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Background: Pediatric molecular imaging requires a balance between administering an activity that will yield sufficient diagnostic image quality while maintaining patient radiation exposure at acceptable levels. In current clinical practice, this balance is arrived at by the current North American Consensus Guidelines in which patient weight is used to recommend the administered activity (AA). Purpose: We have previously demonstrated that girth (waist circumference at the level of the kidneys) is better at equalizing image quality than patient weight for pediatric Tc‐99m DMSA renal function imaging. However, the correlation between image quality (IQ), AA, and patient girth has not been rigorously and systematically developed. In this work, we generate a series of curves showing the tradeoff between AA and IQ as a function of patient girth, providing the data for standards bodies to develop the next generation of dosing guideline for pediatric DMSA SPECT. Methods: An anthropomorphic phantom series that included variations in age (5, 10, and 15 years), gender (M, F), local body morphometry (5, 10, 50, 90, and 95th girth percentiles), and kidney size (±15% standard size), was used to generate realistic SPECT projections. A fixed and clinically challenging defect‐to‐organ volume percentage (0.49% of renal cortex value) was used to model a focal defect with zero uptake (i.e., full local loss of renal function). Task‐based IQ assessment methods were used to rigorously measure IQ in terms of renal perfusion defect detectability. This assessment was performed at multiple count levels (corresponding to various AAs) for groups of patients that had similar girths and defect sizes. Receiver‐operating characteristics (ROC) analysis was applied; the area under the ROC curve (AUC) was used as a figure‐of‐merit for task performance. Curves showing the tradeoff between AUC and AA were generated for these groups of phantoms. Results: Overall, the girth‐based dosing method suggested different amounts of AA compared to weight‐based dosing for the phantoms that had a relatively large body weight but a small girth or phantoms with relatively small bodyweight but large girth. Reductions of AA to 62.9% compared to weight‐based dosing guidelines can potentially be realized while maintaining a baseline (AUC = 0.80) IQ for certain 15‐year‐olds who have a relatively small girth and large defect size. Note that the task‐based IQ results are heavily dependent on the simulated defect size for the defect detection task and the appropriate AUC value must be decided by the physicians for this diagnostic task. These results are based purely on simulation and are subject to future clinical validation. Conclusions: The study provides simulation‐based IQ‐AA data for a girth‐based dosing method for pediatric renal SPECT, suggesting that patient waist circumference at the level of kidneys should be considered in selecting the AA needed to achieve an acceptable IQ. This data may be useful for standards bodies to develop girth‐based dosing guidelines. [ABSTRACT FROM AUTHOR]

Background: Both the development of kidney function in healthy children and autoregulation ability of kidney function in patients with asymmetric kidneys are important in clinical diagnosis and treatment of kidney-related diseases, but there are however only limited studies. This study aimed to investigate development of kidney function in normal children with healthy symmetric kidneys and autoregulation of the healthy kidney compensating the functional loss of a diseased one in children with asymmetric kidneys. Methods: Two hundred thirty-seven children (156 male, 81 female) from 0 to 20y (average 4.6y ± 5.1) undergoing 99mTc-MAG3 renography were included, comprising 134 with healthy symmetrically functioning kidneys and 103 with asymmetric kidneys. Clearance was calculated from kidney uptakes at 1–2 min. A developmental model between MAG3 clearance (CL) and patient age in normal group was identified (CL = 84.39Age0.395 ml/min, r = 0.957, p < 0.001). The clearance autoregulation rate in abnormal group with asymmetric kidneys was defined as the ratio of the measured MAG3 clearance and the normal value predicted from the renal developmental model of normal group. Results: No significant difference of MAG3 clearance (p = 0.723) was found between independent abnormal group and normal group. The autoregulation rate of kidney clearance in abnormal group was 94.2% on average, and no significant differences were found between two age groups (p = 0.49), male and female (p = 0.39), and left kidney and right kidney (p = 0.92) but two different grades of asymmetric kidneys (p = 0.02). Conclusions: The healthy kidney of two asymmetric kidneys can automatically regulate total kidney function up to 94% of two symmetric kidneys in normal children. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) has been widely used in paediatric oncology. 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is the most commonly used radiopharmaceutical for PET imaging. For oncological brain imaging, different amino acid PET radiopharmaceuticals have been introduced in the last years. The purpose of this document is to provide imaging specialists and clinicians guidelines for indication, acquisition, and interpretation of [18F]FDG and radiolabelled amino acid PET in paediatric patients affected by brain gliomas. There is no high level of evidence for all recommendations suggested in this paper. These recommendations represent instead the consensus opinion of experienced leaders in the field. Further studies are needed to reach evidence-based recommendations for the applications of [18F]FDG and radiolabelled amino acid PET in paediatric neuro-oncology. These recommendations are not intended to be a substitute for national and international legal or regulatory provisions and should be considered in the context of good practice in nuclear medicine. The present guidelines/standards were developed collaboratively by the EANM and SNMMI with the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group and the Response Assessment in Paediatric Neuro-Oncology (RAPNO) working group. They summarize also the views of the Neuroimaging and Oncology and Theranostics Committees of the EANM and reflect recommendations for which the EANM and other societies cannot be held responsible. [ABSTRACT FROM AUTHOR]

