1,720,997 research outputs found
18F-FDG-PET in Mouse Models of Alzheimer's Disease
Suitable animal models and in vivo biomarkers are essential for development and evaluation of new therapeutic strategies in Alzheimer's disease (AD). 18F-Fluorodeoxyglucose (18F-FDG)-positron-emission tomography (PET) is an imaging biomarker that allows the assessment of cerebral glucose metabolism in vivo. While 18F-FDG-PET/CT is an established tool in the evaluation of AD patients, its role in preclinical studies with AD mouse models remains unclear. Here, we want to review available studies on 18F-FDG-PET/CT in AD mouse models in order to evaluate the method and its impact in preclinical AD research. Only a limited number of studies using 18F-FDG-PET in AD mice were carried out so far showing contradictory findings in cerebral FDG uptake. Methodological differences as well as underlying pathological features of used mouse models seem to be accountable for those varying results. However, 18F-FDG-PET can be a valuable tool in longitudinal in vivo therapy monitoring with a lot of potential for future studies
Comparison between amyloid-PET and CSF amyloid-β biomarkers in a clinical cohort with memory deficits
Case Report: The Role of Neuropsychological Assessment and Imaging Biomarkers in the Early Diagnosis of Lewy Body Dementia in a Patient With Major Depression and Prolonged Alcohol and Benzodiazepine Dependence
Dementia with Lewy bodies (DLB) is the second most common form of dementia and is assumed to be often under- or misdiagnosed, especially in early stages. Here we present a complex case of probable DLB with major depression and alcohol and benzodiazepine dependence in which DLB was ruled out initially. This case highlights the challenging diagnostic workup of DLB patients. Core clinical features can be missing and indicative biomarkers can be negative, especially in early stages of the disease. Initially, Fluorodeoxyglucose positron emission tomography as well as neuropsychological assessment were suspicious for a possible DLB diagnosis in our patient while core clinical criteria were missing and the indicative biomarker 123I-FP-CIT SPECT was negative. Follow up was performed two years later and the patients showed several core and supportive clinical features of DLB and 123I-FP-CIT SPECT showed a pathological pattern. Extensive neuropsychological assessment in combination with PET imaging might provide crucial evidence for DLB even in early stages. If neuropsychology and PET imaging point to an early DLB diagnosis careful follow-up should be performed as core symptoms and indicative biomarkers might appear in later stages of the disease.Open-Access-Publikationsfonds 202
18F-FDG-PET and Multimodal Biomarker Integration: A Powerful Tool for Alzheimer’s Disease Diagnosis
Abstract An early, biomarker-based diagnosis of Alzheimer’s Disease (AD) is crucial, especially with the emerging availability of novel therapeutic options. However, the role of 18 F-FDG-PET and its relationship to other PET and CSF biomarkers remains unclear. Therefore, the aim of this study was the evaluation of the role of 18 F-FDG-PET in AD diagnosis and its relationship to other commonly used fluid and PET biomarkers and their individual and multimodal accuracy in AD diagnosis. We included n = 157 AD patients, n = 603 MCI patients, and n = 380 cognitively normal participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) that underwent PET imaging with 18 F-FDG or 18 F-Florbetapir. Clinical and imaging data including patient characteristics, CSF biomarkers, cognition tests, 18 F-FDG-PET, 18 F-Florbetapir-PET, and 18 F-Flortaucipir-PET were retrospectively analyzed. PET images were quantified in several brain regions. The uptake of 18 F-FDG was inversely correlated with 18 F-Florbetapir and positively correlated with CSF Aβ42 in several brain regions commonly affected by AD. Additionally, 18 F-FDG uptake showed an inverse correlation with both forms of CSF tau, t-tau and p-tau, in various brain regions, but did not correlate with 18 F-Flortaucipir uptake. Moreover, regional 18 F-FDG uptake was positively correlated with cognitive function. Diagnostic accuracies were similarly high for 18 F-FDG uptake in the PCC/Precuneus region, 18 F-Florbetapir uptake, CSF Aβ42, CSF p-tau, and 18 F-Flortaucipir uptake in differentiating AD from cognitively normal individuals. 18 F-FDG-PET and its combination with CSF p-tau/ Aβ42 ratio showed the highest predictive power for disease severity. The study underscores the potential of integrating 18 F-FDG-PET with CSF biomarkers to enhance the diagnosis, prognosis, and monitoring of AD, highlighting the complexity and regional specificity of biomarker interactions in neurodegeneration
The relationship of 18 F-FDG-PET to other common biomarkers of dementia in a clinical cohort with memory deficits
