FDG-PET in the diagnosis of primary progressive aphasia: a systematic review.

Primary progressive aphasia (PPA) is a disease known to affect the frontal and temporal regions of the left hemisphere. PPA is often an indication of future development of dementia, specifically semantic dementia (SD) for frontotemporal dementia (FTD) and logopenic progressive aphasia (LPA) as an atypical presentation of Alzheimer's disease (AD). The purpose of this review is to clarify the value of 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-positron emission tomography (PET) in the detection and diagnosis of PPA. A comprehensive review of literature was conducted using Web of Science, PubMed, and Google Scholar. The three PPA subtypes show distinct regions of hypometabolism in FDG-PET imaging with SD in the anterior temporal lobes, LPA in the left temporo-parietal junction, and nonfluent/agrammatic Variant PPA (nfvPPA) in the left inferior frontal gyrus and insula. Despite the distinct patterns, overlapping hypometabolic areas can complicate differential diagnosis, especially in patients with SD who are frequently diagnosed with AD. Integration with other diagnostic tools could refine the diagnostic process and lead to improved patient outcomes. Future research should focus on validating these findings in larger populations and exploring the therapeutic implications of early, accurate PPA diagnosis with more targeted therapeutic interventions.

The utility of PET imaging in depression.

This educational review article aims to discuss growing evidence from PET studies in the diagnosis and treatment of depression. PET has been used in depression to explore the neurotransmitters involved, the alterations in neuroreceptors, non-neuroreceptor targets (e.g., microglia and astrocytes), the severity and duration of the disease, the pharmacodynamics of various antidepressants, and neurobiological mechanisms of non-pharmacological therapies like psychotherapy, electroconvulsive therapy, and deep brain stimulation therapy, by showing changes in brain metabolism and receptor and non-receptor targets. Studies have revealed alterations in neurotransmitter systems such as serotonin, dopamine, GABA, and glutamate, which are linked to the pathophysiology of depression. Overall, PET imaging has furthered the neurobiological understanding of depression. Despite these advancements, PET findings have not yet led to significant changes in evidence-based practices. Addressing the reasons behind inconsistencies in PET imaging results, conducting large sample size studies with a more standardized methodological approach, and investigating further the genetic and neurobiological aspects of depression may better leverage PET imaging in future studies.

The Role of FDG-PET in the Evaluation of Hidradenitis Suppurativa: A Systematic Review.

Hidradenitis suppurativa (HS) is a chronic skin disorder characterized by nodules, comedones, and sinus tracts that often leave prominent scarring. In recent years, non-invasive imaging techniques have been used to assess the inflammatory activity, vascularization, and treatment response of lesions. Specifically, fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans may aid in identifying systemic inflammation in patients with HS, improving diagnosis. Inflamed hypermetabolic tissues exhibit a greater uptake of FDG due to increased glucose uptake and vascularity. A systematic review was conducted to summarize the utility of nuclear imaging techniques in the diagnosis and treatment follow-up of HS. PubMed, Scopus, and ScienceDirect databases were utilized for relevant articles discussing the utility of PET scans in managing HS. A total of 51 citations were identified in the initial search. Following the review of titles, abstracts, and duplicates, 43 articles were excluded, leaving a total of eight articles for analysis. Data were extracted from each article, encompassing the number of patients, imaging techniques employed, and final results. An analysis of the data demonstrated that FDG-PET showed evidence of identifying subclinical lesions of the disease, improving the visualization of HS, and providing an objective method of assessing severity.

Machine learning in the positron emission tomography imaging of Alzheimer's disease.

The utilization of machine learning techniques in medicine has exponentially increased over the last decades due to innovations in computer processing, algorithm development, and access to big data. Applications of machine learning techniques to neuroimaging specifically have unveiled various hidden interactions, structures, and mechanisms related to various neurological disorders. One application of interest is the imaging of Alzheimer's disease, the most common cause of progressive dementia. The diagnoses of Alzheimer's disease, mild cognitive impairment, and preclinical Alzheimer's disease have been difficult. Molecular imaging, particularly via PET scans, holds tremendous value in the imaging of Alzheimer's disease. To date, many novel algorithms have been developed with great success that leverage machine learning in the context of Alzheimer's disease. This review article provides an overview of the diverse applications of machine learning to PET imaging of Alzheimer's disease.

Neurological and Psychiatric Manifestations of Long COVID-19 and Their [18F]FDG PET Findings: A Review.

