Association of Radiology Findings with Etiology of Community Acquired Pneumonia among Children.

OBJECTIVE: To evaluate the association between consolidation on chest radiograph and typical bacterial etiology of childhood community acquired pneumonia (CAP) in the Etiology of Pneumonia in the Community study. STUDY DESIGN: Hospitalized children <18 years of age with CAP enrolled in the Etiology of Pneumonia in the Community study at 3 children's hospitals between January 2010 and June 2012 were included. Testing of blood and respiratory specimens used multiple modalities to identify typical and atypical bacterial, or viral infection. Study radiologists classified chest radiographs (consolidation, other infiltrates [interstitial and/or alveolar], pleural effusion) using modified World Health Organization pneumonia criteria. Infiltrate patterns were compared according to etiology of CAP. RESULTS: Among 2212 children, there were 1302 (59%) with consolidation with or without other infiltrates, 910 (41%) with other infiltrates, and 296 (13%) with pleural effusion. In 1795 children, at least 1 pathogen was detected. Among these patients, consolidation (74%) was the most frequently observed pattern (74% in typical bacterial CAP, 58% in atypical bacterial CAP, and 54% in viral CAP). Positive and negative predictive values of consolidation for typical bacterial CAP were 12% (95% CI 10%-15%) and 96% (95% CI 95%-97%) respectively. In a multivariable model, typical bacterial CAP was associated with pleural effusion (OR 7.3, 95% CI 4.7-11.2) and white blood cell ≥15 000/mL (OR 3.2, 95% CI 2.2-4.9), and absence of wheeze (OR 0.5, 95% CI 0.3-0.8) or viral detection (OR 0.2, 95% CI 0.1-0.4). CONCLUSIONS: Consolidation predicted typical bacterial CAP poorly, but its absence made typical bacterial CAP unlikely. Pleural effusion was the best predictor of typical bacterial infection, but too uncommon to aid etiology prediction.

The use of imaging to identify immunocompromised children requiring biopsy for invasive fungal rhinosinusitis.

BACKGROUND AND PURPOSE: Children with severe immunocompromise due to cancer therapy or hematopoietic cell transplant are at risk both for potentially lethal invasive fungal rhinosinusitis (IFRS), and for complications associated with gold-standard biopsy diagnosis. We investigated whether early imaging could reliably identify or exclude IFRS in this population, thereby reducing unnecessary biopsy. METHODS: We reviewed clinical/laboratory data and cross-sectional imaging from 31 pediatric patients evaluated for suspicion of IFRS, 19 without (age 11.8 ± 5.4 years) and 12 with proven IFRS (age 11.9 ± 4.6 years). Imaging examinations were graded for mucosal thickening (Lund score), for fungal-specific signs (FSS) of bone destruction, extra-sinus inflammation, and nasal mucosal ulceration. Loss of contrast enhancement (LoCE) was assessed separately where possible. Clinical and imaging findings were compared with parametric or nonparametric tests as appropriate. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) analysis. Positive (+LR) and negative likelihood ratios (-LR) and probabilities were calculated. RESULTS: Ten of 12 patients with IFRS and one of 19 without IFRS had at least one FSS on early imaging (83% sensitive, 95% specific, +LR = 15.83, -LR = 0.18; P < .001). Absolute neutrophil count (ANC) ≤ 200/mm3 was 100% sensitive and 58% specific for IFRS (+LR = 2.38, -LR = 0; P = .001). Facial pain was the only discriminating symptom of IFRS (P < .001). In a symptomatic child with ANC ≤ 200/m3 , the presence of at least one FSS indicated high (79%) probability of IFRS; absence of FSS suggested low (<4%) probability. CONCLUSION: In symptomatic, severely immunocompromised children, the presence or absence of fungal-specific imaging findings may effectively rule in or rule out early IFRS, potentially sparing some patients the risks associated with biopsy.

Community-acquired pneumonia requiring hospitalization among U.S. children.

