18F-THK5351 Uptake May Not Estimate Neurofibrillary Tangles in In Vivo Images: A Comparison With 18F-MK-6240 Uptake.

ABSTRACT: Currently, monoamine oxidase B is recognized as the primary target of 18F-THK5351, although 18F-THK5351 was initially developed to target neurofibrillary tangles (NFTs) in Alzheimer disease. When clinically applying 18F-THK5351 PET to visualize ongoing astrogliosis via estimating monoamine oxidase B levels, a crucial concern is how much degree 18F-THK5351 uptake reflects NFTs in in vivo images. To unravel this concern, a head-to-head comparison between 18F-THK5351 and 18F-MK-6240 (estimating NFT) images in the NFT lesion ideally without accompanying astrogliosis is essential. Here, we present such a case suggesting that 18F-THK5351 uptake may not estimate NFTs in in vivo images.

Clinicopathological study of dementia with grains presenting with parkinsonism compared with a typical case.

Argyrophilic grain disease (AGD) is one of the major pathological backgrounds of senile dementia. Dementia with grains refers to cases of dementia for which AGD is the sole background pathology responsible for dementia. Recent studies have suggested an association between dementia with grains and parkinsonism. In this study, we aimed to present two autopsy cases of dementia with grains. Case 1 was an 85-year-old man who exhibited amnestic dementia and parkinsonism, including postural instability, upward gaze palsy, and neck and trunk rigidity. The patient was clinically diagnosed with progressive supranuclear palsy and Alzheimer's disease. Case 2 was a 90-year-old man with pure amnestic dementia, clinically diagnosed as Alzheimer's disease. Recently, we used cryo-electron microscopy to confirm that the tau accumulated in both cases had the same three-dimensional structure. In this study, we compared the detailed clinical picture and neuropathological findings using classical staining and immunostaining methods. Both cases exhibited argyrophilic grains and tau-immunoreactive structures in the brainstem and basal ganglia, especially in the nigrostriatal and limbic systems. However, Case 1 had more tau immunoreactive structures. Considering the absence of other disease-specific structures such as tufted astrocytes, astrocytic plaques and globular glial inclusions, lack of conspicuous cerebrovascular disease, and no history of medications that could cause parkinsonism, our findings suggest an association between AGD in the nigrostriatal system and parkinsonism.

Applications of artificial intelligence in dementia.

The recent evolution of artificial intelligence (AI) can be considered life-changing. In particular, there is great interest in emerging hot topics in AI such as image classification and natural language processing. Our world has been revolutionized by convolutional neural networks and transformer for image classification and natural language processing, respectively. Moreover, these techniques can be used in the field of dementia. We introduce some applications of AI systems for treating and diagnosing dementia, including image-classification AI for recognizing facial features associated with dementia, image-classification AI for classifying leukoaraiosis in MRI images, object-detection AI for detecting microbleeding in MRI images, object-detection AI for support care, natural language-processing AI for detecting dementia within conversations, and natural language-processing AI for chatbots. Such AI technologies can significantly transform the future of dementia diagnosis and treatment. Geriatr Gerontol Int 2024; 24: 25-30.

Diagnostic performance of the cingulate island sign ratio for differentiating dementia with Lewy bodies from Alzheimer's disease changes depending on the mini-mental state examination score.

BACKGROUND: The cingulate island sign (CIS) ratio is a diagnostic adjunct for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). A recent study showed that the CIS ratio in DLB changed depending on the Mini-Mental State Examination (MMSE) score. We aimed to evaluate whether the diagnostic performance (sensitivity and specificity) of the CIS ratio for differentiating DLB from AD changes depending on the MMSE score. METHODS: Twenty-two patients with DLB and 26 amyloid-positive patients with AD, who underwent 18F-FDG PET and completed an MMSE examination, were classified into three groups according to MMSE scores: Group A (MMSE >24), Group B (20 ≤ MMSE ≤24), and Group C (MMSE <20). In each group, we compared the CIS ratio between patients with DLB and AD and conducted receiver operating characteristic (ROC) curve analysis to calculate the sensitivity and specificity. RESULTS: Within Group B, the CIS ratio in DLB was significantly higher than that in AD (p = 0.0005), but not within Groups A (p = 0.5117) and C (p = 0.8671). ROC curve analyses showed that the sensitivities and specificities of the CIS ratio for differentiating DLB from AD were 66.7% and 77.8% in Group A, 91.7% and 100.0% in Group B, and 75.0% and 66.7% in Group C, respectively. CONCLUSIONS: The present study suggests that the diagnostic performance of the CIS ratio for differentiating DLB from AD changes depending on the MMSE score, with higher sensitivity and specificity at MMSE scores of 20-24.

