Development and autoregulation of kidney function in children: a retrospective study using 99mTc-MAG3 renography.

BACKGROUND: Both the development of kidney function in healthy children and autoregulation ability of kidney function in patients with asymmetric kidneys are important in clinical diagnosis and treatment of kidney-related diseases, but there are however only limited studies. This study aimed to investigate development of kidney function in normal children with healthy symmetric kidneys and autoregulation of the healthy kidney compensating the functional loss of a diseased one in children with asymmetric kidneys. METHODS: Two hundred thirty-seven children (156 male, 81 female) from 0 to 20y (average 4.6y ± 5.1) undergoing 99mTc-MAG3 renography were included, comprising 134 with healthy symmetrically functioning kidneys and 103 with asymmetric kidneys. Clearance was calculated from kidney uptakes at 1-2 min. A developmental model between MAG3 clearance (CL) and patient age in normal group was identified (CL = 84.39Age0.395 ml/min, r = 0.957, p < 0.001). The clearance autoregulation rate in abnormal group with asymmetric kidneys was defined as the ratio of the measured MAG3 clearance and the normal value predicted from the renal developmental model of normal group. RESULTS: No significant difference of MAG3 clearance (p = 0.723) was found between independent abnormal group and normal group. The autoregulation rate of kidney clearance in abnormal group was 94.2% on average, and no significant differences were found between two age groups (p = 0.49), male and female (p = 0.39), and left kidney and right kidney (p = 0.92) but two different grades of asymmetric kidneys (p = 0.02). CONCLUSIONS: The healthy kidney of two asymmetric kidneys can automatically regulate total kidney function up to 94% of two symmetric kidneys in normal children.

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

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

Estimation of Split Renal Function With 99mTc-DMSA SPECT: Comparison Between 3D Volumetric Assessment and 2D Coronal Projection Imaging.

OBJECTIVE: Split renal function (SRF) can be estimated with 99mTc-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 99mTc-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, 99mTc-DMSA SPECT renal scintigraphy 2D coronal projection images perform as well as and are simpler to analyze than 3D images.

The ionic charge of copper-64 complexes conjugated to an engineered antibody affects biodistribution.

The development of biomolecules as imaging probes requires radiolabeling methods that do not significantly influence their biodistribution. Sarcophagine (Sar) chelators form extremely stable complexes with copper and are therefore a promising option for labeling proteins with (64)Cu. However, initial studies using the first-generation sarcophagine bifunctional chelator SarAr to label the engineered antibody fragment ch14.18-ΔCH2 (MW 120 kDa) with (64)Cu showed high tracer retention in the kidneys, presumably because the high local positive charge on the Cu(II)-SarAr moiety resulted in increased binding of the labeled protein to the negatively charged basal cells of the glomerulus. To test this hypothesis, ch14.18-ΔCH2 was conjugated with a series of Sar derivatives of decreasing positive charge and three commonly used macrocyclic polyaza polycarboxylate (PAC) bifunctional chelators (BFC). The immunoconjugates were labeled with (64)Cu and injected into mice, and PET/CT images were obtained at 24 and 48 h postinjection (p.i.). At 48 h p.i., ex vivo biodistribution was assessed. In addition, to demonstrate the potential of metastasis detection using (64)Cu-labeled ch14.18-ΔCH2, a preclinical imaging study of intrahepatic neuroblastoma tumors was performed. Reducing the positive charge on the Sar chelators decreased kidney uptake of Cu-labeled ch14.18-ΔCH2 by more than 6-fold, from >45 to <6% ID/g, whereas the uptake in most other tissues, including liver, was relatively unchanged. However, despite this dramatic decrease, the renal uptake of the PAC BFCs was generally lower than that of the Sar derivatives, as was the liver uptake. Uptake of (64)Cu-labeled ch14.18-ΔCH2 in neuroblastoma hepatic metastases was detected using PET.

RYR1-related myopathies: a wide spectrum of phenotypes throughout life.

