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Purpose: The authors introduce a novel method for defining standardized uptake values (SUVs) in PET∕CT based on routinely collected CT data. The goal of the study is to reduce, if possible, the variability of SUV in a heterogeneous population. Two well established methods for defining SUV are based on body weight (BW) and lean body mass, calculated as a function of height, weight, and sex with an empirical formula (LBM). The authors investigate two novel models, CT1 and CT2, that estimate the lean mass from CT Hounsfield Unit values. The authors compare the four methods, assessing the variability of hepatic SUV in (18)F-FDG studies., Methods: CT images from 252 cancer patients were segmented into regions representing lean tissues, fat, and bone. The fraction of lean tissue in the scanned region was extrapolated to the entire body with a naive method (CT1) and a method that modeled typical FDG uptake patterns (CT2). For each method, SUV-based measurements of the liver were calculated for all patients and dependence on body weight was assessed. Coefficients of variation (CVs) were evaluated. Several sub-cohorts were analyzed, including those with low and high body mass index (BMI). The extrapolation technique was tested in 19 melanoma patients who received head to toe PET∕CT scans. CT-based weight predictions were compared with actual patient weight in melanoma studies and in PET∕CT scans of pigs., Results: Only the SUV based on BW method depended significantly on body weight. CVs for the BW, LBM, CT1, and CT2 methods were, respectively, 18.0%, 15.5%, 15.9%, and 14.9%. In the high-BMI cohort, CVs were 18.2%, 16.2%, 16.2%, and 15.1%. Mean SUV of the 14 most obese patients agreed most closely with mean SUV of 120 lean patients when the CT2 method was used. SUV based on truncated CT agreed with head to toe predictions within 5% for the CT1 method and 1% for the CT2 method. CT-based weight estimate recovered 97.4% of the weight in head to toe studies of humans and 99.7% in pig studies., Conclusions: The novel CT1 and CT2 methods were less variable than the BW method and were comparable to the LBM method. SUV were little affected by missing CT data.

Objective: To evaluate the repeatability of gallium-68 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA)-D-Phe1-Try3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) in neuroendocrine tumors., Methods: Five patients with neuroendocrine tumors were imaged with 68Ga-DOTATOC PET twice within 5 days. Maximum and mean standardized uptake values (SUVmax and SUVmean) and kinetic parameters (K-Patlak and K-influx) of target lesions were measured. The repeatability of these measurements was investigated., Results: Forty-seven target lesions were identified on whole-body PET and 21 lesions on dynamic images. There was excellent repeatability with intraclass correlation coefficient of 0.99 for SUVmax, SUVmean, and K-Patlak, and 0.85 for K-influx. The median absolute percent differences and the interquartile ranges (IQR) between 2 scans for SUVmax and SUVmean were 7.4% (IQR, 14.1%) and 9.3% (IQR, 10.6%), respectively. The median absolute percent differences for K-Patlak and K-influx were 12.5% (IQR, 12.6%) and 29.9% (IQR, 22.4%), respectively. The SUVmax of target lesions did not differ by more than 25% between the 2 scans., Conclusions: 68Ga-DOTATOC PET imaging of neuroendocrine tumors is highly reproducible. A difference of more than 25% in SUVmax represents a change that is larger than the measurement error observed on repeated studies and should reflect a significant change in the biological character of the tumor.

Multiple myeloma is a hematologic malignancy characterized by the proliferation of neoplastic plasma cells in the bone marrow. Although the first-to-market proteasome inhibitor bortezomib (Velcade) has been successfully used to treat patients with myeloma, drug resistance remains an emerging problem. In this study, we identify signatures of bortezomib sensitivity and resistance by gene expression profiling (GEP) using pairs of bortezomib-sensitive (BzS) and bortezomib-resistant (BzR) cell lines created from the Bcl-XL/Myc double-transgenic mouse model of multiple myeloma. Notably, these BzR cell lines show cross-resistance to the next-generation proteasome inhibitors, MLN2238 and carfilzomib (Kyprolis) but not to other antimyeloma drugs. We further characterized the response to bortezomib using the Connectivity Map database, revealing a differential response between these cell lines to histone deacetylase (HDAC) inhibitors. Furthermore, in vivo experiments using the HDAC inhibitor panobinostat confirmed that the predicted responder showed increased sensitivity to HDAC inhibitors in the BzR line. These findings show that GEP may be used to document bortezomib resistance in myeloma cells and predict individual sensitivity to other drug classes. Finally, these data reveal complex heterogeneity within multiple myeloma and suggest that resistance to one drug class reprograms resistant clones for increased sensitivity to a distinct class of drugs. This study represents an important next step in translating pharmacogenomic profiling and may be useful for understanding personalized pharmacotherapy for patients with multiple myeloma., (©2013 AACR)

Purpose: The purpose of this work was to develop and validate fully automated methods for uptake measurement of cerebellum, liver, and aortic arch in full-body PET/CT scans. Such measurements are of interest in the context of uptake normalization for quantitative assessment of metabolic activity and/or automated image quality control., Methods: Cerebellum, liver, and aortic arch regions were segmented with different automated approaches. Cerebella were segmented in PET volumes by means of a robust active shape model (ASM) based method. For liver segmentation, a largest possible hyperellipsoid was fitted to the liver in PET scans. The aortic arch was first segmented in CT images of a PET/CT scan by a tubular structure analysis approach, and the segmented result was then mapped to the corresponding PET scan. For each of the segmented structures, the average standardized uptake value (SUV) was calculated. To generate an independent reference standard for method validation, expert image analysts were asked to segment several cross sections of each of the three structures in 134 F-18 fluorodeoxyglucose (FDG) PET/CT scans. For each case, the true average SUV was estimated by utilizing statistical models and served as the independent reference standard., Results: For automated aorta and liver SUV measurements, no statistically significant scale or shift differences were observed between automated results and the independent standard. In the case of the cerebellum, the scale and shift were not significantly different, if measured in the same cross sections that were utilized for generating the reference. In contrast, automated results were scaled 5% lower on average although not shifted, if FDG uptake was calculated from the whole segmented cerebellum volume. The estimated reduction in total SUV measurement error ranged between 54.7% and 99.2%, and the reduction was found to be statistically significant for cerebellum and aortic arch., Conclusions: With the proposed methods, the authors have demonstrated that automated SUV uptake measurements in cerebellum, liver, and aortic arch agree with expert-defined independent standards. The proposed methods were found to be accurate and showed less intra- and interobserver variability, compared to manual analysis. The approach provides an alternative to manual uptake quantification, which is time-consuming. Such an approach will be important for application of quantitative PET imaging to large scale clinical trials., (© 2012 American Association of Physicists in Medicine.)

