Standardized Uptake Value Ratio Research Articles

The cerebellar glucose metabolism in moyamoya vasculopathy and its correlation with neurocognitive performance after cerebral revascularization surgery: a [18F]FDG PET study.

The vascular cognitive impairment (VCI) is quite common in moyamoya vasculopathy (MMV). However, the abnormality of cerebellar glucose metabolism in MMV and its relationship with patients' neurocognitive performance were few reported. In this study, we aimed to investigate the relationship between neurocognitive performance and cerebellar glucose metabolism. Furthermore, the cerebellar glucose metabolism changes after combined revascularization surgery were also researched. We retrospectively analyzed the 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography ([18F]FDG PET) images and their neuropsychological scales in 93 eligible MMV patients by comparing their cerebellar standardized uptake values ratio (SUVR) and metabolic covariant network (MCN) among different neurocognitive groups. Then, forty-two MMV patients with VCI who underwent combined revascularization surgery were prospectively observed. According to their neuropsychological performance at 6-month follow-up, these patients were assigned to cognitive improved group (n = 22) and non-improved group (n = 20). The cerebellar SUVR and MCN changes were also analyzed. SUVR of right Lobule VI/Crus II/VIII decreased when cognitive impairment progression (P < 0.05, Least-Significant Difference [LSD] post hoc analysis). The cerebellar glucose metabolic pattern can be divided into two parts, in which the cerebellar posterior lobe was positively related to patients' neurocognitive performance, while the vermis and anterior lobe showed negative relationship with the neurocognitions (P < 0.001). Further MCN analysis expound that the degree of right Lobule VI/Crus II/VIII displayed decreased tendency as cognitive impairment worsened (P < 0.05, LSD post hoc analysis). After revascularization surgery, the SUVR of right cerebellar posterior lobe significantly promoted in improved group (P < 0.001). Besides, we also witnessed the SUVR improvement in left cerebral hemisphere, thalamus, and red nucleus (P < 0.001). The MCN analysis revealed that the posterior connective strength improvement among right Lobule VI and several cerebral regions significantly correlated with memory and executive screening (MES) score (P < 0.001, false discovery rate corrected). We found that the hypometabolism of cerebellar posterior lobe, especially in the right Lobule VI, was associated with MMV patients' neuropsychological performance, while the anterior lobe and vermis showed opposites tendencies. Combined revascularization surgery improved the posterior cerebellar metabolism and was associated with favorable neurocognitive outcomes, which might be related to the activation of cortico-rubral-cerebellar pathway.

Test-Retest performance of [18F]MK-6240 tau burden and relative delivery indices in cognitively normal older subjects using PET/MRI

Abstract Accurate interpretation of quantitative PET outcomes hinges on understanding the test-retest variability (T-RT). Previous studies of the tau-PET ligand [18F]MK-6240 reported adequate T-RT performance of tau burden estimates over a short-term 21-day and over a longer-term 6-month T-RT period, primarily involving Alzheimer’s disease (AD) and cognitively normal (CN) subjects, respectively. However, several T-RT characteristics have not yet been reported, particularly in older CN (oCN) subjects. Here, we investigate the short-term T-RT performance of dynamic [18F]MK-6240 outcomes in a group largely consisting of oCN. We report T-RT for uptake in potential reference regions, for extracerebral off-target signal, and for estimates of tau burden and relative delivery indices in tau-bearing target regions. Eight participants (7 oCN, 1 AD) underwent baseline dynamic [18F]MK-6240 PET/MRI (Biograph mMR) and a retest follow-up PET/MRI scan within approximately 3 weeks. T-RT was evaluated using absolute percentage differences and intraclass correlation coefficients (ICC) in three groups of regions: 1) potential reference regions using standardized-uptake-values 90-110 minutes post-injection (SUV90-110min); 2) target regions using SUV ratios (SUVR90-110min), distribution volume ratios (DVR), and relative delivery (R1); and 3) extracerebral region using SUVR90-110min. A voxel-based partial volume correction (PVC) was applied. T-RT was evaluated with and without PVC. In oCN subjects, the SUV90-110min T-RT in the evaluated reference regions ranged from 6-11% (ICC &amp;gt; 0.9); target region T-RT was similar for SUVR90-110min (4-9%, ICC: 0.62-0.97), DVR (3-10%, ICC: 0.66-0.92), and R1 (3-14%, ICC: 0.52-0.97). PVC had minimal impact on reference region SUV90-110min T-RT, but increased target region T-RT variability (SUVR90-110min: 10-26%; DVR: 6-22%; R1: 4-20%). Extracerebral SUVR90-110min exhibited higher T-RT variability (~12%, ICC: 0.85) than other target regions (average 6%) and increased to ~15% after PVC. Our findings are consistent with previous reports and provide further evidence of acceptable [18F]MK-6240 T-RT in low-signal oCN subjects. Our results suggest [18F]MK-6240 is suitable for detecting early tau deposition and longitudinal changes over time, and further support the viability of [18F]MK-6240 R1 to evaluate longitudinal changes in perfusion. PVC increased T-RT variability in tau burden and R1 outcomes. Notably, the extracerebral signal exhibited higher T-RT variability than other target and reference regions and may affect their signal.

