain cortical regions between the groups. However, in a subgroup analysis of the rats that did not survive (n = 7), those in the TH group (n = 3) displayed significantly higher SUVRpons values across most cortical regions compared to those in the non-TH group (n = 4), with statistical significance after false-discovery rate correction (p < 0.05). Conclusions: The enhancement in SUVRpons due to TH intervention was only observed in the cortical regions of rats with severe encephalopathy that subsequently died. These findings suggest that the beneficial effects of TH on brain glucose metabolism in this asphyxia CA model may be confined to cases of severe ischemic encephalopathy. [ABSTRACT FROM AUTHOR]

We present a rare case of focal F-18-2-fluoro-2-deoxyglucose (FDG) uptake in the liver observed during a modified dual-time-point F-18 FDG positron emission tomography (PET)/computed tomography (CT), so-called early delayed scanning, in a 53-year-old woman diagnosed with breast cancer. This metastatic lesion was revealed in 80 min delayed images after FDG injection, but not in the usual one-hour images after injection. Modified dual-time-point F-18 FDG PET/CT is convenient because compared to the 2 h delayed images of dual-time-point PET/CT, it has a shorter scanning time and avoids additional radiation exposure. [ABSTRACT FROM AUTHOR]

Background: Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) has been suggested as a useful imaging method for diagnosing cyst infections in patients with autosomal dominant polycystic kidney disease (ADPKD). The aim of this article is to provide evidence-based data in this setting. Methods: A systematic literature review (exploring several bibliographic databases) and a bivariate meta-analysis were carried out to calculate the pooled diagnostic performance of [18F]FDG PET/CT in diagnosing probable cyst infection in ADPKD. Results: Ten studies (282 PET/CT scans and 249 patients) were included in the analysis. The pooled sensitivity and specificity of [18F]FDG PET/CT in this setting were 84.6% (95% confidence interval: 75.4–90.7) and 94.9% (95% confidence interval: 72.6–99.2), respectively, without statistical heterogeneity or significant publication bias. [18F]FDG PET/CT significantly changed patient management in more than half of ADPKD patients with suspected cyst infection. Conclusions: [18F]FDG PET/CT has high performance in diagnosing probable cyst infections in ADPKD patients with an impact on management in the majority of patients. Although more studies are warranted, the provided evidence-based data are an important step towards the integration of [18F]FDG PET/CT in clinical and diagnostic guidelines on probable cyst infection in ADPKD patients. [ABSTRACT FROM AUTHOR]

The accurate estimation of the tracer arterial blood concentration is crucial for reliable quantitative kinetic analysis in PET. In the current work, we demonstrate the automatic extraction of an image-derived input function (IDIF) from a CT AI-based aorta segmentation subsequently resliced to a dynamic PET series acquired on a Siemens Vision Quadra long-axial field of view scanner in 10 human subjects scanned with [15O]H2O. We demonstrate that the extracted IDIF is quantitative and in excellent agreement with a delay- and dispersion-corrected sampled arterial input function (AIF). Perfusion maps in the brain are calculated and compared from the IDIF and AIF, respectively, showed a high degree of correlation. The results demonstrate the possibility of defining a quantitatively correct IDIF compared with AIFs from the new-generation high-sensitivity and high-time-resolution long-axial field-of-view PET/CT scanners. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a condition characterized by inflammation in the arteries, is the main cause of cardiovascular disease (CVD), including heart attacks and strokes. While current treatments focus on lowering cholesterol levels, new anti-inflammatory strategies are being explored as potential therapies for atherosclerosis. These strategies involve targeting the immune system's role in atherosclerosis and have shown promise in reducing CVD risk. However, challenges such as the risk of infections and individual variability in drug response need to be addressed. Advances in technologies like single-cell transcriptomics and PET imaging are aiding in the deeper understanding of the immune landscape of atherosclerosis and the identification of potential drug targets and biomarkers. These developments may lead to personalized therapies for atherosclerosis in the future. [Extracted from the article]

Objective: To report our experience with 18F‐fluoro‐ethyl‐tyrosine (FET) positron emission tomography‐computed tomography (PET‐CT) co‐registered with magnetic resonance imaging (MRI) (FET‐PET/MRICR) in the care trajectory for persistent acromegaly. Design: Prospective case series. Patients: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options. Measurements: FET‐PET/MRICR was used to support decision‐making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery. Results: FET‐PET/MRICR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET‐PET/MRICR was fully concordant with conventional MRI, and in one patient partially concordant. FET‐PET/MRICR identified suggestive new foci in four other patients. Surgical re‐exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET‐PET/MRICR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF‐1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients. Conclusions: In patients with persisting acromegaly without a clear surgical target on MRI, FET‐PET/MRICR is a new tracer to provide additional information to aid decision‐making by the multidisciplinary pituitary team. [ABSTRACT FROM AUTHOR]

Background: Tau‐first cognitive proteinopathy (TCP) denotes a clinical phenotype of Alzheimer disease (AD) showing Florzolotau(18F) positron emission tomography (PET) positivity but a negative amyloid status. Aim: We explored the biological property of tau using longitudinal cognitive and neuroimaging data in TCP and compared with late‐onset AD (LOAD). Method: We enrolled 56 patients with LOAD, 34 patients with TCP, and 26 cognitive unimpaired controls. All of the participants had historical data of 2 to 4 three‐dimensional T1 images and 2 to 6 annual cognitive evaluations over a follow‐up period of 7 years. Tau topography was measured using Florzolotau(18F) PET. In the LOAD and TCP groups, we constructed tau or gray matter clusters covarying with the cognitive measurements. We used mediator analysis to explore the regional tau load as predictor, gray matter partitions as mediators, and significant cognitive test scores as outcomes. Longitudinal cognitive decline and cortical thickness degeneration pattern were analyzed using a linear mixed‐effects model. Results: The TCP group had longitudinal declines in nonexecutive domains. The deterministic factor predicting the short‐term memory score in TCP was the hippocampal volume and not directly via the medial and lateral temporal tau load. These features formed the conceptual differences with LOAD. Discussion: The biological properties of tau and the longitudinal cognitive‐imaging trajectory support the conceptual distinction between TCP and LOAD. TCP represents one specific entity featuring salient short‐term memory impairment, declines in nonexecutive domains, a slower gray matter degenerative pattern, and a restricted impact of tau. [ABSTRACT FROM AUTHOR]