The growing fetus depends upon transfer of glucose from maternal blood to fetal tissues. Insulin and glucocorticoid impact maternal glucose metabolism, but the effects of these hormones on fetal glucose assimilation in vivo are understudied. We thus used positron emission tomography imaging to determine the disposition of [(18)F]fluorodeoxyglucose (FDG) in rats on gestational d 20, quantifying the kinetic competition of maternal tissues and fetus for glucose. Three fasting maternal states were studied: after 2-d dexamethasone (DEX), during euglycemic hyperinsulinemic clamp insulin receiving (INS), and control (CON). In CON and DEX mothers, FDG accumulation in fetuses and placentae was substantial, rivaling that of maternal brain. By contrast, FDG accumulation was reduced in INS fetuses, placentae, and maternal brain by approximately 2-fold, despite no diminution in FDG extraction kinetics from maternal blood into these structures. The reduced FDG accumulation was due to more rapid clearance of FDG from the circulation in INS mothers, related to increased FDG avidity in INS select maternal tissues, including skeletal muscle, brown adipose tissue, and heart. DEX treatment of mothers reduced fetal weight by nearly 10%. Nonetheless, the accumulation of FDG into placentae and fetuses was similar in DEX and CON mothers. In our rat model, fetal growth restriction induced by DEX does not involve diminished glucose transport to the fetus. Maternal insulin action has little effect on the inherent avidity of the fetal-placental unit for glucose but increases glucose utilization by maternal tissues, thus indirectly reducing the glucose available to the fetus.

Background: Complex but common maternal diseases such as diabetes and obesity contribute to adverse fetal outcomes. Understanding of the mechanisms involved is hampered by difficulty in isolating individual elements of complex maternal states in vivo. We approached this problem in the context of maternal diabetes and sought an approach to expose the developing fetus in vivo to isolated hyperglycemia in the pregnant rat., Methodology and Principal Findings: We hypothesized that glucose infused into the arterial supply of one uterine horn would more highly expose fetuses in the ipsilateral versus contralateral uterine horn. To test this, the glucose tracer [18F]fluorodeoxyglucose (FDG) was infused via the left uterine artery. Regional glucose uptake into maternal tissues and fetuses was quantified using positron emission tomography (PET). Upon infusion, FDG accumulation began in the left-sided placentae, subsequently spreading to the fetuses. Over two hours after completion of the infusion, FDG accumulation was significantly greater in left compared to right uterine horn fetuses, favoring the left by 1.9+/-0.1 and 2.8+/-0.3 fold under fasted and hyperinsulinemic conditions (p<10(-11) n=32-35 and p<10(-12) n=27-45) respectively. By contrast, centrally administered [3H]-2-deoxyglucose accumulated equally between the fetuses of the two uterine horns. Induction of significant hyperglycemia (10(3) mg/dL) localized to the left uterine artery was sustained for at least 48 hours while maternal euglycemia was maintained., Conclusions and Significance: This approach exposes selected fetuses to localized hyperglycemia in vivo, minimizing exposure of the mother and thus secondary effects. Additionally, a set of less exposed internal control fetuses are maintained for comparison, allowing direct study of the in vivo fetal effects of isolated hyperglycemia. Broadly, this approach can be extended to study a variety of maternal-sided perturbations suspected to directly affect fetal health.

Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer., Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (K(FLT)) and the Patlak constant (K(Patlak)) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined., Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08+/-0.66, K(FLT)=0.045+/-0.016 min(-1) and K(Patlak)=0.039+/-0.013 min(-1). After treatment, these values were SUV=0.74+/-0.19, K(FLT)=0.011+/-0.005 min(-1) and K(Patlak)=0.005+/-0.002 min(-1). Compartmental analysis revealed a significant drop in k(3) in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease., Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT., ((c( 2010 Elsevier Inc. All rights reserved.)

Unlabelled: The purpose of this study was to investigate the kinetic behavior of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) before and early after initiation of chemoradiation therapy in patients with squamous cell head and neck cancer., Methods: A total of 8 patients with head and neck cancer underwent (18)F-FLT PET scans (7 patients at baseline and after 5 d [10 Gy] of radiation therapy given with concomitant chemotherapy and 1 patient only at baseline). Dynamic PET images were obtained with concurrent arterial or venous blood sampling. Kinetic parameters including the flux constant of (18)F-FLT based on compartmental analysis (K-FLT), the Patlak influx constant (K-Patlak), and standardized uptake value (SUV) were calculated for the primary tumor and (18)F-FLT-avid cervical lymph nodes for all scans., Results: Mean pretreatment values of uptake for the primary tumor and cervical nodes were 0.075 +/- 0.006 min(-1), 0.042 +/- 0.004 min(-1), and 3.4 +/- 0.5 (mean +/- SD) for K-FLT, K-Patlak, and SUV, respectively. After 10 Gy of radiation therapy, these values were 0.040 +/- 0.01 min(-1), 0.018 +/- 0.016 min(-1), and 1.8 +/- 1.1 for K-FLT, K-Patlak, and SUV, respectively. For all lesions seen on pretherapy and midtherapy scans, the correlation was 0.90 between K-FLT and K-Patlak, 0.91 between K-FLT and SUV, and 0.99 between K-Patlak and SUV., Conclusion: The initial (18)F-FLT uptake and change early after treatment in squamous head and neck tumors can be adequately characterized with SUV obtained at 45-60 min, which demonstrates excellent correlation with influx parameters obtained from compartmental and Patlak analyses.

