Search

Peptide receptor radionuclide therapy (PRRT) is an effective treatment for metastatic neuroendocrine tumors. Delivering a sufficient tumor radiation dose remains challenging because of critical-organ dose limitations. Adding 131I-metaiodobenzylguanidine (131I-MIBG) to PRRT may be advantageous in this regard. Methods: A phase 1 clinical trial was initiated for patients with nonoperable progressive neuroendocrine tumors using a combination of 90Y-DOTATOC plus 131I-MIBG. Treatment cohorts were defined by radiation dose limits to the kidneys and the bone marrow. Subject-specific dosimetry was used to determine the administered activity levels. Results: The first cohort treated subjects to a dose limit of 1,900 cGy to the kidneys and 150 cGy to the marrow. No dose-limiting toxicities were observed. Tumor dosimetry estimates demonstrated an expected dose increase of 34%–83% using combination therapy as opposed to 90Y-DOTATOC PRRT alone. Conclusion: These findings demonstrate the feasibility of using organ dose for a phase 1 escalation design and suggest the safety of using 90Y-DOTATOC and 131I-MIBG.

In 2018, the National Cancer Institute (NCI) and the NRG Oncology partnered for the first time to host a joint Workshop on Systemic Radiopharmaceutical Therapy (RPT) to specifically address issues and strategies of dosimetry for future clinical trials. The workshop focused on (1) current dosimetric approaches for clinical trials, (2) strategies under development that would provide optimal dose reporting, and (3) future desired/optimized approaches for the new and novel emerging radionuclides and carriers in development. In this proceedings, we review the main approaches that are applied clinically to calculate the absorbed dose: These include absorbed doses calculated over a variety of spatial scales including organ, suborgan, and voxel, all achievable within the Medical Internal Radiation Dose (MIRD) schema (S-value) can be calculated with analytic methods or Monte Carlo methods, the latter in most circumstances. This proceeding will also contrast currently available methods and tools with those used in the past, to propose a pathway whereby dosimetry helps the field by optimizing the biological effect of the treatment and trial design in the drug approval process to reduce financial and logistical costs. We will also discuss the dosimetric equivalent of biomarkers to help bring a precision medicine approach to RPT implementation-when merited by evidence collected during early-phase trial investigations. Advances in the methodology and related tools have made dosimetry the optimum biomarker for RPT.

Rationale and Objectives To assess the nature of the satisfaction of search (SOS) effect in chest radiography when observers are fatigued; determine if we could replicate recent findings that have documented the nature of the SOS effect to be due to a threshold shift rather than a change in diagnostic accuracy as in earlier film-based studies. Materials and Methods Nearing or at the end of a clinical workday, 20 radiologists read 64 chest images twice, once with and once without the addition of a simulated pulmonary nodule. Half of the images had different types of “test” abnormalities. Decision thresholds were analyzed using the center of the range of false-positive (FP) and true-positive (TP) fractions associated with each receiver operating characteristic (ROC) point for reporting test abnormalities. Detection accuracy was assessed with ROC technique and inspection time was recorded. Results The SOS effect was confirmed to be a reduction in willingness to respond (threshold shift). The center of the FP range was significantly reduced (FP = 0.10 without added nodules, FP = 0.05 with added nodules, F(1,18) = 19.85, P = 0.0003). The center of the TP range was significantly reduced (TP = 0.39 without added nodules, TP = 0.33 with added nodules, F(1,18) = 10.81, P = 0.004). Conclusions This study suggests that fatigue does not change the nature of the SOS effect, but rather may be additive with the SOS effect. SOS reduces both TP and FP responses, whereas fatigue reduces TPs more than FPs.

Two decades have passed since the publication of laboratory studies of satisfaction of search (SOS) in chest radiography. Those studies were performed using film. The current investigation tests for SOS effects in computed radiography of the chest.Sixty-four chest computed radiographs half demonstrating various "test" abnormalities were read twice by 20 radiologists, once with and once without the addition of a simulated pulmonary nodule. Receiver-operating characteristic detection accuracy and decision thresholds were analyzed to study the effects of adding the nodule on detecting the test abnormalities. Results of previous studies were reanalyzed using similar modern techniques.In the present study, adding nodules did not influence detection accuracy for the other abnormalities (P = .93), but did induce a reluctance to report them (P.001). Adding nodules did not affect inspection time (P = .58) so the reluctance to report was not associated with reduced search. Reanalysis revealed a similar decision threshold shift that had not been recognized in the early studies of SOS in chest radiography (P.01) in addition to reduced detection accuracy (P.01).The nature of SOS in chest radiography has changed, but it is not clear why.SOS may be changing as a function of changes in radiology education and practice.

Purpose: Nuclear medicinequality control programs require daily evaluation for the presence of potential non‐uniformities by commonly utilizing a traditional pixel value‐based assessment (Integral CFOVUniformity). While this method effectively captures regional non‐ uniformities in the image, it does not adequately reflect subtle periodic structures that are visually apparent and clinically unacceptable, therefore requiring the need for additional visual inspection of the image. The goal of this project was to develop a new uniformity assessment metric by targetingstructural patterns and more closely correlating with visual inspection.Methods: The new quantitative uniformity assessment metric is based on the 2D Noise Power Spectrum (NPS). A full 2D NPS was performed on each image. The NPS was thresholded to remove quantum noise and further filtered by the visual response function. A score, the Structure Noise Index (SNI), was then applied to each based on the average magnitude of the structured noise in the processed image. To verify the validity of the new metric, 50 daily uniformity images with varying degrees of visual structured and non‐structured non‐uniformity were scored by 5 expert nuclear medicinephysicists. The correlation between the visual score and SNI were assessed. The Integral CFOV was also compared against the visual score. Results: Our new SNI assessment metric compared to the Integral CFOV showed in increase in sensitivity from 67% to 100% in correctly identifying structured non‐uniformities. The overall positive predictive value also increased from 55% to 72%. Conclusions: Our new uniformity metric correlates much more closely with visual assessment of structured non‐ uniform NM images than the traditional pixel‐based method. Using this new metric in conjunction with the traditional pixel value‐based assessment will allow a more accurate quantitative assessment of nuclear medicineuniformity.

Previous studies have demonstrated that fatigue impacts diagnostic accuracy, especially for those in training. We continued this line of investigation to determine if fatigue has any impact on a common source of errors – satisfaction of search (SOS). SOS requires subjects to participate in 2 sessions (SOS and non-SOS) and so does fatigue (fatigued and not fatigued) so we ran subjets in only the fatigued condition and used a previous non-fatigued study as the comparison. We used 64 chest computed radiographs half demonstrating various ‘‘test’’ abnormalities were read twice by 20 radiologists, once with and once without the addition of a simulated pulmonary nodule. Receiver-operating characteristic detection accuracy and decision thresholds were analyzed to study the effects of adding the nodule on detecting the test abnormalities. Adding nodules did not influence detection accuracy (ROC AUC SOS = 0.667; non-SOS = 0.679), but did induce a reluctance to report them. Adding nodules did not affect inspection time so the reluctance to report was not associated with reduced search. Fatigue did not appear to exacerbate the SOS effect. A second study with fractures revealed the same shift in performance but did reduce viewing times when fatigued. The results of these two studies suggest that the impact of fatigue on SOS is more complicated than expected and thus may require more investigation to fully understand its impact in the clinic.

