The Neuroimaging Center of the Pediatric Brain Tumor Consortium-collaborative neuroimaging in pediatric brain tumor research: a work in progress.

As an essential part of the National Cancer Institute (NCI)-funded Pediatric Brain Tumor Consortium (PBTC), the Neuroimaging Center (NIC) is dedicated to infusing the study of pediatric brain tumors with imaging "best practice" by producing a correlative research plan that 1) resonates with novel therapeutic interventions being developed by the wider PBTC, 2) ensures that every PBTC protocol incorporates an imaging "end point" among its objectives, 3) promotes the widespread implementation of standardized technical protocols for neuroimaging, and 4) facilitates a quality assurance program that complies with the highest standards for image data transfer, diagnostic image quality, and data integrity. To accomplish these specific objectives, the NIC works with the various PBTC sites (10 in all, plus NCI/ National Institute of Neurological Diseases and Stroke representation) to ensure that the overarching mission of the consortium--to better understand tumor biology and develop new therapies for central nervous system tumors in children--is furthered by creating a uniform body of imaging techniques, technical protocols, and standards. Since the inception of the NIC in 2003, this broader mandate has been largely accomplished through a series of site visits and meetings aimed at assessing prevailing neuroimaging practices against NIC-recommended protocols, techniques, and strategies for achieving superior image quality and executing the secure transfer of data to the central PBTC. These ongoing evaluations periodically examine investigations into targeted drug therapies. In the future, the NIC will concentrate its efforts on improving image analysis for MR imaging and positron-emission tomography (PET) and on developing new ligands for PET; imaging markers for radiation therapy; and novel systemic, intrathecal, and intralesional therapeutic interventions.

Metabolic significance of the pattern, intensity and kinetics of 18F-FDG uptake in malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma is an aggressive neoplasm with a highly variable course. This pilot study evaluated the significance of the pattern, intensity and kinetics of 18F-FDG uptake in mesothelioma in the context of histopathology and surgical staging. METHODS: Sixteen consecutive patients with pleural disease on CT scan underwent 18F-FDG imaging. Imaging was performed with a dual detector gamma camera operating in coincidence mode. Semiquantitative image analysis was performed by obtaining lesion-to-background ratios (18F-FDG uptake index) and calculating the increment of 18F-FDG lesion uptake over time (malignant metabolic potential index (MMPi)). RESULTS: Twelve patients had histologically proven malignant mesotheliomas (10 epithelial, two sarcomatoid). Thirty two lesions were positive for tumour. Patterns of uptake matched the extent of pleural and parenchymal involvement observed on CT scanning and surgery. Mean (SD) 18F-FDG uptake index for malignant lesions was 3.99 (1.92), range 1.5-9.46. Extrathoracic spread and metastases had higher 18F-FDG uptake indices (5.17 (2)) than primary (3.42 (1.52)) or nodal lesions (2.99 (1)). No correlation was found between histological grade and stage. The intensity of lesion uptake had poor correlation with histological grade but good correlation with surgical stage. 18F-FDG lesion uptake increased over time at a higher rate in patients with more advanced disease. The MMPi was a better predictor of disease aggressiveness than the histological grade. CONCLUSIONS: This pilot study suggests that the pattern, intensity, and kinetics of 18F-FDG uptake in mesothelioma are good indicators of tumour aggressiveness and are superior to the histological grade in this regard.

Synthesis and biodistribution of a Lipophilic 64Cu-labeled monocationic Copper(II) complex.

The lipophilic, monocationic copper(II) complex of the diiminedioxime ligand 2,10-di-n-butyl-3,9-dimethyl-1,4,8,11-tetraazaundeca-1,3,8,10-tetraen-1,11-dione dioxime was synthesized and labeled with 64Cu. The biological properties of the 64Cu-labeled complex were measured in vivo and in vitro. In vivo, the complex shows uptake by the heart similar to that of 99mTc-tetrofosmin. In vitro, its uptake by multidrug resistant and non-resistant MES-SA tumor cells parallels that of 99mTc-MIBI, a well-characterized marker of multidrug resistance. These results suggest that this class of copper complexes may form the basis for the development of a 64Cu PET radiopharmaceutical for the functional imaging of multidrug resistance and/or myocardial perfusion.