BACKGROUND: Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed. METHODS: We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists. RESULTS: From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2358 children (21%) required intensive care, and 3 (<1%) died. Among 2222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval [CI], 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%). CONCLUSIONS: The burden of hospitalization for children with community-acquired pneumonia was highest among the very young, with respiratory viruses the most commonly detected causes of pneumonia. (Funded by the Influenza Division of the National Center for Immunization and Respiratory Diseases.).

Routine pre- and post-hematopoietic stem cell transplant computed tomography of the abdomen for detecting invasive fungal infection has limited value.

The diagnostic utility of obtaining chest and abdomen computed tomography (CT) to evaluate for invasive fungal infection (IFI) before and after hematopoietic stem cell transplant (HSCT) remains unclear. The study was conducted as a quality improvement project. Chest and abdomen CT of patients who underwent an allogeneic HSCT over a 13-month period were reviewed. Scans included those performed pretransplant in all patients and days 0 to 100 post-transplant in selected patients. Sixty-six patients had chest and abdomen CT scans pretransplant. Chest CT was suggestive of IFI in 9 patients (13.6%), including 3 patients with prior history of IFI. After transplant, 37 patients had an initial chest CT and 14 patients an initial abdominal CT. The first chest CT post-transplant was suggestive of IFI in 3 patients; all had an abnormal CT pretransplant. After the initial post-transplant evaluation, 15 patients had 28 additional CT scans of the chest and 12 patients 19 additional CT scans of the abdomen. An abnormal chest CT with proven evidence of IFI was seen in only 1 patient. None of the 99 abdominal CT scans performed pre- or post-transplant had evidence of IFI. There is little benefit in obtaining abdominal CT scans in HSCT patients for detecting IFI either pre- or post-transplant.

A Comprehensive Risk Assessment Method for Pediatric Patients Undergoing Research Examinations Using Ionizing Radiation: How We Answered the Institutional Review Board.

OBJECTIVE: The objectives of this study are to establish a comprehensive method for radiation dose estimates for the most common imaging examinations performed for research, for internal use of institutional review board (IRB) and radiation safety committees; to provide investigators with relative examination doses so that they may better assess the potential radiation effects and risks for research subjects; and to provide simplified language that investigators can use in consent documents. MATERIALS AND METHODS: Nineteen common radiation-based examinations used in clinical research at our institution were identified. For each modality (CT, digital radiography, dual-energy x-ray absorptiometry, PET/CT, and nuclear medicine), a comprehensive patient-specific dosimetry method was established. Effective dose was calculated according to average population calculated doses for the following age groups: 0-1, 2-8, 9-13, 14-15, and older than 15 years. RESULTS: Estimated effective dose values were tabulated and posted on our institutional IRB intranet site for use by IRB and radiation safety committee members and institutional investigators. Relative examination dose levels were compared for all ages and for all examinations. A three-tiered approach to establish consent language for radiation exposure was established for research subjects receiving an effective dose less than 3 mSv, a dose between 3 and 50 mSv, and a dose greater than 50 mSv. CONCLUSION: The method to estimate effective dose was tabulated for 19 of the most common ionizing radiation examinations at our institute. These results will act as a resource to help investigators better understand the implications of radiation exposure in research and can assist investigators in protocol development and correct categorization of radiation exposure risk.

How to Appropriately Calculate Effective Dose for CT Using Either Size-Specific Dose Estimates or Dose-Length Product.

OBJECTIVE: The purpose of this study is to show how to calculate effective dose in CT using size-specific dose estimates and to correct the current method using dose-length product (DLP). MATERIALS AND METHODS: Data were analyzed from 352 chest and 241 abdominopelvic CT images. Size-specific dose estimate was used as a surrogate for organ dose in the chest and abdominopelvic regions. Organ doses were averaged by patient weight-based populations and were used to calculate effective dose by the International Commission on Radiological Protection (ICRP) report 103 method using tissue-weighting factors (EICRP). In addition, effective dose was calculated using population-averaged CT examination DLP for the chest and abdominopelvic region using published k-coefficients (EDLP = k × DLP). RESULTS: EDLP differed from EICRP by an average of 21% (1.4 vs 1.1) in the chest and 42% (2.4 vs 3.4) in the abdominopelvic region. The differences occurred because the published kcoefficients did not account for pitch factor other than unity, were derived using a 32-cm diameter CT dose index (CTDI) phantom for CT examinations of the pediatric body, and used ICRP 60 tissue-weighting factors. Once it was corrected for pitch factor, the appropriate size of CTDI phantom, and ICRP 103 tissue-weighting factors, EDLP improved in agreement with EICRP to better than 7% (1.4 vs 1.3) and 4% (2.4 vs 2.5) for chest and abdominopelvic regions, respectively. CONCLUSION: Current use of DLP to calculate effective dose was shown to be deficient because of the outdated means by which the k-coefficients were derived. This study shows a means to calculate EICRP using patient size-specific dose estimate and how to appropriately correct EDLP.