Overview: The American Board of Radiology offers certification in three specialties of medical physics: Therapeutic Medical Physics, Diagnostic Medical Physics, and Nuclear Medical Physics. Of these specialties, medical nuclear physics has the fewest active diplomates, only a few hundred. The diagnostic medical physics specialty certification incudes a variety of modalities (ultrasound, radiography, computed tomography, and magnetic resonance imaging) yet does not address nuclear medicine imaging or therapy. This separation dates to the beginning of the ABR certification process for medical physicists in 1947; originally there were three certificates available: X‐ray and Radium Physics, Medical Nuclear Physics and, as combination of these two, Radiological Physics. Over the span of 75 years since the Medical Nuclear Physics certification was created, much has changed in the scope and proliferation of the nuclear medicine endeavor and the question arises as to the need for change in the preparation process for medical physicists in the field. I offer thanks to our contributors and note that they are writing in the classic style of a debate, the opinions that they argue may or may not reflect their personal views. [ABSTRACT FROM AUTHOR]

99mTc-DMSA is one of the most commonly used pediatric nuclear medicine imaging agents. Nevertheless, there are no pharmacokinetic (PK) models for 99mTc-DMSA in children, and currently available pediatric dose estimates for 99mTc-DMSA use pediatric S values with PK data derived from adults. Furthermore, the adult PK data were collected in the mid-70's using quantification techniques and instrumentation available at the time. Using pediatric imaging data for DMSA, we have obtained kinetic parameters for DMSA that differ from those applicable to adults. Methods: We obtained patient data from a retrospective re-evaluation of clinically collected pediatric SPECT images of 99mTc-DMSA in 54 pediatric patients from Boston's Children Hospital (BCH), ranging in age from 1 to 16 years old. These were supplemented by prospective data from twenty-three pediatric patients (age range: 4 months to 6 years old). Results: In pediatric patients, the plateau phase in fractional kidney uptake occurs at a fractional uptake value closer to 0.3 than the value of 0.5 reported by the International Commission on Radiological Protection (ICRP) for adult patients. This leads to a 27% lower time-integrated activity coefficient in pediatric patients than in adults. Over the age range examined, no age dependency in uptake fraction at the clinical imaging time was observed. Female pediatric patients had a 17% higher fractional kidney uptake at the clinical imaging time than males (P < 0.001). Conclusions: Pediatric 99mTc-DMSA kinetics differ from those reported for adults and should be considered in pediatric patient dosimetry. Alternatively, the differences obtained in this study could reflect improved quantification methods and the need to re-examine DMSA kinetics in adults. [ABSTRACT FROM AUTHOR]

March 2021 will mark the eightieth anniversary of targeted radionuclide therapy, recognizing the first use of radioactive iodine to treat thyroid disease by Dr. Saul Hertz on March 31, 1941. The breakthrough of Dr. Hertz and collaborator physicist Arthur Roberts was made possible by rapid developments in the fields of physics and medicine in the early twentieth century. Although diseases of the thyroid gland had been described for centuries, the role of iodine in thyroid physiology had been elucidated only in the prior few decades. After the discovery of radioactivity by Henri Becquerel in 1897, rapid advancements in the field, including artificial production of radioactive isotopes, were made in the subsequent decades. Finally, the diagnostic and therapeutic use of radioactive iodine was based on the tracer principal that was developed by George de Hevesy. In the context of these advancements, Hertz was able to conceive the potential of using of radioactive iodine to treat thyroid diseases. Working with Dr. Roberts, he obtained the experimental data and implemented it in the clinical setting. Radioiodine therapy continues to be a mainstay of therapy for hyperthyroidism and thyroid cancer. However, Hertz struggled to gain recognition for his accomplishments and to continue his work and, with his early death in 1950, his contributions have often been overlooked until recently. The work of Hertz and others provided a foundation for the introduction of other radionuclide therapies and for the development of the concept of theranostics. [ABSTRACT FROM AUTHOR]