Natural history of vesicoureteral reflux in girls after age 5 years.

PURPOSE: Expectations concerning the likelihood that vesicoureteral reflux will resolve during a given interval are predominantly based on experience with children younger than 5 years. We assess the natural course of vesicoureteral reflux in girls older than 5 years. MATERIALS AND METHODS: We reviewed the diagnostic and followup cystograms, medical records and renal imaging studies of 200 girls with vesicoureteral reflux, of whom 97 were diagnosed before age 60 months and 103 were diagnosed at or after age 60 months. Vesicoureteral reflux was considered to have resolved when a followup radionuclide cystogram demonstrated no reflux. RESULTS: Vesicoureteral reflux demonstrated at or after age 60 months by a radionuclide or radiographic examination (index study) resolved in 43% of cases during a mean followup interval of 41 months. The yearly percent chance of resolution approached or exceeded 20% through age 11 years. For girls with moderate vesicoureteral reflux on the index study unilateral moderate vesicoureteral reflux was associated with a higher overall percent chance of resolution and a shorter time from index study to resolution. Evidence of new or progressive parenchymal injury was not indicated in any of 92 girls who underwent serial renal ultrasonograms. CONCLUSIONS: Vesicoureteral reflux resolution continues after age 5 years at a rate similar to that in younger children. Continued medical management in the anticipation of spontaneous resolution is safe and appropriate for most patients.

Assessment of the clinical significance of asymptomatic lower extremity uptake abnormality in young athletes.

UNLABELLED: This study was undertaken to evaluate our hypothesis that most asymptomatic lower extremity uptake abnormalities are of no clinical consequence and to assess whether these findings should affect patient care. METHODS: One hundred consecutive young athletes referred for bone scintigraphy by a sports medicine clinic because of low back pain were evaluated for the presence of asymptomatic bone scan abnormalities in the lower extremities. The patients were then reexamined by the referring sports medicine physician, who had full knowledge of the bone scan results. Scintigraphic findings were correlated with the clinical evaluation at the time of scintigraphy and on follow-up evaluations ranging from 8 to 14 mo later. RESULTS: Asymptomatic lower extremity abnormalities were present in 34% of patients. There were abnormalities of the feet in 30 patients (focal uptake in 26 patients, diffuse uptake in 10 patients), the tibia in 13 patients (2 focal uptake, 11 diffuse uptake), and the femur in 2 patients (both with diffuse uptake). None of the regions of abnormal lower extremity uptake was symptomatic at the time of initial evaluation. There was no change in the clinical management of any patient because of the scan findings. None of the patients was advised to restrict the activity level because of the asymptomatic scan findings. None of the regions of scan abnormality became symptomatic on follow-up evaluation. CONCLUSION: This study shows that asymptomatic bone scintigraphic abnormalities of the feet, as well as diffuse abnormalities of the tibia, are common in young athletes. These findings are most likely of no clinical consequence and do not require a change in the activity level. Focal abnormalities of the femur or tibia are not commonly seen in asymptomatic young athletes.

Differentiation of anterior tibial stress fracture from osteoid osteoma.

The authors present a case in which skeletal scintigraphy helped them to differentiate an anterior tibial stress fracture from a possible osteoid osteoma. Important scintigraphic clues to the correct diagnosis included a linear rather than a round to oval configuration to the focus of intense uptake shown by pinhole imaging, absence of focally increased tracer localization on the angiographic and tissue phases, and a symmetrically positioned, less-conspicuous contralateral abnormality.

Effect of chronic, low-pressure, sterile vesicoureteral reflux on renal growth and function in a porcine model: a radiologic and pathologic study.

