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Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS) affect millions and present significant challenges in healthcare and treatment costs. The debate in the field pivots around two hypotheses: synaptic spread and selective vulnerability. Pioneers like Virginia Lee and John Trojanowski have been instrumental in identifying key proteins (tau, alpha-synuclein, TDP-43) central to these diseases. The synaptic spread hypothesis suggests a cell-to-cell propagation of pathogenic proteins across neuronal synapses, influencing disease progression, with studies highlighting the role of proteins like alpha-synuclein and amyloid-beta in this process. In contrast, the selective vulnerability hypothesis proposes inherent susceptibility of certain neurons to degeneration due to factors like metabolic stress, leading to protein aggregation. Recent advancements in neuroimaging, especially PET/MRI hybrid imaging, offer new insights into these mechanisms. While both hypotheses offer substantial evidence, their relative contributions to neurodegenerative processes remain to be fully elucidated. This uncertainty underscores the necessity for continued research, with a focus on these hypotheses, to develop effective treatments for these devastating diseases.

Background: Cardiovascular disease is a leading cause of illness and death globally, primarily due to atherosclerosis. This disease reduces blood flow and oxygen delivery to organs, and when it affects the carotid arteries, it can lead to cognitive impairment and dementia. In a population of 104 individuals, comprising both healthy controls and individuals at elevated risk for developing cardiovascular diseases (CVD) due to identified risk factors, we used PET imaging with 18F-fluorodeoxyglucose (FDG) to assess cerebral glucose metabolism and 18F-sodium fluoride (NaF) to detect atherosclerotic calcification. Our statistical analysis revealed significant differences in metabolic activity between healthy and at-risk individuals in specific brain regions. 18F-FDG uptake in the brain varied inversely with respect to the clinical assessment of cardiovascular risk in regions such as the cuneus (β = −0.030, SE = 0.014, p = 0.035), middle occipital gyrus (β = −0.032, SE = 0.011, p = 0.005), and posterior cingulate gyrus (β = −0.032, SE = 0.015, p = 0.044). In contrast, areas including the basis pontis (β = 0.025, SE = 0.012, p = 0.038) and the pons (β = 0.034, SE = 0.013, p = 0.008) exhibited direct correlations. Notably, carotid 18F-NaF uptake had inverse associations with 18F-FDG uptake in the cerebellum (β = −0.825, SE = 0.354, p = 0.021), medulla (β = −0.888, SE = 0.405, p = 0.029), and posterior cingulate gyrus (β = −1.253, SE = 0.567, p = 0.028), while increased carotid calcification influenced metabolic activity in the fusiform gyrus (β = 1.660, SE = 0.498, p = 0.001) and globus pallidus (β = 1.505, SE = 0.571, p = 0.009). We observed that atherosclerotic plaque accumulation, especially in the carotid arteries, has potential implications for metabolic changes in brain regions governing cognition, emotion, sensory perception, and motor activities. Our findings underscore the possible early interventions that can be used to preempt or delay cognitive deterioration linked with cardiovascular ailments.

Langerhans cell histiocytosis (LCH) is a complex disorder characterized by the clonal proliferation of Langerhans cells, primarily affecting children and adolescents. This condition exhibits a wide spectrum of clinical presentations, necessitating a multidisciplinary approach for diagnosis, treatment, and follow-up. Cutaneous manifestations of LCH are significant, mimicking common dermatoses and posing diagnostic challenges. [18F]Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) has emerged as an important tool in the evaluation of pediatric LCH, offering insights into disease activity, extent, and therapeutic response. Moreover, FDG-PET provides a non-invasive means to distinguish between active LCH skin lesions and other dermatological conditions with similar clinical appearances, enhancing diagnostic accuracy and aiding in disease monitoring. This educational review summarizes the utility of nuclear imaging techniques, with a focus on PET scans, in the diagnosis and management of cutaneous pediatric LCH. A comprehensive literature search identified seven relevant articles, including retrospective studies and case reports. These studies highlight the efficacy of FDG-PET in localizing active LCH skin lesions, monitoring disease activity, and guiding treatment decisions. FDG-PET represents a valuable imaging modality for dermatologists, oncologists, and pediatricians managing pediatric LCH patients with cutaneous involvement. This non-invasive technique contributes to improved diagnostic accuracy and facilitates early intervention, ultimately enhancing patient care and outcomes.

