Randolph K. Otto

Pediatric CT: Strategies to Lower Radiation Dose

OBJECTIVEnThe introduction of MDCT has increased the utilization of CT in pediatric radiology along with concerns for radiation sequelae. This article reviews general principles of lowering radiation dose, the basic physics that impact radiation dose, and specific CT integrated dose-reduction tools focused on the pediatric population.nnnCONCLUSIONnThe goal of this article is to provide a comprehensive review of the recent literature regarding CT dose reduction methods, their limitations, and an outlook on future developments with a focus on the pediatric population. The discussion will initially focus on general considerations that lead to radiation dose reduction, followed by specific technical features that influence the radiation dose.

Longitudinal features of stir bright signal in FSHD1

Introduction: Magnetic resonance imaging of muscle shows short tau‐inversion recovery (STIR) brightness in autosomal dominant facioscapulohumeral muscular dystrophy (FSHD1) suggestive of active inflammation/injury. We measured the longitudinal stability/progression of this potential disease biomarker. Methods: Nine subjects underwent calf MRI imaging over 2 years. Two radiologists evaluated qualitative muscle changes. Results: In 3/9 subjects, calf muscles demonstrated moderate/severe STIR hyperintensity at Time 1 that had progressed to fatty replacement 2 years later (Time 2). In the remaining subjects, moderate/severe muscle STIR abnormalities, when present, were consistent between exams. Mild STIR+ elevations had roughly similar patterns between exams. Conclusions: Moderate/severe STIR hyperintensities often foreshadow fatty replacement over a 2‐year interval. Whether longer time courses are required to observe muscle degeneration and fatty replacement in some subjects remains to be explored. Muscle Nerve 49: 257–260, 2014

Estimation of fish and ω-3 fatty acid intake in pediatric nonalcoholic fatty liver disease.

Aims: Fish and &ohgr;-3 fatty acids are reported to be beneficial in pediatric nonalcoholic fatty liver disease (NAFLD), but no studies have assessed their relation to histological severity. The objectives of this study were to evaluate the dietary intake of fish and &ohgr;-3 fatty acids in children with biopsy-proven NAFLD, and examine their association with serological and histological indicators of disease. Methods: This was a cross-sectional analysis of 223 children (6–18 years) who participated in the Treatment of Nonalcoholic Fatty Liver Disease in Children trial or the NAFLD Database study conducted by the Nonalcoholic Steatohepatitis Clinical Research Network. The distribution of fish and &ohgr;-3 fatty acid intake was determined from responses to the Block Brief 2000 Food Frequency Questionnaire, and analyzed for associations with serum alanine aminotransferase, histological features of fatty liver disease, and diagnosis of steatohepatitis after adjusting for demographic, anthropometric, and dietary variables. Results: The minority of subjects consumed the recommended 8 ounces of fish per week (22/223 [10%]) and 200 mg of long-chain &ohgr;-3 fatty acids per day (12/223 [5%]). Lack of fish and long-chain &ohgr;-3 fatty acid intake was associated with greater portal (Pu200a=u200a0.03 and Pu200a=u200a0.10, respectively) and lobular inflammation (Pu200a=u200a0.09 and Pu200a=u200a0.004, respectively) after controlling for potential confounders. Conclusions: Fish and &ohgr;-3 fatty acid intake was insufficient in children with NAFLD, which may increase susceptibility to hepatic inflammation. Patients with pediatric NAFLD should be encouraged to consume the recommended amount of fish per week.

Growth Hormone–Releasing Hormone Effects on Brain γ-Aminobutyric Acid Levels in Mild Cognitive Impairment and Healthy Aging

