Sociodemographic factors and Child Opportunity Index disparities associated with missed care opportunities in pediatric patients with lymphoma and leukemia referred for FDG-PET/CT.

BACKGROUND: Little data exists on the association of missed care opportunities (MCOs) in children referred for nuclear medicine/nuclear oncology imaging examinations and socioeconomic disparities. OBJECTIVE: To determine the prevalence of MCOs in children with lymphoma/leukemia scheduled for fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the impact of sociodemographic factors and Child Opportunity Index (COI). MATERIALS AND METHODS: Retrospective analysis of MCOs in children with lymphoma/leukemia scheduled for FDG-PET/CT (2012 to 2022) was performed. In univariate analysis, patient, neighborhood, and appointment data were assessed across MCOs and completed appointments. Logistic regression evaluated independent effects of patient-, neighborhood-, and appointment-level factors with MCOs. Two-sided P-value < .05 was considered statistically significant. RESULTS: In 643 FDG-PET/CT appointments (n = 293 patients; median age 15 years (IQR 11.0-17.0 years); 37.9% female), there were 20 MCOs (3.1%) involving 16 patients. Only 8.2% appointments involved Black/African American non-Hispanic/Latino patients, yet they made up a quarter of total MCOs. Patients living in neighborhoods with very low or low COI experienced significantly higher MCOs versus zip codes with very high COI (6.9% vs. 0.8%; P = 0.02). Logistic regression revealed significantly increased likelihood of MCOs for patients aged 18 to 21 [odds ratio (OR) 4.50; 95% CI 1.53-13.27; P = 0.007], Black/African American non-Hispanic/Latino (OR 3.20; 95% CI 1.08-9.49; P = 0.04), zip codes with very low or low COI (OR 9.60; 95% CI 1.24-74.30; P = 0.03), and unknown insurance status. CONCLUSION: Children with lymphoma/leukemia, living in zip codes with very low or low COI, and who identified as Black/African American non-Hispanic/Latino experienced more MCOs. Our study supports the need to address intersecting sociodemographic, neighborhood, and health system factors that will improve equitable access to necessary healthcare imaging for children.

Translation and validation of oral health impact profile-49 questionnaire for use in hindi-speaking population.

Context: The subjective dimension of oral health has become a focus area for healthcare researchers in last decades. There has been an increase in scales measuring the self-perceived oral health outcomes. Oral health impact profile (OHIP-49) was developed in English, and for its use in Hindi-speaking population, translation and validation along with cross cultural adaptation are needed. Aim: To translate and validate OHIP-49 questionnaire for use in Hindi-speaking population. Settings and Design: Translation and validation of OHIP-49 questionnaire were carried out in a cross-sectional study conducted from January 2017 to October 2017 at a tertiary care centre. Methods and Material: A systematic random sample of 303 subjects reporting with orofacial pain was included in the study. The original English version OHIP-49 was initially translated and cross-culturally adapted to Hindi following WHO guidelines and then, subsequently validated. Statistical Analysis Used: The OHIP subscale measures were computed using Thurston's method. Internal consistency of the translated questionnaire was quantified in terms of Cronbach's alpha and average inter-item correlations for each domain. Results: The standardized overall Cronbach's alpha value derived from the correlation matrix was 0.88 (excellent). The average inter-item correlation coefficient was within the range of 0.3-0.5 for all the domains except for handicap domain. Conclusions: The OHIP-46-H questionnaire has an acceptable validity and reliability for use in Hindi-speaking population. It provides a possibility to narrate in details how frequently oral diseases affect the quality of life.

Use of intraoperative bone scintigraphy for resection of spinal osteoid osteoma.