Aim: Cognitive impairment is a common comorbidity in individuals with temporal lobe epilepsy (TLE), yet the underlying mechanisms remain unknown. This study explored the putative association between in vivo synaptic loss and cognitive outcomes in TLE patients by PET imaging of synaptic vesicle glycoprotein 2A (SV2A). Methods: We enrolled 16 TLE patients and 10 cognitively normal controls. All participants underwent SV2A PET imaging using [18F]SynVesT‐1 and cognitive assessment. Lithium chloride‐pilocarpine‐induced rats with status epilepticus (n = 20) and controls (n = 6) rats received levetiracetam (LEV, specifically binds to SV2A), valproic acid (VPA), or saline for 14 days. Then, synaptic density was quantified by [18F]SynVesT‐1 micro‐PET/CT. The novel object recognition and Morris water maze tests evaluated TLE‐related cognitive function. SV2A expression was examined and confirmed by immunohistochemistry. Results: Temporal lobe epilepsy patients showed significantly reduced synaptic density in hippocampus, which was associated with cognitive performance. In the rat model of TLE, the expression of SV2A and synaptic density decreased consistently in a wider range of brain regions, including the entorhinal cortex, insula, hippocampus, amygdala, thalamus, and cortex. We treated TLE animal models with LEV or VPA to explore whether synaptic loss contributes to cognitive deficits. It was found that LEV significantly exerted protective effects against brain synaptic deficits and cognitive impairment. Conclusion: This is the first study to link synaptic loss to cognitive deficits in TLE, suggesting [18F]SynVesT‐1 PET could be a promising biomarker for monitoring synaptic loss and cognitive dysfunction. LEV might help reverse synaptic deficits and ameliorate learning and memory impairments in TLE patients. [ABSTRACT FROM AUTHOR]

Introduction In the dopamine system, the mesolimbic pathway, including the dorsal striatum, underlies the reinforcing properties of tobacco smoking, and the mesocortical pathway, including the dorsolateral prefrontal cortex (dlPFC), is critical for cognitive functioning. Dysregulated dopamine signaling has been linked to drug-seeking behaviors and cognitive deficits. The dorsal striatum and dlPFC are structurally and functionally connected and are key regions for cognitive functioning. We recently showed that people who smoke have lower dlPFC dopamine (D2/3R) receptor availability than people who do not, which is related to poorer cognitive function. Aims and Methods The goal of this study was to examine the same brain-behavior relationship in the dorsal striatum. Twenty-nine (18 males) recently abstinent people who smoke and 29 sex-matched healthy controls participated in 2 same-day [11C]-(+)-PHNO positron emission tomography scans before and after amphetamine administration to provoke dopamine release. D2/3R availability (binding potential; BP ND) and amphetamine-induced dopamine release (%Δ BP ND) were calculated. Cognition (verbal learning and memory) was assessed with the CogState computerized battery. Results There were no group differences in baseline BP ND. People who smoke have a smaller magnitude %Δ BP ND in dorsal putamen than healthy controls (p  = .022). People who smoke perform worse on immediate (p  = .035) and delayed (p  = .011) recall than healthy controls. In all people, lower dorsal putamen BP ND was associated with worse immediate (p  = .006) and delayed recall (p  = .049), and lower %Δ BP ND was related to worse delayed recall (p  = .022). Conclusions Lower dorsal putamen D2/3R availability and function are associated with disruptions in cognitive function that may underlie difficulty with resisting smoking. Implications This study directly relates dopamine imaging outcomes in the dorsal striatum to cognitive function in recently abstinent people who smoke cigarettes and healthy controls. The current work included a well-characterized subject sample in terms of demographics, smoking characteristics, and a validated neurocognitive test of verbal learning and memory. The findings of this study extend previous literature relating dopamine imaging outcomes to cognition in recently abstinent people who smoke and people who do not smoke, expanding our understanding of brain-behavior relationships. [ABSTRACT FROM AUTHOR]

Background: Microvascular invasion (MVI) is a risk factor for postoperative recurrence of hepatocellular carcinoma (HCC), even in early-stage HCC. In small HCC ≤ 3 cm, treatment options include anatomical resection or non-anatomical resection, and MVI has a major effect on treatment decisions. We aimed to identify the predictors of MVI in small HCC ≤ 3 cm. Methods: We retrospectively studied 129 patients with very early or early-stage HCC ≤ 3 cm who had undergone 18F-fluorodeoxyglucose positron emission tomography/computed tomography and subsequent hepatic resection from January 2016 to August 2023. These patients were divided into the derivation cohort (n = 86) and validation cohort (n = 43). We examined the risk factors for MVI using logistic regression analysis, and established a predictive scoring system in the derivation cohort. We evaluated the accuracy of our scoring system in the validation cohort. Results: In the derivation cohort, a Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), prothrombin induced by vitamin K deficiency or antagonist-II (PIVKA-II), and metabolic tumor volume (MTV) were independent predictors of MVI. We established the scoring system using these three factors. In the validation test, there were no MVI-positive cases with a score of 0 and 1, and all cases were MVI-positive with a score of 4. Moreover, with a score ≥ 2, the sensitivity, specificity, and accuracy of our scoring system were 100%, 71.4%, and 81.4%, respectively. Conclusions: Our scoring system can accurately predict MVI in small HCC ≤ 3 cm, and could contribute to establishing an appropriate treatment strategy. [ABSTRACT FROM AUTHOR]

Introduction: Aims of the study were to assess the differences in the diagnostic efficacy of 68Ga-somatostatin receptor analogs (68Ga-SSAs) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting bone metastases in neuroendocrine neoplasm (NEN) and to analyze the correlation between imaging features and clinical features of BMs. Methods: We retrospectively analyzed the clinical and imaging data of 213 NEN patients who underwent 68Ga-SSA PET/CT and were finally diagnosed as BMs by pathology or follow-up. Of those, 103 patients underwent 18F-FDG PET/CT within 7 days after 68Ga-SSA PET/CT. Result: The BM detection rate of 68Ga-SSA PET/CT was higher than 18F-FDG PET/CT (86.4% vs. 66.0%, p = 0.02) in 103 patients with dual scanning. Meanwhile, the number of positive lesions in 68Ga-SSA PET/CT was significantly more than in 18F-FDG PET/CT (3.37 ± 1.95 vs. 2.23 ± 2.16, t = 4.137, p < 0.001). Most bone metastasis lesions presented as osteogenic change in CT (55.4%, 118/213). Concerning the primary tumor, the most frequent were of pancreatic origin (26.3%, 56/213), followed by rectal origin (22.5%, 48/213), thymic origin in 33 cases (15.5%), pulmonary origin in 29 cases (13.6%), paraganglioma in 20 cases (9.4%). The efficiency of 68Ga-SSA PET/CT to detect BMs was significantly correlated with the primary site (p = 0.02), with thymic carcinoid BMs being the most difficult to detect, and the positive rate was only 60.6% (20/33). However, 18F-FDG PET/CT positive rate was 76.92% (10/13) in thymic carcinoid BMs. In addition, the BMs of 7 patients in this study were detected by 68Ga-SSA PET earlier than CT for 4.57 months (range: 2–10 months). Conclusion:68Ga-SSA PET/CT has higher sensitivity for detecting the BMs of NEN than 18F-FDG and detects the BM earlier than CT. Moreover, 18F-FDG PET/CT should be a complement for diagnosing the BMs of thymic carcinoids. [ABSTRACT FROM AUTHOR]

