Standardized Uptake Value Ratio Research Articles

The mediating effect of 18F-FDG metabolism in right caudate between depressive symptoms and cognitive function in Alzheimer's disease.

The objective of this study was to investigate the accumulation of 18F-fluorodeoxyglucose (18F-FDG) in the whole brain between Alzheimer's disease (AD) with depressive (ADD) symptoms compared with AD without depressive (ADND) symptoms using positron emission tomography/magnetic resonance imaging (PET/MRI). Additionally, this study aimed to explore the associations among the accumulation of 18F-FDG in the brain, depressive symptoms, and cognitive function in ADD patients. In this study, 25 AD patients and 22 healthy controls were enrolled. The AD patients were stratified into two groups, namely ADD and ADND, based on their scores of the Hamilton Depression Scale (HAMD). Both AD patients and healthy controls underwent an 18F-FDG PET/MRI scan. A standardized uptake value ratio (SUVR) was calculated to examine the accumulation of 18F-FDG in the brain. A simple mediation model was employed to examine the mediation effect between SUVR, depressive symptoms and cognitive function in ADD patients. The ADD group exhibited significant cognitive impairment compared to the ADND group (p < 0.001) and healthy controls (p < 0.001). The ADD patients exhibited the reduced SUVR (0.228 ± 0.126) in the right caudate (the voxel level p < 0.005, cluster level p < 0.05, after false discovery rate (FDR) correction) compared to ADND patients (0.459 ± 0.064) and healthy controls (0.706 ± 0.122). The SUVR of the right caudate was correlated with the HAMD scores (r = -0.792, p < 0.001) and mini-mental state examination (MMSE) (r = 0.738, p < 0.01). The relationship between depressive symptoms and the cognitive function in ADD patients is mediated by the right caudate SUVR (total effects = -0.385, direct effects = -0.02, total indirect effects = -0.405). The ADD group exhibited the reduced SUVR in the right caudate compared to the ADND group and healthy controls. The relationship between depressive symptoms and the cognitive ability of AD patients was mediated by the right caudate SUVR. The results contribute to a deeper understanding of the neurobiological mechanisms related to AD with depressive symptoms.

Inter-scanner Aβ-PET harmonization using barrel phantom spatial resolution matching.

The standardized uptake value ratio (SUVR) is used to measure amyloid beta-positron emission tomography (Aβ-PET) uptake in the brainDifferences in PET scanner technologies and image reconstruction techniques can lead to variability in PET images across scanners. This poses a challenge for Aβ-PET studies conducted in multiple centers. The aim of harmonization is to achieve consistent Aβ-PET measurements across different scanners. In this study, we proposean Aβ-PET harmonization methodof matching spatial resolution, as measured viaabarrel phantom, across PET scanners. Our approach wasvalidated using paired subject data, for whichpatients were imaged on multiple scanners. In this study, three different PET scanners were evaluated: the Siemens Biograph Vision 600, Siemens Biograph molecular computed tomography (mCT), and Philips Gemini TF64. A total of five, eight, and five subjects were each scanned twice with [18F]-NAV4694 across Vision-mCT, mCT-Philips, and Vision-Philips scanner pairs. The Vision and mCT scans were reconstructed using various iterations, subsets, and post-reconstruction Gaussian smoothing, whereas only one reconstruction configuration was used for the Philips scans. The full-width at half-maximum (FWHM) of each reconstruction configuration was calculated using [18F]-filled barrel phantom scans with the Society of Nuclear Medicine and Molecular Imaging (SNMMI) phantom analysis toolkit. Regional SUVRs were calculated from 72 brain regions using the automated anatomical labelling atlas 3 (AAL3) atlas for each subject and reconstruction configuration. Statistical similarity between SUVRs was assessed using paired (within subject) t-tests for each pair of reconstructions across scanners; the higher the p-value, the greater the similarity between the SUVRs. Vision-mCT harmonization: Vision reconstruction with FWHM=4.10mm and mCT reconstruction with FWHM=4.30mm gave the maximal statistical similarity (maximum p-value) between regional SUVRs. Philips-mCT harmonization: The FWHM of the Philips reconstruction was 8.2mm and the mCT reconstruction with the FWHM of 9.35mm, which gave the maximal statistical similarity between regional SUVRs. Philips-Vision harmonization: The Vision reconstruction with an FWHM of 9.1mm gave the maximal statistical similarity between regional SUVRs when compared with the Philips reconstruction of 8.2mm and were selected as the harmonized for each scanner pair. Based on data obtained from three sets of participants, each scanned on a pair of PET scanners, it has been verified that using reconstruction configurations that produce matched-barrel, phantom spatial resolutions results in maximally harmonized Aβ-PET quantitation between scanner pairs. This finding is encouraging for the use of PET scanners in multi-center trials or updates during longitudinal studies. Question: Does the process of matching the barrel phantom-derived spatial resolution between scanners harmonize amyloid beta-standardized uptake value ratio (Aβ-SUVR) quantitation? Pertinent findings: It has been validated that reconstruction pairs with matched barrel phantom-derived spatial resolution maximize the similarity between subjects paired Aβ-PET (positron emission tomography) SUVR values recorded on two scanners. Implications for patient care: Harmonization between scanners in multi-center trials and PET camera updates in longitudinal studies can be achieved using a simple and efficient phantom measurement procedure, beneficial for the validity of Aβ-PET quantitation measurements.