Distinguishing Osteomyelitis From Ewing Sarcoma on Radiography and MRI.

OBJECTIVE: The purpose of this study was to determine whether clinical and imaging features can distinguish osteomyelitis from Ewing sarcoma (EWS) and to assess the accuracy of percutaneous biopsy versus open biopsy in the diagnosis of these diseases. MATERIALS AND METHODS: Three radiologists reviewed the radiographs and MRI examinations of 32 subjects with osteomyelitis and 31 subjects with EWS to determine the presence of 36 imaging parameters. Information on demographic characteristics, history, physical examination findings, laboratory findings, biopsy type, and biopsy results were recorded. Individual imaging and clinical parameters and combinations of these parameters were tested for correlation with findings from histologic analysis. The diagnostic accuracy of biopsy was also determined. RESULTS: On radiography, the presence of joint or metaphyseal involvement, a wide transition zone, a Codman triangle, a periosteal reaction, or a soft-tissue mass, when tested individually, was more likely to be noted in subjects with EWS (p ≤ 0.05) than in subjects with osteomyelitis. On MRI, permeative cortical involvement and soft-tissue mass were more likely in subjects with EWS (p ≤ 0.02), whereas a serpiginous tract was more likely to be seen in subjects with osteomyelitis (p = 0.04). African Americans were more likely to have osteomyelitis than EWS (p = 0). According to the results of multiple regression analysis, only ethnicity and soft-tissue mass remained statistically significant (p ≤ 0.01). The findings from 100% of open biopsies (18/18) and 58% of percutaneous biopsies (7/12) resulted in the diagnosis of osteomyelitis, whereas the findings from 88% of open biopsies (22/25) and 50% of percutaneous biopsies (3/6) resulted in a diagnosis of EWS. CONCLUSION: Several imaging features are significantly associated with either EWS or osteomyelitis, but many features are associated with both diseases. Other than ethnicity, no clinical feature improved diagnostic accuracy. Compared with percutaneous biopsy, open biopsy provides a higher diagnostic yield but may be inconclusive, especially for cases of EWS. Our findings underscore the need for better methods of diagnosing these disease processes.

Pediatric CT: implementation of ASIR for substantial radiation dose reduction while maintaining pre-ASIR image noise.

PURPOSE: To determine a comprehensive method for the implementation of adaptive statistical iterative reconstruction (ASIR) for maximal radiation dose reduction in pediatric computed tomography (CT) without changing the magnitude of noise in the reconstructed image or the contrast-to-noise ratio (CNR) in the patient. MATERIALS AND METHODS: The institutional review board waived the need to obtain informed consent for this HIPAA-compliant quality analysis. Chest and abdominopelvic CT images obtained before ASIR implementation (183 patient examinations; mean patient age, 8.8 years ± 6.2 [standard deviation]; range, 1 month to 27 years) were analyzed for image noise and CNR. These measurements were used in conjunction with noise models derived from anthropomorphic phantoms to establish new beam current-modulated CT parameters to implement 40% ASIR at 120 and 100 kVp without changing noise texture or magnitude. Image noise was assessed in images obtained after ASIR implementation (492 patient examinations; mean patient age, 7.6 years ± 5.4; range, 2 months to 28 years) the same way it was assessed in the pre-ASIR analysis. Dose reduction was determined by comparing size-specific dose estimates in the pre- and post-ASIR patient cohorts. Data were analyzed with paired t tests. RESULTS: With 40% ASIR implementation, the average relative dose reduction for chest CT was 39% (2.7/4.4 mGy), with a maximum reduction of 72% (5.3/18.8 mGy). The average relative dose reduction for abdominopelvic CT was 29% (4.8/6.8 mGy), with a maximum reduction of 64% (7.6/20.9 mGy). Beam current modulation was unnecessary for patients weighing 40 kg or less. The difference between 0% and 40% ASIR noise magnitude was less than 1 HU, with statistically nonsignificant increases in patient CNR at 100 kVp of 8% (15.3/14.2; P = .41) for chest CT and 13% (7.8/6.8; P = .40) for abdominopelvic CT. CONCLUSION: Radiation dose reduction at pediatric CT was achieved when 40% ASIR was implemented as a dose reduction tool only; no net change to the magnitude of noise in the reconstructed image or the patient CNR occurred.

