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Clinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1. We assessed tryptophan and glucose metabolism by performing baseline C11-labeled α-methyl tryptophan (C11-AMT) and fluorodeoxyglucose (FDG) PET imaging of tumor lesions in a prospective clinical trial of pembrolizumab in MM (clinicaltrials.gov,NCT03089606). We found higher protein expression of all TMEs and LAT1 in melanoma cells than tumor-infiltrating lymphocytes (TILs) within MM tumors (n=68). Melanoma cell-specific TPH1 and LAT1 expression are significantly anti-correlated with TIL presence in MM. High melanoma cell-specific LAT1 and low IDO1 expression were associated with worse overall survival (OS) in MM. Exploratory optimal cut-point survival analysis of pretreatment ‘high’ vs. ‘low’ C11-AMT SUVmaxof the hottest tumor lesion per patient revealed that the ‘low’ C11-AMT SUVmaxwas associated with longer progression-free and OS in our clinical trial (n=26). We saw no such trends with pretreatment FDG PET SUVmax. Treatment of melanoma cell lines with telotristat, a TPH1 inhibitor, increased IDO expression and kynurenine production in addition to suppression of serotonin production. High melanoma tryptophan metabolism is a poor predictor of pembrolizumab response and an adverse prognostic factor. Serotoninergic but not kynurenine pathway activation may be significant. Melanoma cells outcompete adjacent TILs, eventually depriving the latter of an essential amino acid.

Because cancer patients are especially endangered by SARS-CoV-2 infection and have worse disease course and outcomes, it is crucial to protect them from this infection. This study was aimed at assessing protective antibodies after patients received mRNA-based SARS-CoV-2 vaccines. Protective antibodies (e.g., anti-SARS-CoV-2 S1 IgG antibodies) were assessed in patients’ blood before vaccination, after the first and second doses and 3 months after a complete primary course vaccination. Patients’ oncological treatment was unaffected by the vaccination received. The results of protective antibodies were also compared with healthy control subjects who were vaccinated in the same manner. More than 110 cancer patients participated and agreed to have their blood samples analyzed. The rate of antibody production was 96% after a complete primary course of vaccination and was similar with that of healthy control subjects. However, there were some differences noted regarding the oncological treatment that the patients were receiving, with patients who were treated with targeted therapy achieving the highest levels of protective antibodies. Adverse events after vaccination were mostly mild and did not interfere with patients’ general performance. The rate of antibody production for cancer patients after SARS-CoV-2 vaccination is high and similar to that in healthy control subjects but varies with regard to the oncological treatment that patients are receiving. However, antibodies decline substantially after 3 months, and thus a third vaccination is desirable. There were no new safety concerns after vaccination, and most adverse events were mild and short-lived.

Background: SARS-CoV-2 vaccination in cancer patients is crucial since they are at increased risk of severe COVID-19 disease course, but data on efficacy and safety of vaccination are scarce.Methods: We performed a prospective observational study of patients with solid cancers on active anticancer treatment (chemotherapy, immunotherapy with immune checkpoint inhibitors (ICI) or targeted therapy) that received mRNA-based SARS-CoV-2 vaccination at two institutions in Slovenia. The immunogenicity was assessed by the detection of anti-SARS-CoV-2 S1 IgG antibodies in serum; patients were sampled before, 2-3 weeks after the first dose, 2-3 weeks after the second dose, and 3 months after the complete primary course of vaccination. The results were also compared to controls, sampled at similar time points.Results: Between March and July 2021 112 patients were included in the analysis. The seroconversion rate in patients without prior COVID-19 infection was 96% after the complete primary course of vaccination with 2 doses, compared to 100% for healthy controls. The seroconversion rate after vaccination for patients on chemotherapy, ICI, and targeted therapy was 100%, 91%, and 97%, respectively. All controls and the majority of patients on chemotherapy and targeted therapy, but only 83% for patients on ICI were adequate responders (anti-SARS-CoV-2 S1 IgG ≥ 880 ng/ml). Three months after the vaccination, a significant drop in antibody levels was observed in patients receiving ICI compared to controls (P < 0.001). Adverse events were mostly mild and predictable, none of the patients experienced serious adverse events after vaccination.Conclusions: Immunogenicity after mRNA-based vaccination against SARS-CoV-2 in cancer patients is only slightly impaired, but influenced by the type of anticancer therapy received. Patients on ICI have the slightest and gradual antibody production. Since antibody levels decline after three months, a third vaccination dose is reasonable to provide adequate protection against severe COVID-19 disease course.The study was approved by the National Ethics Committee (No. 0120-39/2021/6)

The scientific basis of nuclear medicine is the radiotracer, with its union of a pharmaceutical and a radionuclide. There are a number of existing tracers approved for use in the United States and elsewhere, but by far the most commonly used (and the only one used for melanoma and sarcoma) is fluorodeoxyglucose (FDG). FDG is a positron emitter, with the emitted positron being annihilated and producing two photons detected by the ring of detectors in the PET scanner. The PET is done together with a CT scan, which is used for both anatomic localization and attenuation correction. FDG is selectively taken up by cancer cells due to their heavy anaerobic metabolism, though other causes such as inflammation can also produce an increase in uptake. Common alterations in biodistribution include elevated glucose levels and/or insulin secretion and brown fat activation. The SUV (standardized uptake value) has been created as a semiquantitative measure of local uptake, correlates with prognosis, and is sometimes used for therapy assessment, but has technical problems resulting in significant variability.

