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

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

Positron emission tomography instrumentation.

Positron emission tomography scanning has evolved over the past 40 years from a tool used predominantly for research to a valued clinical imaging modality. Current PET scanners must perform high-quality whole-body PET and brain PET. There are several levels of PET devices from the dedicated, high-end scanners down to the hybrid PET-SPECT systems offering varying levels of performance. The next generation of PET scanners will most likely involve the use of new scintillating materials. There is also a growing interest in dedicated devices for specific applications, such as high-resolution scanners for imaging small animals.

Emission tuned-aperture computed tomography: a novel approach to scintimammography.

UNLABELLED: Emission tuned-aperture computed tomography (ETACT) is a new approach to acquiring and processing scintimammography data. A gamma camera with a pinhole collimator is used to acquire projections of the radionuclide distribution within the breast. Fiducial markers are used to reconstruct these projections into tomographic slices. Simulation and phantom experiments were performed to evaluate the potential of the ETACT method. METHODS: In the simulation study, a hemispheric object of 15 cm in diameter was constructed to model a breast. A ray-tracing technique was used to generate ideal projections. These were blurred and noise was added to create images that resemble scintigraphic images. Tumor size, pinhole size, and target-to-nontarget radioactivity ratios (TNTs) were varied. The simulated projections were reconstructed into slices, and contrast and contrast-to-noise ratios were calculated to evaluate the effect of pinhole size. These results were compared with a simulated planar acquisition of the same object. A preliminary phantom evaluation was performed using an 8-mm "tumor" with a 10:1 TNT to validate the simulation results. RESULTS: A 3-mm pinhole was shown by the simulation study to be the optimal size. The ETACT images consistently yielded higher contrast than simulated planar images. The phantom study validated the simulation results and showed the feasibility of ETACT in a simulated clinical environment. CONCLUSION: ETACT is shown to be useful for imaging tumors <1 cm in diameter. Because ETACT requires only a gamma camera with a pinhole collimator, it has the potential to be applied in any hospital in a simple, flexible, and practical manner.

Reduced regional and global cerebral blood flow during fenoldopam-induced hypotension in volunteers.

UNLABELLED: Dopamine has a wide spectrum of receptor and pharmacologic actions that may affect cerebral blood flow (CBF). A new, selective dopamine-1 agonist, fenoldopam, is a potent systemic vasodilator with moderate alpha(2)-receptor affinity. However, the effects of fenoldopam on the cerebral circulation are undefined. We therefore hypothesized that infusion of fenoldopam would decrease mean arterial blood pressure (MAP) and might concurrently decrease CBF via vascular alpha(2)-adrenoreceptor activation in awake volunteers. We studied nine healthy normotensive subjects, using positron emission tomography to measure CBF in multiple cortical and subcortical regions of interest. In addition, bioimpedance cardiac output and middle cerebral artery blood flow velocity were determined during fenoldopam-induced hypotension. Three men and four women, aged 25-43 yr, completed the study. Fenoldopam infused at 1.3 +/- 0.4 microg. kg(-1). min(-1) (mean +/- SD) reduced MAP 16% from baseline: from 94 (89-100) mm Hg (mean [95% confidence interval]) to 79 [74-85] mm Hg (P < 0.0001). During the fenoldopam infusion, both cardiac output (+39%), and heart rate (+45%) increased significantly, whereas global CBF decreased from baseline, 45.6 [35.6-58.5] mL. 100 g(-1). min(-1), to 37.7 [33.9-42.0] mL. 100 g(-1). min(-1) (P < 0.0001). Despite restoration of baseline MAP with a concurrent infusion of phenylephrine, global CBF remained decreased relative to baseline values at 37.9 [34.0-42.3] mL. 100 gm(-1). min(-1) (P < 0.0001). Changes in middle cerebral artery velocity did not correlate with positron emission tomography-measured changes of CBF induced by fenoldopam, with or without concurrent phenylephrine. IMPLICATIONS: In awake volunteers with (presumably) intact cerebral autoregulation,fenoldopam-induced hypotension significantly decreased global cerebral bloodflow (CBF). Clinicians should be aware of these pharmacodynamic effects when choosing a vasodilator to control blood pressure, especially in situations where control of CBF, cerebral blood volume, and intracranial pressure are therapeutic priorities.

Cortical activity related to accuracy of letter recognition.