Is routine pelvic surveillance imaging necessary in patients with Wilms tumor?

BACKGROUND: It is unclear whether routine pelvic imaging is needed in patients with Wilms tumor. Thus, the primary objective of the current study was to examine the role of routine pelvic computed tomography (CT) in a cohort of pediatric patients with Wilms tumor. METHODS: With institutional review board approval, the authors retrospectively identified 110 patients who had Wilms tumor diagnosed between January 1999 and December 2009 with surveillance imaging that continued through March 2011. The authors estimated overall survival (OS), event-free survival (EFS), and dosimetry from dose length product (DLP) conversion to the effective dose (ED) for every CT in a subgroup of 80 patients who had CT studies obtained using contemporary scanners (2002-2011). Metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters were placed within organs of anthropomorphic phantoms to directly calculate the truncal ED. ED(DLP) was correlated with ED(MOSFET) to calculate potential pelvic dose savings. RESULTS: Eighty patients underwent 605 CT examinations that contained DLP information, including 352 CT scans of the chest, abdomen, and pelvis; 123 CT scans of the chest and abdomen; 102 CT scans of the chest only; 18 CT scans of the abdomen and pelvis; 9 CT scans of the abdomen only; and 1 CT that was limited to the pelvis. The respective 5-year OS and EFS estimates were 92.8% ± 3% and 2.6% ± 4.3%. Sixteen of 110 patients (15%) developed a relapse a median of 11.3 months (range, 5.0 months to 7.3 years) after diagnosis, and 4 patients died of disease recurrence. Three patients developed pelvic relapses, all 3 of which were symptomatic. The estimated ED savings from sex-neutral CT surveillance performed at a 120-kilovolt peak without pelvic imaging was calculated as 30.5% for the average patient aged 1 year, 30.4% for the average patient aged 5 years, 39.4% for the average patient aged 10 years, and 44.9% for the average patient aged 15 years. CONCLUSIONS: Omitting pelvic CT from the routine, off-therapy follow-up of patients with Wilms tumor saved an average 30% to 45% of the ED without compromising disease detection.

Magnetic resonance imaging is the preferred method to assess treatment-related skeletal changes in children with brain tumors.

PURPOSE: To evaluate the growing skeleton for potential altered skeletalgenesis associated with antiangiogenesis therapy. PATIENTS AND METHODS: Knee radiographs and magnetic resonance imaging (MRI) were prospectively obtained on patients enrolled on two consecutive clinical trials using vandetanib, a potent oral (VEGF receptor 2) VEGFR-2 inhibitor alone or combined with dasatinib, a multiple tyrosine kinase inhibitor, in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). RESULTS: Fifty-nine patients (32 females) underwent 119 MRIs; 51 patients underwent 89 radiographs of the knees. The median age at enrollment was 6.2 years (range, 2.4-17.6 years). The dose of vandetanib ranged from 50 to 145 mg/m(2) /day. The median treatment duration was 205 days. Only two patients have not experienced disease progression after 18 and 60 months from diagnosis. MRI identified clinically significant premature physeal fusion in both knees of one patient, focal physeal thickening in one, osteonecrosis in eight patients (present at enrollment in one), and bony spicules crossing the physis in two patients (bilateral in one). MRI follow-up period averaged 5.3 months (range, 0-25.5 months; median, 3.5 months). Radiographs delineated normally fused physes in two patients but no cases of premature physeal fusion, osteonecrosis or bony spicules. CONCLUSIONS: As MRI provided greater information than radiographs, and thus would be a more sensitive test to assess skeletalgenesis in pediatric patients.