Exposure duration and cerebral amyloidosis in the olfactory cortex of World Trade Center responders: A positron emission tomography and magnetic resonance imaging study.

Amyloid-β proteins, a hallmark of Alzheimer's disease, are believed to play an adaptive role in the cerebral immune response. Amyloid is believed to play a role in cerebral immune response and could play a similar role in response to air pollution exposures. In the present study, we examined whether WTC exposure duration was associated with cerebral amyloidosis in WTC responders. WTC responders (aged 44-65 years) who varied in exposure duration but did not use personalized protective equipment were assessed using positron-emission tomography with [18F]-Florbetaben. The outcome was the cortical [18F]-Florbetaben burden, measured using regional standardized uptake value ratios (SUVRs) in 34 Desikan-Killiany regions of interest. Spearman's ρ and generalized linear models were used to estimate correlations between WTC exposure duration and cortical [18F]-Florbetaben SUVR. Cognitive and behavioral symptoms were measured. Magnetic resonance imaging was used to measure cortical thickness and diffusivity. The mean age of imaged responders was 56 years old. WTC exposure duration was associated with olfactory [18F]-Florbetaben SUVR (Spearman's ρ = 0.43, p = 0.011), which was in turn associated with elevated [18F]-Florbetaben SUVR in ventral regions (ρ = 0.41, p = 0.016). Cortical [18F]-Florbetaben in ventral regions was associated with reduced response speed (ρ = -0.72, p < 0.001), was co-located with cortical diffusivity across regions in the parietal and frontal lobes and reduced cortical thickness in the isthmus cingulate (ρ = -0.53, p = 0.001). Low-grade amyloidosis in the olfactory and frontal lobes was associated with WTC exposure duration. Future work should examine whether low-grade amyloidosis is correlated with the location or distribution of neurofibrillary tangles in WTC responders.

Head-to-head comparison of tau PET tracers [18F]PI-2620 and [18F]RO948 in non-demented individuals with brain amyloid deposition: the TAU-PET FACEHBI cohort

BackgroundSecond-generation tau tracers for positron emission tomography (PET) show high affinity for paired helical filaments tau deposits characteristic of Alzheimer´s disease and low off-target binding. Differences in their chemical structure though may lead to variations in their regional tau uptake and off-target signal. In this work, we aimed to compare the in-vivo uptake of tau tracers [18F]PI-2620 and [18F]RO948 in the early stages of the AD continuum.MethodsData from the TAU-PET FACEHBI clinical trial (EUDRA-CT 2021–000473-83) were analyzed. All participants were non-demented and underwent tau imaging with [18F]PI-2620 and [18F]RO948 PET within 3 months, amyloid imaging with [18F]Florbetaben and brain magnetic resonance imaging. Tau PET standardized uptake values ratios (SUVR) were calculated in Braak and typical off-target regions using the inferior cerebellar cortex as a reference region.ResultsThe cohort consisted of 18 individuals with subjective cognitive decline (n = 13) and mild cognitive impairment (n = 5), with centiloid values ranging from 17 to 159. Both tau tracers showed similar tau pathology distribution but presented a distinct off-target signal pattern on visual read. SUVR measurements for [18F]PI-2620 and [18F]RO948 were highly correlated in all Braak regions (R2 range [0.65–0.80]). Regarding off-target signal, [18F]PI-2620 had higher SUVRs in vascular structures, and [18F]RO948 had higher SUVRs in the skull/meninges.ConclusionsIn a cohort of individuals at early stages of the AD continuum, tau PET tracers [18F]PI-2620 and [18F]RO948 showed similar in-vivo uptake in all Braak regions and distinct off-target signal. These preliminary results support the development of standardized quantification scales for tau deposition that are tracer-independent.Trial registrationAEMPS EudraCT 2021–000473-83. Registered 30 December 2021.

Comparison of intravoxel incoherent motion and diffusion kurtosis imaging and 18- FDG PET/CT in response assessment in rectosigmoid carcinoma.

