Performance evaluation of a whole-body PET scanner using the NEMA protocol. National Electrical Manufacturers Association

This study evaluates the performance of the newly developed high-resolution whole-body PET scanner ECAT EXACT HR+. METHODS: The scanner consists of four rings of 72 bismuth germanate block detectors each, covering an axial field of view of 15.5 cm with a patient port of 56.2 cm. A single block detector is divided into an 8 x 8 matrix, giving a total of 32 rings with 576 detectors each. The dimensions of a single detector element are 4.39 x 4.05 x 30 mm3. The scanner is equipped with extendable tungsten septa for two-dimensional two-dimensional measurements, as well as with three 68Ge line sources for transmission scans and daily quality control. The spatial resolution, scatter fraction, count rate, sensitivity, uniformity and accuracy of the implemented correction algorithms were evaluated after the National Electrical Manufacturers Association protocol using the standard acquisition parameters. RESULTS: The transaxial resolution in the two-dimensional mode is 4.3 mm (4.4 mm) in the center and increases to 4.7 mm (4.8 mm) tangential and to 8.3 mm (8.0 mm) radial at a distance of r = 20 cm from the center. The axial slice width measured in the two-dimensional mode varies between 4.2 and 6.6 mm FWHM over the transaxial field of view. In the three-dimensional mode the average axial resolution varies between 4.1 mm FWHM in the center and 7.8 mm at r = 20 cm. The scatter fraction is 17.1% (32.5%) for a lower energy discriminator level of 350 keV. The maximum true event count rate of 263 (345) kcps was measured at an activity concentration of 142 (26.9) kBq/ml. The total system sensitivity for true events is 5.7 (27.7) cps/Bq/ml. From the uniformity measurements, we obtained a volume variance of 3.9% (5.0%) and a system variance of 1.6% (1.7%). The implemented three-dimensional scatter correction algorithm reveals very favorable properties, whereas the three-dimensional attenuation correction yields slightly inaccurate results in low- and high-density regions. CONCLUSION: The ECAT EXACT HR+ has an excellent, nearly isotropic spatial resolution, which is advantageous for brain and small animal studies. While the relatively low slice sensitivity may hamper the capability for performing fast dynamic two-dimensional studies, the scanner offers a sufficient sensitivity and count rate capacity for fully three-dimensional whole-body imaging.     

Effects of heart rate on vulnerability to fibrillation in a computer model

The SET-2400W is a newly designed whole-body PET scanner with a large axial field of view (20 cm). Its physical performance was investigated and evaluated. The scanner consists of four rings of 112 BGO detector units (22.8 mm in-plane x 50 mm axial x 30 mm depth). Each detector unit has a 6 (in-plane) x 8 (axial) matrix of BGO crystals coupled to two dual photomultiplier tubes. They are arranged in 32 rings giving 63 two-dimensional image planes. Sensitivity for a 20-cm cylindrical phantom was 6.1 kcps/kBq/ml (224 kcps/microCi/ml) in the 2D clinical mode, and to 48.6 kcps/kBq/ml (1.8 Mcps/microCi/ml) in the 3D mode after scatter correction. In-plane spatial resolution was 3.9 mm FWHM at the center of the field-of-view, and 4.4 mm FWHM tangentially, and 5.4 mm FWHM radially at 100 mm from the center. Average axial resolution was 4.5 mm FWHM at the center and 5.8 mm FWHM at a radial position 100 mm from the center. Average scatter fraction was 8% for the 2D mode and 40% for the 3D mode. The maximum count rate was 230 kcps in the 2D mode and 350 kcps in the 3D mode. Clinical images demonstrate the utility of an enlarged axial field-of-view scanner in brain study and whole-body PET imaging.     

