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Reliable attenuation correction methods for quantitative emission CT (ECT) require accurate delineation of the body contour and often necessitate knowledge of internal anatomic structure. Two broad classes of methods have been used to calculate the attenuation map: transmission-less and transmission-based attenuation correction techniques. Whereas calculated attenuation correction belonging to the first class of methods is appropriate for brain studies, more adequate methods must be performed in clinical applications, where the attenuation coefficient distribution is not known a priori, and for areas of inhomogeneous attenuation such as the chest. Measured attenuation correction overcomes this problem and uses different approaches to determine this map, including transmission scanning, segmented magnetic resonance images, or appropriately scaled CT scans acquired either independently on separate or simultaneously on multimodality imaging systems. Combination of data acquired from different imagers suffers from the usual problems of working with multimodality images--namely, accurate co-registration from the different modalities and assignment of attenuation coefficients. A current trend in ECT is to use transmission scanning to reconstruct the attenuation map. Combined ECT/CT imaging is an interesting approach; however, it considerably complicates both the scanner design and the data acquisition and processing protocols. Moreover, the cost of such systems may be prohibitive for small nuclear medicine departments. A dramatic simplification could be made if the attenuation map could be obtained directly from the emission projections, without the use of a transmission scan. This is being investigated either using a statistical model of emission data or applying the consistency conditions that allow one to identify the operator of the problem and, thus, to reconstruct the attenuation map. This article presents the physical and methodologic basis of attenuation correction and summarizes recent developments in algorithms used to compute the attenuation map in ECT. Other potential applications are also discussed.

Unlabelled: The purpose of our study was to determine the effect of tumor-targeted radiation in neuroblastoma by correlating administered (131)I-metaiodobenzylguanidine (MIBG) activity to tumor and whole-body dosimetry, tumor volume change, overall response, and hematologic toxicity., Methods: Eligible patients had MIBG-positive lesions and tumor-free, cryopreserved hematopoietic stem cells. Activity was administered according to body weight and protocol as part of a phase I and phase II study. The whole-body radiation dose was derived from daily 1-m exposure measurements, the tumor self-absorbed radiation dose (TSARD) was determined from scintillation-camera conjugate views, and the tumor volume was measured using CT or MRI., Results: Forty-two patients with refractory neuroblastoma (16 with prior hematopoietic stem cell transplant) received a median activity of 555 MBq/kg (15 mCi/kg) (range, 93-770 MBq/kg) and a median total activity of 11,470 MBq (310 mCi) (range, 3,330-30,969 MBq). The median whole-body radiation dose was 228 cGy (range, 57-650 cGy) and the median TSARD was 3,300 cGy (range, 312-30,500 cGy). Responses among evaluable patients included 16 partial response, 3 mixed response, 14 stable disease, and 9 progressive disease. Higher TSARD values predicted better overall disease response (P < 0.01). The median decrease in tumor volume was 19%; 18 tumors decreased, 4 remained stable, and 5 increased in size. Correlation was seen between administered activity per kilogram and whole-body dose as well as hematologic toxicity (assessed by blood platelet and neutrophil count nadir) (P < 0.05). The median whole-body dose was higher in the 11 patients who required hematopoietic stem cell infusion for prolonged neutropenia versus the 31 patients who did not (323 vs. 217 cGy; P = 0.03)., Conclusion: Despite inaccuracies inherent in dosimetry methods, (131)I-MIBG activity per kilogram correlated with whole-body radiation dose and hematologic toxicity. The TSARD by conjugate planar imaging predicted tumor volume decrease and also correlated with overall tumor response.