To evaluate the performance of intravoxel incoherent motion and diffusion kurtosis imaging (IVIM- DKI) in response assessment of rectosigmoid carcinoma to chemo-radiotherapy (CRT) and compare with 18-FDG PET/CT parameters. A total of 30 patients of recto-sigmoid cancer on CRT underwent baseline staging and follow-up with IVIM - DKI. Out of this cohort, 20 patients underwent 18-FDG PET/CT. IVIM- DKI MRI and PET/CT parameters were noted from both pre and post-chemoradiotherapy (done at 6 weeks after completion) scans. Quantitative IVIM-DKI parameters, viz. apparent (ADC) and molecular (D) diffusion coefficient, perfusion coefficient (f), and kurtosis (K) were measured from non-necrotic areas and semi-quantitative PET parameters including SUV max, SUV ratio, metabolic tumor volume (MTV), total lesion glycolysis (TLG) were also measured. All these parameters correlated with the patient's response keeping RECIST 1.1 criteria as reference standard. A statistically significant increase in D and ADC with a significant decline in K was noted after therapy in the entire cohort. These changes were observed in both responders as well as non-responders. No significant differences were observed in the percentage changes of these parameters post therapy amongst both groups. Among 20 patients with follow-up PET/CT imaging, a significant decline in all parameters of primary lesion was seen post-therapy. Responders (n = 12) showed a significant decline in MTV and TLG from baseline after therapy, whereas non-responders did not show any such decline. Change in TLG (ɗ TLG), followed by ɗ MTV had the strongest correlation with a positive response. A ɗ TLG value of ≥ 54.19 carried a 79% sensitivity and 83% specificity in differentiating responders from non responders. 18-FDG PET/CT is a more accurate single modality for assessing both response and tumor burden post therapy, while ADC and D from IVIM MRI are useful adjuncts to response assessment.

Sensitivity of unconstrained quantitative magnetization transfer MRI to amyloid burden in preclinical Alzheimer’s disease

Abstract Magnetization transfer MRI is sensitive to semisolid macromolecules, including amyloid beta, and has previously been used to discriminate Alzheimer’s disease (AD) patients from controls. Here, we fit an unconstrained 2-pool quantitative MT (qMT) model, that is, without constraints on the longitudinal relaxation rate R1s of semisolids, and investigate the sensitivity of the estimated parameters to amyloid accumulation in preclinical participants. We scanned 15 cognitively normal volunteers, of which 9 were amyloid positive by [18F]florbetaben PET. A 12 min hybrid-state qMT scan with an effective resolution of 1.24 mm isotropic and whole-brain coverage was acquired to estimate the unconstrained 2-pool qMT parameters. Group comparisons and correlations with florbetaben PET standardized uptake value ratios were analyzed at the lobar level. We find that the exchange rate and semisolid pool’s R1s were sensitive to the amyloid concentration, while morphometric measures of cortical thickness derived from structural MRI were not. Changes in the exchange rate are consistent with previous reports in clinical AD, while changes in R1s have not been reported previously as its value is typically constrained in the literature. Our results demonstrate that qMT MRI may be a promising surrogate marker of amyloid beta without the need for contrast agents or radiotracers.

Divergent neurodegenerative patterns: comparison of fluorodeoxyglucose-PET and MRI-based Alzheimer’s disease subtypes

Abstract [18F] fluorodeoxyglucose (FDG)-PET and MRI are key imaging markers for neurodegeneration in Alzheimer's disease. It has been well established that parieto-temporal hypometabolism on FDG-PET is closely associated with medial temporal atrophy on MRI in Alzheimer's disease. Substantial biological heterogeneity, expressed as distinct subtypes of hypometabolism or atrophy patterns, has been previously described in Alzheimer's disease using data-driven and hypothesis-driven methods. However, the link between these two imaging modalities has not yet been explored in the context of Alzheimer's disease subtypes. To investigate this link, the current study utilised FDG-PET and MRI scans from 180 amyloid-beta positive Alzheimer's disease dementia patients, 339 amyloid-beta positive mild cognitive impairment and 176 amyloid-beta negative cognitively normal controls from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Random forest hierarchical clustering, a data-driven model for identifying subtypes, was implemented in the two modalities: one with standard uptake value ratios and the other with grey matter volumes. Five hypometabolism- and atrophy-based subtypes were identified, exhibiting both cortical-predominant and limbic-predominant patterns although with differing percentages and clinical presentations. Three cortical-predominant hypometabolism subtypes found were: Cortical Predominant (32%), Cortical Predominant+ (11%), Cortical Predominant posterior (8%); and two limbic-predominant hypometabolism subtypes: Limbic Predominant (36%) and Limbic Predominant frontal (13%). In addition, little atrophy (minimal) and widespread (diffuse) neurodegeneration subtypes were observed from the MRI data. The five atrophy subtypes were found: Cortical Predominant (19%), Limbic Predominant (27%), Diffuse (29%), Diffuse+ (6%) and Minimal (19%). Inter-modality comparisons showed that all FDG-PET subtypes displayed medial temporal atrophy, whereas the distinct MRI subtypes showed topographically similar hypometabolic patterns. Further, allocations of FDG-PET and MRI subtypes were not consistent when compared at an individual-level. Additional analysis comparing the data-driven clustering model with prior hypothesis-driven methods showed only partial agreement between these subtyping methods. FDG-PET subtypes had greater differences between limbic-predominant and cortical-predominant patterns and MRI subtypes had greater differences in severity of atrophy. In conclusion, this study highlighted that Alzheimer's disease subtypes identified using both FDG-PET and MRI capture distinct pathways showing cortical- versus limbic-predominance of neurodegeneration. However, the subtypes do not share a bidirectional relationship between modalities and are thus not interchangeable.