To evaluate the repeatability of gallium-68 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA)-D-Phe1-Try3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) in neuroendocrine tumors.Five patients with neuroendocrine tumors were imaged with 68Ga-DOTATOC PET twice within 5 days. Maximum and mean standardized uptake values (SUVmax and SUVmean) and kinetic parameters (K-Patlak and K-influx) of target lesions were measured. The repeatability of these measurements was investigated.Forty-seven target lesions were identified on whole-body PET and 21 lesions on dynamic images. There was excellent repeatability with intraclass correlation coefficient of 0.99 for SUVmax, SUVmean, and K-Patlak, and 0.85 for K-influx. The median absolute percent differences and the interquartile ranges (IQR) between 2 scans for SUVmax and SUVmean were 7.4% (IQR, 14.1%) and 9.3% (IQR, 10.6%), respectively. The median absolute percent differences for K-Patlak and K-influx were 12.5% (IQR, 12.6%) and 29.9% (IQR, 22.4%), respectively. The SUVmax of target lesions did not differ by more than 25% between the 2 scans.68Ga-DOTATOC PET imaging of neuroendocrine tumors is highly reproducible. A difference of more than 25% in SUVmax represents a change that is larger than the measurement error observed on repeated studies and should reflect a significant change in the biological character of the tumor.

To minimize radiation exposure in children and reduce resource use, we implemented an age-specific algorithm to evaluate cervical spine injuries at a Level 1 trauma center. The effects of protocol implementation on computed tomography (CT) use in children (≤ 10 y) were determined.With institutional review board approval, we conducted a retrospective review using the institutional trauma registry. All pediatric patients (≤ 10 y) (n = 324) between January 2007 and present were reviewed. We excluded cases in which no imaging or outside imaging was performed. Patients were evaluated by physical exam alone, with the aid of plain radiograms or with cervical spine CT. All patients who required head CT also had CT of cervical spine to C3. We analyzed demographic, injury, and outcome data using STATA to perform chi-square and t-test, and to determine P value. P0.05 was defined as significant. We used the WinDose program to calculate the radiation-effective dose used in cervical spine CT.There were 123 and 124 patients in the pre-protocol and post-protocol groups, respectively. Demographics, GCS, and injury analysis, specifically head-neck and face Injury Severity Scores showed no significant difference between groups. There was a 60% (P0.001) decrease in the use of full CTs after protocol implementation. We estimated that the protocol reduced the exposed area by 50% and decreased the radiation dose to the thyroid by80%. We extrapolated the combined effect results in a threefold reduction in radiation exposure.Implementation of a cervical spine protocol led to a significant reduction in radiation exposure among children.

Rationale and Objectives We tested whether satisfaction of search (SOS) effects that occur in computed tomography (CT) examination of the chest on detection of native abnormalities are produced by the addition of simulated pulmonary nodules. Materials and Methods Two experiments were conducted. In the first experiment, 70 CT examinations, half that demonstrated diverse, subtle abnormalities and half that demonstrated no native lesions, were read by 18 radiology residents and fellows under two experimental conditions: presented with and without pulmonary nodules. In a second experiment, many of the examinations were replaced to include more salient native abnormalities. This set was read by 14 additional radiology residents and fellows. In both experiments, detection of the natural abnormalities was studied. Receiver operating characteristic (ROC) curve areas for each reader-treatment combination were estimated using empirical and proper ROC models. Additional analyses focused on decision thresholds and visual search time on abnormality-free CT slice ranges. Institutional review board approval and informed consent from 32 participants were obtained. Results Observers more often missed diverse native abnormalities when pulmonary nodules were added, but also made fewer false-positive responses. There was no change in ROC area, but decision criteria grew more conservative. The SOS effect on decision thresholds was accompanied by a reduction in search time on abnormality-free CT slice ranges. Conclusion The SOS effect in CT examination of the chest is similar to that found in contrast examination of the abdomen, involving induced visual neglect.

In human emission tomography, combined PET/CT and SPECT/CT cameras provide accurate attenuation maps for sophisticated scatter and attenuation corrections. Having proven their potential, these scanners are being adapted for small animal imaging using similar correction approaches. However, attenuation and scatter effects in small animal imaging are substantially less than in human imaging. Hence, the value of sophisticated corrections is not obvious for small animal imaging considering the additional cost and complexity of these methods. In this study, using GATE Monte Carlo package, we simulated the Inveon small animal SPECT (single pinhole collimator) scanner to find the scatter fractions of various sizes of the NEMA-mouse (diameter: 2-5.5 cm , length: 7 cm), NEMA-rat (diameter: 3-5.5 cm, length: 15 cm) and MOBY (diameter: 2.1-5.5 cm, length: 3.5-9.1 cm) phantoms. The simulations were performed for three radionuclides commonly used in small animal SPECT studies:99mTc (140 keV), 111In (171 keV 90% and 245 keV 94%) and 125I (effective 27.5 keV). For the MOBY phantoms, the total Compton scatter fractions ranged (over the range of phantom sizes) from 4-10% for 99mTc (126-154 keV), 7-16% for 111In (154-188 keV), 3-7% for 111In (220-270 keV) and 17-30% for 125I (15-45 keV) including the scatter contributions from the tungsten collimator, lead shield and air (inside and outside the camera heads). For the NEMA-rat phantoms, the scatter fractions ranged from 10-15% (99mTc), 17-23% 111In: 154-188 keV), 8-12% (111In: 220-270 keV) and 32-40% (125I). Our results suggest that energy window methods based on solely emission data are sufficient for all mouse and most rat studies for 99mTc and 111In. However, more sophisticated methods may be needed for 125I.

To better understand fundamental issues, perception studies of the fusion display would best be performed with a panel of lesions of variable location, size, intensity, and background. There are compelling reasons to use synthetic images that contain artificial lesions for perception research. A consideration of how to obtain this panel of lesions is the nucleus of the present review. This article is a conjoint effort of 3 groups that have joined together to review results from work that they and others have performed. The techniques we review include (1) substitution of lesions into a preexisting image matrix (either using actual prior patient-derived lesions or mathematically modeled artificial lesions), (2) addition of images (either in the attenuation-corrected image space or at an earlier stage before image reconstruction), and (3) simulation of the entire patient image. A judicious combination of the techniques discussed in this review may represent the most efficient pathway of simulating statistically varied but realistic appearing lesions.

In human emission tomography, an additional transmission scan (x-ray CT or external gamma-source) is often required to obtain accurate attenuation maps for attenuation correction (AC) and scatter correction (SC). These transmission-based correction methods have been translated to small animal imaging although the impact of photon interactions on the mouse/rat-reconstructed images is substantially less than that in human imaging. Considering the additional complexity in design and cost of these systems, the necessity of these correction methods is questionable for small animal emission tomography. In this study, we evaluate the requirement of these corrections for small animal positron emission tomography (PET) through Monte Carlo simulations of the Inveon PET scanner using various sizes of MOBY voxelized phantoms. The 3D sinogram data obtained from simulations were reconstructed in 6 different conditions: Accurate AC+SC, simple (water) AC+SC, accurate AC only, simple AC only, SC only and no correction (NC). Mean error% for 8 different ROIs and 6 different MOBY sizes were obtained against the accurate scatter and attenuation corrections (first on the list). In addition to simulations, real mouse data obtained from an Inveon PET scanner were analyzed using similar methods. Results from both simulation and real mouse data showed that attenuation correction based on solely emission data should be sufficient for imaging animals smaller than 4 cm diameter. For larger sizes, a scatter correction employing an additional transmission scan can also be included depending on the objective of the study.