Investigation of American Association of Physicists in Medicine Report 204 size-specific dose estimates for pediatric CT implementation.

PURPOSE: To compare five methodologies the American Association of Physicists in Medicine Report 204 used to calculate size-specific dose estimates (SSDEs) for pediatric computed tomography (CT). MATERIALS AND METHODS: The institutional review board waived consent for this HIPAA-compliant retrospective study. The five SSDE methodologies were investigated for calculation variation based on volumetric CT dose index (CTDI), or CTDI(vol), of chest, abdominal, and pelvic CT. SSDE calculations were derived from a predominantly pediatric population of 186 patients retrospectively and consecutively analyzed from June through November 2011. Eighty (43%) of the 186 patients were female, and 106 (57%) were male. Mean patient age was 8.6 years ± 6.3 (standard deviation), the age range was 1 month to 28 years, and mean weight was 37.7 kg ± 33.1, with a range of 3.4-146.6 kg. SSDE conversion factors were derived from anteroposterior (AP) and lateral dimensions measured on the patient's CT radiograph. The measurements were either used independently, or as a summation, or to calculate the patient's effective diameter; additionally, SSDE was derived on the basis of the patient's age (International Commission on Radiation Units Report 74 data). SSDE conversion factors were applied to CTDI(vol) data that corrected for both 16- and 32-cm-diameter CTDI phantom measurements. SSDE data were summarized by using the patient's originally prescribed weight-based CT scanning protocols. Data were summarized by using descriptive statistics. RESULTS: SSDEs derived from individual measurements varied 2%-12%. The combination of measurements (sum or effective diameter) varied 0.9%-2%. The age approach varied by an average of 2% (in the younger population [0-13 years]), but up to 44%, with an average of 18% (in the older population [14-18 years]). No SSDE correction was required for patients of varying size who weighed 36 kg or less when CTDI(vol) was measured by using a 16-cm CTDI phantom or for patients weighing 100-140 kg when CTDI(vol) was measured by using a 32-cm phantom. CTDI(vol) measured by using a 32-cm phantom in patients weighing between 36 and 100 kg and patients weighing more than 140 kg differed from SSDE by an average of 35%. An average difference of 1% was found between male and female SSDE-corrected values when the two sexes were compared within the same CT weight scanning categories. CONCLUSION: The combination of AP and lateral measurements should be used to determine SSDE correction factors when possible. For pediatric patients, CTDI(vol) calculated with a 32-cm phantom requires SSDE conversion to more accurately estimate patient dose; CTDI(vol) calculated with a 16-cm phantom for pediatric patients weighing 36 kg or less does not require SSDE conversion.

Utility of Induced Sputum in Assessing Bacterial Etiology for Community-Acquired Pneumonia in Hospitalized Children.