Aims: Mutations in the MAPT gene encoding tau protein can cause autosomal dominant neurodegenerative tauopathies including frontotemporal dementia (often with Parkinsonism). In Alzheimer's disease, the most common tauopathy, synapse loss is the strongest pathological correlate of cognitive decline. Recently, Positron Emission Tomography (PET) imaging with synaptic tracers revealed clinically relevant loss of synapses in primary tauopathies; however, the molecular mechanisms leading to synapse degeneration in primary tauopathies remain largely unknown. In this study, we examined post‐mortem brain tissue from people who died with frontotemporal dementia with tau pathology (FTDtau) caused by the MAPT intronic exon 10 + 16 mutation, which increases splice variants containing exon 10 resulting in higher levels of tau with four microtubule‐binding domains. Methods: We used RNA sequencing and histopathology to examine temporal cortex and visual cortex, to look for molecular phenotypes compared to age, sex and RNA integrity matched participants who died without neurological disease (n = 12 FTDtau10 + 16 and 13 controls). Results: Bulk tissue RNA sequencing reveals substantial downregulation of gene expression associated with synaptic function. Upregulated biological pathways in human MAPT 10 + 16 brain included those involved in transcriptional regulation, DNA damage response and neuroinflammation. Histopathology confirmed increased pathological tau accumulation in FTDtau10 + 16 cortex as well as a loss of presynaptic protein staining and region‐specific increased colocalization of phospho‐tau with synapses in temporal cortex. Conclusions: Our data indicate that synaptic pathology likely contributes to pathogenesis in FTDtau10 + 16 caused by the MAPT 10 + 16 mutation. [ABSTRACT FROM AUTHOR]

• Endometriosis diagnosis is delayed on average by 6–7 years and requires invasive surgery. • PET imaging has shown potential as a non-invasive technique for detection of endometriosis. • Systematic review of the literature found 18F-FDG PET does not consistently identify endometriotic lesions. • Other existing PET tracers with biological plausibility in the detection of endometriosis warrant further investigation. Despite the profound impact of endometriosis worldwide, delays in diagnosis and suboptimal surveillance techniques are well-recognised issues. Case studies have reported incidental uptake of 18F-FDG PET tracer in endometriotic lesions. However, the utility of PET imaging as a non-invasive diagnostic tool for endometriosis is currently unclear. The purpose of this systematic review was to summarise the existing evidence and determine the value of available PET scanning techniques in the detection and monitoring of endometriosis. MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science were searched from conception to 05/03/23. Eligible studies included participants with a history of known or suspected endometriosis who underwent a PET scan for any indication. All PET tracers and protocols were eligible. Outcomes included correlation of PET tracer uptake with the presence of endometriosis seen at laparoscopy or confirmed on histology, sensitivity of tracer uptake, specificity of tracer uptake, site of lesions with tracer uptake, stage of lesions with tracer uptake, SUV max of endometriosis lesions and adverse reactions to PET imaging. The protocol for this review was registered with PROSPERO (ID: CRD42023405260). Eight studies describing 110 participants were eligible for inclusion. Six studies assessed 18F-FDG with combined PET-CT, one study assessed 18F-FDG PET alone, and the remaining study assessed PET-CT with an alternative tracer, 68Ga-DOTATATE. For 18F-FDG imaging, the correlation of PET avidity with lesions or sites of endometriosis ranged from 0-55 %. Pre-operative 68Ga-DOTATATE PET-CT detected endometriosis in 33 % of cases. All included studies were cohort studies, six were assessed to have low risk of bias, one with moderate risk and one with high risk of bias. Overall, 18F-FDG PET scanning does not appear to consistently identify endometriotic lesions, and therefore its reliability and usefulness in endometriosis diagnosis is limited. The utility of 68Ga-DOTATATE PET-CT remains uncertain. Findings are constrained by limited available evidence reporting outcomes of PET imaging for endometriosis. Other existing PET tracers with biological plausibility in the detection or monitoring of endometriosis warrant further investigation. [ABSTRACT FROM AUTHOR]

The evidence in the field of diagnosis, staging, and treatment of localised prostate cancer (PCa) is evolving rapidly. The 2024 European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management. The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa. The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence. A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment. The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management. This article is the summary of the guidelines for "curable" prostate cancer. Prostate cancer is "found" through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with "active surveillance", a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making. [ABSTRACT FROM AUTHOR]

Background and Objectives Amyloid positron emission tomography scans can enhance the accuracy of dementia diagnoses. However, the perspectives and experiences of people with cognitive impairment and their care partners undergoing an amyloid scan are less well understood. Therefore, this review aimed to identify and summarize qualitative studies exploring patient and care partner experiences of undergoing an amyloid scan. Research Design and Methods We searched Embase, MEDLINE, and PsychInfo in March 2024. Articles were screened for inclusion by 2 reviewers and critically appraised using the Joanna Briggs Institute Critical Appraisal Tool for Qualitative Studies. Data from the included studies were synthesized using thematic synthesis. Results We identified 10 papers from 6 studies. We identified 4 themes: (1) motivations for undergoing an amyloid scan, (2) experiences of receiving the result, (3) emotional responses to the result, and (4) actions in light of the scan result. Participants reported undergoing the scan to determine the cause of cognitive impairment. They described the information gained from the scan as helpful but struggled to recall the correct terminology or implications of the scan. Emotional responses to the scan varied depending on the scan result. In light of the scan result, the most common action was making advanced plans; however, this was mainly discussed among participants with elevated amyloid. Discussions and Implications Amyloid scans can provide useful and actionable information. However, learning the scan result could be distressing. Future research is needed to balance the potential benefits and harms of amyloid scans. [ABSTRACT FROM AUTHOR]