Unlabelled: We have evaluated a method for absolute in vivo quantification of 99mTc-sestamibi uptake in a porcine model of myocardial perfusion., Methods: Correlated CT and radionuclide images were obtained from eight adult pigs using a combined CT-SPECT imaging system. In each case, the CT image is used to generate an object-specific attenuation map that is incorporated into an iterative algorithm for reconstruction and attenuation correction of the radionuclide image. Anatomic information available from the correlated CT image is used to correct the radionuclide image for partial-volume errors by mathematically modeling the radionuclide imaging process. A volume of interest, or template, that approximates the geometric extent of the myocardium is defined from the CT image. Once defined, the template is assigned unit activity and is mathematically projected using a realistic physical model of the radionuclide imaging process including nonideal collimation and object-specific attenuation. The template is then reconstructed from these projections to obtain a pixel-by-pixel partial-volume correction for the myocardium in the radionuclide image. The CT image is also used to delimit the anatomic boundaries of the myocardium for quantification of the radionuclide images. The pixel intensities in the corrected radionuclide image are calibrated in units of activity concentration (MBq/g) and compared with the ex vivo activity concentration measured directly from the excised myocardium., Results: Without corrections, the measured in vivo activity concentration in the porcine myocardium was only 10% of the true value. Correcting for object-specific attenuation improved the accuracy of this measurement but resulted in values that were still only 42% of the true value. By correcting for both attenuation and partial-volume errors, we were able to achieve absolute quantification with an accuracy error near 10%., Conclusion: We have shown that, by applying object-specific attenuation corrections and suitable partial-volume corrections, absolute regional activity concentration can be measured accurately in the porcine myocardium.

Unlabelled: High-dose administration of 131I-metaiodobenzylguanidine (131I-MIBG) continues to be a promising treatment for neuroblastoma. However, currently used methods of estimating 131I-MIBG uptake in vivo may be too inaccurate to properly monitor patient radiation exposure doses. To improve localization and uptake measurements over currently practiced techniques, we evaluated different methodologies that take advantage of the correlated patient data available from a combined CT-scintillation camera imaging system., Methods: Serial CT and radionuclide scans of three patients were obtained on a combined imaging system. SPECT images were reconstructed using both filtered backprojection and maximum-likelihood expectation maximization (MLEM). Volumes of interest (VOIs) were defined on anatomic images and automatically correlated to spatial volumes in reconstructed SPECT images. Several radionuclide quantification methods were then compared. First, the mean reconstructed values within coregistered SPECT VOIs were estimated from MLEM reconstructed images. Next, we assumed that reconstructed activity in SPECT voxels were linear combinations of activities present in individual objects, weighted by geometric factors derived from CT images. After calculating the weight factors by modeling the SPECT imaging process with anatomically defined VOIs, least-squares fitting was used to estimate the activities within lesion volumes. We also estimated the lesion activities directly from planar radionuclide images of the patients using similar linearity assumptions. Finally, for comparison, lesion activities were estimated using a standard conjugate view method., Results: Activities were quantified from three patients having a total of six lesions with volumes ranging from 0.67 to 117 mL. Methods that used CT data to quantify lesion activities gave similar results for planar and tomographic radionuclide data. Estimating activity directly from mean VOI values in MLEM-reconstructed images alone consistently provided estimates lower than CT-aided methods because of the limited spatial resolution of SPECT. Values obtained with conjugate views produced differences up to fivefold in comparison with CT-aided methods., Conclusion: These results show that anatomic information available from coregistered CT images may improve in vivo localization and measurement of 131I-MIBG uptake in tumors.

Unlabelled: We have developed a software-based method for processing dual-energy 201TI SPECT emission projection data with the goal of calculating a spatially dependent index of the local impact of gamma-ray attenuation. We refer to this method as intrinsic dual-energy processing (IDEP)., Methods: IDEP exploits the differential attenuation of lower energy emissions (69-83 keV) and higher energy emissions (167 keV) resulting from the decay of 201TI to characterize the relative degree of low-energy gamma-ray attenuation throughout the myocardium. In particular, IDEP can be used to estimate the relative probability that a low-energy gamma-ray emitted from a particular region of the myocardium is detected during the acquisition of SPECT projection data. Studies on phantoms and healthy human volunteers were performed to determine whether the IDEP method yielded detection probability images with systematic structure visible above the noise of these images and whether the systematic structure in the detection probability images could be rationalized physically. In patient studies, the relative regional detection probabilities were applied qualitatively to determine the likely effects of attenuation on the distribution of mapped photon emissions., Results: Measurements of the detection probability in uniform phantoms showed excellent agreement with those obtained from computer simulations for both 180 degrees and 360 degrees acquisitions. Additional simulations with digital phantoms showed good correlation between IDEP-estimated detection probabilities and calculated detection probabilities. In patient studies, the IDEP-derived detection probability maps showed qualitative agreement with known nonuniform attenuation characteristics of the human thorax. When IDEP data were integrated with the findings on the emission scan, the correlation with coronary anatomy (known in 6 patients and hypothesized on the basis of clinical and electrocardiographic parameters in 5 patients) was improved compared with evaluating the mapped emission image alone., Conclusion: The IDEP method has the potential to characterize the attenuation properties of an object without use of a separate transmission scan. Coupled with the emission data, it may aid coronary diagnosis.

