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Abstract: Leukemia spread in the bone marrow typically is greater in the axial skeleton than in the appendicular skeleton. We report an unusual pattern of FDG-avid bone marrow infiltration that is more prominent in the appendicular skeleton than the axial skeleton in a pediatric patient with B-cell acute lymphoblastic leukemia., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Context: The American Thyroid Association (ATA) Pediatric Guidelines recommend patients not receive radioactive iodine therapy (RAIT) for differentiated thyroid cancer (DTC) confined to the thyroid. Since publication, there is ongoing concern whether withholding RAIT will result in a lower rate of remission., Objective: This study explores whether ATA low-risk patients treated with and without RAIT achieved similar remission rates., Methods: Medical records of patients <19 years old diagnosed with DTC and treated with total thyroidectomy between 2010 and 2020 were reviewed. Multivariate logistic regression was performed to evaluate factors influencing RAIT administration and remission rate., Results: Ninety-five patients with ATA low-risk DTC were analyzed: 53% (50/95) and 47% (45/95) were treated with and without RAIT, respectively. RAIT was used to treat 82% of patients before 2015 compared with 33% of patients after 2015 (P < .01). No significant difference in 1-year remission rate was found between patients treated with and without RAIT, 70% (35/50) vs 69% (31/45), respectively. With longer surveillance, remission rates increased to 82% and 76% for patients treated with and without RAIT, respectively. Median follow-up was 5.8 years (IQR 4.3-7.9, range 0.9-10.9) and 3.6 years (IQR 2.7-6.6; range 0.9-9.3) for both cohorts. No risk factors for persistent or indeterminate disease status were found, including RAIT administration, N1a disease, and surgery after 2015., Conclusion: Withholding RAIT for pediatric patients with ATA low-risk DTC avoids exposure to radiation and does not have a negative impact on remission rates. Dynamic risk stratification at 1-year after initial treatment is a suitable time point to assess the impact of withholding RAIT for these patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Expert representatives from 11 professional societies, as part of an autonomous work group, researched and developed appropriate use criteria (AUC) for lymphoscintigraphy in sentinel lymph node mapping and lymphedema. The complete findings and discussions of the work group, including example clinical scenarios, were published on October 8, 2022, and are available at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=42021 The complete AUC document includes clinical scenarios for scintigraphy in patients with breast, cutaneous, and other cancers, as well as for mapping lymphatic flow in lymphedema. Pediatric considerations are addressed. These AUC are intended to assist health care practitioners considering lymphoscintigraphy. Presented here is a brief overview of the AUC, including the rationale and methodology behind development of the document. For detailed findings of the work group, the reader should refer to the complete AUC document online., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

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 99m Technetium sestamibi, 82 rubidium or 13 N-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 13 N-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., (© 2019. American Society of Nuclear Cardiology.)

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.

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.

Introduction: Increasingly, emerging technologies are expanding instructional possibilities, with new methods being adopted to improve knowledge acquisition and retention. Within medical education, many new techniques have been employed in the undergraduate setting, with less utilization thus far in the continuing medical education (CME) sphere. This paper discusses the use of a new method for CME-the "flipped classroom," widely used in undergraduate medical education. This method engages learners by providing content before the live ("in class") session that aids in preparation and fosters in-class engagement., Methods: A flipped classroom method was employed using an online image-rich case-based module and quiz prior to a live CME session at a national nuclear medicine meeting. The preparatory material provided a springboard for in-depth discussion at the live session-a case-based activity utilizing audience response technology. Study participants completed a survey regarding their initial experience with this new instructional method. In addition, focus group interviews were conducted with session attendees who had or had not completed the presession material; transcripts were qualitatively analyzed., Results: Quantitative survey data (completed by two-thirds of the session attendees) suggested that the flipped method was highly valuable and met attendee educational objectives. Analysis of focus group data yielded six themes broadly related to two categories-benefits of the flipped method for CME and programmatic considerations for successfully implementing the flipped method in CME., Discussion: Data from this study have proven encouraging and support further investigations around the incorporation of this innovative teaching method into CME for nuclear imaging specialists.

Background: Pretransplant functional imaging (FI), particularly a negative positron emission tomography (PET), is a strong predictor of outcome in adults with relapsed or refractory Hodgkin lymphoma (HL), but data in pediatrics are limited., Methods: The medical records of 49 consecutive pediatric patients, who received autologous transplant at a single institution, were retrospectively analyzed. All patients had either gallium or PET scan before transplant and were conditioned with carmustine, etoposide, cytarabine, and melphalan (BEAM). Deauville scores were retrospectively assigned for patients with PET (score ≥ 4 positive)., Results: Of the 49 patients (median age, 16.2 years), 41 (84%) were pretransplant FI negative and eight (16%) were pretransplant FI positive, after first- to fourth-line salvage therapy, and a median of two salvage cycles. Eighteen patients (37%) received posttransplant radiation. At a median follow up of 46 months, 45 patients (92%) were alive and disease free, and there were three nonrelapse deaths and only one relapse death (Deauville score of 5). The 4-year progression-free survival (PFS) for the entire cohort was 92% (95% confidence interval [CI]: 78-97), and PFS based on pretransplant disease status was 95% (95% CI: 82-99%) in the negative FI group versus 75% (95% CI: 31-93) if positive FI (P = 0.057)., Conclusion: Our analysis revealed outstanding outcomes for children and adolescents with relapsed/refractory HL. There were too few relapses to identify the predictive value of pretransplant metabolic status, but pediatric patients with relapsed/refractory HL and a negative pretransplant FI had excellent survival., (© 2017 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.)