Plasma pTau217 ratio predicts continuous regional brain tau accumulation in amyloid-positive early Alzheimer's disease.

This study examines whether phosphorylated plasma Tau217 ratio (pTau217R) can predict tau accumulation in different brain regions, as measured by positron emission tomography (PET) standardized uptake value ratio (SUVR), for staging Alzheimer's disease (AD). Plasma pTau217R was measured using immunoprecipitation-mass spectrometry. Models for predicting tau PET SUVR, developed with 144 early AD individuals using [18F]MK6240, were validated in two validation sets, VS1 (98 early AD) and VS2 (47 preclinical/early AD with a different tracer, flortaucipir (Tauvid)), all amyloid-beta positive (Aβ+). The pTau217R-based model predicted tau levels up to an SUVR of 2 in multiple brain regions, effectively assessing tau status at different tau levels with receiver operating characteristic (ROC) curve areas of 0.84-0.95 in VS1 and 0.71-0.88 in VS2 (using a different tracer). It reduced PET scan needs by 65% while maintaining 95% sensitivity. PTau217R reliably predicts regional tau accumulation in early AD, reducing reliance on tau PET scans and broadening its clinical application. NCT03887455 (ClarityAD) HIGHLIGHTS: Developed a model using plasma pTau217R to predict tau levels across brain regions. pTau217R model outperformed models based on clinical, MRI, and other blood biomarkers. The model reliably predicted tau levels exceeding tau positivity and higher thresholds. Screening with pTau217R could reduce tau PET scans by 65% at 95% sensitivity. pTau217R model aids in disease staging and monitoring in early AD.

Predictive Model of Paraaortic Lymph Node Involvement in cN0 Locally Advanced Cervical Cancers: PET/CT Technology Matters.

Background: The aim is to propose a model for predicting occult paraaortic lymph node (PALN) involvement in locally advanced cervical cancer (LACC) patients by including parameters such as reconstruction detection technology (use of time-of-flight) and parameters related to the primary tumor. This model will then be compared with the scores used in routine clinical practice; Methods: This retrospective observational cohort study included patients diagnosed with LACC who underwent 18F-FDG PET/CT prior to PALN surgical staging between February 2012 and May 2020. The following parameters were collected on PET/CT: tumor SUVmax, tumor MTV, number of common and distal pelvic node involvements. A multivariate regression analysis estimating the probability of PALN involvement was performed, with optimal thresholds determined via ROC curves; Results: In total, 71 patients met the inclusion criteria. Occult PALN involvement was detected in 12.7% of patients. A derived multivariate PET model selected four variables: number of common and distal iliac lymph nodes (OR 5.9 and 2.7, respectively), tumor-to-liver SUV ratio (OR 0.9) and the use of time-of-flight technology (OR 21.4 if no time-of-flight available). At the optimal threshold, a sensitivity of 77.8% and specificity of 88.7% was found. The model's performances varied significantly between patients whose PET/CT used time-of-flight and those whose PET/CT did not. No significant differences were found between our model and the one used in clinical practice (p = 0.55); Conclusions: This study shows that PET/CT technology influences the ability to detect occult PALN involvement in LACC. This parameter should be considered in the regular revision of PET-based scores.

Positron emission tomography harmonization in the Alzheimer's Disease Neuroimaging Initiative: A scalable and rigorous approach to multisite amyloid and tau quantification.

A key goal of the Alzheimer's Disease NeuroImaging Initiative (ADNI) positron emission tomography (PET) Core is to harmonize quantification of β-amyloid (Aβ) and tau PET image data across multiple scanners and tracers. We developed an analysis pipeline (Berkeley PET Imaging Pipeline, B-PIP) for ADNI Aβ and tau PET images and applied it to PET data from other multisite studies. Steps include image pre-processing, refacing, magnetic resonance imaging (MRI)/PET co-registration, visual quality control (QC), quantification of tracer uptake, and standardization of Aβ and tau standardized uptake value ratios (SUVrs) across tracers. Measurements from 10,105 cross-sectional and longitudinal Aβ and tau PET scans acquired in several studies between 2010 and 2024 can be processed, harmonized, and directly merged across tracers and cohorts. The B-PIP developed in ADNI is a scalable image harmonization approach used in several observational studies and clinical trials that facilitates rigorous Aβ and tau PET quantification and data sharing. Quantitative results from ADNI Aβ and tau PET data are generated using a rigorous, scalable image processing pipeline This pipeline has been applied to PET data from several other large, multisite studies and trials Quantitative outcomes are harmonizable across studies and are shared with the scientific community.