Background: Metaiodobenzylguanidine (MIBG) labeled with 131I has been used for targeted radiotherapy of neural crest tumors, with bone marrow suppression being the primary dose-limiting toxicity. The purpose of this study was to examine the engraftment and toxicity of higher myeloablative doses of 131I-MIBG with autologous bone marrow support., Procedure: Twelve patients with refractory neuroblastoma were given infusions of their autologous, cryopreserved bone marrow following 1-4 doses of 131I-MIBG. The median cumulative administered activity per kilogram of 131I-MIBG was 18.0 mCi/kg (range 14.1-50.2 mCi/kg), the median total activity was 594 mCi (range 195-1,353 mCi), and the median cumulative whole body irradiation from 131I-MIBG was 426 cGy (range 256-800 cGy). A median of 2.5 x 10(8) viable cells/kg (range 0.9-4.7 x 10(8) cells/kg) was given in the bone marrow infusion., Results: All 12 patients achieved an absolute neutrophil count > 500/microliter with a median of 19 days, but only 5/11 evaluable patients achieved red cell transfusion independence, in a median of 44 days; and 4/11 evaluable patients achieved platelet count > 20,000/microliter without transfusion, in a median of 27 days., Conclusions: Autologous bone marrow transplantation may allow complete hematopoietic reconstitution following ablative 131I-MIBG radiotherapy in patients with neuroblastoma. Risk factors for lack of red cell or platelet recovery include extensive prior chemotherapy, progressive disease at the time of transplant, especially in the bone marrow, and a history of prior myeloablative therapy with stem cell support.

Unlabelled: This study compared attenuation compensated, myocardial SPECT images reconstructed from 180 degrees and 360 degrees data to determine if either data acquisition method might yield improved image quality. Specifically, this study analyzed how the use of either 180 degrees or 360 degrees data affects: (a) the relative count density distribution, (b) defect contrast and (c) level of statistical noise in the left ventricular (LV) wall in the reconstructed SPECT images., Methods: Using the three-dimensional MCAT phantom simulating 201Tl uptake in the upper torso and the SIMSET Monte Carlo code, noise-free projection datasets for both 180 degrees (45 degrees LPO to 45 degrees RAO) and 360 degrees acquisition were generated with the effects of nonuniform attenuation, collimator-detector response and scatter. In addition, low-noise experimental phantom data were acquired over 180 degrees and 360 degrees. Assuming the same total acquisition time, four sets of noisy projection data were simulated from scaled noise-free, simulated data for the following acquisitions: (a) 180 degrees and (b) 360 degrees data acquired on a 90 degrees dual-detector system and (c) 180 degrees and (d) 360 degrees data acquired on a 120 degrees triple-detector system. For each of the four acquisition schemes, 400 realizations of noisy projection data were generated, and the normalized s.d. in the reconstructed images was calculated for five ROIs in the LV wall. Images were reconstructed with nonuniform attenuation compensation using ML-EM algorithm for 25, 50 and 75 iterations., Results: Both the simulated noise-free and experimental low-noise images reconstructed from 180 degrees and 360 degrees data showed nearly identical count densities and defect contrasts in the LV wall. For the 90 degrees dual-detector system, 180 degrees images showed less noise, while for the 120 degrees triple-detector system, 360 degrees showed less noise; however, these differences in noise level were extremely small after a smoothing filter was applied. The 180 degrees images acquired with the 90 degrees dual-detector system showed the same noise level as the 360 degrees images acquired with the 120 degrees triple-detector system, so neither system geometry had an advantage with respect to reduced noise in the SPECT images., Conclusion: When nonuniform attenuation compensation is included in the reconstruction, the count density in the LV wall is nearly identical for 180 degrees and 360 degrees SPECT images, and the 90 degrees dual-detector and 120 degrees triple-detector SPECT systems produced similar SPECT images for the same total acquisition time.