High sensitivity of asymmetric 18F-THK5351 PET abnormality in patients with corticobasal syndrome.

Corticobasal syndrome (CBS) is characterized by symptoms related to the asymmetric involvement of the cerebral cortex and basal ganglia. However, early detection of asymmetric imaging abnormalities can be challenging. Previous studies reported asymmetric 18F-THK5351 PET abnormalities in CBS patients, but the sensitivity for detecting such abnormalities in larger patient samples, including early-stage cases, remains unclear. Patients clinically diagnosed with CBS were recruited. All patients displayed asymmetric symptoms in the cerebral cortex and basal ganglia. Asymmetric THK5351 PET abnormalities were determined through visual assessment. Brain MRI, perfusion SPECT, and dopamine transporter (DAT) SPECT results were retrospectively reviewed. The 15 patients had a median age of 72 years (59-86 years) and a disease duration of 2 years (0.5-7 years). Four patients met the probable and 11 met the possible CBS criteria according to Armstrong criteria at the time of PET examination. All patients, including early-stage cases, exhibited asymmetric tracer uptake contralateral to their symptom-dominant side in the cerebral cortex/subcortical white matter and striatum (100%). The sensitivity for detecting asymmetric imaging abnormalities contralateral to the symptom-dominant side was 86.7% for brain MRI, 81.8% for perfusion SPECT, and 90% for DAT SPECT. White matter volume reduction was observed in the subcortical region of the precentral gyrus with increased THK5351 uptake, occurring significantly more frequently than gray matter volume reduction. THK5351 PET may be a sensitive imaging technique for detecting asymmetric CBS pathologies, including those in early stages.

Correlations between cerebrospinal fluid homovanillic acid and dopamine transporter SPECT in degenerative parkinsonian syndromes.

Both cerebrospinal fluid (CSF) homovanillic acid (HVA) and striatal dopamine transporter (DAT) binding on single-photon emission computed tomography (SPECT) reflect nigrostriatal dopaminergic function, but studies on the relationship between the two have been limited. It is also unknown whether the reported variance in striatal DAT binding among diseases reflects the pathophysiology or characteristics of the subjects. We included 70 patients with Parkinson's disease (PD), 12 with progressive supranuclear palsy (PSP), 12 with multiple system atrophy, six with corticobasal syndrome, and nine with Alzheimer's disease as disease control, who underwent both CSF analysis and 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane (123I-ioflupane) SPECT. We evaluated the correlation between CSF HVA concentration and the specific binding ratio (SBR) of striatal DAT binding. We also compared the SBR for each diagnosis, controlling for CSF HVA concentration. The correlations between the two were significant in patients with PD (r = 0.34, p = 0.004) and PSP (r = 0.77, p = 0.004). The mean SBR value was the lowest in patients with PSP and was significantly lower in patients with PSP than in those with PD (p = 0.037) after adjusting for CSF HVA concentration. Our study demonstrates that striatal DAT binding correlates with CSF HVA concentration in both PD and PSP, and striatal DAT reduction would be more advanced in PSP than in PD at an equivalent dopamine level. Striatal DAT binding may correlate with dopamine levels in the brain. The pathophysiology of each diagnosis may explain this difference.

Measurement of erythrocyte creatine might be useful for diagnosing latent hemolysis.

OBJECTIVES: Whereas HbA1c values are low relative to glycemia in patients with hemolytic anemia, including compensatory anemia, low HbA1c levels along with negative results for conventional hemolysis indicators have been reported in patients with latent hemolysis. Conversely, glycated albumin (GA) is a glycemic control indicator unaffected by hemolysis. Erythrocyte creatine (EC) is a hemolysis indicator that reflects the mean age of red blood cells (MRBC). We recently reported a formula for obtaining MRBC based on EC. The present study examined the usefulness of EC measurements and MRBC calculated with EC for diagnosing latent hemolysis. MATERIALS AND METHODS: Two patients with latent hemolysis and low HbA1c values relative to glycemia were investigated, while controls comprised 214 patients (including patients with hemolysis and/or type 2 diabetes mellitus). HbA1c was expressed in International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) units (iA1c). GA/iA1c ratios, reticulocyte counts, EC, and MRBC in patients with latent hemolysis were compared to non-hemolysis, compensatory hemolysis, and hemolytic anemia patients. RESULTS: Both reticulocyte counts and haptoglobin levels were within reference ranges in patients with latent hemolysis. GA/iA1c ratios and EC were higher than reference values in patients with latent hemolysis, and MRBC values were 41.6 and 48.4 days, respectively, shorter than the reference range (49.1-66.8 days). CONCLUSIONS: EC measurement and MRBC values calculated on the basis of EC might be useful for diagnosing latent hemolysis.