We attempted to monitor the nigrostriatal dopaminergic system in rats with positron emission tomography (PET) during the progression of two experimental disease states. One model was 6-hydroxydopamine (6-OHDA) lesioning and the other was direct gene transfer of the microtubule-associated protein tau to the substantia nigra using an adeno-associated virus vector (AAV9). The PET ligand was 6-[18F]fluoro-L-m-tyrosine (FMT), imaged prior to, and at two intervals after initiating dopaminergic neurodegeneration. The striatum was delineated with the aid of repeated PET imaging (FMT and sodium fluoride for bone), realignment to subsequent computed axial tomography scans, and registration to an atlas, which proved essential to tracking disease progression. The striata on the two sides of the brain were compared over time after unilateral lesioning treatments. 6-OHDA reduced uptake on the ipsilateral side relative to the untreated contralateral side at both 1 and 4 weeks after lesioning, while the AAV9 tau led to reduced uptake of the tracer in the striatum at 4 weeks, but not 1 week after treatment. The amplitude of the loss of FMT uptake in striatum at 4 weeks with either model was subtle relative to the postmortem histological analysis of the tissue, but the multi-modal imaging analysis yielded statistical effects that matched well with the histology in terms of the timing of the loss of dopaminergic markers. Live longitudinal imaging successfully tracked two distinct types of disease progression in individual rats, although the FMT is not a sensitive ligand to monitor the extent of the lesion.

Unlabelled: Although the pathophysiology underlying the pain of fibromyalgia syndrome (FMS) remains unknown, a variety of clinical and investigational findings suggests a dysregulation of dopaminergic neurotransmission. We therefore investigated presynaptic dopaminergic function in 6 female FMS patients in comparison to 8 age- and gender-matched controls as assessed by positron emission tomography with 6-[(18)F]fluoro-L-DOPA as a tracer. Semiquantitative analysis revealed reductions in 6-[(18)F]fluoro-L-DOPA uptake in several brain regions, indicating a disruption of presynaptic dopamine activity wherein dopamine plays a putative role in natural analgesia. Although the small sample size makes these findings preliminary, it appears that FMS might be characterized by a disruption of dopaminergic neurotransmission., Perspective: An association between FMS and reduced dopamine metabolism within the pain neuromatrix provides important insights into the pathophysiology of this mysterious disorder.

Introduction: Pediatric patients have an increased risk of radiation-induced malignancies due to their ongoing development and long remaining life span. Thus, optimization of PET protocols is an important task in pediatric nuclear medicine. Long axial field-of-view (LAFOV) PET/CT has shown a significant increase in sensitivity, which provides an ideal opportunity for reduction of injected tracer activity in the pediatric population. In this study we aim to evaluate the clinical performance of a 2-[18F]FDG-tracer reduction from 3 MBq/kg to 1.5 MBq/kg on the Biograph Vision Quadra LAFOV PET/CT. Materials and methods: The first 50 pediatric patients referred for clinical whole-body PET/CT with 1.5 MBq/kg 2-[18F]FDG, were included. A standard pediatric protocol was applied. Five reconstructions were created with various time, filter and iteration settings. Image noise was computed as coefficient-ofvariance (COV = SD/mean standardized-uptake-value) calculated from a spherical 20--50 mm (diameter) liver volume-of-interest. Sets of reconstructions were reviewed by one nuclear medicine physicians, who reported image lesions on a pre-defined list of sites. Paired comparison analysis was performed with significance at PB < 0.05 (Bonferroni corrected). Results: All reconstructions, except one, achieved a COVmean (0.08--0.15) equal to or lower than current clinical acceptable values (COVref ≤ 0.15). Image noise significantly improved with increasing acquisition time, lowering iterations (i) from 6i to 4i (both with five subsets) and when applying a 2 mm Gauss filter (PB < 0.001). Significant difference in lesion detection was seen from 150s to 300s and from 150s to 600s (PB = 0.006--0.007). 99% of all lesions rated as malignant could be found on the 150s reconstruction, while 100% was found on the 300s, when compared to the 600s reconstruction. Conclusion: Injected activity and scan time can be reduced to 1.5 MBq/kg 2-[18F] FDG with 5 min acquisition time on LAFOV PET/CT, while maintaining clinical performance in the pediatric population. These results can help limit radiation exposure to patients and personnel as well as shorten total scan time, which can help increase patient comfort, lessen the need for sedation and provide individually tailored scans. [ABSTRACT FROM AUTHOR]

Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted. [ABSTRACT FROM AUTHOR]

Background: Pancreatic neuroendocrine tumors (P-NETs) constitute a subset of pancreatic mass lesions characterized by diverse clinical presentations. Despite their inherent malignant potential, the timely identification and treatment of these tumors are critical for achieving favorable clinical outcomes. This study aims to shed light on the heterogeneous tumor biology of P-NETs and the management strategies employed at a tertiary care center in Pakistan. Method: A retrospective study encompassing all patients with a biopsy-confirmed diagnosis of P-NETs at Shifa International Hospital between January 1st, 2016, and June 30th, 2021, was conducted. Meticulous data extraction from pathology records and thorough searches of medical records were performed to gather relevant demographic and clinical information. Results: A total of 24 patients were retrieved from our database, with 13 (54%) female patients. The mean age was 49.5 ± 16.3 years. Eight out of the 24 patients presented with abdominal pain. Most patients (14 out of 24) had lesions in the pancreatic head region. In three cases, lesions exhibited multicentricity. The mean lesion size measured 4.4 ± 2.3 cm. Three of the 24 patients displayed distant liver metastasis at the presentation time. 19 out of the 24 patients underwent surgical resections, while endoscopic ultrasound (EUS)-guided biopsy was performed in 4 out of 24 cases. EUS-guided tissue biopsy yielded accurate diagnoses in all four cases. Conclusion: Most P-NETs are non-functional, and there is an almost equal distribution between male and female patients. Solitary lesions predominate, and metastasis is uncommon at initial presentation. EUS-guided fine needle biopsy stands out as a dependable diagnostic modality for P-NETs. [ABSTRACT FROM AUTHOR]