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.

Purpose: Accurate staging of neuroblastoma requires multiple imaging examinations. The purpose of this study was to determine the relative contribution of 99m Tc-methylene diphosphonate (MDP) bone scintigraphy (bone scan) versus metaiodobenzylguanidine scintigraphy (MIBG scan) for accurate staging of neuroblastoma., Methods: A medical record search by the identified patients with neuroblastoma from 1993 to 2012 who underwent both MIBG and bone scan for disease staging. Cross-sectional imaging was used to corroborate the scintigraphy results. Clinical records were used to correlate imaging findings with clinical staging and patient management., Results: One hundred thirty-two patients underwent both MIBG and bone scan for diagnosis. All stage 1 (n = 12), 2 (n = 8), and 4S (n = 4) patients had a normal bone scan with no skeletal MIBG uptake. Six of 30 stage 3 patients had false (+) bone scans. In the 78 stage 4 patients, 58/78 (74%) were both skeletal MIBG(+)/bone scan (+). In 56 of the 58 cases, skeletal involvement detected with MIBG was equal to or greater than that detected by bone scan. Only 3/78 had (-) skeletal MIBG uptake and (+) bone scans; all 3 had other sites of metastatic disease. Five of 78 had (+) skeletal MIBG with a (-) bone scan, while 12/78 had no skeletal involvement by either MIBG or bone scan. In no case did a positive bone scan alone determine a stage 4 designation., Conclusion: In the staging of neuroblastoma, 99m Tc-MDP bone scintigraphy does not identify unique sites of disease that affect disease stage or clinical management, and in the majority of cases bone scans can be omitted from the routine neuroblastoma staging algorithm., (© 2017 Wiley Periodicals, Inc.)

Nuclear medicine has an important role in the evaluation of various congenital and acquired pediatric chest diseases. Although the radiopharmaceuticals and nuclear medicine examinations used in children are broadly the same as in adults, there are some key differences in clinical indications and underlying disorders. This article provides the reader with an up-to-date review of practice of nuclear medicine as it relates to the pediatric chest, including its current role and future applications., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Lymphedema is the chronic enlargement of tissue due to inadequate lymphatic function. Diagnosis is made by history and physical examination and confirmed with lymphoscintigraphy. The purpose of this study was to assess the accuracy of lymphoscintigraphy for the diagnosis of lymphedema and to determine characteristics of patients with false-negative tests., Methods: Individuals referred to our lymphedema program with "lymphedema" between 2009 and 2016 were analyzed. Subjects were assessed by history, physical examination, and lymphoscintigraphy. Patient age at presentation, duration of lymphedema, location of disease, gender, previous infections, and lymphedema type were analyzed., Results: The study included 227 patients (454 limbs); lymphedema was diagnosed clinically in 169 subjects and confirmed by lymphoscintigraphy in 162 (117 primary, 45 secondary; 96% sensitivity). Fifty-eight patients were thought to have a condition other than lymphedema, and all had negative lymphoscintigrams (100% specificity). A subgroup analysis of the 7 individuals with lymphedema clinically, but normal lymphoscintigrams, showed that all had primary lymphedema; duration of disease and infection history were not different between true-positive and false-negative lymphoscintigram results ( P = 0.5). Two patients with a false-negative test underwent repeat lymphoscintigraphy, which then showed lymphatic dysfunction consistent with lymphedema., Conclusion: Lymphoscintigraphy is very sensitive and specific for lymphedema. All patients with false-negative studies had primary lymphedema. A patient with a high clinical suspicion of lymphedema and a normal lymphoscintigram should be treated conservatively for the disease and undergo repeat lymphoscintigraphy., Competing Interests: Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors.

Background: Massive localized lymphedema (MLL) is an area of skin and subcutaneous overgrowth associated with obesity. The purpose of this study was to determine whether MLL results from obesity-induced lymphedema (OIL) and to characterize the prevalence and risk factors for the condition., Study Design: Patients evaluated in our Lymphedema Program between 2009 and 2016 were reviewed for obese individuals (BMI ≥30 kg/m 2 ) who had lower-extremity lymphatic function evaluated by lymphoscintigraphy. Candidate variables included age, sex, BMI, duration of lymphedema, infection history, and lymphoscintigraphy findings. A possible association between candidate variables and presence of MLL was determined using multivariable logistic regression. Optimal cutoff for BMI in predicting MLL was identified by receiver operating characteristic curve analysis., Results: Eighty-two patients were included in the study population. In patients with MLL (n = 17), all had OIL and none had primary or secondary lymphedema (median BMI 66 kg/m 2 ; interquartile range 62 to 78). Massive localized lymphedema involved the thigh (n = 16; bilateral = 10, unilateral = 6), genitalia (n = 3), and suprapubic area (n = 2). Control patients without MLL (n = 65) had primary (46%), secondary (37%), or obesity-induced (17%) lymphatic dysfunction (median BMI 36 kg/m 2 ; interquartile range 32 to 45). Logistic regression indicated a significant relationship between BMI and MLL condition; patients with a BMI >56 kg/m 2 had a 213-times greater odds of MLL developing vs patients with BMI ≤56 kg/m 2 (p < 0.0001). Age, sex, duration of obesity, and infection history were not associated with development of MLL (all p > 0.2)., Conclusions: Massive localized lymphedema is a consequence of OIL and affects approximately 60% of obese patients with lower-extremity dysfunction; a BMI >56 kg/m 2 significantly increases the risk. Obese individuals should be referred to a bariatric weight-loss center before their BMI reaches a threshold for OIL and MLL to develop., (Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Split renal function (SRF) can be estimated with 99m Tc-labeled dimercaptosuccinic acid (DMSA) SPECT cortical renal scintigraphy on either 2D projected images or 3D images. The purpose of this study was to determine whether there is a significant difference between SRF values calculated with the 2D method and those calculated with the 3D method., Materials and Methods: This retrospective study was performed with 99m Tc-DMSA SPECT images of 316 patients (age range, 1-26 years). All images were reconstructed by filtered back projection. An automated computational method was developed to estimate SRF using both 2D projection images and direct 3D images. A paired t test was used to evaluate the difference between SRFs determined with the two methods and the association between the magnitude of the differences and kidney size, patient age, and SRF., Results: There was strong correlation between SRFs estimated with the 2D and 3D methods (r = 0.94, p < 0.001). There was small significant difference (0.14% ± 0.86%, p = 0.003) in SRFs obtained with the two methods. The difference was clinically negligible and independent of renal length (p = 0.698), volume (p = 0.297), and patient age (p = 0.768) but was associated with SRF (p = 0.018)., Conclusion: For determination of split renal function, 99m Tc-DMSA SPECT renal scintigraphy 2D coronal projection images perform as well as and are simpler to analyze than 3D images.