We developed fully automated software for dynamic susceptibility contrast (DSC) MR perfusion-weighted imaging (PWI) to efficiently and reliably derive critical hemodynamic information for acute stroke treatment decisions. Brain MR PWI was performed in 80 consecutive patients with acute nonlacunar ischemic stroke within 24h after onset of symptom from January 2008 to August 2009. These studies were automatically processed to generate hemodynamic parameters that included cerebral blood flow and cerebral blood volume, and the mean transit time (MTT). To develop reliable software for PWI analysis, we used computationally robust algorithms including the piecewise continuous regression method to determine bolus arrival time (BAT), log-linear curve fitting, arrival time independent deconvolution method and sophisticated motion correction methods. An optimal arterial input function (AIF) search algorithm using a new artery-likelihood metric was also developed. Anatomical locations of the automatically determined AIF were reviewed and validated. The automatically computed BAT values were statistically compared with estimated BAT by a single observer. In addition, gamma-variate curve-fitting errors of AIF and inter-subject variability of AIFs were analyzed. Lastly, two observes independently assessed the quality and area of hypoperfusion mismatched with restricted diffusion area from motion corrected MTT maps and compared that with time-to-peak (TTP) maps using the standard approach. The AIF was identified within an arterial branch and enhanced areas of perfusion deficit were visualized in all evaluated cases. Total processing time was 10.9+/-2.5s (mean+/-s.d.) without motion correction and 267+/-80s (mean+/-s.d.) with motion correction on a standard personal computer. The MTT map produced with our software adequately estimated brain areas with perfusion deficit and was significantly less affected by random noise of the PWI when compared with the TTP map. Results of image quality assessment by two observers revealed that the MTT maps exhibited superior quality over the TTP maps (88% good rating of MTT as compared to 68% of TTP). Our software allowed fully automated deconvolution analysis of DSC PWI using proven efficient algorithms that can be applied to acute stroke treatment decisions. Our streamlined method also offers promise for further development of automated quantitative analysis of the ischemic penumbra.

SPECT is a rapidly changing field, and the past several years have produced new developments in both hardware technology and image-processing algorithms. At the component level there have been improvements in scintillators and photon transducers as well as a greater availability of semiconductor technology. These devices permit the fabrication of smaller and more compact systems that can be customized for particular applications. New clinical devices include high-count sensitivity cardiac SPECT systems that do not use conventional collimation and the introduction of diagnostic-quality hybrid SPECT/CT systems. While there has been steady progress with reconstruction algorithms, exciting new processing algorithms have become commercially available that promise to provide substantial reductions in SPECT acquisition time without sacrificing diagnostic quality. Preclinical small-animal SPECT systems have become a major focus in nuclear medicine. These systems have pushed the limits of SPECT into the submillimeter range, making them valuable molecular imaging tools capable of providing information unavailable from other modalities.

Rationale and Objectives We propose a novel segmentation-based interpolation method to reduce the metal artifacts caused by surgical aneurysm clips. Materials and Methods Our method consists of five steps: coarse image reconstruction, metallic object segmentation, forward-projection, projection interpolation, and final image reconstruction. The major innovations are 2-fold. First, a state-of-the-art mean-shift technique in the computer vision field is used to improve the accuracy of the metallic object segmentation. Second, a feedback strategy is developed in the interpolation step to adjust the interpolated value based on the prior knowledge that the interpolated values should not be larger than the original ones. Physical phantom and real patient datasets are studied to evaluate the efficacy of our method. Results Compared to the state-of-the-art segmentation-based method designed previously, our method reduces the metal artifacts by 20–40% in terms of the standard deviation and provides more information for the assessment of soft tissues and osseous structures surrounding the surgical clips. Conclusion Mean shift technique and feedback strategy can help to improve the image quality in terms of reducing metal artifacts.

OBJECTIVES The bladder pressure at the onset of reflux may reflect the competence of the ureterovesical junction. The predictive value of the bladder pressure at the onset of vesicoureteral reflux, as measured by nuclear cystometrography, was assessed relative to subsequent reflux resolution. METHODS Nuclear cystometrograms of 67 children were reviewed to determine the presence of reflux, bladder pressure at the onset of reflux, and bladder volume at the onset of reflux. The data were analyzed for significant relationships between the nuclear cystometrogram results and patient outcomes using a Cox proportional hazards regression model, controlling for the duration of follow-up and for patients with bilateral reflux. RESULTS Data were gathered for reflux occurring in 85 ureters. As expected, reflux of a greater grade was less likely to resolve spontaneously (P = 0.005). The pressure at the onset of reflux was also highly predictive of spontaneous resolution (P = 0.0005). Reflux occurring at greater pressures was more likely to resolve spontaneously, independent of the reflux grade or bladder volume at the onset of reflux. Patient age (P = 0.45), normalized volume of urine refluxed (P = 0.97), and normalized bladder volume at the onset of reflux (P = 0.18) were not significant predictors of reflux resolution. CONCLUSIONS The findings of this report have demonstrated for the first time, to our knowledge, that the bladder pressure at the onset of vesicoureteral reflux, as determined by nuclear cystometrography, is a significant independent predictor of vesicoureteral reflux resolution in children.

Although a checklist has been recommended for preventing satisfaction of search (SOS) errors, a previous research study did not demonstrate that benefit. However, observers in that study had to turn away from the image display to use the checklist. The current study tested a vocalized checklist to avoid this constraint.A total of 64 chest computed radiographs, half containing various "test" abnormalities, were read twice by 20 radiologists, once with and once without the addition of a simulated pulmonary nodule. Readers used a vocalized checklist-directing search. Receiver operating characteristic (ROC) detection accuracy and decision thresholds were analyzed to study the effects of adding the nodule on detecting the test abnormalities.Adding nodules induced a substantial reluctance to report the other abnormalities (P 0.001), as had been the case in the most recent study of the SOS effect in radiography.The vocalized checklist did not reduce nor eliminate the SOS effect on readiness to report further abnormalities. Although useful for organizing search and reporting, particularly among students, a vocalized checklist does not prevent SOS effects.

Rationale and Objectives Image perception studies have been difficult to perform using clinical images because of the problems associated with obtaining proven abnormalities and appropriate normal controls. The objective of this research was to develop and evaluate interactive software that allows the seamless removal, archiving and insertion of abnormal areas from computed tomography (CT) lung image sets for use in image perception research. Materials and Methods The software tools for removing, archiving, and adding lesions are described in detail. The efficacy of the software to remove abnormal areas of lung CT studies was evaluated by having radiologists select the one altered image from a display of four. The software for adding lesions was evaluated by having radiologists classify displayed CT slices with lesions as real or artificial along with their confidence level. Results Observers could not reliably detect when images had been altered by the software. In the lesion-removal experiment, the observers correctly identified the altered display in only 15.8 ± 2.8 of 56 sets. In the lesion-add experiment, the observers correctly identified the artificially placed lesions in 38.2 ± 3.9 of 77 sets. The frequency distribution of the correct responses did not differ from that expected from chance selection. Conclusions The results from both of these experiments demonstrate that radiologists could not distinguish between original and altered images. We conclude that this software can be used with volumetric CT lung images for creating normal control and target data sets for medical image perception research.