In vitro studies showed that MK-912 ((2S, 12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octahydro -2H-benzo[b]furo[2,3-a]quinolizine)-2,4'-pyrimidin-2'-one) is a potent alpha2-adrenergic receptor antagonist with high affinity (Ki = 0.42, 0.26 and 0.03 nM to alpha2A, alpha2B and alpha2C, respectively) and high selectivity (alpha2A/alpha1A = 240; alpha2A/D-1 = 3600; alpha2A/D-2 = 3500; alpha2A/5-HT1 = 700; alpha2A/5-HT2 = 4100). The compound was labeled with 11C and evaluated in rodents and monkey as a specific radioligand for studying alpha2-adrenergic receptors using PET. [11C]MK-912 was synthesized by methylation of its desmethyl precursor, L-668,929, with [11C]CH3I in (Bu3O)P=O at 85 degrees C for 8 min followed by purification with HPLC in 18% yield in a synthesis time of 45 min from end of bombardment (EOB). The specific activity was 0.83-0.93 Ci/micromol and the radiochemical purity was 97%. The initial uptake of [11C]MK-912 in mouse brain, heart, lung, liver and kidney was high (5%, 4%, 5%, 17% and 8% per gram of organ, respectively, at 5 min postinjection) and the activities were then slowly cleared from these organs. The uptake of [11C]MK-912 in rat olfactory tubercle, a brain region with high density of alpha2-adrenergic receptors, was reduced by 30%, and the ratio of radioactivity in olfactory tubercle/cerebellum was reduced from 2:1 to 1:1 by coinjection of [11C]MK-912 with a potent alpha2-adrenergic receptor antagonist, atipamezole (3 mg/kg), indicating that compound 2 binds to alpha2-adrenergic receptors. However, a PET study in a rhesus monkey revealed that the initial influx of [11C]MK-912 into various brain regions (cerebellum, cortex, olfactory tubercle and striatum) was high (0.02%/cc), and the radioactivity was then washed out slowly and without significantly differential retention in these brain regions. This, coupled with the fact that none of the high-density alpha2-adrenergic receptor brain regions exceeds a few millimeters in diameter, suggests that [11C]MK-912 is probably not an ideal radioligand for studying alpha2-adrenergic receptors in humans using commercially available PET.

We compared the abilities of positron emission tomography and computed tomography to detect N2 or N3 lymph node metastases (N2 or N3) in patients with lung cancer. Positron emission tomography detects increased rates of glucose uptake, characteristic of malignant cells. Patients with peripheral tumors smaller than 2 cm and a normal mediastinum were ineligible. All patients underwent computed tomography, positron emission tomography, and surgical staging. The American Thoracic Society lymph node map was used. Computed and positron emission tomographic scans were read by separate radiologists blinded to surgical staging results. Lymph nodes were "positive" by computed tomography if larger than 1.0 cm in short-axis diameter. Standardized uptake values were recorded from areas on positron emission tomography corresponding to those from which biopsy specimens were taken; if greater than 4.2, they were called "positive." Seventy-five lymph node stations (2.8 per patient) were analyzed in 27 patients. Computed tomography incorrectly staged the mediastinum as positive for metastases in three patients and as negative for metastases in three patients. Sensitivity and specificity of computed tomographic scans were 67% and 83%, respectively. Positron emission tomography correctly staged the mediastinum in all 27 patients. When analyzed by individual node station, there were four false positive and four false negative results by computed tomography (sensitivity = 60%, specificity = 93%, positive predictive value = 60%). Positron emission tomography mislabeled one node station as positive (100% sensitive, 98% specific, positive predictive value 91%). The differences were significant when the data were analyzed both for individual lymph node stations (p = 0.039) and for patients (p = 0.031) (McNemar test). Positron emission tomography and computed tomography are more accurate than computed tomography alone in detecting mediastinal lymph node metastases from non-small-cell lung cancer.

Preliminary data indicate that positron emission tomography (PET) following injection of fluorodeoxyglucose F18 (FDG) is sensitive and specific for detecting malignant cells in chest tumors and mediastinal lymph nodes. We report a case of non-small cell lung cancer metastatic to clinically normal scalene lymph nodes that was correctly staged by FDG-PET.

No-carrier-added (NCA) (+-)-p-[18F]fluoroamphetamine (2a) and (+-)-6-[18F]fluoro-3,4-methylene-dioxy-amphetamine (2b) were synthesized through a multistep synthesis by nucleophilic substitution of the appropriate precursors (p-nitrobenzaldehyde, 1a and 6-nitropiperonal 1b, respectively) with [18F]fluoride followed by condensation with nitroethane and reduction with LAH in 20-30% yield (EOB) in a synthesis time of 90-109 min from EOB. NCA (-)-[11C]methamphetamine (4a) and (+-)-3,4-methylene-dioxy-N-[11C]methamphetamine (4b) were synthesized by methylation of the appropriate desmethyl precursors 3a and 3b with [11C]H3I in 40-60% yield (EOB) in a synthesis time of 30 min from EOB. Animal studies in mouse and rat revealed that the relative tissue uptake of these radiotracers was kidneys > lungs > liver > spleen > brain > heart > blood. The uptakes of these radiotracers in mouse brain were high and similar at 5 min post-injection (approx. 5%/g) but radioactivity then declined rapidly (approx. 1%/g at 60 min post-injection). For compounds 2a and 2b, the activity in the femur did not increase with time indicating in vivo defluorination may not be the major route of metabolism. Monoamine uptake inhibitors (nomifensine, fluoxetine and nisoxetine) did not inhibit but enhance the uptake of (-)-[11C]methamphetamine (4a) in the rat brain by greater than 50%. A PET study in a Rhesus monkey revealed that the uptakes of (-)-[11C]methamphetamine in different brain regions were similar and the retention of the radioactivity in these regions remained constant throughout the study. Analysis of arterial plasma by HPLC showed that 50% of radioactivity remained as 4a at 60 min post-injection.

The purpose of these experiments was to label an alpha 2-adrenergic receptor ligand with a positron emitting isotope and then test this radioligand in vivo. No-carrier-added [11C]WY26703 was synthesized by methylation of its desmethyl precursor, WY27050 with [11C]H3I followed by purification with HPLC in 14% yield in a synthesis time of 35 min from EOB. Ki values for unlabeled WY26703, ranged from 0.52-1.55 nM in tissues that express a single alpha 2-adrenergic receptor subtype. Tail vein injections of [11C]WY26703 in mice revealed that the compound was distributed in the brain, heart, lungs, spleen, and kidneys. In the brains of rats treated with atipamezole, an alpha 2-adrenergic receptor antagonist, there was no decrease in [11C] accumulation indicating a lack of observable specific binding of the radioligand. When brain tissue was homogenized and filtered, however, atipamezole decreased [11C] activity by 53%. Therefore, [11C]WY26703 crosses the blood-brain barrier and specifically binds to alpha 2-adrenergic receptors with high affinity. Atipamezole treatment decreased only the area of the locus coeruleus [11C] value of the various regions of the brain. The affinity, however, of [11C]WY26703 does not appear to distinguish alpha 2-receptors from nonspecific binding sites. PET study of [11C]WY26703 in a Rhesus monkey showed that influx of [11C]WY26703 into the brain was high for the first few minutes but radioactivity then declined rapidly and did not retain in a specific brain region. This suggests that [11C]WY26703 may not be a useful ligand for imaging human alpha 2-adrenergic receptors by positron emission tomography.

