Nuclear Medicine

The severity of obstructive sleep apnea syndrome cannot predict the accumulation of brain amyloid by imaging with [11C]-Pittsburgh compound B PET computed tomography in patients with a normal cognitive function Abstract Objective Disturbed sleep due to obstructive sleep apnea syndrome (OSAS) might accelerate amyloidβ (Aβ) deposition, which can be a crucial factor in Alzheimer’s disease. We studied Aβ deposition in untreated OSAS patients with normal cognition. Method We performed polysomnography (PSG) and Aβ imaging with [11C]-Pittsburgh compound B PET computed tomography (11C-PiB PET CT) in 14 untreated OSAS patients (apnea–hypopnea index: 43.8 ± 26.3/h). Results The abnormal accumulation of enhanced 11C-PiB PET was observed only one patient with severe, but not the most severe. Conclusions The OSAS severity alone may not predict Aβ deposition in OSAS patients with normal cognition.

Overall survival and progression-free survival in patients with primary brain tumors after treatment: is the outcome of [ 18 F] FDOPA PET a prognostic factor in these patients? Abstract Aim To investigate the progression-free survival (PFS) and the overall survival (OS) in a population affected by primary brain tumors (PBT) evaluated by [18F]-l-dihydroxyphenylalanine ([18F] FDOPA) positron emission tomography/computed tomography (PET/CT). Materials and methods 133 subjects with PBT (65 women and 68 men, mean age 45 ± 10 years old) underwent 18F FDOPA PET/CT after treatment. Of them, 68 (51.2%) were Grade II, 34 (25.5%) were Grade III and 31 (23.3%) were Grade IV. PET/CT was scored as positive or negative and standardized uptake value ratio (SUVr) was calculated as the ratio between SUVmax of the lesion vs. that of the background. Patients have been observed for a mean of 24 months. Results The outcome of [18F] FDOPA PET/CT scan was significantly related to the OS and PFS in Grade II gliomas. In Grade II PBT, the OS proportions at 24 months were 100% in subjects with a negative PET/CT scan and 82% in those with a positive scan. Gehan–Breslow–Wilcoxon test showed a significant difference in the OS curves (P = 0.03) and the hazard-ratio was equal to 5.1 (95% CI of ratio 1.1–23.88). As for PFS, the proportion at 24 months was 90% in subjects with a negative PET/CT scan and 58% in those with a positive scan. Gehan–Breslow–Wilcoxon test showed a significant difference in the OS curves (P = 0.007) and the hazard-ratio was equal to 4.1 (95% CI of ratio 1.3–8). We did not find any significant relationship between PET outcome and OS and PFS in Grade III and IV PBT. Conclusions A positive [18F] FDOPA PET/CT scan is related to a poor OS and PFS in subjects with low-grade PBT. This imaging modality could be considered as a prognostic factor in these subjects.

A systematic performance evaluation of head motion correction techniques for 3 commercial PET scanners using a reproducible experimental acquisition protocol Abstract Purposes Subject’s motion during brain PET scan degrades spatial resolution and quantification of PET images. To suppress these effects, rigid-body motion correction systems have been installed in commercial PET scanners. In this study, we systematically compare the accuracy of motion correction among 3 commercial PET scanners using a reproducible experimental acquisition protocol. Methods A cylindrical phantom with two 22Na point sources was placed on a customized base to enable two types of motion, 5° yaw and 15° pitch rotations. Repetitive PET scans (5 min × 5 times) were performed at rest and under 2 motion conditions using 3 clinical PET scanners: the Eminence STARGATE G/L PET/CT (STARGATE) (Shimadzu Corp.), the SET-3000 B/X PET (SET-3000) (Shimadzu Corp.), and the Biograph mMR PET/MR (mMR) (Siemens Healthcare) systems. For STARGATE and SET-3000, the Polaris Vicra (Northern Digital Inc.) optical tracking system was used for frame-by-frame motion correction. For Biograph mMR, sequential MR images were simultaneously acquired with PET and used for LOR-based motion correction. All PET images were reconstructed by FBP algorithm with 1 × 1 mm pixel size. To evaluate the accuracy of motion correction, FWHMs and spherical ROI values were analyzed. Results The percent differences (%diff) in averaged FWHMs of point sources at 4 cm off-center between motion-corrected and static images were 0.77 ± 0.16 (STARGATE), 2.4 ± 0.34 (SET-3000), and 11 ± 1.0% (mMR) for a 5° yaw and 2.3 ± 0.37 (STARGATE) and 1.1 ± 0.60 (SET-3000) for a 15° pitch respectively. The averaged %diff between ROI values of motion-corrected images and static images were less than 2.0% for all conditions. Conclusions In this study, we proposed a reproducible experimental framework to allow the systematic validation and comparison of multiple motion tracking and correction methodologies among different PET/CT and PET/MR commercial systems. Our proposed validation platform may be useful for future studies evaluating state-of-the-art motion correction strategies in clinical PET imaging.