The shielding of positron emission tomography (PET) and PET/CT (computed tomography) facilities presents special challenges. The 0.511 MeV annihilation photons associated with positron decay are much higher energy than other diagnostic radiations. As a result, barrier shielding may be required in floors and ceilings as well as adjacent walls. Since the patient becomes the radioactive source after the radiopharmaceutical has been administered, one has to consider the entire time that the subject remains in the clinic. In this report we present methods for estimating the shielding requirements for PET and PET/CT facilities. Information about the physical properties of the most commonly used clinical PET radionuclides is summarized, although the report primarily refers to fluorine-18. Typical PET imaging protocols are reviewed and exposure rates from patients are estimated including self-attenuation by body tissues and physical decay of the radionuclide. Examples of barrier calculations are presented for controlled and noncontrolled areas. Shielding for adjacent rooms with scintillation cameras is also discussed. Tables and graphs of estimated transmission factors for lead, steel, and concrete at 0.511 MeV are also included. Meeting the regulatory limits for uncontrolled areas can be an expensive proposition. Careful planning with the equipment vendor, facility architect, and a qualified medical physicist is necessary to produce a cost effective design while maintaining radiation safety standards.

Y-90-DOTA-Phe1-Tyr3-Octreotide (90Y-SMT 487, OctreoTher) has shown potential for effectively treating patients with neuroendocrine tumors. The dose-limiting organ for this agent is the kidney. The purpose of this work is to assess the effectiveness of a commercially available amino acid solution on reducing renal uptake of 90Y-SMT 487 and determine the safety profile of this solution. Subjects with In-111 pentetreotide positive tumors and normal creatinine levels were treated with 3 cycles of 90Y-SMT 487, 120 mCi/cycle, at 6-9 week intervals. During each treatment two liters of an amino acid solution containing arginine and lysine (Aminosyn II 7%, Abbott Laboratories, Abbott Park, IL) were infused IV over 4 hours. Adverse events were recorded. To assess the effect of Aminosyn II on renal uptake of 90Y-SMT 487, a subgroup of subjects underwent bremsstrahlung imaging 24 hours following infusion. Kidney to liver (K/L) count density ratios were generated from the baseline In-111 pentetreotide images (performed without amino acid infusion) and the 90Y bremsstrahlung images. Follow-up creatinine levels were obtained. Thirty-seven subjects received a total of 89 90Y-SMT 487 treatments. The number of amino-acid infusions associated with one or more episodes of emesis was 53 (62%). During 13 (15%) of these infusions, the Aminosyn II rate had to be reduced because of severe nausea and vomiting. Symptomatic flushing occurred during 16 (18%) of the infusions. One subject experienced a near syncopal event shortly after completing the infusion. Creatinine levels remained normal in 34 of 36 subjects during a mean follow-up period of 9.8 months. Fourteen subjects underwent bremsstrahlung imaging following infusion of 90Y-SMT 487. Kidney uptake appeared to decrease with administration of the amino acid solution in 13 of 14 subjects. For the 28 individual kidneys, the mean percent decrease in the Kidney/Liver uptake ratio with the amino acid solution was found to be 32%. We conclude that 2 L of Aminosyn II 7% infused over 4 hours appears to notably reduce renal uptake of 90Y-SMT 487. Aminosyn is generally well tolerated, particularly at lower infusion rates with occasional moderate to severe nausea and vomiting at higher rates.

Reflux grade predicts resolution and influences followup and treatment. Bladder pressure at the onset of reflux may reflect the ureterovesical junction competence. By combining simultaneous cystometry with nuclear cystography (nuclear cystometrogram) we determined bladder pressure at the onset of reflux.Nuclear cystometrograms were performed in 40 children to determine bladder pressure at the onset of reflux, reflux volume and bladder capacity at the onset of reflux. The effect of bladder pressure and capacity at the onset of reflux was assessed with a reflux pressure volume index.A weak inverse correlation existed between bladder pressure at the onset of reflux and a normalized volume of reflux (r = -0.32, p = 0.018). A stronger correlation existed between reflux pressure and bladder volume at reflux (r = 0.47, p = 0.0002). An inverse correlation of the reflux pressure-volume index and reflux volume was significant (r = -0.49, p = 0.0002) as was the correlation between bladder volume at reflux and amount of reflux (r = -0.47, p = 0.0003). The reflux pressure-volume index for patients with persistent reflux at followup (median 1.89) was significantly smaller than that for those without reflux (median = 8.71, p = 0.02). A difference existed in normalized bladder volume at reflux between resolved and persistent reflux (p = 0.003). No difference was detected with respect to reflux volume and resolution (p = 0.738).A nuclear cystometrogram is no more invasive than a standard cystogram and permits determination of bladder pressure at the onset of reflux. Factors such as reflux pressure and bladder volume at reflux provide additional characterization of the ureterovesical junction and may help determine the prognosis for reflux resolution.

The purpose of this study was to determine whether there is evidence for hepatocellular radiation injury following treatment with (90)Y-SMT487 ((90)Y-DOTA-tyr3-octreotide, OctreoTher(TM)) in patients with extensive liver metastases from neuroendocrine tumors. Patients reported in this study participated in a Phase II trial of efficacy and safety of (90)Y-SMT487. The trial design called for three treatment cycles of 120 mCi each (4400 MBq) of (90)Y-SMT487. (111)In-pentetreotide SPECT images were used to determine the extent of liver metastases. Serum AST, ALT, and alkaline phosphatase levels were obtained at baseline and following each cycle of therapy. Least squares fit was applied to the serial liver enzyme measurements in patients with extensive liver metastases. Post-therapy liver enzyme measurements were also evaluated using WHO common toxicity criteria. Repeated-measures ANOVA and paired t-test were applied to the serial enzyme measures. There were 21 subjects. Fifteen of these had hepatic metastases with 12 demonstrating extensive (defined as 25% or more) liver involvement. In only 4 of these 15 did any of the three enzyme levels increase in WHO toxicity grade from baseline to final follow-up. We conclude that patients with diffuse SSTR positive hepatic metastases can be treated with a cumulative administered activity of 360 mCi (90)Y-SMT487 with only a small chance of developing mild acute or subacute hepatic radiation injury.

Purpose: Securing two intravenous lines, one for injection and one for blood sampling, can be nearly impossible in compromised patients, therefore, a need exists to quantify the potential error when simplified techniques are employed. Method: Two venous catheters were placed. 2-deoxy-2-[18F]fluoro-glucose (FDG) was infused through one of the catheters. Venous blood samples were drawn from each line. Triplicate aliquots of plasma were analyzed in duplicate. Results: Concentrations from the infusion line were 2.0% higher than the concentrations from the noninfusion line. The average error was 3.3%, 2.0%, and 0.7% higher for the first, second, and third samples, respectively. Conclusions: Blood sampling through the infusion catheter is a viable alternative to the placement of separate venous catheters. Sampling from the injection catheter, even with tubing flush and replacement, will potentially incur small (generally < 10%) overestimations in concentration in initial samples. Subsequent sampling reduces the error to essentially zero by the third sample.

