Joint EANM/SIOPE/RAPNO practice guidelines/SNMMI procedure standards for imaging of paediatric gliomas using PET with radiolabelled amino acids and [18F]FDG: version 1.0.

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.

Development and autoregulation of kidney function in children: a retrospective study using 99mTc-MAG3 renography.

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.

Celebrating eighty years of radionuclide therapy and the work of Saul Hertz.

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.

Pediatric Solid Gastric Emptying Scintigraphy: Normative Value Guidelines and Nonstandard Meal Alternatives.

INTRODUCTION: Adult standards for gastric emptying scintigraphy, including the type of meal and range of normative values for percent gastric emptying, are routinely used in pediatric practice, but to date have not been validated. The purpose of this study is to determine whether the use of adult criteria for gastric emptying scintigraphy is valid for children and whether alternative nonstandard meals can also be offered based on these criteria. METHODS: This retrospective study analyzed patients (n = 1,151 total) who underwent solid-phase gastric emptying scintigraphy. Patients were stratified into normal and delayed gastric emptying cohorts based on adult criteria, i.e., with normal gastric emptying defined as ≤10% gastric retention at 4 hours. Patients were further stratified based on the type of meal, namely complete or partial adult standard meals or alternative cheese-based meals. Percent gastric retention values at 1, 2, 3, and 4 hours were compared. RESULTS: The median (95% upper reference limit) percentage gastric retention values for the complete standard meal were 72% (93%) at 1 hour, 39% (65%) at 2 hours, 15% (33%) at 3 hours, and 6% (10 %) at 4 hours. By comparison, the values for cheese-based meals were 60% (87%) at 1 hour, 29% (61%) at 2 hours, 10% (30%) at 3 hours, and 5% (10%) at 4 hours. Consumption of at least 50% of the standard meal yielded similar retention percentages; 68% (89%) at 1 hour, 32% (57%) at 2 hours, 10% (29%) at 3 hours, and 5% (10%) at 4 hours. There were no significant age- or sex-specific differences using the adult criteria. DISCUSSION: The adult normative standards for gastric emptying scintigraphy are applicable for use in the pediatric population. These same standards can be also be applied to nonstandard meal options, including cheese-based alternative meals and partial standard meals.

Stomach frame-count-based attenuation correction of dynamic posterior view gastric emptying scintigraphy with continuous acquisition in children.

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.

Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment.

Osteoblasts and endothelium constitute functional niches that support haematopoietic stem cells in mammalian bone marrow. Adult bone marrow also contains adipocytes, the number of which correlates inversely with the haematopoietic activity of the marrow. Fatty infiltration of haematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia. To explore whether adipocytes influence haematopoiesis or simply fill marrow space, we compared the haematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. Here we show, by flow cytometry, colony-forming activity and competitive repopulation assay, that haematopoietic stem cells and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 'fatless' mice, which are genetically incapable of forming adipocytes, and in mice treated with the peroxisome proliferator-activated receptor-gamma inhibitor bisphenol A diglycidyl ether, which inhibits adipogenesis, marrow engraftment after irradiation is accelerated relative to wild-type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone-marrow microenvironment, and indicate that antagonizing marrow adipogenesis may enhance haematopoietic recovery in clinical bone-marrow transplantation.

A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors.