Performance characteristics of a whole-body PET scanner

METHODS: This study characterizes the performance of a newly developed whole-body PET scanner (Advance, General Electric Medical Systems, Milwaukee, WI). The scanner consists of 12,096 bismuth germinate crystals (4.0 mm transaxial by 8.1 mm axial by 30 mm radial) in 18 rings, giving 35 two-dimensional image planes through an axial field of view of 15.2 cm. The rings are separated by retractable tungsten septa. Intrinsic spatial resolution, scatter fraction, sensitivity, high count rate performance and image quality are evaluated. RESULTS: Transaxial resolution (in FWHM) is 3.8 mm at the center and increases to 5.0 mm tangential and 7.3 mm radial at R = 20 cm. Average axial resolution decreases from 4.0 mm FWHM at the center to 6.6 mm at R = 20 cm. Scatter fraction is 9.4% and 10.2% for direct and cross slices, respectively. With septa out, the average scatter fraction is 34%. Total system sensitivity for true events (in kcps/(microCi/cc)) is 223 with septa in and 1200 with septa out. Dead-time losses of 50% correspond to a radioactivity concentration of 4.9 (0.81) microCi/cc and a true event count rate of 489 (480) kcps with septa in (out). Noise-equivalent count rate (NECR) for the system as a whole shows a maximum of 261 (159) kcps at a radioactivity concentration of 4.1 (0.65) microCi/cc with septa in (out). NECR is insensitive to changes in lower gamma-energy discrimination between 250-350 keV. CONCLUSIONS: The results show the performance of the newly designed PET scanner to be well suited for clinical and research applications.     

Interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1), chemokines essentially involved in inflammatory and immune reactions

We analyzed the noise characteristics of two-dimensional (2-D) and three-dimensional (3-D) images obtained from the GE Advance positron emission tomography (PET) scanner. Three phantoms were used: a uniform 20-cm phantom, a 3-D Hoffman brain phantom, and a chest phantom with heart and lung inserts. Using gated acquisition, we acquired 20 statistically equivalent scans of each phantom in 2-D and 3-D modes at several activity levels. From these data, we calculated pixel normalized standard deviations (NSD's), scaled to phantom mean, across the replicate scans, which allowed us to characterize the radial and axial distributions of pixel noise. We also performed sequential measurements of the phantoms in 2-D and 3-D modes to measure noise (from interpixel standard deviations) as a function of activity. To compensate for the difference in axial slice width between 2-D and 3-D images (due to the septa and reconstruction effects), we developed a smoothing kernel to apply to the 2-D data. After matching the resolution, the ratio of image-derived NSD values (NSD2D/NSD3D)2 averaged throughout the uniform phantom was in good agreement with the noise equivalent count (NEC) ratio (NEC3D/NEC2D). By comparing different phantoms, we showed that the attenuation and emission distributions influence the spatial noise distribution. The estimates of pixel noise for 2-D and 3-D images produced here can be applied in the weighting of PET kinetic data and may be useful in the design of optimal dose and scanning requirements for PET studies. The accuracy of these phantom-based noise formulas should be validated for any given imaging situation, particularly in 3-D, if there is significant activity outside the scanner field of view.     

Dedicated PET scanners for breast imaging

We have used computer simulations to compare two designs for a PET scanner dedicated to breast imaging with a whole-body PET scanner. The new designs combine high spatial resolution, high sensitivity, and good energy resolution to detect small, low-contrast masses. The detectors are position sensitive NaI(Tl) scintillators. The first design is a ring scanner surrounding the breast and the second consists of two planar detectors placed on opposite sides of the breast. We have employed standard performance measures to compare the different designs: contrast, percentage standard deviation of the background, and signal-to-noise ratios of reconstructed images. The results of the simulations show that both of the proposed designs have better lesion detectability than a whole-body scanner. The results also show that contrast is higher in the ring breast system but that the noise is lower in the planar breast system. Overall, the ring system yields images with the best signal-to-noise ratios, although the planar system offers practical advantages for imaging the breast and axilla.     

Squamous intraepithelial lesions in young female university students]

Positron emission tomography and nuclear magnetic resonance spectroscopy are non-invasive techniques that allow serial metabolic measurements to be obtained in a single subject. Significant advantages could be obtained if both types of scans could be acquired with a single machine. A small-scale PET scanner, designed to operate in a high magnetic field, was therefore constructed and inserted into the top half of a 7.3 cm bore, 9.4 T NMR magnet and its performance characterized. The magnetic field did not significantly affect either the sensitivity (approximately 3 kcps/MBq) or the spatial resolution (2.0 mm full width at half maximum, measured using a 0.25 mm diameter line source) of the scanner. However, the presence of the PET scanner resulted in a small decrease in field homogeneity. The first, simultaneous 31P NMR spectra (200, 80 degrees pulses collected at 6 s intervals) and PET images (transverse, mid-ventricular slices at the level of the mitral value) from isolated, perfused rat hearts were acquired using a specially designed NMR probe inserted into the bottom half of the magnet. The PET images were of excellent quality, enabling the left ventricular wall and interventricular septum to be clearly seen. In conclusion, we have demonstrated the simultaneous acquisition of PET and NMR data from perfused rat hearts; we believe that the combination of these two powerful techniques has tremendous potential in both the laboratory and the clinic.     