BACKGROUND AND PURPOSE: Although several recent studies have implicated RYR1 mutations as a common cause of various myopathies and the malignant hyperthermia susceptibility (MHS) trait, many of these studies have been limited to certain age groups, confined geographical regions or specific conditions. The aim of the present study was to investigate the full spectrum of RYR1-related disorders throughout life and to use this knowledge to increase vigilance concerning malignant hyperthermia. METHODS: A retrospective cohort study was performed on the clinical, genetic and histopathological features of all paediatric and adult patients in whom an RYR1 mutation was detected in a national referral centre for both malignant hyperthermia and inherited myopathies (2008-2012). RESULTS: The cohort of 77 non-related patients (detection rate 28%) included both congenital myopathies with permanent weakness and 'induced' myopathies such as MHS and non-anaesthesia-related episodes of rhabdomyolysis or hyperCKemia, manifested throughout life and triggered by various stimuli. Sixty-one different mutations were detected, of which 24 were novel. Some mutations are present in both dominant (MHS) and recessive modes (congenital myopathy) of inheritance, even within families. Histopathological features included an equally wide spectrum, ranging from only subtle abnormalities to prominent cores. CONCLUSIONS: This broad range of RYR1-related disorders often presents to the general paediatric and adult neurologist. Its recognition is essential for genetic counselling and improving patients' safety during anaesthesia. Future research should focus on in vitro testing by the in vitro contracture test and functional characterization of the large number of RYR1 variants whose precise effects currently remain uncertain.

Radiation doses for pediatric nuclear medicine studies: comparing the North American consensus guidelines and the pediatric dosage card of the European Association of Nuclear Medicine.

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.

Paediatric radiopharmaceutical administration: harmonization of the 2007 EANM paediatric dosage card (version 1.5.2008) and the 2010 North American consensus guidelines.

In 2008 the EANM published their paediatric dosage card. In 2011 the North American consensus guidelines recommended a set of administered activities for paediatric nuclear medicine. During the EANM congress in 2012 a working group of the EANM and the SNMMI met to study the possibility of harmonizing these guidelines. The purpose of this work was to identify differences between these guidelines and suggest changes in both guidelines to achieve a level of harmonization. In addition, the new version of the EANM paediatric dosage card (version 01.02.2014) is provided.

Beyond current guidelines: reduction in minimum administered radiopharmaceutical activity with preserved diagnostic image quality in pediatric hepatobiliary scintigraphy.

PURPOSE: To determine if the minimum administered radiopharmaceutical activity for hepatobiliary scintigraphy can be reduced while preserving diagnostic image quality using enhanced planar processing (EPP). METHODS: A total of 40 infants between 10 and 270 days old (body mass 2.2 - 6.5 kg) had hepatobiliary scintigraphy during the period 2004 - 2010 following the intravenous administration of either (99m)Tc-mebrofenin (18 patients) or (99m)Tc-disofenin (22 patients). Due to the small size of these patients, they all received the minimum administered activity of 18.5 MBq consistent with the North American Consensus Guidelines. Six nuclear medicine physicians subjectively graded the acceptability of the image quality for clinical interpretation using a four-point scale (not acceptable, fair, good, excellent). Each physician independently graded seven image sets including the original study (full activity) and simulated reduced activity studies using binomial subsampling (50% of full activity, 25% of full activity and activity reduced by weight), with and without EPP. RESULTS: For full-activity studies, 98% were deemed acceptable by the six physicians for clinical interpretation. The percentages of acceptable 50% reduced activity studies with and without EPP were not significantly different from the percentage of acceptable full-activity studies (P = 0.193 and P = 0.998, respectively). The percentage of acceptable 25% reduced activity studies without EPP was significantly different from the percentage of acceptable full-activity studies (P < 0.001); however, this difference vanished when EPP was applied (P = 0.482). The activity reduced by weight ranged from 1.85 to 4.81 MBq (10% to 26% of full dose) and the percentages of acceptable studies with and without EPP were significantly different from the percentage of acceptable full-activity studies (P < 0.001 and P = 0.02, respectively). CONCLUSION: Clinically interpretable hepatobiliary scintigraphy images can be obtained in infants when the minimum administered activity is substantially reduced. Without EPP, clinically acceptable images may be produced with a reduction of 50%, and with EPP, a reduction of 75% or more may be possible.

Detection of pars injury by SPECT in patients younger than age 10 with low back pain.

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.

Radiation Dose to Pediatric Patients From Radiopharmaceuticals.