Preoperative metabolic parameters of 18F-FDG PET/CT are associated with TNM stage and prognosis of colorectal cancer patients.

Colorectal cancer (CRC) is the third most frequent cause of cancer-related death, while tumor/node/metastasis (TNM) stage of American Joint Committee on Cancer is the guideline of making treatment strategy and predicting survival. The aim of this study is to investigate the association of preoperative 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT), TNM stage, and prognosis of patients with CRC. From September 2016 to August 2022, a total of 132 patients were retrospectively and consecutively enrolled in this cross-sectional study, who were diagnosed as CRC by histopathology and received preoperative 18F-FDG PET/CT. Firstly, the correlation between the metabolic parameters and clinicopathological features of the primary tumors was investigated. Secondly, univariate and multivariate logistic regression analyses were used to estimate the odds ratio of the association between the clinical and metabolic parameters and the advanced TNM stage (stage III-IV). Thirdly, progression-free survival (PFS) was analyzed using Kaplan-Meier curves and Log-rank test. The results revealed that the metabolic tumor volume (MTV) >6.6 cm3 and serum carcinoembryonic antigen (CEA) >5.84 ng/mL were independently associated with advanced TNM stage (P=0.0009, 0.0011, respectively). Larger tumor size, higher tumor-to-liver standardized uptake value ratio, MTV, and total lesion glycolysis (TLG) were significantly correlated with advanced pT stage (stage 4), and higher TLG and MTV were significantly correlated with advanced pN stage (stage 1-2) (P<0.05), while no metabolic parameters were significantly correlated with metastasis status (P>0.05). Higher serum CEA and carbohydrate antigen 19-9 levels were significantly correlated with advanced pT, pN stage, and metastasis status (P<0.05). Patients were followed up for at least 1 year. The MTV >6.6 cm3 was significantly associated with worse PFS (P=0.032). 18F-FDG PET-CT can serve as a noninvasive tool for preoperatively staging CRC. The MTV >6.6 cm3 might be associated with advanced TNM stage and worse PFS.

Relationship Between Amyloid Positivity and Sleep Characteristics in the Elderly With Subjective Cognitive Decline.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognition and performance of daily activities. Recent studies have attempted to establish the relationship between AD and sleep. It is believed that patients with AD pathology show altered sleep characteristics years before clinical symptoms appear. This study evaluated the differences in sleep characteristics between cognitively asymptomatic patients with and without some amyloid burden. Sleep characteristics of 76 subjects aged 60 years or older who were diagnosed with subjective cognitive decline (SCD) but not mild cognitive impairment (MCI) or AD were measured using Fitbit® Alta HR, a wristwatch-shaped wearable device. Amyloid deposition was evaluated using brain amyloid plaque load (BAPL) and global standardized uptake value ratio (SUVR) from fluorine-18 florbetaben positron emission tomography. Each component of measured sleep characteristics was analyzed for statistically significant differences between the amyloid-positive group and the amyloid-negative group. Of the 76 subjects included in this study, 49 (64.5%) were female. The average age of the subjects was 70.72±6.09 years when the study started. 15 subjects were classified as amyloid-positive based on BAPL. The average global SUVR was 1.598±0.263 in the amyloid-positive group and 1.187±0.100 in the amyloid-negative group. Time spent in slow-wave sleep (SWS) was significantly lower in the amyloid-positive group (39.4±13.1 minutes) than in the amyloid-negative group (49.5±13.1 minutes) (p=0.009). This study showed that SWS is different between the elderly SCD population with and without amyloid positivity. How SWS affects AD pathology requires further research.

Alzheimer Disease Pathology and Neurodegeneration in Midlife Obesity: A Pilot Study.

Obesity and excess adiposity at midlife are risk factors for Alzheimer disease (AD). Visceral fat is known to be associated with insulin resistance and a pro-inflammatory state, the two mechanisms involved in AD pathology. We assessed the association of obesity, MRI-determined abdominal adipose tissue volumes, and insulin resistance with PET-determined amyloid and tau uptake in default mode network areas, and MRI-determined brain volume and cortical thickness in AD cortical signature in the cognitively normal midlife population. Thirty-two middle-aged (age: 51.27±6.12 years, 15 males, body mass index (BMI): 32.28±6.39 kg/m2) cognitively normal participants, underwent bloodwork, brain and abdominal MRI, and amyloid and tau PET scan. Visceral and subcutaneous adipose tissue (VAT, SAT) were semi-automatically segmented using VOXel Analysis Suite (Voxa). FreeSurfer was used to automatically segment brain regions using a probabilistic atlas. PET scans were acquired using [11C]PiB and AV-1451 tracers and were analyzed using PET unified pipeline. The association of brain volumes, cortical thicknesses, and PiB and AV-1451 standardized uptake value ratios (SUVRs) with BMI, VAT/SAT ratio, and insulin resistance were assessed using Spearman's partial correlation. VAT/SAT ratio was associated significantly with PiB SUVRs in the right precuneus cortex (p=0.034) overall, controlling for sex. This association was significant only in males (p=0.044), not females (p=0.166). Higher VAT/SAT ratio and PiB SUVRs in the right precuneus cortex were associated with lower cortical thickness in AD-signature areas predominantly including bilateral temporal cortices, parahippocampal, medial orbitofrontal, and cingulate cortices, with age and sex as covariates. Also, higher BMI and insulin resistance were associated with lower cortical thickness in bilateral temporal poles. In midlife cognitively normal adults, we demonstrated higher amyloid pathology in the right precuneus cortex in individuals with a higher VAT/SAT ratio, a marker of visceral obesity, along with a lower cortical thickness in AD-signature areas associated with higher visceral obesity, insulin resistance, and amyloid pathology.