For more than two years, lingering sequalae of COVID-19 have been extensively investigated. Approximately 10% of individuals infected by COVID-19 have been found to experience long-term symptoms termed "long COVID-19". The neurological and psychiatric manifestations of long COVID-19 are of particular concern. While pathogenesis remains unclear, emerging imaging studies have begun to better elucidate certain pathological manifestation. Of specific interest is imaging with [18F]FDG PET which directly reflects cellular glycolysis often linked to metabolic and inflammatory processes. Seeking to understand the molecular basis of neurological features of long COVID-19, this review encompasses the most recent [18F]FDG PET literature in this area.

Stroke and molecular imaging: a focus on FDG-PET.

Stroke is the leading cause of disability worldwide, the second most common cause of dementia and the third leading cause of death. Though the etiology of stroke has been explored extensively, there remains open questions in the scientific and clinical study of stroke. Traditional imaging techniques, such as magnetic resonance imaging and computed tomography, have been applied extensively and remain mainstays in clinical practice. Nevertheless, positron emission tomography has proven to be a powerful molecular imaging tool in exploring the scientific aspects of neurological disease, and stroke remains an area of great interest. This review article examines the role of positron emission tomography in the study of stroke including its contributions to elaborating related pathophysiology and delving into possible clinical applications.

A prospective 18 F-fluorodeoxyglucose positron emission tomography/computed tomography study of the neurometabolic effects in cocaine use and HIV infection.

OBJECTIVES: HIV affects 36 million people globally with prevalence decreasing due to antiretroviral therapy (ART) and social awareness; transmission occurs during substance use. Cocaine usage independently affects brain activity and may result in reduced ART adherence. This study evaluates brain glucose metabolism measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in cocaine users with HIV infection. DESIGN: Sixty-three participants were categorized into groups: 36 HIV infected (HIV+) and 27 non-HIV infected (HIV-) individuals. Each group was further split into cocaine users (CO+) and non-cocaine users (CO-). Of the HIV+, half were cocaine users and half were not. Of the HIV-, 14 were cocaine users and 13 were not. 18 F-FDG-PET and low dose CT scans were performed on all participants. METHODS: Brain glucose metabolism was evaluated by 18 F-FDG uptake in the whole brain, cortex, basal ganglia, and cerebellum 120 min after injection. ROVER software was used for image analysis and regions of interest masks were applied via an adaptive threshold system. ANOVA tests and t -tests were performed to assess the respective differences between the four groups. RESULTS: Generally, the HIV+/CO+ group (group A) displayed the lowest levels of uptake whereas the HIV-/CO- group (group D) showed the highest; the HIV+/CO- and HIV-/CO+ groups (groups B and C) showed intermediate levels of activity across the whole brain, cortex, basal ganglia, and cerebellum. CONCLUSION: HIV infection and cocaine usage were independently associated with a decrease in brain glucose uptake as measured by 18 F-FDG PET/CT. When combined, positive HIV status and cocaine patients showed the most decreased 18 F-FDG uptake.

Role of Molecular Imaging with PET/MR Imaging in the Diagnosis and Management of Brain Tumors.

Gliomas are the most common primary brain tumors. Hybrid PET/MR imaging has revolutionized brain tumor imaging, allowing for noninvasive, simultaneous assessment of morphologic, functional, metabolic, and molecular parameters within the brain. Molecular information obtained from PET imaging may aid in the detection, classification, prognostication, and therapeutic decision making for gliomas. 18F-fluorodeoxyglucose (FDG) has been widely used in the setting of brain tumor imaging, and multiple techniques may be employed to optimize this methodology. More recently, a number of non-18F-FDG-PET radiotracers have been applied toward brain tumor imaging and are used in clinical practice.

A review of different methods used for quantification and assessment of FDG-PET/CT in multiple myeloma.