Nuclear medicine provides methods and techniques in that has benefited pediatric patients and their referring physicians for over 40 years. Nuclear medicine provides qualitative and quantitative information about overall and regional function of organs, systems, and lesions in the body. This involves applications in many organ systems including the skeleton, the brain, the kidneys and the heart as well as in the diagnosis and treatment of cancer. The practice of nuclear medicine requires the administration of radiopharmaceuticals which expose the patient to very low levels of ionizing radiation. Advanced approaches in the estimation of radiation dose from the internal distribution of radiopharmaceuticals in patients of various sizes and shapes have been developed in the past 20 years. Although there is considerable uncertainty in the estimation of the risk of adverse health effects from radiation at the very low exposure levels typically associated with nuclear medicine, some considers it prudent to be more cautious when applied to children as they are generally considered to be at higher risk than adults. Standard guidelines for administered activities for nuclear medicine procedures in children have been established including the North American consensus guidelines and the Paediatric Dosage Card developed by the European Association of Nuclear Medicine. As we move into the future, these guidelines would likely be reviewed in response to changes in clinical practice, a better understanding of radiation dosimetry as applied to children as well as new clinical applications, new advancements in the field with respect to both instrumentation and image reconstruction and processing.

Reduction in radiation dose in mercaptoacetyltriglycerine renography with enhanced planar processing.

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.

Optimizing analysis, visualization, and navigation of large image data sets: one 5000-section CT scan can ruin your whole day.

UNLABELLED: The technology revolution in image acquisition, instrumentation, and methods has resulted in vast data sets that far outstrip the human observers' ability to view, digest, and interpret modern medical images by using traditional methods. This may require a paradigm shift in the radiologic interpretation process. As human observers, radiologists must search for, detect, and interpret targets. Potential interventions should be based on an understanding of human perceptual and attentional abilities and limitations. New technologies and tools already in use in other fields can be adapted to the health care environment to improve medical image analysis, visualization, and navigation through large data sets. This historical psychophysical and technical review touches on a broad range of disciplines but focuses mainly on the analysis, visualization, and navigation of image data performed during the interpretive process. Advanced postprocessing, including three-dimensional image display, multimodality image fusion, quantitative measures, and incorporation of innovative human-machine interfaces, will likely be the future. Successful new paradigms will integrate image and nonimage data, incorporate workflow considerations, and be informed by evidence-based practices. This overview is meant to heighten the awareness of the complexities and limitations of how radiologists interact with images, particularly the large image sets generated today. Also addressed is how human-machine interface and informatics technologies could combine to transform the interpretation process in the future to achieve safer and better quality care for patients and a more efficient and effective work environment for radiologists. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11091276/-/DC1.

Identifying ureteropelvic junction obstruction by fluorescence imaging: a comparative study of imaging modalities to assess renal function and degree of obstruction in a mouse model.

PURPOSE: Radiological imaging is the mainstay of diagnosing ureteropelvic junction obstruction. Current established radiological modalities can potentially differentiate the varying degrees of obstruction but they are limited in functionality, applicability and/or comprehensiveness. Of particular concern is that some tests require radiation, which has long-term consequences, especially in children. MATERIALS AND METHODS: We investigated the novel use of Genhance™ 680 dynamic fluorescence imaging to assess ureteropelvic junction obstruction in 20 mice that underwent partial or complete unilateral ureteral obstruction. Ultrasound, mercaptoacetyltriglycine renography, magnetic resonance imaging and fluorescence imaging were performed. RESULTS: Our model of partial and complete obstruction could be distinguished by ultrasound, mercaptoacetyltriglycine renography and magnetic resonance imaging, and was confirmed by histological analysis. Using fluorescence imaging distinct vascular and urinary parameters were identified in the partial and complete obstruction groups compared to controls. CONCLUSIONS: Fluorescence imaging is a feasible alternative radiological imaging modality to diagnose ureteropelvic junction obstruction. It provides continuous, detailed imaging without the risk of radiation exposure.

RYR1 mutations are a common cause of congenital myopathies with central nuclei.