Prognostic value of lymph node-to-primary tumor ratio of PET standardized uptake value for nasopharyngeal carcinoma: a recursive partitioning risk stratification analysis.

Induction chemotherapy (IC) combined with concurrent chemoradiotherapy has become the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Data on the prognostic value of the lymph node-to-primary tumor ratio (NTR) of positron emission tomography (PET) standardized uptake value (SUV) for patients treated with IC were limited. To evaluate the prognostic value of the SUV NTR for patients with LA-NPC treated with IC. In all, 467 patients with pretreatment 18F-fluorodeoxyglucose PET/computed tomography (CT) scans between September 2017 and November 2020 were retrospectively reviewed. The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value of SUV NTR. Kaplan-Meier method was used to evaluate survival rates. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. The optimal cutoff value of SUV NTR was 0.74. Multivariate analyses showed that SUV NTR and overall stage were independent predictors for distant metastasis-free survival (DMFS) and regional recurrent-free survival (RRFS). Therefore, an RPA model based on the endpoint of DMFS was generated and categorized the patients into three distinct risk groups: RPA I (low risk: SUV NTR < 0.74 and stage III), RPA II (medium risk: SUV NTR < 0.74 and stage IVa, or SUV NTR ⩾ 0.74 and stage III), and RPA III (high risk: SUV NTR ⩾ 0.74 and stage IVa), with a 3-year DMFS of 98.9%, 93.4%, and 84.2%, respectively. ROC analysis showed that the RPA model had superior predictive efficacy than the SUV NTR or overall stage alone. SUV NTR was an independent prognosticator for distant metastasis and regional recurrence in locoregionally advanced NPC. The RPA risk stratification model based on SUV NTR provides improved DMFS and RRFS prediction over the eighth edition of the TNM (Tumor Node Metastasis) staging system.

18F-FP-DTBZ PET/CT detectable associations between monoaminergic depletion in the putamen with rigidity and the pallidus with tremor in Parkinson's disease

IntroductionThe motor subtypes of Parkinson's disease (PD) are widely accepted and implemented. However, the motor subtypes have been thought to represent different stages of PD recently because some patients experience tremor-dominant (TD) conversion to the non-tremor-dominant subtype, such as postural instability–gait difficulty (PIGD). In this study, we explore the monoaminergic denervation features of the striatal and extra-striatal areas in patients with different subtypes of PD with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ) PET/CT. MethodsSixty-five patients diagnosed with PD were included and classified as TD (n = 25) and PIGD (n = 40). We evaluated the difference of monoaminergic features of each subregion of brain between motor subtypes of PD, as well as associations between these features and Parkinsonian motor symptoms. ResultsThe striatal standardized uptake value ratios (SUVR) showed that dopaminergic disruption of patients with PIGD was more symmetrical in the posterior ventral putamen (p < 0.001) and more severe in the ipsilateral posterior dorsal putamen (p < 0.001 corrected) compared with that of patients with TD. The severity of PIGD scores was associated with striatal dopaminergic depletion, while tremor was associated with monoaminergic changes in extra-striatal areas, including pallidus, thalamus, and raphe nuclie. ConclusionThese results indicate that patients with different motor subtypes may have different underlying mechanisms of PD pathogenesis. Therefore, accurate diagnosis of PD subtypes can aid prognosis evaluation and treatment decision-making.

Frontal and anterior temporal hypometabolism post chemoradiation in head and neck cancer: A real-world PET study.

Adverse neurological effects after cancer therapy are common, but biomarkers to diagnose, monitor, or risk stratify patients are still not validated or used clinically. An accessible imaging method, such as fluorodeoxyglucose positron emission tomography (FDG PET) of the brain, could meet this gap and serve as a biomarker for functional brain changes. We utilized FDG PET to evaluate which brain regions are most susceptible to altered glucose metabolism after chemoradiation in patients with head and neck cancer (HNCa). Real-world FDG PET images were acquired as standard of care before and after chemoradiation for HNCa in 68 patients. Linear mixed-effects voxelwise models assessed changes after chemoradiation in cerebral glucose metabolism quantified with standardized uptake value ratio (SUVR), covarying for follow-up time and patient demographics. Voxelwise analysis revealed two large clusters of decreased glucose metabolism in the medial frontal and polar temporal cortices following chemoradiation, with decreases of approximately 5% SUVR after therapy. These findings provide evidence that standard chemoradiation for HNCa can lead to decreased neuronal glucose metabolism, contributing to literature emphasizing the vulnerability of the frontal and anterior temporal lobes, especially in HNCa, where these areas may be particularly vulnerable to indirect radiation-induced injury. FDG PET shows promise as a sensitive biomarker for assessing these changes.