BACKGROUND: Cediranib (AZD2171), an oral pan-vascular endothelial growth factor (VEGF) inhibitor, was evaluated in this phase I study to determine its toxicity profile, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics in children and adolescents with recurrent or refractory primary central nervous system (CNS) tumors. METHODS: Children and adolescents <22 years were enrolled into one of two strata: stratum I­those not receiving enzyme-inducing anticonvulsant drugs (EIACD) and stratum II­those receiving EIACDs. Dose-level selection was based on the continual reassessment method (CRM). RESULTS: Thirty-six eligible patients with median age of 12.7 years (range, 5.4-21.7 years) in stratum I (24 males) and 12 patients (7 males) in stratum II with median age of 13.4 years (range, 8.9-19.5 years) were initially assessed over a 4-week DLT evaluation period, modified to 6 weeks during the study. An MTD of 32 mg/m(2)/day was declared; however, excessive toxicities (transaminitis, proteinuria, diarrhea, hemorrhage, palmer-planter syndrome, reversible posterior leukoencephalopathy) in the expansion cohort treated at this dose suggested that it might not be tolerated over a longer time period. An expansion cohort at 20 mg/m(2)/day also demonstrated poor longer-term tolerability. Diffusion and perfusion MRI and PET imaging variables as well as biomarker analysis were performed and correlated with outcome. At 20 mg/m(2)/day, the median plasma area under the concentration-time curve at steady state was lower than that observed in adults at similar dosages. CONCLUSIONS: While the MTD of once daily oral cediranib in children with recurrent or progressive CNS tumors was initially defined as 32 mg/m(2)/day, this dose and 20 mg/m(2)/day were not considered tolerable over a protracted time period.

Radiation doses for pediatric nuclear medicine studies: comparing the North American consensus guidelines and the pediatric dosage card of the European Association of Nuclear Medicine.

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.

AAPM/SNMMI Joint Task Force: report on the current state of nuclear medicine physics training.

The American Association of Physicists in Medicine (AAPM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) recognized the need for a review of the current state of nuclear  medicine physics training and the need to explore pathways for improving nuclear medicine physics training opportunities. For these reasons, the two organizations formed a joint AAPM/SNMMI Ad Hoc Task Force on Nuclear Medicine Physics  Training. The mission of this task force was to assemble a representative group of stakeholders to:• Estimate the demand for board-certified nuclear medicine physicists in the next 5-10 years,• Identify the critical issues related to supplying an adequate number of physicists who have received the appropriate level of training in nuclear medicine physics, and• Identify approaches that may be considered to facilitate the training of nuclear medicine physicists.As a result, a task force was appointed and chaired by an active member of both organizations that included representation from the AAPM, SNMMI, the American Board of Radiology (ABR), the American Board of Science in Nuclear Medicine (ABSNM), and the Commission for the Accreditation of Medical Physics Educational Programs (CAMPEP). The Task Force first met at the AAPM Annual Meeting in Charlotte in July 2012 and has met regularly face-to-face, online, and by conference calls. This manuscript reports the findings of the Task Force, as well as recommendations to achieve the stated mission.

Beyond current guidelines: reduction in minimum administered radiopharmaceutical activity with preserved diagnostic image quality in pediatric hepatobiliary scintigraphy.

PURPOSE: To determine if the minimum administered radiopharmaceutical activity for hepatobiliary scintigraphy can be reduced while preserving diagnostic image quality using enhanced planar processing (EPP). METHODS: A total of 40 infants between 10 and 270 days old (body mass 2.2 - 6.5 kg) had hepatobiliary scintigraphy during the period 2004 - 2010 following the intravenous administration of either (99m)Tc-mebrofenin (18 patients) or (99m)Tc-disofenin (22 patients). Due to the small size of these patients, they all received the minimum administered activity of 18.5 MBq consistent with the North American Consensus Guidelines. Six nuclear medicine physicians subjectively graded the acceptability of the image quality for clinical interpretation using a four-point scale (not acceptable, fair, good, excellent). Each physician independently graded seven image sets including the original study (full activity) and simulated reduced activity studies using binomial subsampling (50% of full activity, 25% of full activity and activity reduced by weight), with and without EPP. RESULTS: For full-activity studies, 98% were deemed acceptable by the six physicians for clinical interpretation. The percentages of acceptable 50% reduced activity studies with and without EPP were not significantly different from the percentage of acceptable full-activity studies (P = 0.193 and P = 0.998, respectively). The percentage of acceptable 25% reduced activity studies without EPP was significantly different from the percentage of acceptable full-activity studies (P < 0.001); however, this difference vanished when EPP was applied (P = 0.482). The activity reduced by weight ranged from 1.85 to 4.81 MBq (10% to 26% of full dose) and the percentages of acceptable studies with and without EPP were significantly different from the percentage of acceptable full-activity studies (P < 0.001 and P = 0.02, respectively). CONCLUSION: Clinically interpretable hepatobiliary scintigraphy images can be obtained in infants when the minimum administered activity is substantially reduced. Without EPP, clinically acceptable images may be produced with a reduction of 50%, and with EPP, a reduction of 75% or more may be possible.