Cerebrovascular disease (CVD) is a global health concern, and early detection is crucial for effective intervention. This case report presents a 31-year-old male patient with multiple cardiac risk factors who underwent positron emission tomography/computed tomography (PET/CT) with 18F-sodium fluoride (NaF) and 18F-fluorodeoxyglucose (FDG) to evaluate for the presence and degree of atherosclerosis in the aorta, carotid arteries, coronary arteries, iliac arteries, and the femoral arteries. Elevated NaF uptake within the bilateral carotid arteries signified substantial ongoing vascular microcalcification. Reduced global brain metabolism and region-specific hypometabolism measured with FDG PET indicated potential cerebrovascular mechanisms that may be influencing neurological function. The findings highlight the potential of emerging PET tracers, such as NaF, to improve the diagnostic accuracy and therapeutic management of CVD. This case emphasizes the importance of a comprehensive diagnostic approach as well as continued investigation into CVD pathophysiology using PET-based techniques, which may guide the development of innovative therapeutic strategies.

Introduction Atherosclerosis, the occlusion of arteries due to the accumulation of fatty substances, cholesterol, calcium, and fibrin in the arterial walls, can result in reduced blood flow and a subsequent decrease in oxygen delivery to the organs supplied by the affected artery, including the brain. Positron emission tomography‐computed tomography (PET‐CT) utilizing 18F‐fluorodeoxyglucose (FDG) and 18F‐Sodium Fluoride (NaF) have demonstrated efficacy in the assessment of cerebral glucose metabolism and atherosclerotic calcification, respectively. However, the reported literature has not clearly correlated arterial disease throughout the body with cerebral hypometabolism. Utilizing a novel integration of FDG and NaF PET/CT imaging, our study explores the link between cardiovascular risk factors and regional cerebral metabolism. Methods We compared 79 healthy controls (mean age 44.5 ± 13.8 years, 53.2% males) and 40 individuals (mean age 55.9 ± 11.9 years, 50% males) at increased risk for cardiovascular disease (CVD) as assessed by the systematic coronary risk evaluation (SCORE) tool. All subjects underwent whole‐body FDG‐PET/CT imaging. [18F]fluoride PET/CT imaging was performed using hybrid PET/CT scanners with image correction and reconstruction processes following standard protocols. The quantitative regional analysis of PET images was performed using MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, Ohio). 70 whole brain structures were analyzed in each subject. MIMneuro provided region‐based analysis, with z‐scores generated by comparing the patient to the selected age‐matched set of normal controls. Using OsiriX MD software, [18F]fluoride PET/CT scans were analyzed with regions of interest (ROIs) manually drawn to assess carotid calcification and standardized uptake value mean (SUVmean), along with ROI volume values. Correlations between the degree of molecular calcification and cerebral FDG uptake in patients with cardiovascular risk factors were evaluated using Pearson’s R, with the significance threshold set at P < 0.05. Results Unhealthy patients demonstrated significant negative correlations between increased calcification in the carotid arteries, as assessed by NaF‐PET, and metabolic activity in the anterior cingulate (r = ‐0.42, p = 0.008) and cingulate regions (r = ‐0.34, p = 0.036). Conversely, healthy patients exhibited significant positive correlations in the pons (r = 0.25, p = 0.042) and pontine tegmentum (r = 0.34, p = 0.005), suggestive of a compensatory mechanism to maintain autonomic and motor functions. Conclusion The present study provides insight regarding the interplay between arterial calcification and neural metabolic activity, particularly as it pertains to regions supplied by the anterior cerebral artery. Our investigation suggests that calcification in the carotid arteries, which give rise to the ACA, has a deleterious impact on the function of the cingulate gyrus. Additionally, the observed positive correlation in the pons and pontine tegmentum in healthy individuals raises intriguing questions regarding potential compensatory mechanisms that may help maintain autonomic and motor functions despite vascular impediments. Understanding the temporal progression of vascular calcification allows for the optimization of surgical strategy and timing, potentially reducing stroke risk and improving patient outcomes. These findings underscore the necessity of persistent surveillance and targeted management strategies concerning carotid calcification.