In the evaluation of soft tissue sarcomas (STSs) and melanoma, hybrid imaging modalities such as F-18 FDG PET/CT and PET/MRI, which combine functional and anatomical images, have become extremely useful. These hybrid modalities, with the use of fluorine-18 fluorodeoxy-glucose (F-18 FDG or FDG), are able to evaluate the metabolic status of tissue suspected or known to be malignant, as well as to observe treatment response or monitor for potential residual or recurrent disease. When selecting hybrid imaging for evaluation, it is important to select the most appropriate hybrid imaging modality, PET/CT or PET/MRI, to extract the desired information.

Significant variability in the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin (PLD) exists. PLD undergoes clearance via the mononuclear phagocyte system (MPS). Technetium Tc 99m sulfur colloid (TSC) is approved for imaging MPS cells. We investigated TSC as a phenotypic probe of PLD pharmacokinetics and pharmacodynamics in women with epithelial ovarian cancer. TSC 10 mCi IVP was administered and followed by dynamic planar and SPECT/CT imaging and blood pharmacokinetics sampling. PLD 30–40 mg/m2 IV was administered with or without carboplatin, followed by plasma pharmacokinetics sampling. There was a linear relationship between TSC clearance and encapsulated doxorubicin clearance (R 2 = 0.61, p = 0.02), particularly in patients receiving PLD alone (R 2 = 0.81, p = 0.04). There was a positive relationship (ρ = 0.81, p = 0.01) between maximum grade palmar-plantar erythrodysesthesia toxicity developed and estimated encapsulated doxorubicin concentration in hands. TSC is a phenotypic probe for PLD pharmacokinetics and pharmacodynamics and may be used to individualize PLD therapy in ovarian cancer and for other nanoparticles in development.

The Roman domination problem is considered. An improvement of two existing Integer Linear Programing (ILP) formulations is proposed and a comparison between the old and new ones is given. Correctness proofs show that improved linear programing formulations are equivalent to the existing ones regardless of the variables relaxation and usage of lesser number of constraints. [Projekat Ministarstva nauke Republike Srbije, br. TR36006]

3556 Background: Molecular imaging of metabolic pathways critical for effector T cell response other than glucose could predict response to PD1 inhibitors. We have previously shown that high expression of tryptophan metabolic pathway enzymes in stage III/IV melanoma correlates with reduced abundance of tumor-infiltrating lymphocytes (TILs, ASCO 2019, e21014). Here we investigated C11-AMT, a PET tracer that images tryptophan metabolism, as a predictor of response to pembro in patients (pts) with PD1 inhibitor-naïve MM. Methods: In this trial (NCT03089606) pts must have had measurable MM by RECIST, have undergone IV contrast CT, FDG-PET, and C11-AMT PET scan (30-40 min dynamic imaging), plus a mandatory tumor biopsy prior to pembro treatment. Results: 21 pts (16 males; 15 stage IV; median age 61) had all 3 baseline scans and evaluable research biopsies. 13 pts were non-progressors (CR = 4, PR = 6, and SD = 3). At a median f/u of 13.7 mons (2.8-25.1+), 6 pts are dead from MM, 11 are alive without MM and 4 are alive with MM. 46 tumor lesions were assessed by all 3 scans. Of the pts with tumor lesion, C11-AMT PET SUVmax < 7 and skewness < +0.3 of the tumor lesion with the highest C11-AMT SUVmax was associated with non-progression by RECIST (SUVmax < 7/skewness < +0.3 in progressors vs. non-progressors; Fisher’s 2-tail test p= 0.055). The corresponding association between baseline FDG-PET (SUVmax < 14 and skewness < +0.3) with treatment response was insignificant ( p= 0.08). There was a weak (Spearman ρ= 0.33) but significant correlation ( p= 0.001) in SUVmax between FDG-PET and C11-AMT among the 46 tumors analyzed. There was no significant correlation between melanoma-specific expression of the tryptophan- (TPH1, TPH2, IDO1, TDO2, LAT1) and glucose-metabolizing enzymes (GLUT1, HK1, HK3) by immunohistochemistry. Response to pembro trends to associate with present TILs (Fisher’s p= 0.087). Conclusions: Baseline C11-AMT PET imaging using simple radiomics measures (highest metabolic activity, SUVmax, and tumor heterogeneity, skewness) may better predict clinical benefit from pembro in MM than FDG PET. Variability in C11-AMT’s SUVmax cannot be solely explained by FDG-PET’s SUVmax, suggesting that these two imaging modalities may provide complementary information about intratumoral metabolic dysregulation that may relate with pembro response. Texture analysis using LifeX v4.0 will be presented at the meeting. Clinical trial information: NCT03089606 .