Previous imaging and neurophysiological studies have suggested that the posterior inferior temporal region participates in tasks requiring the recognition of objects, including faces, words, and letters; however, the relationship between accuracy of recognition and activity in that region has not been systematically investigated. In this study, positron emission tomography was used to estimate glucose metabolism in 60 normal adults performing a computer-generated letter-recognition task. Both a region of interest and a voxel-based method of analysis, with subject state and trait variables statistically controlled, found task accuracy to be: (1) negatively related to metabolism in the left ventrolateral inferior temporal occipital cortex (Brodmann's area 37, or ventrolateral BA 37) and (2) positively related to metabolism in a region of the right ventrolateral frontal cortex (Brodmann's areas 47 and 11, or right BA 47/11). Left ventrolateral BA 37 was significantly related both to hits and to false alarms, whereas the right BA 47/11 finding was related only to false alarms. The results were taken as supporting an automaticity mechanism for left ventrolateral BA 37, whereby task accuracy was associated with automatic letter recognition and in turn to reduced metabolism in this extrastriate area. The right BA 47/11 finding was interpreted as reflecting a separate component of task accuracy, associated with selectivity of attention broadly and with inhibition of erroneous responding in particular. The findings are interpreted as supporting the need for control of variance due to subject and task variables, not only in correlational but also in subtraction designs.

Evaluation of brain activity in FDG PET studies.

PURPOSE: A tool (Gemini) was developed for quantifying regions of interest (ROIs) in registered MR and PET data. Its use was validated through phantom and simulated studies. METHOD: Hot spheres were imaged in a phantom (3:1 and 5:1 target-to-nontarget ratios). The computerized 3D Hoffman brain phantom was used to simulate PET studies. Spherical local activity features of two diameters (4 and 10 mm) and five intensities (5, 15, 25, 50, and 100% increase over gray matter) were added to the data in the thalamus and Brodmann area 37. The data were reprojected into sinograms and blurred with a 7 mm kernel. Poisson noise was added, and the sinograms were then reconstructed and analyzed using both SPM96 and Gemini spherical ROIs. RESULTS: Based on phantom and simulated data, the 95th percentile of intensity within a Gemini ROI afforded a reasonable joint optimization of variance (reliability) and accuracy (validity). SPM96 and Gemini results were similar for the larger (10 mm) feature, but in this application, Gemini was more sensitive than SPM96 for the small feature (4 mm). CONCLUSION: Gemini, a tool for display and measurement of spherical ROIs in registered PET and MR data, is precise and accurate for testing hypotheses of differences in localized brain activity, comparing favorably with SPM96.

Lag phase quantification for solid gastric emptying studies.

UNLABELLED: This study compared the different calculation methods of the solid gastric emptying lag phase and evaluated the effect of the temporal sampling interval on the calculated value using the modified power exponential (MPE) method. METHODS: Twenty normal control subjects and 42 patients had anterior and posterior image acquisition on a multihead gamma camera, one frame per minute x 90. ROIs were selected for the stomach, gastric antrum and small bowel. Time-activity curves (TACs) were generated for anterior, posterior and geometric mean data. The lag phase was calculated using various methods such as transition point, starting index, first appearance of bowel activity (FABA), MPE and antral peak filling time. To determine the importance of the temporal sampling rate on the calculation of the lag phase by the MPE, intervals between 1 and 20 min were analyzed. RESULTS: The transition point, starting index and FABA correlated extremely high (r = > or = 0.92) in normal control subjects and patients. Normal lag phase values were mean 22-24 +/- 10 min for transition point, starting index and FABA compared with 47 +/- 18 min for the MPE method (p < 0.0001). The MPE correlated poorly with the other method (r = 0.74). Antral peak filling time correlated poorly (r = 0.47) with transition point, starting index and FABA, but somewhat better with the MPE (r = 0.70). Comparing 15-min versus 1-min sampling intervals using the MPE, 35% of subjects had values that differed by > or = 7.5 min and 10% had values differing by > or = 15 min. CONCLUSION: The lag phase calculated by the MPE correlated poorly with other methods, and its accuracy was limited by the rate of the temporal sampling. The transition point, starting index and FABA all highly correlated with each other; the latter is a particularly reliable physiological indicator and is easily quantified using a small-bowel TAC.

Intermodality, retrospective image registration in the thorax.

UNLABELLED: The purpose of this study was to develop an accurate, retrospectively applicable procedure for registering thoracic studies from different modalities in a short amount of time and with minimal operator intervention. METHODS: CT and PET studies were acquired from six patients. The pleural surfaces in both image sets were determined by segmenting based on 50% of the maximum soft-tissue value in the study. These surfaces were converted into three-dimensional volumes and used to register the CT and PET studies in three dimensions using a sum of least squares fitting approach. The registered PET study was then displayed in a hot metal scale overlayed on top of the gray scale CT study. The accuracy of the fit was evaluated through a phantom study and preliminary clinical evaluation. RESULTS: A phantom study was performed to determine the limits of this technique. The accuracy was determined to be less than 2.3 mm in the x and y direction and 3 mm in the z direction. Preliminary clinical evaluation was also performed with encouraging results. CONCLUSION: This technique accurately registers PET and CT images of the thorax, retrospectively, without the need for external fiducial markers or other a priori action.