Context: Most thyroid nodules are benign and their accurate identification can avoid unnecessary procedures. In adult patients, documentation of nodule autonomy is accepted as reassurance of benign histology and as justification to forgo biopsy or thyroidectomy. In contrast, the negative predictive value of nodule autonomy in children is uncertain. Some recent publications recommend surgical resection as initial management, but few address the degree of TSH suppression or the specific scintigraphic criteria used to diagnose autonomy., Objective: The objective of the study was to study the presenting features and cancer risk of children with autonomous nodules., Design and Setting: Medical records of all 31 children diagnosed with autonomous nodules at our center from 2003 to 2014 were retrospectively reviewed., Patients and Results: All children met full diagnostic criteria for autonomous nodules, defined by both autonomous 123 I uptake into the nodule and the suppression of uptake in the normal thyroid parenchyma on scintigraphy performed during hypothyrotropinemia. The median age of presentation was 15 years (range 3-18 y) with a female to male ratio of 15:1. Fifty-eight percent of patients had solitary nodules and 42% had multiple nodules. The median size of each patient's largest autonomous nodule was 39 mm (range 18-67 mm). Most of the children in this series (68%) had diagnostic biopsies and/or operative pathology of their largest autonomous nodule, which showed benign cytology or histology in all cases., Conclusions: In this pediatric series, the cancer rate observed in biopsied or resected autonomous nodules was 0%. Whereas larger studies are needed to confirm our findings, these results agree with earlier reports suggesting that thyroid cancer is rare in rigorously defined autonomous nodules and support that conservative management may be offered to selected children who meet strict diagnostic criteria for autonomous nodules, deferring definitive therapies until adulthood when the risks of thyroidectomy and 131 I ablation are lower.

Background: Lymphedema is the chronic, progressive enlargement of tissue due to inadequate lymphatic function. Although lymphedema is a specific condition, patients with a large extremity are often labeled as having "lymphedema," regardless of the underlying cause. The purpose of this study was to characterize referrals to a center to determine if lymphedema should be managed by specialists., Methods: Patients treated in our Lymphedema Program between 2009 and 2013 were reviewed. Diagnosis was determined based on history, physical examination, photographs, and imaging studies. Lymphedema type (primary or secondary), location of swelling, patient age, sex, and previous management were documented. The accuracy of referral diagnosis and the geographic origin of the patients also were analyzed., Results: Two hundred twenty-five patients were referred with a diagnosis of "lymphedema"; 71% were women and 29% were children. Lymphedema was confirmed in 75% of the cohort: primary (49%) and secondary (51%). Twenty-five percent of patients labeled with "lymphedema" had another condition. Before referral 34% of patients with lymphedema received tests that are nondiagnostic for the disease, and 8% were given a diuretic which does not improve the condition. One third of patients resided outside our local referral area. The average time between onset of lymphedema and referral to our Lymphedema Program was 7.7 years (range, 1-59 years)., Conclusions: Patients presenting to a center with "lymphedema" often have another condition, and may be suboptimally managed before their referral. Patients with suspected lymphedema should be referred to specialists focused on this disease.

Purpose of Review: Graves' disease is the most common cause of hyperthyroidism in the pediatric population. It occurs more often in adolescence and in girls; however, prepubertal children tend to have more severe disease, require longer medical therapy, and have a lower rate of remission as compared with pubertal children. The choice of which of the three therapeutic options to use (medical therapy, radioactive iodine ablation, or surgery) must be individualized. This update will focus on the current diagnostic and treatment modalities available, as well as address the controversy that exists with regards to permanent therapy., Recent Findings: The diagnosis of Graves' disease is often made clinically. With the development of second-generation and third-generation thyroid-stimulating hormone receptor antibody assays, it can be more reliably confirmed. An improved understanding of the underlying autoimmune process and genetics is underway; however, remission rates in children and adolescents remain low. Because of its ease of administration and long-term follow-up, there is a trend towards permanent therapy with radioactive iodine ablation when remission cannot be achieved with medical therapy., Summary: New genes and susceptibility loci have been identified with the hope of better understanding the refractory nature of Graves' disease. Despite the low rates of remission, permanent therapy with radioactive iodine remains a good option.