The expression of hepatic transporters, including organic anion transporting polypeptides (OATPs) and multidrug resistance-associated proteins (MRPs), is altered in nonalcoholic steatohepatitis (NASH); however, functional data in humans are lacking. In this study, 99m Tc-mebrofenin (MEB) was used to evaluate OATP1B1/1B3 and MRP2 function in NASH patients. Healthy subjects (n = 14) and NASH patients (n = 7) were administered MEB (∼2.5 mCi). A population pharmacokinetic model was developed to describe systemic and hepatic MEB disposition. Study subjects were genotyped for SLCO1B1 variants. NASH increased systemic and hepatic exposure (median ± 2 SE, healthy vs. NASH) to MEB (AUC0-300,blood : 1,780 ± 242 vs. 2,440 ± 775 μCi*min/L, P = 0.006; AUC0-180,liver : 277 ± 36.9 vs. 433 ± 40.3 kcounts*min/sec, P < 0.0001) due to decreased biliary clearance (0.035 ± 0.008 vs. 0.017 ± 0.002 L/min, P = 0.0005) and decreased Vcentral (11.1 ± 0.57 vs. 6.32 ± 1.02 L, P < 0.0001). MEB hepatic CLuptake was reduced in NASH and also in healthy subjects with SLCO1B1 *15/*15 and *1A/*15 genotypes. The pharmacokinetics of drugs that are OATP1B1/1B3 and MRP2 substrates may be substantially altered in NASH.

To date, there are limited radiation dose data on CT-guided procedures in pediatric patients. Our goal was to quantify the radiation dose associated with pediatric CT-guided drain placement and follow-up drain evaluations in order to estimate effective dose. We searched the electronic medical record and picture archiving and communication system (PACS) to identify all pediatric (

Full-energy peak efficiencies of germanium detectors are frequently investigated at γ -ray energies below 4 MeV using calibrated radioactive sources, while very accurate peak efficiencies for higher photon energies are essentially non-existent. Peak efficiencies in the energy range of E γ = 4 – 12 MeV are crucial for a number of applications, including nuclear astrophysics measurements of fusion reactions and resonance fluorescence experiments. We report on a novel method, using the 163 keV resonance in the B 11 ( p , γ ) C 12 reaction, of measuring accurately the ratio of full-energy peak efficiencies at 4.44 and 11.66 MeV. We derive this ratio for three different detector-target distances (3, 12 and 26 cm) directly from measured peak intensities and demonstrate that corrections are small ( γ -ray branching ratios, angular correlations, coincidence summing). Our measured full-energy peak efficiency ratios have a precision of 1.4–1.6%. Another important goal of our study was to determine to what precision full-energy peak efficiencies at high γ -ray energies can be predicted using the simulation codes Geant3 and Geant4 . We imaged our detector using computed tomography and radiographs in order to extract reliable detector crystal dimensions. Based on these results, extensive computer simulations are performed. We find that the simulation results agree with the measured peak efficiency ratios within an uncertainty of 1.6% for Geant4 and 2.6% for Geant3 . Our results are useful for assigning uncertainties when peak efficiencies are extrapolated from low energy data to high energies based on simulations only.

OBJECTIVE To evaluate the expression of glucose transporters (Gluts) 1 and 3 in Hodgkin and nonHodgkin lymphoma and to assess the association between their expression and the tumor intensity on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). METHODS All 31 lymphoma patients in whom the histologic diagnosis was made and who had also undergone a prechemotherapy PET scan at our institution between June 2001 and December 2005 were included in this retrospective study. The percentage of tumor cells in the various lymphoma subtypes was estimated by comparison of hematoxylin and eosin stain with a lineage-associated immunohistochemical stain on the same block of tissue. Tissue specimens were stained with Glut1 and Glut3 antibodies. The percentages of Glut1+ and Glut3+ cells in the entire cell population (lymphoma cells and nonlymphomatous cells) and among the lymphoma cells were estimated. FDG PET images were reviewed and the tumor intensity was assessed by calculating the maximum standard uptake value (SUVmax). Correlation coefficients between SUVmax and the percentage of Glut1+ and Glut3+ cells in the entire cell population were calculated. RESULTS In all 31 cases, tumors were visible on FDG PET and positive for Glut1 and Glut3. The correlation between the percentage of Glut1+ cells and SUVmax was statistically significant across all 31 cases (r = 0.73, P

Objectives This study compares 2 measures of effective dose, E1990 and E2007, for 8 dentoalveolar and maxillofacial cone-beam computerized tomography (CBCT) units and a 64-slice multidetector CT (MDCT) unit. Study design Average tissue-absorbed dose, equivalent dose, and effective dose were calculated using thermoluminescent dosimeter chips in a radiation analog dosimetry phantom. Effective doses were derived using 1990 and the superseding 2007 International Commission on Radiological Protection (ICRP) recommendations. Results Large-field of view (FOV) CBCT E2007 ranged from 68 to 1,073 μSv. Medium-FOV CBCT E2007 ranged from 69 to 560 μSv, whereas a similar-FOV MDCT produced 860 μSv. The E2007 calculations were 23% to 224% greater than E1990. Conclusions The 2007 recommendations of the ICRP, which include salivary glands, extrathoracic region, and oral mucosa in the calculation of effective dose, result in an upward reassessment of fatal cancer risk from oral and maxillofacial radiographic examinations. Dental CBCT can be recommended as a dose-sparing technique in comparison with alternative medical CT scans for common oral and maxillofacial radiographic imaging tasks.