Diagnostic performance of 18 F-FDG PET-CT for large vessel involvement assessment in patients with suspected giant cell arteritis and negative temporal artery biopsy Abstract Objective The purpose of our study was to assess the diagnostic performance of 18F-FDG PET-CT for large vessel involvement in patients with suspected giant cells arteritis (GCA) and a negative temporal artery biopsy (TAB). Methods We conducted a retrospective study in a cohort of patients with suspected GCA and negative TAB who underwent an 18F-FDG PET-CT. Ten vascular segments were studied using a visual score and a semi-quantitative method based on SUVmax ratio with respect to liver uptake. The diagnosis of GCA was established during a mean follow-up of 42 months, based on the presence of clinical symptoms, laboratory results, and imaging data compatible with GCA, good response to corticosteroid therapy, and no differential diagnosis after a follow-up of at least 18 months. Results We included 63 patients (30 men and 33 women, aged 67 ± 12 years). 18F-FDG PET-CT showed large vessel involvement in 22 patients, 14 of whom were finally diagnosed with GCA. Forty-one patients were 18F-FDG PET-CT negative, 9 of whom were finally diagnosed with GCA. Overall, 18F-FDG uptake by large vessel yielded 61% sensitivity, 80% specificity, 64% positive predictive value, 78% negative predictive value, and 73% diagnostic accuracy. A significant number of patients were treated by corticosteroids before 18F-FDG PET-CT. However, corticosteroid therapy did not impact significantly the diagnostic performance, although there was a trend to a lower sensitivity in patients receiving corticosteroid therapy for more than 3 days. Conclusions 18F-FDG PET-CT is a useful imaging technique to assess large vessel involvement in patients with suspected GCA and negative TAB.

Factors affecting accuracy of S values and determination of time-integrated activity in clinical Lu-177 dosimetry Abstract Introduction In any radiotherapy, the absorbed dose needs to be estimated based on two factors, the time-integrated activity of the administered radiopharmaceutical and the patient-specific dose kernel. In this study, we consider the uncertainty with which such absorbed dose estimation can be achieved in a clinical environment. Methods To calculate the total error of dose estimation we considered the following aspects: The error resulting from computing the time-integrated activity, the difference between the S-value and the patient specific full Monte Carlo simulation, the error from segmenting the volume-of-interest (kidney) and the intrinsic error of the activimeter. Results The total relative error in dose estimation can amount to 25.0% and is composed of the error of the time-integrated activity 17.1%, the error of the S-value 16.7%, the segmentation error 5.4% and the activimeter accuracy 5.0%. Conclusion Errors from estimating the time-integrated activity and approximations applied to dose kernel computations contribute about equally and represent the dominant contributions far exceeding the contributions from VOI segmentation and activimeter accuracy.

