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Auditory-based targeted cognitive training (ATCT) programs are emerging pro-cognitive therapeutic interventions which aim to improve auditory processing to attenuate cognitive impairment in a "bottom up" manner. Biomarkers of early auditory information processing (EAIP) like mismatch negativity (MMN) and P3a have been used successfully to predict gains from a full 40 h course of ATCT in schizophrenia (SZ). Here we investigated the ability of EAIP biomarkers to predict ATCT performance in a group of subjects (n = 26) across SZ, MDD, PTSD and GAD diagnoses. Cognition was assessed via the MATRICS Consensus Cognitive Battery (MCCB) and MMN/P3a were collected prior to completing 1 h of "Sound Sweeps," a representative ATCT exercise. Baseline and final performance over the first two levels of cognitive training served as the primary dependent variables. Groups had similar MMN, but the SZ group had attenuated P3a. MMN and MCCB cognitive domain t-scores, but not P3a, were strongly correlated with most ATCT performance measures, and explained up to 61% of variance in ATCT performance. Diagnosis was not a significant predictor for ATCT performance. These data suggest that MMN can predict ATCT performance in heterogeneous neuropsychiatric populations and should be considered in ATCT studies across diagnostically diverse cohorts., Competing Interests: Declaration of Competing Interest Dr. Light is a consultant for Johnson & Johnson, Neurocrine, NeuroSig, and Sosei-Heptares. All other authors have no actual or potential conflicts to report, financial or otherwise., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients., Methods: Cross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N=1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia-2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB)., Results: ACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage., Conclusions: Anticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes-including psychotropics used in usual care-should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.

We investigated PET image quantification when using a uniform attenuation coefficient ( μ ) for attenuation correction (AC) of anthropomorphic density phantoms derived from high-resolution breast CT scans. A breast PET system was modeled with perfect data corrections except for AC. Using uniform μ for AC resulted in quantitative errors roughly proportional to the difference between μ used in AC ( μ AC ) and local μ , yielding approximately ± 5% bias, corresponding to the variation of μ for 511 keV photons in breast tissue. Global bias was lowest when uniform μ AC was equal to the phantom mean μ ( μ mean ). Local bias in 10-mm spheres increased as the sphere μ deviated from μ mean , but remained only 2-3% when the μ sphere was 6.5% higher than μ mean . Bias varied linearly with and was roughly proportional to local μ mismatch. Minimizing local bias, e.g., in a small sphere, required the use of a uniform μ value between the local μ and the μ mean . Thus, biases from using uniform- μ AC are low when local μ sphere is close to μ mean . As the μ sphere increasingly differs from the phantom μ mean , bias increases, and the optimal uniform μ is less predictable, having a value between μ sphere and the phantom μ mean .

The goal for positron emission tomography (PET)/X is measuring changes in radiotracer uptake for early assessment of response to breast cancer therapy. Upper bounds for detecting such changes were investigated using simulation and two image reconstruction algorithms customized to the PET/X rectangular geometry. Analytical reconstruction was used to study spatial resolution, comparing results with the distance of the closest approach (DCA) resolution surrogate that is independent of the reconstruction method. An iterative reconstruction algorithm was used to characterize contrast recovery in small targets. Resolution averaged [Formula: see text] full width at half maximum when using depth-of-interaction (DOI) information. Without DOI, resolution ranged from [Formula: see text] to [Formula: see text] for scanner crystal thickness between 5 and 15 mm. The DCA resolution surrogate was highly correlated to image-based FWHM. Receiver-operating characteristic analysis showed specificity and sensitivity over 95% for detecting contrast change from 5:1 to 4:1 (area under curve [Formula: see text]). For PET/X parameters modeled here, the ability to measure contrast changes benefited from higher photon absorption efficiency of thicker crystals while being largely unaffected by degraded resolution obtained with thicker crystals; DOI provided marginal improvements. These results assumed perfect data corrections and other idealizations, and thus represent an upper bound for detecting changes in small lesion radiotracer uptake of clinical interest using the PET/X system.

Positron emission tomography (PET) images are potential quantitative biomarkers. Understanding long-term (months/years) biomarker variability is important for establishing confidence intervals on studies using such biomarkers over these time frames. PET biomarkers are derived from activity concentration ([Formula: see text]) extracted from PET images. Over 30 months, we measured the stability of decay-normalized counts ([Formula: see text]) and [Formula: see text] by scanning the same 4.5-cm-diameter Ge-68 cylinder weekly, the same Na-22 point source daily, and a refilled 20-cm F-18 cylinder phantom monthly on a clinical TOF-PET/CT scanner. Longitudinal and adjacent-measurement variability was characterized. We found no drift in [Formula: see text] or [Formula: see text] for properly calibrated images over 24 months. During this time, [Formula: see text] ranged [Formula: see text] to 6% for count-matched Ge-68 and F-18 images, with coefficient of variation (COV) across time of 2.3% (Ge-68, 81 scans) and 3.2% (F-18, 24 scans). At typical patient image count levels the Ge-68 [Formula: see text] ([Formula: see text]) COV across time was 6.9% (9.6%). Changes in [Formula: see text] between adjacent F-18 scans ([Formula: see text]) ranged between [Formula: see text], with corresponding date-matched changes in Ge-68 [Formula: see text] ranging [Formula: see text]. We recommend (1) tracking trends in [Formula: see text] with image [Formula: see text] as a check of quantitative data corrections/calibrations and (2) tracking both mean and COV of [Formula: see text] (single time point measures) to hundredths precision using standardized uptake values.

A PET detector featuring a pseudo-monolithic crystal is being developed as a more cost-effective alternative to a full monolithic crystal PET detector. This work evaluates different methods to localize the scintillation events in quartered monolithic crystals that are optically coupled. A semi-monolithic crystal assembly was formed using four 26  ×  26  ×  10 mm 3 LYSO crystals optically coupled together using optical adhesive, to mimic a 52  ×  52  ×  10 mm 3 monolithic crystal detector. The crystal assembly was coupled to a 64-channel multi-anode photomultiplier tube using silicon grease. The detector was calibrated using a 34  ×  34 scan grid. Events were first filtered and depth separated using a multi-Lorentzian fit to the collected light distribution. Next, three different techniques were explored to generate the look up tables for the event positioning. The first technique was 'standard interpolation' across the interface. The second technique was 'central extrapolation', where a bin was placed at the midpoint of the interface and events positioned within the interface region were discarded. The third technique used a 'central overlap' method where an extended region was extrapolated at each interface. Events were then positioned using least-squares minimization and maximum likelihood methods. The least-squares minimization applied to the look up table generated with the standard interpolation technique had the best full width at half maximum (FWHM) intrinsic spatial resolution and the lowest bias. However, there were discontinuities in the event positioning that would most likely lead to artifacts in the reconstructed image. The central extrapolation technique also had discontinuities and a 30% sensitivity loss near the crystal-crystal interfaces. The central overlap technique had slightly degraded performance metrics, but it still provided ~2.1 mm intrinsic spatial resolution at the crystal-crystal interface and had a symmetric and continuously varying response function. Results using maximum likelihood positioning were similar to least-squares minimization for the central overlap data.