Rationale and Objectives This study was conducted to compare the magnetic resonance (MR) contrast medium enhancement of abdominal organs in vivo with the signal intensity (SI) values of known in vitro gadolinium solutions. Materials and Methods A phantom was imaged with the MR contrast medium gadodiamide (Omniscan; Nycomed, Princeton, NJ) of solutions at full-strength (0.5 mmol/mL), one-third, 1/10, and 1/100 concentrations. A fat-suppressed fast spoiled gradient-echo pulse sequence with flip angles ranging from 10° to 170° (at 20° increments) was performed with a 1.5-T magnet. In 12 subjects, the SIs of abdominal organs were determined with identical imaging parameters, before and after administration of gadodiamide injection at 0.1 mmol/kg. Results As anticipated, the plot of SI in relation to gadodiamide concentration is nonlinear, with a decrease in SI due to T2 effects at concentrations above 0.05 mmol/mL. The kidney showed the highest SI after gadodiamide enhancement (125.2 ± 11.6 [standard error] at 2.5 minutes), followed by the liver (76.5 ± 11.5 at 1 minute) and spleen (57.26 ± 9.35 at 30 seconds). The SI of the renal medulla (114.2 ± 9.8 at 4.5 minutes) was approximately one-third that in phantom observations. Conclusion The authors observed a marked discrepancy between empirical contrast medium performance in abdominal organs and SI values for comparable gadodiamide concentrations in vitro. One possible reason is the intracellular compartmentalization of water molecules in vivo. These results suggest a need for a better understanding of MR contrast medium performance in vivo.

Rationale and Objectives The authors assessed the feasibility of using magnetic resonance (MR) urography to acquire functional, dynamic, and anatomic information in human subjects with normal and hydronephrotic kidneys. Materials and Methods In subjects known to have or suspected of having hydronephrosis, split renal filtration fractions were measured with a customized magnetization-prepared, inversion-prepared gradient-recalled echo sequence to determine the T1 of flowing blood in the inferior vena cava and aorta before and after contrast medium administration and in the renal veins and arteries after contrast medium administration. Multiple timed sets of coronal fast spoiled gradient-echo 70° flip-angle images were acquired before and after contrast medium administration to derive MR renograms from changes in the signal intensity of the cortex and medulla. Precontrast T2-weighted images were obtained with a three-dimensional fast spoiled gradient-echo maximum intensity projection pulse sequence, and postcontrast T1 maximum intensity projection images were also obtained to depict the renal anatomy. Results Split filtration fraction differentiated normal from hydronephrotic kidneys. MR renograms depicted vascular, tubular, and ductal phases and differentiated between normal and hydronephrotic kidneys (P Conclusion The preliminary findings show promise for the use of MR urography in the comprehensive assessment of renal function, dynamics, and anatomy.

“Eighty percent of success is just showing up.”Woody AllenPediatric CT radiation dose optimization is a challenging process for pediatric-focused facilities and community hospitals alike. Ongoing experience and trial-and-error approaches to dose reduction in the large academic hospital setting may position these centers to help community hospitals who strive for CT quality improvement. In this pilot project, we describe our hands-on approach to develop a partnership between an academic medical center and a community hospital to develop a toolkit for implementing CT dose reduction. Our aims were to 1) assess the acceptability of an interactive educational program and electronic toolkit booklet, 2) conduct a limited test of the efficacy of the toolkit in promoting knowledge and readiness to change, and 3) assess the acceptability and practicality of a collaborative approach to implementing dose-reduction protocols in community hospitals. In partnering with the community hospital, we found that they had size specific radiation doses 2 to 3 times higher than those at our center. Survey results following a site visit with interactive educational presentations revealed an increase in knowledge, stronger opinions about the health risks of radiation from CT scans, and willingness and perceived ability to reduce pediatric CT doses.