Girth-based administered activity for pediatric 99m Tc-DMSA SPECT.

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.

Fetal Dose from PET and CT in Pregnant Patients.

When pregnancy is discovered during or after a diagnostic examination, the physician or the patient may request an estimate of the radiation dose received by the fetus as per guidelines and standard operating procedures. This study provided the imaging community with dose estimates to the fetus from PET/CT with protocols that are adapted to University of Michigan low-dose protocols for patients known to be pregnant. Methods: There were 9 patients analyzed with data for the first, second, and third trimesters, the availability of which is quite rare. These images were used to calculate the size-specific dose estimate (SSDE) from the CT scan portion and the SUV and 18F-FDG uptake dose from the PET scan portion using the MIRD formulation. The fetal dose estimates were tested for correlation with each of the following independent measures: gestational age, fetal volume, average water-equivalent diameter of the patient along the length of the fetus, SSDE, SUV, and percentage of dose from 18F-FDG. Stepwise multiple linear regression analysis was performed to assess the partial correlation of each variable. To our knowledge, this was the first study to determine fetal doses from CT and PET images. Results: Fetal self-doses from 18F for the first, second, and third trimesters were 2.18 mGy (single data point), 0.74-1.82 mGy, and 0.017-0.0017 mGy, respectively. The combined SSDE and fetal self-dose ranged from 1.2 to 8.2 mGy. These types of images from pregnant patients are rare. Conclusion: Our data indicate that the fetal radiation exposure from 18F-FDG PET and CT performed, when medically necessary, on pregnant women with cancer is low. All efforts should be made to minimize fetal radiation exposure by modifying the protocol.

Gastric emptying in children: what is the best acquisition method?

OBJECTIVES: The geometric mean is the recommended method for calculating gastric emptying in adults to correct for variable attenuation during the study. In children, it has been reported that a single posterior acquisition is sufficient. Our objective was to evaluate the relation between the values of gastric emptying in children obtained by posterior view only and by the geometric mean of conjugate anterior and posterior views. METHODS: The gastric residual of a standard meal was calculated in 81 children of different ages. The calculation of the gastric residual was performed with different methods, posterior only and geometric mean of anterior and posterior acquisitions. The variation between these 2 methods was evaluated in different age groups and different body weights. RESULTS: There was a high correlation (r = 0.942) between the values using posterior as compared with geometric mean for all of the patients. For children younger than 8 years and weighing <30 kg, there was no significant difference between the 2 methods for either liquid or solid meals (P = 0.89 and P = 0.11 for age; P = 0.95 and P = 0.80 for weight). For children older than 8 years and weighing >30 kg, there was no significant difference between the 2 methods for liquids (P = 0.57 for age; P = 0.69 for weight), but there was a significant difference with solids (P < 0.0001 for both age and weight). CONCLUSIONS: In children younger than 8 years and weighing <30 kg, acquisition of a single posterior image is sufficient for calculating gastric emptying at 1 hour postingestion for either liquid or solid meals. In children older than 8 years and weighing >30 kg, acquisition of both anterior and posterior images with geometric mean calculation is recommended when a solid meal is used. If a liquid meal is used in patients older than 8 years, the posterior only may be adequate.

Radiation Dose to Pediatric Patients From Radiopharmaceuticals.