[18F]AlF‐NOTA‐octreotide ([18F]AlF‐OC) is a promising alternative for [68Ga]Ga‐DOTA‐somatostatin analogs (SSAs) in positron emission tomography (PET) imaging of the somatostatin receptor (SSTR). Our aim is to assess changes in TNM staging and differences in patient management between [18F]AlF‐OC PET/CT and [68Ga]Ga‐DOTA‐SSA PET/CT in the work‐up of neuroendocrine tumor (NET) patients. Patients who underwent both [18F]AlF‐OC and [68Ga]Ga‐DOTA‐TATE or [68Ga]Ga‐DOTA‐NOC PET/CT in our multicenter study (Pauwels et al., J Nucl Med.2023;63:632–638) with a NET were included for analysis. TNM staging was determined and compared for both tracers. For each patient, the blinded [68Ga]Ga‐DOTA‐SSA or [18F]AlF‐OC PET/CT images were presented in random order at a multidisciplinary team board. The images were presented together with clinical information and compared with previous SSTR and [18F]FDG PET/CT imaging. After a consensus decision for patient management was recorded, the board was presented with the PET/CT images from the other SSTR tracer and a decision was made for the second tracer. Differences in management were classified as major if it entailed an intermodality change and minor if it led to an intramodality change. Compared with [68Ga]Ga‐DOTA‐SSA, the use of [18F]AlF‐OC led to a change in 16/75 patients: TNM staging changes in 10/75 patients (13.3%; downstaging in 3/10, upstaging in 7/10) and differences in clinical management were seen in 10/75 patients (13.3%), leading to a major difference in 7/10 cases and a minor change in 3/10 cases. All 10 cases with a difference in patient management between both PET tracers were caused by additional lesion detection by [18F]AlF‐OC. The use of [18F]AlF‐OC did not impact TNM staging or clinical management in the large majority of the patients (86.7%), further validating the potential for routine clinical use of [18F]AlF‐OC PET/CT as an alternative for [68Ga]Ga‐DOTA‐SSA PET/CT. The trial is registered under ClinicalTrials.gov identifier NCT04552847 and EudraCT 2020–000549‐15. [ABSTRACT FROM AUTHOR]

Somatostatin receptor positron emission tomography with computerised tomography imaging (SRI) has a high sensitivity for the detection of small intestinal neuroendocrine tumors (siNET), which makes it ideal for follow‐up. The aim of the present study was to investigate whether follow‐up with SRI in patients with siNET led to any change in the treatment of the patient and if patient and/or tumour factors were associated with such change. Adults with siNET who had undergone at least two SRI scans between 2013 and 2021 were identified. Data on age, sex, comorbidities, tumour stage, grade, and most recent levels of serum Chromogranin A (CgA) and 24‐h urine 5‐hydroxyindoleacetic acid (5‐HIAA) before each SRI scan were obtained. The major change was defined as new treatment previously not received or discontinuation of ongoing treatment. Univariate and multivariate mixed models logistic regression on variables with a presumed biological relationship with major change and with backwards stepwise exclusion of variables with p >.1 was performed. A total of 164 patients with siNET diagnosis had undergone 570 SRI scans. The median follow‐up was 3.1 years. Only 82 of 570, 14%, of SRI scans led to a major change in treatment. Female sex, age below 75 years, elevated or missing CgA, elevated or missing urine 5‐HIAA, progress on last SRI scan and distant extrahepatic disease were all independently associated with increased odds ratios for major change after follow‐up with SRI. A small proportion of SRI scans (14%) led to a major change in treatment. Six independent risk factors with increased odds of major change, all available before each SRI scan, were identified. While validation of these risk factors is needed in a separate cohort, these findings could help clinicians individualise follow‐up for siNET patients in the future. In a retrospective cohort of 164 patients with siNET in the follow‐up setting, somatostatin receptor imaging led to major change of treatment in only 14% of cases. Female sex, age below 75 years, elevated or missing CgA, elevated or missing urine 5‐HIAA, progress on last SRI scan and distant extrahepatic disease were all independently associated with increased odds ratios for major change. The use of these risk factors might help to individualize follow‐up for siNET patients in the future. [ABSTRACT FROM AUTHOR]

Background: The physical function of elderly individuals reflects whether they have had a history of regular physical activity over the long term. Such indicators have been found to have a certain connection with cognitive function these years. However, there is limited research that associates it with mechanisms such as cerebral Aβ deposition. We aim to investigate this relationship and unveil the underlying mechanisms. Method: Physical function and cognition data of 4189 participants were obtained from the Chinese preclinical Alzheimer's disease study. Participants were divided into six groups according to disease severity. Among them, 1048 participants underwent the positron emission tomography‐computed tomography (PET‐CT) and plasma biomarker test. Grip strength and gait were combined into a score indicating physical function. Multiple linear regression models and logistic regression models were mainly used to conduct the analysis. Results: There was a significant positive correlation between physical function and cognitive function (R = 0.48, p < 0.001), independent of sex, age, apolipoprotein E‐ε4 genotype, and disease stages (p < 0.001). Physical function was effective in distinguishing individuals with cognitive impairment from those without (AUC = 0.835). Physical function was negatively associated with brain Aβ deposition (p = 0.008) and brain Aβ had an intermediary effect (p < 0.01) on the association between physical function and cognition in women. This association was mainly evident in the lateral parietal, lateral temporal, posterior cingulate, frontal, occipital, and precuneus regions. Physical function was negatively associated with plasma neurofilament light‐chain (Nfl) level (p < 0.001). Conclusions: Physical function is strongly associated with cognitive function in the Chinese elderly, and brain Aβ deposition partly mediates the linkage in women. Plasma Nfl can be used as a potential target for exercise intervention in cognitive function. Improving physical function will contribute to the alleviation of cognition decline. [ABSTRACT FROM AUTHOR]