Introduction Patients with cognitive impairment often have a history of cardiovascular disease (CVD) or multiple cardiovascular risk factors (CRFs) such as hypertension, obesity, and hypercholesterolemia. The literature reports that CVD with CRFs may increase the risk of developing vascular dementia and Alzheimer’s Disease. 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) allows for the in vivo study of cerebral glucose metabolism, and can detect metabolic alterations in several neurological diseases. As we age, the brain undergoes both structural and functional changes; the regional distribution of these alterations mirrors cognitive decline. This study aims to assess the effect of aging on regional glucose uptake in subjects with known cardiovascular risk factors. Methods In total, 40 subjects (mean age 55.9 ± 11.89 years, 50% males) with known cardiovascular risk factors underwent FDG‐PET scanning, and 70 whole brain structures were analyzed in each subject. Participants were recruited from a group of patients with chest pain syndromes who were referred for coronary CT angiography. All subjects underwent whole‐body FDG‐PET/CT imaging 180 minutes after the administration of 4.0 MBq/kg dose of FDG. The quantitative regional analysis of PET images was performed using MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, Ohio). MIMneuro provides region‐based analysis, with z‐scores generated by comparing the patient to the selected age‐matched set of normal controls. Pearson’s R was calculated and evaluated for significance in all variables. The threshold for significance was set at P < 0.05. Results Various significant associations between age and FDG uptake across all 70 brain regions of interest were observed. In particular, age was found to have an inverse correlation with regional metabolism in the middle temporal gyrus (r= ‐0.364, p=0.021), superior frontal gyrus (r= ‐0.433, p=0.005), superior parietal lobule (r= ‐0.354, p=0.025), supplementary motor area (r= ‐0.436, p=0.005), and temporal operculum (r= ‐0.370, p=0.019). Conclusion The results demonstrate a significant inverse correlation between age and FDG uptake in five regions among individuals with cardiovascular risk factors. This information may be useful in the determination of whether such scans might be useful in the evaluation of patients with a history of CVD/CRF or with mild cognitive impairment (MCI). Previous literature has reported that increased medial temporal gyrus atrophy is a predictor of dementia in subjects with MCI, and alterations within this lobe mark the beginning of the disease process. Our strongest inverse correlation, the superior frontal gyrus, has been shown to be related to working memory; hypometabolism in this region has previously correlated with severity of cognitive impairments in attention, executive function, and language. Further research is needed to determine the potential for using FDG‐PET imaging as a tool for early detection and intervention for cognitive decline. If patients with CVD or CRFs can be properly diagnosed, if there exists a metabolic signature of regional functional change, intervention may prove highly beneficial for cognitive function, quality of life, and overall well‐being.

Introduction Atherosclerosis, the hardening and narrowing of the arteries, occurs due to the buildup of plaque on the inner walls of the arteries which can result in reduced blood flow to the organs and tissues. Risk factors such as smoking, chronic kidney disease, and aging can contribute to plaque formation. The gradual loss of elasticity in arterial walls and the presence of other risk factors, such as high blood pressure and diabetes, contribute to the increased risk of cardiovascular disease (CVD) observed in aging populations. Early detection through sensitive and specific imaging methods is important for the detection and treatment of CVD. 18F‐Sodium Fluoride positron emission tomography/computerized tomography (NaF‐PET/CT) can be utilized to detect and quantify molecular calcification and therefore early atherosclerosis in patients with CVD. Research has shown a positive correlation between NaF uptake in the common carotid arteries/thoracic aorta and cardiovascular/thromboembolic risk. This study aims to assess the effect of aging on NaF uptake in the left common carotid artery (LCC) in subjects with known cardiovascular risk factors. Methods In total, 36 subjects (mean age 55.4 ± 12.3 years, 50% males) with known cardiovascular risk factors underwent FDG‐PET/CT. Participants were recruited from a group of patients with chest pain syndromes who were referred for coronary CT angiography. Individuals who were not taking any blood pressure medications and who had a greater than 1% increased risk of fatal CVD, estimated by the systematic coronary risk evaluation tool, were eligible for inclusion into the at‐risk for CVD group. NaF PET/CT was performed 90 min after the intravenous injection of 2.2 MBq of NaF/kg. NaF uptake in the LCC was quantitatively assessed by measuring the blood‐pool‐corrected maximum standardized uptake value (SUVmean) on each axial slice. Pearson’s R was calculated and evaluated for significance in all variables. The threshold for significance was set at P < 0.05. Results A significant association between age in patients with cardiovascular risk factors and NaF uptake in the LCC artery was found. Age positively correlated with NaF uptake (r=0.472, p= 0.004) across all 36 patients. Conclusion Our results demonstrate that NaF uptake increases in the LCC with age in subjects with known cardiovascular risk factors. The strong association between age and calcification of the carotid arteries within a population of individuals with unfavorable cardiovascular and thromboembolic risk profiles demonstrates the potential of NaF PET/CT. NaF PET/CT may allow physicians to evaluate effectiveness of treatment and determine a patient's risk for CVD. However, additional trials are needed to further evaluate the associations found in this study and determine relevance in a clinical setting.