Nuclear medicine provides methods and techniques in that has benefited pediatric patients and their referring physicians for over 40 years. Nuclear medicine provides qualitative and quantitative information about overall and regional function of organs, systems, and lesions in the body. This involves applications in many organ systems including the skeleton, the brain, the kidneys and the heart as well as in the diagnosis and treatment of cancer. The practice of nuclear medicine requires the administration of radiopharmaceuticals which expose the patient to very low levels of ionizing radiation. Advanced approaches in the estimation of radiation dose from the internal distribution of radiopharmaceuticals in patients of various sizes and shapes have been developed in the past 20 years. Although there is considerable uncertainty in the estimation of the risk of adverse health effects from radiation at the very low exposure levels typically associated with nuclear medicine, some considers it prudent to be more cautious when applied to children as they are generally considered to be at higher risk than adults. Standard guidelines for administered activities for nuclear medicine procedures in children have been established including the North American consensus guidelines and the Paediatric Dosage Card developed by the European Association of Nuclear Medicine. As we move into the future, these guidelines would likely be reviewed in response to changes in clinical practice, a better understanding of radiation dosimetry as applied to children as well as new clinical applications, new advancements in the field with respect to both instrumentation and image reconstruction and processing.

Impact of reconstruction parameters on lesion detection and localization in joint ictal/inter-ictal SPECT reconstruction.

PURPOSE: Previously, a joint ictal/inter-ictal SPECT reconstruction was proposed to reconstruct a differential image representing the change of brain SPECT image from an inter-ictal to an ictal study. The so-called joint method yielded better performance for epileptic foci localization than the conventional subtraction method. In this study, we evaluated the performance of different reconstruction settings of the joint reconstruction of ictal/inter-ictal SPECT data, which creates a differential image showing the difference between ictal and inter-ictal images, in lesion detection and localization in epilepsy imaging. METHODS: Differential images reconstructed from phantom data using the joint and the subtraction methods were compared based on lesion detection performance (channelized Hotelling observer signal-to-noise ratio (SNRCHO) averaged across four lesion-to-background contrast levels) at the optimal iteration. The joint-initial method which was the joint method that was initialized by the subtraction method at optimal iteration was also used to reconstruct differential images. These three methods with respective optimal iteration and the subtraction method with four iterations were applied to epileptic patient datasets. A human observer lesion localization study was performed based on localization receiver operating characteristic (LROC) analysis. RESULTS: From the phantom study, at their respective optimal iteration, the joint method yielded an improvement in lesion detection performance over the subtraction method of 26%, which increased to 145% when using the joint-initial method. From the patient study, the joint-initial method yielded the highest area under the LROC curve as compared with those of the joint and the subtraction methods with optimal iteration and with 4 iterations (0.44 vs 0.41, 0.39 and 0.36, respectively). CONCLUSIONS: In lesion detection and localization, the joint method at optimal iteration outperformed the subtraction method at optimal iteration and at iteration typically used in clinical practice. Furthermore, initialization by the subtraction method improved the performance of the joint method.

Reduction in radiation dose in mercaptoacetyltriglycerine renography with enhanced planar processing.

PURPOSE: To determine the minimum dose of technetium 99m ((99m)Tc) mercaptoacetyltriglycerine (MAG3) needed to perform dynamic renal scintigraphy in the pediatric population without loss of diagnostic quality or accurate quantification of renal function and to investigate whether adaptive noise reduction could help further reduce the minimum dose required. MATERIALS AND METHODS: Approval for this retrospective study was obtained from the institutional review board, with waiver of informed consent. A retrospective review was conducted in 33 pediatric patients consecutively referred for a (99m)Tc-MAG3 study. In each patient, a 20-minute dynamic study was performed after administration of 7.4 MBq/kg. Binomial subsampling was used to simulate studies performed with 50%, 30%, 20%, and 10% of the administered dose. Four nuclear medicine physicians independently reviewed the original and subsampled images, with and without noise reduction, for image quality. Two observers independently performed a quantitative analysis of renal function. Subjective rater confidence was analyzed by using a logistic regression model, and the quantitative analysis was performed by using the paired Student t test. RESULTS: Reducing the administered dose to 30% did not substantially affect image quality, with or without noise reduction. When the dose was reduced to 20%, there was a slight but significant decrease (P = .0074) in image quality, which resolved with noise reduction. Reducing the dose to 10% caused a decrease in image quality (P = .0003) that was not corrected with noise reduction. However, the dose could be reduced to 10% without a substantial change in the quantitative evaluation of renal function independent of the application of noise reduction. CONCLUSION: Decreasing the dose of (99m)Tc-MAG3 from 7.4 to 2.2 MBq/kg did not compromise image quality. With noise reduction, the dose can be reduced to 1.5 MBq/kg without subjective loss in image quality. The quantitative evaluation of renal function was not substantially altered, even with a theoretical dose as low as 0.74 MBq/kg.