BACKGROUND: Diagnostic testing for bacterial etiology of community-acquired pneumonia (CAP) is insensitive. Induced sputum (IS) is an attractive option for the evaluation of the lower respiratory tract. METHODS: Children aged 0-18 years with CAP were enrolled in the Etiology of Pneumonia in the Community (EPIC) study between 2010 and 2012. Blood and respiratory specimens were assessed by culture and polymerase chain reaction (PCR). The radiographic CAP was determined by a study radiologist. Sputum was induced with hypertonic saline. IS specimen was high quality (HQ) if Gram stain showed >25 white blood and <10 epithelial cells per low-powered field; all others were low quality (LQ). We compared IS pathogen prevalence between HQ and LQ IS, and by radiographic pneumonia. Pathogen concordance with EPIC etiology was assessed. Length of stay (LOS) was compared by receipt of IS pathogen-concordant antibiotics. RESULTS: Out of 977 children, 916 (94%) children enrolled in Memphis, Tennessee, produced IS; 794 (87%) had radiographic CAP and 174 (19%) were HQ. HQ IS yielded pathogenic bacteria more often than LQ (64% vs 44%; P < .01); however, pathogens were isolated at similar rates in HQ IS in patients with and without radiographic CAP (64% vs. 63%; P = .6). Pathogens from study specimens matched an IS pathogen in only 9/42 (21%) patients with radiographic CAP. Median LOS was similar among patients with radiographic CAP regardless of receipt of IS pathogen-concordant antibiotics (3.1 days), non-pathogen-concordant antibiotics (2.7 days), or no antibiotics (3.2 days; P = .5). CONCLUSIONS: Bacterial pathogens were isolated from most IS cultures regardless of radiographic CAP and quality of IS. IS cultures infrequently corresponded with sterile site cultures. Isolation of pathogens from pediatric IS reflects oropharyngeal carriage and is insufficient to determine bacterial etiology of CAP.

PET/CT characterization of fibroosseous defects in children: 18F-FDG uptake can mimic metastatic disease.

OBJECTIVE: The purpose of this study was to characterize the anatomic appearance and metabolic activity of nonossifying fibromas, fibrous cortical defects, and cortical desmoids on PET/CT images. CONCLUSION: Over a 14-month period, we identified eight nonossifying fibromas, four fibrous cortical defects, and two cortical desmoids in 330 children who underwent PET/CT for the evaluation of a known or suspected malignancy. CT, conventional radiography, MRI, or clinical follow-up was used to confirm the diagnoses of these fibroosseous lesions. Eleven of the 14 children underwent multiple PET/CT examinations; thus, 34 studies were included. The lesions showed variable metabolic activity as indicated by 18F-FDG uptake: 19 PET/CT examinations showed lesions with mild 18F-FDG uptake, eight showed moderate 18F-FDG uptake, and seven showed intense uptake. When PET reveals metabolically active osseous abnormalities in children who are at risk for bone metastases, benign fibroosseous lesions should be considered in the differential diagnosis before additional diagnostic procedures are undertaken. Benign fibroosseous lesions may be metabolically active and thus mimic metastatic osseous disease in children with underlying malignancies. Correlative CT or other anatomic imaging can confirm the benign nature of these lesions.

Tissue segmentation of computed tomography images using a Random Forest algorithm: a feasibility study.

There is a need for robust, fully automated whole body organ segmentation for diagnostic CT. This study investigates and optimizes a Random Forest algorithm for automated organ segmentation; explores the limitations of a Random Forest algorithm applied to the CT environment; and demonstrates segmentation accuracy in a feasibility study of pediatric and adult patients. To the best of our knowledge, this is the first study to investigate a trainable Weka segmentation (TWS) implementation using Random Forest machine-learning as a means to develop a fully automated tissue segmentation tool developed specifically for pediatric and adult examinations in a diagnostic CT environment. Current innovation in computed tomography (CT) is focused on radiomics, patient-specific radiation dose calculation, and image quality improvement using iterative reconstruction, all of which require specific knowledge of tissue and organ systems within a CT image. The purpose of this study was to develop a fully automated Random Forest classifier algorithm for segmentation of neck-chest-abdomen-pelvis CT examinations based on pediatric and adult CT protocols. Seven materials were classified: background, lung/internal air or gas, fat, muscle, solid organ parenchyma, blood/contrast enhanced fluid, and bone tissue using Matlab and the TWS plugin of FIJI. The following classifier feature filters of TWS were investigated: minimum, maximum, mean, and variance evaluated over a voxel radius of 2 (n) , (n from 0 to 4), along with noise reduction and edge preserving filters: Gaussian, bilateral, Kuwahara, and anisotropic diffusion. The Random Forest algorithm used 200 trees with 2 features randomly selected per node. The optimized auto-segmentation algorithm resulted in 16 image features including features derived from maximum, mean, variance Gaussian and Kuwahara filters. Dice similarity coefficient (DSC) calculations between manually segmented and Random Forest algorithm segmented images from 21 patient image sections, were analyzed. The automated algorithm produced segmentation of seven material classes with a median DSC of 0.86 ± 0.03 for pediatric patient protocols, and 0.85 ± 0.04 for adult patient protocols. Additionally, 100 randomly selected patient examinations were segmented and analyzed, and a mean sensitivity of 0.91 (range: 0.82-0.98), specificity of 0.89 (range: 0.70-0.98), and accuracy of 0.90 (range: 0.76-0.98) were demonstrated. In this study, we demonstrate that this fully automated segmentation tool was able to produce fast and accurate segmentation of the neck and trunk of the body over a wide range of patient habitus and scan parameters.