Unlabelled: We evaluated a novel combined x-ray CT and SPECT medical imaging system for quantitative in vivo measurements of 99mTc-sestamibi uptake in an animal model of myocardial perfusion., Methods: Correlated emission-transmission myocardial images were obtained from 7- to 10-kg pigs. The x-ray CT image was used to generate an object-specific attenuation map that was incorporated into an iterative ML-EM algorithm for reconstruction and attenuation correction of the coregistered SPECT images. The pixel intensities in the SPECT images were calibrated in units of radionuclide concentrations (MBq/g), then compared against in vitro 99mTc activity concentration measured from the excised myocardium. In addition, the coregistered x-ray CT image was used to determine anatomical boundaries for quantitation of myocardial regions with low perfusion., Results: The accuracy of the quantitative measurement of in vivo activity concentration in the porcine myocardium was improved by object-specific attenuation correction. However, an additional correction for partial volume errors was required to retrieve the true activity concentration from the reconstructed SPECT images., Conclusion: Accurate absolute SPECT quantitation required object-specific correction for attenuation and partial volume effects. Additional anatomical information from the x-ray CT image was helpful in defining regions of interest for quantitation of the SPECT images.

We have developed an emission-transmission CT (ETCT) system capable of both single-photon emission computed tomography (SPECT) imaging and x-ray transmission CT imaging using a common photon counting detector. In principle, SPECT and x-ray CT projection data can be acquired simultaneously with the ETCT system; however, doing so results in contamination of the SPECT projection data due to pulse pile-up caused by the relatively high x-ray fluence rate. In this study, we characterize the effects of pulse pile-up for simultaneous ETCT imaging through computer simulation and experimental studies. We demonstrate that pulse pile-up in the SPECT energy window can be well approximated by a simple quadratic relationship between the pile-up rate and the x-ray fluence rate for sufficiently small x-ray fluence rates. Using this quadratic relationship, we developed a simple pile-up correction scheme that subtracts the pile-up counts from the emission data and also truncates the exterior regions of the emission projection data. Analysis of difference images and profiles indicate that this method permits us to reconstruct SPECT images with no apparent noise or resolution degradation in comparison to those obtained via sequential emission and transmission scans.

Basis material decomposition represents dual-energy x-ray attenuation measurements in terms of the attenuation coefficients or thickness of two standard materials which, when combined, produce attenuation equivalent to the object being measured. In tomographic imaging, the reconstructed attenuation coefficient is calculated in terms of the attenuation coefficients of the basis materials, while in projection imaging, the thicknesses of two materials can be specified in terms of the basis materials. This analysis shows that basis material decomposition is exact in a dual-monoenergetic system, but for broad spectra, x-ray beam hardening introduces a bias into quantitative measurements. The error is small enough that it can be ignored when dual-energy imaging is used primarily to enhance the contrast of one material over another. The magnitude of the error in quantitative measurements depends on the details of the specific application including the energy of the x-ray beam, and the composition and thickness of the materials included in the object. The magnitude of the error for dual-energy bone densitometry has been analyzed using a first-order propagation of error analysis and the calculations verified by computer simulation. This analysis shows that the magnitude of the systematic error can be as high as 3% for 1 g/cm2 of bone mineral when aluminum and acrylic basis materials are used for the calibration. This systematic error is eliminated when the basis materials are the same as the materials that are being quantified (i.e., bone mineral and water).

Metaiodobenzylguanidine (MIBG) is a guanethidine derivative that is selectively concentrated in sympathetic nervous tissue. MIBG labeled with 123I or 131I has proven to be a specific and sensitive tool for detection of primary and metastatic pheochromocytoma and neuroblastoma. Eleven patients, with refractory stage IV neuroblastoma were treated with a total of 23 courses of 131I-MIBG, 100-400 mCi/m2/course. Total activity administered per course ranged from 90-550 mCi; maximum cumulative radioactivity per patient was 1356 mCi. The 131I-MIBG was given as a 2 hour infusion. Total body dose was calculated from whole body activity measurements, ranging from 73-250 cGy. The main toxicity was thrombocytopenia, with platelet nadirs to less than 25,000/microL in 5/23 courses (5 patients), all occurring in patients with greater than 25% replacement by tumor in the bone marrow. Neutropenia to a nadir of less than 500/microL was seen in only 2 patients, both with greater than 50% bone marrow replacement after 2 and 4 courses of 131I-MIBG, respectively. Tumor doses were calculated in patients with an evaluable measurable lesion, and ranged from 312-6329 cGy per course. Two of the eleven patients had partial responses, with one long-term survivor with stage IV neuroblastoma with no evidence of active disease now 4 years off treatment. Two other patients survive with stable disease after 3 treatments, at 3+ and 5+ months. Seven patients died with progressive disease. This study shows that treatment with 131I-MIBG is safe and can be effective in refractory neuroblastoma, particularly in patients who do not have extensive bone and bone marrow involvement.