Notch3 in human breast cancer cell lines regulates osteoblast-cancer cell interactions and osteolytic bone metastasis.

Breast cancer preferentially metastasizes to bone. We therefore addressed the role of Notch signaling in osteoblast-cancer cell interactions and in bone metastasis. Human bone marrow osteoblasts selectively enhanced the expression of Notch3 and its ligand Jagged1 in human breast cancer cell lines. Osteoblasts also stimulated cancer cell colony formation in soft agar, which was reduced by a chemical inhibitor of Notch signaling and anti-transforming growth factor beta1 (TGFbeta1) antibody. TGFbeta1, a major prometastatic product of osteoblasts, also stimulated cancer cell Notch3 expression. Notch3 knockdown in the cancer cells by stable short hairpin RNA interference decreased the osteoblast- and TGFbeta1-stimulated colony formation as well as TGFbeta1-mediated Smad3/Smad2 phosphorylation; Jagged1 level was coordinately reduced. In addition, expression of snail, a regulator of epithelial-mesenchymal transition, and the mesenchymal markers fibronectin and vimentin was attenuated by reducing Notch3 levels. To study the role of Notch3 signaling in bone metastasis, cancer cells were inoculated into athymic mice, either into femoral bone marrow cavities or into the systemic circulation via the left ventricle. Compared with robust osteolysis in mice receiving control cells, osteolytic lesions were significantly reduced following inoculation of cells with constitutively reduced Notch3 expression. Taken together, our results suggest that enhanced Notch3 expression in breast cancer cells, triggered by osteoblasts and their secretion of TGFbeta1 in the bone marrow niche, may stand as a novel mechanism for promoting bone metastasis.

Residency training for diagnostic imaging physicists should be expanded to include nuclear medicine physics.

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.

PET/computed tomography in inpatients: part 1, international survey.

PURPOSE: The purposes of this study are to (1) identify patterns of inpatient PET/computed tomography (CT) use in and outside of the USA and (2) characterize inpatient PET/CT use by location and indication. MATERIALS AND METHODS: The study was deemed exempt by the Institutional Review Board. A survey link through REDCap was emailed to the Society of Nuclear Medicine and Molecular Imaging (SNMMI) members and PET Centers of Excellence members and posted on the SNMMI website. Data were collected from May 2018 to August 2018. Analyses were conducted using SAS Software 9.4 with the NPAR1WAY procedure. Differences were evaluated using the Kruskal-Wallis test with statistical significance defined as P ≤ 0.05. RESULTS: A total of 124 people responded to the survey, 71.8% (89/124) in the USA, and 26.6% (33/124) outside the USA [1.6% (2/124) no response]. 81.5% (101/124) read inpatient PET/CTs. Median percent of inpatient PET/CTs was 8.0% (range 0-100). Use of inpatient PET/CT was different (P < 0.0001) in the USA (5%, range 0-80%) versus outside USA (17.7%, range 0-100%). Use of inpatient PET/CT was different by institution type: median percent of inpatient PET/CTs in community teaching hospitals was 4.5% (range 0-50) versus 1.1% (range 0-20) in community nonteaching, 10% (range 0-80) in academic medical centers, and 20.0% (range 6.3-40) in government-affiliated institutions (P = 0.0001). CONCLUSIONS: Most US and non-US respondents read inpatients PET/CTs. Non-US respondents read a higher percentage of inpatient PET/CTs than US respondents. Respondents in government-affiliated institutions read the highest percent of inpatient PET/CTs and community nonteaching institutions the least. Results of this survey may help physicians evaluate whether their practice of providing inpatient PET/CT fits with current practice patterns.