Bone scintigraphy (BS) is widely utilized for the assessment of bone metastases (BMs) of neuroblastoma (NB). Since 111 In-pentetreotide scintigraphy (PS) has been used to image NB with high sensitivity, we compared the sensitivity and specificity of PS with that of BS for the detection of BMs of NB. Nine patients with NB underwent both PS and BS for staging and/or restaging of their disease. The sensitivity and specificity of both imaging approaches were compared based on the findings of histopathology, other conventional imaging methods and subsequent clinical follow-up. In five of the nine patients, both PS and BS were negative for BMs. Radiographic bone surveys (RBSs) were also negative in these patients, except in one who showed a suspicious tibial lesion, but a computed tomography-guided biopsy failed to show evidence of disease. These patients remained without clinical evidence of BMs after a median duration of more than 15 months (range, 6-19 months). In three of four remaining patients, both PS and BS were positive for BMs, whilst only PS was positive in one patient. Overall, PS showed a greater number of BMs (30 vs. 7) with greater conspicuity compared with BS. The initial experience comparing BS with PS suggests that PS may provide a better assessment of the extent of BMs of NB, and that it may be useful as an adjunct to BS at institutions in which 131 I- or 123 I-metaiodobenzylguanidine is not available, particularly if BS is negative. In patients with similarly positive BS, PS might still provide unique prognostic information beyond that provided by BS. Further studies are therefore warranted.

Vitamin A deficiency (VAD) remains an important health problem among children in developing countries. Children living in these areas have a higher mortality from respiratory infections, which likely results in part from suboptimal nutrition, including VAD. Bronchial hyperreactivity can follow viral respiratory infections and may complicate the recovery. To investigate whether VAD promotes bronchial hyperreactivity, we have assessed methacholine-induced bronchoconstriction in VAD and vitamin A-sufficient rats. Bronchial constriction developed at lower concentrations of inhaled methacholine in VAD than in vitamin A-sufficient rats. This did not result from an increase in the bronchial wall thickness or the clearance of a small molecule (with a size similar to methacholine) from the air space. The function and abundance of the muscarinic M2 receptors in bronchial tissue were reduced in VAD rats, suggesting that this receptor may contribute to these animals' diminished ability to limit cholinergic-mediated bronchoconstriction. A similar reduction in muscarinic M2 receptor function has been observed in asthma. Vitamin A (retinol) and its congeners (retinoids) may be required to regulate bronchial responsiveness in addition to maintaining a normal bronchial epithelium.

Background . Few fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) nonsmall cell lung cancer (NSCLC) trials have had sufficient patients to adequately evaluate PET for mediastinal staging. We question whether once PET is performed, is mediastinoscopy necessary? Methods . We performed a 5-year retrospective analysis of operable patients with known or suspicious NSCLC. Standard PET techniques were used. Inclusion criteria were (1) surgical mediastinal nodal sampling by mediastinoscopy within 31 days of the PET and (2) definitive diagnosis. Results . There were 237 patients who met the evaluation criteria; ninety-nine patients with NSCLC and 138 with suspicious lesions (137 men and 100 women; aged 20 to 88 years). The PETs were performed from 0 to 29 days before mediastinoscopy (median, 7 days). The standardized uptake value for the primary lesion was 0 to 24.6 (7.9 ± 5.0). Nine primary lesions had no FDG uptake (1 benign, 8 NSCLCs). Seventy-one patients (31%) had mediastinal PET positive disease, and 44 patients (19%) had histologic positive mediastinal disease; N 2 41 patients (17%) and N 3 9 patients (4%). In 6 patients (3%), the initial frozen sections were negative, but PET positivity encouraged further biopsies that were positive for cancer. The PET sensitivity was 82%, specificity 82%, accuracy 82%, negative predictive value 95%, and positive predictive value was 51%. All primary lesions with a standardized uptake value less than 2.5 and a negative mediastinal PET were negative histologically (n = 29). Logistic regression analysis resulted in 100% specificity for PET in this group. Conclusions . In NSCLC PET may reduce the necessity for mediastinoscopy when the primary lesion standardized uptake value is less than 2.5 and the mediastinum is PET negative. Accepting this approach in our patient population, the need for mediastinoscopy would have been reduced by 12%.

Our goal was to ascertain how fatigue affects performance in reading computed tomography (CT) examinations of patients with multiple injuries. CT images with multiple fractures from a previous study of satisfaction of search (SOS) were read by radiologists after a day of clinical work. Performance in this study with fatigued readers was compared to a previous study in which readers were not fatigued. Detection accuracy for obvious injuries was not affected by fatigue, but accuracy for subtle fractures was reduced ([Formula: see text]). An SOS effect on decision thresholds was evident mirroring recent studies. Without fatigue, readers spent more time interpreting and reporting findings as the number of the injuries increased. When fatigued, readers did not increase reading time as fracture number increased. Without fractures, reading time for not-fatigued and fatigued readers was the same ([Formula: see text]) but was significant ([Formula: see text]) with an added subtle fracture. The difference increased with a major injury ([Formula: see text]) and increased further with both a major injury and subtle fracture ([Formula: see text]). Fatigue and multiple abnormalities have independent effects on detection performance but do interact in determining search time.

Background Peptide receptor radionuclide therapy (PRRT) is an effective form of treatment for patients with metastatic neuroendocrine tumors (NETs). However, delivering sufficient radiation dose to the tumor to result in a high percentage of long-term tumor remissions remains challenging because of the limits imposed on administered activity levels by radiation damage to normal tissues. The goal of this study was to evaluate the dosimetric advantages of adding 131I meta-iodobenzylguanidine (131I-MIBG) to 90Y DOTA Phe1-Tyr3-octreotide (90Y-DOTATOC) in patients with advanced stage midgut NETs. Methods Ten patients were imaged simultaneously with 131I-MIBG and 111In-pentetreotide (as a surrogate for 90Y-DOTATOC) on days 1, 2, and 3 post-administration. Blood samples were obtained at the same time points. Using dosimetry measures from this data and our previously published methodology for calculating optimal combined administered activity levels for therapy, we determined the amount of 131I-MIBG that could be added to 90Y-DOTATOC without exceeding normal organ dose limits (marrow and kidneys) along with the expected increase in associated tumor dose, if any. Results We found that a median value of 34.6 GBq of 131I-MIBG could be safely added to 90Y-DOTATOC (delivered over multiple cycles) by reducing the maximum total deliverable 90Y-DOTATOC by a median value of 24.5%. Taking this treatment approach, we found that there would be a median increase in deliverable tumor dose of 4,046 cGy in six of the ten subjects. Of note, there were a small number of metastases that were positive for only one or the other of these radiopharmaceuticals within the same subject. Conclusions We conclude that approximately half of the patients with midgut NETs that are eligible for PRRT could reasonably be expected to benefit from the addition of 131I-MIBG to 90Y-DOTATOC.

Objective Standard uptake values (SUVs) are widely used for quantifying the uptake of 18 F-fluorodeoxyglucose ( 18 F-FDG) in tumours. The objective of this study was to evaluate the accuracy of SUVs for malignancy in lung nodules/masses and to analyse the effects of tumour size, blood glucose levels and different body weight corrections on SUV. Methods One hundred and twenty-seven patients with suspicious lung lesions imaged with 18 F-FDG positron emission tomography (PET) were studied retrospectively. Pathology results were used to establish lesion diagnosis in all cases. SUVs based on maximum pixel values were obtained by placing regions of interest around the focus of abnormal 18 F-FDG uptake in the lungs. The SUVs were calculated using the following normalizations: body weight (BW), lean body weight (LBW), scaled body surface area (BSA), blood glucose level (Glu) and tumour size (Tsize). Receivers operating characteristic (ROC) curves were generated to compare the accuracy of different methods of SUV calculation. Results The areas under the ROC curves for SUV BW , SUV BW+Glu , SUV LBW , SUV LBW+Glu , SUV BSA , SUV BSA+Glu and SUV BW+Tsize were 0.915, 0.912, 0.911, 0.912, 0.916, 0.909 and 0.864, respectively. Conclusion The accuracy of SUV analysis for malignancy in lung nodules/masses is not improved by correction for blood glucose or tumour size or by normalizing for body surface area or lean body weight instead of body weight.