Current guidelines for administered activity (AA) in pediatric nuclear medicine imaging studies are based on a 2016 harmonization of the 2010 North American Consensus guidelines and the 2007 European Association of Nuclear Medicine pediatric dosage card. These guidelines assign AA scaled to patient body mass, with further constraints on maximum and minimum values of radiopharmaceutical activity. These guidelines, however, are not formulated based upon a rigor-ous evaluation of diagnostic image quality. In a recent study of the renal cortex imaging agent 99mTc-DMSA (Li Y et al 2019), body mass-based dosing guidelines were shown to not give the same level of image quality for patients of differing body mass. Their data suggest that patient girth at the level of the kidneys may be a better morphometric parameter to consider when selecting AA for renal nuclear medicine imaging. The objective of the present work was thus to develop a dedicated series of computational phantoms to support image quality and organ dose studies in pediatric renal imaging using 99mTc-DMSA or 99mTc-MAG3. The final library consists of 50 male and female phantoms of ages 0 to 15 years, with percentile variations (5th to 95th) in waist circumference (WC) at each age. For each phantom, nominal values of kidney volume, length, and depth were incorporated into the phantom design. Organ absorbed doses, detriment-weighted doses, and stochastic risks were assessed using ICRP reference biokinetic models for both agents. In Monte Carlo radiation transport simulations, organ doses for these agents yielded detriment-weighted dose coefficients (mSv/MBq) that were in general larger than current ICRP values of the effective dose coefficients (age and WC-averaged ratios of eDW/e were 1.40 for the male phantoms and 1.49 for the female phantoms). Values of risk index (ratio of radiation-induced to natural background cancer incidence risk x 100) varied between 0.062 (newborns) to 0.108 (15-year-olds) for 99mTc-DMSA and between 0.026 (newborns) to 0.122 (15-year-olds) for 99mTc-MAG3. Using tallies of photon exit fluence as a rough surrogate for uniform image quality, our study demonstrated that through body region-of-interest optimization of AA, there is the potential for further dose and risk reductions of between factors of 1.5 to 3.0 beyond simple weight-based dosing guidance. [ABSTRACT FROM AUTHOR]

Skeletal scintigraphy is most performed in pediatric patients using the radiopharmaceutical 99mTc labelled methylene diphosphonate (99mTc-MDP). Reference biokinetic models for 99mTc-MDP indicate 50% of the administered activity is uniformly localized to the interior bone surfaces (trabecular and cortical regions), yet imaging data clearly show some preferential uptake to the epiphyseal growth plates of the long bones. To explore the dosimetric consequences of these regional activity concentrations, we have modified mesh-type computational phantoms of the International Commission on Radiological Protection (ICRP) reference pediatric series to explicitly include geometric models of the epiphyseal growth plates (2 mm in thickness) within the left/right, distal/proximal ends of the humeri, radii, ulnae, femora, tibia, and fibulae. Bone mineral activity from the ICRP Publication 128 biokinetic model for 99mTc-MDP (ICRP 2015) was then partitioned to the growth plates at values of 0.5%, 4.4%, 8.3%, 12.2%, 16.1%, and 20%. Radiation transport simulations were performed to compute 99mTc S-values and organ dose coefficients to the soft tissues and to bone site-specific regions of spongiosa. As the percentage of bone activity assigned to the growth plates was increased (from 0.5% to 20%), absorbed doses to the soft tissue organs, active bone marrow, bone endosteum (BE), as well as the detriment-weighted dose, were shown to decrease from their nominal values (no substantial growth plate activity), while epiphyseal plate self-doses increased. In the 15 year old male phantom, moving from 0.5% to 20% relative bone activity within the epiphyseal plates resulted in a 15% reduction in active marrow (AM) and BE dose, a 10% reduction in mean soft tissue and detriment-weighted dose, and a 6.3-fold increase in epiphyseal plate self-dose. In the newborn female phantom, we observed a 18% decrease in AM and BE dose, a 10% decrease in mean soft tissue dose, a 15% decrease in detriment-weighted dose, and 12.8-fold increase in epiphyseal plate self-dose. Increases (to 3 mm) and decreases (to 1 mm) in the assumed growth plate thickness of our models were shown to impact only the growth plate self-dose. Future work in differential quantification of 99mTc-MDP activity—growth plates versus other bone surfaces—is required to provide clinically realistic data on activity partitioning as a function of patient age, and perhaps skeletal site. The phantom series presented here may be used to develop more optimized age-related guidance on 99mTc-MDP administered activities to children. [ABSTRACT FROM AUTHOR]