Striatal Dopaminergic Depletion Pattern Reflects Pathological Brain Perfusion Changes in Lewy Body Diseases.

PURPOSE: In Lewy body diseases (LBD), various symptoms occur depending on the distribution of Lewy body in the brain, and the findings of brain perfusion and dopamine transporter single-photon emission computed tomography (DAT-SPECT) also change accordingly. We aimed to evaluate the correlation between brain perfusion SPECT and quantitative indices calculated from DAT-SPECT in patients with LBD. PROCEDURES: We retrospectively enrolled 35 patients with LBD who underwent brain perfusion SPECT with N-isopropyl-p-[123I] iodoamphetamine and DAT-SPECT with 123I-ioflupane. Mini-mental state examination (MMSE) data were also collected from 19 patients. Quantitative indices (specific binding ratio [SBR], putamen-to-caudate ratio [PCR], and caudate-to-putamen ratio [CPR]) were calculated using DAT-SPECT. These data were analysed by the statistical parametric mapping procedure. RESULTS: In patients with LBD, decreased PCR index correlated with hypoperfusion in the brainstem (medulla oblongata and midbrain) (uncorrected p < 0.001, k > 100), while decreased CPR index correlated with hypoperfusion in the right temporoparietal cortex (family-wise error corrected p < 0.05), right precuneus (uncorrected p < 0.001, k > 100), and bilateral temporal cortex (uncorrected p < 0.001, k > 100). However, there was no significant correlation between decreased SBR index and brain perfusion. Additionally, the MMSE score was correlated with hypoperfusion in the left temporoparietal cortex (uncorrected p < 0.001). CONCLUSIONS: This study suggests that regional changes in striatal 123I-ioflupane accumulation on DAT-SPECT are related to brain perfusion changes in patients with LBD.

Autopsy Validation of the Diagnostic Accuracy of 123I-Metaiodobenzylguanidine Myocardial Scintigraphy for Lewy Body Disease.

BACKGROUND AND OBJECTIVES: 123I-meta-iodobenzyl-guanidine (123I-MIBG) myocardial scintigraphy is used as a diagnostic imaging test to differentiate Lewy body diseases (LBDs), including Parkinson disease and dementia with Lewy bodies, from other similar diseases. However, this imaging test lacks validation of its diagnostic accuracy against the gold standard. Our aim was to validate the diagnostic accuracy of 123I-MIBG myocardial scintigraphy for LBD against autopsy, the gold standard. METHODS: This retrospective, cross-sectional study included consecutive autopsy patients from the Brain Bank for Aging Research who had undergone 123I-MIBG myocardial scintigraphy. We compared the 123I-MIBG myocardial scintigraphy findings with autopsy findings. Furthermore, the proportion of residual tyrosine hydroxylase (TH)-immunoreactive sympathetic fibers in the anterior wall of the left ventricle was investigated to assess the condition of the cardiac sympathetic nerves assumed to cause reduced 123I-MIBG uptake in LBDs. RESULTS: We analyzed the data of 56 patients (30 with pathologically confirmed LBDs and 26 without LBD pathology). Compared with the neuropathologic diagnosis, the early heart-to-mediastinum (H/M) ratio had a sensitivity and specificity of 70.0% (95% CI 50.6%-85.3%) and 96.2% (95% CI 80.4%-99.9%), respectively. The delayed H/M ratio had a sensitivity and specificity of 80.0% (95% CI 61.4%-92.3%) and 92.3% (95% CI 74.9%-99.1%), respectively. The washout rate had a sensitivity and specificity of 80.0% (95% CI 61.4%-92.3%) and 84.6% (95% CI 65.1%-95.6%), respectively. The proportion of residual TH-immunoreactive cardiac sympathetic fibers strongly correlated with the amount of cardiac 123I-MIBG uptake when assessed with early and delayed H/M ratio values (correlation coefficient 0.75 and 0.81, respectively; p < 0.001). DISCUSSION: This clinicopathologic validation study revealed that 123I-MIBG myocardial scintigraphy could robustly differentiate LBDs from similar diseases. Abnormal 123I-MIBG myocardial scintigraphy findings strongly support the presence of LBD and cardiac sympathetic denervation. However, LBD pathology should not necessarily be excluded by normal myocardial scintigraphy results, especially when other biomarkers suggest the presence of comorbid Alzheimer disease pathology. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that 123I-MIBG myocardial scintigraphy accurately identifies patients with LBD.