Unlabelled: The purpose of this study was to characterize obesity as a novel cause of lower extremity lymphedema. Fifty-one patients with a body mass index greater than 30 kg/m(2) without any potential cause of lymphedema were evaluated with lymphoscintigraphy. Group 1 patients (n = 33) were at their maximum body mass index; individuals with lymphatic dysfunction had a greater body mass index (72.0 kg/m(2)) compared with subjects with normal function (37.7 kg/m(2)) (p < 0.0001). Body mass index predicted the lymphoscintigram result, which was abnormal if the body mass index was greater than 60 kg/m(2) and normal if it was less than 50 kg/m(2). Group 2 patients (n = 18) had lost weight and were not at their maximum body mass index: patients who reduced their body mass index from greater than 60 kg/m to less than 50 kg/m(2) had normal (n = 4) or abnormal (n = 3) lymphatic function. Patients with obesity-induced lymphedema, or who were at risk for the condition, were referred to a surgical weight loss center., Clinical Question/level of Evidence: Risk, III.

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.

18F-fluoride PET/CT has been used for a wide variety of indications in children and young adults. Nearly all pediatric 18F-fluoride PET/CTs are performed to evaluate benign conditions. The most common indication is the evaluation of back pain in a wide variety of circumstances, including patients with sports injuries, scoliosis, trauma, and back pain after surgery. The high image quality of 18F-fluoride PET/CT can make it particularly useful for evaluating benign skeletal lesions such as osteoid osteoma and Langerhans cell histiocytosis. Quantitative assessment of bone turnover with 18F-fluoride PET/CT may make it useful for assessing the skeleton in patients with metabolic bone diseases, eating disorders, and avascular necrosis. There is little pediatric experience using 18F-fluoride PET/CT for evaluation of skeletal or soft tissue disease in childhood cancers., (Copyright © 2014 Elsevier Inc. All rights reserved.)

(18)F-FDG PET and PET/CT have a wide variety of indications in children and young adults. Oncologic indications are the most common, but others include neurology, sports medicine, cardiology, and infection imaging. Accurate interpretation of pediatric (18)F-FDG PET and PET/CT requires a technically adequate study and knowledgeable interpretation of the images. A successful pediatric (18)F-FDG PET requires age-appropriate patient preparation and consideration of patient age and developmental stage. Accurate interpretation of the study requires familiarity with normal patterns of physiologic (18)F-FDG uptake in children at all stages of development., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: (131)I-MIBG provides molecularly targeted radiotherapy for pediatric neuroblastoma patients with relapsed or refractory disease. At our institution, designated family caregivers and nurses participate in the care of the child during hospital isolation for approximately 3-5 days post-administration. The purpose of this study was to measure radiation exposure to family caregivers and nurses caring for children with neuroblastoma during their stay in the hospital for (131)I-MIBG therapy., Methods: Iodine-(131)I-MIBG therapy was administered to 14 children (mean age 6.7 ± 3.8 years, range 3-13 years) for relapsed or refractory neuroblastoma from 2009 to 2010. The administered activity ranged from 5.92 to 23.31 GBq (mean 13.65 ± 5.22 GBq). The mean administered activities were 8.77 ± 2.07 GBq (range 5.92-11.1 GBq) and 17.32 ± 3.4 GBq (range 11.84-23.31 GBq) for children less than 7 and 7 years or older, respectively. One or two designated caregivers received specific radiation safety training prior to treatment. One caregiver was allowed to stay in a room adjacent to the child to provide general patient care as instructed by nursing. Nurses assigned to the care of the patient also received specific radiation instructions. The total caregiver and nursing whole body radiation dose was determined using real-time personal dosimetry., Results: There was no correlation between caregiver (r = -0.068, P = 0.817) or nursing (r = -0.031, P = 0.916) whole-body radiation dose and the patient-administered activity. The overall mean caregiver radiation dose was 1.79 ± 1.04 mSv, but the range of caregiver radiation doses varied by more than an order of magnitude (0.35-3.81 mSv), with no caregiver receiving more than 4.0 mSv. The overall mean nursing radiation dose was 0.44 ± 0.27 mSv per treatment, ranging from 0.15 to 1.08 mSv, with no nurse receiving more than 1.1 mSv. When grouped by patient age, there was no significant difference (P = 0.673) in the mean caregiver exposure for children less than 7 years, 1.94 ± 1.17 mSv (n = 6, range 0.7-3.81 mSv), compared to 1.69 ± 0.99 mSv (n = 8, range 0.35-3.37 mSv) for children 7 years or older. Similarly, there was no significant difference (P = 0.511) in mean nursing exposure for children less than 7 years, 0.5 ± 0.31 mSv (n = 6, range 0.18-1.08 mSv), compared to 0.4 ± 0.24 mSv (n = 8, range 0.15-0.94 mSv) for children 7 years or older., Conclusion: There was no significant correlation between caregiver or nursing radiation exposure and patient-administered activity or no significant difference between patient age. This may suggest that older children who tend to receive higher administered activities may require less direct caregiver support during their hospital stay. Most importantly, all caregivers and nurses received radiation doses allowed under current regulations for individuals exposed to therapy patients during hospital isolation (<5.0 mSv), although this does not include exposure the caregivers may receive once the patient leaves the hospital.