BACKGROUND: The location and proximity to the spinal cord in spinal osteoid osteoma can increase the likelihood of an incomplete resection. Intraoperative bone scintigraphy (IOBS) can be used to verify location and complete surgical resection. OBJECTIVE: To review our experience using IOBS for resection of intraspinal osteoid osteoma. METHODS: IRB approved, retrospective review of IOBS-guided resection over 10 years. Patients underwent injection of 200 uCi/kg (1-20 mCi) 99mTc-MDP 3-4 h prior surgery. Portable single-headed gamma camera equipped with a pinhole collimator (3- or 4-mm aperture) was used. Images were obtained pre-operatively, at the start of the procedure, and intraoperatively. Operative notes were reviewed. Evaluation of recurrence and clinical follow-up was performed. RESULTS: Twenty IOBS-guided resections were performed in 18 patients (median age 13.5 years, 6-22 years, 12 males). Size ranged 5-16 mm, with 38.9% (7/18) cervical, 22.2% (4/18) thoracic, 22.2% (4/18) lumbar, and 16.7% (3/18) sacral. In all cases, IOBS was able to localize the lesion. After suspected total excision, IOBS altered the surgical plan in 75% of cases (15/20), showing residual activity prompting further resection. Median length of follow-up was 6 months (range 1-156 months) with 90% (18/20) showing complete resection without recurrence. Two patients had osteoid osteoma recurrence at 7 and 10 months following the original resection, requiring re-intervention. CONCLUSIONS: IOBS is a useful tool for real-time localization and assessment of spinal osteoid osteoma resection. In all cases, IOBS was able to localize the lesion and changed surgical planning in 75% of cases. Ninety percent of patients achieved complete resection and remain recurrence free.

Ischemic Stroke and Dietary Vitamin B12 Deficiency in Old-Aged Females: Impaired Motor Function, Increased Ischemic Damage Size, and Changed Metabolite Profiles in Brain and Cecum Tissue.

A vitamin B12 deficiency (vit. B12 def.) is common in the elderly, because of changes in metabolism. Clinical studies have reported that a vit. B12 def. results in worse outcome after stroke, and the mechanisms through which a vit. B12 def. changes the brain requires further investigation. This study investigated the role of vit. B12 def. on stroke outcome and mechanisms using aged female mice. Eighteen-month-old females were put on a control or vit. B12 def. diet for 4 weeks, after which an ischemic stroke was induced in the sensorimotor cortex. After damage, motor function was measured, the animals were euthanized, and tissues were collected for analysis. Vit. B12 def. animals had increased levels of total homocysteine in plasma and liver, and choline levels were also increased in the liver. Vit. B12 def. animals had larger damage volume in brain tissue and more apoptosis. The cecum tissue pathway analysis showed dysfunction in B12 transport. The analysis of mitochondrial metabolomics in brain tissue showed reduced levels of metabolites involved in the TCA cycle in vit. B12 def. animals. Motor function after stroke was impaired in vit. B12 def. animals. A dietary vit. B12 def. impairs motor function through increased apoptosis and changes in mitochondrial metabolism in brain tissue.

Case Report: A Neuro-Ophthalmological Assessment of Vision Loss in a Pediatric Case of McCune-Albright Syndrome.

Patients diagnosed with McCune-Albright Syndrome (MAS) frequently manifest craniofacial fibrous dysplasia (FD). Craniofacial FD can impinge nerve fibers causing visual loss as well as craniofacial pain. Surgical decompression of affected nerves is performed, with variable efficacy, in an attempt to restore function or alleviate symptoms. Here, we present a case of a 12-year-old MAS patient with visual deficits, particularly in the left eye (confirmed by enlarged blind spots on Goldmann visual field testing), and craniofacial pain. Decompression surgery of the left optic nerve mildly improved vision, while persistent visual deficits were noted at a 3-month follow-up assessment. An in-depth, imaging-based evaluation of the visual system, including the retinal nerve fiber layer, optic nerves, and central nervous system (CNS) visual pathways, revealed multiple abnormalities throughout the visual processing stream. In the current FD/MAS patient, a loss of white matter fiber density within the left optic radiation and functional changes involving the left primary visual cortex were observed. Aberrant structural and functional abnormalities embedded within central visual pathways may play a role in facilitating deficits in vision in FD/MAS and contribute to the variable outcome following peripheral nerve decompression surgery.

68 Ga-DOTATATE PET and functional imaging in pediatric pheochromocytoma and paraganglioma.

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors in childhood. Up to 40% of PPGL are currently thought to be associated with a hereditary predisposition. Nuclear medicine imaging modalities such as fluorodeoxyglucose positron emission tomography (18 F-FDG PET), 68 Ga-DOTATATE PET, and 123 I-metaiodobenzylguanidine (123 I-MIBG) scintigraphy play an essential role in the staging, response assessment, and determination of suitability for targeted radiotherapy in patients with PPGL. Each of these functional imaging modalities targets a different cellular characteristic and as such can be complementary to anatomic imaging and to each other. With the recent US Food and Drug Administration approval and increasing use of 68 Ga-DOTATATE for imaging in children, the purpose of this article is to use a case-based approach to highlight both the advantages and limitations of DOTATATE imaging as it is compared to current radiologic imaging techniques in the staging and response assessment of pediatric PPGL, as well as other neuroendocrine malignancies.