Inconsistencies between Alzheimer's disease (AD) clinical trials and prevention studies using omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation can be largely attributed to differences in age, environmental factors, genetic factors, baseline n-3/n-6 intake, and disease stage. Changes in docosahexaenoic acid (DHA) brain uptake throughout AD progression are influenced by the apolipoprotein E ε4 (APOE4) allele and lifestyle factors, such as DHA intake or exercise, and can be monitored by DHA positron emission tomography (PET) brain imaging. APOE4 carriers are more susceptible to blood–brain barrier dysfunction, oxidative stress, neuroinflammation, and fatty acid oxidation with aging compared to noncarriers. We hypothesize that increasing n-3 PUFA intake provides APOE4 carriers with the highest potential for protection against AD dementia when implemented early in life, many years before the onset of cognitive decline. During the AD dementia phase, alternative strategies targeting neuroinflammation and PUFA metabolism may offer potential benefits. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), have important roles in human nutrition and brain health by promoting neuronal functions, maintaining inflammatory homeostasis, and providing structural integrity. As Alzheimer's disease (AD) pathology progresses, DHA metabolism in the brain becomes dysregulated, the timing and extent of which may be influenced by the apolipoprotein E ε4 (APOE4) allele. Here, we discuss how maintaining adequate DHA intake early in life may slow the progression to AD dementia in cognitively normal individuals with APOE4 , how recent advances in DHA brain imaging could offer insights leading to more personalized preventive strategies, and how alternative strategies targeting PUFA metabolism pathways may be more effective in mitigating disease progression in patients with existing AD dementia. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Trisomy 21, or Down syndrome (DS), predisposes individuals to early‐onset Alzheimer's disease (AD). While monoclonal antibodies (mAbs) targeting amyloid are approved for older AD patients, their efficacy in DS remains unexplored. This study examines amyloid positron emission tomography (PET) positivity (A+), memory function, and clinical status across ages in DS to guide mAb trial designs. METHODS: Cross‐sectional data from the Alzheimer Biomarker Consortium–Down Syndrome (ABC‐DS) was analyzed. PET amyloid beta in Centiloids classified amyloid status using various cutoffs. Episodic memory was assessed using the modified Cued Recall Test, and clinical status was determined through consensus processes. RESULTS: Four hundred nine DS adults (mean age = 44.83 years) were evaluated. A+ rates increased with age, with mean amyloid load rising significantly. Memory decline and cognitive impairment are also correlated with age. DISCUSSION: These findings emphasize the necessity of tailoring mAb trials for DS, considering age‐related AD characteristics. Highlights: There is rapid increase in prevalence of amyloid beta (Aβ) positron emission tomography (PET) positivity in Down syndrome (DS) after the age of 40 years.Aβ PET positivity thresholds have significant impact on prevalence rates in DS.There is a significant lag between Aβ PET positivity and clinical symptom onset in DS. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Spatial extent‐based measures of how far amyloid beta (Aβ) has spread throughout the neocortex may be more sensitive than traditional Aβ‐positron emission tomography (PET) measures of Aβ level for detecting early Aβ deposits in preclinical Alzheimer's disease (AD) and improve understanding of Aβ's association with tau proliferation and cognitive decline. METHODS: Pittsburgh Compound‐B (PIB)‐PET scans from 261 cognitively unimpaired older adults from the Harvard Aging Brain Study were used to measure Aβ level (LVL; neocortical PIB DVR) and spatial extent (EXT), calculated as the proportion of the neocortex that is PIB+. RESULTS: EXT enabled earlier detection of Aβ deposits longitudinally confirmed to reach a traditional LVL‐based threshold for Aβ+ within 5 years. EXT improved prediction of cognitive decline (Preclinical Alzheimer Cognitive Composite) and tau proliferation (flortaucipir‐PET) over LVL. DISCUSSION: These findings indicate EXT may be more sensitive to Aβ's role in preclinical AD than level and improve targeting of individuals for AD prevention trials. Highlights: Aβ spatial extent (EXT) was measured as the percentage of the neocortex with elevated Pittsburgh Compound‐B.Aβ EXT improved detection of Aβ below traditional PET thresholds.Early regional Aβ deposits were spatially heterogeneous.Cognition and tau were more closely tied to Aβ EXT than Aβ level.Neocortical tau onset aligned with reaching widespread neocortical Aβ. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Amyloid positron emission tomography (PET) acquisition timing impacts quantification. METHODS: In florbetaben (FBB) PET scans of 245 adults with and without cognitive impairment, we investigated the impact of post‐injection acquisition time on Centiloids (CLs) across five reference regions. CL equations for FBB were derived using standard methods, using FBB data collected between 90 and 110 min with paired Pittsburgh compound B data. Linear mixed models and t‐tests evaluated the impact of acquisition time on CL increases. RESULTS: CL values increased significantly over the scan using the whole cerebellum, cerebellar gray matter, and brainstem as reference regions, particularly in amyloid‐positive individuals. In contrast, CLs based on white matter–containing reference regions decreased across the scan. DISCUSSION: The quantification of CLs in FBB PET imaging is influenced by both the overall scan acquisition time and the choice of reference region. Standardized acquisition protocols or the application of acquisition time–specific CL equations should be implemented in clinical protocols. Highlights: Acquisition timing affects florbetaben positron emission tomography (PET) scan quantification, especially in amyloid‐positive participants.The impact of acquisition timing on quantification varies across common reference regions.Consistent acquisitions and/or appropriate post‐injection adjustments are needed to ensure comparability of PET data. [ABSTRACT FROM AUTHOR]

Despite periodic changes in the clinical definition of ARDS, imaging of the lung remains a central component of its diagnostic identification. Several imaging modalities are available to the clinician to establish a diagnosis of the syndrome, monitor its clinical course, or assess the impact of treatment and management strategies. Each imaging modality provides unique insight into ARDS from structural and/or functional perspectives. This review will highlight several methods for lung imaging in ARDS, emphasizing basic operational and physical principles for the respiratory therapist. Advantages and disadvantages of each modality will be discussed in the context of their utility for clinical management and decision-making. [ABSTRACT FROM AUTHOR]

Purpose: Alzheimer’s disease (AD) dementia may not be a single disease entity. Early-onset AD (EOAD) and late-onset AD (LOAD) have been united under the same eponym of AD until now, but disentangling the heterogeneity according to the age of sonset has been a major tenet in the field of AD research. Materials and Methods: Ninety-nine patients with AD (EOAD, n=54; LOAD, n=45) and 66 cognitively normal controls completed both [18F]THK5351 and [18F]flutemetamol (FLUTE) positron emission tomography scans along with structural magnetic resonance imaging and detailed neuropsychological tests. Results: EOAD patients had higher THK retention in the precuneus, parietal, and frontal lobe, while LOAD patients had higher THK retention in the medial temporal lobe. Intravoxel correlation analyses revealed that EOAD presented narrower territory of local FLUTE-THK correlation, while LOAD presented broader territory of correlation extending to overall parieto-occipito-temporal regions. EOAD patients had broader brain areas which showed significant negative correlations between cortical thickness and THK retention, whereas in LOAD, only limited brain areas showed significant correlation with THK retention. In EOAD, most of the cognitive test results were correlated with THK retention. However, a few cognitive test results were correlated with THK retention in LOAD. Conclusion: LOAD seemed to show gradual increase in tau and amyloid, and those two pathologies have association to each other. On the other hand, in EOAD, tau and amyloid may develop more abruptly and independently. These findings suggest LOAD and EOAD may have different courses of pathomechanism. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? What is the relationship between apathy, obtained by both self and study partner report, and in vivo Alzheimer's disease (AD) pathology in community-dwelling older adults during the earliest stages of AD? • What is the main finding of this study? Higher study partner-reported participant apathy, but not self-reported apathy, is cross-sectionally associated with cortical amyloid-β and temporal lobe tau. Findings held when we controlled for depressive symptoms and were observed starting in the preclinical stage of Alzheimer's disease (AD). • What is the meaning of the finding? Our findings suggest that AD-pathology-associated apathy in older adults may arise in preclinical AD, at the transition to cognitive impairment, and best be captured by study partner or collateral report. We examined relationships between apathy (self and study-partner-reported) and markers of Alzheimer's disease (AD) in older adults. The study utilized a well-characterized sample of participants from the Harvard Aging Brain Study (HABS), a longitudinal cohort study. Participants were cognitively unimpaired without clinically significant neuropsychiatric symptoms at HABS baseline. The dependent variables, apathy evaluation scale-self (AES-S) and informant (AES-I), were administered cross-sectionally between years 6–9 and compared to the independent variables, amyloid and tau PET neuroimaging, from the same year. Community-dwelling participants assessed at research visits in an academic medical center. Participants (n = 170) completed assessments within 1.5 years of their neuroimaging visit. At the time of apathy assessment, N = 156 were cognitively unimpaired and 14 had progressed to mild cognitive impairment (n = 8) or dementia (n = 6). We utilized linear regression models to assess cross-sectional associations of AES-S and AES-I with AD PET imaging measures (beta-amyloid (Pittsburgh Compound B) and tau (Flortaucipir)), covarying for age, sex, education, and the time between PET scan-apathy assessment. AES-I was significantly associated with beta-amyloid and temporal lobe tau, and the associations were retained after further adjusting for depressive symptoms. The associations between AES-S and AD biomarkers were not significant. In an exploratory subgroup analysis of cognitively unimpaired individuals with elevated Aβ, we observed an association between AES-I and inferior temporal tau. Study-partner-reported, but not self-reported, apathy in older adults is associated with AD pathology, and we observed this relationship starting from the preclinical stage. Our findings highlight the importance of collateral information in capturing AD-related apathy. [ABSTRACT FROM AUTHOR]