Size-specific dose estimate (SSDE) provides a simple method to calculate organ dose for pediatric CT examinations.

PURPOSE: To investigate the correlation of size-specific dose estimate (SSDE) with absorbed organ dose, and to develop a simple methodology for estimating patient organ dose in a pediatric population (5-55 kg). METHODS: Four physical anthropomorphic phantoms representing a range of pediatric body habitus were scanned with metal oxide semiconductor field effect transistor (MOSFET) dosimeters placed at 23 organ locations to determine absolute organ dose. Phantom absolute organ dose was divided by phantom SSDE to determine correlation between organ dose and SSDE. Organ dose correlation factors (CF(organ)(SSDE)) were then multiplied by patient-specific SSDE to estimate patient organ dose. The [CF(organ)(SSDE)) were used to retrospectively estimate individual organ doses from 352 chest and 241 abdominopelvic pediatric CT examinations, where mean patient weight was 22 kg ± 15 (range 5-55 kg), and mean patient age was 6 yrs ± 5 (range 4 months to 23 yrs). Patient organ dose estimates were compared to published pediatric Monte Carlo study results. RESULTS: Phantom effective diameters were matched with patient population effective diameters to within 4 cm; thus, showing appropriate scalability of the phantoms across the entire pediatric population in this study. Individual CF(organ)(SSDE) were determined for a total of 23 organs in the chest and abdominopelvic region across nine weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7-1.4) and abdominopelvic region (average 0.9; range 0.7-1.3) was near unity. For organ/tissue that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1-0.4) for both the chest and abdominopelvic regions, respectively. A means to estimate patient organ dose was demonstrated. Calculated patient organ dose, using patient SSDE and CF(organ)(SSDE), was compared to previously published pediatric patient doses that accounted for patient size in their dose calculation, and was found to agree in the chest to better than an average of 5% (27.6/26.2) and in the abdominopelvic region to better than 2% (73.4/75.0). CONCLUSIONS: For organs fully covered within the scan volume, the average correlation of SSDE and organ absolute dose was found to be better than ± 10%. In addition, this study provides a complete list of organ dose correlation factors (CF(organ)(SSDE)) for the chest and abdominopelvic regions, and describes a simple methodology to estimate individual pediatric patient organ dose based on patient SSDE.

Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma.

PURPOSE: The addition of immunotherapy, including a combination of anti-GD2 monoclonal antibody (mAb), ch14.18, and cytokines, improves outcome for patients with high-risk neuroblastoma. However, this therapy is limited by ch14.18-related toxicities that may be partially mediated by complement activation. We report the results of a phase I trial to determine the maximum-tolerated dose (MTD), safety profile, and pharmacokinetics of hu14.18K322A, a humanized anti-GD2 mAb with a single point mutation (K322A) that reduces complement-dependent lysis. PATIENTS AND METHODS: Eligible patients with refractory or recurrent neuroblastoma received escalating doses of hu14.18K322A ranging from 2 to 70 mg/m(2) per day for 4 consecutive days every 28 days (one course). RESULTS: Thirty-eight patients (23 males; median age, 7.2 years) received a median of two courses (range, one to 15). Dose-limiting grade 3 or 4 toxicities occurred in four of 36 evaluable patients and were characterized by cough, asthenia, sensory neuropathy, anorexia, serum sickness, and hypertensive encephalopathy. The most common non-dose-limiting grade 3 or 4 toxicities during course one were pain (68%) and fever (21%). Six of 31 patients evaluable for response by iodine-123 metaiodobenzylguanidine score had objective responses (four complete responses; two partial responses). The first-course pharmacokinetics of hu14.18K322A were best described by a two-compartment linear model. Median hu14.18K322A α (initial phase) and ß (terminal phase) half-lives were 1.74 and 21.1 days, respectively. CONCLUSION: The MTD, and recommended phase II dose, of hu14.18K322A is 60 mg/m(2) per day for 4 days. Adverse effects, predominately pain, were manageable and improved with subsequent courses.