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.

Dietary folic acid deficiency impacts hippocampal morphology and cortical acetylcholine metabolism in adult male and female mice.

OBJECTIVE: One-carbon (1C) metabolism is a metabolic network that integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. There are sex differences in hepatic 1C metabolism, however, it is unclear whether sex differences in 1C impact the brain. The aim of this study was to investigate if sex modulates the effects of dietary folic acid deficiency, the main component of 1C, in brain tissue using a mouse model. METHODS: Male and female C57Bl/6J mice were placed on a folic acid deficient (FD) or control diet (CD) at six weeks until six months of aged. After which brain tissue and serum were collected for analysis. In brain tissue, hippocampal volume, morphology, and apoptosis as well as cortical acetylcholine metabolism were measured. RESULTS: Male and female FD mice had reduced serum levels of folate. Both males and females maintained on a FD showed a decrease in the thickness of the hippocampal CA1-CA3 region. Interestingly, there was a sex difference in the levels of active caspase-3 within the CA3 region of the hippocampus. In cortical tissue, there were increased levels of neuronal ChAT and reduced levels of AChE in FD females and male mice. CONCLUSIONS: The results indicated that FD impacts hippocampal morphology and cortical neuronal acetylcholine metabolism. The data from our study indicate that there was only one sex difference and that was in hippocampal apoptosis. Our study provides little evidence that sex modulates the effects of dietary folate deficiency on hippocampal morphology and cortical neuronal acetylcholine metabolism.

Detecting lumbar lesions in 99m Tc-MDP SPECT by deep learning: Comparison with physicians.

PURPOSE: 99m Tc-MDP single-photon emission computed tomography (SPECT) is an established tool for diagnosing lumbar stress, a common cause of low back pain (LBP) in pediatric patients. However, detection of small stress lesions is complicated by the low quality of SPECT, leading to significant interreader variability. The study objectives were to develop an approach based on a deep convolutional neural network (CNN) for detecting lumbar lesions in 99m Tc-MDP scans and to compare its performance to that of physicians in a localization receiver operating characteristic (LROC) study. METHODS: Sixty-five lesion-absent (LA) 99m Tc-MDP studies performed in pediatric patients for evaluating LBP were retrospectively identified. Projections for an artificial focal lesion were acquired separately by imaging a 99m Tc capillary tube at multiple distances from the collimator. An approach was developed to automatically insert lesions into LA scans to obtain realistic lesion-present (LP) 99m Tc-MDP images while ensuring knowledge of the ground truth. A deep CNN was trained using 2.5D views extracted in LP and LA 99m Tc-MDP image sets. During testing, the CNN was applied in a sliding-window fashion to compute a 3D "heatmap" reporting the probability of a lesion being present at each lumbar location. The algorithm was evaluated using cross-validation on a 99m Tc-MDP test dataset which was also studied by five physicians in a LROC study. LP images in the test set were obtained by incorporating lesions at sites selected by a physician based on clinical likelihood of injury in this population. RESULTS: The deep learning (DL) system slightly outperformed human observers, achieving an area under the LROC curve (AUCLROC ) of 0.830 (95% confidence interval [CI]: [0.758, 0.924]) compared with 0.785 (95% CI: [0.738, 0.830]) for physicians. The AUCLROC for the DL system was higher than that of two readers (difference in AUCLROC [ΔAUCLROC ] = 0.049 and 0.053) who participated to the study and slightly lower than that of two other readers (ΔAUCLROC  = -0.006 and -0.012). Another reader outperformed DL by a more substantial margin (ΔAUCLROC  = -0.053). CONCLUSION: The DL system provides comparable or superior performance than physicians in localizing small 99m Tc-MDP positive lumbar lesions.

Reducing radiation dose from myocardial perfusion imaging in subjects with complex congenital heart disease.