To study in vivo the bioactivity of biodegradable magnesium implants and other possible biomaterials, we are proposing a previously unexplored application of PET-CT imaging, using available tracers to follow soft tissue and bone remodelling and immune response in the presence of orthopaedic implants. Female Wistar rats received either implants (Ti6Al7Nb titanium or WE43 magnesium) or corresponding transcortical sham defects into the diaphyseal area of the femurs. Inflammatory response was followed with [18F]FDG and osteogenesis with [18F]NaF, over the period of 1.5 months after surgery. An additional pilot study with [68Ga]NODAGA-RGD tracer specific to α v β 3 integrin expression was performed to follow the angiogenesis for one month. [18F]FDG tracer uptake peaked on day 3 before declining in all groups, with Mg and Ti groups exhibiting overall higher uptake compared to sham. This suggests increased cellular activity and tissue response in the presence of Mg during the initial weeks, with Ti showing a subsequent increase in tracer uptake on day 45, indicating a foreign body reaction. [18F]NaF uptake demonstrated the superior osteogenic potential of Mg compared to Ti, with peak uptake on day 7 for all groups. [68Ga]NODAGA-RGD pilot study revealed differences in tracer uptake trends between groups, particularly the prolonged expression of α v β 3 integrin in the presence of implants. Based on the observed differences in the uptake trends of radiotracers depending on implant material, we suggest that PET-CT is a suitable modality for long-term in vivo assessment of orthopaedic biomaterial biocompatibility and underlying tissue reactions. The study explores the novel use of positron emission tomography for the assessment of the influence that biomaterials have on the surrounding tissues. Previous related studies have mostly focused on material-related effects such as implant-associated infections or to follow the osseointegration in prosthetics, but the use of PET to evaluate the materials has not been reported before. The approach tests the feasibility of using repeated PET-CT imaging to follow the tissue response over time, potentially improving the methodology for adopting new biomaterials for clinical use. [Display omitted] [ABSTRACT FROM AUTHOR]

This cohort study investigates the association of changes in levels of plasma tau phosphorylated at threonine 181 and neurofilament light chain protein with psychotic symptoms in Alzheimer disease. Key Points: Question: Are longitudinal changes in levels of plasma tau phosphorylated at threonine 181 (p-tau181) and neurofilament light chain protein (NfL) associated with the emergence of psychotic symptoms in the context of Alzheimer disease (AD)? Findings: In this cohort study of 752 patients with mild cognitive impairment (MCI) and AD, the emergence of psychotic symptoms (delusions and hallucinations) was associated with increases in plasma p-tau181 and NfL levels. Meaning: Findings suggest that plasma levels of p-tau181 and NfL may be used as a biomarker for psychosis in MCI and AD, with potential implications for disease monitoring and treatment strategies. Importance: The emergence of psychotic symptoms in Alzheimer disease (AD) is associated with accelerated cognitive and functional decline that may be related to disease pathology. Objective: To investigate the longitudinal dynamics of plasma tau phosphorylated at threonine 181 (p-tau181) and neurofilament light chain protein (NfL) levels in association with the emergence of psychotic symptoms (delusions and hallucinations) in the context of AD. Design, Setting, and Participants: This cohort study used longitudinal data from the Alzheimer Disease Neuroimaging Initiative (ADNI). Baseline analyses compared patients with mild cognitive impairment (MCI) and AD (both with psychosis [AD+P] and without psychosis [AD-P]) and participants who were cognitively unimpaired (CU). For the longitudinal analysis, participants with MCI and AD were subdivided into patients with evidence of psychosis at baseline (AD+P baseline) and patients free of psychosis at baseline who showed incidence of psychosis over the course of the study (AD+P incident). Study data were analyzed between June and November 2023. Exposures: Plasma p-tau181 and NfL measures in individuals with MCI and AD, both with and without psychosis. Main Outcomes and Measures: Plasma p-tau181 and NfL quantifications up to 48 months and concurrent assessments of presence or absence of delusions and hallucinations via the Neuropsychiatric Inventory (NPI) questionnaire. Results: The cohort included 752 participants with AD (mean [SD] age, 74.2 [7.7] years; 434 male [57.7%]). A total of 424 CU participants had a mean (SD) age of 75.4 (6.6) years of whom 222 were female (52.4%). In the longitudinal analysis of p-tau181 trajectories of the AD+P group, the group of patients who showed incidence of psychosis over the course of follow-up (AD+P incident) demonstrated an associated increase in plasma p-tau181 levels compared with the group of patients who had psychosis at baseline (AD+P baseline) and showed an associated decrease in plasma p-tau181 levels (F4, 117 = 3.24; P =.01). The mean slope of p-tau181 change was significantly different in AD+P incident and AD+P baseline groups (F5,746 = 86.76, P <.0001) and when only individuals with amyloid-β positivity (Aβ+), which was determined using positron emission tomography, were compared (F5,455 = 84.60, P <.001). Patients who experienced psychosis at any time had increased levels of NfL relative to those who never experienced psychosis. Conclusions and Relevance: Results of this cohort study suggest that the emergence of psychosis in AD was associated with elevations in plasma levels of p-tau181, highlighting the potential utility of plasma p-tau181 as a biomarker of neuropsychiatric illness in AD, which could have implications for predictive and treatment response strategies. [ABSTRACT FROM AUTHOR]