The quantification of positron emission tomography/computed tomography (PET/CT) in multiple myeloma (MM) is challenging. Different methods of PET/CT quantification for assessment of fluorodeoxyglucose (FDG) uptake in myeloma patients have been suggested. This is the first review article that focuses on the advantages and disadvantages of each approach. Use of the maximum standardized uptake value (SUVmax) showed some promise in prognostic stratification of MM patients. However, it is affected by noise and time of flight and is subject to high variability. Volumetric PET metrics such as total lesion glycolysis and metabolic tumor volume are other proposed approaches. The high number of osteolytic lesions in MM patients makes this approach difficult in clinical practice. In addition, evaluation of small focal lesions is subject to partial volume correction. CT-based segmentation for assessment of FDG radiotracer is recently introduced. The methodologies are highly reproducible, but the clinical values of the approaches are unclear and still under investigation. We also discuss the Italian Myeloma criteria for PET Use (IMPeTUs), which is a qualitative approach, as a point of comparison. The reproducibility of IMPeTUs depends heavily on the level of user experience. We recommend further studies for assessing the prognostic significance of CT-threshold approaches in the assessment of MM patients.

A Quasi-Experimental Study of Medicaid Expansion and Urban Mortality in the American Northeast.

Objectives: To investigate the association of state-level Medicaid expansion and non-elderly mortality rates from 1999 to 2018 in Northeastern urban settings. Methods: This quasi-experimental study utilized a synthetic control method to assess the association of Medicaid expansion on non-elderly urban mortality rates [1999-2018]. Counties encompassing the largest cities in the Northeastern Megalopolis (Washington D.C., Baltimore, Philadelphia, New York City, and Boston) were selected as treatment units (n = 5 cities, 3,543,302 individuals in 2018). Cities in states without Medicaid expansion were utilized as control units (n = 17 cities, 12,713,768 individuals in 2018). Results: Across all cities, there was a significant reduction in the neoplasm (Population-Adjusted Average Treatment Effect = -1.37 [95% CI -2.73, -0.42]) and all-cause (Population-Adjusted Average Treatment Effect = -2.57 [95%CI -8.46, -0.58]) mortality rate. Washington D.C. encountered the largest reductions in mortality (Average Treatment Effect on All-Cause Medical Mortality = -5.40 monthly deaths per 100,000 individuals [95% CI -12.50, -3.34], -18.84% [95% CI -43.64%, -11.67%] reduction, p = < 0.001; Average Treatment Effect on Neoplasm Mortality = -1.95 monthly deaths per 100,000 individuals [95% CI -3.04, -0.98], -21.88% [95% CI -34.10%, -10.99%] reduction, p = 0.002). Reductions in all-cause medical mortality and neoplasm mortality rates were similarly observed in other cities. Conclusion: Significant reductions in urban mortality rates were associated with Medicaid expansion. Our study suggests that Medicaid expansion saved lives in the observed urban settings.

Tau-PET imaging as a molecular modality for Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative condition. The definitive diagnosis of AD remains a post-mortem neuropathological study of the brain. Unfortunately, there are no established diagnostic criteria to achieve an accurate diagnosis of AD in a similarly objective fashion among living patients. Molecular imaging provides one way of enhancing clinical criteria where objective measures of AD correlate to the presence and progression of disease. In this article, the amyloid and tau hypotheses are considered with respect to pathological, imaging, and therapeutic studies. The value of beta-amyloid (Aß) PET and tau PET are ascertained. Subsequently, the binding characteristics and quality of Aß and tau tracers are explored. Finally, the value of Aß and tau imaging in AD can be determined relevant from in-vivo studies of AD patients. Considering the evolving literature in AD and PET imaging, it has become clear that PET can play a role in the diagnosis and prognosis of AD. The use of Aß imaging has been extensively studied with mixed results suggesting a limited clinical utility. Conversely, tau-PET has shown early success in similar applications as Aß imaging. Specifically, we find that there is value in FDG-PET and prospective utility in tau-PET. Ultimately, the community must acknowledge that the role of Aß imaging for diagnosing and managing AD is very limited and that FDG-PET will remain the study of choice at this time. Moreover, research efforts must continue to determine the prospective value of tau imaging to the assessment of this disease.

An Update on the State of Tau Radiotracer Development: a Brief Review.

Evolving scientific evidence has begun to point towards hyperphosphorylated tau as a major neurotoxic component in the pathophysiological development of many major neurodegenerative conditions. In response to a need for accurate and reliable diagnosis and disease monitoring in clinical and trial settings, there has been great effort put into the development of tau radiotracers. While first-generation and second-generation radiotracers have provided a basis for assessing tau, concerns of inadequate specificity and selectivity have continued to motivate further study of these radiotracers and the development of novel radiopharmaceuticals. Given the prospective scientific and clinical value of a valid tau radiotracer, the molecular neuroimaging community must be aware of the most recent developments in the realm of tau radiotracer development. This brief review article will critically overview the most established tau radiotracers and, most importantly, concentrate on the progress of more recently developed tau radiotracers.