A prototype Emission-Transmission Computed Tomography (ETCT) system is being developed that will acquire single-slice x-ray transmission CT images simultaneously with single photon emission computed tomography (SPECT) images. This system will permit the correlation of anatomical information from x-ray CT with functional information from SPECT images. The patient-specific attenuation map derived from the x-ray CT images can be used to perform attenuation correction of the SPECT images, so that accurate quantitative information can be obtained. The fan-beam scanning geometry and the use of a segmented HPGe detector array impose special constraints on the design of the collimator for the system. Based on a signal detection model, an efficiency-resolution figure of merit (ERFM) as a function of the collimator geometric efficiency, system resolution width, and object diameter is defined. The ERFM is proportional to the square of the detection signal-to-noise ratio. The collimator design parameters can then be optimized by optimizing the ERFM for an anticipated object diameter. The collimator point-spread function, geometric efficiency, and resolution are calculated. The collimator optimized for the detection of a 1-cm object will have a single-slice point source efficiency of 1.2 X 10(-4), and a FWHM of 6.5 mm at the center of the reconstruction circle, at 12 cm from the collimator face. The minimum object contrast which will give a detection SNR of 5 is 74%, for a total accumulated count per slice of 2 X 10(6).

A data-acquisition system designed for x-ray medical imaging utilizes a segmented high-purity germanium (HPGe) detector array with 2-mm wide and 6-mm thick elements. The detectors are contained within a liquid-nitrogen cryostat designed to minimize heat losses. The 50-ns pulse-shaping time of the preamplifier electronics is selected as the shortest time constant compatible with the 50-ns charge collection time of the detector. This provides the detection system with the fastest count-rate capabilities and immunity from microphonics, with moderate energy resolution performance. A theoretical analysis of the preamplifier electronics shows that its noise performance is limited primarily by its input capacitance, and is independent of detector leakage current up to approximately 100 nA. The system experimentally demonstrates count rates exceeding 1 million counts per second per element with an energy resolution of 7 keV for the 60-keV gamma ray photon from 241Am. The results demonstrate the performance of a data acquisition system utilizing HPGe detector systems which would be suitable for dual-energy imaging as well as systems offering simultaneous x-ray transmission and radionuclide emission imaging.

Several investigators have approximated the scatter component of digital radiographic images by applying a constant weighting factor to a convolved version of the detected image. The scatter approximation is then subtracted from the detected image. When a constant weighting factor is used, the scatter in areas of low transmission is underestimated. We have extended this technique by allowing for a spatially variable weighting factor based on the local image intensity. This technique improves the scatter estimate and should provide better results for general videodensitometric applications.

A minicomputer-based technique compiles objective indicators of scintigraphic system performance. The evaluation begins with the acquisition of a single image of an orthogonal hole pattern from which quantitative and regional measurements of point-source sensitivity, spatial resolution, and spatial linearity are derived. Two computer programs offer the user different but complementary features. The first program is the basis of an evaluation performed by a technologist for purposes of quality control. Operator intervention is minimal, and the entire protocol, including data acquisition and processing, can be completed in 20 min. The results are automatically compiled and displayed as graphs showing 100 consecutive sets of daily performance measurements. A second computer program is designed as an interactive diagnostic and research tool to display measurements as histograms and functional images. The operator can use the program to determine the quantitative and spatial characteristics of the system's intrinsic performance measurements made during the quality-control evaluations.