Development of anatomically and lesion contrast-guided partial volume correction: new 3D formalisms and validation in phantom and clinical studies Abstract Purpose The aim of the study was to correct for partial volume effect in positron emission imaging studies which is the most influential factors using three-dimensional (3D) representation of the recovery coefficients (RCs) to improve standardized uptake value (SUV) calculations. Methods Several phantom studies were conducted at significantly wide range of lesion contrast, range 2:1 up to 15:1. It was then classified into two groups: one for generating 3D function taking into consideration the sphere size as well lesion contrast whereas the other group was used for functions validation. A segmentation threshold algorithm for lesion delineation and volume determination was generated based on lesion contrast and lesion size. In addition, five 3D functions of the RC of the SUV were formulated considering lesion size and lesion contrast. Validation of the new algorithms has considered both phantom and clinical studies. Results The error in threshold 3D function was well below 10%. For lesions ≤ 2 cm in diameter, there was no statistical difference of the functions developed for SUVmax as well as those functions generated for SUVmean. However, the median SUVmax has increased significantly when compared with data before correction. For SUVmean, the increase in median value was also significantly high. Conclusion It has been successful to generate 3D mathematical formulations of the SUV RC taking into consideration the most influential factors including lesion size and lesion contrast. Validation studies were suggestive of the good performance of the new mathematical algorithms generated to correct for PVE. However, further studies are underway to ensure the performance of the proposed algorithms in clinical PET studies.

A novel biomarker, active whole skeletal total lesion glycolysis (WS-TLG), as a quantitative method to measure bone metastatic activity in breast cancer patients Abstract Objective There is no good response evaluation method for skeletal metastasis. We aimed to develop a novel quantitative method to evaluate the response of skeletal metastasis, especially lytic lesions, for treatment. Methods A method to measure active bone metastatic burden quantitatively using F-18 fluorodeoxyglucose positron emission tomography with computed tomography (FDG–PET/CT) in breast cancer patients, whole skeletal total lesion glycolysis (WS-TLG), a summation of each skeletal lesion’s TLG, was developed. To identify active bone lesions, a tentative cutoff value was decided using FDG–PET/CT in 85 breast cancer patients without skeletal metastasis and 35 with skeletal metastasis by changing the cutoff value. Then, the WS-TLG method was evaluated by comparing to PET Response Criteria in Solid Tumor (PERCIST) or European Organization for Research and Treatment of Cancer (EORTC) criteria for only bone in 15 breast cancer patients with skeletal metastasis who were treated. Results A cutoff value of the standardized uptake value (SUV) = 4.0 gave 91% (77/85) specificity and 97% (34/35) sensitivity. We decided on SUV = 4.0 as a tentative cutoff value. Skeletal metastases of lytic and mixed types showed higher WS-TLG values than those of blastic or intertrabecular types, although statistical significance was not tested. All 15 patients showed agreement with PERCIST or EORTC in the therapeutic bone response. Conclusion This quantitative WS-TLG method appears to be a good biomarker to evaluate skeletal metastasis in breast cancer patients, especially lytic or mixed types. Further clinical studies are warranted to assess the clinical values of this new WS-TLG method.

The difference of risk factors predicting cardiac events in patients with chronic kidney disease between with and without diabetes Abstract Objective Chronic kidney disease (CKD) and diabetes are both associated with cardiovascular disease, but the effects of diabetes in patients with CKD remain unknown. This study aimed to compare the risk factors of cardiac events between patients with CKD accompanied and not by diabetes using myocardial perfusion imaging. Methods We initially classified 529 patients with CKD from the Japanese Assessment of Cardiac Events and Survival Study-3 (J-ACCESS-3) study who had been assessed by gated single-photon emission-computed tomography based on whether they had diabetes (n = 220) or not (n = 309) and then separated them into four subgroups based on the ejection fraction (EF) calculated by quantitative gated SPECT. After 3-year follow-up, the incidence of major cardiac events (cardiac death, sudden death, non-fatal myocardial infarction, and heart failure requiring hospitalization), risk factors among each group, and the ability of myocardial perfusion image to predict prognosis were evaluated. Results Major cardiac events occurred in 12.7% and 10.3% of patients with and without diabetes (not significant), and heart failure requiring hospitalization was the most frequent (75% and 78%, respectively) in both groups. Event-free survival rates were lower in the subgroups with low EF and high summed stress scores (SSS). Independent risk factors comprised currently smoking and a higher SSS, among patients with diabetes, while higher left ventricular end diastolic volumes and serum C-reactive protein values among those without diabetes. Conclusions In patients with CKD, while the risk factors of major cardiac events differ between in patients with and without diabetes, quantitation with gated MPI could be used effectively in both groups.

Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in mantle cell lymphoma Abstract Objective Mantle cell lymphoma (MCL) is an aggressive lymphoma sub-type with poor prognosis and high 18F-FDG avidity at PET/CT; nowadays, no validated criteria for PET/CT in treatment response evaluation and prediction of outcome are present. The aim of study was to investigate whether the metabolic PET/CT features may predict treatment evaluation and prognosis in MCL. Methods We retrospectively enrolled 87 patients who underwent baseline 18F-FDG PET/CT and 85 end-of-treatment (eot) PET/CT. The baseline PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), lesion-to-liver SUVmax ratio (L-L SUV R), lesion-to-blood pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). EotPET/CT was visually interpreted according to the criteria of the Deauville 5-point scale (DC). Survival curves were plotted according to the Kaplan–Meier method. Results At a median follow-up of 40 months, relapse/progression occurred in 47 and death in 23 patients. Median PFS and OS were 30 and 41 months. Baseline MTV and TLG were significantly higher in patients with progressive metabolic response compared to complete/partial response group. EotPET/CT results using DC significantly correlated with PFS, not with OS. MTV and TLG were demonstrated to be independent prognostic factors for PFS; instead the other metabolic parameters were not related to outcome survival. Considering OS, no variable was significantly associated. Conclusions EotPET/CT results (using DC), MTV and TLG were significantly correlated with response to treatment and PFS.

Comparison between the different doses of radioactive iodine ablation prescribed in patients with intermediate-to-high-risk differentiated thyroid cancer Abstract Objective This study aimed to compare the clinical outcomes of patients who received radioactive iodine (RAI) ablation after undergoing thyroidectomy for intermediate-to-high-risk differentiated thyroid carcinoma (DTC) according to the American Thyroid Association (ATA) criteria. Methods We retrospectively examined patients who underwent RAI ablation for DTC after surgical resection without macroscopic residual lesions or metastatic lesions between December 2011 and August 2016. Among 147 patients who underwent RAI ablation, those whose initial pathological stages or RAI ablation results were unknown and whose distant metastases were confirmed during RAI ablation were excluded. Low-dose therapy was defined as administration of 1110 MBq of 131iodine (131I), while high-dose therapy referred to administration of 2960–3700 MBq of 131I. We defined initial success of RAI ablation as a serum thyroglobulin concentration of < 2.0 ng/mL without thyroid-stimulating hormone stimulation and disappearance of 131I uptake in the thyroid bed on 131I scintigraphy 6–12 months after RAI ablation. RAI ablation success rates were compared between the low-dose and high-dose groups using Fisher’s exact test, and inverse probability of treatment weighting (IPTW) analysis was performed for adjusting potential biases. Results Among the 119 patients examined in this study (39 men and 80 women), 79 were classified as having intermediate risk, while 40 were classified as having high risk based on the ATA guideline. Initial RAI ablation success was achieved in 50/68 (73.5%) patients from the low-dose group and in 36/51 patients (70.6%) from the high-dose group (p = 0.84). Moreover, IPTW analysis showed no significant difference between the low-dose and high-dose groups. However, the success rate tended to be superior in high-risk patients who received high-dose therapy (86.2%) than in those who received low-dose therapy (72.7%) (p = 0.37). Conclusion There was no significant difference in the RAI ablation success rate between the low-dose and high-dose groups involving patients with intermediate-to-high-risk DTC. However, high-dose RAI ablation may be recommended in high-risk patients.