Evaluation of event position reconstruction in monolithic crystals that are optically coupled.

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 mm3 LYSO crystals optically coupled together using optical adhesive, to mimic a 52 × 52 × 10 mm3 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.

FPGA-Based Pulse Pile-Up Correction With Energy and Timing Recovery.

Modern field programmable gate arrays (FPGAs) are capable of performing complex discrete signal processing algorithms with clock rates well above 100 MHz. This, combined with FPGA's low expense, ease of use, and selected dedicated hardware make them an ideal technology for a data acquisition system for a positron emission tomography (PET) scanner. The University of Washington is producing a high-resolution, small-animal PET scanner that utilizes FPGAs as the core of the front-end electronics. For this scanner, functions that are typically performed in dedicated circuits, or offline, are being migrated to the FPGA. This will not only simplify the electronics, but the features of modern FPGAs can be utilized to add significant signal processing power to produce higher quality images. In this paper we report on an all-digital pulse pile-up correction algorithm that has been developed for the FPGA. The pile-up mitigation algorithm will allow the scanner to run at higher count rates without incurring large data losses due to the overlapping of scintillation signals. This correction technique utilizes a reference pulse to extract timing and energy information for most pile-up events. Using pulses acquired from a Zecotech Photonics MAPD-N with an LFS-3 scintillator, we show that good timing and energy information can be achieved in the presence of pile-up utilizing a moderate amount of FPGA resources.

Effective count rates for PET scanners with reduced and extended axial field of view.

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.

FPGA-Based Pulse Pileup Correction.

Modern Field Programmable Gate Arrays (FPGAs) are capable of performing complex discrete signal processing algorithms with clock rates above 100MHz. This combined with FPGA's low expense, ease of use, and selected dedicated hardware make them an ideal technology for a data acquisition system for a positron emission tomography (PET) scanner. The University of Washington is producing a high-resolution, small-animal PET scanner that utilizes FPGAs as the core of the front-end electronics. For this next generation scanner, functions that are typically performed in dedicated circuits, or offline, are being migrated to the FPGA. This will not only simplify the electronics, but the features of modern FPGAs can be utilizes to add significant signal processing power to produce higher resolution images. In this paper we report on an all-digital pulse pileup correction algorithm that is being developed for the FPGA. The pileup mitigation algorithm will allow the scanner to run at higher count rates without incurring large data losses due to the overlapping of scintillation signals. This correction technique utilizes a reference pulse to extract timing and energy information for most pileup events. Using pulses were acquired from a Zecotech Photonics MAPDN with an LFS-3 scintillator, we show that good timing and energy information can be achieved in the presence of pileup.

Evolution of the Design of a Second Generation FireWire Based Data Acquisition System.

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.

An 8×8 Row-Column Summing Readout Electronics for Preclinical Positron Emission Tomography Scanners.

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.

Measured count-rate performance of the Discovery STE PET/CT scanner in 2D, 3D and partial collimation acquisition modes.

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.

Parametric positioning of a continuous crystal PET detector with depth of interaction decoding.

Here we demonstrate a parametric positioning method on a continuous crystal detector. Three different models for the light distribution were tested. Diagnosis of the residues showed that the parametric model fits the experimental data better than Gaussian and Cauchy models in our particular experimental setup. Based on the correlation between the spread and the peak value of the light distribution model with the depth of interaction (DOI), we were able to estimate the three-dimensional position of a scintillation event. On our continuous miniature crystal element (cMiCE) detector module with 8 mm thick LYSO crystal, the intrinsic spatial resolution is 1.06 mm at the center and 1.27 mm at the corner using a maximum-likelihood estimation (MLE) method and the parametric model. The DOI resolution (full width at half maximum) is estimated to be approximately 3.24 mm. The positioning method using the parametric model outperformed the Gaussian and Cauchy models, in both MLE and weighted least-squares (WLS) fitting methods. The key feature of this technique is that it requires very little calibration of the detector, but still retains high resolution and high sensitivity.

Design of a Second Generation Firewire Based Data Acquisition System for Small Animal PET Scanners.

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.

Depth of interaction decoding of a continuous crystal detector module.