18F‐Florzolotau PET Imaging Unveils Tau Pathology in Dementia with Lewy Bodies

AbstractBackgroundDementia with Lewy bodies (DLB) commonly exhibits a complex neuropathology, sharing characteristics with Alzheimer's disease (AD), including tau aggregates. However, studies using the 18F‐AV‐1451 tau tracer have shown inconsistent findings regarding both the extent and topographical distribution of tau pathology in DLB.ObjectivesOur aim was to elucidate the topographical patterns of tau deposition in DLB and to investigate the in vivo pathological distinction between DLB and AD in virtue of the 18F‐Florzolotau positron emission tomography (PET) imaging.MethodsThis cross‐sectional study enrolled patients with DLB (n = 24), AD (n = 43), and cognitively healthy controls (n = 18). Clinical assessments and 18F‐Florzolotau PET imaging were performed. 18F‐Florzolotau binding was quantitatively assessed on PET images using standardized uptake value ratios and voxel‐wise analysis.Results18F‐Florzolotau PET imaging revealed widespread tau deposition across various cortical regions in DLB, uncovering heterogeneous topographical patterns. Among patients, 54.17% showed patterns similar to AD, whereas 16.67% exhibited distinct patterns. Compared to AD, DLB exhibited a unique in vivo neuropathological profile, characterized by a lower tau protein burden, heterogeneous topographical distributions, and a specific role of the medial temporal lobe in tau pathology.Conclusions18F‐Florzolotau PET imaging elucidated tau pathology patterns in DLB, providing valuable insights for future in vivo pathological differentiation and potential disease‐modifying therapies. © 2024 International Parkinson and Movement Disorder Society.

MRI-free processing of tau PET images for early detection

Abstract Tau positron emission tomography (PET) imaging in Alzheimer’s Disease (AD) is becoming increasingly common to assess in vivo tau burden. MR images are often acquired to assist with processing of PET data, including for region-of-interest definitions in native space and for normalization to template space. However, in the real-world setting, corresponding MRIs may not be available and PET processing may require MRI-free pipelines. This is particularly important and challenging as the field moves towards early detection among clinically unimpaired (CU) individuals where changes in tau PET signal are expected to be subtle. We used two independent [18F]Flortaucipir tau PET datasets to evaluate whether MRI-free PET processing can detect subtle tau PET uptake differences in Amyloid+ (A+) CU individuals (preclinical AD) versus A-. Standardized Uptake Value Ratios (SUVRs) from MRI-free compared to MRI-based methods were evaluated using linear regression and linear mixed-effects regression models. Effect size differences between A+/- CU groups in MRI-free processed cross-sectional and longitudinal tau PET SUVRs were compared to differences quantified through MRI-based processing. Regional MRI-free SUVRs were highly correlated with MRI-based SUVRs within CU individuals (average ICC = 0.90 for ADNI CU and 0.81 for A4 CU). MRI-free and MRI-based pipelines resulted in similar estimates of cross-sectional and longitudinal differences between A- and A+ CU, even in early focal regions within the medial temporal lobe.

Extracerebral Normalization of 18F-FDG PET Imaging Combined with Behavioral CRS-R Scores Predict Recovery from Disorders of Consciousness.

Identifying patients likely to regain consciousness early on is a challenge. The assessment of consciousness levels and the prediction of wakefulness probabilities are facilitated by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). This study aimed to develop a prognostic model for predicting 1-year postinjury outcomes in prolonged disorders of consciousness (DoC) using 18F-FDG PET alongside clinical behavioral scores. Eighty-seven patients with prolonged DoC newly diagnosed with behavioral Coma Recovery Scale-Revised (CRS-R) scores and 18F-FDG PET/computed tomography (18F-FDG PET/CT) scans were included. PET images were normalized by the cerebellum and extracerebral tissue, respectively. Images were divided into training and independent test sets at a ratio of 5:1. Image-based classification was conducted using the DenseNet121 network, whereas tabular-based deep learning was employed to train depth features extracted from imaging models and behavioral CRS-R scores. The performance of the models was assessed and compared using the McNemar test. Among the 87 patients with DoC who received routine treatments, 52 patients showed recovery of consciousness, whereas 35 did not. The classification of the standardized uptake value ratio by extracerebral tissue model demonstrated a higher specificity and lower sensitivity in predicting consciousness recovery than the classification of the standardized uptake value ratio by cerebellum model. With area under the curve values of 0.751 ± 0.093 and 0.412 ± 0.104 on the test sets, respectively, the difference is not statistically significant (P = 0.73). The combination of standardized uptake value ratio by extracerebral tissue and computed tomography depth features with behavioral CRS-R scores yielded the highest classification accuracy, with area under the curve values of 0.950 ± 0.027 and 0.933 ± 0.015 on the training and test sets, respectively, outperforming any individual mode. In this preliminary study, a multimodal prognostic model based on 18F-FDG PET extracerebral normalization and behavioral CRS-R scores facilitated the prediction of recovery in DoC.