Background Early biomarker-based diagnosis of Alzheimer's disease (AD) is essential, particularly with the increasing availability of new therapeutic options. However, the relationship between imaging and cerebrospinal fluid (CSF) biomarkers, especially in the context of 18 Fluorine-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET), remains insufficiently understood. Objective The aim of this study was the evaluation of the relationship between 18 F-FDG-PET and other common fluid and imaging AD-biomarkers in a clinical cohort of patients with cognitive decline and suspected AD. Methods We included n = 90 patients with cognitive decline and clinically suspected AD that underwent 18 F-FDG-PET imagining at our facility. Clinical and imaging data including patient characteristics, CSF biomarkers, Mini-Mental State Examination (MMSE), 18 F-FDG-PET and 18 F-Florbetaben-PET were retrospectively analyzed. PET images were quantified in several brain regions. Results 18 F-FDG uptake correlated with CSF amyloid-β (Aβ) 40 , Aβ 42 , and the Aβ 42/40 ratio in several brain regions, but not with regional 18 F-Florbetaben uptake. 18 F-FDG uptake inversely correlated with t-tau and p-tau in CSF. Furthermore, a correlation between MMSE and 18 F-FDG uptake was also detected in several brain regions. 18 F-FDG-PET and its combination with CSF markers showed the highest predictive power for disease severity. Conclusions The study highlights the potential of integrating 18 F-FDG-PET with CSF biomarkers to improve the diagnosis, prognosis, and monitoring of AD, emphasizing the complexity and regional specificity of biomarker interactions in neurodegeneration.Open-Access-Publikationsfonds 202
Assessing Nigrostriatal Dopaminergic Pathways via 123I-FP-CIT SPECT in Dementia With Lewy Bodies in a Psychiatric Patient Cohort
Background (123)-I-2-ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortro- pane single photon emission computed tomography (123I-FP-CIT SPECT) was validated to distinguish Alzheimer’s dementia from dementia with Lewy Bodies (DLB) by European medical agencies. Little evidence exists that validates 123 I-FP-CIT SPECT as a supplementary method to diagnose probable DLB in a psychiatric cohort of patients with psychiatric symptomatology and suspected DLB. We aim to elucidate differences in the clinical phenotype of DLB between those patients with and those without a positive 123 I-FP-CIT SPECT indicating a nigrostriatal deficit. Methods To investigate this, we included 67 patients from the Department of Psychiatry and Psychotherapy at University Medical Center Göttingen (UMG) in our study who had undergone 123I-FP-CIT SPECT in the Department of Nuclear Medicine (UMG) by evaluating their patient files. Results 55% with a positive-123I-FP-CIT SPECT and probable DLB after the 123I-FP-CIT SPECT exhibited psychiatric features. The number of probable DLB patients in those exhibiting psychiatric symptoms was higher post-123I-FP-CIT SPECT than pre-123I-FP-CIT SPECT assessed cross-sectionally over a 6-year period ( p < 0.05). In addition, prodromal DLB and prodromal DLB patients with a psychiatric-phenotype yielded higher numbers post-123I-FP-CIT SPECT than pre-123I-FP-CIT SPECT ( p < 0.05). Furthermore, we discovered no phenotypical differences between those DLB patients with a positive and those with a negative 123I-FP-CIT SPECT. 123I-FP-CIT SPECT-positive DLB patients in our psychiatric cohort revealed a psychiatric onset more often (52%); DLB was less often characterized by an MCI onset (26%) ( p < 0.005). Conclusions Our findings support 123I-FP-CIT SPECT as an adjuvant tool for improving the diagnosis of probable DLB and prodromal DLB in a cohort of psychiatric patients with often concomitant psychiatric symptomatology. The psychiatric-onset is more frequent than an MCI-onset in DLB patients presenting nigrostriatal dysfunction, giving us an indication of the relevance of deep clinical phenotyping in memory clinics that includes the assessment of psychopathology.Background (123)-I-2-ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortro- pane single photon emission computed tomography (123I-FP-CIT SPECT) was validated to distinguish Alzheimer’s dementia from dementia with Lewy Bodies (DLB) by European medical agencies. Little evidence exists that validates 123 I-FP-CIT SPECT as a supplementary method to diagnose probable DLB in a psychiatric cohort of patients with psychiatric symptomatology and suspected DLB. We aim to elucidate differences in the clinical phenotype of DLB between those patients with and those without a positive 123 I-FP-CIT SPECT indicating a nigrostriatal deficit. Methods To investigate this, we included 67 patients from the Department of Psychiatry and Psychotherapy at University Medical Center Göttingen (UMG) in our study who had undergone 123I-FP-CIT SPECT in the Department of Nuclear Medicine (UMG) by evaluating their patient files. Results 55% with a positive-123I-FP-CIT SPECT and probable DLB after the 123I-FP-CIT SPECT exhibited psychiatric features. The number of probable DLB patients in those exhibiting psychiatric symptoms was higher post-123I-FP-CIT SPECT than pre-123I-FP-CIT SPECT assessed cross-sectionally over a 6-year period ( p < 0.05). In addition, prodromal DLB and prodromal DLB patients with a psychiatric-phenotype yielded higher numbers post-123I-FP-CIT SPECT than pre-123I-FP-CIT SPECT ( p < 0.05). Furthermore, we discovered no phenotypical differences between those DLB patients with a positive and those with a negative 123I-FP-CIT SPECT. 123I-FP-CIT SPECT-positive DLB patients in our psychiatric cohort revealed a psychiatric onset more often (52%); DLB was less often characterized by an MCI onset (26%) ( p < 0.005). Conclusions Our findings support 123I-FP-CIT SPECT as an adjuvant tool for improving the diagnosis of probable DLB and prodromal DLB in a cohort of psychiatric patients with often concomitant psychiatric symptomatology. The psychiatric-onset is more frequent than an MCI-onset in DLB patients presenting nigrostriatal dysfunction, giving us an indication of the relevance of deep clinical phenotyping in memory clinics that includes the assessment of psychopathology.Open-Access-Finanzierung durch die Universitätsmedizin Göttingen 202