Quantitative PET imaging is an important tool for clinical trials evaluating the response of cancers to investigational therapies. The standardized uptake value, used as a quantitative imaging biomarker, is dependent on multiple parameters that may contribute bias and variability. The use of long-lived, sealed PET calibration phantoms offers the advantages of known radioactivity activity concentration and simpler use than aqueous phantoms. We evaluated scanner and dose calibrator sources from two batches of commercially available kits, together at a single site and distributed across a local multicenter PET imaging network. We found that radioactivity concentration was uniform within the phantoms. Within the regions of interest drawn in the phantom images, coefficients of variation of voxel values were less than 2%. Across phantoms, coefficients of variation for mean signal were close to 1%. Biases of the standardized uptake value estimated with the kits varied by site and were seen to change in time by approximately ±5%. We conclude that these biases cannot be assumed constant over time. The kits provide a robust method to monitor PET scanner and dose calibrator biases, and resulting biases in standardized uptake values.

Background: This study aimed to determine whether patients with lower abdominal symptoms can be investigated quickly using results of faecal haemoglobin concentration (f-Hb) measurements, and whether this test could form part of a diagnostic pathway for significant colorectal disease., Methods: Nine hundred and nine consecutive patients referred from primary care for colonoscopy were invited: 507 submitted samples for f-Hb measurement with a quantitative faecal immunochemical test for haemoglobin (FIT) (HM-JACKarc, Kyowa-Medex, Japan) and a diagnostic colonoscopy was completed in 484 patients., Results: Colorectal cancer (CRC), higher risk adenoma (HRA), inflammatory bowel disease (IBD) and/or colitis was found in 45 patients (9.3%); these had significantly higher (p<0.0001) f-Hb than the group of 243 with normal colonoscopy plus the 196 patients with less significant clinical findings. The 11 (2.2%) patients with CRC all had f-Hb >190 μg Hb/g faeces. Using a f-Hb cut-off of 10 μg Hb/g faeces, for the group with CRC or HRA or IBD or colitis, sensitivity was 68.9%, specificity 80.2%, positive predictive value (PPV) 26.3% and negative predictive value (NPV) 96.2%. Sensitivity and NPV were 100% for CRC suggesting f-Hb is a good rule-in test for CRC. Of the 243 patients with normal colonoscopy, 81.2% had f-Hb<10 μg Hb/g faeces., Conclusions: The high NPV for significant colorectal diseases suggests that f-Hb could be used as a rule-out test in this context. Potential exists for using f-Hb measurements to investigate symptomatic patients and guide the use of colonoscopy resources: detailed algorithms for the introduction of f-Hb measurements requires further exploration.

Unlabelled: We studied the effects of reduced (18)F-FDG injection activity on interpretation of positron emission mammography (PEM) images and compared image interpretation between 2 postinjection imaging times., Methods: We performed a receiver-operating-characteristic (ROC) study using PEM images reconstructed with different count levels expected from injected activities between 23 and 185 MBq. Thirty patients received 2 PEM scans at postinjection times of 60 and 120 min. Half of the patients were scanned with a standard protocol; the others received one-half of the standard activity. Images were reconstructed using 100%, 50%, and 25% of the total counts acquired. Eight radiologists used a 5-point confidence scale to score 232 PEM images for the presence of up to 3 malignant lesions. Paired images were analyzed with conditional logistic regression and ROC analysis to investigate changes in interpretation., Results: There was a trend for increasing lesion detection sensitivity with increased image counts: odds ratios were 2.2 (P = 0.01) and 1.9 (P = 0.04) per doubling of image counts for 60- and 120-min uptake images, respectively, without significant difference between time points (P = 0.7). The area under the ROC curve (AUC) was highest for the 100%-count, 60-min images (0.83 vs. 0.75 for 50%-counts, P = 0.02). The 120-min images had a similar trend but did not reach statistical significance (AUC = 0.79 vs. 0.73, P = 0.1). Our data did not yield significant trends between specificity and image counts. Lesion-to-background ratios increased between 60- and 120-min scans (P < 0.001)., Conclusion: Reducing the image counts relative to the standard protocol decreased diagnostic accuracy. The increase in lesion-to-background ratio between 60- and 120-min uptake times was not enough to improve detection sensitivity in this study, perhaps in part due to fewer counts in the later scan., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Purpose: Previous studies have demonstrated how imaging of the breast with patients lying prone using a supportive positioning device markedly facilitates longitudinal and/or multimodal image registration. In this contribution, the authors' primary objective was to determine if there are differences in the standardized uptake value (SUV) derived from [(18)F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in breast tumors imaged in the standard supine position and in the prone position using a specialized positioning device., Methods: A custom positioning device was constructed to allow for breast scanning in the prone position. Rigid and nonrigid phantom studies evaluated differences in prone and supine PET. Clinical studies comprised 18F-FDG-PET of 34 patients with locally advanced breast cancer imaged in the prone position (with the custom support) followed by imaging in the supine position (without the support). Mean and maximum values (SUVpeak and SUVmax, respectively) were obtained from tumor regions-of-interest for both positions. Prone and supine SUV were linearly corrected to account for the differences in 18F-FDG uptake time. Correlation, Bland-Altman, and nonparametric analyses were performed on uptake time-corrected and uncorrected data., Results: SUV from the rigid PET breast phantom imaged in the prone position with the support device was 1.9% lower than without the support device. In the nonrigid PET breast phantom, prone SUV with the support device was 5.0% lower than supine SUV without the support device. In patients, the median (range) difference in uptake time between prone and supine scans was 16.4 min (13.4-30.9 min), which was significantly-but not completely-reduced by the linear correction method. SUVpeak and SUVmax from prone versus supine scans were highly correlated, with concordance correlation coefficients of 0.91 and 0.90, respectively. Prone SUVpeak and SUVmax were significantly lower than supine in both original and uptake time-adjusted data across a range of index times (P < < 0.0001, Wilcoxon signed rank test). Before correcting for uptake time differences, Bland-Altman analyses revealed proportional bias between prone and supine measurements (SUVpeak and SUVmax) that increased with higher levels of FDG uptake. After uptake time correction, this bias was significantly reduced (P < 0.01). Significant prone-supine differences, with regard to the spatial distribution of lesions relative to isocenter, were observed between the two scan positions, but this was poorly correlated with the residual (uptake time-corrected) prone-supine SUVpeak difference (P = 0.78)., Conclusions: Quantitative 18F-FDG-PET/CT of the breast in the prone position is not deleteriously affected by the support device but yields SUV that is consistently lower than those obtained in the standard supine position. SUV differences between scans arising from FDG uptake time differences can be substantially reduced, but not removed entirely, with the current correction method. SUV from the two scan orientations is quantitatively different and should not be assumed equivalent or interchangeable within the same subject. These findings have clinical relevance in that they underscore the importance of patient positioning while scanning as a clinical variable that must be accounted for with longitudinal PET measurement, for example, in the assessment of treatment response.

