Frederick D. Grant

Skeletal PET with 18F-Fluoride: Applying New Technology to an Old Tracer

Although 18F-labeled NaF was the first widely used agent for skeletal scintigraphy, it quickly fell into disuse after the introduction of 99mTc-labeled bone-imaging agents. Recent comparative studies have demonstrated that 18F-fluoride PET is more accurate than 99mTc-diphosphonate SPECT for identifying both malignant and benign lesions of the skeleton. Combining 18F-fluoride PET with other imaging, such as CT, can improve the specificity and overall accuracy of skeletal 18F-fluoride PET and probably will become the routine clinical practice for 18F-fluoride PET. Although 18F-labeled NaF and 99mTc-diphosphonate have a similar patient dosimetry, 18F-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 18F radiopharmaceuticals, prior limitations to the routine use of 18F-fluoride bone imaging have largely been overcome. The favorable imaging performance and the clinical utility of 18F-fluoride PET, compared with 99mTc-diphosphonate scintigraphy, support the reconsideration of 18F-fluoride as a routine bone-imaging agent.

c-fos Expression in Vasopressin and Oxytocin Neurons Reveals Functional Heterogeneity within Magnocellular Neurons

The c-fos protein is rapidly induced in hypothalamic magnocellular nuclei following hemorrhage. We used specific antibodies directed against c-fos and either vasopressin (AVP) or oxytocin (OT) neurophysin to investigate c-fos activation in individual AVP and OT neurons. AVP and OT neurons expressed c-fos in response to hypovolemic stimuli. Following a protocol of incremental hemorrhage, AVP and OT neurons expressed c-fos with a graded response that correlated with stimulus intensity. As the volume of hemorrhage increased, there was an increase in the number of cells expressing c-fos as well as in the amount of c-fos immunoreactivity per cell. These increases correlated with the amount of hormone released into the peripheral blood. In addition, a differential pattern of activation for AVP neurons occurred in response to hemorrhagic stimuli. AVP neurons in the supraoptic nucleus (SON) had a lower threshold for response than those in the paraventricular nucleus (PVN). For OT, activation required a greater blood loss than AVP and c-fos expression encompassed both SON and PVN neurons. We conclude that c-fos expression is proportional to stimulus intensity and reveals functional heterogeneity among magnocellular neurons.

Lower-Extremity Lymphedema and Elevated Body-Mass Index

This letter reports lymphedema in 5 of 15 morbidly obese patients and suggests that morbid obesity may constitute a novel cause of lymphedema.

Skeletal Trauma in Child Abuse: Detection with 18F-NaF PET

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.

Deferasirox pharmacokinetics in patients with adequate versus inadequate response

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.

Nuclear Medicine in the First Year of Life

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.

Management of Primary and Secondary Lymphedema: Analysis of 225 Referrals to a Center.

BackgroundLymphedema 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. MethodsPatients 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. ResultsTwo 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). ConclusionsPatients 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.

Mucoepidermoid carcinoma of bronchus in a pediatric patient: 18 F-FDG PET findings

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-(18F)-fluoro-2-deoxy-d-glucose positron emission tomography (18F-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 18F-FDG PET findings.

Costs and Consequences of Universal Sibling Screening for Vesicoureteral Reflux: Decision Analysis

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

The Value of SPECT in the Detection of Stress Injury to the Pars Interarticularis in Patients with Low Back Pain

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