NIMG-80. IMPACT OF KETOGENIC DIET ON MOLECULAR METABOLIC IMAGING WITH [18F]FDG AND [18F]DASA-23 POSITRON EMISSION TOMOGRAPHY IN A PATIENT WITH GLIOBLASTOMA

Abstract The standard-of-care for neuroimaging in patients with glioblastoma is contrast-enhanced MRI, which does not provide tumor metabolism information. Although [18F]FDG PET is used to image tumor metabolism in many solid organ cancers, it has limited benefit in atients with brain tumors due to the high level of glucose uptake in normal brain cells. [18F]DASA-23 is a novel PET radiotracer that assesses the levels of pyruvate kinase M2 (PKM2), a protein highly expressed in cancer cells, which undergo aberrant glycolysis. Despite [18F]DASA-23 having a higher tumor-to-background ratio (TBR) of standardized uptake values (SUVs) in the brain compared to [18F]FDG, both may be susceptible to altered carbohydrate metabolism in the setting of a ketogenic diet (KD). We report the case of a patient with glioblastoma on a KD, whose [18F]FDG and [18F]DASA-23 PET brain scans were limited in identifying disease progression (PD). Background was defined as the white matter contralateral to the tumor, at the level of the centrum semiovale, for TBR of SUVmax. A 39-year-old man was diagnosed with right temporal glioblastoma after previous diagnoses of grade 2 gliofibrillary oligodendroglioma (age 20) and grade 3 anaplastic oligodendroglioma (age 22). He began a KD after the glioblastoma diagnosis. 21 months later, TBR on [18F]DASA-23 PET was 1.38. One month later, surveillance brain MRI showed PD. Ten days later, TBR on [18F]FDG PET was 1.03. The patient died 15 months later. Despite MRI-based PD, the TBR of each radiotracer was not markedly elevated, although the [18F]DASA-23 TBR 1-month pre-PD was 34% greater than the [18F]FDG PET TBR 10-days post-PD. This may suggest a limitation of metabolic imaging by PET in the setting of a KD, and provide an opportunity to develop novel PET radiotracers that are not susceptible to the patient’s diet.

Evaluation of ComBat Harmonization for Reducing Across-Tracer Differences in Regional Amyloid PET Analyses.

Differences in amyloid positron emission tomography (PET) radiotracer pharmacokinetics and binding properties lead to discrepancies in amyloid-β uptake estimates. Harmonization of tracer-specific biases is crucial for optimal performance of downstream tasks. Here, we investigated the efficacy of ComBat, a data-driven harmonization model, for reducing tracer-specific biases in regional amyloid PET measurements from [18F]-florbetapir (FBP) and [11C]-Pittsburgh compound-B (PiB). One hundred thirteen head-to-head FBP-PiB scan pairs, scanned from the same subject within 90 days, were selected from the Open Access Series of Imaging Studies 3 (OASIS-3) dataset. The Centiloid scale, ComBat with no covariates, ComBat with biological covariates, and GAM-ComBat with biological covariates were used to harmonize both global and regional amyloid standardized uptake value ratios (SUVR). Variants of ComBat, including longitudinal ComBat and PEACE, were also tested. Intraclass correlation coefficient (ICC) and mean absolute error (MAE) were computed to measure the absolute agreement between tracers. Additionally, longitudinal amyloid SUVRs from an anti-amyloid drug trial were simulated using linear mixed effects modeling. Differences in rates-of-change between simulated treatment and placebo groups were tested, and change in statistical power/Type-I error after harmonization was quantified. In the head-to-head tracer comparison, ComBat with no covariates was the best at increasing ICC and decreasing MAE of both global summary and regional amyloid PET SUVRs between scan pairs of the same group of subjects. In the clinical trial simulation, harmonization with both Centiloid and ComBat increased statistical power of detecting true rate-of-change differences between groups and decreased false discovery rate in the absence of a treatment effect. The greatest benefit of harmonization was observed when groups exhibited differing FBP-to-PiB proportions. ComBat outperformed the Centiloid scale in harmonizing both global and regional amyloid estimates. Additionally, ComBat improved the detection of rate-of-change differences between clinical trial groups. Our findings suggest that ComBat is a viable alternative to Centiloid for harmonizing regional amyloid PET analyses.

SV2A PET shows hippocampal synaptic loss in cognitively unimpaired APOE ε4/ε4 homozygotes.