To reduce the number of output channels and associated cost in PET detectors, strategies to multiplex the signal channels have been investigated by several researchers. This work aims to find an optimal multiplexing strategy for detector modules consisting of a monolithic LYSO scintillator coupled to a 64-channel PMT. We apply simulated multiplexing strategies to measured data from two continuous miniature crystal element (cMiCE) detector modules. The strategies tested include standard methods such as row column summation and its variants, as well as new data-driven methods involving the principal components of measured data and variants of those components. The detector positioning resolution and bias are measured for each multiplexing strategy and the results are compared. The mean FWHM over the entire detector was 1.23 mm for no multiplexing (64 channels). Using 16 principal component channels yielded a mean FWHM resolution of 1.21 mm, while traditional row/column summation (16 channels) yielded 1.28 mm. Using 8 principal component output channels resulted in a resolution of 1.30 mm. Using the principal components of the calibration data to guide the multiplexing scheme appears to be a viable method for reducing the number of output data channels. Further study is needed to determine if the depth-of-interaction resolution can be preserved with this multiplexing scheme.

We used simulations to investigate the relationship between sensitivity and spatial resolution as a function of crystal thickness in a rectangular PET scanner intended for quantitative assessment of breast cancers. The system had two 20 × 15-cm 2 and two 10 × 15-cm 2 flat detectors forming a box, with the larger detectors separated by 4 or 8 cm. Depth-of-interaction (DOI) resolution was modeled as a function of crystal thickness based on prior measurements. Spatial resolution was evaluated independent of image reconstruction by deriving and validating a surrogate metric from list-mode data ( d FWHM ). When increasing crystal thickness from 5 to 40 mm, and without using DOI information, the d FWHM for a centered point source increased from 0.72 to 1.6 mm. Including DOI information improved d FWHM by 12% and 27% for 5- and 40-mm-thick crystals, respectively. For a point source in the corner of the FOV, use of DOI information improved d FWHM by 20% (5-mm crystal) and 44% (40-mm crystal). Sensitivity was 7.7% for 10-mm-thick crystals (8-cm object). Increasing crystal thickness on the smaller side detectors from 10 to 20 mm (keeping 10-mm crystals on the larger detectors) boosted sensitivity by 24% (relative) and degraded d FWHM by only ~3%/8% with/without DOI information. The benefits of measuring DOI must be evaluated in terms of the intended clinical task of assessing tracer uptake in small lesions. Increasing crystal thickness on the smaller side detectors provides substantial sensitivity increase with minimal accompanying loss in resolution.

We have developed a Monte-Carlo photon-tracking and readout simulator called SCOUT to study the stochastic behavior of signals output from a simplified rectangular scintillation-camera design. SCOUT models the salient processes affecting signal generation, transport, and readout of a scintillation camera. In this work, we compare output signal statistics from SCOUT to experimental results for both a discrete and a monolithic camera. We also benchmark the speed of this simulation tool and compare it to existing simulation tools. We find this modeling tool to be relatively fast and predictive of experimental results. Depending on the modeled camera geometry, we found SCOUT to be 4 to 140 times faster than other modeling tools.

Purpose: To quantify the concentration of soft-tissue components of water, fat, and calcium through the decomposition of the x-ray spectral signatures in multi-energy CT images., Methods: Decomposition of dual-energy and multi-energy x-ray data into basis materials can be performed in the projection domain, image domain, or during image reconstruction. In this work, the authors present methodology for the decomposition of multi-energy x-ray data in the image domain for the application of soft-tissue characterization. To demonstrate proof-of-principle, the authors apply several previously proposed methods and a novel content-aware method to multi-energy images acquired with a prototype photon counting CT system. Data from phantom and ex vivo specimens are evaluated., Results: The number and type of materials in a region can be limited based on a priori knowledge or classification strategies. The proposed difference classifier successfully classified the image into air only, water+fat, water+fat+iodine, and water+calcium regions. Then, the content-aware material decomposition based on weighted least-square optimization generated quantitative maps of concentration. Bias in the estimation of the concentration of water and oil components in a phantom study was <0.10 ± 0.15 g/cc on average. Decomposition of ex vivo carotid endarterectomy specimens suggests the presence of water, lipid, and calcium deposits in the plaque walls., Conclusions: Initial application of the proposed methodology suggests that it can decompose multi-energy CT images into quantitative maps of water, adipose, iodine, and calcium concentrations.

Purpose: To characterize the relationship between lesion detection sensitivity and injected activity as a function of lesion size and contrast on the PEM (positron emission mammography) Flex Solo II scanner using phantom experiments., Methods: Phantom lesions (spheres 4, 8, 12, 16, and 20 mm diameter) were randomly located in uniform background. Sphere activity concentrations were 3 to 21 times the background activity concentration (BGc). BGc was a surrogate for injected activity; BGc ranged from 0.44-4.1 kBq∕mL, corresponding to 46-400 MBq injections. Seven radiologists read 108 images containing zero, one, or two spheres. Readers used a 5-point confidence scale to score the presence of spheres., Results: Sensitivity was 100% for lesions ≥12 mm under all conditions except for one 12 mm sphere with the lowest contrast and lowest BGc (60% sensitivity). Sensitivity was 100% for 8 mm spheres when either contrast or BGc was high, and 100% for 4 mm spheres only when both contrast and BGc were highest. Sphere contrast recovery coefficients (CRC) were 49%, 34%, 26%, 14%, and 2.8% for the largest to smallest spheres. Cumulative specificity was 98%., Conclusions: Phantom lesion detection sensitivity depends more on sphere size and contrast than on BGc. Detection sensitivity remained ≥90% for injected activities as low as 100 MBq, for lesions ≥8 mm. Low CRC in 4 mm objects results in moderate detection sensitivity even for 400 MBq injected activity, making it impractical to optimize injected activity for such lesions. Low CRC indicates that when lesions <8 mm are observed on PEM images they are highly tracer avid with greater potential of clinical significance. High specificity (98%) suggests that image statistical noise does not lead to false positive findings. These results apply to the 85 mm thick object used to obtain them; lesion detectability should be better (worse) for thinner (thicker) objects based on the reduced (increased) influence of photon attenuation.