Background: Evaluation of extension-based low back pain in young athletes with suspected pars injury may include a referral for skeletal single photon emission computed tomography (SPECT). However, the diagnostic yield of this technique in children with low back pain before the age of 10 years remains uncertain. We examined a series of consecutive SPECT scans to address this question., Materials and Methods: A retrospective review of department databases revealed 107 consecutive skeletal Tc-99m MDP SPECT scans performed between January 1, 2007 and December 31, 2009 in children less than 10 years of age. Of these, 72 studies were performed for a referral diagnosis of back pain. There were 43 girls (44 studies) and 28 boys (28 studies). The mean age was 7.2 years (range, 1.9 to 9.9 y). All SPECT scans were reviewed and positive findings documented. In addition, all available anatomic imaging, imaging reports (computed tomography, magnetic resonance, and x-ray) and clinical notes were reviewed, and results were compared with those of SPECT studies., Results: Of the 72 SPECT studies, 35 (49%) identified a focal area in the spine of abnormal increased uptake, with 17 in the region of the pars interarticularis. With additional imaging, 1 case was demonstrated not to be a pars injury (computed tomography showed a transverse process fracture) and 2 patients with negative SPECT scans were shown to have pars injuries that SPECT scan had not detected, for a total of 18 pars injuries (25%) in this cohort. Reported participation in gymnastics or football was related to pars injury (odds ratio 4.3, P=0.04)., Conclusions: Pars injury was found in 25% of children referred for SPECT scan with back pain below 10 years of age. SPECT scan was highly sensitive for this injury as well as in identifying other potential sites of pathology, and should be considered in the workup of persistent low back pain in young children., Level of Evidence: Level II, diagnostic study.

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.

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., (© RSNA, 2011.)

In the chest, the indications for nuclear medicine studies are broader and more varied in children than in adults. In children, nuclear medicine studies are used to evaluate congenital and developmental disorders of the chest, as well as diseases more typical of adults. In the chest, pediatric nuclear medicine uses the same radiopharmaceuticals and imaging techniques as used in adults to evaluate cardiac and pulmonary disease, aerodigestive disorders, and pediatric malignancies. The introduction of PET (mostly using (18)F-FDG) has transformed pediatric nuclear oncology, particular for imaging malignancies in the chest., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Patients with high-risk neuroblastoma have a poor prognosis, especially in cases of recurrent or relapsed disease. Iodine-131-labeled meta-iodobenzylguanidine ((131)I-MIBG) can be an effective and relatively well-tolerated agent for the treatment of refractory neuroblastoma. Establishing an MIBG therapy program requires a great deal of planning, availability of hospital resources, and the commitment of individuals with training and expertise in multiple disciplines. Providing (131)I-MIBG therapy requires physical facilities and procedures that permit patient care in compliance with the standards for occupational and community exposure to radiation. Establishment of a successful (131)I-MIBG therapy program also requires a detailed operational plan and appropriate education for caregivers, parents, and patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Lymphedema results from maldevelopment of the lymphatic system (primary) or injury to lymphatic vasculature (secondary). Primary lymphedema is far less common than the secondary condition. The purpose of this study was to determine the clinical features of primary lymphedema in the pediatric age group., Methods: The authors' Vascular Anomalies Center database was reviewed for patients evaluated between 1999 and 2010 with onset of lymphedema before 21 years of age. Cause, sex, age of onset, location, and familial/syndromic association were determined. Morbidity, progression, and treatment were analyzed., Results: Lymphedema was confirmed in 142 children: 138 cases (97.2 percent) were primary and four (2.8 percent) were secondary. Analysis of the primary cohort showed that 58.7 percent of the patients were female. Age of onset was infancy, 49.2 percent; childhood, 9.5 percent; or adolescence, 41.3 percent. Boys most commonly presented in infancy (68.0 percent), whereas girls usually developed swelling in adolescence (55.3 percent). Lymphedema involved an extremity (81.9 percent), genitalia (4.3 percent), or both (13.8 percent). The lower limb was most commonly affected (91.7 percent), and 52.9 percent had bilateral lower extremity disease. Eleven percent of patients had familial or syndromic lymphedema. Cellulitis occurred in 18.8 percent of children; 13.0 percent required hospitalization. The majority of patients (57.9 percent) had progression of their disease. Treatment was compression garments alone (75.4 percent) or in combination with pneumatic compression (19.6 percent); 13.0 percent had operative intervention., Conclusions: Pediatric primary lymphedema usually involves the lower extremities. Boys typically are affected at birth, and girls most often present during adolescence. Most patients do not have major morbidity, are successfully managed by compression, and do not require surgical treatment.

Nuclear medicine has an important role in the care of newborns and children less than 1 y old. Patients in this age group present with a spectrum of diseases different from those of older children or adults. These patients can benefit from the full range of nuclear medicine studies. In these young children, nuclear medicine studies are more likely to be used to evaluate a wide range of congenital conditions but also can be helpful for evaluating acquired conditions such as infection, cancer, and trauma. This review first will cover the general aspects of nuclear medicine practice with these patients, including the special considerations that can help achieve successful diagnostic imaging. These topics will include clinical indications, imaging technology, instrumentation, software, positioning and immobilization, sedation, local and general anesthesia, radiopharmaceutical doses, radiation risk, and dose reduction. The review then will discuss the specific nuclear medicine studies that typically are obtained in patients in this age group. With extra care and attention to the special needs of this population, nuclear medicine departments can successfully study patients less than 1 y old.