Quantitation of SPECT performance: Report of Task Group 4, Nuclear Medicine Committee.

A comprehensive performance testing program is an essential ingredient of high-quality single-photon emission computed tomography (SPECT). Many of the procedures previously published are complicated, time consuming, or require a special testing environment. This Task Group developed a protocol for evaluating SPECT imaging systems that was simple, practical, required minimal test equipment, and could be performed in a few hours using processing software available on all nuclear medicine computers. It was designed to test rotational stability of uniformity and sensitivity, tomographic spatial resolution, uniformity and contrast, and the accuracy of attenuation correction. It can be performed in less than three hours and requires only a Co-57 flood source, a line source, and a tomographic cylindrical phantom. The protocol was used 51 times on 42 different cameras (seven vendors) by four different individuals. The results were used to establish acceptable ranges for the measured parameters. The variation between vendors was relatively small and appeared to reflect slight differences in basic camera performance, collimation, and reconstruction software. Individuals can use the tabulated values to evaluate the performance of individual systems.

Evaluation of emission-transmission registration in thoracic PET.

UNLABELLED: The intent of this investigation was to quantitate the amount of misregistration between PET emission and transmission scans of the thorax that occurs in a normal clinical environment. METHODS: The data from 17 FDG myocardial studies were evaluated. Prior to injection, a transmission study was acquired for 15 min using a 68Ge/68Ga ring source. The location of the cross-hairs from a laser alignment system was marked on the patient who was then removed from the scanner and injected with 10 mCi of FDG. After 45 min, the patient was placed back on the table and repositioned with the previously placed marks and a 15-min emission scan was acquired. The outline of the lungs on both the transmission and emission images was manually segmented. Both attenuation-corrected and noncorrected emission images were evaluated and the one that provided clearer visualization of the outline of the lungs was chosen for segmentation. The segmented contours of the transmission and emission scans were then registered with the method described by Pelizzari et al. using the transmission image as the "head" and the emission image as the "hat." The allowable transformations were x and y shifts and rotation in the transverse plane. RESULTS: Shifts in the x-axis averaged 2.4 mm (range: 0.2-7.3 mm, 80% less than 3.3 mm) with shifts in the y-axis averaging 2.6 mm (range: 0.1-8.7 mm, 80% less than 2.4 mm) and rotations in the transverse plane averaging 1.6 degrees (range: 0.2 to 5.1 degrees, 80% less than 2.4 degrees). A phantom study indicated that the accuracy of this method of evaluating misregistration was 2.35 mm and 1.81 mm in the x and y directions, respectively. CONCLUSION: Our preliminary evaluation indicates that careful application of laser alignment is an adequate method of registration in most cases.

Sensitivity, resolution and image quality with a multi-head SPECT camera.

This investigation sought to determine which collimation factors were most important in providing superior image quality with a three-headed SPECT device. The relationship between sensitivity, resolution and SPECT image quality was studied. Two different sets of parallel-hole collimators were used. The ultrahigh-resolution collimators have higher spatial resolution (8.9 versus 11.0 mm), but only 55% of the sensitivity of the high-resolution collimators. A phantom with hot rods was imaged with both collimator sets. Observers compared images with the ultrahigh-resolution collimators to images of varying counts with the high-resolution collimators and determined which high-resolution images matched the ultrahigh-resolution images in image quality. Eleven patient studies were acquired with both collimator sets for equal time, and observers chose which image set they preferred. Transverse images of brain and liver studies were simulated with varying resolution and counts and subjectively compared. The phantom study indicated that the improvement in resolution led to image quality comparable to increasing the number of counts by a factor of 2.5 to 3.4. The clinical studies showed that the ultrahigh-resolution collimators were preferred in a large majority of the cases. These trends were also seen in the simulation study. These results confirm that higher resolution collimators should be used with multihead SPECT devices. The improvement in resolution more than compensates for the loss in sensitivity, leading to an overall improvement in image quality.

Biphasic solid and liquid gastric emptying in normal controls and diabetics using continuous acquisition in LAO view.