IMPORTANCEnGrowth hormone-releasing hormone (GHRH) has been previously shown to have cognition-enhancing effects. The role of neurotransmitter changes, measured by proton magnetic resonance spectroscopy, may inform the mechanisms for this response.nnnOBJECTIVEnTo examine the neurochemical effects of GHRH in a subset of participants from the parent trial.nnnDESIGNnRandomized, double-blind, placebo-controlled substudy of a larger trial.nnnSETTINGnClinical research unit at the University of Washington School of Medicine.nnnPARTICIPANTSnThirty adults (17 with mild cognitive impairment [MCI]), ranging in age from 55 to 87 years, were enrolled and successfully completed the study.nnnINTERVENTIONSnParticipants self-administered daily subcutaneous injections of tesamorelin (Theratechnologies Inc), a stabilized analogue of human GHRH (1 mg/d), or placebo 30 minutes before bedtime for 20 weeks. At baseline and weeks 10 and 20, participants underwent brain magnetic resonance imaging and spectroscopy protocols and cognitive testing and provided blood samples after fasting. Participants also underwent glucose tolerance tests before and after intervention.nnnMAIN OUTCOMES AND MEASURESnBrain levels of glutamate, inhibitory transmitters γ-aminobutyric acid (GABA) and N-acetylaspartylglutamate (NAAG), and myo-inositol (MI), an osmolyte linked to Alzheimer disease in humans, were measured in three 2u2009×u20092u2009×u20092-cm3 left-sided brain regions (dorsolateral frontal, posterior cingulate, and posterior parietal). Glutamate, GABA, and MI levels were expressed as ratios to creatine plus phosphocreatine, and NAAG was expressed as a ratio to N-acetylaspartate.nnnRESULTSnAfter 20 weeks of GHRH administration, GABA levels were increased in all brain regions (Pu2009<u2009.04), NAAG levels were increased (Pu2009=u2009.03) in the dorsolateral frontal cortex, and MI levels were decreased in the posterior cingulate (Pu2009=u2009.002). These effects were similar in adults with MCI and older adults with normal cognitive function. No changes in the brain levels of glutamate were observed. In the posterior cingulate, treatment-related changes in serum insulin-like growth factor 1 were positively correlated with changes in GABA (ru2009=u20090.47; Pu2009=u2009.001) and tended to be negatively correlated with MI (ru2009=u2009-0.34; Pu2009=u2009.06). Consistent with the results of the parent trial, a favorable treatment effect on cognition was observed in substudy participants (Pu2009=u2009.03). No significant associations were observed between treatment-related changes in neurochemical and cognitive outcomes. Glucose homeostasis in the periphery was not reliably affected by GHRH administration and did not account for treatment neurochemical effects.nnnCONCLUSIONSnTwenty weeks of GHRH administration increased GABA levels in all 3 brain regions, increased NAAG levels in the frontal cortex, and decreased MI levels in the posterior cingulate. To our knowledge, this is the first evidence that 20 weeks of somatotropic supplementation modulates inhibitory neurotransmitter and brain metabolite levels in a clinical trial, and it provides preliminary support for one possible mechanism to explain favorable GHRH effects on cognition in adults with MCI and in healthy older adults. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00257712.

A simulation-based comparison of two methods for determining relaxation rates from relaxometry images

When assessing liver iron content using relaxometry, an average relaxation rate (R1, R2 or R2*) is usually determined from a region of interest or the entire liver. This is commonly performed by fitting the signal decay in individual voxels to an appropriate relaxation function. The voxel-level parameters resulting from the fits are combined to determine the average relaxation rate, and an empirically derived calibration curve is used to convert this single value to iron content. The goal of this study was to compare the precision and accuracy of this voxel-wise fitting to an alternative method that relies on first averaging the signals from all voxels within the region of interest and then determining the relaxation rate from a single fit. Systematic differences were observed when both methods were applied to clinical images. Mathematical simulations were employed to determine which method provided more robust estimates of the true relaxation rate. The mathematical simulations were then expanded to include a range of conditions expected in typical relaxometry images. The results show that voxel-wise fitting skews the relaxation rate estimates and increases variance, particularly when the true relaxation rate is moderate to fast, as it would be in liver with high iron content. The potential impact of these results on clinical decisions is discussed.

Neuromuscular Hip Dysplasia in Charcot-Marie-Tooth Disease Type 1A.

Charcot–Marie–Tooth disease (CMT) is one of the most common inherited neurological disorders, affecting 36 in 100 000 people. CMT type 1A (hereditary motor and sensory neuropathy) is the most frequent form of this disease, affecting 60 to 80% of the CMT population, but its diagnosis may be delayed because of inconsistent clinical signs and symptoms and a considerable variability in age at onset. Here, we report on four children (aged 10–17y) who presented with neuromuscular hip dysplasia and other orthopedic abnormalities but were only later diagnosed with CMT 1A. Hip dysplasia may be the initial clinical sign in CMT, so children with late‐manifesting hip disease (i.e. age >8y) should be examined for signs of peripheral neuropathy, particularly when presenting with a ‘waddling’ or broad‐based gait.