It is estimated that nearly one-third of solitary pulmonary nodules (SPNs) may represent bronchogenic carcinoma. The noninvasive imaging methods used currently (ie, plain radiography, computed tomography) are not reliable for accurate detection of malignancy in most SPNs. The authors prospectively evaluated use of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) for identification of malignancy in 20 patients with noncalcific, radiographically indeterminate SPNs. PET-FDG imaging demonstrated focal hypermetabolism in 13 biopsy-proved malignant nodules, whereas no increased FDG uptake was seen in the seven benign SPNs. Semiquantitative analysis with computation of differential uptake ratios also helped clearly differentiate benign nodules (mean +/- standard deviation, 0.56 +/- 0.27) from malignant nodules (mean +/- standard deviation, 5.63 +/- 2.38) (P less than .001). Thus, PET-FDG imaging may be a potentially useful noninvasive technique for accurate differentiation of benign and malignant SPNs that are radiographically indeterminate.

18F-labeled (E)-beta-fluoromethylene-DL-m-tyrosine (FMMT) was prepared by the direct reaction of FMMT with [18F]acetylhypofluorite (AcOF) resulting into three product isomers. Extensive 1H, 13C and 19F-NMR spectroscopic analysis identify these products to be 2-fluoro, 6-fluoro-FMMT and 2,6-difluoro-FMMT. The HPLC isolated radiochemical EOB yields of these products were 22, 25 and 14%, respectively, based on starting [18F]AcOF. The specific activity at the end of a synthesis time of an hour was ca 200 mCi/mmol. With the possible advantage of "metabolic trapping" in dopamine nerve terminals via covalent binding to MAO and reduced metabolite formation, [18F]F-FMMT may potentially be the optimal PET tracer for CNS dopamine nerve terminals.

Clinically oriented imaging with position emission tomography (PET) has come of age. Given an adequate referral base and physician interest, a compelling argument can be made at all levels of the review process for setting up a PET program in a clinical setting. PET is expensive. It is obvious that the cost of running a PET service depends heavily on an institution's ability to obtain reasonable financing. Educational institutions have the opportunity to acquire special funding through a variety of sources. On the other hand, money can be expensive for private entrepreneurs. It appears that in the near future PET centers will probably remain at educational institutions or large well-financed community hospitals able to raise money at reasonable rates until reimbursement issues are better resolved. Finally, the future of clinical PET may hinge significantly on the ability of commercial radiopharmaceutical suppliers to provide regional fluorodeoxyglucose distribution. As an institutional program development, PET offers opportunities by providing unique clinical data aiding the referral pattern. PET may serve as a magnet for recruitment in many areas and may promote interdisciplinary cooperation. A clinical PET center serves both as a model for future and more widespread use of PET and as a training ground for medical personnel. Finally, the unique capabilities of PET may facilitate grant opportunities.

Background: Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases. Methods: For this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified by the most commonly used PET parameter, the maximum tumor voxel normalized by dose and body weight (SUVmax) and also by the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals for SUVmax and SULpeak were used to determine the limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment. Results: The mean relative difference of SUVmax and SULpeak in 38 bone tumors of the first cohort were 4.3% and 6.7%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and − 16.3% for SUVmax, and 21.2% and − 17.5% for SULpeak. 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification using SULpeak for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria for SULpeak changed the status of 3 patients compared to the standard Positron Emission Tomography Response Criteria in Solid Tumors of ± 30% SULpeak. Conclusion: In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG SUVmax, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions in these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response. [ABSTRACT FROM AUTHOR]

Objective approaches to treatment. [ABSTRACT FROM AUTHOR]

Background: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. Methods: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). Results: In 20,887 screened references, 79 articles (82.5% in 2017–2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5–52,000, median 21) and large-span sample size (range 80–3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. Conclusion: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field. [ABSTRACT FROM AUTHOR]

Circulating tumor DNA (ctDNA), which circulates in the blood after being shed from cancer cells in the body, has recently gained attention as an excellent tumor marker. The purpose of this study was to evaluate whether ct human papillomavirus (HPV) 16 DNA (ctHPV16DNA) levels were associated with quantitative PET parameters in patients with HPV-positive head and neck (HN) squamous cell carcinoma (SCC). Fifty patients with oropharyngeal SCC (OPSCC) and 5 with SCC of unknown primary (SCCUP) before treatment were included. They all underwent blood sampling to test ctHPV16DNA levels and FDG PET-CT examinations. Quantitative PET parameters included SUVmax, metabolic tumor volume (MTV), MTV of whole-body lesions (wbMTV), and 56 texture features. ctHPV16DNA levels were compared to texture features of primary tumors in OPSCC patients (Group A) or the largest primary or metastatic lymph node lesions in OPSCC and SCCUP patients (Group B) and to other PET parameters. Spearman rank correlation test and multiple regression analysis were used to confirm the associations between ctHPV16DNA levels and PET parameters. ctHPV16DNA levels moderately correlated with wbMTV, but not with SUVmax or MTV in Groups A and B. ctHPV16DNA levels exhibited a weak negative correlation with low gray-level zone emphasis in Groups A and B. Multiple regression analysis revealed that wbMTV and high gray-level zone emphasis were the significant factors for ctHPV16DNA levels in Group B. These results were not observed in Group A. This study demonstrated that ctHPV16DNA levels correlated with the whole-body tumor burden and tumor heterogeneity visualized on FDG PET-CT in patients with HPV-positive HNSCC. [ABSTRACT FROM AUTHOR]

Introduction: Functional informaton is introduced as the mechanism to adapt cancer therapies uniquely to individual patients based on changes defined by qualified tumor biomarkers. Methods: To demonstrate the methodology, a tumor volume biomarker model, characterized by a tumor volume reduction rate coefficient, is used to adapt a tumor cell survival bioresponse radiotherapy model in terms of therapeutic radiation dose. Tumor volume, acquired from imaging data, serves as a surrogate measurement for tumor cell death, but the biomarker model derived from this data cannot be used to calculate the radiation dose absorbed by the target tumor. However, functional information does provide a mathematical connection between the tumor volume biomarker model and the tumor cell survival bioresponse model by quantifying both data sets in the units of information, thus creating an analytic conduit from bioresponse to biomarker. Results: The information guided process for individualized dose adaptations using information values acquired from the tumor cell survival bioresponse model and the tumor volume biomarker model are presented in detailed form by flowchart and tabular data. Clinical data are used to generate a presentation that assists investigator application of the information guided methodology to adaptive cancer therapy research. Conclusions: Information guided adaptation of bioresponse using surrogate data is extensible across multiple research fields because functional information mathematically connects disparate bioresponse and biomarker data sets. Thus, functional information offers adaptive cancer therapy by mathematically connecting immunotherapy, chemotherapy, and radiotherapy cancer treatment processes to implement individualized treatment plans. [ABSTRACT FROM AUTHOR]