INTRODUCTION: The prevalence of defects and effective radiation dose from various myocardial perfusion imaging (MPI) strategies in congenital heart disease (CHD) is unknown. METHODS: We studied 75 subjects with complex CHD (ages 5 to 80 years) referred for MPI between 2002 and 2015. A rest and exercise or pharmacologic stress MPI was performed using 99mTechnetium sestamibi, 82rubidium or 13N-ammonia, and Sodium iodide SPECT (single-photon emission computed tomography), SPECT/CT or Cadmium zinc telluride (CZT) SPECT or PET (positron emission tomography)/CT scanners. Deidentified images were interpreted semi-quantitatively in three batches: stress only MPI, stress/rest MPI, and stress/rest MPI with taking into account a history of ventricular septal defect repair. Effective radiation dose was estimated for stress/rest MPI and predicted for 1-day stress-first (normal stress scans), and for 2-day stress/rest MPI (abnormal stress scans). RESULTS: The median age was 18.6 years. The most common type of CHD was transposition of the great arteries (63%). Rest/stress MPI was abnormal in 43% of subjects and 25% of the abnormal scans demonstrated reversible defects. Of the subjects with abnormal MPI, 33% had significant underlying anatomic coronary artery obstruction. Estimated mean effective radiation dose ranged from 2.1 ± 0.6 mSv for 13N-ammonia PET/CT to 12.5 ± 0.9 mSv for SPECT/CT. Predicted effective radiation dose was significantly lower for stress-first MPI and for 2-day stress/rest protocols. CONCLUSIONS: Due to the relatively high prevalence of abnormal stress MPI, tailored protocols with a stress-first MPI as well as the use of 2-day protocols and advanced imaging technologies including CZT SPECT, novel image reconstruction software, and PET MPI could substantially reduce radiation dose in complex CHD.

The Antioxidant Role of One-Carbon Metabolism on Stroke.

One-carbon (1C) metabolism is a metabolic network that is centered on folate, a B vitamin; it integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. This metabolic pathway also reduces levels of homocysteine, a non-protein amino acid. High levels of homocysteine are linked to increased risk of hypoxic events, such as stroke. Several preclinical studies have suggested that 1C metabolism can impact stroke outcome, but the clinical data are unclear. The objective of this paper was to review preclinical and clinical research to determine whether 1C metabolism has an antioxidant role on stroke. To accomplish the objective, we searched for publications using the following medical subject headings (MeSH) keywords: antioxidants, hypoxia, stroke, homocysteine, one-carbon metabolism, folate, methionine, and dietary supplementation of one-carbon metabolism. Both pre-clinical and clinical studies were retrieved and reviewed. Our review of the literature suggests that deficiencies in 1C play an important role in the onset and outcome of stroke. Dietary supplementation of 1C provides beneficial effects on stroke outcome. For stroke-affected patients or individuals at high risk for stroke, the data suggest that nutritional modifications in addition to other therapies could be incorporated into a treatment plan.

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.

Gastric emptying of milk in infants and children up to 5 years of age: normative data and influencing factors.

BACKGROUND: Gastric emptying scintigraphy is widely used in infants and children, but there is a lack of age-specific normative data. OBJECTIVE: The objectives of this retrospective study were: 1) to establish a range of gastric emptying of milk or formula as a surrogate for normal gastric emptying in infants and young children ≤5 years of age, and 2) to investigate the effects of patient age, feeding volume, feeding route and gastroesophageal reflux on gastric emptying. MATERIALS AND METHODS: The reports of 5,136 gastric emptying studies of children ≤5 years of age performed at Children's National Medical Center from January 1990 to August 2012 were reviewed. Demographic data, 1-h and 3-h gastric emptying values and gastroesophageal reflux status of all patients were stored in a database. Using stringent inclusion and exclusion criteria, the studies of patients as similar to healthy children as possible were selected for this study. RESULTS: The study group included 2,273 children (57% male) ages 0-59 months (median: 4.6 months). The median 1-h gastric emptying was 43% (interquartile range [IQR] 34-54%). The median 3-h gastric emptying was 91% (IQR 79-98%). Sixty-one percent of patients with 1-h gastric emptying value of <50% had 3-h gastric emptying ≥80%. Gastric emptying was significantly faster in children ≤6 months as compared with all older age groups. In each age group, the median gastric emptying decreased with increasing feeding volume. Gastric emptying was significantly faster in patients fed via combined nasogastric tube and oral routes as compared with those fed exclusively orally. There was no significant difference in gastric emptying of children with and without gastroesophageal reflux. CONCLUSION: Although there are statistically significant differences in gastric emptying based on age, volume and route of feeding, the data suggest that overall normal liquid gastric emptying in infants and children ≤5 years of age is ≥80% at 3 h. One-hour emptying measurements are not reliable for detecting delayed gastric emptying.