PURPOSE: To study the effects of chronic, low-pressure, sterile vesicoureteral reflux (VUR) on renal growth and function in a porcine model. MATERIALS AND METHODS: Unilateral VUR was created in five pigs, with the contralateral kidney serving as a control. Preoperatively, and 1 year later, ultrasonography, technetium 99m-dimercaptosuccinic acid (DMSA) scintigraphy, contrast material-enhanced computed tomography (CT), and contrast-enhanced magnetic resonance (MR) imaging were performed. Morphologic abnormalities and relative uptake of (99m)Tc-DMSA were recorded. The postcontrast enhancement ratios for parenchymal regions of interest at CT and MR imaging were determined. Ruthenium 103-labeled microspheres were used to determine regional blood flow. After the pigs were sacrificed, the kidneys were excised, weighed, and analyzed pathologically. RESULTS: Two of five refluxing kidneys had less than 45% function at scintigraphy. One of these two kidneys was small at postmortem examination. There were no other imaging or gross pathologic abnormalities. There was no significant difference in regional blood flow between the refluxing and nonrefluxing kidneys. In all of the operated on kidneys, histologic examination showed focal chronic inflammation and fibrosis. CONCLUSION: Low-pressure sterile reflux into previously normal kidneys led to mild, focal, chronic interstitial inflammation and fibrosis after 1 year. Imaging findings were normal apart from a subtle decrease in tubular function in two refluxing kidneys.

99m Technetium dimercapto-succinic acid renal scintigraphy abnormalities in infants with sterile high grade vesicoureteral reflux.

PURPOSE: Although vesicoureteral reflux associated with bacteriuria may cause renal scarring, sterile reflux is thought not to cause renal injury. We determined the incidence and associated characteristics of renal abnormalities using 99mtechnetium(Tc) dimercapto-succinic acid (DMSA) renal scintigraphy in infants with high grade vesicoureteral reflux but no history of urinary tract infection. MATERIALS AND METHODS: We retrospectively reviewed the results of 99mTc-DMSA renal scintigraphy and renal ultrasonography performed during the first 6 months of life in infants with vesicoureteral reflux detected during the postnatal evaluation of prenatal hydronephrosis or sibling reflux screening. Those with a history of urinary tract infection, or evidence of ureteropelvic junction or bladder outlet obstruction were excluded from study. RESULTS: Of the 28 male and 6 female infants who met study criteria vesicoureteral reflux was bilateral in 25 and unilateral in 9. Reflux grade was IV or V, II or III and I in 38, 18 and 3 of the 59 refluxing renal units, respectively. 99mTc-DMSA renal scintigraphy revealed parenchymal abnormalities in 24 refluxing renal units (41%) in 22 patients (65%), of whom 19 (86%) were male and 15 (68%) had bilateral reflux. We noted differential uptake less than 40% with and without cortical defects in 10 and 7 refluxing units, respectively, and cortical defects only in 7. Of the 24 refluxing units with abnormalities 21 were associated with grade IV or V and 3 with grade II or III reflux. Ultrasound showed evidence of renal injury in only 7 of the 17 patients (41%) in whom 99mTc-DMSA scintigraphy was abnormal. CONCLUSIONS: In our study the majority of infants with high grade reflux had decreased differential function and/or cortical defects. Parenchymal defects detected by 99mTc-DMSA renal scintigraphy were often not identified by renal ultrasound. Therefore, 99mTc-DMSA renal scintigraphy is especially useful for initially evaluating infants with high grade, sterile vesicoureteral reflux.

Reproducibility of renal length measurements with 99mTc-DMSA SPECT.