Introduction Emerging evidence suggests a robust association between cardiovascular disease (CVD) and cognitive decline, accentuating the necessity for early detection and intervention. 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) has proven efficacious in identifying metabolic neurological changes at a molecular level, even before conventional imaging methods can detect structural changes. This study analyzed regional glucose metabolism in individuals with known CVD risk factors. The detection of such metabolic changes could assist in determining the necessity and timing of vascular interventions, such as carotid endarterectomy (CEA) or carotid artery angioplasty with stenting (CAS), contributing to improved patient outcomes and reduced postoperative complications. Methods We compared 79 healthy controls (mean age 44.5 ± 13.8 years, 53.2% males) and 40 individuals (mean age 55.9 ± 11.9 years, 50% males) at increased risk for cardiovascular disease (CVD) as assessed by the systematic coronary risk evaluation tool. All subjects were grouped into two age‐matched cohorts: younger (

Glioblastomas (GBM) are highly invasive, malignant primary brain tumors. The overall prognosis is poor, and management of GBMs remains a formidable challenge, necessitating novel therapeutic strategies such as dendritic cell vaccinations (DCVs). While many early clinical trials demonstrate an induction of an antitumoral immune response, outcomes are mixed and dependent on numerous factors that vary between trials. Optimization of DCVs is essential; the selection of GBM-specific antigens and the utilization of 18F-fludeoxyglucose Positron Emission Tomography (FDG-PET) may add significant value and ultimately improve outcomes for patients undergoing treatment for glioblastoma. This review provides an overview of the mechanism of DCV, assesses previous clinical trials, and discusses future strategies for the integration of DCV into glioblastoma treatment protocols. To conclude, the review discusses challenges associated with the use of DCVs and highlights the potential of integrating DCV with standard therapies.

Atherosclerosis, a leading cause of mortality and morbidity worldwide, involves inflammatory processes that result in plaque formation and calcification. The early detection of the molecular changes underlying these processes is crucial for effective disease management. This study utilized positron emission tomography/computed tomography (PET/CT) with [18F] sodium fluoride (NaF) as a tracer to visualize active calcification and inflammation at the molecular level. Our aim was to investigate the association between cardiovascular risk factors and [18F] NaF uptake in the left and right common carotid arteries (LCC and RCC). A cohort of 102 subjects, comprising both at-risk individuals and healthy controls, underwent [18F] NaF PET/CT imaging. The results revealed significant correlations between [18F] NaF uptake and cardiovascular risk factors such as age (β = 0.005, 95% CI 0.003–0.008, p < 0.01 in LCC and β = 0.006, 95% CI 0.004–0.009, p < 0.01 in RCC), male gender (β = −0.08, 95% CI −0.173–−0.002, p = 0.04 in LCC and β = −0.13, 95% CI −0.21–−0.06, p < 0.01 in RCC), BMI (β = 0.02, 95% CI 0.01–0.03, p < 0.01 in LCC and β = 0.02, 95% CI 0.01–0.03, p < 0.01 in RCC), fibrinogen (β = 0.006, 95% CI 0.0009–0.01, p = 0.02 in LCC and β = 0.005, 95% CI 0.001–0.01, p = 0.01), HDL cholesterol (β = 0.13, 95% CI 0.04–0.21, p < 0.01 in RCC only), and CRP (β = −0.01, 95% CI −0.02–0.001, p = 0.03 in RCC only). Subjects at risk showed a higher [18F] NaF uptake compared to healthy controls (one-way ANOVA; p = 0.02 in LCC and p = 0.04 in RCC), and uptake increased with estimated cardiovascular risk (one-way ANOVA, p < 0.01 in LCC only). These findings underscore the potential of [18F] NaF PET/CT as a sensitive tool for the early detection of atherosclerotic plaque, assessment of cardiovascular risk, and monitoring of disease progression. Further research is needed to validate the technique’s predictive value and its potential impact on clinical outcomes.