We investigated hippocampal synaptic density using synaptic vesicle 2A positron emission tomography (PET), and its association with amyloid beta (Aβ) and cognitive performance in healthy apolipoprotein E (APOE) ε4 carriers. Synaptic density was assessed in 46 individuals (APOE ε4/ε4 n=14; APOE ε3/ε4 n=16; APOE ε3/ε3 n=16) with [11C]UCB-J-PET standardized uptake value ratios (SUVRs), by using the centrum semiovale as a reference region. Differences in hippocampal [11C]UCB-J SUVRs were analyzed with analysis of variance (ANOVA) and linear models. Associations among [11C]UCB-J SUVR, Aβ, hippocampal volume, and cognitive variables were analyzed with Spearman correlation. Hippocampal synaptic density was different among the APOE groups (PANOVA=0.016): APOE ε4/ε4 carriers had lower [11C]UCB-J SUVRs compared to APOE ε3/ε3 (p=0.013). Hippocampal synaptic density did not correlate with Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score (rho=-0.052, p=0.74), Alzheimer's Prevention Initiative Preclinical Cognitive Composite (APCC) score (rho=0.17, p=0.28), or [11C]PiB uptake (rho=-0.10, p=0.50). Hippocampal synaptic loss emerges early in the AD continuum and is measurable in vivo in cognitively unimpaired high-risk individuals. Synaptic density was studied in vivo in healthy older adults using [11C]UCB-J positron emission tomography. Apolipoprotein E (APOE) ε4/ε4 carriers had lower hippocampal synaptic density compared to APOE ε3/ε3. Synaptic density was not associated with cognitive performance in this population. Hippocampal synaptic alterations occur before clinical symptoms in APOE ε4/ε4 carriers.

18F]PI-2620 Tau PET signal across the aging and Alzheimer’s disease clinical spectrum

Abstract [18F]PI-2620 is a second generation tracer that has shown high binding affinity for tau aggregation in Alzheimer’s disease (AD). However, [18F]PI-2620 signal in a large sample spanning the healthy aging and AD clinical spectrum as well as the stability of signal across different acquisition time windows has not yet been examined. Here, amyloid negative (Aβ-) cognitively unimpaired (CU; n = 49), amyloid positive (Aβ+) CU (n = 37), CU individuals with unknown amyloid status (n = 5), mild cognitive impairment (MCI; n = 14), dementia due to AD (n = 19), and non-AD neurodegenerative disorder (n = 54) participants were scanned with [18F]PI-2620 using a 45–75 min and/or 60–90 min acquisition time window. The impact of acquisition time on standardized uptake value ratio (SUVR) magnitude was first quantified with linear mixed models, and in participants and regions with high [18F]PI-2620 signal, SUVRs increased linearly up to 0.04 SUVR with each additional 5 min past injection time. We then accounted for differences in acquisition time using a voxel-wise correction approach and showed high correlations (all r’s ≥ 0.986) between SUVRs calculated from 45–75 min data and SUVRs from 60–90 min data that were interpolated to the 45–75 min scale in 15 participants who were scanned across both time windows. Using real and interpolated 45–75 min data, we next examined [18F]PI-2620 signal in Braak regions of interest and an off-target binding region (putamen) in Aβ- and Aβ+ CU, Aβ+ MCI, and Aβ+ AD dementia (n = 115) and showed that SUVRs in all Braak regions increased with greater disease severity. Within CU, higher Braak I SUVR was significantly associated with greater CSF pTau-181 (n = 35), and higher SUVRs were significantly associated with worse memory and language (n = 57). Thus, voxel-wise acquisition time corrections can be applied to combine [18F]PI-2620 datasets collected at different post-injection times, and once acquisition time is accounted for, [18F]PI-2620 signal shows the expected increases across the AD spectrum and can be used for detection of early tau elevations.

The Association Between Constipation and Positron Emission Tomography and Blood-Based Biomarkers in Older Cognitively Unimpaired Adults with Higher Amyloid-β Burden.

Constipation may be linked to cognitive decline and a higher risk of Alzheimer's disease (AD). We aimed to investigate the association between constipation and positron emission tomography (PET) and blood-based AD biomarkers in older cognitively unimpaired (CU) adults with higher Aβ burden. Constipation was diagnosed according to Rome IV criteria and the severity of constipation was evaluated by using a validated self-reported questionnaire. The participants underwent the examination of plasma AD biomarkers and 18F-florbetapir PET and 18F-MK6240 PET scans; the latter was only performed in the validation cohort. Correlation and multiple linear regression analyses were used to investigate the association between constipation and AD biomarkers. Two cohorts were included in our study. A total of 404 older participants with 126 of whom Aβ-PET positive were enrolled in the development cohort. Multiple linear regression analysis showed constipation was associated with plasma t-Tau, p-Tau-181, and neurofilament light chain (NfL) in participants with Aβ-PET (+). Meanwhile, no/mild constipation was associated with lower Aβ-PET standard uptake value ratio. The association between constipation and plasma biomarkers was different in the subgroups stratified by age, sex and APOE ε4 genotype. The above associations were further validated in the validation cohort containing 36 Aβ-PET (+) participants. Importantly, no/mild constipation was associated with lessTau burden evaluated by 18F-MK6240 PET Braak stages. Our data indicate that no/mild constipation may be associated with lower plasma t-Tau, p-Tau-181, and NfL as well as less Aβ and Tau burden in older CU adults with Aβ deposition. Improving constipation and being away from defecation disorders may help reduce the risk of AD development.