Tau Imaging in Late Traumatic Brain Injury: A [18F]MK-6240 Positron Emission Tomography Study.

Epidemiological studies have identified prior traumatic brain injury (TBI) as a risk factor for developing Alzheimer's disease (AD). Neurofibrillary tangles (NFTs) are common to AD and chronic traumatic encephalopathy following repetitive mild TBI. However, it is unclear if a single TBI is sufficient to cause accumulation of NFTs. We performed a [18F]MK-6240 positron emission tomography (PET) imaging study to assess NFTs in patients who had sustained a single TBI at least 2 years prior to study inclusion. Fourteen TBI patients (49 ± 20 years; 5 M/9 F; 8 moderate-severe, 1 mild-probable, 5 symptomatic-possible TBI) and 40 demographically similar controls (57 ± 19 years; 19 M/21 F) underwent simultaneous [18F]MK-6240 PET and magnetic resonance imaging (MRI) as well as neuropsychological assessment including the Cambridge Neuropsychological Test Automated Battery (CANTAB). A region-based voxelwise partial volume correction was applied, using parcels obtained by FreeSurfer v6.0, and standardized uptake value ratios (SUVR) were calculated relative to the cerebellar gray matter. Group differences were assessed on both a voxel- and a volume-of-interest-based level and correlations of [18F]MK-6240 SUVR with time since injury as well as with clinical outcomes were calculated. Visual assessment of TBI images did not show global or focal increases in tracer uptake in any subject. On a group level, [18F]MK-6240 SUVR was not significantly different in patients versus controls or between subgroups of moderate-severe TBI versus less severe TBI. Within the TBI group, One Touch Stockings problem solving and spatial working memory (executive function), reaction time (attention), and Mini-Mental State Examination (MMSE) (global cognition) were associated with [18F]MK-6240 SUVR. We found no group-based increase of [18F]MK-6240 brain uptake in patients scanned at least 2 years after a single TBI compared with healthy volunteers, which suggests that no NFTs are building up in the first years after a single TBI. Nonetheless, correlations with cognitive outcomes were found that warrant further investigation.

Investigating neural dysfunction with abnormal protein deposition in Alzheimer’s disease through magnetic resonance spectroscopic imaging, plasma biomarkers, and positron emission tomography

In Alzheimer’s disease (AD), aggregated abnormal proteins induce neuronal dysfunction. Despite the evidence supporting the association between tau proteins and brain atrophy, further studies are needed to explore their link to neuronal dysfunction in the human brain. To clarify the relationship between neuronal dysfunction and abnormal proteins in AD-affected brains, we conducted magnetic resonance spectroscopic imaging (MRSI) and assessed the neurofilament light chain plasma levels (NfL). We evaluated tau and amyloid-β depositions using standardized uptake value ratios (SUVRs) of florzolotau (18F) for tau and 11C-PiB for amyloid-β positron emission tomography in the same patients. Heatmaps were generated to visualize Z scores of glutamate to creatine (Glu/Cr) and N-acetylaspartate to creatine (NAA/Cr) ratios using data from healthy controls. In AD brains, Z score maps revealed reduced Glu/Cr and NAA/Cr ratios in the gray matter, particularly in the right dorsolateral prefrontal cortex (rDLPFC) and posterior cingulate cortex (PCC). Glu/Cr ratios were negatively correlated with florzolotau (18F) SUVRs in the PCC, and plasma NfL levels were elevated and negatively correlated with Glu/Cr (P = 0.040, r = −0.50) and NAA/Cr ratios (P = 0.003, r = −0.68) in the rDLPFC. This suggests that the abnormal tau proteins in AD-affected brains play a role in diminishing glutamate levels. Furthermore, neuronal dysfunction markers including Glu/tCr and NAA/tCr could potentially indicate favorable clinical outcomes. Using MRSI provided spatial information about neural dysfunction in AD, enabling the identification of vulnerabilities in the rDLPFC and PCC within the AD’s pathological context.