We present a clustering method to extract the depth of interaction (DOI) information from an 8 mm thick crystal version of our continuous miniature crystal element (cMiCE) small animal PET detector. This clustering method, based on the maximum-likelihood (ML) method, can effectively build look-up tables (LUT) for different DOI regions. Combined with our statistics-based positioning (SBP) method, which uses a LUT searching algorithm based on the ML method and two-dimensional mean-variance LUTs of light responses from each photomultiplier channel with respect to different gamma ray interaction positions, the position of interaction and DOI can be estimated simultaneously. Data simulated using DETECT2000 were used to help validate our approach. An experiment using our cMiCE detector was designed to evaluate the performance. Two and four DOI region clustering were applied to the simulated data. Two DOI regions were used for the experimental data. The misclassification rate for simulated data is about 3.5% for two DOI regions and 10.2% for four DOI regions. For the experimental data, the rate is estimated to be approximately 25%. By using multi-DOI LUTs, we also observed improvement of the detector spatial resolution, especially for the corner region of the crystal. These results show that our ML clustering method is a consistent and reliable way to characterize DOI in a continuous crystal detector without requiring any modifications to the crystal or detector front end electronics. The ability to characterize the depth-dependent light response function from measured data is a major step forward in developing practical detectors with DOI positioning capability.

Expanding SimSET to include block detectors: performance with pseudo-blocks and a true block model.

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.

New Directions for dMiCE - a Depth-of-Interaction Detector Design for PET Scanners.

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.

A comparison of normalization effects on three whole-body cylindrical 3D PET systems.

Normalization coefficients in three-dimensional positron emission tomography (3D PET) are affected by parameters such as camera geometry and the design and arrangement of the block detectors. In this work, normalization components for three whole-body 3D-capable tomographs (the GE Advance, the Siemens/CTI962/HR+ and the Siemens/CTI951R) are compared by means of a series of scans using uniform cylindrical and rotating line sources. Where applicable, the manufacturers' normalization methods are validated, and it is shown that these methods can be improved upon by using previously published normalization protocols. Those architectural differences between the three tomographs that affect normalization are discussed with a view to drawing more general conclusions about the effect of machine architecture on normalization. The data presented suggest that uniformity of system response becomes easier to achieve as the uniformity of crystal response within the detector block is improved.

PET imaging using dual-headed gamma cameras: an update.

Interest in clinical fluorodeoxyglucose (FDG) imaging with dual-headed gamma cameras continues to grow. In 1996, Jarritt and Acton published a review article of the use of gamma-camera systems for FDG imaging [1]. Since that article was published, considerable progress has been made in the adaptation of dual-headed camera systems for coincidence imaging. We review the basic principles of dual-headed coincidence imaging and some of the major limitations and challenges in the development of such technology. Since much of the current clinical experience with FDG imaging is based on the use of dedicated position emission tomographic (PET) systems, some comparisons of the performance limitations between dual-headed gamma-camera and dedicated PET systems are provided.

Carbon-11-thymidine and FDG to measure therapy response.

UNLABELLED: This study was performed to determine if PET imaging with 11C-thymidine could measure tumor response to chemotherapy early after the initiation of treatment. Imaging of deoxyriboneucleic acid biosynthesis, quantitated with 11C-thymidine, was compared with measurements of tumor energetics, obtained by imaging with 18F-fluorodeoxyglucose (FDG). METHODS: We imaged four patients with small cell lung cancer and two with high-grade sarcoma both before and approximately 1 wk after the start of chemotherapy. Thymidine and FDG studies were done on the same day. Tumor uptake was quantified by standardized uptake values (SUVs) for both tracers by the metabolic rate of FDG and thymidine flux constant (K(TdR)) using regions of interest placed on the most active part of the tumor. RESULTS: In the four patients with clinical response to treatment, both thymidine and FDG uptake markedly declined 1 wk after therapy. Thymidine measurements of SUV and K(TdR) declined by 64% +/- 15% and 84% +/- 33%, respectively. FDG SUV and the metabolic rate of FDG declined by 51% +/- 9% and 63% +/- 23%, respectively. In the patient with metastatic small cell lung cancer who had disease progression, the thymidine SUV decreased by only 8% (FDG not done). In a patient with abdominal sarcoma and progressive disease, thymidine SUV was essentially unchanged (declined by 3%), whereas FDG SUV increased by 69%. CONCLUSION: Images show a decline in both cellular energetics and proliferative rate after successful chemotherapy. In the two patients with progressive disease, thymidine uptake was unchanged 1 wk after therapy. In our limited series, K(TdR) measurements showed a complete shutdown in tumor proliferation in patients in whom FDG showed a more limited decrease in glucose metabolism.