Background: Chronic postsurgical pain (CPP) markedly impairs patients' quality of life. Research has shown that chronic stress may extend incisional nociception in male mice. Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) are integral to stress-related mental disorders (including major depressive disorder, anxiety disorders, and PTSD) and pain. However, the impact of chronic social defeat stress (CSDS) on mesolimbic dopamine (DA) transmission in the development of CPP is yet to be established. It remains uncertain whether the dopamine signals in the rostral anterior cingulate cortex (rACC), which regulate pain, derive from the VTA. This study aims to explore the role of VTA-rACC dopaminergic circuits in a mouse model of CPP induced by CSDS. Methods: We conducted CSDS on C57BL/6 J wild-type male mice (n = 12–16 mice/group) and DAT-cre male mice (n = 10–12 mice/group). After 10 days of CSDS, a left posterior plantar incision was made to establish a mouse model of CPP. Paw withdrawal thresholds (PWTs) were evaluated using Von-Frey fibre stimulation. The open field test (OFT) and elevated plus maze test (EPM) were used to assess pain-related negative emotions. We used immunofluorescence staining and Western Blot to analyse D1, D2, c-Fos, and TH expression. DAergic fibre projections in the VTA-rACC neural pathway were traced using retrograde tracing and immunofluorescence staining. Optogenetics and Chemogenetics were employed to manipulate DAergic neurons in the VTA and their axons in the rACC. Results: The ipsilateral PWTs in male C57BL/6 J mice significantly decreased after surgery, returning to baseline after seven days. Conversely, in CSDS mice, ipsilateral PWTs remained reduced for at least 30 days post-incision. A significant reduction in TH-positive neurons expressing c-Fos in the VTA of CPP mice was observed 15 days post-incision. Activating DAergic neurons significantly improved ipsilateral PWTs and locomotor performance in the OFT and EPM in CPP mice post-incision. Additionally, D1 expression in the rACC was found to decrease in CPP mice, and this reduction counteracted the increase in PWTs caused by activating DAergic neuron axon terminals in the rACC. Conclusion: CSDS results in chronicity of postsurgical nociception and anxiety-like negative emotions, with alterations in DA transmission playing a role in CPP. Specific activation of DAergic neurons mitigates nociceptive responses and anxiety-like bahaviors, possibly mediated by D1 receptors in the rACC. [ABSTRACT FROM AUTHOR]

INTRODUCTION: 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 propose an Aβ‐PET harmonization method of matching spatial resolution, as measured via a barrel phantom, across PET scanners. Our approach was validated using paired subject data, for which patients were imaged on multiple scanners. METHODS: 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. RESULTS: Vision‐mCT harmonization: Vision reconstruction with FWHM = 4.10 mm and mCT reconstruction with FWHM = 4.30 mm gave the maximal statistical similarity (maximum p‐value) between regional SUVRs. Philips‐mCT harmonization: The FWHM of the Philips reconstruction was 8.2 mm and the mCT reconstruction with the FWHM of 9.35 mm, which gave the maximal statistical similarity between regional SUVRs. Philips–Vision harmonization: The Vision reconstruction with an FWHM of 9.1 mm gave the maximal statistical similarity between regional SUVRs when compared with the Philips reconstruction of 8.2 mm and were selected as the harmonized for each scanner pair. CONCLUSION: 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. Highlights: 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. [ABSTRACT FROM AUTHOR]

PET/CT and radioisotope therapy are diagnostic and therapeutic arms of Nuclear Medicine, respectively. With the emergence of better technology, PET/CT has become an accessible modality. Diagnostic tracers exploring diseasespecific targets has led the clinicians to look beyond FDG PET. Moreover, with the emergence of theranostic pairs of radiopharmaceuticals, radioisotope therapy is gradually making it's way into treatment algorithm of common cancers in India. We therefore would like to discuss in detail the updates in PET/CT imaging and radionuclide therapy and generate a consensus-driven evidence based document which would guide the practitioners of Oncology. [ABSTRACT FROM AUTHOR]

The direct electrophilic radiofluorination of m-tyrosine using [18F]acetylhypofluorite was investigated. Results showed that this reaction was both rapid and efficient with recovered decay corrected yield of 71% radiofluorinated m-tyrosines based on starting [18F]acetylhypofluorite. Specific activity of the product obtained in this study was 100-200 mCi/mmol although 1-5 Ci/mmol are easily achievable with our improved production of [18F]AcOF. Three positional isomers were found and identified by 19F-NMR to be 2-, 4-, 6-fluoro-m-tyrosine with a distribution of 36:11:52, respectively. This measured distribution allowed the assignment of the radio-HPLC peaks. Biological studies are currently underway in our laboratory using these fluoro-m-tyrosines to determine which isomer would be most suited for the evaluation of the dopamine system by positron tomography.