Background: There are many causes for a large lower limb in the pediatric age group. These children are often mislabeled as having lymphedema, and incorrect diagnosis can lead to improper treatment. The purpose of this study was to determine the differential diagnosis in pediatric patients referred for lower extremity "lymphedema" and to clarify management., Methods: The authors' Vascular Anomalies Center database was reviewed between 1999 and 2010 for patients referred with a diagnosis of lymphedema of the lower extremity. Records were studied to determine the correct cause for the enlarged extremity. Alternative diagnoses, sex, age of onset, and imaging studies were also analyzed., Results: A referral diagnosis of lower extremity lymphedema was given to 170 children; however, the condition was confirmed in only 72.9 percent of patients. Forty-six children (27.1 percent) had another disorder: microcystic/macrocystic lymphatic malformation (19.6 percent), noneponymous combined vascular malformation (13.0 percent), capillary malformation (10.9 percent), Klippel-Trenaunay syndrome (10.9 percent), hemihypertrophy (8.7 percent), posttraumatic swelling (8.7 percent), Parkes Weber syndrome (6.5 percent), lipedema (6.5 percent), venous malformation (4.3 percent), rheumatologic disorder (4.3 percent), infantile hemangioma (2.2 percent), kaposiform hemangioendothelioma (2.2 percent), or lipofibromatosis (2.2 percent). Age of onset in children with lymphedema was older than in patients with another diagnosis (p = 0.027)., Conclusions: "Lymphedema" is not a generic term. Approximately one-fourth of pediatric patients with a large lower extremity are misdiagnosed as having lymphedema; the most commonly confused causes are other types of vascular anomalies. History, physical examination, and often radiographic studies are required to differentiate lymphedema from other conditions to ensure the child is managed appropriately.

Objective: Athletes can have pain derived from fractures or alternate pathology. Skeletal scintigraphy may detect abnormalities before anatomic imaging and provides a practical tool for whole-body imaging. However, study interpretation in children can be challenging. This pictorial essay describes a technique for pediatric skeletal scintigraphy and reviews findings commonly encountered in athletes., Conclusion: Skeletal scintigraphy complements anatomic findings in pediatric athletes. Familiarity with imaging technique and study interpretation can improve diagnosis.

Objective: Our objective was to evaluate screening for vesicoureteral reflux (VUR) among siblings of patients with VUR, in terms of cost, radiation exposure, and number of febrile urinary tract infections (fUTIs) averted., Methods: We constructed a Markov model to evaluate 2 competing management options, that is, universal screening (cystographic evaluation of all siblings without symptoms) and usual care (cystographic evaluation of siblings only after fUTIs). Published data were used to inform all model inputs. Costs were estimated by using a societal perspective., Results: Universal screening yielded 2980 fUTIs, whereas usual care yielded 6330. Therefore, universal screening for VUR in a cohort of 100,000 siblings 1 year of age without symptoms resulted in the prevention of 1 initial fUTI per 3360 siblings, at an excess cost of $55,600 per averted fUTI, in comparison with usual care. These estimates were heavily dependent on screening age and the effectiveness of antibiotic prophylaxis; prevention of a single fUTI would require screening of 166 siblings 5 years of age and 694 siblings 10 years of age. Similarly, if prophylaxis was ineffective in preventing fUTIs, then up to 10,000 siblings would need to be screened for prevention of a single fUTI., Conclusions: Prevention of a single fUTI would require screening of 30 to 430 siblings 1 year of age without symptoms, at an estimated excess cost of $56,000 to $820,000 per averted fUTI. These estimates are heavily dependent on screening age and the effectiveness of antibiotic prophylaxis.

Purpose: It has been shown that warming patients prior to and during (18)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 (18)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 degrees 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 degrees 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 degrees C., Results: Uptake by BAT occurred in 9% of studies performed after patient warming (24 degrees C), compared to 27% of studies performed on the control group (21 degrees 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 degrees 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.

Although uncommon, musculoskeletal malignancies are major contributors to morbidity and mortality in children and young adults. (18)F-Fluorodeoxyglucose (FDG)-PET can play an important role in disease management, including staging, assessing response to therapy, and evaluating for recurrence. Advantages of (18)F-FDG-PET and (18)F-FDG-PET/computed tomography (CT) include the capability to assess tumor activity and a large field of view that can include the whole body or torso. (18)F-FDG-PET does not always discriminate benign and malignant musculoskeletal lesion, but it can serve to guide diagnostic procedures, such as needle biopsy. In patients with osteosarcoma, FDG-PET/CT cannot replace a 99mTc-methyldiphosphonate bone scan for localization of skeletal metastases. FDG-PET may be useful for the evaluation of non-rhabdomyosarcoma sarcomas on a case-by-case basis. (18)F-FDG-PET or PET/CT is most useful for identifying sites of distant disease in patients with newly diagnosed or recurrent Ewing sarcoma, rhabdomyosarcoma, or osseous lymphoma., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the sensitivity of fluorine 18-labeled sodium fluoride ((18)F-NaF) positron emission tomography (PET) for assessment of skeletal trauma in pediatric patients suspected of having been abused and to compare the diagnostic performance of this examination with that of high-detail skeletal survey., Materials and Methods: The institutional review board approved this retrospective study and determined that it was in accordance with regulations of HIPAA privacy rule 45, Code of Federal Regulations parts 160 and 164, and that the criteria for waived patient authorization were met. The baseline skeletal survey and PET images obtained in 22 patients younger than 2 years between September 2007 and January 2009 were reviewed. Fourteen patients also underwent follow-up skeletal survey. The PET images were interpreted by two pediatric nuclear medicine physicians. The initially obtained skeletal survey images were interpreted blindly by a pediatric radiologist. A second pediatric radiologist interpreted the follow-up skeletal survey images in conjunction with the baseline survey images and rendered a final interpretation for the 14 patients in whom both baseline and follow-up skeletal survey data were available, which served as the reference standard., Results: A total of 156 fractures were detected at baseline skeletal survey, and 200 fractures were detected at PET. Compared with the reference standard (findings in the 14 patients who underwent baseline and follow-up skeletal survey), PET had sensitivities of 85% for the detection of all fractures, 92% for the detection of thoracic fractures (ribs, sternum, clavicle, and scapula), 93% for the detection of posterior rib fractures, and 67% for the detection of classic metaphyseal lesions (CMLs), defined as a series of microfractures across the metaphysis. Compared with the reference standard, baseline skeletal survey had sensitivities of 72% for the detection of all fractures, 68% for the detection of thoracic fractures, 73% for the detection of posterior rib fractures, and 80% for the detection of CMLs., Conclusion: (18)F-NaF PET had greater sensitivity in the overall detection of fractures related to child abuse than did baseline skeletal survey. (18)F-NaF PET was superior in the detection of rib fractures in particular. Thus, (18)F-NaF PET is an attractive choice for evaluation of suspected child abuse, an application in which high sensitivity is desirable. Because of the lower sensitivity of PET in the detection of CMLs, a characteristic fracture in child abuse, initial radiographic evaluation remains necessary., (RSNA, 2010)