We evaluate the accuracy of scaling CT images for attenuation correction of PET data measured for bone. While the standard tri-linear approach has been well tested for soft tissues, the impact of CT-based attenuation correction on the accuracy of tracer uptake in bone has not been reported in detail. We measured the accuracy of attenuation coefficients of bovine femur segments and patient data using a tri-linear method applied to CT images obtained at different kVp settings. Attenuation values at 511 keV obtained with a (68)Ga/(68)Ge transmission scan were used as a reference standard. The impact of inaccurate attenuation images on PET standardized uptake values (SUVs) was then evaluated using simulated emission images and emission images from five patients with elevated levels of FDG uptake in bone at disease sites. The CT-based linear attenuation images of the bovine femur segments underestimated the true values by 2.9 ± 0.3% for cancellous bone regardless of kVp. For compact bone the underestimation ranged from 1.3% at 140 kVp to 14.1% at 80 kVp. In the patient scans at 140 kVp the underestimation was approximately 2% averaged over all bony regions. The sensitivity analysis indicated that errors in PET SUVs in bone are approximately proportional to errors in the estimated attenuation coefficients for the same regions. The variability in SUV bias also increased approximately linearly with the error in linear attenuation coefficients. These results suggest that bias in bone uptake SUVs of PET tracers ranges from 2.4% to 5.9% when using CT scans at 140 and 120 kVp for attenuation correction. Lower kVp scans have the potential for considerably more error in dense bone. This bias is present in any PET tracer with bone uptake but may be clinically insignificant for many imaging tasks. However, errors from CT-based attenuation correction methods should be carefully evaluated if quantitation of tracer uptake in bone is important.

Objective: The study objective was to assess the correlation between (18)F-FDG uptake values on positron emission mammography (PEM), expressed as maximum uptake value and lesion-to-background ratio, and receptor status (i.e., estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]), tumor histology, and tumor grade. We also evaluated for the correlation between maximum uptake value on PEM and maximum uptake value on a whole-body PET/CT., Materials and Methods: We retrospectively reviewed our database for patients with newly diagnosed breast cancer who were referred for PEM between June 2007 and September 2009. A subset of patients also underwent a whole-body PET/CT scan. The original pathology reports were reviewed to establish the histologic type, grade, and receptor status., Results: The study involved 98 patients with 100 lesions. ER-negative tumors and PR-negative tumors had significantly higher mean lesion-to-background ratio than did their respective receptor-positive tumors (p = 0.02). Triple-negative tumors (i.e., ER-negative, PR-negative, and HER2-negative tumors) had statistically higher mean lesion-to-background ratio than did ER-positive PR-positive HER2-negative tumors (p = 0.04). Infiltrating ductal carcinomas had significantly higher PEM FDG uptake values than did infiltrating lobular carcinomas (p = 0.02-0.04). Breast tumors with higher histologic grade also had significantly higher PEM FDG uptake values than did those with lower grade (p = 0.03 and p < 0.001). A moderately high correlation (0.76-0.79) was seen between whole-body PET/CT and PEM uptake values., Conclusion: This study shows a correlation between PEM FDG uptake values and the prognostic factors that have been shown to predict breast cancer survival.

We investigated the relationship between noise equivalent count (NEC) and axial field of view (AFOV) for PET scanners with AFOVs ranging from one-half to twice those of current clinical scanners. PET scanners with longer or shorter AFOVs could fulfill different clinical needs depending on exam volumes and site economics. Using previously validated Monte Carlo simulations, we modeled true, scattered and random coincidence counting rates for a PET ring diameter of 88 cm with 2, 4, 6, and 8 rings of detector blocks (AFOV 7.8, 15.5, 23.3, and 31.0 cm). Fully 3D acquisition mode was compared to full collimation (2D) and partial collimation (2.5D) modes. Counting rates were estimated for a 200 cm long version of the 20 cm diameter NEMA count-rate phantom and for an anthropomorphic object based on a patient scan. We estimated the live-time characteristics of the scanner from measured count-rate data and applied that estimate to the simulated results to obtain NEC as a function of object activity. We found NEC increased as a quadratic function of AFOV for 3D mode, and linearly in 2D mode. Partial collimation provided the highest overall NEC on the 2-block system and fully 3D mode provided the highest NEC on the 8-block system for clinically relevant activities. On the 4-, and 6-block systems 3D mode NEC was highest up to ∼300 MBq in the anthropomorphic phantom, above which 3D NEC dropped rapidly, and 2.5D NEC was highest. Projected total scan time to achieve NEC-density that matches current clinical practice in a typical oncology exam averaged 9, 15, 24, and 61 min for the 8-, 6-, 4-, and 2-block ring systems, when using optimal collimation. Increasing the AFOV should provide a greater than proportional increase in NEC, potentially benefiting patient throughput-to-cost ratio. Conversely, by using appropriate collimation, a two-ring (7.8 cm AFOV) system could acquire whole-body scans achieving NEC-density levels comparable to current standards within long, but feasible, scan times.

Purpose: The goal of this work was to investigate the effects of MRI surface coils on attenuation-corrected PET emission data. The authors studied the cases where either an MRI or a CT scan would be used to provide PET attenuation correction (AC). Combined MR/PET scanners that use the MRI for PET AC (MR-AC) face the challenge of absent surface coils in MR images and thus cannot directly account for attenuation in the coils. Combining MR and PET images could be achieved by transporting the subject on a stereotactically registered table between independent MRI and PET scanners. In this case, conventional PET CT-AC methods could be used. A challenge here is that high atomic number materials within MR coils cause artifacts in CT images and CT based AC is typically not validated for coil materials., Methods: The authors evaluated PET artifacts when MR coils were absent from AC data (MR-AC), or when coil attenuation was measured by CT scanning (CT-AC). They scanned PET phantoms with MR surface coils on a clinical PET/CT system and used CT-AC to reconstruct PET data. The authors then omitted the coil from the CT-AC image to mimic the MR-AC scenario. Images were acquired using cylinder and anthropomorphic phantoms. They evaluated and compared the following five scenarios: (1) A uniform cylinder phantom and head coil scanned and reconstructed using CT-AC; (2) similar emission data (with head coil present) were reconstructed without the head coil in the AC data; (3) the same cylinder scanned without the head coil present (reference scan); (4) a PET torso phantom with a full MR torso coil present in both PET and CT; (5) only half of the separable torso coil present in the PET/CT acquisition. The authors also performed analytic simulations of the first three scenarios., Results: Streak artifacts were present in CT images containing MR surface coils due to metal components. These artifacts persisted after the CT images were converted for PET AC. The artifacts were significantly reduced when half of the separable coil was removed during the scan. CT scans tended to over-estimate the linear attenuation coefficient (micro) of the metal components when using conventional methods for converting from CT number to micro(511 keV). Artifacts were visible outside the phantom in some of the PET emission images, corresponding to the MRI coil geometry. However, only subtle artifacts were apparent in the emission images inside the phantoms. On the other hand, the PET emission image quantitative accuracy was significantly affected: the activity was underestimated by 19% when AC did not include the head coil, and overestimated by 28% when the CT-AC included the head coil., Conclusions: The presence of MR coils during PET or PET/CT scanning can cause subtle artifacts and potentially important quantification errors. Alternative CT techniques that mitigate artifacts should be used to improve AC accuracy. When possible, removing segments of an MR coil prior to the PET/CT exam is recommended. Further, MR coils could be redesigned to reduce artifacts by rearranging placement of the most attenuating materials.