MUSCLE MITOCHONDRIAL FUNCTION PREDICTS COGNITIVE IMPAIRMENT AND IS ASSOCIATED WITH PET AND BLOOD BIOMARKERS OF AD

Abstract Mitochondrial dysfunction is a hallmark of aging. Whether mitochondrial dysfunction is related to future cognitive impairment and biomarkers of Alzheimer’s disease (AD) is unknown. In the Baltimore Longitudinal Study of Aging, we used Cox regression to examine the association of skeletal muscle mitochondrial function (post-exercise recovery rate of phosphocreatine, kPCr) via MR spectroscopy with future MCI or dementia over an average follow-up of 3.3 years among 460 initially cognitively normal participants (mean age=76.8±11.0 years, 56.7% women, 22.4% Black). We also examined associations with PiB-distribution volume ratio (DVR) for β-amyloid (Aβ)(n=115), Flortaucipir (FTP)-standardized uptake value ratio (SUVR) for tau(n=70), and blood biomarkers of AD pathology (Aβ42/Aβ40 ratio,n=299; pTau181,n=505), neuronal injury (NfL)(n=299), and astrocyte-mediated neuroinflammation (GFAP)(n=299) using linear regression. After adjustment for age, sex, and race, each SD higher kPCr (i.e. 0.005) was associated with 45% lower hazards of developing cognitive impairment (19 MCI, 4 dementia) (p=0.04). In the PET sample, each SD higher kPCr was associated with 51% lower odds of being PiB positive(p=0.003). Higher kPCr was specifically associated with lower DVR in precentral and postcentral gyri, superior parietal lobe, and pallidum (FDR-adjusted p&amp;lt;0.05). In samples with blood biomarkers, higher kPCr was associated with lower GFAP(p=0.01) and showed a trend toward significance with lower pTau181(p=0.08). Preserved skeletal muscle mitochondrial function is associated with reduced risk of cognitive impairment and PET and blood biomarkers of AD. Future studies are needed to investigate the role of mitochondrial function of the central nervous system in dementia risk and the progression of AD pathologic change.

LOCALIZATION OF Β-AMYLOID PLAQUES IN THE BRAINS OF WAR VETERANS, PARTICIPANTS OF THE DOD-ADNI STUDY

Abstract We examined the allocation of β-amyloid (Aβ) plaques in the brains of Veterans, long-time survivors of traumatic brain injury (TBI), and those, who did not report brain trauma, and compared it with a spatial distribution of Aβ plaques in the brains of participants of the ADNI program as well as with the pattern of the spatial distribution of Aβ in the brains of participants of ADNI with Alzheimer’s disease. This study included 675 community-dwelling male participants from the ADNI and DoD-ADNI databases (137 veterans, 131 cases of TBI, and 123 AD cases) 62 years old or older. We performed regression analysis, using a pseudo-randomization algorithm, and propensity-score inverse-probability weighting to equalize the subsamples for fourteen outcomes, 12 standardized uptake value ratio variables, and 0.79 and 1.11 cutoffs. Race, educational level, geriatric depression score, age when florbetapir-18 (18F) PET scans were performed, APOE genotype, and Modified Hachinski Ischemic Score were used as predictors. The pattern common for AD showed the highest levels of β-amyloid in the cingulate cortex as well as in the frontal, parietal, and temporal lobes. Veterans have shown a statistically significant increase of 18F concentration in the cerebellum gray matter along with a lower concentration of it in the whole cerebrum as well as in neocortical regions than patients, who did not participate in combats. The continuous exposition to micro-TBI events, which does not necessarily suppose the loss of consciousness or severe contusion likely can explain the high concentration of 18F in cerebellum gray matter in ex-combatants.

Morphological and metabolic asymmetries of the thalamic subregions in temporal lobe epilepsy predict cognitive functions

Both morphological and metabolic imaging were used to determine how asymmetrical changes of thalamic subregions are involved in cognition in temporal lobe epilepsy (TLE). We retrospectively recruited 24 left-TLE and 15 right-TLE patients. Six thalamic subnuclei were segmented by magnetic resonance imaging, and then co-registered onto Positron emission tomography images. We calculated the asymmetrical indexes of the volumes and normalized standard uptake value ratio (SUVR) of the entire and individual thalamic subnuclei. The SUVR of ipsilateral subnuclei were extensively and prominently decreased compared with the volume loss. The posterior and medial subnuclei had persistently lower SUVR in both TLE cases. Processing speed is the cognitive function most related to the metabolic asymmetry. It negatively correlated with the metabolic asymmetrical indexes of subregions in left-TLE, while positively correlated with the subnuclei volume asymmetrical indexes in right-TLE. Epilepsy duration negatively correlated with the volume asymmetry of most thalamic subregions in left-TLE and the SUVR asymmetry of ventral and intralaminar subnuclei in right-TLE. Preserved metabolic activity of contralateral thalamic subregions is the key to maintain the processing speed in both TLEs. R-TLE had relatively preserved volume of the ipsilateral thalamic volume, while L-TLE had relatively decline of volume and metabolism in posterior subnucleus.