Problems related to file structures, transfer and networking plays an important role is in medical imaging in the early detection of cancers. Radiologists often have difficulty locating and accurately identifying cancer tissue, even with the aid of structural information such as CT and MRI because of the low contrast between the cancer and the surrounding tissues in CT and MRI images. Using SPECT and radioactively labeled monoclonal antibodies it is possible to obtain high contrast images of the concentration of antibodies in tumors. However, sometimes it is difficult to determine the precise location ofthe high concentration of the radioactive isotope in SPECT or PET images in relation to anatomic structures, such as vital organs and surrounding healthy tissue. Image registration is a visualization tool that can significantlyaid in the early detection oftumors and other diseases, and aid in improving the accuracy of diagnosis. The problems related to multimodality imaging can be separated into three groups; a) problems related to file structures, transfer and networking, b) registration, and c) visualization of the composite images. an image with normal uptake properties to an image with suspected abnormalities. In addition, image registration of SPECT and PET images and the registration of SPECT and PET images with anatomic atlases, provide an important means to evaluate comparative uptake properties of SPECT and PET radiopharmaceuticals, and to correlate uptake properties with anatomy. Medical image registration has been applied to the diagnosis of breast cancer, colon cancer, cardiac studies, wrist and other injuries, inflammatory diseases and different neurological disorders including brain tumors, Alzheimer's disease and schizophrenia. This method has also been utilized in radiotherapy, mostly for brain tumors, and by cranio-facial surgeons to prepare for and simulate complexsurgical procedures. One area where image registration Two basic types of medical images are made: functional body images (such as SPECT or PET scans), which provide physiological information, and structural images (such as CT or MRI), which provide an anatomic map of the body. Different medical imaging techniques may provide scans with complementary and occasionally conflicting information. The combination of images can often lead to additional clinical information not apparent in the separate images. The goal of image fusion is to impose a structural anatomic framework on functional images. Often in a functional image, there simply isn't enough anatomic detail to determine the position ofa tumor or other lesion. Although, the construction of a composite, overlapping medical image described in the field as medical image registration has been primarily used in the fusion offunctional and anatomical images, it has also been applied to a series of the same modality images. Examples of this are registration of SPECT images of the same subject in follow-up studies or in a comparison of Functional imaging using single photon emission computed tomography (SPECT) and positron emission tomography (PET) is extremely valuable in the diagnosis of various disorders. Uncertainty in the anatomic definition on SPECT and PET images, however, sometimes limits their usefulness. To overcome this problem, a combination ofmagnetic resonance images (MRI) and X-ray computed tomography (CT) images with functional SPECT or PET images of the same sections of the body, is used. This provides complementary anatomic (MRI or CT) and physiological (SPECT or PET) information that is of great importance to research, diagnosis, and treatment.

To determine the weighted average sensitivity of magnetic resonance (MR) imaging in the prospective detection of acute neck injury and to compare these findings with those of a comprehensive conventional radiographic assessment.Conventional radiography and MR imaging were performed in 199 patients presenting to a level 1 trauma center with suspected cervical spine injury. Weighted sensitivities and specificities were calculated, and a weighted average across eight vertebral levels from C1 to T1 was formed. Fourteen parameters indicative of acute injury were tabulated.Fifty-eight patients had 172 acute cervical injuries. MR imaging depicted 136 (79%) acute abnormalities and conventional radiography depicted 39 (23%). For assessment of acute fractures, MR images (weighted average sensitivity, 43%; CI: 21%, 66%) were comparable to conventional radiographs (weighted average sensitivity, 48%; CI: 30%, 65%). MR imaging was superior to conventional radiography in the evaluation of pre- or paravertebral hemorrhage or edema, anterior or posterior longitudinal ligament injury, traumatic disk herniation, cord edema, and cord compression. Cord injuries were associated with cervical spine spondylosis (P.05), acute fracture (P.001), and canal stenosis (P.001).MR imaging is more accurate than radiography in the detection of a wide spectrum of neck injuries, and further study is warranted of its potential effect on medical decision making, clinical outcome, and cost-effectiveness.

An algorithm to automatically detect and eliminate motion in projection data from triple scan SPECT imaging is proposed. The approach relies on a protocol where each head acquires projections over a full 360 degrees orbit rather than over the conventional 120 degrees partial orbit. Projection acquisition times are reduced to one third of that used for the partial orbit protocol to keep comparable total scan times. This protocol permits the acquisition of three full sets of SPECT data which can be adequately combined in order to reconstitute a motion-free set of projection data. Cross-correlation of the projection sets as a function of angle are used to detect motion. Plateaus of high correlation are estimated and matched in order to identify projections corresponding to the same position of a subject throughout a study. The motion correction algorithm was tested on experimental data obtained by manually moving a cardiac phantom at different times. In all cases, it was possible to reconstitute the evolution of the motion during the study. When no motion occurred during an interval equal to at least one third of the total acquisition time, high correlation plateaus were identified and complete sets of consistent projections were assembled from the longest matching plateaus. When more frequent motion occurred, an averaging of the three sets provided a means to improve the quality of the reconstructed slices compared to conventional imaging protocol.

The common imaging practice of each detector on a multidetector SPECT imaging system to acquire only a fraction of the total number of projections in a 360/spl deg/ projection set introduces the possibility of imbalances in system response which can cause artifacts and changes in image quality. Here we evaluate the effect of variations in detector sensitivity caused by differences in the position of the photopeak window, window width, and different collimators on reconstructed image quality. Analytical simulations of cardiac phantom geometries and experimental measurements with Data Spectrum's Cardiac and Deluxe SPECT phantoms on a three detector SPECT imaging system were used in the evaluation. The relative efficiency of one of three detectors was changed over a series of values between 100 and 0%, while the efficiency of the remaining two detectors was maintained at 100%. The results show that decreased activity and geometric distortions occur along directions perpendicular to the projections with altered sensitivity. The degree of distortion and decrease of activity depends on the geometry of the activity distribution and the reduction in sensitivity. The relative count ratios in the regions with decreased activity varied over a range of 1.0 to 0.59 as the detector sensitivity is decreased from 100 to 0% of the full energy window. Variations in detector sensitivity can degrade spatial resolution and uniformity and create artifacts in reconstructed tomographic slices.