Decreased imaging time of amyloid PET using [18F]florbetapir can maintain quantitative accuracy.

Shortening the amount of time required to acquire amyloid positron emission tomography (PET) brain images while maintaining the accuracy of quantitative evaluation would help to overcome motion artifacts associated with Alzheimer's disease patients. The present study aimed to validate the quantitative accuracy of [18F]florbetapir ([18F]FBP) imaging over a shorter acquisition duration. Forty participants were injected with [18F]FBP, and PET images were acquired for 50-55, 50-60, and 50-70 min after injection. Three physicians visually assessed the reprocessed [18F]FBP images using a binary scale to classify them as amyloid ß (Aß) negative or positive. A mean composite standard uptake value ratio (cSUVR) > 1.075 was defined as Aß-positive based on receiver operating characteristic curves. Inter-reader and inter-acquisition duration agreements with visual assessment were evaluated using Cohen's kappa (κ). Binary visual discrimination of 102 for the 120 [18F]FBP images, was consistent among the three readers. Sixteen, sixteen, and fourteen of the 40 [18F]FBP images acquired for 50-55, 50-60, and 50-70 min after injection, respectively, were deemed Aß-positive by visual assessment. The inter-rater agreement was high, and the inter-acquisition duration agreement was almost perfect. The cSUVR did not change significantly among the acquisition durations, and the acquisition duration did not affect the outcome of discrimination based on the cSUVR cutoff. A shorter acquisition duration changed the visual assessment outcomes. Stable quantitative values were derived from [18F]FBP images acquired within 5 min. cSUVR helped to improve the performance and confidence in the outcomes of visual assessment.

Validity of the γ-Ray Evaluation with iodoamphetamine for Cerebral Blood Flow Assessment (REICA) method for quantification of cerebral blood flow including acetazolamide challenge test.

OBJECTIVE: The γ-Ray Evaluation with iodoamphetamine for Cerebral Blood Flow Assessment (REICA) is a new method for quantifying cerebral blood flow (CBF) using single-photon emission computed tomography (SPECT) and [123I]N-isopropyl-p-iodoamphetamine (123I-IMP). The present study aimed to validate the REICA method using data including acetazolamide challenge test. METHODS: The REICA and Graph-Plot (GP) methods were used to calculate mean CBF (mCBF) for 92 acquisitions (rest: 57, stress: 35) and cerebrovascular reactivity (CVR) in 33 patients. To obtain stress data, 15 mg/kg of acetazolamide was injected intravenously 10 min before the administration of 123I-IMP, and blood samples were collected under the same conditions as rest data. The reference standard was the Autoradiograph (ARG) method using arterial blood sampling, and the accuracy of the REICA method was analyzed by comparing it with each method. RESULTS: For mCBF, the correlation coefficients (r) were 0.792 for the REICA method and 0.636 for the GP method. For CVR, r values were 0.660 for the REICA method and 0.578 for the GP method. In both acquisitions, the REICA method had a stronger correlation with the ARG method than the GP method. For mCBF, there was a significant difference in the correlation coefficient between the two correlation coefficients (p < 0.01). CONCLUSIONS: The REICA method was more accurate than the GP method in quantifying CBF and closer to the ARG method. The REICA method, which is a noninvasive method of cerebral blood flow quantification using 123I-IMP, has great medical usefulness.

Brain 11 C-ITMM PET to longitudinally assess type 1 metabotropic glutamate receptor availability in Alzheimer's disease.