Assessment of unilateral condylar hyperplasia with quantitative SPECT/CT

PurposeThe current study aimedto assess condylar activityin patients with unilateral condylar hyperplasia (UCH) with quantitative SPECT/CT. Patients and methodsThis retrospective study included patients with UCH who underwent quantitative SPECT/CT. SPECT analysis and quantification of SPECT/CT were performed, and the maximum count per pixel and SUVmax of either side of the condyles were calculated. Results39 patients were included in the analysisand classified into three subgroups according to the percentile differential right-left ratio: inactive group, left active (LA) group, and right active (RA) group. Totally, the SUVmax of the affected side is significantly higher than the unaffected side (active:5.93 ± 2.43 vs inactive:3.62 ± 1.76, P < 0.001), SUVmax-based ratios correlated well with the ratios based on maximum count (R = 0.944, P < 0.001). ROC analysis showed poorSUVmaxperformance in differentiation between theactive condyles and the inactive condyles due to the lower area under the curve (AUC) (0.588). In subgroup analysis, the affected side is significantly higher than the unaffected side in active groups with SUVmax, no significant difference was found between the active sides or the inactive sides of active groups. Interestingly, the SUVmax of the left side was statistically higher than that of the right sidein the inactive group (P = 0.01),while the left side of the right active group has significantlylower activitythan that in the inactive group, meanwhile,the right side showed no significant difference. Furthermore, each side showed no significant difference between the left active group and the inactive group. ConclusionsSUVmax is not an optimal measurement effectively used to evaluate active condyles. However, SUV ratios correlated well with the count ratios, and the left side of condyles showed a peculiar feature in condyle growth status reflected in radioactivity quantified with SPECT/CT, which needs further study to determine the role in the development of the UCH.

Predicting positron emission tomography brain amyloid positivity using interpretable machine learning models with wearable sensor data and lifestyle factors

BackgroundDeveloping a screening method for identifying individuals at higher risk of elevated brain amyloid burden is important to reduce costs and burden to patients in clinical trials on Alzheimer’s disease or the clinical setting. We developed machine learning models using objectively measured lifestyle factors to predict elevated brain amyloid burden on positron emission tomography.MethodsOur prospective cohort study of non-demented, community-dwelling older adults aged ≥ 65 years was conducted from August 2015 to September 2019 in Usuki, Oita Prefecture, Japan. One hundred and twenty-two individuals with mild cognitive impairment or subjective memory complaints (54 men and 68 women, median age: 75.50 years) wore wearable sensors and completed self-reported questionnaires, cognitive test, and positron emission tomography imaging at baseline. Moreover, 99 individuals in the second year and 61 individuals in the third year were followed up. In total, 282 eligible records with valid wearable sensors, cognitive test results, and amyloid imaging and data on demographic characteristics, living environments, and health behaviors were used in the machine learning models. Amyloid positivity was defined as a standardized uptake value ratio of ≥ 1.4. Models were constructed using kernel support vector machine, Elastic Net, and logistic regression for predicting amyloid positivity. The mean score among 10 times fivefold cross-validation repeats was utilized for evaluation.ResultsIn Elastic Net, the mean area under the receiver operating characteristic curve of the model using objectively measured lifestyle factors alone was 0.70, whereas that of the models using wearable sensors in combination with demographic characteristics and health and life environment questionnaires was 0.79. Moreover, 22 variables were common to all machine learning models.ConclusionOur machine learning models are useful for predicting elevated brain amyloid burden using readily-available and noninvasive variables without the need to visit a hospital.Trial registrationThis prospective study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of Oita University Hospital (UMIN000017442). A written informed consent was obtained from all participants. This research was performed based on the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.

An automated pipeline for Centiloid quantification of amyloid‐β using multiple 11C‐PiB‐PET and 18F‐PET tracers

AbstractBackgroundQuantitative measures of amyloid‐ß (Aß) pathology using positron emission tomography (PET) imaging are sensitive to identify pathological changes early in Alzheimer’s disease (AD). The Centiloid scale aims to standardize these in vivo amyloid quantifications to a 100‐point scale, where an average value of zero signifies high certainty of amyloid negativity and 100 identifies average typical AD Aß‐pathology load (Klunk et al., 2015). The current study developed and validated a single and fully automated Centiloid quantification pipeline for multiple amyloid PET compounds.MethodQyScore’s® fully automated pipeline was validated on 11C‐PiB‐PET and 18F‐PET images from the Centiloid project (https://www.gaain.org/centiloid‐project): 34 young controls [age = 31.5 ± 6.3 years] and 47 AD patients [age = 67.5 ± 10.5 years; CDR = 0.5–1]. 18F tracers included Florbetapir (FBP, N = 46), Forbetaben (FBB, N = 35), Flutemetamol (FTM, N = 74) and NAV4694 (NAV, N = 55). PET/MR image pairs were both co‐registered and normalized in the MNI template space. The fully automated segmentation from QyScore®, a CE‐marked and FDA‐cleared neuroimaging medical device, parcellated the masks of the grey matter tissue (target) and of the cerebellum (reference) region (Figure 1). The standardized uptake value ratio (SUVr) was computed as the ratio of the mean signal in both regions. Correlations of 11C‐PiB‐PET and 18F‐PET SUVr values with published SUVr data were computed. Further, correlations between 18F‐PET SUVr and paired 11C‐PiB‐PET SUVr were computed. Correlation coefficients (R2) &gt; 0.7 were required to consider the Centiloid calibration valid.ResultQyScore’s® fully automated quantitative pipeline produced SUVr values well within the bounds defined by the Centiloid method (SUVr_AD‐100 = 2.08 +/‐ 0.2; SUVr_YC‐0 = 1.01+/‐ 0.05; R2 = 0.99; slope = 1.00; intercept = ‐0.44). 11C‐PiB SUVr correlation coefficients with published values were above 0.99 (Figure 2). Correlation coefficients of 18F‐PET SUVr with 11C‐PiB‐PET SUVr were respectively 0.91, 0.95, 0.96, 0.99 (Figure 3). Equations for converting to Centiloid were respectively: • Centiloid = 177.79 FBP_SUVr ‐ 183.56 • Centiloid = 153.08 FBB_SUVr – 152.93 • Centiloid = 122.39 FTM_SUVr – 120.97 • Centiloid = 90.20 NAV_SUVr – 91.61ConclusionWe demonstrate the feasibility and reliability of a fully automated amyloid PET pipeline for multiple amyloid‐PET compounds (11C‐PiB and 18F) suitable for implementation in clinical trials.