We performed a randomized trial to compare nebulized and viscous topical corticosteroid treatments for eosinophilic esophagitis (EoE). Subjects with incident EoE (n = 25) received budesonide 1 mg twice daily, either nebulized and then swallowed (NEB) or as an oral viscous slurry (OVB), for 8 weeks. Baseline eosinophil counts for the NEB and OVB groups were 101 and 83 (P = .62). Posttreatment counts were 89 and 11 (P = .02). The mucosal medication contact time, measured by scintigraphy, was higher for the OVB group than the NEB group (P.005) and was inversely correlated with eosinophil count (R = -0.67; P = .001). OVB was more effective than NEB in reducing numbers of esophageal eosinophils in patients with EoE. OVB provided a significantly higher level of esophageal exposure to the therapeutic agent, which correlated with lower eosinophil counts.

OBJECTIVE. A novel PET radiotracer, 124I-cG250, is currently under clinical investigation to distinguish clear cell renal cell carcinoma from other benign and malignant renal masses. In this article, we will make suggestions on the data needed to maximize the use of this radiotracer. CONCLUSION. Although the published data are promising, further data are needed to assess the potential usefulness of this agent when dealing with indeterminate renal masses.

Standard uptake values, SUV, are commonly used semiquantitative parameters in tumor diagnosis, staging and monitoring therapy response. However, their accuracy and reproducibility is affected by the glucose level, length of the uptake period, and body weight and composition. The aim of this study is to evaluate the effects of PET acquisition parameters (count rate, SNR, 2D vs 3D, object geometry) and image reconstruction parameters (Filtered backprojection, (FBP), iterative reconstruction (OSEM), filter selection) on calculated SUVs. The evaluation was done using circular and elliptical cylinders with spherical sources from 0.6-3.5 cm in dia, with sphere to background activity concentration varied from 2:1 to 20:1. Coincidence count rate varied from 5 kcps to 600 kcps. All studies were acquired in 2D and 3D mode, with variable emission (3-10 min) and transmission time durations (2-10 min). Reconstruction was performed with both FBP and OSEM with 2-10 iterations and 8-32 subsets. SUVs were estimated using the average and the maximum count density from ROIs placed in the center of the structure of interest The evaluation was done on the CTI ECAT HR + high resolution PET scanner and the biograph PET/CT LSO system. The variation in the calculated SUVs as a function of selected acquisition and processing parameters in addition to the variations due to patient dependent parameters indicated that distinguishing between benign and malignant disease based on SUVs, and using SUVs as semiquantitative parameters in the follow-up studies has to be interpreted with caution.

Rationale and Objectives This study was conducted to define and characterize magnetic resonance (MR) contrast medium enhancement of the renal cortex, medulla, and pelvocaliceal system in normal and hydronephrotic kidneys with and without furosemide administration. Materials and Methods In 30 subjects known or suspected to have unilateral hydronephrosis and normal serum creatinine levels, multiple timed sets of coronal fast spoiled gradient-echo images were acquired before and after contrast medium administration. MR renograms were derived from changes in the signal intensity (SI) of the cortex, medulla, and pelvocaliceal system. Ten subjects received 40 mg of intravenous furosemide approximately 10 minutes before contrast medium administration. Results The following values were significantly different between subjects who were given furosemide and those who were not: the peak cortical, medullary, and pelvocaliceal system SIs measured in the normal kidneys during the 4 1 2 minutes following contrast medium administration (163.2 ± 17.7 [mean arbitrary units plus or minus standard error] vs 120.5 ± 10.2 [P = .033], 155.5 ± 18.8 vs 111.5 ± 9.4 [P = .025], and 332.5 ± 27.2 vs 229.3 ± 31.9 [P = .026], respectively); the crossover time between the SI curves of the pelvocaliceal system and the medulla in the normal kidney (2.45 minutes ± 0.2 vs 3.27 minutes ± 0.25 [P = .02]); and the peak SIs of the cortex, medulla, and pelvocaliceal system in the unilateral obstructive hydronephrotic kidneys throughout the first 4 1 2 minutes after contrast medium administration (174.6 ± 16.4 vs 90.6 ± 13.7 [P = .003], 117.6 ± 14.1 vs 86.7 ± 11.8 [P = .015], and 337.2 ± 41.4 vs 143.1 ± 74.4 [P = .034], respectively). Conclusion MR renography can be used to depict three separate components of renal enhancement: cortical, medullary, and pelvocaliceal. Furosemide-induced diuresis increases renal parenchymal and pelvocaliceal SI and urinary flow rates.

Conventional partial orbit SPECT acquisition (90/spl deg/, 120/spl deg/ or 180/spl deg/ depending on number of camera heads) on multihead cameras enhance the problems caused by patient motion or change in organ position ("cardiac creep"), since the misplaced data are present at several intervals in the projection set. The authors investigated the effects of source motion and developed new image motion correction methods based on 360/spl deg/ acquisition of each detector on a three camera SPECT system. Experimental measurements with point sources and cardiac phantom were used to evaluate the influence of source motion on SPECT images. A point source phantom was rotated 5-30/spl deg/ CCW and moved axially 0.5-4.0 cm. A cardiac phantom was moved in laterally (0.5-4.0 cm) and in the axial direction (0.5-4.0 cm). Cross-correlation of images from different heads at the same angular position is used to detect and correct for motion. Two correction methods were investigated: (1) summation of complete 360/spl deg/ projection sets without correction, (2) time normalization of projection frames without motion to replace frames affected by motion. The first method corrects for small displacement of the source (