OBJECTIVE: Centronuclear myopathy (CNM) is a rare congenital myopathy characterized by prominence of central nuclei on muscle biopsy. CNM has been associated with mutations in MTM1, DNM2, and BIN1 but many cases remain genetically unresolved. RYR1 encodes the principal sarcoplasmic reticulum calcium release channel and has been implicated in various congenital myopathies. We investigated whether RYR1 mutations cause CNM. METHODS: We sequenced the entire RYR1 coding sequence in 24 patients with a diagnosis of CNM from South Africa (n = 14) and Europe (n = 10) and identified mutations in 17 patients. The most common genotypes featured compound heterozygosity for RYR1 missense mutations and mutations resulting in reduced protein expression, including intronic splice site and frameshift mutations. RESULTS: The high incidence in South African patients (n = 12/14) in conjunction with recurrent RYR1 mutations associated with common haplotypes suggested the presence of founder effects. In addition to central nuclei, prominent histopathological findings included (often multiple) internalized nuclei and type 1 fiber predominance and hypotrophy with relative type 2 hypertrophy. Although cores were not typically seen on oxidative stains, electron microscopy revealed subtle abnormalities in most cases. External ophthalmoplegia, proximal weakness, and bulbar involvement were prominent clinical findings. INTERPRETATION: Our findings expand the range of RYR1-related phenotypes and suggest RYR1 mutations as a common cause of congenital myopathies with central nuclei. Corresponding to recent observations in X-linked CNM, these findings indicate disturbed assembly and/or malfunction of the excitation-contraction machinery as a key mechanism in CNM and related myopathies.

Image Gently: progress and challenges in CT education and advocacy.

Significant progress has been made in radiation protection for children during the last 10 years. This includes increased awareness of the need for radiation protection for pediatric patients with international partnerships through the Alliance for Radiation Safety in Pediatric Imaging. This paper identifies five areas of significant progress in radiation safety for children: the growth of the Alliance; the development of an adult radiation protection campaign Image Wisely™; increased collaboration with government agencies, societies and the vendor community; the development of national guidelines in pediatric nuclear medicine, and the development of a size-based patient dose correction factor by the American Association of Physicists in Medicine, Task Group 204. However, many challenges remain. These include the need for continued education and change of practice at adult-focused hospitals where many pediatric CT exams are performed; the need for increased emphasis on appropriateness of pediatric imaging and outcomes research to validate the performance of CT studies, and the advancement of the work of the first pediatric national dose registry to determine the "state of the practice" with the final goal of establishing ranges of optimal CT technique for specific scan indications when imaging children with CT.

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

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

DeepAMO: a multi-slice, multi-view anthropomorphic model observer for visual detection tasks performed on volume images.

Purpose: We propose a deep learning-based anthropomorphic model observer (DeepAMO) for image quality evaluation of multi-orientation, multi-slice image sets with respect to a clinically realistic 3D defect detection task. Approach: The DeepAMO is developed based on a hypothetical model of the decision process of a human reader performing a detection task using a 3D volume. The DeepAMO is comprised of three sequential stages: defect segmentation, defect confirmation (DC), and rating value inference. The input to the DeepAMO is a composite image, typical of that used to view 3D volumes in clinical practice. The output is a rating value designed to reproduce a human observer's defect detection performance. In stages 2 and 3, we propose: (1) a projection-based DC block that confirms defect presence in two 2D orthogonal orientations and (2) a calibration method that "learns" the mapping from the features of stage 2 to the distribution of observer ratings from the human observer rating data (thus modeling inter- or intraobserver variability) using a mixture density network. We implemented and evaluated the DeepAMO in the context of Tc 99 m -DMSA SPECT imaging. A human observer study was conducted, with two medical imaging physics graduate students serving as observers. A 5 × 2 -fold cross-validation experiment was conducted to test the statistical equivalence in defect detection performance between the DeepAMO and the human observer. We also compared the performance of the DeepAMO to an unoptimized implementation of a scanning linear discriminant observer (SLDO). Results: The results show that the DeepAMO's and human observer's performances on unseen images were statistically equivalent with a margin of difference ( Δ AUC ) of 0.0426 at p < 0.05 , using 288 training images. A limited implementation of an SLDO had a substantially higher AUC (0.99) compared to the DeepAMO and human observer. Conclusion: The results show that the DeepAMO has the potential to reproduce the absolute performance, and not just the relative ranking of human observers on a clinically realistic defect detection task, and that building conceptual components of the human reading process into deep learning-based models can allow training of these models in settings where limited training images are available.