Background: When performing dynamic gastric emptying scintigraphy with continuous acquisition in children, a single posterior view acquisition is preferred because it allows the young patient to more easily interact with a parent or technologist even though this method tends toward overestimating gastric emptying.Objectives: The objective of our study was to develop a new attenuation correction (AC) method to improve the accuracy of the time activity curve and the measurement of residual gastric emptying from 1-h posterior images of gastric emptying scintigraphy with continuous acquisition.Materials and Methods: We developed a frame-count-based AC for gastric emptying scintigraphy from the posterior view (posterior AC method). We retrospectively reviewed 122 gastric emptying studies performed in children using conjugated posterior and anterior views, and evaluated the statistical differences between posterior only (without AC) and posterior AC using the geometric mean method as a reference standard.Results: The residual values obtained using posterior AC were not significantly different (P=0.813) compared to those using the geometric mean while the values using the posterior only were significantly different (P<0.001) from the geometric mean.Conclusion: The proposed method can replace the geometric mean method to estimate gastric emptying residual fraction using patient-friendly posterior view without a significant difference in 1-h gastric emptying scintigraphy with continuous acquisition. [ABSTRACT FROM AUTHOR]

Background: Estimated radiation dose is important for assessing and communicating the risks and benefits of pediatric nuclear medicine studies. Radiation dose depends on the radiopharmaceutical, the administered activity, and patient factors such as age and size. Most radiation dose estimates for pediatric nuclear medicine have not been based on administered activities of radiopharmaceuticals recommended by established practice guidelines. The dosage card of the European Association of Nuclear Medicine (EANM) and the North American consensus guidelines each provide recommendations of administered activities of radiopharmaceuticals in children, but there are substantial differences between these two guidelines.Objective: For 12 commonly performed pediatric nuclear medicine studies, two established pediatric radiopharmaceutical administration guidelines were used to calculate updated radiation dose estimates and to compare the radiation exposure resulting from the recommendations of each of the guidelines.Materials and Methods: Estimated radiation doses were calculated for 12 common procedures in pediatric nuclear medicine using administered activities recommended by the dosage card of the EANM (version 1.5.2008) and the 2010 North American consensus guidelines for radiopharmaceutical administered activities in pediatrics. Based on standard models and nominal age-based weights, radiation dose was estimated for typical patients at ages 1, 5, 10 and 15 years and adult. The resulting effective doses were compared, with differences greater than 20% considered significant.Results: Following either the EANM dosage card or the 2010 North American guidelines, the highest effective doses occur with radiopharmaceuticals labeled with fluorine-18 and iodine-123. In 24% of cases, following the North American consensus guidelines would result in a substantially higher radiation dose. The guidelines of the EANM dosage card would lead to a substantially higher radiation dose in 39% of all cases, and in 62% of cases in which patients were age 5 years or younger.Conclusion: For 12 commonly performed pediatric nuclear medicine studies, updated radiation dose estimates can guide efforts to reduce radiation exposure and provide current information for discussing radiation exposure and risk with referring physicians, patients and families. There can be substantial differences in radiation exposure for the same procedure, depending upon which of these two guidelines is followed. This discordance identifies opportunities for harmonization of the guidelines, which may lead to further reduction in nuclear medicine radiation doses in children. [ABSTRACT FROM AUTHOR]

Phagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. The voltage-gated proton channel Hv1 enables NOX function by compensating cellular loss of electrons with protons. Accordingly, we investigated whether NOX-mediated brain damage in stroke can be inhibited by suppression of Hv1. We found that mouse and human brain microglia, but not neurons or astrocytes, expressed large Hv1-mediated currents. Hv1 was required for NOX-dependent ROS generation in brain microglia in situ and in vivo. Mice lacking Hv1 were protected from NOX-mediated neuronal death and brain damage 24 h after stroke. These results indicate that Hv1-dependent ROS production is responsible for a substantial fraction of brain damage at early time points after ischemic stroke and provide a rationale for Hv1 as a therapeutic target for the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Background. The traditional initial imaging approach following pediatric urinary tract infection is the “bottom-up” approach (cystogram and renal ultrasound). Recently, the “top-down” approach (nuclear renal scan followed by cystogram for abnormal scans only) has gained increasing attention. The relative cost and radiation doses of these are unknown Methods. The authors used a decision model to evaluate these imaging approaches. Cost and effective radiation dose estimates, including sensitivity analyses, were based on one-time imaging only. Results. Comparing hypothetical cohorts of 100 000 children, the top-down imaging approach cost $82.9 million versus $59.2 million for the bottom-up approach. Per-capita effective radiation dose was 0.72 mSv for top-down compared with 0.06 mSv for bottom-up. Conclusions. Routine use of nuclear renal scans in children following initial urinary tract infection diagnosis would result in increased imaging costs and radiation doses as compared to initial cystogram and ultrasound. Further data are required to clarify the long-term clinical implications of this increase. [ABSTRACT FROM PUBLISHER]

Purpose: It has been shown that warming patients prior to and during F-FDG uptake by controlling the room temperature can decrease uptake by brown adipose tissue (BAT). The aim of this study is to determine if this effect is subject to seasonal variation. Methods: A retrospective review was conducted of all patients referred for whole-body F-FDG PET between December 2006 and December 2008. After December 2007, all patients were kept in the PET injection room at a constant 24°C for 30 min before and until 1 h following FDG administration. Patients over 22 years of age and those who received pre-medication known to reduce FDG uptake by BAT were excluded. One hundred and three patients were warmed to 24°C prior to scanning. The number of patients showing uptake by BAT in this group was compared to a control group of 99 patients who underwent PET prior to December 2007 when the injection room temperature was 21°C. Results: Uptake by BAT occurred in 9% of studies performed after patient warming (24°C), compared to 27% of studies performed on the control group (21°C) ( p < 0.00001). The effect of warming on decreasing FDG accumulation in BAT was statistically significant in the winter ( p < 0.005) and summer ( p < 0.001). However, in the spring and autumn, though the effect of warming on decreasing FDG accumulation in BAT was evident, it was not statistically significant ( p > 0.05). Conclusion: Maintaining room temperature at a constant 24°C for 30 min prior to and 1 h after IV tracer administration significantly decreases FDG uptake by BAT in children. This effect is greatest in the summer and winter. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the variability in quantitation of positron emission tomography (PET) data acquired within the context of a multicenter consortium. Methods: PET quantitation phantoms designed by American Association of Physicists in Medicine/Society of Nuclear Medicine Task Group 145 were sent to the ten member sites of the Pediatric Brain Tumor Consortium (PBTC), a NIH-funded research consortium investigating the biology and therapies for brain tumors in children. The phantoms were water-filled cylinders (18.6 cm inside height and 20.4 cm inside diameter) based on the standard ACR phantom with four small, “hot” cylinders of varying diameters (8, 12, 16, 25 mm, all with 38 mm height), consisting of an equilibrium mixture of 68Ge/68Ga in an epoxy matrix. At each site, the operator added the appropriate amount of 18F to the water in the background in order to attain a feature-to-background ratio of roughly 4:1. The phantom was imaged and reconstructed as if it were a brain PET scan for the PBTC. An approximately 12 mm circular region of interest (ROI) was placed over each feature and in a central area in the background. The mean and maximum pixel values for each ROI were requested from local sites in units of activity concentration (Bq/ml) and the standard uptake value (SUV) (g/mL) based on bodyweight. The activity concentration was normalized by the decay-corrected known activity concentration for the features, and reported as the absolute recovery coefficient (RC). In addition, central analyses were performed by two observers. Results: The ten sites successfully imaged the phantom within 5 months and submitted the quantitative results and the phantom image data to the PBTC Operations and Biostatistics Center. The local site-based and central analyses yielded similar mean values for RC. Local site-based SUV measurements of the hot cylindrical features yielded greater variability than central analysis (COV range of 29.9%–42.8% compared to 7.7%–23.2%). Correcting for miscalculations in the local site reported SUVs substantially reduced the variation to levels similar to the central analysis (COV range of 8.8%–18.4%) and also led to the local sites providing a similar mean of the SUV values to those from the central analysis. In the central analysis, the use of mean SUV in place of maximum SUV for an ROI of fixed size substantially reduced the variation in the SUV values (COV ranges of 7.7%–11.3% vs 9.3%–23.2%). Conclusions: Based on this investigation, a SUV variability in the range of 10%–25% due solely to instrument and analysis factors can be expected in the context of a multicenter consortium if a central reading is used and quality assurance and quality control procedures are followed. The overall SUV variability can be expected to be larger than this due to biological and protocol factors. [ABSTRACT FROM AUTHOR]