Recent studies show Tl-201 and Tc-99m MIBI to have high sensitivity for detecting and differentiating tumor from benign lesions in the breast. A study was conducted to optimize the design of a multi-pinhole collimator for high spatial resolution SPECT imaging of the breast to detect small tumors (0.5/spl times/0.5 cm). High sensitivity is achieved by using multiple pinholes, and rotating the camera 90-180 degrees around the breast. Monte Carlo simulation studies and analytical methods are applied to determine the number of holes, hole position, hole aperture size, conical field of view, and focal length of the collimator to optimize spatial resolution and sensitivity for breast imaging. Shielding is optimized to accommodate an energy range of 50-511 keV. An image reconstruction algorithm for cone beam imaging geometry for rotating single pinhole SPECT will be modified to accommodate simultaneous imaging from multiple pinholes with limited angular sampling. Special emphasis is placed on evaluation of imaging with small pinhole apertures (1-2 mm diameter), that are required to achieve the resolution of 3-7 mm at the distance of 10-15 cm with radionuclides having energies /spl les/140 keV. Complete 360/spl deg/ acquisition of the breast tumor model was simulated to study the artifacts in reconstructed images due to limited angle acquisition and to select an optimal reconstruction algorithm.

An algorithm to automatically detect and eliminate motion in projection data from triple head SPECT systems is proposed. The approach relies on a specific protocol in which each camera rotates 3 times faster than in conventional acquisitions and performs a full 360-degree orbit, instead of the usual partial 120 degrees orbit. This permits to obtain three full sets of data. The hypothesis is that by adequately combining the sets, it is possible in most eases to reconstitute a motion-free set of projection data. The motion detection consists of searching consistent frames through the study by cross-correlating the projection sets as a function of the angle. Plateaus of high correlation are estimated and matched in order to identify projections corresponding to the same position of the subject throughout the study. Different motion situations were created by manually moving a cardiac phantom at different times. In all cases, it was possible to reconstitute the evolution of the motion during the study. When no motion occurred during an interval equal to at least one third of the total acquisition time, high correlation plateaus could be identified. It was then possible to build an optimal complete set of consistent frames from the longest matching plateaus regardless of the frequency and magnitude of motion. Otherwise, an averaging of the three sets was performed, which still improved the quality of the reconstructed slices compared to conventional imaging protocol.

Rationale and Objectives The authors performed this study to assess the effects of furosemide-induced diuresis on paramagnetic contrast material enhancement at magnetic resonance (MR) imaging of the kidney, liver, spleen, and psoas muscle. Materials and Methods Twenty-five patients (average age, 44.9 years; age range, 23–74 years; 13 men, 12 women) who were suspected of having unilateral renal hydronephrosis received 0.1 mmol/kg contrast material with a standardized injection and imaging protocol to assess organ signal intensity at 0–5 minutes after injection. All patients had a normal serum creatinine level. Imaging was performed with a 1.5-T magnet by using a fat-suppressed fast spoiled gradient-echo pulse sequence and a 70° flip angle. Eight patients received 40 mg of furosemide 10 minutes before contrast material injection. Results The areas of the renal cortical and medullary signal intensity curves minus baseline in the unilateral normal kidneys were significantly greater in the group who received furosemide (P = .026 and P = .037, respectively). The areas of the renal cortical and medullary signal intensity minus baseline in the unilateral hydronephrotic kidneys were also significantly greater in the group that received furosemide (P = .036 and P = .026, respectively). There was a statistically significant increase in splenic enhancement (P = .02) and a tendency for increased liver (P = .09) and psoas muscle (P = .08) enhancement. Conclusion Furosemide-induced diuresis appears to potentiate the cortical and medullary MR renogram, as well as the MR splenogram. A rapid shift in water compartmentalization from the intracellular to the extracellular space and increased renal water content with diuresis are possible explanations.

Aims: This study compares effective doses associated with 2D lateral, oblique, and AP radiographs with 3D MDCT and Cone Beam CT images of the foot and ankle. Methods: An anthropomorphic phantom of the foot and ankle was constructed from an adult human skeleton and soft tissue equivalent material. Optical stimulated dosimeters were placed at 21 locations within and on tissues and anatomy of interest. Effective dose was calculated following 2007 ICRP recommendations. Three projections were exposed to simulate conventional 2D imaging. Standard and optimized dose MDCT scans were exposed to simulate typical CT options. Ten, 20, and 30cm fields of view, 100 and 120kVp and 4.5 and 6.8mAs exposures were tested using a PedCAT® CBCT device designed for weightbearing imaging. Dose was calculated for an adult as well as for a 5 and 10-year-old child to assess the impact of age on risk estimation. Results: Standard adult effective doses for single foot imaging were 0.6µSv for 2D, 3.8µSv for CBCT, and 25µSv for MDCT ( p = 0.0013). Dose differed significantly with age ( p = 0.0185). For a 5-year-old, doses rise to 0.8µSv for 2D, 18µSv for CBCT, and 200µSv for MDCT. Small and medium CBCT fields produced adult doses of 2.3 mSv and 0.9 mSv respectively. Conclusions: The effective dose for small FOV CBCT or conventional 2D series examinations is comparable to a few hours of equivalent background dose. Such doses are negligible; therefore, the dose of radiation should not be a concern when considering the use of CBCT imaging for foot/ankle examination.