Purpose: The authors discuss the design and evaluate the performance of combined event estimation and image reconstruction algorithms designed for a proposed high-resolution rectangular breast PET scanner (PETX). The PETX scanner will be capable of measuring the depth of interaction by utilizing detector modules composed of depth-of-interaction microcrystal element (dMiCE) crystal pairs. This design allows a unique combination of event estimation and fast projection methods., Methods: The authors implemented a Monte Carlo simulator to model the PETX system using only true coincident events. The performance of the dMiCE crystal pairs was determined experimentally over a range of depths of interaction. This distribution was used to simulate the noisy dMiCE detector signals and to estimate the line of response for each decay. Three different statistical methods were implemented to determine photon event positioning. Images were reconstructed from these line of response estimators with the exact planogram frequency distance rebinning algorithm, which is an exact analytical reconstruction algorithm for planar systems. Reconstructed images were analyzed with contrast, noise, and spatial resolution metrics., Results: The authors' simulations demonstrate the ability for the PETX system to produce quantitatively accurate images from true coincident events with a contrast recovery coefficient of greater than 0.8 for 5 mm spheres at the axial center of the scanner and a spatial resolution (FWHM) of 3 mm throughout most of the imaging field of view., Conclusions: The authors' proposed positioning and reconstruction algorithms for the PETX system show the potential for creating high-quality, high-resolution, and quantitatively accurate images within a clinically feasible reconstruction time.

Unlabelled: The purpose of this study was to measure the errors introduced by regular calibration of PET/CT scanners and to minimize the effect of calibration error on standardized uptake value measurements., Methods: Global calibration factors from 2 PET/CT scanners were recorded for 3.5 and 1.8 y, comparing manufacturer-recommended protocols with modified protocols to evaluate error contributions due to operator-influenced procedures. Dose calibrator measurements were evaluated using National Institute of Standards and Technology-traceable sources., Results: Dose calibrator variability was less than 1%, although there was a consistent bias. Global scaling variability was reduced from 6% to 4% for scanner 1 and from 11% to 4% for scanner 2 when quality assurance and quality control procedures were applied to the calibration protocol. When calibrations were done using a (68)Ge/(68)Ga phantom, the variability for both scanners was reduced to approximately 3%., Conclusion: Applying quality assurance and quality control procedures to scanner calibration reduces variability, but there is a still a residual longitudinal scanner variability of 3%-4%. The procedures proposed here reduce the impact of operator error on scanner calibration and thereby minimize longitudinal variability in standardized uptake value measurements.

Introduction: Anemia is associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). It remains unclear whether this association can be modified with more aggressive use of red blood cell (RBC) transfusions. The degree to which restrictive thresholds have been adopted in neurocritical care patients remains unknown., Methods: We performed a survey of North American academic neurointensivists, vascular neurosurgeons and multidisciplinary intensivists who regularly care for patients with SAH to determine hemoglobin (Hb) concentrations which commonly trigger a decision to initiate transfusion. We also assessed minimum and maximum acceptable Hb goals in the context of a clinical trial and how decision-making is influenced by advanced neurological monitoring, clinician characteristics and patient-specific factors., Results: The survey was sent to 531 clinicians, of whom 282 (53%) responded. In a hypothetical patient with high-grade SAH (WFNS 4), the mean Hb concentration at which clinicians administered RBCs was 8.19 g/dL (95% CI, 8.07 to 8.30 g/dL). Transfusion practices were comparatively more restrictive in patients with low-grade SAH (mean Hb 7.85 g/dL (95% CI, 7.73 to 7.97 g/dL)) (P < 0.0001) and more liberal in patients with delayed cerebral ischemia (DCI) (mean Hb 8.58 g/dL (95% CI, 8.45 to 8.72 g/dL)) (P < 0.0001). In each setting, there was a broad range of opinions. The majority of respondents expressed a willingness to study a restrictive threshold of ≤8 g/dL (92%) and a liberal goal of ≥10 g/dl (75%); in both cases, the preferred transfusion thresholds were significantly higher for patients with DCI (P < 0.0001). Neurosurgeons expressed higher minimum Hb goals than intensivists, especially for patients with high-grade SAH (β = 0.46, P = 0.003), and were more likely to administer two rather than one unit of RBCs (56% vs. 19%; P < 0.0001). Institutional use of transfusion protocols was associated with more restrictive practices. More senior clinicians preferred higher Hb goals in the context of a clinical trial. Respondents were more likely to transfuse patients with brain tissue oxygen tension values <15 mmHg and lactate-to-pyruvate ratios >40., Conclusions: There is widespread variation in the use of RBC transfusions in SAH patients. Practices are heavily influenced by the specific dynamic clinical characteristics of patients and may be further modified by clinician specialty and seniority, the use of protocols and advanced neurological monitoring.

Our laboratory has previously reported on the basic design concepts of an updated FireWire based data acquisition system for depth-of-interaction detector systems designed at the University of Washington. The new version of our data acquisition system leverages the capabilities of modern field programmable gate arrays (FPGA) and puts almost all functions into the FPGA, including the FireWire elements, the embedded processor, and pulse timing and integration. The design is centered around an acquisition node board (ANB) that includes 64 serial ADC channels, one high speed parallel ADC, FireWire 1394b support, the FPGA, a serial command bus and signal lines to support a rough coincidence window implementation to reject singles events from being sent on the FireWire bus. Adapter boards convert detector signals into differential paired signals to connect to the ANB. In this paper we discuss many of the design details, including steps taken to minimize the number of layers in the printed circuit board and to avoid skewing of parallel signals and unwanted bandwidth limitations.

We have developed a Monte-Carlo photon-tracking and readout simulator called SCOUT to study the stochastic behavior of signals output from a simplified rectangular scintillation-camera design. SCOUT models the salient processes affecting signal generation, transport, and readout. Presently, we compare output signal statistics from SCOUT to experimental results for both a discrete and a monolithic camera. We also benchmark the speed of this simulation tool and compare it to existing simulation tools. We find this modeling tool to be relatively fast and predictive of experimental results. Depending on the modeled camera geometry, we found SCOUT to be 4 to 140 times faster than other modeling tools.