BACKGROUND AND PURPOSE: Little evidence exists on the role of type 1 metabotropic glutamate receptor (mGluR1) in the pathophysiology of Alzheimer's disease (AD), although mGluR1 may be involved in the regulation of neuronal excitability and synaptic plasticity. We have recently reported that mGluR1 availability in the early stage of AD is equivalent to that in healthy subjects. This study aimed to address whether mGluR1 availability changes with the progression of AD. METHODS: Eight patients with AD (79.1 ± 4.6 years) underwent a total of two positron emission tomography (PET) examinations using the mGluR1 radioligand during the early-to-middle stages of AD. The mean interval was 2.8 years. Volumes-of-interest were placed on the frontal, parietal, and temporal cortices, hippocampus, anterior and posterior lobes, and vermis in the cerebellum. The binding potential (BPND ) was calculated to estimate mGluR1 availability, applying partial volume correction to the BPND values. RESULTS: No significant difference was observed in BPND values between the first and second PET examinations in the frontal cortex (p = 0.94), parietal cortex (p = 0.67), temporal cortex (p = 0.20), hippocampus (p = 0.17), anterior lobe (p = 0.73), posterior lobe (p = 0.21), and vermis (p = 0.22). CONCLUSION: This study suggests that mGluR1 availability is unchanged in the follow-up period of a few years during the early-to-middle stages of AD.

Screening of Alzheimer's disease by facial complexion using artificial intelligence.

Despite the increasing incidence and high morbidity associated with dementia, a simple, non-invasive, and inexpensive method of screening for dementia is yet to be discovered. This study aimed to examine whether artificial intelligence (AI) could distinguish between the faces of people with cognitive impairment and those without dementia.121 patients with cognitive impairment and 117 cognitively sound participants were recruited for the study. 5 deep learning models with 2 optimizers were tested. The binary differentiation of dementia / non-dementia facial image was expressed as a "Face AI score". Xception with Adam was the model that showed the best performance. Overall sensitivity, specificity, and accuracy by the Xception AI system and AUC of the ROC curve were 87.31%, 94.57%, 92.56%, and 0.9717, respectively. Close and significant correlations were found between Face AI score and MMSE (r = -0.599, p < 0.0001). Significant correlation between Face AI score and chronological age was also found (r = 0.321, p < 0.0001). However, MMSE score showed significantly stronger correlation with Face AI score than chronological age (p < 0.0001). The study showed that deep learning programs such as Xception have the ability to differentiate the faces of patients with mild dementia from that of patients without dementia, paving the way for future studies into the development of a facial biomarker for dementia.

Estimation of the hemoglobin glycation rate constant.

In a previous study, a method of obtaining mean erythrocyte age ([Formula: see text]) from HbA1c and average plasma glucose (AG) was proposed. However, the true value of the hemoglobin glycation constant ([Formula: see text] dL/mg/day), required for this model has yet to be well characterized. Another study also proposed a method of deriving [Formula: see text] from erythrocyte creatine (EC). Utilizing these formulae, this study aimed to determine a more accurate estimate of [Formula: see text]. One hundred and seven subjects including 31 patients with hemolytic anemia and 76 subjects without anemia were included in this study. EC and HbA1c data were analyzed, and [Formula: see text] using HbA1c, AG and the newly-derived constant, [Formula: see text] were compared to [Formula: see text] using traditional [Formula: see text] in three patients whose data were taken from previous case studies. A value of [Formula: see text] dL/mg/day was determined for [Formula: see text]. [Formula: see text] using HbA1c, AG and [Formula: see text] were found to no be significantly different (paired t-test, [Formula: see text]) to [Formula: see text] using traditional [Formula: see text]. [Formula: see text] enables the estimation of [Formula: see text] from HbA1c and AG.

A diagnostic strategy for Parkinsonian syndromes using quantitative indices of DAT SPECT and MIBG scintigraphy: an investigation using the classification and regression tree analysis.