Case Report: Two Cases of Subacute Thyroiditis Following SARS-CoV-2 Vaccination
Subacute thyroiditis is an inflammatory thyroid disorder associated with viral infections. Rare cases of subacute thyroiditis have also been described following vaccination. Recently, a few cases of subacute thyroiditis following SARS-CoV-2 vaccination have also been reported. Here, we present two cases of cytological proven subacute thyroiditis after receiving the first dose of a SARS-CoV-2 vaccination. We describe clinical, laboratory, imaging and cytological findings in two cases of subacute thyroiditis that presented in our department 2 weeks after SARS-CoV-2 vaccination with Spikevax (Moderna Biotech, Spain) and Vaxzevria (AstraZeneca; Sweden). Both cases did not have a previous history of thyroid disorders and presented with anterior and lateral neck pain. Clinical test results as well as cytological findings were consistent with subacute thyroiditis. Subacute thyroiditis may develop following a SARS-CoV-2 vaccination and should be considered as a possible side effect in cases that present with thyroid pain
99mTc-Besilesomab-SPECT/CT in Infectious Endocarditis: Upgrade of a Forgotten Method?
Infective endocarditis displays a serious condition with high mortality rates. Establishing a reliable diagnosis can be challenging. This study evaluates granulocyte imaging with 99mTc-Besilesomab-SPECT/CT in order to determine the clinical value of the method and its possible redefinition through the addition of hybrid imaging. The study comprises 26 consecutive patients with suspected infectious endocarditis or prosthetic valve infection that underwent 99mTc-Besilesomab-SPECT/CT in our facility between December 2016 and September 2018. 99mTc-Besilesomab-SPECT/CT images were reviewed by two independent and blinded observers and results were evaluated by transesophageal echocardiography (TEE) and blood culture results as well as by pathological, bacteriological, and clinical findings. Target-to-Background-Ratios were calculated for semi-quantitative analysis. 13/26 patients were in a post-surgical stage. 99mTc-Besilesomab-SPECT/CT was positive in 6 cases. All 6 cases were true positive confirmed by pathological or clinical findings according to the modified Duke Criteria for infective endocarditis. Remaining 19/26 cases were true negative. Target-to-Background ratios were significantly higher in patients that were visually scored positive compared to negative cases. Inter-observer agreement was very good of deciding whether a scan was positive or negative. Sensitivity of 99mTc-Besilesomab-SPECT/CT was 86–100% and specificity was 100%. 99mTc-Besilesomab-SPECT/CT is a useful imaging method for the diagnosis of endocarditis, especially in difficult cases with prosthetic valves or cardiac devices and inconclusive findings in echocardiography. The added value of SPECT/CT was mainly finding and localizing increased uptake at a certain valve, prosthesis, or device cable
In vivo Imaging With 18F-FDG- and 18F-Florbetaben-PET/MRI Detects Pathological Changes in the Brain of the Commonly Used 5XFAD Mouse Model of Alzheimer's Disease
Imaging biomarkers of Alzheimer's disease (AD) that are able to detect molecular changes in vivo and transgenic animal models mimicking AD pathologies are essential for the evaluation of new therapeutic strategies. Positron-emission tomography (PET) using either 18F-Fluorodeoxyglucose (18F-FDG) or amyloid-tracers is a well-established, non-invasive tool in the clinical diagnostics of AD assessing two major pathological hallmarks. 18F-FDG-PET is able to detect early changes in cerebral glucose metabolism and amyloid-PET shows cerebral amyloid load. However, the suitability of 18F-FDG- and amyloid-PET in the widely used 5XFAD mouse model of AD is unclear as only a few studies on the use of PET biomarkers are available showing some conflicting results. The aim of this study was the evaluation of 18F-FDG-PET and amyloid-PET in 5XFAD mice in comparison to neurological deficits and neuropathological changes. Seven- and 12-month-old male 5XFAD mice showed a significant reduction in brain glucose metabolism in 18F-FDG-PET and amyloid-PET with 18F-Florbetaben demonstrated an increased cerebral amyloid deposition (n = 4–6 per group). Deficits in spatial reference memory were detected in 12-month-old 5XFAD mice in the Morris Water Maze (n = 10–12 per group). Furthermore, an increased plaque load and gliosis could be proven immunohistochemically in 5XFAD mice (n = 4–6 per group). PET biomarkers 18F-FDG and 18F-Florbetaben detected cerebral hypometabolism and increased plaque load even before the onset of severe memory deficits. Therefore, the 5XFAD mouse model of AD is well-suited for in vivo monitoring of AD pathologies and longitudinal testing of new therapeutic approaches.Open-Access-Publikationsfonds 202
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