The purpose of this study was to investigate the various phases of gastric emptying using a dual-isotope liquid-solid meal ([99mTc]SC egg sandwich and [111In]DPTA in water) and continuous acquisition in the left anterior oblique view. The study groups consisted of 10 normal controls and 20 diabetics with symptoms suggestive of diabetic gastroparesis. Solid-phase emptying in both groups almost always had a lag phase followed by linear emptying. Liquid-phase emptying was biexponential in 4/10 normals and 12/20 diabetics, with a short early rapid emptying rate (mean T1/2 = 48 min in normals and 79 min in diabetics). Solid emptying was delayed in 10, normal in eight, and rapid in two diabetics. Liquid emptying was delayed in 9/10 diabetics who had delayed solid emptying. Diabetics as a group had a significantly delayed solid lag phase (P less than 0.025), rate of emptying (P less than 0.05) and percent emptying at 90 min (P less than 0.025) compared to normal controls. Diabetic liquid emptying was also significantly delayed (P less than 0.025). The second component of liquid emptying strongly correlated with the solid rate of emptying (r = 0.826 in normals and 0.855 in diabetics). Continuous acquisition of gastric emptying studies in the LAO view has allowed us to better define the various phases of solid and liquid gastric emptying.

Calculation of a gallbladder ejection fraction: advantage of continuous sincalide infusion over the three-minute infusion method.

The purpose of this study was to investigate alternative methods of infusing sincalide for calculation of a gallbladder ejection fraction (GBEF) during cholescintigraphy (5 mCi 99mTc-mebrofenin). After gallbladder filling, three methods of infusion were compared in 23 normal volunteers: (1) 0.02 microgram/kg as a 3-min infusion, (2) 0.02 microgram/kg as a 30-min infusion, and (3) 0.01 microgram/kg as a 30-min infusion (14 subjects), all performed on separate days. With the 3-min infusion, the emptying pattern was usually exponential and completed in 15 min. The mean (GBEF) was 52% +/- 26% at 20 min and 56% +/- 27% at 30 min (range 0%-100%). GBEFs were less than 35% in six subjects and 35%-38% in four. Side effects were noted by 11/23 subjects. With the slow infusions, emptying was linear; no side effects were noted. With 0.02 microgram/kg, the mean GBEF was 50% +/- 27% at 20 min and 70% +/- 22% at 30 min (range 26%-95%). Similar results were seen with 0.01 microgram/kg, but the data were more limited. The 30-min infusion had a higher normalcy rate than the 3-min method (91% versus 74%). Females had significantly lower GBEFs than males (p less than 0.05%). We conclude that the slow infusion method is preferable; it is more physiological, results in more complete emptying, has no side effects, has less normal variability, and should improve the specificity of this test. The lower mean female GBEF may have pathophysiological significance.

3-D SPECT simulations of a complex 3-D mathematical brain model: effects of 3-D geometric detector response, attenuation, scatter, and statistical noise.

The quantitative imaging characteristics of ultrahigh-resolution parallel-hole SPECT, including 3-D geometric detector response, attenuation, scatter, and statistical noise, were investigated by simulations based on a complex digitized 3-D brain model of the gray and white matter distributions. The projection data resulting from a uniform distribution of gray and white matter radioactivity, in a ratio of 5:1, were simulated. The results demonstrate significant qualitative and quantitative artifacts in reconstructed human brain images. In the absence of attenuation, scatter, and noise, artifactual variation caused inaccuracies in regional radioactivity quantification. Inclusion of attenuation scatter, and noise in the simulation caused additional artifacts, and resulted in reconstructed images which qualitatively and quantitatively corresponded very closely to reconstructed images of the actual 3-D brain phantom which was constructed from the same set of data as the mathematical 3-D brain model. It is concluded that the major degrading factor in SPECT neuroimaging is the 3-D geometric detector response function.

Improved detection of small cavernous hemangiomas of the liver with high-resolution three-headed SPECT.

The purpose of this study was to review our experience with 99mTc-red blood cell scintigraphy for diagnosis of cavernous hemangiomas of the liver using a new three-headed, high-resolution dedicated SPECT system. Of 19 patients referred with a total of 38 lesions seen on CT, US, or MRI, 14 patients had 24 lesions that were hemangioma-positive with SPECT (all true-positives). Six of these 14 patients also had 9 hemangioma-negative lesions; all were less than or equal to 1.3 cm in size and false-negative. The remaining five patients had hemangioma-negative lesions only (1 false-negative, 4 true-negatives). Two hemangiomas were seen by SPECT that were not detected by CT, US, or MR. The sensitivity for hemangiomas greater than or equal to 1.4 cm. was 100% (20/20). The sensitivity was 33% for lesions 0.9-1.3 cm, and 20% for lesions less than or equal to 0.8 cm. The smallest hemangioma detected was 0.5 cm. These results show a definite improvement in sensitivity with high-resolution triple-headed SPECT over previously reported results using single-headed SPECT. High-resolution SPECT has improved our ability to detect small cavernous hemangiomas of the liver.