Contrast-enhanced breast magnetic resonance imaging (MRI) is currently recommended as a screening tool for high-risk women and has been advocated for women with radiologically dense breast tissue. While breast MRI is acknowledged for its high sensitivity (with an exception for lower-grade ductal carcinoma in situ (DCIS) where emerging techniques like diffusion-weighted imaging offer improvement), its limitations include sensitivity to hormonal changes and a relatively high false-positive rate, potentially leading to overdiagnosis, increased imaging uncertainty, and unnecessary biopsies. These factors can exacerbate patient anxiety and impose additional costs. Molecular imaging with breast-targeted Positron Emission Tomography (PET) has shown the capability to detect malignancy independent of breast density and hormonal changes. Furthermore, breast-targeted PET has shown higher specificity when compared with MRI. However, traditional PET technology is associated with high radiation dose, which can limit its widespread use particularly in repeated studies or for undiagnosed patients. In this case report, we present a clinical application of low-dose breast imaging utilizing a breast-targeted PET camera (Radialis PET imager, Radialis Inc). The case involves a 33-year-old female patient who had multiple enhanced lesions detected on breast MRI after surgical removal of a malignant phyllodes tumor from the right breast. A benign core biopsy was obtained from the largest lesion seen in the left breast. One month after the MRI, 18F-fluorodeoxyglucose (18F-FDG) PET imaging session was performed using the Radialis PET Imager. Although the Radialis PET Imager has proven high count sensitivity and the capability to detect breast lesions with low metabolic activity (at a dose similar to mammography), no areas of increased 18F-FDG uptake were visualized in this particular case. The patient underwent a right-sided nipplesparing mastectomy and left-sided lumpectomy, with bilateral reconstruction. The excised left breast tissue was completely benign, as suggested by both core biopsy and the PET results. The case presented highlights a promising clinical application of low-dose breast-targeted PET imaging to mitigate the uncertainty associated with MRI while keeping radiation doses within the safe range typically used in X-ray mammography. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) targeted tracers show increased uptake in several malignancies, indicating a potential for peptide radioligand therapy. Intra-arterial injection of radiotracers can increase the therapeutic window. This study aimed to evaluate the feasibility of intra-arterial injection of [68Ga]Ga-PSMA-11 for intrahepatic cholangiocarcinoma and compare tracer uptake after intrahepatic arterial injection and intravenous injection. Three patients with intrahepatic cholangiocarcinoma received [68Ga]Ga-PSMA-11 through a hepatic arterial infusion pump, followed by positron emission tomography/computed tomography (PET/CT). Two-three days later, patients underwent PET/CT after intravenous [68Ga]Ga-PSMA-11 injection. All tumours showed higher uptake on the intra-arterial scan compared with the intravenous scan: the intra-arterial / intravenous standardised uptake value normalised by lean body mass ratios were 1.40, 1.46, and 1.54. Local intra-arterial PSMA injection is possible in patients with intrahepatic cholangiocarcinoma. Local injection increases tumour-to-normal tissue ratios, increasing the therapeutic window for theranostic applications. Relevance statement: Intra-arterial Prostate specific membrane antigen (PSMA) injection increases the therapeutic window for potential theranostic application in intrahepatic cholangiocarcinoma. Key Points: Three patients with intrahepatic cholangiocarcinoma underwent PET/CT after intra-arterial and intravenous injection of [68Ga]Ga-PSMA-11. Intra-arterial injection showed higher uptake than intravenous injection. PSMA-targeted imaging could be valuable for a subset of intrahepatic cholangiocarcinoma patients. [ABSTRACT FROM AUTHOR]

Objective: To identify whether Banxia Xiexin Decoction (BXD) alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 mice. Methods: Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table (n=15 per group), including a model group (MG), a liraglutide group (LG) and a BXD group (BG). Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group (CG). Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg•d) for 3 months, while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection (25 nmol/kg) for 3 months. Firstly, liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of BXD. Then, the cognitive deficits, Aβ pathological change and synaptic plasticity markers, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), were measured in APP/PS1 mice. Brain glucose uptake was detected by micropositron emission tomography. Intestinal microbial constituents were detected by 16S rRNA sequencing. The levels of intestinal glucagon-like peptide 1 (GLP-1) and cerebral GLP-1 receptor (GLP-1R), as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3β (PI3K/Akt/GSK3β) insulin signaling pathway were determined by immunohistochemical (IHC) staining and Western blot analysis, respectively. Results: BXD ameliorated cognitive deficits and Aβ pathological features (P<0.01). The expressions of SYP and PSD95 in the BG were higher than those in the MG (P<0.01). Brain glucose uptake in the BG was higher than that in the MG (P<0.01). The intestinal microbial composition in the BG was partially reversed. The levels of intestinal GLP-1 in the BG were higher than those in the MG (P<0.01). Compared with the MG, the expression levels of hippocampal GLP-1R, Akt, PI3K and p-PI3K in the BG were significantly increased (P<0.01), while the levels of GSK3β were reduced (P<0.01). Conclusion: BXD exhibited protective effects against Alzheimer's disease by regulating the gut microbiota/GLP-1/GLP-1R, enhancing PI3K/Akt/GSK3β insulin signaling pathway, and improving brain glucose metabolism. [ABSTRACT FROM AUTHOR]

This study explores a multi-modal machine-learning-based approach to classify solitary pulmonary nodules (SPNs). Non-small cell lung cancer (NSCLC), presenting primarily as SPNs, is the leading cause of cancer-related deaths worldwide. Early detection and appropriate management of SPNs are critical to improving patient outcomes, necessitating efficient diagnostic methodologies. While CT and PET scans are pivotal in the diagnostic process, their interpretation remains prone to human error and delays in treatment implementation. This study proposes a machine-learning-based network to mitigate these concerns, integrating CT, PET, and manually extracted features in a multi-modal manner by integrating multiple image modalities and tabular features). CT and PET images are classified by a VGG19 network, while additional SPN features in combination with the outputs of VGG19 are processed by an XGBoost model to perform the ultimate diagnosis. The proposed methodology is evaluated using patient data from the Department of Nuclear Medicine of the University Hospital of Patras in Greece. We used 402 patient cases with human annotations to internally validate the model and 96 histopathological-confirmed cases for external evaluation. The model exhibited 97% agreement with the human readers and 85% diagnostic performance in the external set. It also identified the VGG19 predictions from CT and PET images, SUVmax, and diameter as key malignancy predictors. The study suggests that combining all available image modalities and SPN characteristics improves the agreement of the model with the human readers and the diagnostic efficiency. [ABSTRACT FROM AUTHOR]