Tens of thousands of transfusion-dependent (eg, thalassemia) patients worldwide suffer from chronic iron overload and its potentially fatal complications. The oral iron chelator deferasirox has become commercially available in many countries since 2006. Although this alternative to parenteral deferoxamine has been a major advance for patients with transfusional hemosiderosis, a proportion of patients have suboptimal response to the maximum approved doses (30 mg/kg per day), and do not achieve negative iron balance. We performed a prospective study of oral deferasirox pharmacokinetics (PK), comparing 10 transfused patients with inadequate deferasirox response (rising ferritin trend or rising liver iron on deferasirox doses > 30 mg/kg per day) with control transfusion-dependent patients (n = 5) with adequate response. Subjects were admitted for 4 assessments: deferoxamine infusion and urinary iron measurement to assess readily chelatable iron; quantitative hepatobiliary scintigraphy to assess hepatic uptake and excretion of chelate; a 24-hour deferasirox PK study following a single 35-mg/kg dose of oral deferasirox; and pharmacogenomic analysis. Patients with inadequate response to deferasirox had significantly lower systemic drug exposure compared with control patients (P < .00001). Cmax, volume of distribution/bioavailability (Vd/F), and elimination half-life (t(1/2)) were not different between the groups, suggesting bioavailability as the likely discriminant. Effective dosing regimens for inadequately responding patients to deferasirox must be determined. This trial has been registered at http://www.clinicaltrials.gov under identifier NCT00749515.

Purpose: The aim of this study was to determine if warming patients prior to and during (18)F-FDG uptake by controlling the room temperature could decrease uptake by brown adipose tissue (BAT)., Methods: A group of 40 children underwent (18)F-FDG PET after being kept in the injection room at a constant temperature of 24 degrees C for half an hour before and 1 hour after intravenous tracer administration. The rate of uptake by BAT in this group was compared to the uptake in a control group of 45 patients who underwent PET when the injection room temperature was 21 degrees C., Results: Uptake by BAT occurred in 5% of studies in the temperature-controlled room compared to 31% of studies performed when the injection room temperature was 21 degrees C (p<0.002)., Conclusion: Maintaining room temperature at a constant 24 degrees C, half an hour prior to and during the period of FDG uptake significantly decreases accumulation of FDG in BAT in children.

Although (18)F-labeled NaF was the first widely used agent for skeletal scintigraphy, it quickly fell into disuse after the introduction of (99m)Tc-labeled bone-imaging agents. Recent comparative studies have demonstrated that (18)F-fluoride PET is more accurate than (99m)Tc-diphosphonate SPECT for identifying both malignant and benign lesions of the skeleton. Combining (18)F-fluoride PET with other imaging, such as CT, can improve the specificity and overall accuracy of skeletal (18)F-fluoride PET and probably will become the routine clinical practice for (18)F-fluoride PET. Although (18)F-labeled NaF and (99m)Tc-diphosphonate have a similar patient dosimetry, (18)F-fluoride PET offers shorter study times (typically less than 1 h), resulting in a more efficient workflow, improved patient convenience, and faster turnarounds of reports to the referring physicians. With the widespread availability of PET scanners and the improved logistics for the delivery of (18)F radiopharmaceuticals, prior limitations to the routine use of (18)F-fluoride bone imaging have largely been overcome. The favorable imaging performance and the clinical utility of (18)F-fluoride PET, compared with (99m)Tc-diphosphonate scintigraphy, support the reconsideration of (18)F-fluoride as a routine bone-imaging agent.