Three-dimensional SPECT simulations of a complex three-dimensional mathematical brain model and measurements of the three-dimensional physical brain phantom.

We have developed a three-dimensional computer simulation of SPECT imaging. We have applied the simulation procedure to the realistic mathematical Hoffman three-dimensional brain model to generate the projection data (in the absence of attenuation, scatter, or noise) of both a parallel-hole and a multidetector SPECT system with point-focusing collimators. The simulated projection data were then reconstructed using standard software. The projection data resulting from the distribution of grey matter alone, or grey and white matter, were simulated. The results of these simulations indicate the existence of significant qualitative and quantitative artifacts in reconstructed human brain images. For example, the reconstructed values for grey matter along a cortical circumferential profile in a transverse slice through the basal ganglia varied by a factor of 2.40 (parallel-hole) and 2.99 (point-focusing), although the original grey matter values were identical in all cortical regions in the model. We have compared the simulated reconstructed images with those obtained by imaging the physical three-dimensional Hoffman brain phantom, which was constructed based upon the same set of data from which the mathematical three-dimensional Hoffman brain model was derived. Although the simulation did not include all of the degrading factors present in the physical imaging, the two images were in good agreement, indicating the applicability of the simulation to a realistic situation and the importance of the detector resolution effect.

Digital image processing of radiation therapy portal films.

Digital image processing has the potential to enhance and improve several functions of a modern radiation oncology department. These functions may include improving perception of information for low contrast films, electronic transfer of images to remote facilities and back, and reducing storage space requirements for archiving once treatment is finished. This paper gives an overview of the digitization process and of image processing fundamentals. The clinical evaluation of digitized portal films is also discussed. The authors conclude that digitizing low contrast radiation therapy portal films is feasible with present technology and will produce images acceptable for routine clinical use in most instances. The role of image enhancement is less well established and remains investigational.

Left anterior oblique projection and peak-to-scatter ratio for attenuation compensation of gastric emptying studies.

Compensation for soft-tissue attenuation is necessary for accurate quantitation of nuclear gastric emptying studies. We sought an attenuation compensation method that would require the acquisition of images from a single projection, thus allowing for continuous dynamic acquisition. We investigated the use of the left anterior oblique (LAO) projection and the peak-to-scatter ratio (P/S) method. Phantom studies indicated that the P/S was not only a function of the amount of overlying attenuating material but also a function of the activity in the small intestine. Two models for the P/S method were developed, one that considered the activity in the small intestine and one that did not. A series of 27 patients (21 for solid gastric emptying and six for liquid gastric emptying) were studied comparing the results using the geometric mean (GM) method with the two P/S methods, the LAO and the uncorrected anterior (ANT) projection. The uncorrected ANT view for solid gastric emptying underestimated the percent emptying at 60 min by approximately 7%. The P/S method did not adequately compensate for attenuation. The use of the LAO projection yielded results that were highly correlated and unbiased when compared to the GM method. Accurate estimates of liquid gastric emptying can be obtained without attenuation compensation.

Characterization of the rotating display.

The rotating display is a useful method for reviewing single photon emission computed tomography (SPECT) data. This study evaluated the requirements for a subjectively pleasing and useful implementation of this technique. Twelve SPECT data sets were modified and viewed by several observers who recorded the minimum framing rates for apparent smooth rotation, 3D effect, effects of image size, and other parameters. The results showed that a minimum of 16 frames was needed for a useful display. Smaller image sizes and more frames were preferred. The recommended minimal framing rate for a 64-frame study is 16-17 frames per second and for a 32-frame study, 12-13 frames per second. Other enhancements also were useful.

Renal scans in pregnant transplant patients.

This study demonstrates the normal technetium-99m diethylenetriaminepentaacetic acid ([99mTc]DTPA) renal scan in pregnant patients with transplanted kidneys. Five pregnant renal transplant patients had seven [99mTc]DTPA renal studies to assess allograft perfusion and function. All scans showed the uteroplacental complex. The bladder was always compressed and distorted. The transplanted kidney was frequently rotated to a more vertical position. In all patients allograft flow and function were maintained. There was calyceal retention on all studies and ureteral retention activity in three of five patients. Using the MIRD formalism, the total radiation absorbed dose to the fetus was calculated to be 271 mrad. This radiation exposure is well within NRCP limits for the fetus of radiation workers and an acceptable low risk in the management of these high risk obstetric patients.