An automated pipeline for Centiloid quantification of amyloid‐β using multiple 11C‐PiB‐PET and 18F‐PET tracers

AbstractBackgroundQuantitative measures of amyloid‐β (Aβ) pathology using positron emission tomography (PET) imaging are sensitive to identify pathological changes early in Alzheimer’s disease (AD). The Centiloid scale aims to standardize these in vivo amyloid quantifications to a 100‐point scale, where an average value of zero signifies high certainty of amyloid negativity and 100 identifies average typical AD Aβ‐pathology load (Klunk et al., 2015). The current study developed and validated a single and fully automated Centiloid quantification pipeline for multiple amyloid PET compounds.MethodQyScore’s® fully automated pipeline was validated on 11C‐PiB‐PET and 18F‐PET images from the Centiloid project (https://www.gaain.org/centiloid‐project): 34 young controls [age = 31.5 ± 6.3 years] and 47 AD patients [age = 67.5 ± 10.5 years; CDR = 0.5–1]. 18F tracers included Florbetapir (FBP, N = 46), Forbetaben (FBB, N = 35), Flutemetamol (FTM, N = 74) and NAV4694 (NAV, N = 55). PET/MR image pairs were both co‐registered and normalized in the MNI template space. The fully automated segmentation from QyScore®, a CE‐marked and FDA‐cleared neuroimaging medical device, parcellated the masks of the grey matter tissue (target) and of the cerebellum (reference) region (Figure 1). The standardized uptake value ratio (SUVr) was computed as the ratio of the mean signal in both regions. Correlations of 11C‐PiB‐PET and 18F‐PET SUVr values with published SUVr data were computed. Further, correlations between 18F‐PET SUVr and paired 11C‐PiB‐PET SUVr were computed. Correlation coefficients (R2) &gt; 0.7 were required to consider the Centiloid calibration valid.ResultQyScore’s® fully automated quantitative pipeline produced SUVr values well within the bounds defined by the Centiloid method (SUVr_AD‐100 = 2.08 +/‐ 0.2; SUVr_YC‐0 = 1.01+/‐ 0.05; R2 = 0.99; slope = 1.00; intercept = ‐0.44). 11C‐PiB SUVr correlation coefficients with published values were above 0.99 (Figure 2). Correlation coefficients of 18F‐PET SUVr with 11C‐PiB‐PET SUVr were respectively 0.91, 0.95, 0.96, 0.99 (Figure 3).Equations for converting to Centiloid were respectively o Centiloid = 177.79 FBP_SUVr ‐ 183.56 o Centiloid = 153.08 FBB_SUVr – 152.93 o Centiloid = 122.39 FTM_SUVr – 120.97 o Centiloid = 90.20 NAV_SUVr – 91.61ConclusionWe demonstrate the feasibility and reliability of a fully automated amyloid PET pipeline for multiple amyloid‐PET compounds (11C‐PiB and 18F) suitable for implementation in clinical trials.

Eligibility in the INTERCEPT‐AD trial: visual amyloid classification for equivocal SUVrs in early Alzheimer’s disease

AbstractBackgroundPET tracers enable the in‐vivo measurement of amyloid in the brain and have been incorporated in eligibility criteria for clinical trials. Automated quantitative image analysis enables the calculation of a standardised uptake value ratio (SUVr) which can enable a rapid amyloid classification without requiring a visual read. However, quantitative analysis may have an equivocal range where amyloid classification does require a visual read. The range of SUVrs that is equivocal is not well understood.MethodParticipants in the INTERCEPT‐AD trial of ACU193 (Siemers et al., J Prev Alzheimers Dis. 2023;10(1):19‐24) underwent an amyloid [18F] Florbetapir PET scan and T1‐weighted MRI scans. MRIs were segmented using the LEAP algorithm (Wolz et al., NeuroImage. 2010;49(2):1316‐1325), registered to the PET image, and the global cortical average (GCA) SUVr based on brain regions typically with high amyloid load in Alzheimer’s disease (Klunk et al., Alzheimers Dement. 2015;11(1):1‐15) was calculated, using the whole cerebellum as the reference region. SUVrs greater than 1.2 were classified as amyloid positive, SUVrs less than 1.0 were classified as amyloid negative, and SUVrs in the equivocal range were assessed by visual read by trained central radiologists.ResultsOf 194 participants who underwent screening, 188 had an SUVr available from automated analysis. Of these, 64 were within the equivocal range (SUVr 1.0 – 1.2) and had a visual read performed. For PET scans in the equivocal range, 53 (83%) were classified as amyloid negative and 11 (17%) were classified as amyloid positive by visual read. Within the equivocal range, there was no difference in SUVrs between the images classified by visual read as amyloid negative or positive.ConclusionSUVrs may be used as an objective quantitative amyloid classification method at values &gt; 1.2 for trial inclusion; however, in the equivocal range, the GCA SUVr did not correspond with amyloid classification based on a visual read. Further study is required to investigate the equivocal range and the use of combined quantitative measures and visual reads.