Although standardized uptake values (SUV) are widely used to quantify the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours, there are systematic differences in the way this index is applied by different investigators. The aims of this study were to compare the effects of using maximum or mean region counts in the calculation of SUV and to investigate an alternative technique based on a fixed fraction of the maximum counts. Simulated PET projections of the thorax were generated together with spherical lesions that varied in diameter from 1.6 to 4.8 cm with uptake values of 2, 4 and 8. The lesion SUVs were determined using either the maximum (SUVmax) or mean count (SUVmean) values found in regions circumscribing the lesion. In addition, average values were calculated that only included region pixels that exceeded a selected fraction of maximum value (SUV0.6max or SUV0.75max). These methods were also applied to six clinical 18F-FDG PET studies with a total of 12 lesions. The SUVs for these lesions were determined independently by four observers. Decreases with respect to SUVmax of 57%, 23% and 14% were found for SUVmean, SUV0.6max and SUV0.75max approaches respectively in the simulation study. The variation in SUVmean with region size was 35%, while the SUV0.6max and SUV0.75max was less than 3%. Similar results were obtained for the clinical data. We conclude that the proposed technique produces SUVs that are essentially independent of lesion region size and shape. It is expected that this will provide a more stable and reliable result than current approaches.

Rationale and Objectives. It is often difficult to classify information in medical images from derived features. The purpose of this research was to investigate the use of evolutionary programming as a tool for selecting important features and generating algorithms to classify computed tomographic (CT) images of the lung. Materials and Methods. Training and test sets consisting of 11 features derived from multiple lung CT images were generated, along with an indicator of the target area from which features originated. The images included five parameters based on histogram analysis, 11 parameters based on run length and co-occurrence matrix measures, and the fractal dimension. Two classification experiments were performed. In the first, the classification task was to distinguish between the subtle but known differences between anterior and posterior portions of transverse lung CT sections. The second classification task was to distinguish normal lung CT images from emphysematous images. The performance of the evolutionary programming approach was compared with that of three statistical classifiers that used the same training and test sets. Results. Evolutionary programming produced solutions that compared favorably with those of the statistical classifiers. In separating the anterior from the posterior lung sections, the evolutionary programming results were better than two of the three statistical approaches. The evolutionary programming approach correctly identified all the normal and abnormal lung images and accomplished this by using less features than the best statistical method. Conclusion. The results of this study demonstrate the utility of evolutionary programming as a tool for developing classification algorithms.

Following androgen ablation therapy, skeletal metastases from prostate cancer appear in some instances to show an increase in 99 Tc m -methylene diphosphonate ( 99 Tc m -MDP) uptake. Such a phenomenon could represent a mechanism to increase delivery of bone-seeking therapeutic agents to skeletal metastatic sites. The aim of this study was to characterize more precisely the potential increase in 99 Tc m -MDP in skeletal metastases from prostate cancer following initiation of hormone therapy. Baseline bone scans were performed within 1 week of onset of hormone therapy in patients with stage D2 prostate cancer followed by multiple repeat bone scans for up to 4-6 weeks. The count density within metastatic lesions was divided by the average count density from several areas of normal bone to obtain a lesion to normal bone uptake ratio (L/N) for each lesion in each scan. Altogether, 61 skeletal metastases were identified on bone scans from five subjects. Eighty-four percent (51/61) of these lesions showed an increase in 99 Tc m -MDP activity relative to normal bone following initiation of hormone therapy with a mean peak increase of 39%. Thirty-nine of these 51 metastatic lesions showed maximum uptake at 3 weeks post-onset of hormone treatment. From our findings, it appears that approximately 3 weeks following initiation of hormone blockade, most skeletal metastases from prostate cancer will demonstrate significantly enhanced 99Tcm uptake relative to normal bone. Consequently, it may be possible to improve the uptake and effectiveness of therapeutic bone-seeking radiopharmaceuticals by administering these agents following hormone therapy in patients with prostate cancer metastases.

Nuclear medicine is a medical field where radioactive materials are administered to patients to either obtain diagnostic information or deliver a therapeutic radiation dose. Although the therapeutic application of nuclear medicine is primarily limited to the treatment for hyperthyroid conditions and several cancers (e.g., thyroid cancer, lymphoma, and bone metastases palliation), there are diagnostic nuclear medicine procedures for virtually every tissue and organ system of the body. Table 11.1 summarizes common nuclear medicine procedures. Table 11.1 Example nuclear medicine procedures Procedures Indication Radiopharmaceutical Brain perfusion Stroke and epilepsy Tc-99 m HMPAO, Tc-99 m ECD, F-18 FDG*(PET) Thyroid scan Graves disease, thyroid cancer I-123 NaI, Tc-99 m pertechnetate Bone scintigraphy Metastatic cancer, hairline fractures Tc-99 m MDP Myocardial perfusion Coronary artery disease Tc-99 m sestamibi, Tc- 99 m tetrofosmin, Tl- 201 chloride, Rb-82 chloride (PET) Lung ventilation/perfusion Pulmonary embolism Tc-99 m DTPA aerosol, Tc-99 m MAAA Hepatobiliary function Acute cholecystitis, common bile duct obstruction Tc-99 m mebrofenin Renal function Renal obstruction, acute tubular necrosis Tc-99 m MAG3, Tc- 99 m DTPA GI bleeding Identify sites of active bleeding Tc-99 m labeled red blood cells Gastric emptying Gastroparesis, gastroesophageal reflux Tc-99 m sulfur colloid Lymphoscintigraphy Sentinel node location for melanoma and breast cancer Tc-99 m sulfur colloid PET whole-body Imaging Lung, colon, breast, thyroid cancer F-18 FDG* *(fluorodeoxyglucose)

Purpose The satisfaction-of-search (SOS) effect occurs when an abnormality on an image is missed because another is found. The aim of this experiment was to test whether severe distracting fractures control the magnitude of SOS on other fractures when both appear in a single CT image. Methods The institutional review board approved this study. The experimental (SOS) condition included 35 cervical spine CT cases, all of which contained severe cervical spine injuries. For each of these cases, a similar case was found that had no injuries. Image modification software was developed to add simulated fractures to each pair of cases, with and without a major injury. Sixteen different minor fractures were added to 16 of the 35 pairs of images. The 35 cases without native injuries constituted a control (non-SOS) condition mixed in a random order. Twenty radiologists read 35 mixed cases in each of two sessions. False-positive evaluations were collected only for cases without simulated fractures. Results An SOS effect on the detection of simulated fractures was not observed. There was a nonsignificant ( P = .07) finding of poorer detection in the presence of cases with severe injuries. However, the magnitude of the effect was no greater than has been observed for less severe distracting injuries. Conclusions The outcome agrees with the results of two previous experiments that failed to yield an SOS effect associated with detecting severe injuries, suggesting that the severity of a distracting injury does not determine whether a second injury is discovered.