PURPOSE: We aimed to evaluate the diagnostic performances of quantitative indices obtained from dopamine transporter (DAT) single-photon emission computed tomography (SPECT) and 123I-metaiodobenzylguanidine (MIBG) scintigraphy for Parkinsonian syndromes (PS) using the classification and regression tree (CART) analysis. METHODS: We retrospectively enrolled 216 patients with or without PS, including 80 without PS (NPS) and 136 with PS [90 Parkinson's disease (PD), 21 dementia with Lewy bodies (DLB), 16 progressive supranuclear palsy (PSP), and 9 multiple system atrophy (MSA). The striatal binding ratio (SBR), putamen-to-caudate ratio (PCR), and asymmetry index (AI) were calculated using DAT SPECT. The heart-to-mediastinum uptake ratio (H/M) based on the early (H/M [Early]) and delayed (H/M [Delay]) images and cardiac washout rate (WR) were calculated from MIBG scintigraphy. The CART analysis was used to establish a diagnostic decision tree model for differentiating PS based on these quantitative indices. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 87.5, 96.3, 93.3, 92.9, and 93.1 for NPS; 91.1, 78.6, 75.2, 92.5, and 83.8 for PD; 57.1, 95.9, 60.0, 95.4, and 92.1 for DLB; and 50.0, 98.0, 66.7, 96.1, and 94.4 for PSP, respectively. The PCR, WR, H/M (Delay), and SBR indices played important roles in the optimal decision tree model, and their feature importance was 0.61, 0.22, 0.11, and 0.05, respectively. CONCLUSION: The quantitative indices showed high diagnostic performances in differentiating NPS, PD, DLB, and PSP, but not MSA. Our findings provide useful guidance on how to apply these quantitative indices in clinical practice.

A Novel Proposal for an Index for Regional Cerebral Perfusion Pressure - A Theoretical Approach Using Fluid Dynamics.

Cerebral blood flow (CBF) / cerebral blood volume (CBV) ratio derived by [15O] H2O/ CO2 and CO positron emission tomography (PET) examination has been used as an index for cerebral perfusion pressure (CPP). CBF/CBV was demonstrated to be related mean arterial pressure (MAP) in baboons. However, this formula has not been confirmed to be proportionate to CPP. We have developed a new index for CPP using the Poiseuille equation based on a simple model. Our model suggests that CBF/CBV2 is proportionate to CPP and that it is mathematically a more accurate index than CBF/CBV. This new index needs experimental validation in the future.

Comparison of 18F-FDG PET/CT and 67Ga-SPECT for the diagnosis of fever of unknown origin: a multicenter prospective study in Japan.

OBJECTIVE: The aim of this multicenter prospective study was to compare the sensitivity of 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) with that of 67Ga single photon emission computed tomography (SPECT) for the identification of the site of greatest importance for the final diagnosis of the cause of fever of unknown origin (FUO). METHODS: The study participants consisted of patients with an axillary temperature ≥ 38.0 °C on ≥ 2 occasions within 1 week, with repeated episodes for ≥ 2 weeks prior to providing consent, and whose final diagnosis after undergoing specific examinations, including a chest-to-abdomen CT scan, was uncertain. All the patients underwent FDG-PET/CT imaging first, followed by 67Ga-SPECT imaging within 3 days. The results of the FDG-PET/CT and 67Ga-SPECT examinations were reviewed by the central image interpretation committee (CIIC), which was blinded to all other clinical information. The sensitivities of FDG-PET/CT and 67Ga-SPECT were then evaluated with regard to identifying the site of greatest importance for a final diagnosis of the cause of the fever as decided by the patient's attending physician. The clinical impacts (four grades) of FDG-PET/CT and 67Ga-SPECT on the final diagnosis were evaluated. RESULTS: A total of 149 subjects were enrolled in this study between October 2014 and September 2017. No adverse events were identified among the enrolled subjects. Twenty-one subjects were excluded from the study because of deviations from the study protocol. Among the 128 remaining subjects, a final diagnosis of the disease leading to the appearance of FUO was made for 92 (71.9%) subjects. The final diagnoses in these 92 cases were classified into four groups: noninfectious inflammatory disease (52 cases); infectious disease (31 cases), malignancy (six cases); and other (three cases). These 92 subjects were eligible for inclusion in the study's analysis, but one case did not meet the PET/CT image acquisition criteria; thus, PET/CT results were analyzed for 91 cases. According to the patient-based assessments, the sensitivity of FDG-PET/CT (45%, 95% CI 33.1-58.2%) was significantly higher than that for 67Ga-SPECT (25%, 95% CI 15.5-37.5%) (P = 0.0029). The clinical impact of FDG-PET/CT (91%) was also significantly higher than that for 67Ga-SPECT (57%, P < 0.001). CONCLUSIONS: FDG-PET/CT showed a superior sensitivity to 67Ga-SPECT for the identification of the site of greatest importance for the final diagnosis of the cause of FUO.