Background: Modern PET reconstruction algorithms incorporate point-spread-function (PSF) correction to mitigate partial volume effect. However, PSF correction can introduce edge artifacts that lead to quantification errors. Consequently, current international guidelines advise against using PSF correction in brain PET reconstruction., Purpose: We aimed to investigate PSF-induced quantification errors in recent digital PET systems and identify conditions that mitigate them. This study utilized brain PET imaging with alginate-based realistic phantoms, simulating lesion-to-background activity ratios of 10:1 and 2:1, with eleven reconstruction parameter sets., Methods: Phantoms were prepared using a commercial anthropomorphic head phantom and two homemade inserts. Each insert contained a homogeneous 18 F-FDG alginate background with hot spheres of varying diameter (3, 4, 6, 8, 10, 12, and 15 mm). PET imaging was conducted on a digital PET-CT system Biograph Vision 600 (Siemens), with a 10 min scan duration. Imaging was performed with and without PSF correction, with 2, 4, 6, 12, 18, or 24 iterations in reconstruction, and with or without additional Gaussian postfiltering. We assessed the recovery coefficient (RC), contrast recovery coefficient (CRC), variability, and CRC-to-variability ratios for each sphere size and reconstruction parameter set., Results: PSF-corrected images of the 10:1 spheres exhibited a nonmonotonic CRC-to-sphere diameter relationship due to edge artifacts overshoot in the 10 mm-diameter sphere. In contrast, PSF images of the 2:1 spheres showed a monotonically increasing relationship. Non-PSF images of both phantoms showed an expected monotonically increasing CRC-to-sphere diameter relationship but with lower CRC values compared to PSF images. The nonmonotonic relationship observed with 10:1 spheres was mitigated by applying a 3-mm FWHM Gaussian postfiltering. For both phantoms, reconstructions with 6 iterations, PSF correction, and additional 3-mm FWHM Gaussian postfiltering demonstrated the highest CRC-to-variability ratios., Conclusions: Our findings indicate that Gaussian postfiltering suppresses PSF artifacts. This parameter set corrected the nonmonotonic CRC-to-sphere diameter relationship and improved the CRC-to-variability ratio compared to non-PSF reconstructions. Therefore, to enhance lesion detectability without compromising quantification accuracy, PSF correction coupled with Gaussian postfiltering should be used in brain PET., (© 2024 American Association of Physicists in Medicine.)

Although peptide radionuclide therapy (PRRT) using a somatostatin analog (SSA) radiolabeled with a beta- emitter: [ 177 Lu]Lu-DOTATATE has shown a good clinical efficacy in neuroendocrine tumors (NETs), most of the patients only achieved tumoral stabilization and rare but severe long-term hematological toxicities have been reported. One of the promising options to improve PRRT is targeted alpha therapy. It is therefore essential to propose animal models that can mimic systemic spread disease, especially microscopic disease such as early stage of NET liver metastases to explore targeted alpha therapy. Herein, we report the evaluation of efficacy and toxicity of [ 225 Ac]Ac-DOTATOC in an original preclinical murine model simulating the development of well-characterized liver metastases of pancreatic NETs with SSTR overexpression., Methods: A mouse model of liver metastases of pancreatic NETs was developed by intraportal injection of AR42J cells and explored using [ 68  Ga]Ga-DOTATOC and [ 18 F]F-FDG PET/MRI. Biodistribution study and radiation dosimetry of [ 225 Ac]Ac-DOTATOC were determined in subcutaneous tumor-bearing NMRI-nude mice. Efficacy and toxicity were determined by intravenous injection of increasing activities of [ 225 Ac]Ac-DOTATOC 10 days after intraportal graft., Results: Liver tumors showed a high uptake of [ 68  Ga]Ga-DOTATOC and no uptake of [ 18 F]F-FDG confirming the well-differentiated phenotype. All groups treated with [ 225 Ac]Ac-DOTATOC showed a significant increase in overall survival compared with DOTATOC-treated mice, especially those treated with the highest activities: 53 days with 240 kBq (p = 0.0001), and 58 days with 2 × 120 kBq (p < 0.0001) vs 28 days with non-radiolabeled DOTATOC. On blood tests, a transient and moderate decreased in white blood cells count after treatment and no severe hepatic or renal toxicity were observed after treatment which was consistent with pathological and radiation dosimetry findings., Conclusion: [ 225 Ac]Ac-DOTATOC exhibit a favorable efficacy and toxicity profile in a mouse model of liver micrometastatic pancreatic NET., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Point-spread-function (PSF) correction is not recommended for amyloid PET images due to Gibbs artifacts. Q.Clear™, a Bayesian Penalized Likelihood (BPL) reconstruction method without incorporating PSF correction reduces these artifacts but degrades image contrast by our previous findings. The present study aimed to recover lost contrast by optimizing reconstruction parameters in time-of-flight (TOF) BPL reconstruction of amyloid PET images without PSF correction. We selected candidate conditions based on a phantom study and then determined which were optimal in a clinical study. Phantom images were reconstructed under conditions of 1‒9 iterations, β 300-1000 and γ factors from 2 to 10 in TOF-BPL without PSF correction. We evaluated the %contrast and the coefficients of variation (CV, %). Standardized uptake value ratios (SUVr) and Centiloid scales (CL) were calculated from PET images acquired from 71 participants after an [ 18 F]flutemetamol injection. Both %contrast and CV were independent of iterations, whereas a trade-off was found between γ factors and β. We selected a γ factors of 5 without PSF correction (iterations, 1; β, 500) and of 10 without PSF correction (iterations, 1; β, 800) as candidates for clinical investigation. The SUVr and CL remained stable across various conditions, and CL scales effectively discriminated amyloid PET using measured values. The optimal reconstruction parameters of TOF-BPL for [ 18 F]flutemetamol PET images were γ factor 10, iterations 1 and β 800, without PSF correction., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

Attenuation correction (AC) is essential for quantitative positron emission tomography (PET) images. Attenuation coefficient maps (μ-maps) are usually generated from computed tomography (CT) images when PET-CT combined systems are used. If CT has been performed prior to PET imaging, pre-acquired CT can be used for brain PET AC, because the human head is almost rigid. This pre-acquired CT-based AC approach is suitable for stand-alone brain-dedicated PET, such as VRAIN (ATOX Co. Ltd., Tokyo, Japan). However, the headrest of PET is different from the headrest in pre-acquired CT images, which may degrade the PET image quality. In this study, we prepared three different types of μ-maps: (1) based on the pre-acquired CT, where namely the headrest is different from the PET system (μ-map-diffHr); (2) manually removing the headrest from the pre-acquired CT (μ-map-noHr); and (3) artificially replacing the headrest region with the headrest of the PET system (μ-map-sameHr). Phantom images by VRAIN using each μ-map were investigated for uniformity, noise, and quantitative accuracy. Consequently, only the uniformity of the images using μ-map-diffHr was out of the acceptance criteria. We then proposed an automated method for removing the headrest from pre-acquired CT images. In comparisons of standardized uptake values in nine major brain regions from the 18F-fluoro-2-deoxy-D-glucose-PET of 10 healthy volunteers, no significant differences were found between the μ-map-noHr and the μ-map-sameHr. In conclusion, pre-acquired CT-based AC with automated headrest removal is useful for brain-dedicated PET such as VRAIN. [ABSTRACT FROM AUTHOR]