Satisfaction of search (SOS) occurs wh en an abnormality is missed because another abnormality has been detected in radiology examinations. This research includes our study of whether the severity of a detected fracture determines whether subsequent fractures are overlooked. Each of 70 simulated multitrauma patients presented radiographs of three anatomic areas. Readers evaluated each patient under two experi mental conditions: when the images of the first anatomic area included a severe fracture (the SOS condition), and when it did not (the control condition). The SOS effect was measured on detection accuracy for subtle test fractures presented on examinations of the second or third anatomic areas. SOS reduction in ROC area for detecting subtle test fractures with the addition of a ma jor fracture to the first radiograph was not observed. The same absence of SOS that had been observed when high-morbidity added fractures were presented on CT was replicated with the high-morbidity added fractures presented on radiographs. This finding rules out the possibility that there was no SOS in the prior study with CT because SOS effects do not extend from one imaging modality to another. Taken together, the evidence rejects the hypothesis that the seve rity of a detected fracture determines the SOS for subs equently viewed fractures. Key Words . Diagnostic radiology; observer performance; images, interpretation; quality assurance.

This prospective study was designed to compare the sensitivity and specificity of a relatively simple examination, 201Tl chloride single-photon emission CT (SPECT), with a more complex examination, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), in patients thought to have recurrent brain tumor. Because both agents have been shown to be markers of viable tumor, we hypothesized that their sensitivity and specificity should be the same.Nineteen patients with evidence of recurrent tumor on CT or MR images were studied with both 201Tl SPECT and FDG PET imaging. Two patients were examined twice, so a total of 21 studies were evaluated. The 201Tl SPECT and FDG PET examinations were performed on the same day in 17 patients, and the remaining four examinations were done within 1 week of one another. Three reviewers independently interpreted each Tl SPECT and PET scan. Inappropriate regional increases in 201Tl or FDG activity were considered indicative of tumor recurrence. Sensitivity and specificity values were based on biopsy results and clinical follow-up. The final diagnosis was tumor recurrence in 16 cases and radiation necrosis in 5 cases. The relationship of scan results to survival was analyzed.The sensitivity and specificity of the 201Tl examination for detecting tumor recurrence were 11 (69%) of 16 and two (40%) of five, respectively; values for the FDG PET examination were 13 (81%) of 16 and 2 (40%) of 5, respectively. In patients with recurrent tumors less than 1.6 cm in size, results were false-negative in four 201Tl SPECT examinations and three FDG PET studies. All tumor lesions 1.6 cm or larger (n = 8) were detected. Agreement among the three nuclear medicine specialists was complete for each of the 201Tl SPECT scans. There was disagreement on the interpretation of five (24%) of the 21 FDG PET scans, which was resolved by consensus. Scintigraphic findings did not correlate with patients' survival times.We were unable to detect a statistically significant difference in sensitivity or specificity between the 201Tl SPECT and FDG PET scans. Both techniques were sensitive for tumor recurrence with lesions less than 1.6 cm or larger. However, given the greater availability, simplicity, and ease of interpretation and the lower cost of the 201Tl SPECT studies, this technique should be considered for detection of tumor recurrence with lesions that are demonstrated to be 1.6 cm or larger on CT or MR examinations.

Ten young normal adults had pelvic and lumbar vertebral body bone marrow blood flow examined using [15O]water and positron emission tomography (PET) in a study designed to assess the feasibility and reproducibility of the PET technique for measuring marrow blood flow to various marrow regions. The procedure was well tolerated. Repeated blood flow measurements obtained from two consecutive [15O]water exams on each individual subject were highly reproducible. In addition, there was minimal variation in marrow blood flow from individual to individual and no gender differences were noted. In contrast, mean+/-SD bone marrow blood flows (expressed as milliliters per minute per 100 g) at selected anatomical sites were significantly different and were as follows: lower lumbar vertebral bodies, 17.6+/-3.1; most posterior and superior pelvis (conventional site of percutaneous bone marrow biopsy), 14.3+/-3.1; and total superior pelvis, 11.1+/-2.0. We conclude that PET is a relatively noninvasive, simple, and reproducible technique for measuring bone marrow blood flow. Marrow blood flow is consistent between normal young subjects, but varies significantly between different anatomic regions of the marrow.

Purpose The aim of this experiment was to test whether radiographs of major injuries, those having serious consequences for life and limb, produce a satisfaction-of-search (SOS) effect on the detection of subtle, nondisplaced test fractures. Methods Institutional review board approval and informed consent from 24 participants were obtained. Seventy simulated patients with multiple trauma injuries were constructed from radiographs of 3 different anatomic areas demonstrated only skeletal injuries. Readers evaluated each patient under 2 conditions: first, in the non-SOS condition, no injuries were present in the first anatomic images, and second, in the SOS condition, the first anatomic images included major injuries requiring immediate medical intervention. The SOS effect was measured on detection accuracy using receiver operating characteristic analysis for subtle test fractures presented on examinations of the second or third anatomic areas. Results Satisfaction-of-search reduction in receiver operating characteristic experiments for detecting subtle test fractures with the addition of a major injury was not observed. Conclusions Satisfaction of search was absent when major injuries were presented on radiographs. This finding rejects the hypothesis that SOS arises primarily from injuries requiring major intervention. Similar results have been found previously when major injuries were presented on CT but test fractures were presented on radiographs. This new finding rejects the possibility that SOS is absent because added and test fractures appear on different imaging modalities.

Purpose A previous study demonstrated decreased diagnostic accuracy for finding fractures and decreased ability to focus on skeletal radiographs after a long working day. Skeletal radiographic examinations commonly have images that are displayed statically. The aim of this study was to investigate whether diagnostic accuracy for detecting pulmonary nodules on CT of the chest displayed dynamically would be similarly affected by fatigue. Methods Twenty-two radiologists and 22 residents were given 2 tests searching CT chest sequences for a solitary pulmonary nodule before and after a day of clinical reading. To measure search time, 10 lung CT sequences, each containing 20 consecutive sections and a single nodule, were inspected using free search and navigation. To measure diagnostic accuracy, 100 CT sequences, each with 20 sections and half with nodules, were displayed at preset scrolling speed and duration. Accuracy was measured using receiver operating characteristic curve analysis. Visual strain was measured via dark vergence, an indicator of the ability to keep the eyes focused on the display. Results Diagnostic accuracy was reduced after a day of clinical reading ( P = .0246), but search time was not affected ( P > .05). After a day of reading, dark vergence was significantly larger and more variable ( P = .0098), reflecting higher levels of visual strain, and subjective ratings of fatigue were also higher. Conclusions After their usual workday, radiologists experience increased fatigue and decreased diagnostic accuracy for detecting pulmonary nodules on CT. Effects of fatigue may be mitigated by active interaction with the display.

Collecting clinical cases for medical imaging perception studies is often challenging. We have developed a suite of software tools for manipulating medical tomographic image sets that overcome these difficulties. In our initial development, abnormalities were removed or inserted on a slice-by-slice basis. To circumvent the problem with potential artifacts in orthogonal views, we have redesigned the tools so that they operate in 3 dimensions. An operator controlled ellipsoid mask region is used to select the removal and the replacement areas. This new approach has been validated on PET data sets and has also been implemented for CT studies.