High-resolution motion compensation for brain PET imaging using real-time electromagnetic motion tracking.

Substantial improvements in spatial resolution in brain positron emission tomography (PET) scanners have greatly reduced partial volume effect, making head movement the main source of image blur. To achieve high-resolution PET neuroimaging, precise real-time estimation of both head position and orientation is essential for accurate motion compensation. A high-resolution electromagnetic motion tracking (EMMT) system with an event-by-event motion correction is developed for PET-CTscanners. EMMT is comprised of a source, an array of sensors, and a readout electronic unit (REU). The source acts as a transmitter and emits an EM dipole field. It is placed in close proximity to the sensor array and detects changes in EM flux density due to sensor movement. The REU digitizes signals from each sensor and captures precise rotational and translational movements in real time. Tracked motion in the EMMT coordinate system is synchronized with the PET list-mode data and transformed into the scanner coordinate system by locating paired positions in both systems. The optimal rigid motion is estimated using singular value decomposition. The rigid motion and depth-of-interaction (DOI) parallax effect are corrected by event-by-event rebinning of mispositioned lines-of-response (LORs). We integrated the EMMT with our recently developed ultra-high resolution Prism-PET prototype brain scanner and a commercial Siemens Biograph mCT PET-CT scanner. We assessed the imaging performance of the Prism-PET/EMMT system using multi-frame motion of point sources and phantoms. The mCT/EMMT system was validated using a set of point sources attached to both a mannequin head and a human volunteer, for simulating multiframe and continuous motions, respectively. Additionally, a human subject for [18F]MK6240 PET imaging wasincluded. The tracking accuracy of the Prism-PET/EMMT system was quantified as a root-mean-square (RMS) error of 0.49 for 100 axial rotations, and an RMS error of 0.15 mm for 100 mm translations.The percent difference (%diff) in average full width at half maximum (FWHM) of point source between motion-corrected and static images, within a motion range of and 10 mm from the center of the scanner's field-of-view (FOV), was 3.9%. The measured recovery coefficients of the 2.5-mm diameter sphere in the activity-filled partial volume correction phantom were 23.9%, 70.8%, and 74.0% for the phantom with multi-frame motion, with motion and motion compensation, and without motion, respectively. In the mCT/EMMT system, the %diff in average FWHM of point sources between motion-corrected and static images, within a motion range of and 10 mm from the center of the FOV, was 14%. Applying motion correction to the [18F]MK6240 PET imaging reduced the motion-induced spill-in artifact in the lateral ventricle region, lowering its standardized uptake value ratio (SUVR) from 0.70 to 0.34. The proposed EMMT system is a cost-effective, high frame-rate, and none-line-of-sight alternative to infrared camera-based tracking systems and is capable of achieving high rotational and translational tracking accuracies for mitigating motion-induced blur in high-resolution brain dedicated PETscanners.

Prognostic Value and Clinical Implication of Lymph Node-to-Primary Tumor SUV Ratio in Node-Positive Hypopharyngeal Squamous Cell Carcinoma Treated With Radiotherapy With or Without Chemotherapy.

The aim of this was to evaluate the prognostic significance of the nodal-to-primary tumor SUVmax ratio (NTR) in patients with node-positive hypopharyngeal squamous cell carcinoma (HPSCC) treated with radiotherapy with or without concurrent chemotherapy. The study aims to enhance prognostic accuracy by incorporating NTR into the American Joint Committee on Cancer (AJCC) staging system. This retrospective study included 191 patients with biopsy-proven node-positive HPSCC treated from 2005 to 2013. NTR was calculated as the ratio of SUVmax of metastatic lymph nodes to the primary tumor's SUVmax. Survival analyses were conducted using Cox regression models and Kaplan-Meier analysis. Receiver operating characteristic analysis compared the prognostic performance of the modified and AJCC staging systems. The median follow-up was 8.27 years, with 135 deaths (70.7%). High NTR (≥0.63) was significantly associated with worse overall survival (OS) and was an independent prognostic factor in multivariable analysis (adjusted hazards ratio [HR] = 1.63, P = 0.007). Median OS for high NTR was 17.4 months, compared with 75.2 months for low NTR. High NTR significantly predicted worse OS within AJCC stage IVA patients (HR = 6.09, P = 0.014). Patients in modified stage IVA (AJCC stage IVA with low NTR) had significantly longer OS than those in modified stage IVB (AJCC stage IVA with high NTR and AJCC stage IVB) (HR = 8.62, P = 0.003). The modified staging system incorporating NTR showed superior prognostic performance compared with the AJCC staging system. NTR is a significant independent prognostic factor for OS in node-positive HPSCC patients. Integrating NTR into the AJCC staging system improves prognostic accuracy.