Objective: Non-blinded image deblurring with deep learning was performed on blurred numerical brain images without point spread function (PSF) reconstruction to obtain edge artifacts (EA)-free images. This study uses numerical simulation to investigate the mechanism of EA in PSF reconstruction based on the spatial frequency characteristics of EA-free images. Methods: In 256 × 256 matrix brain images, the signal values of gray matter (GM), white matter, and cerebrospinal fluid were set to 1, 0.25, and 0.05, respectively. We assumed ideal projection data of a two-dimensional (2D) parallel beam with no degradation factors other than detector response blur to precisely grasp EA using the PSF reconstruction algorithm from blurred projection data. The detector response was assumed to be a shift-invariant and one-dimensional (1D) Gaussian function with 2–5 mm full width at half maximum (FWHM). Images without PSF reconstruction (non-PSF), PSF reconstruction without regularization (PSF) and with regularization of relative difference function (PSF-RD) were generated by ordered subset expectation maximization (OSEM). For non-PSF, the image deblurring with a deep image prior (DIP) was applied using a 2D Gaussian function with 2–5 mm FWHM. The 1D object-specific modulation transfer function (1D-OMTF), which is the ratio of 1D amplitude spectrum of the original and reconstructed images, was used as the index of spatial frequency characteristics. Results: When the detector response was greater than 3 mm FWHM, EA in PSF was observed in GM borders and narrow GM. No remarkable EA was observed in the DIP, and the FWHM estimated from the recovery coefficient for the deblurred image of non-PSF at 5 mm FWHM was reduced to 3 mm or less. PSF of 5 mm FWHM showed higher spatial frequency characteristics than that of DIP up to around 2.2 cycles/cm but was lower than the latter after 3 cycles/cm. PSF-RD showed almost the same spatial frequency characteristics as that of DIP above 3 cycles/cm but was inferior below 3 cycles/cm. PSF-RD has a lower spatial resolution than DIP. Conclusions: Unlike DIP, PSF lacks high-frequency components around the Nyquist frequency, generating EA. PSF-RD mitigates EA while simultaneously suppressing the signal, diminishing spatial resolution. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of a clinical-MRI radiomics model based on clinical characteristics and T2-weighted imaging (T2WI) for preoperatively evaluating lymph node (LN) metastasis in patients with MRI-predicted low tumor (T) staging rectal cancer (mrT1, mrT2, and mrT3a with extramural spread ≤ 5 mm). Methods: This retrospective study enrolled 303 patients with low T-staging rectal cancer (training cohort, n = 213, testing cohort n = 90). A total of 960 radiomics features were extracted from T2WI. Minimum redundancy and maximum relevance (mRMR) and support vector machine were performed to select the best performed radiomics features for predicting LN metastasis. Multivariate logistic regression analysis was then used to construct the clinical and clinical-radiomics combined models. The model performance for predicting LN metastasis was assessed by receiver operator characteristic curve (ROC) and clinical utility implementing a nomogram and decision curve analysis (DCA). The predictive performance for LN metastasis was also compared between the combined model and human readers (2 seniors). Results: Fourteen radiomics features and 2 clinical characteristics were selected for predicting LN metastasis. In the testing cohort, a higher positive predictive value of 75.9% for the combined model was achieved than those of the clinical model (44.8%) and two readers (reader 1: 54.9%, reader 2: 56.3%) in identifying LN metastasis. The interobserver agreement between 2 readers was moderate with a kappa value of 0.416. A clinical-radiomics nomogram and decision curve analysis demonstrated that the combined model was clinically useful. Conclusion: T2WI-based radiomics combined with clinical data could improve the efficacy in noninvasively evaluating LN metastasis for the low T-staging rectal cancer and aid in tailoring treatment strategies. [ABSTRACT FROM AUTHOR]

In radiomics research, the issue of different instruments being used is significant. In this study, we compared three correction methods to reduce the batch effects in radiogenomic data from fluorodeoxyglucose (FDG) PET/CT images of lung cancer patients. Texture features of the FDG PET/CT images and genomic data were retrospectively obtained. The features were corrected with different methods: phantom correction, ComBat method, and Limma method. Batch effects were estimated using three analytic tools: principal component analysis (PCA), the k-nearest neighbor batch effect test (kBET), and the silhouette score. Finally, the associations of features and gene mutations were compared between each correction method. Although the kBET rejection rate and silhouette score were lower in the phantom-corrected data than in the uncorrected data, a PCA plot showed a similar variance. ComBat and Limma methods provided correction with low batch effects, and there was no significant difference in the results of the two methods. In ComBat- and Limma-corrected data, more texture features exhibited a significant association with the TP53 mutation than in those in the phantom-corrected data. This study suggests that correction with ComBat or Limma methods can be more effective or equally as effective as the phantom method in reducing batch effects. [ABSTRACT FROM AUTHOR]

Background: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are common in Veterans and linked to behavioral disturbances, increased risk of cognitive decline, and Alzheimer's disease. Objective: We studied the synergistic effects of PTSD and TBI on behavioral, cognitive, and neuroimaging measures in Vietnam war Veterans. Methods: Data were acquired at baseline and after about one-year from male Veterans categorized into: PTSD, TBI, PTSD+TBI, and Veteran controls without PTSD or TBI. We applied manual tractography to examine white matter microstructure of three fiber tracts: uncinate fasciculus (N = 91), cingulum (N = 87), and inferior longitudinal fasciculus (N = 95). ANCOVAs were used to compare Veterans' baseline behavioral and cognitive functioning (N = 285), white matter microstructure, amyloid-β (N = 230), and tau PET (N = 120). Additional ANCOVAs examined scores' differences from baseline to follow-up. Results: Veterans with PTSD and PTSD+TBI, but not Veterans with TBI only, exhibited poorer behavioral and cognitive functioning at baseline than controls. The groups did not differ in baseline white matter, amyloid-β, or tau, nor in behavioral and cognitive functioning, and tau accumulation change. Progression of white matter abnormalities of the uncinate fasciculus in Veterans with PTSD compared to controls was observed; analyses in TBI and PTSD+TBI were not run due to insufficient sample size. Conclusions: PTSD and PTSD+TBI negatively affect behavioral and cognitive functioning, while TBI does not contribute independently. Whether progressive decline in uncinate fasciculus microstructure in Veterans with PTSD might account for cognitive decline should be further studied. Findings did not support an association between PTSD, TBI, and Alzheimer's disease pathology based on amyloid and tau PET. [ABSTRACT FROM AUTHOR]