This work presents a row/column summing readout electronics for an 8×8 silicon photomultiplier array. The summation circuit greatly reduces the number of electronic channels, which is desirable for pursuing higher resolution positron emission tomography scanners. By using a degenerated common source topology in the summation circuit, more fan-in is possible and therefore a greater reduction in the number of electronic channels can be achieved. The timing signal is retrieved from a common anode, which allows the use of a single fast-sampling analog to digital converter (ADC) for the timing channel and slower, lower power ADCs for the 64 spatial channels. Preliminary results of one row summation of the 8×8 readout electronics exhibited FWHM energy resolution of 17.8% and 18.3% with and without multiplexing, respectively. The measured timing resolution is 2.9ns FWHM.

We are conducting a two-phase study, which aims to select design parameters of a long-axis positron emission tomography (PET) scanner that are a compromise between detection performance and cost. In this first phase, we examine the effects of axial length, detector thickness and collimator geometry on the noise equivalent count rate per axial length (λNEC) and noise equivalent count rate per slice (dNEC). We use these metrics as approximate, but quickly computed, indicators of a PET-scanner's performance at a detection task. From this first phase, we select a subset of scanner designs for which we can conduct a detailed study of tumor detectability and quantitation accuracy in whole-body PET imaging.

We are developing a prototype monolithic scintillation camera with optical sensors on the entrance surface (SES) for use with statistically-estimated depth-of-interaction in a continuous scintillator. We opt to use Geiger-Müller mode avalanche photodiodes (GM-APDs) for the SES camera since they possess many desirable properties; for the intended application (SES and PET/MR imaging), they offer a thin attenuation profile and an operational insensitivity to large magnetic fields. However, one issue that must be addressed in using GM-APDs in an RF environment (as in MR scanners) is the thermal dissipation that can occur in this semiconductor material.Signals of GM-APDs are strongly dependent on junction temperature. Consequently, we are developing a temperature-controlled GM-APD-based PET camera whose monitored temperature can be used to dynamically account for the temperature dependence of the output signals. Presently, we aim to characterize the output-signal dependence on temperature and bias for a GM-APD-based scintillation camera.We've examined two GM-APDs, a Zecotek prototype MAPD-3N, and a SensL commercial SPMArray2. The dominant effect of temperature on gain that we observe results from a linear dependence of breakdown voltage on temperature (0.071 V/°C and 0.024 V/°C, respectively); at 2.3 V excess bias (voltage above breakdown) the resulting change in gain with temperature (without adjusting bias voltage) is -8.5% per °C for the MAPD-3N and -1.5 % per °C for the SPMArray2. For fixed excess bias, change in dark current with temperature varied widely, decreasing by 25% to 40% as temperature was changed from 20 °C to 10 °C and again by 20% to 35% going from 10 °C to 0 °C. Finally, using two MAPD-3N to read out a pair of 3.5-by-3.5-by-20 mm(3) Zecotek LFS-3 scintillators in coincidence, we observe a decrease from 1.7 nsec to 1.5 nsec in coincidence-time resolution as we lowered temperature from 23 °C to 10 °C.

We develop a statistical line of response (LOR) estimator of the three-dimensional interaction positions of a pair of annihilation photons in a PET detector module with depth of interaction capability. The three-dimensional points of interaction of a coincidence pair of photons within the detector module are estimated by calculation of an expectation of the points of interaction conditioned on the signals measured by the photosensors. This conditional expectation is computed from estimates of the probability density function of the light collection process and a model of the kinetics of photon interactions in the detector module. Our algorithm is capable of handling coincidences where each annihilation photon interacts any number of times within the detector module before being completely absorbed or escaping. In the case of multiple interactions, our algorithm estimates the position of the first interaction for each of the coincidence photons. This LOR estimation algorithm is developed for a high-resolution PET detector capable of providing depth-of-interaction information. Depth of interaction is measured by tailoring the light shared between two adjacent detector elements. These light-sharing crystal pairs are referred to as dMiCE and are being developed in our lab. Each detector element in the prototype system has a 2 x 2 mm(2) cross section and is directly coupled to a micro-pixel avalanche photodiode (MAPD). In this set-up, the distribution of the ratio of light shared between two adjacent detector elements can be expressed as a function of the depth of interaction. Monte Carlo experiments are performed using our LOR estimation algorithm and compared with Anger logic. We show that our LOR estimation algorithm provides a significant improvement over Anger logic under a variety of parameters.

Our laboratory is developing a high-resolution PET detector capable of providing depth-of-interaction information (dMiCE) by tailoring the light sharing between two adjacent detector elements. Each detector element in the prototype system has a 2×2 mm(2) cross section and is directly coupled to a micro-pixel avalanche photodiode (MAPD). In this setup the distribution of the ratio of light shared between two adjacent detector elements can be expressed as a function of the depth of interaction. The three-dimensional points of interaction of a coincidence pair of photons within the detector module is estimated by numerical calculation of an expectation of the points of interaction conditioned on the signals measured by the MAPDs (Bayesian estimate). This conditional expectation is computed from estimates of the probability density function of the light collection process and a model of the kinetics of photon interactions in the detector module. Our algorithm is capable of handling coincidences where each photon interacts any number of times within the detector module before being completely absorbed or escaping. In the case of multiple interactions our algorithm estimates the position of the first interaction for each of the coincidence photons.

The University of Washington developed a Firewire based data acquisition system for the MiCES small animal PET scanner. Development work has continued on new imaging scanners that require more data channels and need to be able to operate within a MRI imaging system. To support these scanners, we have designed a new version of our data acquisition system that leverages the capabilities of modern field programmable gate arrays (FPGA). The new design preserves the basic approach of the original system, but puts almost all functions into the FPGA, including the Firewire elements, the embedded processor, and pulse timing and pulse integration. The design has been extended to support implementation of the position estimation and DOl algorithms developed for the cMiCE detector module. The design is centered around an acquisition node board (ANB) that includes 65 ADC channels, Firewire 1394b support, the FPGA, a serial command bus and signal lines to support a rough coincidence window implementation to reject singles events from being sent on the Firewire bus. Adapter boards convert detector signals into differential paired signals to connect to the ANB.