Pediatric ovarian torsion: a pictorial review.

Imaging is crucial in expediting the diagnosis and guiding definitive therapy in children with ovarian torsion. This article reviews the multimodality spectrum of imaging findings in pediatric ovarian torsion, focusing primarily on US appearances. We describe predisposing conditions that can lead to torsion, the pathological basis of the radiologic findings in ovarian torsion, and the common diagnostic pitfalls.

Callosal alterations in pyridoxine-dependent epilepsy

While there have been isolated reports of callosal morphology differences in pyridoxine‐dependent epilepsy (PDE), a rare autosomal disorder caused by ALDH7A1 gene mutations, no study has systematically evaluated callosal features in a large sample of patients. This study sought to overcome this knowledge gap.

Limitations of using logarithmic transformation and linear fitting to estimate relaxation rates in iron-loaded liver

BackgroundMRI is being increasingly used to evaluate tissue relaxation in the setting of iron overload. Diagnostic accuracy is strongly dependent upon the acquisition and analysis methods employed. Typically, a multi-echo train of relaxation data is acquired, the resulting curve is fit using a non-linear (exponential) function, and the derived relaxation time is converted to iron concentration by a calibration formula derived from paired MRI-biopsy samples. A theoretically valid processing alternative is to fit a straight line to the relaxation data after logarithmic transformation (log-linear). This log-linear method is more computationally efficient, allowing a full relaxation map to be generated in near real time. This method is present on all scanner platforms and has been published for use in assessing iron concentration. These factors imply methodological validity.ObjectiveTo use in vivo and simulation data to show that log-linear fitting can generate highly erroneous relaxation results in iron-loaded tissues.Materials and methodsAfter IRB approval, exponential and linear fitting were compared in a cohort of 20 patients being evaluated for hepatic iron overload. Simulation analyses were performed to characterize the main factors impacting derived results.ResultsIn human subjects, log-linear analyses demonstrated gross deviation from exponential results at a moderate relaxation shortening (T2* ~5xa0ms). Simulation analyses demonstrated that the discrepancy was caused by noise effects and additional signal components violating mono-exponential function shape.ConclusionLog-linear processing results in increasingly erroneous estimation of T2* with iron-loading. Therefore, this method should not be employed for measurement of relaxation behavior in clinical samples.

Nasoseptal Flap Reconstruction of Pediatric Sellar Defects A Radiographic Feasibility Study and Case Series

Objectives In this study, we used computed tomography measurements to investigate the feasibility of nasoseptal flap reconstruction of sellar defects in children, and we reviewed our institutional experience with the procedure. Study Design Cross-sectional and case series. Setting Pediatric tertiary care facility. Methods We obtained 10 normal maxillofacial scans for each year of age from birth to 18. Computer-assisted nasal and skull-base measurements were performed. Patients with incomplete pneumatization were excluded from analysis. Reconstruction was presumed feasible if the ratio of nasoseptal flap length to associated sellar defect length was greater than 1. Chart review identified surgical patients. Results Of 190 scans, 125 had complete pneumatization. Of these, 120 (96%) displayed a ratio of nasoseptal flap length to sellar defect length greater than 1, suggesting that reconstruction would be feasible. Mean ratio of flap length to defect length for all subjects was 1.47 (SD 0.33; 95% CI, 1.41-1.53). Only 5 of 125 patients (4%) had a ratio less than 1; the median age for these patients was 15 years, which is older than the median age of 12 years for subjects with a ratio greater than 1 (P = .02). An inverse relationship was identified between age and ratio of flap length to defect length (r = −0.49, P < .001). Case series identified 6 children, ages 5 to 17; flap length was never described as a limitation. Conclusions Nasoseptal flap length is not a limiting factor for reconstruction of pediatric sellar defects. When compared with older patients, younger patients tend to have greater nasoseptal flap length relative to sellar defect length.