In human emission tomography, an additional transmission scan is often required to obtain accurate attenuation maps for attenuation correction (AC) and scatter correction (SC). These methods have been translated to small animal imaging, although the impact of photon interactions on the reconstruction of mouse/rat images is substantially less than that in human imaging. In this study, we evaluate the requirement of these corrections for PET small animal imaging through Monte Carlo simulations of the Inveon PET scanner using MOBY voxelized phantoms scaled to different sizes (2.1–6.4 cm diameters). The 3D data were reconstructed in 6 different conditions depending on the attenuation map used: Accurate AC+SC, Simple AC+SC, Accurate AC only, Simple AC only, SC only and No correction. Mean error% for 8 different ROIs and 6 different MOBY sizes were obtained against the accurate reconstruction (first on the list). In addition, real mouse data obtained from an Inveon PET scanner were analyzed using similar methods. The results from simulations and real mouse data showed that attenuation correction based on solely emission data should be sufficient for imaging animals smaller than 4 cm diameter.

The purpose of this study was to conduct a phase I trial of 90Y-DOTATOC to determine the dose-toxicity profile in children and young adults with somatostatin receptor–positive tumors. Methods: A 3 × 3 design was used to determine the highest tolerable dose of 90Y-DOTATOC, with administered activities of 1.11, 1.48, and 1.85 GBq/m2/cycle given in 3 cycles at 6-wk intervals. An amino acid infusion was coadministered with the radiopharmaceutical for renal protection. Eligibility criteria included an age of 2–25 y, progressive disease, a positive lesion on 111In-diethylenetriaminepentaacetic acid-D-Phe1-octreotide scanning, a glomerular filtration rate of 80 mL/min/1.73 m2 or more, bone marrow cellularity of 40% or more or stored autologous hematopoietic stem cells, 60% or more on the Lansky Play Scale, and informed consent. Results: Seventeen subjects (age, 2–24 y) received at least 1 dose of 90Y-DOTATOC; diagnoses included neuroblastoma, embryonal and astrocytic brain tumors, paraganglioma, multiple endocrine neoplasia IIB, and neuroendocrine tumors. No dose-limiting toxicities and no individual dose reductions due to renal or hematologic toxicity were noted. No complete responses were observed; 2 subjects experienced partial response, 5 had minor responses, 6 experienced stable disease, 2 had progressive disease, and 2 withdrew. Conclusion: Peptide receptor radionuclide therapy with 90Y-DOTATOC is safe in children and young adults and demonstrated a 12% partial response plus 29% minor response rate in patients with somatostatin receptor–positive tumors. No dose-limiting toxicities were observed. The recommended phase II dosing is 3 cycles of 1.85 GBq/m2/dose of 90Y-DOTATOC coadministered with amino acids.

A prototype SPECT (single photon emission computed tomography) system was constructed to demonstrate the performances of a novel multislice design for high-resolution imaging. The system consists of a stationary cylindrical detector composed of multiple bars of NaI(Tl) scintillator and a rotating collimator. The collimator consists of an assembly of multiholed modules arranged with a four quadrant symmetry. The collimator modules are individually focused for discrete sampling in the transverse plane but parallel-collimated for continuous sampling in the axial direction. Fan beam sampling for each detector bar in the transverse plane is accomplished after a 360 degrees rotation of the collimator. An array of photomultiplier tubes coupled to the outside of the detector cylinder identifies the bar and the axial position along the bar for each detected event. The current performance of this prototype system was evaluated. The useful imaging volume has a circular cross section (20-cm diameter) with a 5-cm axial field-of-view. The average local energy resolution is 11.5% and the system sensitivity is 800 cps/ mu Ci/cm/sup 3//cm. The spatial resolution in the reconstructed plane is 8 mm FWHM (full width at half maximum). The tomographic images of resolution and anthropomorphic phantoms demonstrate high image quality. >

In 2D-mode positron emission tomography (PET), scatter is either compensated by approximate methods based on the existing emission data or ignored altogether as the magnitude of the scatter fraction (SF) is within an acceptable range (10-20%). In clinical 3D PET studies, however, attenuation and sophisticated scatter correction methods are required along with CT or radionuclide transmission scans. With the growing interest in small animal imaging, these correction methods are being translated to small animal scanners, but there is little scientific information about the requirements associated with smaller size objects and scatter geometries. In this study, we focused on the magnitude of the scatter through a series of scatter fraction measurements. To determine the scatter as a function of object size, Monte Carlo simulations were performed using GATE (Geant4 application for emission tomography). Models of the ECAT HR+ PET scanner (included in the GATE package) and the Siemens Inveon small animal scanner (generated by the first author) were used. Simulations were performed for several digital phantoms including the NEMA, XCAT and MOBY phantoms over a wide range of sizes. The simulations on the Inveon scanner of the NEMA-like phantoms indicated that for cylindrical objects less than 4 cm diameters (encompassing small rats and all mice), the scatter fraction was lower than 15%. In addition, the scatter fraction values for MOBY phantoms up to 5 cm in diameter and 7.7 cm in length were also less than 15%. On the other hand, the scatter fraction was more than 25% for even the smallest size human NEMA-like and XCAT phantoms. These results suggest that sophisticated scatter correction methods may not be required for the indicated sizes of mice and rats.

The ability to insert abnormalities in clinical tomographic images makes image perception studies with medical images practical. We describe a new insertion technique and its experimental validati on that uses complementary image masks to select an abnormality from a library and place it at a desired location. The me thod was validated using a 4-alternative forced-choice experiment. For each case, four quadrants were simultaneously displayed consisting of 5 consecutive frames of a chest CT with a pulmonary nodule. One quadrant was unaltered, while the other 3 had the nodule from the unaltered quadrant artificially inserted. 26 different sets were generated and repeated with order scrambling for a total of 52 cases. The cases were viewed by radiology staff and resi dents who ranked each quadrant by realistic appearance. On average, the observers were able to co rrectly identify the unaltered quadrant in 42% of cases, and identify the unaltered quadrant both times it appeared in 25% of cases. Consensus, defined by a majority of readers, correctly identified the unaltered quadrant in only 29% of 52 cases. For repeats, the consensus observer successfully identified the unaltered quadrant only once. We conclude that the insertion method can be used to reliably place abnormalities in perception experiments. Keywords: Abnormality insertion, medical image perception, tomographic studies 1. INTRODUCTION Perception studies with actual medical images are difficult becau se of the lack of control of the images and because of the lack of truth data. Clinically normal images may contain a number of benign entities that could act as distractors and otherwise desirable target abnormalities may not be located in suitable locations. As a result, the collection of usable clinical cases for perception research is time cons uming and often requires making compromises. To circumvent these problems, we have developed software that allows the manipulation of images to remove or introduce

We developed image presentation software that mimics the functionality available in the clinic, but also records time-stamped, observer-display interactions and is readily deployable on diverse workstations making it possible to collect comparable observer data at multiple sites. Commercial image presentation software for clinical use has limited application for research on image perception, ergonomics, computer-aids and informatics because it does not collect observer responses, or other information on observer-display interactions, in real time. It is also very difficult to collect observer data from multiple institutions unless the same commercial software is available at different sites. Our software not only records observer reports of abnormalities and their locations, but also inspection time until report, inspection time for each computed radiograph and for each slice of tomographic studies, window/level, and magnification settings used by the observer. The software is a modified version of the open source ImageJ software available from the National Institutes of Health. Our software involves changes to the base code and extensive new plugin code. Our free software is currently capable of displaying computed tomography and computed radiography images. The software is packaged as Java class files and can be used on Windows, Linux, or Mac systems. By deploying our software together with experiment-specific script files that administer experimental procedures and image file handling, multi-institutional studies can be conducted that increase reader and/or case sample sizes or add experimental conditions.