Gallium-68 [t1/2: 67.7 min, β+ (89 %)] has application in PET imaging mainly for prostate cancer and neuroendocrine tumours. Gallium-68 is generally obtained from a 68Ge/68Ga generator. It is therefore an important task to prepare 68Ge (t1/2 = 271 days) radiochemical for the manufacture of 68Ge/68Ga generator to cater for the needs of various nuclear medicine centres. Germanium-68 has been produced successfully after irradiation of indigenously developed Ga–Ni targets in a 30 MeV cyclotron and chemical processing of the irradiated targets using an indigenous semi-automated module. The Ga–Ni targets were prepared by an electroplating method. The 68Ge has been radiochemically separated from irradiated Ga–Ni targets using Sephadex G-25 column chromatography. The chemical separation yield and radionuclidic purity of 68Ge were about 70 % (n = 3) and about 98.3 % (n = 3), respectively. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a reparative response triggered by liver injury. Non‐invasive assessment and staging of liver fibrosis in patients with chronic liver disease are of paramount importance, as treatment strategies and prognoses depend significantly on the degree of fibrosis. Although liver fibrosis has traditionally been staged through invasive liver biopsy, this method is prone to sampling errors, particularly when biopsy sizes are inadequate. Consequently, there is an urgent clinical need for an alternative to biopsy, one that ensures precise, sensitive, and non‐invasive diagnosis and staging of liver fibrosis. Non‐invasive imaging assessments have assumed a pivotal role in clinical practice, enjoying growing popularity and acceptance due to their potential for diagnosing, staging, and monitoring liver fibrosis. In this comprehensive review, we first delved into the current landscape of non‐invasive imaging technologies, assessing their accuracy and the transformative impact they have had on the diagnosis and management of liver fibrosis in both clinical practice and animal models. Additionally, we provided an in‐depth exploration of recent advancements in ultrasound imaging, computed tomography imaging, magnetic resonance imaging, nuclear medicine imaging, radiomics, and artificial intelligence within the field of liver fibrosis research. We summarized the key concepts, advantages, limitations, and diagnostic performance of each technique. Finally, we discussed the challenges associated with clinical implementation and offer our perspective on advancing the field, hoping to provide alternative directions for the future research. [ABSTRACT FROM AUTHOR]

Amyloid plaques and tau tangles are the hallmark pathologic features of Alzheimer's disease (AD). Traditionally, these changes are identified in vivo via cerebrospinal fluid (CSF) analysis or positron emission tomography (PET) scans. However, these methods are invasive, expensive, and resource-intensive. To address these limitations, there has been ongoing research over the past decade to identify blood-based markers for AD. Despite the challenges posed by their extremely low concentrations, recent advances in mass spectrometry and immunoassay techniques have made it feasible to detect these blood markers of amyloid and tau deposition. Phosphorylated tau (p-tau) has shown greater promise in reflecting amyloid pathology as evidenced by CSF and PET positivity. Various isoforms of p-tau, distinguished by their differential phosphorylation sites, have been recognized for their ability to identify amyloid-positive individuals. Notable examples include p-tau181, p-tau217, and p-tau235. Among these, p-tau217 has emerged as a superior and reliable marker of amyloid positivity and, thus, AD in terms of accuracy of diagnosis and ability for early prognosis. In this narrative review, we aim to elucidate the utility of p-tau217 as an AD marker, exploring its underlying basis, clinical diagnostic potential, and relevance in clinical care and trials. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases, particularly myocardial ischemia from coronary artery obstruction, remain a leading cause of global morbidity. This review explores cardiac molecular magnetic resonance imaging (mMRI) and other molecular imaging techniques for the evaluation of myocardial ischemia, scarring, and viability. Results and findings: mMRI imaging methods provide detailed information on myocardial ischemia, edema, and scar tissue using techniques like cine imaging, T1 and T2 mapping, and gadolinium-based contrast agents. These methods enable the precise assessment of the myocardial tissue properties, crucial in diagnosing and treating cardiovascular diseases. Advanced techniques, such as the T1ρ and RAFFn methods, might provide enhanced contrast and sensitivity for the detection of myocardial scarring without contrast agents. Molecular probes, including gadolinium-based and protein-targeted contrast agents, improve the detection of molecular changes, facilitating early diagnosis and personalized treatment. Integrating MRI with positron emission tomography (PET) combines the high spatial and temporal resolution with molecular and functional imaging. Conclusion: Recent advancements in mMRI and molecular imaging have changed the evaluation of myocardial ischemia, scarring, and viability. Despite significant progress, extensive research is needed to validate these techniques clinically and further develop imaging methods for better diagnostic and prognostic outcomes. [ABSTRACT FROM AUTHOR]

Background: The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance. Methods: Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested. Results: MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus. Conclusion: Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance. [ABSTRACT FROM AUTHOR]

The combination of high-density, high-time-resolution inorganic scintillation crystals such as Lutetium Yttrium Oxyorthosilicate (LYSO), Yttrium Orthosilicate (YSO) and Bismuth Germanate (BGO) with Silicon Photomultiplier (SiPM) sensors is widely employed in medical imaging, particularly in Positron Emission Tomography (PET), as well as in modern particle physics detectors for precisely timing sub-detectors and calorimeters. During the assembly of each module, following individual component testing, the crystals and SiPMs are bonded together using optical glue and enclosed in a light-tight, temperature-controlled cooling box. After integration with the readout electronics, the bonding is initially tested. The final readout electronics typically comprise Application-Specific Integrated Circuits (ASICs) or low-power Analog-to-Digital Converters (ADCs) and amplifiers, designed not to heat up the temperature-sensitive SiPM sensors. However, these setups are not optimal for testing the optical bonding. Specific setups were developed to test the LYSO + SiPM modules that are already bonded but not enclosed in a box. Through large data collection, small deviations in bonding can be detected if the SiPMs and LYSOs have been thoroughly tested before our measurement. The Monte Carlo simulations we used to study how parameters—which are difficult to measure in the laboratory (LYSO absorption length, refractive index of the coating)—affect the final result. Our setups for particle physics and PET applications are already in use by research institutes and industrial partners. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) causes major public health problems worldwide. Fighting TB requires sustained efforts in health prevention, diagnosis and treatment. Previous literature has shown that conventional diagnostic methods like X-ray and sputum microscopy often miss early or extrapulmonary TB due to their limited sensitivity. Blood tests, while useful, lack the anatomical detail needed for precise localization of TB lesions. A possible step forward in the fight against TB could be the use of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and Computed Tomography (CT). This meta-analysis discusses the current literature, including the methods, results and implications of using FDG-PET-CT in the early diagnosis of TB. Analysis of the studies showed that the sensitivity of FDG-PET-CT as a potential method for early detection of TB was 82.6%. [ABSTRACT FROM AUTHOR]