Patient motion in gamma camera coincidence imaging results in severe reconstruction artifacts. A protocol is proposed to automatically detect and correct motion from SPECT coincidence studies. The method is based on fractionating the acquisition into three full temporal sets of coincidence data. For each set and camera position, partial sinograms are calculated by rebinning events acquired at the same rotation. Partial sinograms from successive angular positions as well as from successive sets are cross- correlated along their common range of projections. Decreases in the cross-correlation values indicate that data from two successive rotations or sets became inconsistent and permit localization of the motion that occurred during the study. Events acquired during motion are eliminated while pre and post motion events are recombined into sets of consistent rebinned data that are reconstructed independently and fused to provide a motion-artifact free reconstructed image. The methods were tested using a wide range of experimental motion data obtained from cylindrical phantoms containing spheres filled with Fluorine-18. Single arbitrary motions that occurred during the study could be detected and further corrected in all phantom studies when the total number of coincident events acquired was greater than 5x106 for lesion-to-background ratios greater than 5.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Determination of skeletal or bone age is often used in pediatrics and orthopedics. The most commonly used bone age standards in the United States, those published by Greulich and Pyle, were derived from white children of the upper socioeconomic class in 1931-1942. We examined whether these standards apply to the current assessment of bone age in children of diverse ethnicity.Hand radiographs of children less than 19 years old at our institution were evaluated for bone age using the standards of Greulich and Pyle. Differences between bone age and chronologic age were calculated, and the mean differences were compared among subgroups of children on the basis of sex, age, and ethnicity.In Asian and white girls, bone age approximated chronologic age throughout childhood, with the only significant discrepancy being in adolescent white girls, in whom bone age exceeded chronologic age by an average of 4 months. In black girls, bone age exceeded chronologic age except during middle childhood. In late childhood and adolescence, bone age exceeded chronologic age by approximately 10 months. In Hispanic adolescent girls, bone age exceeded chronologic age by nearly 9 months. In black adolescent boys, bone age exceeded chronologic age by 5 months, with no significant discrepancies between bone age and chronologic age at other ages. In white preadolescent boys, bone age lagged behind chronologic age to a statistically significant degree, ranging from approximately 4 to 8 months. Preadolescent Asian boys also showed significant delays in bone age, particularly in middle childhood, when bone age lagged behind chronologic age by nearly 15 months. In adolescent Asian boys, bone age exceeded chronologic age by 9 months 15 days. In adolescent Hispanic boys, bone age exceeded chronologic age by 11 months 15 days. In younger Hispanic boys, delays in bone age occurred but were significant only in early childhood (4-month delay).Using the standards of Greulich and Pyle to determine bone age must be done with reservations, particularly in black and Hispanic girls and in Asian and Hispanic boys in late childhood and adolescence, when bone age may exceed chronologic age by 9 months to 11 months 15 days.

5050 Background: There is significant variability in the PK and PD (efficacy and toxicity) of PLD. Clearance (CL) of PLD has been proposed to occur primarily via uptake by cells of the mononuclear phagocyte system (MPS) mainly located in the liver, spleen, and blood. TSC is a radioactive colloid used clinically for diagnostic and functional imaging of the MPS. Our aim is to evaluate TSC as a phenotypic probe of MPS activity, which may predict PLD PK and PPE toxicity in pts (n=9) with EOC. Methods: Prior to administration of PLD on cycle 1 day 1 (C1D1), TSC was administered at 10 mCi IVP × 1. Dynamic planar and SPECT/CT images of the liver, spleen and hands were acquired using a gamma camera. Blood samples were collected up to 60 min after TSC and analyzed for radioactivity using a gamma counter. On C1D1, PLD was administered at 40 mg/m2 alone or at 30 mg/m2 in combination with carboplatin IV over 1 to 3 h. Serial PK samples were obtained from 0h to 672h post PLD dose. Plasma was processed to measure encapsulated and released doxorubicin (dox) using solid phase separation and HPLC. CL of PLD and TSC were calculated by non-compartmental analysis. The grade of PPE toxicity was determined by NCI CTCAE (v4.03) criteria. Results: Nine patients have undergone TSC imaging and eight patients completed TSC blood PK and PLD plasma PK studies. There was a positive linear relationship between TSC CL and encapsulated dox CL (R2 = 0.61, p=0.02). When patients were subdivided, there was a stronger relationship between TSC CL and encapsulated dox CL (R2 = 0.81, p=0.03) in pts receiving PLD monotherapy. A positive relationship using Spearman’s correlation (ρ=0.84, p=0.006) was also found between maximum grade PPE toxicity developed and estimated AUC of encapsulated dox in hands [(TSC AUCBlood)/(TSC AUCHand)*Encapsulated Dox AUCPlasma]. Conclusions: These results suggest that TSC is a probe for MPS function and PLD PK and PD and may be used to individualize PLD therapy in pts with EOC. In addition, our findings suggest TSC may be able to predict the development of PPE in patients.