Tau Imaging in Head Injury.

Tau proteins play a significant role in a variety of degenerative neurologic conditions. Postmortem neuropathology studies of victims of repeat and severe head trauma have defined a unique spatial expression of neurologic tauopathies in these individuals, known as chronic traumatic encephalopathy. Established and newly developed radiotracers are now being applied to head injury populations with the intent of diagnosis and disease monitoring. This review assesses the role of tau in head injury, the state of tau radiotracer development, and the potential clinical value of tau-PET as derived from head injury studies.

A Critical Review of PET Tracers Used for Brain Tumor Imaging.

The brain is a common site for metastases as well as primary tumors. Although evaluation of these malignancies with contrast-enhanced MR imaging defines current clinical practice, 18F-fluorodeoxyglucose (FDG)-PET has shown considerable utility in this area. In addition, many other tracers targeting various aspects of tumor biology have been developed and tested. This article discusses recent developments in PET imaging and the anticipated role of FDG and other tracers in the assessment of brain tumors.

Assessment of atherosclerosis in multiple myeloma and smoldering myeloma patients using 18F- sodium fluoride PET/CT.

BACKGROUND: To compare the NaF uptake in the thoracic aorta and whole heart, as an early indicator of atherosclerosis, in multiple myeloma (MM) and smoldering multiple myeloma (SMM) patients with a healthy control (HC) group. METHODS: Forty-four untreated myeloma patients (35 MM and nine SMM) and twenty-six age and gender-matched HC subjects were collected. Each individual's NaF uptake in three parts of the aorta (AA: ascending aorta, AR: aortic arch, DA: descending aorta) and the whole heart was segmented. Average global standardized uptake value means were derived by sum of the product of each slice area divided by the sum of those slice areas. Results were reported as target to background ratio (TBR). RESULTS: There was a significant difference between the NaF uptake in the thoracic aorta of myeloma and HC groups [AA (myeloma = 1.82 ± 0.21, HC = 1.24 ± 0.02), AR (myeloma = 1.71 ± 0.19, HC = 1.28 ± 0.03) and DA (myeloma = 1.96 ± 0.28, HC = 1.38 ± 0.03); P-values < 0.001]. The difference in the whole heart NaF uptake between two groups was also significant (P < 0.001). CONCLUSIONS: We observed a higher uptake of NaF in the thoracic aorta and whole heart of myeloma patients in comparison to the matched control group.

Magnetic resonance imaging-based partial volume-corrected 18F-sodium fluoride positron emission tomography in the femoral neck.

OBJECTIVES: 18F-sodium fluoride (NaF) is a radiotracer used in PET that reflects calcium metabolism and osteoblastic activity. In this study, we assessed the construct validity of a novel application of global assessment to measure NaF uptake in the femoral neck as a method of evaluating physiologic changes in osteoblastic metabolism with age. METHODS: Whole-body NaF-PET/computed tomography (CT) images and MRI of 24 male patients with a history of nonmetastatic prostate cancer between the ages of 36 and 82 years (67.8 ± 9.6) were analyzed. A region of interest delineated the entire femoral neck on the PET/CT image to determine the mean standardized uptake value (SUVmean). Correction for the partial volume effect was performed by measuring the volume of inert yellow bone marrow by MRI segmentation. Multiple linear regression was used to assess the relationship of uptake with age and body weight. RESULTS: The SUVmean with and without partial volume correction decreased with respect to age (P = 0.001 and P = 0.002, respectively). Body weight was not significantly related to any measured PET parameter. CONCLUSION: Our results support the use of global NaF uptake with magnetic resonance-derived partial volume correction in the femoral neck. Because osteoblastic metabolism is known to decrease with normal aging, the observed decrease in NaF uptake constitutes evidence for convergent validity, indicating that the proposed methodology likely reflects systemic osteoblastic activity. Future studies of this methodology are warranted in other instances of varying osteoblastic activity such as in metabolic bone diseases and for the evaluation of therapy targeting osteoblastic metabolism.

A critical review of radiotracers in the positron emission tomography imaging of traumatic brain injury: FDG, tau, and amyloid imaging in mild traumatic brain injury and chronic traumatic encephalopathy.