PET/MR Imaging:: Current Updates on Pediatric Applications.

PET/MR imaging is an integrated imaging system that combines the high soft tissue resolution of MR imaging with the quantitative data obtained from PET into a single system. It is a relatively new imaging technique but with potential clinical use in pediatric oncologic and nononcologic processes in additional to its role in research. It is particularly relevant in pediatric patients due to reduced radiation burden compared with PET/CT and the ability to obtain exquisite functional and anatomic imaging in a single imaging session, thereby reducing the number of anesthesia/sedations. This review article focuses on the current as well as future applications of PET/MR imaging in pediatric imaging, including both oncologic and nononcologic indications.

Pediatric Musculoskeletal Imaging: The Indications for and Applications of PET/Computed Tomography.

The use of PET/computed tomography (CT) for the evaluation and management of children, adolescents, and young adults continues to expand. The principal tracer used is 18F-fluorodeoxyglucose and the principal indication is oncology, particularly musculoskeletal neoplasms. The purpose of this article is to review the common applications of PET/CT for imaging of musculoskeletal issues in pediatrics and to introduce the use of PET/CT for nononcologic issues, such as infectious/inflammatory disorders, and review the use of 18F-sodium fluoride in trauma and sports-related injuries.

Chronic Acalculous Cholecystitis in Children With Biliary Symptoms: Usefulness of Hepatocholescintigraphy.

OBJECTIVES: Chronic acalculous cholecystitis (CAC) increasingly is being diagnosed as a cause of recurring biliary symptoms in children, but its clinical diagnosis remains challenging. The primary objective was to evaluate the utility of hepatocholescintigraphy in pediatric patients with suspected CAC. A secondary objective was to describe their clinical follow-up after diagnosis. METHODS: Medical records of patients (aged 9-20 years) who underwent hepatocholescintigraphy from February 2008 to January 2012 were reviewed. Patients with gallstones, and with ≤1 year of clinical follow-up, and studies without gallbladder (GB) stimulation were excluded. GB ejection fraction (GBEF) of <35% after sincalide or fatty meal (Lipomul) stimulation were considered abnormal. Diagnosis of CAC was based on histopathology after cholecystectomy. Patients with negative GB pathology, or complete resolution of symptoms without surgery, or alternative diagnoses for persistent symptoms were considered to not have CAC. RESULTS: Eighty-three patients formed the study group (median age 14.9 years), of which 81.9% were girls. Median duration of symptoms and clinical follow-up were 6 months and 2.9 years, respectively. Fifty-two patients had at least 1 study with sincalide and 36 patients had at least 1 study with Lipomul. Initial cholescintigraphy was 95.0% sensitive and 73.0% specific in diagnosing CAC, with a negative predictive value of 97.9%. Of the 31 patients with abnormal GBEF, 22 underwent cholecystectomy with improvement in pain in 72.7%, whereas all of the 9 without surgery improved. CONCLUSIONS: Hepatocholescintigraphy is useful for excluding CAC, although the clinical implications of an abnormal GBEF need to be further defined.

Esophageal transit scintigraphy in children: a user's guide and pictorial review.

Technical and clinical aspects of esophageal transit scintigraphy in pediatric patients are reviewed via several illustrative cases that highlight its utility in evaluating primary and secondary esophageal motility disorders.

How we read pediatric PET/CT: indications and strategies for image acquisition, interpretation and reporting.

PET/CT plays an important role in the diagnosis, staging and management of many pediatric malignancies. The techniques for performing PET/CT examinations in children have evolved, with increasing attention focused on reducing patient exposure to ionizing radiation dose whenever possible and minimizing scan duration and sedation times, with a goal toward optimizing the overall patient experience. This review outlines our approach to performing PET/CT, including a discussion of the indications for a PET/CT exam, approaches for optimizing the exam protocol, and a review of different approaches for acquiring the CT portion of the PET/CT exam. Strategies for PACS integration, image display, interpretation and reporting are also provided. Most practices will develop a strategy for performing PET/CT that best meets their respective needs. The purpose of this article is to provide a comprehensive overview for radiologists who are new to pediatric PET/CT, and also to provide experienced PET/CT practitioners with an update on state-of-the art CT techniques that we have incorporated into our protocols and that have enabled us to make considerable improvements to our PET/CT practice.