Introduction: High birth and immigration rates in the US-Mexico border region have led to large population increases in recent decades. Two national, 10 state, and more than 100 local government entities deliver reproductive health services to the region's 14 million residents. Limited standardized information about health risks in this population hampers capacity to address local needs and assess effectiveness of public health programs., Methods: We worked with binational partners to develop a system for reproductive health surveillance in the sister communities of Matamoros, Tamaulipas, Mexico, and Cameron County, Texas, as a model for a broader regional approach. We used a stratified, systematic cluster-sampling design to sample women giving birth in hospitals in each community during an 81-day period (August 21-November 9) in 2005. We conducted in-hospital computer-assisted personal interviews that addressed prenatal, behavioral, and lifestyle factors. We evaluated survey response rates, data quality, and other attributes of effective surveillance systems. We estimated population coverage using vital records data., Results: Among the 999 women sampled, 947 (95%) completed interviews, and the item nonresponse rate was low. The study sample included 92.7% of live births in Matamoros and 98.3% in Cameron County. Differences between percentage distributions of birth certificate characteristics in the study and target populations did not exceed 2.0. Study population coverage among hospitals ranged from 92.9% to 100.0%, averaging 97.3% in Matamoros and 97.4% in Cameron County., Conclusion: Results indicate that hospital-based sampling and postpartum interviewing constitute an effective approach to reproductive health surveillance. Such a system can yield valuable information for public health programs serving the growing US-Mexico border population.

We measured count rates and scatter fraction on the Discovery STE PET/CT scanner in conventional 2D and 3D acquisition modes, and in a partial collimation mode between 2D and 3D. As part of the evaluation of using partial collimation, we estimated global count rates using a scanner model that combined computer simulations with an empirical live-time function. Our measurements followed the NEMA NU2 count rate and scatter-fraction protocol to obtain true, scattered and random coincidence events, from which noise equivalent count (NEC) rates were calculated. The effect of patient size was considered by using 27 cm and 35 cm diameter phantoms, in addition to the standard 20 cm diameter cylindrical count-rate phantom. Using the scanner model, we evaluated two partial collimation cases: removing half of the septa (2.5D) and removing two-thirds of the septa (2.7D). Based on predictions of the model, a 2.7D collimator was constructed. Count rates and scatter fractions were then measured in 2D, 2.7D and 3D. The scanner model predicted relative NEC variation with activity, as confirmed by measurements. The measured 2.7D NEC was equal or greater than 3D NEC for all activity levels in the 27 cm and 35 cm phantoms. In the 20 cm phantom, 3D NEC was somewhat higher ( approximately 15%) than 2.7D NEC at 100 MBq. For all higher activity concentrations, 2.7D NEC was greater and peaked 26% above the 3D peak NEC. The peak NEC in 2.7D mode occurred at approximately 425 MBq, and was 26-50% greater than the peak 3D NEC, depending on object size. NEC in 2D was considerably lower, except at relatively high activity concentrations. Partial collimation shows promise for improved noise equivalent count rates in clinical imaging without altering other detector parameters.

Partially collimated PET systems have less collimation than conventional 2-D systems and have been shown to offer count rate improvements over 2-D and 3-D systems. Despite this potential, previous efforts have not established image-based improvements with partial collimation and have not customized the reconstruction method for partially collimated data. This work presents an image reconstruction method tailored for partially collimated data. Simulated and measured sensitivity patterns are presented and provide a basis for modification of a fully 3-D reconstruction technique. The proposed method uses a measured normalization correction term to account for the unique sensitivity to true events. This work also proposes a modified scatter correction based on simulated data. Measured image quality data supports the use of the normalization correction term for true events, and suggests that the modified scatter correction is unnecessary.

We present a study that introduces two approaches to implementing block detectors into SimSET and compares their performance. SimSET is a photon tracking simulation package, which currently incorporates only detectors made of a solid annulus of scinitillator material. A pseudo-block approximation has been imposed on the solid annulus of conventional SimSET by discarding interactions in annulus segments that span the angular block gap. This yields blocks that are annulus segments, not rectangles. This is a quick and easy approximation of block structure, which brings SimSET results closer to actual scanner measurements. Even better agreement is expected with a deeper modification of the SimSET code that implements true rectangular blocks in the detector module (to be released late 2007/early 2008). This approach enables the greatest amount of variability and trueness to detail.We compare results from both block structure implementations to the conventional SimSET results and to measurements from a GE DSTE PET/CT scanner. Differences are evaluated in terms of sensitivities, crystal maps, and energy spectra, as well as in benchmark time tests of the simulation runs and their ease of use.Either implementation of block structure can aid in improving simulation accuracy by ameliorating one known cause of discrepancies, the geometric nature of the block detectors.

Our laboratory has been developing a depth-of-interaction (DOI) detector design based on light sharing between pairs or quadlets of crystals. Work to date has been utilizing 2×2 mm cross section crystals carefully positioned on a multi-anode PMT. However, there is still significant light sharing in the PMT glass envelope and current PMT designs do not allow one-on-one coupling for arrays of smaller cross section crystals. One-on-one coupling is optimal for implementing the DOI estimator. An alternative to PMTs is to take advantage of progress in fabrication of metal resistive-layer semiconductor photodetectors to provide arrays with one-on-one crystal coupling. We report on our initial tests of one manufacturer's devices. The photodetector (MAPD) and scintillator combination (LFS-3) are both products of Zecotek. The LFS-3 crystal is a variant of LFS that has a better spectral match to the MAPD. Measurements show performance equivalent to or better than that obtained with PMTs and LSO, LFS, or LYSO crystals. For example, 2×2×20 mm crystals are providing 11% energy resolution. The high gain of such devices allow flexibility in designs for both the array and the supporting electronics. We are proceeding with the dMiCE development based on the use of MAPD and LFS-3 arrays.

We present the derivation of a live-time model for predicting count rates in computer simulations of PET scanners. Computer models are frequently used to investigate new PET scanner configurations, but they typically do not account for the count losses caused by scanner-specific electronics and processing. The live-time fraction depends strongly on the photon flux incident on the detector. We modeled the live-time of a clinical PET scanner by relating measured and simulated single photon fluxes. Our model used data from a specific scanner, but the approach is generally applicable.We applied the live-time model to partial collimation on a PET scanner; in particular, a scanner with septa positioned between every third detector ring ("2.7D" acquisition mode). The photon flux was measured and simulated for conventional acquisition modes (2D, 3D), and simulated for partial collimation (2.7D). These data were used in the model to predict live-time for partial collimation. The model was then validated against measurements in 2.7D mode. At low activity the model was very accurate at predicting the live-time fraction. Over-estimation of count-rates by the simulations lead to an uncertainly in the live-model. The uncertainty increased with activity concentration, reaching 0.9% and 2.2% at 20 kBq/mL for singles and coincidence live-time, respectively. When applied to 2.7D mode, the model predicted coincidence live-time accurate to 2.2% and 10% at 5 kBq/mL and 20 kBq/mL in the phantom, respectively. The 2.7D singles-counting live-time was predicted to within 0.2% of the measured value for up to 20 kBq/mL in the phantom.