PURPOSE: Positron emission tomography (PET) has been widely utilized in the study of traumatic brain injury (TBI) for decades. While most applications of PET have attempted to assess neuronal function after TBI, more recently, novel radiotracers have sought to image biomarkers in the context of TBI and chronic traumatic encephalopathy (CTE). METHODS: This review will begin with an overview of TBI and CTE along with the acute and chronic pathophysiological consequences of TBI. Next, glycolysis, beta-amyloid, and tau protein radiotracers will be critically assessed in light of the most recent imaging studies available. CONCLUSIONS: Based on the scientific relevance of such radiotracers to the molecular processes of TBI and CTE along with the broader evidence of radiotracer specificity and selectivity, this review will weigh the strengths and weaknesses of each radiotracer. Nonetheless, the evidence indicates that PET will continue to be a powerful modality in the diagnosis of TBI-related conditions.

Correlation of whole-bone marrow dual-time-point 18F-FDG, as measured by a CT-based method of PET/CT quantification, with response to treatment in newly diagnosed multiple myeloma patients.

The practical application of dual-time-point-imaging (DTPI) technique still remains controversial. One of the issues is that current parameters of DTPI quantification suffer from some deficiencies, mainly limited sampling of the diseased sites by confining measurements to specific locations. We aimed to examine the correlation between the percent change from early to delayed scans in whole-bone marrow (WBM) 18F-FDG uptake, as measured by a CT-based method of PET/CT quantification, and response to treatment in multiple myeloma (MM) patients. Pre-treatment 18F-FDG-PET/CT scans of 36 newly diagnosed MM patients were collected in a prospective study at 1 h and 3 h post tracer injection (NCT02187731). A threshold algorithm based on bone Hounsfield units on CT was applied to segment and quantify WBM 18F-FDG uptake. Patients were separated into two treatment groups: high-dose therapy with autologous stem cell transplant (HDT) and non-high dose therapy (non-HDT). The International Response Criteria for MM patients was used to determine each patient's response to treatment. In the HDT group, WBM 18F-FDG uptake increased significantly in patients that had a poor response to treatment, from a median of 1.31 (IQR: 1.13-1.64) at 1 h to a median of 1.85 (1.45-2.10) at 3 h. The median percent change was 37.77% (IQR: 23.47-46.4), with a range of 6.10-50.73 (P = 0.003). However, no significant change in uptake was observed in patients with a complete response (P = 0.24). The same trend was observed for the non-HDT group. WBM uptake of 18F-FDG assessed with dual-time-point imaging may have a role in predicting treatment response in MM.

Comparison of 18F-sodium fluoride uptake in the whole bone, pelvis, and femoral neck of multiple myeloma patients before and after high-dose therapy and conventional-dose chemotherapy.

AIM: To compare the effects of high-dose therapy (HDT consisting of high-dose chemotherapy followed by autologous stem cell transplantation) and conventional-dose chemotherapy (non-HDT) on the uptake of 18F-sodium fluoride (NaF) in the whole bone, pelvis, and femoral neck of multiple myeloma (MM) patients. METHOD: The data of 19 MM patients who received HDT (61.5 (SD 5.6) years) and 11 MM patients who received conventional-dose chemotherapy (70.9 (SD 7.2) years) were collected in a prospective study. NaF PET/CT imaging was performed at baseline, and 8 weeks and 2 weeks after treatment for the HDT group and the non-HDT group, respectively. A CT-based algorithm was applied to segment the bones, and the global mean SUV (GSUVmean) of the whole bone and pelvis was calculated (OsiriX MD v.9.0, Pixmeo SARL; Bernex, Switzerland). In addition, regions of interest for the whole, medial, and lateral femoral neck were delineated bilaterally. Whole bone and pelvis measurements were replicated by two observers. RESULTS: The average GSUVmean in the whole bone and pelvis of the patients who underwent HDT significantly decreased from before to after treatment (- 16.27%, p = 0.02 and - 16.54%, p = 0.01, respectively). A significant decrease in the whole and lateral femoral neck was also observed bilaterally in the HDT group. No significant decrease in average GSUVmean was observed in the non-HDT group. A high level of inter-observer reliability was found in intra-class correlation (ICC for pre-treatment whole bone 0.983, post-treatment whole bone 0.989, pre-treatment whole pelvis 0.998, post-treatment whole pelvis 0.996). CONCLUSION: NaF uptake significantly decreased after treatment in patients who received high-dose therapy. A high level of agreement was observed between two operators for whole bone and pelvis measurements.