UNLABELLED: Renal length measurements are used in evaluating several abnormalities of the pediatric genitourinary tract. This study assesses reproducibility of renal length measurements obtained with 99mTc-dimercaptosuccinic acid (DMSA) SPECT. METHODS: The lengths of 98 kidneys of 51 children (age range, 1-16 y; mean age, 5.4 y) who underwent 99mTc-DMSA SPECT were measured independently by 2 observers. Renal length was calculated by converting pixels between points at the superior and inferior renal margins on a summated coronal image to centimeters. Lengths were measured for kidneys as they appeared in situ and after realignment along their long axes. SPECT reconstruction, choice of display parameters, positioning of points used for measuring, and alignment were performed independently by each observer. Interobserver variability, interobserver correlation, and mean differences between observers' measurements (expressed as measurement of observer 2 - measurement of observer 1) were calculated. RESULTS: Correlation between the observers' measurements was highly significant for both nonaligned and aligned studies (r = 0.95 and 0.97, respectively; both, P < 0.0001). Interobserver variability expressed as 1 SD was 3.6 mm for nonaligned studies and 2.8 mm for aligned studies. The mean difference between the 2 observers' measurements for nonaligned studies was 2.0 +/- 4.8 mm (P < 0.0001) with a range of -11 to 14 mm. For aligned studies the mean difference between the 2 observers' measurements was -0.1 +/- 4.0 mm (P = 0.88) with a range of -20 to 10 mm. Differences between observers were not dependent on absolute renal length (P = 0.68 for nonaligned studies; P = 0.40 for aligned studies). CONCLUSION: The variability in renal length measurements determined by 99mTc-DMSA SPECT is similar to that reported previously using sonography. Because the interobserver differences in renal length are similar to annual renal growth rates during childhood, caution should be applied when incorporating renal length measurements determined by 99mTc-DMSA SPECT into management algorithms. Additional studies are required to further establish interobserver variability, to assess intraobserver variability, and to evaluate means of improving standardization.

Variability of diuresis renography interpretation due to method of post-diuretic renal pelvic clearance half-time determination.

PURPOSE: We assessed variability in the interpretation of diuresis renography that may result from using different methods of clearance half-time determination. MATERIALS AND METHODS: We reviewed 152 diuresis renography studies performed at diagnosis or during followup of 53 children enrolled in a prospective study assessing the natural history of unilateral neonatal hydronephrosis. Studies were classified as nonobstructive, indeterminate or obstructive using 4 methods of half-time determination. Intermethod correlation and agreement were evaluated. We compared the proportion of nonobstructive, indeterminate and obstructive classifications by each method, and the interpretation of individual studies based on each method. RESULTS: Among methods we noted a high degree of correlation and fair to excellent agreement (Spearman rho = 0.86 to 0.92 and kappa = 0.57 to 0.86, respectively). However, in 27.8% of intermethod comparisons the proportion of studies classified as nonobstructive, indeterminate and obstructive differed significantly (p <0.05). The classification of pelvicaliceal drainage varied by method for all but the most severely dilated systems. In individual studies classification by 1 method was discordant with classification by another in 19% of comparisons. Of the discordant interpretations 97.7% involved nonobstructive versus indeterminate or indeterminate versus obstructive classifications. CONCLUSIONS: Variability in classifying drainage patterns based on half-time requires that practitioners be circumspect when applying this parameter for managing asymptomatic hydronephrosis. It also necessitates the description of quantitative methodology in published series of this important clinical problem.

Effect of early emptying on quantitation and interpretation of liquid gastric emptying studies of infants and young children.

UNLABELLED: This study assesses the effect of emptying that occurs during feeding on quantitation and interpretation of liquid gastric emptying studies of infants and young children. METHODS: Forty-nine 99mTc-sulfur colloid liquid gastric emptying studies of 44 children (22 boys, 22 girls; mean age, 20 mo; age range, 2-46 mo) fed orally or by gastrostomy tubes were evaluated. Gastric residuals quantitated by 2 commonly used methods, the first of which does not account for early emptying and the second of which does, were compared. With the first method, residual relative to activity in the stomach at the start of imaging (Rg) was quantified by comparing activity in a region of interest (ROI) drawn about the stomach on the final image to activity in an ROI drawn about only the stomach at the start of imaging. With the second method, residual relative to total dose (Rt) was quantified by comparing activity in the same final ROI to activity in an ROI that included stomach and small bowel at the start of imaging. Studies were interpreted independently for Rg and Rt considering a value >70% as evidence of delayed emptying. RESULTS: Rt was lower than Rg by 15%-16% for the entire population, for patients fed orally, and for patients fed by gastrostomy tube. These differences reached statistical significance (P < 0.0001). In 31 of 49 studies, R1 was lower than Rg by > or =10%. In 8 studies, emptying classified as delayed on the basis of Rg was classified as nondelayed on the basis of Rt. Clinical decisions based on Rt did not require later management changes that would have indicated that treatment of gastric dysmotility had been postponed in any patient. CONCLUSION: Emptying that occurs during feeding should be factored into quantitation of liquid gastric emptying in infants and young children. Not recognizing and accounting for early emptying results in overestimated gastric residuals and can lead to classification of emptying as delayed in children whose residuals of the total administered dose are within a recognized range of normal.