Time-of-flight PET.

Time-of-Flight (TOF) positron emission tomographs (PET) were developed during the 1980s and early 1990s. Initial investigations into the potential improvements in signal-to-noise ratios if TOF information was utilized were published in 1980. By 1982, two groups (Washington University and Commissariat á l'Energie Atomique-Laboratorie d'Electronique et de L'Informatique [CEA-LETI]) were designing and building the first TOF tomographs. A third group at the University of Texas also designed and built a TOF system. These systems were optimized for high count-rate imaging of short-lived radiotracers for applications such as cardiac blood flow. The first system put into operation for patient scans was the Super PETT I built at Washington University by Michel Ter-Pogossian and his colleagues. The Washington University group went on to design two additional versions of TOF systems and the CEA-LETI group developed two basic tomograph designs. As Bismuth Germanate (BGO)-based scanners were refined, it became clear that the TOF systems could not provide the same high spatial resolution as offered by the newer systems. The use of the fast scintillators required for TOF systems also resulted in lower intrinsic sensitivity that was only partially compensated for by the effective gain in sensitivity offered by TOF image reconstruction techniques. Further development of TOF systems was suspended in the early 1990s. With the development of new scintillators that provide more light output and are denser than those available in the 1980s and considerably faster than BGO, there is new interest in the application of TOF techniques for future tomograph designs.

Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: analysis of the FDG lumped constant.

UNLABELLED: Calculation of the glucose metabolic rate (MRGlc) in brain with PET and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) requires knowing the rate of uptake of FDG relative to glucose from plasma into metabolite pools in the tissue. The proportionality factor for this is the FDG lumped constant (LC[FDG]), the ratio of the volumes of distribution of FDG and glucose multiplied by the hexokinase phosphorylation ratio for the two hexoses, Km(Glc) x Vm(FDG)/Km(FDG) x Vm(Glc) x MRGlc equals the FDG metabolic rate (MRFDG) divided by the LC(FDG), i.e., MRGlc = MRFDG/LC(FDG) and LC(FDG) = MRFDG/MRGlc. This investigation tested the hypothesis that LC(FDG) is significantly higher in gliomas than it is in brain uninvolved with tumor. METHODS: We imaged 40 patients with malignant gliomas with 1-[11C]glucose followed by FDG. The metabolic rates MRGlc and MRFDG were estimated for glioma and contralateral brain regions of interest by an optimization program based on three-compartment, four-rate constant models for the two hexoses. RESULTS: The LC(FDG), estimated as MRFDG/MRGlc, in gliomas was 1.40 +/- 0.46 (mean +/- s.d.; range = 0.72-3.10), whereas in non-tumor-bearing contralateral brain, it was 0.86 +/- 0.14 (range = 0.61-1.21) (p < 0.001, glioma versus contralateral brain). CONCLUSION: These data strongly suggest that the glioma LC(FDG) exceeds that of contralateral brain, that quantitation of the glioma MRGlc with FDG requires knowing the LC(FDG) specific for the glioma and that the LC(FDG) of normal brain is higher than previously reported estimates of about 0.50. 2-Fluoro-2-deoxy-D-glucose/PET studies in which glioma glucose metabolism is calculated by the autoradiographic approach with normal brain rate constants and LC(FDG) will overestimate glioma MRGlc, to the extent that the glioma LC(FDG) exceeds the normal brain LC(FDG). "Hot spots" visualized in FDG/PET studies of gliomas represent regions where MRGlc, LC(FDG) or their product is higher in glioma than it is in uninvolved brain tissue.

Energy-based scatter corrections for scintillation camera images of iodine-131.