High resolution multichannel fluorescence detection for capillary electrophoresis. Application to multicomponent analysis

A wavelength-resolved fluorescence detector for laser-induced fluorescence detection in capillary electrophoresis (CE) is described that uses a charge injection device (CID) array detector Post-column fluorescence detection occurs using a sheath flow cell. The limit of detection for fluorescein is 4.8 x 10(-11) M (29,000 molecules), the spectral resolution is 0.56 nm/pixel, and the spectrograph/CID monitors a 250 nm spectrum throughout the 250-875 nm range. Custom array readout, data manipulation and data processing methods are described to convert wavelength/spatial CID images into electropherograms. The application of the system to characterizing bilirubins in human serum is described, demonstrating the ability to match electrophoretic peaks to standards using spectral information.     

PET instrumentation: what are the limits?

This report has emphasized the attributes of positron emission tomography (PET) through a discussion of the historical development with attention to limitations or factors that are of importance in using and further developing this technology. As is the case for all nuclear detector developments, the factors that require consideration are spatial resolution, uniformity of resolution, sensitivity, distortions (attenuation), background noise (scatter and randoms), image volume, data acquisition capabilities (count-rate saturation), and limitations based on allowable radiation doses to the subject. Forty years ago, the fact that dual gamma-cameras could not handle the count-rates from the short half-life radionuclides that had clinical applications at that time (ie, 15O, 11C, 13N) precluded their acceptance in nuclear medicine. With the advent of 18F applications particularly with FDG in oncology, this limitations was no longer a barrier. Twenty years ago and until recently, the promise of time-of-flight PET has been stifled by the fact that the appropriately fast scintillator BaF2 had too low an efficiency (low density) to be useful in improving the signal to noise of a time-of-flight tomograph over contemporary systems. With the development of dense scintillators with high light output and high speed such as LSO30 the time-of-flight potentials are now once again worth pursuing. Twenty years ago systems that theoretically would have improved sensitivity by minimal or no septa with spherical geometric arrangements of detectors were ignored because it appeared that scatter backgrounds would lead to a signal to noise less than 1. But in the last 5 years, cylindrical systems without speta have shown that noise effective sensitivity improvements of a factor of 4 can be realized. With time-of-flight additional improvements in sensitivity will be realized. Horizons for detector development include discovery of new scintillators, new methods of registering scintillation light, deployment of larger field of view systems and methods of compensating for scatter, randoms, attenuation, and irregular sampling associated with new geometries which can encircle most of the body. The expected limit for PET is 2 mm isotropic resolution for the head and appendages including joints and breasts. Clinical realization of this resolution for the thorax and abdomen requires compensation for motion and even in this area strategies are underdevelopment which rely on the improvement in sensitivity being realized by 3D systems.     

FDG PET and dual-head gamma camera positron coincidence detection imaging of suspected malignancies and brain disorders