Clinical and CT features of benign pneumatosis intestinalis in pediatric hematopoietic stem cell transplant and oncology patients.

BACKGROUND: Pneumatosis intestinalis in children is associated with a wide variety of underlying conditions and often has a benign course. The CT features of this condition have not been systematically investigated. OBJECTIVE: Defining benign pneumatosis intestinalis as pneumatosis intestinalis that resolved with medical management alone, we sought to: (1) determine whether the incidence of benign pneumatosis intestinalis had increased at our pediatric cancer hospital; (2) characterize CT features of benign pneumatosis intestinalis; and (3) determine the relationship between imaging features and clinical course of benign pneumatosis intestinalis in this cohort. MATERIALS AND METHODS: Radiology reports from November 1994 to December 2006 were searched for "pneumatosis intestinalis," "free intraperitoneal air," and "portal venous air or gas." Corresponding imaging was reviewed by two radiologists who confirmed pneumatosis intestinalis and recorded the presence of extraluminal free air, degree of intramural gaseous distension, number of involved bowel segments, and time to pneumatosis resolution. RESULTS: The search revealed 12 boys and 4 girls with pneumatosis intestinalis; 11 were hematopoietic stem cell transplant recipients. The annual incidences of benign pneumatosis have not changed at our institution. Increases in intramural distension marginally correlated with the number of bowel segments involved (P=0.08). Three patients had free air and longer times to resolution of pneumatosis (P=0.03). CONCLUSION: Male children may be at increased risk of benign pneumatosis intestinalis. The incidence of benign pneumatosis at our institution is proportional to the number of hematopoietic stem cell transplants. The degree of intramural distension may correlate with the number of bowel segments involved. Patients with free air have a longer time to resolution of benign pneumatosis.

Distinguishing benign from malignant pulmonary nodules with helical chest CT in children with malignant solid tumors.

PURPOSE: To retrospectively assess whether computed tomographic (CT) findings can indicate the benign or malignant nature of pulmonary nodules in pediatric patients with malignant solid primary tumors. MATERIALS AND METHODS: With institutional review board approval, waived parental and patient consent, and HIPAA compliance, the authors determined the incidence of malignancy among 81 pulmonary nodules that were sampled at biopsy within 3 weeks after chest CT (January 1999 to September 2003) in 41 young patients with malignant solid tumors. Three radiologists independently and retrospectively reviewed these scans and the available previously obtained scans, classifying nodules as benign, malignant, or indeterminate on the basis of their number, unilateral versus bilateral distribution, size, margins (indistinct vs distinct), calcification, growth, and associated adenopathy. These classifications were compared with nodule histologic type, and interreviewer agreement was assessed. RESULTS: The median patient age was 14.8 years (mean, 13.7 years; range, 5-21 years). Twenty-four of the 41 patients (58%) had at least one biopsy-proved malignant nodule. Four (10%) patients had both benign and malignant nodules; 17 (42%) had only benign nodules. Reviewer 1 classified 65% (39 of 60) of nodules correctly; reviewer 2, 57% (37 of 65); and reviewer 3, 67% (43 of 64). Interreviewer agreement was slight to moderate (kappa /= .32). CONCLUSION: The frequency of benign nodules and the inconsistency of predictions based on CT features suggest the need for better predictors of pulmonary nodules being malignant or benign, so as to reduce unnecessary thoracotomy in pediatric patients with solid malignancy. .