Planar scintigraphy using 99mTc-labeled methylene diphosphonate (99mTc-MDP) has been established as a method for evaluating mandibular growth and asymmetry. However, 99mTc-MDP single photon emission computed tomography (SPECT) provides improved image contrast and quantitative capability potentially allowing the clinician to make a more accurate assessment of the stage of activity of normal and asymmetric mandibular growth. The purpose of this study was to utilize 99mTc-MDP SPECT in normal subjects to develop a standardized approach to imaging the mandible that could subsequently be used to evaluate patients with potential for mandibular growth abnormalities. Thirty-two patients (22 females, 10 males, 8–25 years of age, mean of 14 years) having 99mTc-MDP bone scans (7.4 MBq/kg, maximum of 518 MBq) for indications not involving the head were asked to have an additional SPECT that included the mandibular condyles. Internal (clivus) and external (source of known activity included within the field of view) standards were both investigated. Two- and three-dimensional (2-D and 3-D) regions of interest (ROI) were drawn over each condyle and the clivus in a single slice containing the maximum pixel value within the structure. A 3-D ROI was also drawn about the external standard. Maximum and average pixel values within the 2-D and 3-D ROIs were recorded. Correlation analysis indicated that essentially the same information was obtained whether the maximum or average pixel value within a 2-D or 3-D ROI was used. The right to left ratio provided a parameter that can be used to assess the magnitude of mandibular metabolic asymmetry. Use of an external standard provides the potential for quantifying condylar uptake for assessment of the activity of mandibular growth. Normal ranges for different age groups were determined for condylar uptake using both internal and external standards. 99mTc-MDP SPECT provides a quantitative method for assessing mandibular condylar uptake as a reflection of the activity of mandibular growth. The maximum pixel value of a 2-D ROI using external standardization and the right to left ratio of the condylar uptake provide the potential for quantitative evaluation of patients with mandibular asymmetry. These parameters will be further evaluated in an upcoming clinical investigation. [ABSTRACT FROM AUTHOR]

The rationale of this study was to investigate the feasibility of three-dimensional (3D) methods to analyze 18F-fluoro-deoxy-glucose (FDG) uptake in children with anaplastic astrocytoma (AA) in a multi-institutional trial, to compare 3D and two-dimensional (2D) methods and explore data associations with progression-free survival (PFS). 3D tumor volumes from pretreatment MR images (fluid attenuation inversion recovery and postgadolinium) of children with recurrent AA on a phase I trial of imatinib mesylate were coregistered to FDG positron emission tomography (PET) images. PET data were normalized. Four metrics were defined: the maximum ratio (maximum pixel value within the 3D tumor volume, normalized), the total ratio (cumulative pixel values within the tumor volume, normalized) and tumor mean ratio (total pixel value divided by volume, normalized). 2D analysis methods were compared. Cox proportional hazards models were used to estimate the association between these methods and PFS. Strongest correlations between 2D and 3D methods were with analyses using postcontrast T1 images for volume of interest (VOI). The analyses suggest 3D maximum tumor and mean tumor ratios, whether normalized by gray matter or white matter, were associated with PFS. This study of a series of pretreatment AA patients suggests that 3D PET methods using VOIs based on postcontrast T1 correlate with 2D methods and are related to PFS. These methods yield an estimate of metabolically active tumor burden and may add prognostic information after tumor grade is determined. Future rigorous multi-institutional protocols with larger numbers of patients will be required for validation. [ABSTRACT FROM AUTHOR]