We investigated the use of partial collimation on a clinical PET scanner by removing septa from conventional 2D collimators. The goal is to improve noise equivalent count-rates (NEC) compared to 2D and 3D scans for clinically relevant activity concentrations. We evaluated two cases: removing half of the septa (2.5D); and removing two-thirds of the septa (2.7D). System performance was first modeled using the SimSET simulation package, and then measured with the NEMA NU2-2001 count-rate cylinder (20 cm dia., 70 cm long), and 27 cm and 35 cm diameter cylinders of the same length. An image quality phantom was also imaged with the 2.7D collimator. SimSET predicted the relative NEC curves very well, as confirmed by measurements, with 2.5D and 2.7D NEC greater than 2D and 3D NEC in the range of ~5-20 mCi in the phantom. We successfully reconstructed images of the image quality phantom from measured 2.7D data using custom 2.7D normalization. Partial collimation shows promise for optimized clinical imaging in a fixed-collimator system.

The Na+/I- symporter (NIS) is a membrane glycoprotein that facilitates the uptake of iodine into thyroid follicular cells. Recently, we and others have demonstrated the feasibility of imaging subcutaneous xenografts expressing exogenous NIS, suggesting that NIS may serve as an imaging reporter gene to monitor vector delivery and therapeutic gene expression. In this study, we established NIS-expressing pulmonary tumors in nude mice to investigate the minimal tumor size required for in vivo detection of pulmonary tumors by single photon emission computed tomography (SPECT) with pinhole collimation. In order to define the anatomic location of NIS-expressing tumor nodules detectable by SPECT, we performed simultaneous, dual-isotope imaging. We injected 1 mCi 99mTc-MAA via tail vein to image pulmonary perfusion and injected 1 mCi Na125I intraperitoneally to image NIS-expressing tumors. Fused images showed that 99mTc-MAA perfusion defects correlated with NIS-mediated 125I uptake. Post-mortem analysis revealed that tumors 3 mm in diameter could be detected by SPECT with pinhole collimation. These studies demonstrate the feasibility of SPECT to detect pulmonary tumors expressing exogenous NIS in mice.

A novel Si-PIN imaging array is under investigation for a charged particle (beta, positron, or alpha) sensitive intraoperative camera to be used for (residual) tumor identification during surgery. This class of collimator-less nuclear imaging device has a higher signal response for direct interactions than its scintillator-optical detector-based counterparts. Monte Carlo simulations with 635 keV betas were performed, yielding maximum and projected ranges of 1.64 and 0.55 mm in Si. Up to 90% of these betas were completely absorbed in the first 0.30 mm. Based on these results, 300 microm thick prototype Si detector arrays were designed in a 16 x 16 crossed-grid arrangement with 0.8 mm wide orthogonal strips on 1.0 mm pitch. A NIM- and CAMAC-based high-density data acquisition and processing system was used to collect the list mode data. The system was calibrated by comparisons of measured spectra to energy deposition simulations or by direct measurement of various >100 keV conversion electron or beta emitters. Mean electronic noise per strip was <3.6 keV FWHM at room temperature. When detecting positrons, which have an accompanying 511 keV annihilation background, the flood irradiated beta/gamma ratio was approximately 40, indicating that beta images could be made without the use of background rejection techniques. The intrinsic spatial resolution corresponds to the 1 x 1 mm2 pixel size, and measurements of beta emitting point and line sources yielded FWHM resolutions of 1.5 (lateral) and 2.5 mm (diagonal), respectively, with the larger widths due to particle range blurting effects. Deconvolution of the finite source size yielded intrinsic resolutions that corresponded to the image pixel size. Transmission images of circle and line phantoms with various hole sizes and pitch were resolved with either pure beta or positron irradiation without a background correction. This novel semiconductor imaging device facilitates high charged particle and low gamma sensitivity, high signal/noise ratio, and allows for compact design to potentially aid surgical guidance by providing in situ images of clinical relevance.

The three-dimensional surface geometry of the medial tarsometatarsal joint ("first metatarsocuneiform") of the first ray was analyzed to determine if the shape of the joint is distinct in the medially deviated first metatarsal with metatarsus primus adductus (MPA). Clinical evaluation of 29 cadaver feet identified 13 feet with MPA and 16 with metatarsus primus rectus (MPR). Three-dimensional (3D) coordinates x, y, z of the first metatarsal and medial cuneiform joint facets of the feet were digitized on a Coordinate Measuring Machine (accuracy = 0.01 mm) and the data fitted with B-spline surfaces from which 3D curvature maps were generated. Comparison of means of surface-averaged maximum and minimum principal curvatures and root-mean-square curvatures showed significant (p < .0005) differences between the MPA and MPR subsets, male and female subsets, and metatarsal and cuneiform subsets. These results show that the articular shape of the medial tarsometatarsal joint in feet with MPA is significantly less contoured, or is flatter, than the same joint in normal or MPR feet. Results also showed that the female joints are more curved than male joints, and that metatarsal and cuneiform facets closely conform in shape to each other. These preliminary results may be related to questions concerning the anatomical and functional basis for the first metatarsal deviation, for radiographic presentation of the joint and surgical options in correcting related forefoot deformities.

This study examined the clinical effects of central cortical EEG feedback training in 8 patients with poorly controlled seizures. After base-line recordings, patients were trained in the laboratory and then initiated on a double or triple crossover design using portable equipment at home, with bimonthly laboratory test sessions. Performance at home was monitored by a strip chart recorder with the portable unit. Training was based on the simultaneous detection of two central cortical (C3--T3) EEG frequency bands (6--9 Hz and either 12--15 or 18--23 Hz), with reward provided for the occurrence of one in the absence of the other. The design consisted of successive 3 month periods of training, with reward contingencies reversed after each period without the subject's knowledge. Seizure incidence records were compared statistically before, during, and after the design. Six of the 8 patients reported significant and sustained seizure reductions, which averaged 74%, following reward for either 12--15 or 18--23 Hz in the absence of 6--9 Hz. Response to positive reward for 12--15 Hz was specific, with seizure rates returning to base line when reinforcement contingencies were reversed. Reduced seizure rates following positive reward for 18--23 Hz were not altered with contingency reversals. A nonspecific interpretation of these effects is rejected in favor of an EEG normalizing hypothesis.

A slow-wave electroencephalographic rhythm recorded from the sensorimotor cortex of the waking cat has been correlated behaviorally with the suppression of movement. Facilitation of this rhythm through conditioning selectively enhances a similar pattern recorded during sleep, the familiar spindle burst. The training also produced longer epochs of undisturbed sleep. The specific neural mechanism manipulated during wakefulness appears to function also in sleep and to be involved with the regulation of phasic motor behavior.