In children, primary neoplasms of the tracheobronchial tree and lungs are rare; most are malignant. Of the primary malignant pulmonary neoplasms arising in childhood, mucoepidermoid carcinoma accounts for approximately 10%. Due to its well-confined local growth within the airway, mucoepidermoid carcinoma commonly produces respiratory symptoms from progressive tracheal or bronchial obstruction. Mucoepidermoid tumor has minimal metastatic potential in children, and local resection alone is the current treatment of choice. Early detection, diagnosis, and surgical resection of mucoepidermoid tumor are especially important in pediatric patients since the bulk of the remaining pulmonary parenchyma can be preserved, thereby decreasing the thoracic deformity and pulmonary functional morbidity. Radiographic and CT imaging findings of bronchial mucoepidermoid carcinoma in children have been described in several case reports. However, to the best of our knowledge, imaging findings of 2-((18)F)-fluoro-2-deoxy-D: -glucose positron emission tomography ((18)F-FDG PET) of mucoepidermoid carcinoma of the bronchus in pediatric patients have not been well established. We report a mucoepidermoid carcinoma arising from the right upper lobe bronchus in a 15-year-old girl with an emphasis on the (18)F-FDG PET findings.

Mars is a compelling astrobiological target, and a human mission would provide an opportunity to collect immense amounts of scientific data. Exploration alone, however, cannot justify the increased risk. Instead, three factors drive a human mission: economics, education, and exploration. A human mission has a unique potential to inspire the next generation of young people to enter critically needed science and engineering disciplines. A mission is economically feasible, and the research and development program put in place for a human mission would propel growth in related high-technology industries. The main hurdles are human physiological responses to 1-2 years of radiation and microgravity exposure. However, enabling technologies are sufficiently mature in these areas that they can be developed within a few decade timescale. Hence, the decision of whether or not to undertake a human mission to Mars is a political decision, and thus, educational and economic benefits are the crucial factors., (c2005 Elsevier Ltd. All rights reserved.)

The Mars Exploration Rover Spirit has traversed a fairly flat, rock-strewn terrain whose surface is shaped primarily by impact events, although some of the landscape has been altered by eolian processes. Impacts ejected basaltic rocks that probably were part of locally formed lava flows from at least 10 meters depth. Some rocks have been textured and/or partially buried by windblown sediments less than 2 millimeters in diameter that concentrate within shallow, partially filled, circular impact depressions referred to as hollows. The terrain traversed during the 90-sol (martian solar day) nominal mission shows no evidence for an ancient lake in Gusev crater.

Defining the genetic basis of common forms of human essential hypertension is most informative when correlated with physiological mechanisms that underlie blood pressure regulation. A polymorphism of the alpha-adducin gene as been associated with elevated blood pressure in the rat, but previous studies of the 460Trp polymorphism of the human alpha-adducin gene have not clearly identified an association with hypertension. In this study, the frequency of the 460Trp allele was 19% and 9 of 279 subjects (3.2%) were homozygous for the 460Trp allele. The systolic blood pressure response to changes in dietary sodium was significantly greater in subjects homozygous for the 460Trp allele (25 +/- 4 mm Hg) compared with subjects heterozygous for 460Trp (12 +/- 2 mm Hg) or homozygous for the 460Gly allele (14 +/- 1 mm Hg). Intracellular erythrocyte sodium content, sodium-lithium countertransport, and renal fractional excretion of sodium were significantly decreased in subjects homozygous for the 460Trp polymorphism (P<0.05). There was a significant association between homozygosity for the 460Trp allele and low-renin hypertension. Subjects heterozygous for the 460Trp allele did not have increased salt-sensitivity or an increased frequency of low-renin hypertension. Therefore, this study demonstrates a common genetic basis for altered cellular sodium homeostasis, impaired renal sodium handling, and salt-sensitivity of systolic blood pressure in individuals homozygous for the 460Trp polymorphism of the alpha-adducin gene. Homozygosity for this alpha-adducin allele may be an important determinant for approximately 10% of individuals with low-renin hypertension.

Background: Therapy with alkylating agents, such as cyclophosphamide, can be associated with irreversible gonadal toxicity in male survivors of adult cancer. To the authors's knowledge the effect of high dose therapy with cyclophosphamide during childhood on adult testicular reproductive and endocrine function has not been established., Methods: Gonadal function was studied in 17 adult male survivors of childhood sarcomas treated with high dose pulse cyclophosphamide therapy as part of a VAC (vincristine, actinomycin, and cyclophosphamide) or Adria-VAC (doxorubicin, vincristine, actinomycin, and cyclophosphamide) chemotherapy regimen. Patients answered a questionnaire concerning sexual functioning and underwent a comprehensive physical examination, semen analysis, and hormonal evaluation., Results: Of the 17 males who underwent semen analysis, 10 (58.8%) had azoospermia, 5 (29.4%) had oligospermia, and only 2 (11.8%) were found to have a normal sperm count. All patients treated prior to the onset of puberty had an abnormal semen analysis. The 2 patients with normal sperm counts received the lowest doses of cyclophosphamide (< 7.5 g/m(2)). The baseline follicle-stimulating hormone level was elevated in only 10 of 14 patients with abnormal sperm counts (71.4%). Testosterone levels were normal in 15 of 16 patients (93.8%); however, the baseline luteinizing hormone (LH) level was elevated in 6 of 15 patients with normal testosterone levels (40%). Gonadotropin-releasing hormone-stimulated LH levels were > 3 times that of baseline in 13 of /14 patients (92.9%), suggesting some degree of Leydig cell insufficiency., Conclusions: The results of the current study show a high risk of gonadal dysfunction in men exposed to cyclophosphamide during childhood as part of a VAC/Adria-VAC chemotherapy regimen. Exposure prior to puberty was not found to be protective, and the risk of infertility appeared to increase with higher doses of therapy. To the authors' knowledge the clinical significance of impaired Leydig cell function beginning at a young age is unknown and merits further study., (Copyright 2001 American Cancer Society.)