Since myocardial infarction is the major cause of perioperative and postoperative death following peripheral vascular surgery, an accurate method of screening for coronary artery disease in this group of patients is needed. Digital subtraction angiography (DSA) with the use of intra-arterial aortic root injection of contrast material was evaluated as a method of screening for coronary artery disease in patients undergoing angiography for peripheral vascular disease. The feasibility of this method was demonstrated in animal experiments. Fifteen milliliters of Renografin-76 was power injected into the aortic root of seven anesthetized 20 kg mongrel dogs. Normal coronary artery anatomy was clearly demonstrated with DSA, and a series of iatrogenically created stenoses and occlusions were accurately identified. Excellent definition of patent grafts to the left anterior descending and circumflex coronary arteries was obtained in two dogs that had undergone previous coronary artery bypass grafting. A balloon occluder on one graft was used to demonstrate partial and near-total obstruction of the bypass graft. We are currently studying the use of aortic root injections using DSA to determine coronary artery disease in patients having standard angiography for peripheral vascular disease. Adequate visualization of coronary arteries and bypass grafts with only 20 ml of contrast has been obtained. The potential ability of this technique to identify and allow treatment of life-threatening coronary artery lesions in patients prior to or simultaneously with peripheral vascular surgery may result in reduced mortality.

To assess the advantages of more complete angular sampling and of more views in the tomographic reconstruction process, tomographic imaging with a 12-pinhole (12PH) collimator has been compared with 7-pinhole tomography (7PH). The 12PH system gives a 50% increase in sensitivity but resolution degrades more rapidly with depth. The 7PH and 12PH systems provide similar accuracy of detection of lesions in a myocardial ring phantom. The 7PH images, however, demonstrated more noise and "ripple" artifacts. The 12PH system offers a larger reconstruction volume and generates fewer artifacts when the collimator is misaligned with the myocardial long-axis, thus making patient positioning less critical than with 7PH. A disadvantage is that individual views are minified by the 12PH collimator, and a 256 X 256 image matrix should be used during image acquisition to limit digital sampling errors.

Contrast-detail curves have been used frequently to describe the low contrast performance characteristics of computed tomography (CT) scanners. However, such curves can produce misleading conclusions if the effects of all variables influencing CT images are not considered. As shown in this experimental study, improperly designed contrast-detail curves disguise differences in CT performance when the same object is imaged with different x-ray spectra. These problems arise because contrast is defined as the difference in system-dependent CT numbers rather than the actual difference in the object. An alternate approach to CT performance evaluation using "difference-detail" curves is offered.

Standard angiography demonstrates the anatomy of arterial occlusive disease but does not define its physiological significance. However, measurement of flow in a compromised vessel at rest and following peripheral dilatation provides important physiological information. Using digital subtraction angiography, femoral arterial flows determined by the cross-correlation transit time technique were compared to measurements by electromagnetic flowmeter. Thirty-five femoral arterial flow measurements were obtained in nine dogs instrumented with an electromagnetic flow probe and balloon occluder. Renografin 76 (7 cc) was power-injected at 14 cc/sec into the distal abdominal aorta. Angiographic flow measurements correlated well with electromagnetic flowmeter measurements (r = 0.94, standard deviation of the difference (SDD) = 15 ml/min). Intravenous studies provided somewhat poorer correlation due to difficulties in defining dimensions (r = 0.72, SDD = 36). Paired contrast injections (2 injections in succession) in 11 studies increased flow from an average of 80 to 250 ml/min (a 210 +/- 100% increase), providing an estimate of a vessel's capacity to provide increased flow during peripheral dilatation. Thus, reliable angiographic flow determinations may be obtained by arterial and intravenous contrast injections, adding physiological information to anatomical definition.

A digital beam attenuator system has been developed to automatically generate patient-specific compensating filters for chest radiography. An initial low-dose test image is used to generate the attenuator, which is fabricated by overprinting multiple layers of a heavy-metal material onto a nonattenuating substrate. The attenuator is subsequently inserted into the x-ray beam for a final compensated radiograph. The effects of focal spot blurring and limited attenuator resolution result in the final compensated image containing only high-spatial frequency information. The frequency response of the process is not strictly describable by a modulation transfer function, but an approximation of the frequencies remaining in the compensated image is obtained for low-contrast conditions. It is found that a 4 X 4 blurring function on the original 64 X 64 test image is required for the attenuator to give appropriate compensated image appearance. A proposed attenuator printing scheme prints the attenuator in a 16 X 16 matrix, staggering successively printed layers to achieve the required 64 X 64 sampling with appropriate blurring. The resulting compensated image has good anatomical definition and contains a frequency response similar to that obtained by compensation techniques being investigated by Plewes and Sorenson.