UNLABELLED: The use of high-dose 131I antibody therapy requires accurate measurement of normal tissue uptake to optimize the therapeutic dose. One of the factors limiting the accuracy of such measurements is scatter and collimator septal penetration. This study evaluated two classes of energy-based scatter corrections for quantitative 131I imaging: window-based and spectrum-fitting. METHODS: The window-based approaches estimate scatter from data in two or three energy windows placed on either side of the 364-keV photopeak using empirical weighting factors. A set of images from spheres in an elliptical phantom were used to evaluate each of the window-based corrections. The spectrum-fitting technique estimates detected scatter at each pixel by fitting the observed energy spectrum with a function that models the photopeak and scatter, and which incorporates the response function of the camera. This technique was evaluated using a set of Rollo phantom images. RESULTS: All of the window-based methods performed significantly better than a single photopeak window (338-389 keV), but the weighting factors were found to depend on the object being imaged. For images contaminated with scatter, the spectrum-fitting method significantly improved quantitation over photopeak windowing. Little difference, however, between any of the methods was observed for images containing small amounts of scatter. CONCLUSION: Most clinical 131I imaging protocols will benefit from qualitative and quantitative improvements provided by the spectrum-fitting scatter correction. The technique offers the practical advantage that it does not require phantom-based calibrations. Finally, our results suggest that septal penetration and scatter in the collimator and other detector-head components are important sources of error in quantitative 131I images.

Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients.

PURPOSE: To assess pretreatment hypoxia in a variety of tumors using positron emission tomography (PET) after injection of the hypoxia-binding radiopharmaceutical [18F]fluoromisonidazole ([18F]FMISO). METHODS AND MATERIALS: Tumor fractional hypoxic volume (FHV) was determined in 21 nonsmall cell lung cancer patients, 7 head and neck cancer patients, 4 prostate cancer patients, and 5 patients with other malignancies by quantitative PET imaging after injection of [18F]FMISO (0.1 mCi/kg). The FHV was defined as the proportion of pixels in the imaged tumor volume with a tissue:blood [18F] activity ratio > or = 1.4 at 120-160 min postinjection. A FHV > 0 was taken as evidence for tumor hypoxia. RESULTS: Hypoxia was observed in 36 of 37 tumors studied with FMISO PET imaging; FHVs ranged from 0 to 94.7%. In nonsmall cell lung cancers (n = 21), the median FHV was 47.6% and the range, 1.3 to 94.7%. There was no correlation between tumor size and FHV. In the seven head and neck carcinomas, the median FHV was 8.8%, with a range from 0.2 to 18.9%. In the group of four prostate cancers, the median and range were 18.2% and 0 to 93.9%, while in a group of five tumors of different types the median FHV was 55.2% (range: 21.4 to 85.8%). CONCLUSIONS: Hypoxia was present in 97% of the tumors studied and the extent of hypoxia varied markedly between tumors in the same site or of the same histology. Hypoxia also was distributed heterogeneously between regions within a single tumor. These results are consistent with O2 electrode measures with other types of human tumors. The intra- and intertumor variability indicate the importance of making oxygenation measures in individual tumors and the necessity to sample as much of the tumor volume as possible.

Scatter and attenuation correction for 111In based on energy spectrum fitting.

A combined scatter and attenuation correction that does not require a transmission scan is proposed for 111In imaging. Estimates of the unscattered intensity at both 171 and 245 keV are obtained by fitting the observed energy spectrum at each pixel or region of interest using the measured scatter-free spectrum and a simple model for scatter. The scatter model for the 171 keV peak accounts for scatter contributed by both the 171 and 245 keV emissions. After correcting for scatter, the attenuation is estimated from the observed ratio of photopeak intensities using the known difference in attenuation at the two emission energies and a model based on a point source in water. Accurate scatter correction is a prerequisite for the success of this method because scatter from the higher energy emission will otherwise contaminate the lower photopeak. This differential attenuation method (DAM) of estimating attenuation is demonstrated and calibrated using a series of point source measurements with a wedge-shaped attenuator. The observed absolute and differential attenuation are in good agreement with the narrow-beam linear attenuation coefficients for water. Estimates of precision suggest a depth resolution of 1.0-2.5 cm for realistic count densities over the clinically relevant depth range (0-25 cm). The accuracy of DAM in a more realistic attenuation environment is assessed using a hot sphere inside the anthropomorphic data spectrum torso phantom viewed from several angles (with differing attenuation). Finally, the potential of DAM for SPECT attenuation correction was investigated by computer simulation using the SIMSET Monte Carlo software. Preliminary results based on measured planar data and simulated SPECT data indicate that DAM can improve the quality and quantitative accuracy of 111In images. In one SPECT simulation study, the average error in tumor to soft-tissue ratios was reduced from 32% for uncorrected data to 8% for data corrected with DAM. However, the technique is susceptible to significant noise amplification and can cause substantial streak artifacts in low-count SPECT studies if sufficient smoothing of the depth estimates is not performed.