Renal 99mTc-DMSA pharmacokinetics in pediatric patients.

99mTc-DMSA is one of the most commonly used pediatric nuclear medicine imaging agents. Nevertheless, there are no pharmacokinetic (PK) models for 99mTc-DMSA in children, and currently available pediatric dose estimates for 99mTc-DMSA use pediatric S values with PK data derived from adults. Furthermore, the adult PK data were collected in the mid-70's using quantification techniques and instrumentation available at the time. Using pediatric imaging data for DMSA, we have obtained kinetic parameters for DMSA that differ from those applicable to adults. METHODS: We obtained patient data from a retrospective re-evaluation of clinically collected pediatric SPECT images of 99mTc-DMSA in 54 pediatric patients from Boston's Children Hospital (BCH), ranging in age from 1 to 16 years old. These were supplemented by prospective data from twenty-three pediatric patients (age range: 4 months to 6 years old). RESULTS: In pediatric patients, the plateau phase in fractional kidney uptake occurs at a fractional uptake value closer to 0.3 than the value of 0.5 reported by the International Commission on Radiological Protection (ICRP) for adult patients. This leads to a 27% lower time-integrated activity coefficient in pediatric patients than in adults. Over the age range examined, no age dependency in uptake fraction at the clinical imaging time was observed. Female pediatric patients had a 17% higher fractional kidney uptake at the clinical imaging time than males (P < 0.001). CONCLUSIONS: Pediatric 99mTc-DMSA kinetics differ from those reported for adults and should be considered in pediatric patient dosimetry. Alternatively, the differences obtained in this study could reflect improved quantification methods and the need to re-examine DMSA kinetics in adults.

Calcium and inositolphosphates in the activation of T cell-mediated cytotoxicity.

Reports from a number of laboratories have shown that mAbs against the T3-Ti receptor complex cause an increase in cytosolic-free Ca2+ [( Ca2+]i) and the hydrolysis of phosphatidylinositolbisphosphate (PIP2) in CTLs. In the present report we show that activation of CTLs by their specific targets causes: (a) release of Ca2+ from intracellular stores; (b) transient formation of inositol trisphosphate (InsP3); and (c) an increased permeability to Ca2+ of CTL plasma membrane. Killing of unrelated targets could be induced by cocentrifugation of the unrelated targets with CTLs in the presence of A23187 or PMA. We conclude that: (a) activation of CTLs by specific antigens triggers the generation of the same intracellular mediators generated by stimulation of lymphocytes with anti-T3-Ti receptor antibodies and/or with polyclonal mitogens; and (b) intracellular signals that mediate the delivery of the lethal hit by CTLs are indistinguishable from those that induce cell proliferation.

Interaction of lymphokine-activated killer cells with susceptible targets does not induce second messenger generation and cytolytic granule exocytosis.

CTL activation by specific targets leads to a rapid rise of inositol phosphates (InsPs) and of cytoplasmic-free Ca2+ concentration ([Ca2+]i). While these events are considered necessary to trigger granule secretion, Ca2+-independent cytolytic mechanisms have been recently proposed in addition or as an alternative to the classical Ca2+-dependent exocytosis model. We observed that lymphokine-activated killer (LAK) cells, obtained after stimulation with supraoptimal concentrations of IL-2 in short- or long-term cultures, kill susceptible targets in the absence of a [Ca2+]i rise and InsP3 formation. Moreover, LAK cell-mediated lysis was not associated with an increase in cytotoxic granule exocytosis, as evaluated by BLT-esterase release into the culture supernatant. Furthermore, using an antigen-specific CTL clone, which acquires LAK-like activity when cultured in medium containing high IL-2 doses, second messenger generation and cytolytic granule content secretion were not detected during lysis of unrelated target cells, while killing of specific targets triggered both these processes. These findings suggest that two lytic pathways may coexist in the same effector cells: a second messenger-dependent pathway involving degranulation, which is activated after TCR interaction with specific targets, and another pathway, independent of any known second messenger generation, responsible for unrelated target cell lysis.