Impact of florbetaben acquisition timing on continuous and dichotomous measures of amyloid burden: implications for real‐world amyloid PET interpretation

AbstractBackgroundThe magnitude of Standardized Uptake Value Ratios (SUVRs) and Centiloid (CL) values increase at later acquisition windows for Florbetaben (FBB). As amyloid PET is anticipated to be utilized for treatment decisions with anti‐amyloid therapeutics (van Dyck, 2022), it is important to understand acquisition factors that influence PET quantification.MethodWe analyzed 120 FBB scans from the Stanford Alzheimer’s Disease Research Center with 5‐minute frame data spanning 70‐110 minutes post‐injection (Table 1). Frame data were motion corrected, summed into 70‐90 and 90‐110‐minute files, and processed through an MRI‐Free pipeline. A global cortical target region and whole cerebellum reference region from the GAAIN atlas were used to create SUVRs and CLs (Klunk, 2014). SUVRs and CLs computed across the two acquisition windows were compared using linear regression to understand the effects of timing acquisition on magnitude. Gaussian Mixture Models (GMM) were used to convert SUVRs to a probability scale separately for 70‐90 and 90‐110 datasets. 10,000 bootstrapped mixed timing datasets were created by randomly selecting either 70‐90 or 90‐110 SUVRs for a given participant, which was then used to understand the impact of GMM‐based classification into A‐ and A+ groups when acquisition time varies within dataset.ResultCLs were systematically lower during the earlier acquisition window (2.01 CL for the CL&lt;10 group, ΔCL range = ‐8.83,9.16; 2.89 CL for the 10‐25 group, ΔCL range = ‐2.18,9.33; 3.62 CL for the 25‐50 group, ΔCL range = ‐0.04,11.34; and 10.94 for the &gt;50 group, ΔCL range = 1.81,26.98) (Fig. 1). GMM classification into A‐ and A+ groups was consistent across the two acquisition windows and in the mixed timing datasets (Table 2).ConclusionGMM is a robust quantitative method that can be used to characterize amyloid PET scans into A‐ and A+ groups when acquisition time varies. However, given the inconsistent impact of acquisition time on CL magnitude, comparison of CL values before and after anti‐amyloid treatments will require adjustment for scan acquisition time. Future work is needed to establish methods that can measure amyloid PET change when acquisition times vary within an individual patient. This is especially important for evaluating the efficacy of currently approved anti‐amyloid therapeutic approaches.

The impact of young controls in the detection of tau load in cognitively impaired and asymptomatic elderly

AbstractBackgroundNeuropathological observations report incipient tau accumulation in the human brain starting in the third decade of life, with the proportion of individuals with some degree of tau deposition increasing with age. Given the high prevalence of tau positive cases among cognitively unimpaired (CU) older adults, one may question whether these individuals constitute an ideal reference group when assessing tau load in symptomatic population. Here, we compare tau biomarker levels of participants with Alzheimer’s disease (AD) and CU of different ages.MethodWe evaluated 35 CU young individuals (aged &lt;26 years) and 124 amyloid‐beta (Aβ)‐ elderly, considered the two control groups. We also assessed 42 Aβ+ CU and 122 Aβ+ cognitively impaired (CI) individuals, diagnosed with either mild cognitive impairment or AD dementia. Participants were assessed with 18F‐MK6240 positron emission tomography (PET) and CSF and plasma pTau181, 217, 231 and 235. We used linear regression to perform voxel‐wise comparisons of tau‐PET signal between groups. We compared the standardized uptake value ratio (SUVR) in medial‐temporal and Braak‐like regions‐of‐interest (ROI) and fluid biomarkers levels using the Wilcoxon rank sum test.ResultIn the voxel‐wise comparisons (Figure 1A‐E), CI participants presented more widespread cortical signal than control groups. Less signal in the parietal cortex was observed in the comparison with CU young. Higher t‐values were observed in Aβ+ CU individuals in the medial temporal region, compared to both control groups, and adjacent neocortex, especially compared to CU young. Temporal and Braak V‐VI SUVR were higher in CI but not in Aβ+ CU individuals compared to controls. Moreover, Braak I‐II and III‐IV SUVR and the fluid biomarkers levels were higher in both Aβ+ groups compared to controls (Figures 2A‐D; 3A‐G). Importantly, Braak I‐II SUVR and the CSF biomarkers levels were higher in CU old Aβ‐ versus young.ConclusionHere, we provide in vivo evidence that tau‐load in age‐matched Aβ‐ controls constitutes a bias for identifying tau pathology, particularly in individuals at early stages of AD pathophysiology. Age‐related tau load should be considered when selecting control groups to assess tau in symptomatic populations, especially those with early AD, and when defining criteria for tau abnormality.