Introduction Cerebrovascular disease (CVD), particularly carotid artery atherosclerosis, contributes substantially to global morbidity and mortality. The ability to precisely detect atherosclerosis is crucial, as it directly influences patient management, including decisions regarding surgical interventions. Given the high prevalence and severe outcomes of CVD, there is an urgent need for improved early detection methods. Utilizing a novel approach, this study pioneers the use of 18F‐sodium fluoride (NaF) PET/CT imaging for the early identification of microcalcification, a key marker of atherosclerosis. A nuanced understanding of vascular calcification's temporal progression may aid in optimally timing surgical interventions, such as carotid endarterectomy or carotid artery stenting, thereby reducing stroke risk. Methods Our study participant is a 31‐year‐old male with atrial fibrillation, multiple cardiovascular risk factors, and class 2 obesity, enrolled in the Cardiovascular Molecular Calcification Assessed by 18F‐NaF PET/CT (CAMONA) study. The patient underwent both FDG‐PET/CT and NaF‐PET/CT imaging. We utilized OsiriX MD software v.13.0.1 (Pixmeo SARL, Bernex, Switzerland), to compute the standardized uptake value (SUVmean), serving as a measure of disease progression in both the global brain and the bilateral carotid arteries. Subsequently, we employed MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, OH, USA) to conduct a comprehensive regional brain metabolism analysis, harnessing the power of an integrated anatomical atlas. Results NaF‐PET/CT imaging revealed elevated NaF uptake in the bilateral carotid arteries (z‐score = 0.012), suggesting notable microcalcification. Conversely, FDG‐PET/CT imaging revealed low FDG uptake in the carotid arteries, with an average SUVmean of 0.66 for both right and left carotids and a z‐score of −2.32. Analysis of global brain metabolism demonstrated decreased FDG uptake detected by FDG‐PET/CT (z‐score = ‐2.32). Concurrently, we identified a decline in regional brain metabolism, with prominent decreases observed in regions including the brainstem (z score = −1.95), medial temporal lobe (z‐score = −1.81), cerebellum (z–score = −2.13), hippocampus (z‐score = −2.13), inferior frontal gyrus (z‐score = −3.53), lateral orbital gyrus (z‐score = −3.24), and putamen (z‐score = −2.47) (Figure 1). Conclusion Our findings highlight the potential of NaF‐PET/CT imaging to enhance early detection of carotid artery atherosclerosis and cerebral hypometabolism. These results highlight the subtle, yet potent, potential of NaF‐PET/CT scans to detect active, asymptomatic cases where FDG‐PET/CT scans may not indicate high activity. The findings suggest that NaF‐PET could play a pivotal role in diagnosing and managing CVD where traditional tracers encounter limitations. Early recognition of these alterations facilitates clinical decision‐making, including determining the necessity and timing of surgical intervention. This advanced diagnostic tool presents an opportunity to improve pre‐operative assessments by providing insights into disease progression prior to macrocalcification development, a clear advantage over existing imaging modalities. The correlation between vascular calcification and decreased cerebral metabolism enhances our understanding of CVD pathophysiology, thereby paving the way for transformative therapeutic interventions. While these findings provide preliminary insight, further research is crucial to corroborate our results and delineate their potentially transformative implications on patient care, particularly in the context of surgical interventions.