Sibling vesicoureteral reflux in multiple gestation births.

BACKGROUND: Vesicoureteral reflux (VUR) is the most commonly inherited disease of the genitourinary tract. Although the majority of evidence supports a genetic cause, the tendency for this condition to spontaneously improve over time has made it difficult to determine the actual mode of transmission. We report the incidence of VUR in siblings of multiple gestation births and for the first time compare the relative incidence of reflux between identical and fraternal twins. METHODS: A database consisting of all radionuclide cystograms and voiding cystourethrograms performed between the years 1986 and 1996 was searched for multiple gestation births. The medical records of each patient were evaluated for age at presentation, zygosity, reflux grade, and time to resolution. Children with secondary causes of VUR (eg, posterior urethral valves) were excluded. Triplets were treated as 2 pairs of twins for statistical analysis. RESULTS: Forty-six pairs met the inclusion criteria (31 dizygotic and 15 monozygotic). Overall, 23 (50%) of 46 siblings of index cases had demonstrable VUR. Comparison of VUR prevalence between identical and nonidentical twins was revealing with 80% (12/15) of identical twins and 35% (11/31) of fraternal twins having VUR. When only the youngest individuals in each group were considered, 100% (7/7) of the monozygotics and 50% (5/10) of the dizygotics demonstrated this trait. CONCLUSIONS: High concordance for VUR in identical twin siblings supports a genetic basis for the transmission of this disease. Results obtained from fraternal twin siblings provides convincing evidence that this trait is transmitted in an autosomal dominant fashion.

Registration of three-dimensional magnetic resonance and radionuclide skeletal images.

PURPOSE: To apply postprocessing techniques to register three-dimensional TI-201 bone SPECT datasets with MRI. This may provide more accurate anatomic-functional correlation when localizing active tumors. MATERIALS AND METHODS: Three-dimensional datasets were constructed from previously acquired MRIs using routine imaging protocols. Registration software was used to coregister the TI-201 SPECT studies and the MRIs in three dimensions. RESULTS: Adequate TI-201 uptake in muscles and soft tissues along with relatively low accumulation in tendons and joint spaces provided adequate landmarks for visually aligning SPECT and MRI datasets. MR abnormalities were more extensive because of surrounding reactive tissue, and more focal TI-201 uptake could be demonstrated within the region of MR signal abnormality, allowing the focal metabolically active tissue to be distinguished from adjacent edema. CONCLUSIONS: Image registration of SPECT and anatomic imaging (CT or MRI) is used routinely to evaluate functional abnormalities within the brain. This technique has now been applied to the combination of TI-201 SPECT and MR data for evaluating bone lesions and may provide additional anatomic information for localizing functional abnormalities. This may be valuable for defining targets for biopsy, planning surgical treatment, and using minimally invasive therapies.

Pediatric applications of pinhole magnification imaging.

Pinhole magnification imaging is an important technique for practitioners of pediatric nuclear medicine. This article reviews basic principles of pinhole magnification imaging and ways for optimizing image acquisition with this technique. Applications to skeletal scintigraphy, scrotal scintigraphy and renal cortical scintigraphy are discussed and illustrated.