The purpose of the study was to compare the diagnostic accuracy of fluorodeoxyglucose (FDG) images obtained with a dual-head coincidence gamma camera (DHC) with those obtained with a dedicated PET in a series of 26 patients. METHODS: Nineteen patients with known or suspected malignancies and 7 patients with neurological disorders underwent PET imaging after injection of approximately 10 mCi of FDG. Whole-body imaging was performed on 19 patients and brain imaging on 7 patients. DHC images were then acquired for 30 min over the region of interest using a dual-head gamma camera equipped with 3/8-in.-thick NaI(TI) crystals and parallel slit-hole collimators. The images were reconstructed in the normal mode, using photopeak/photopeak, photopeak/Compton and Compton/photopeak coincidence events. RESULTS: Although the spatial resolutions of PET with a dedicated PET scanner and of DHC are in the same range, the lesion detectability remains superior with PET (4 mm for PET versus 13.5 mm for DHC in phantom experiments) with a contrast ratio of 5:1. This is most probably attributable to the higher sensitivity of PET (2238 coincidences/min/microCi for PET versus 89 coincidences/min/microCi for DHC). The pattern of uptake and interpretation for brain imaging was similar on both PET and DHC images in all patients. In the 19 oncology patients, 38 lesions ranging from 0.7 to 5 cm were detected by PET. DHC imaging detected 28 (73%) of these lesions. Among the 10 lesions not seen with DHC, 5 were less than 1.2 cm, 2 were located centrally within the liver and suffered from marked attenuation effects and 3 were adjacent to regions with high physiological activity. The nondetectability of some lesions with DHC compared with PET can be explained by several factors: (a) start of imaging time (mean+/-SD: 73+/-16 min for PET versus 115+/-68 min for DHC, leading to FDG decay to 6.75 mCi for PET and 5.2 mCi for DHC); (b) limited efficiency of a 3/8-inch-thick Nal(TI) crystal to detect 18F photons; (c) suboptimal two-dimensional reconstruction algorithm; and (d) absence of soft-tissue attenuation correction for centrally located lesions. CONCLUSION: FDG DHC imaging is a promising technique for oncological and brain imaging.     

Stable attachment for herpes simplex virus penetration into human cells requires glycoprotein D in the virion and cell receptors that are missing for entry-defective porcine cells

In gradient elution separations, it may be required to change either column length (to increase resolution or shorten run time) or column diameter (for an increase in sensitivity or for preparative separations). In either of these changes of column dimensions, it is usually desired to maintain the same relative band spacing (selectivity), so as to increase resolution in proportion to (column plate number)1/2 when increasing column length, or to maintain constant resolution when changing column diameter. A general rule for avoiding changes in band spacing in these situations is to maintain the quantity [(gradient time) x (flow-rate)/(column volume)] constant, while holding the initial and final gradient mobile phase compositions (%B) fixed. This rule is only valid as long as the equipment hold-up volume (dwell volume) is negligible, or if all sample components are strongly retained at the start of the gradient. When neither of the latter conditions apply, then significant changes in band spacing may result when changing column size. Rules are presented for recognizing this potential problem for a given sample/HPLC-equipment combination, and adjustments in separation conditions that can avoid this problem are discussed. Changes in band spacing as a result of change in column size are of special concern when developing procedures for preparative chromatography under gradient conditions.     

Feldkamp and circle-and-line cone-beam reconstruction for 3D micro-CT of vascular networks

Detailed morphometric knowledge of the microvascular network is needed for studies relating structure to haemodynamic function in organs like the lung. Clinical volumetric CT is limited to millimetre-order spatial resolution. Since evidence suggests that small arterioles (50 to 300 micrometres) dominate pulmonary haemodynamics, we built a micro-CT scanner, capable of imaging excised lungs in 3D with 100 microm resolution, for basic physiology research. The scanner incorporates a micro-focal (3 microm) x-ray source, an xyz theta stage and a CCD-coupled image intensifier detector. We imaged phantoms and contrast-enhanced rat lungs, reconstructing the data with either the Feldkamp or the circle-and-line cone-beam reconstruction algorithm. We present reconstructions using 180 views over 360 degrees for the circular trajectory, augmented with views from a linear scan for the circle-and-line algorithm. Especially for platelike features perpendicular to the rotation axis and remote from the midplane, the circle-and-line algorithm produces superior reconstructions compared with Feldkamp's algorithm. We conclude that the use of nonplanar source trajectories to perform micro-CT on contrast-enhanced, excised lungs can provide data useful for morphometric analysis of vascular trees, currently down to the 130 microm level.     

High-resolution 3D Bayesian image reconstruction using the microPET small-animal scanner

A Bayesian method is described for reconstruction of high-resolution 3D images from the microPET small-animal scanner. Resolution recovery is achieved by explicitly modelling the depth dependent geometric sensitivity for each voxel in combination with an accurate detector response model that includes factors due to photon pair non-collinearity and inter-crystal scatter and penetration. To reduce storage and computational costs we use a factored matrix in which the detector response is modelled using a sinogram blurring kernel. Maximum a posteriori (MAP) images are reconstructed using this model in combination with a Poisson likelihood function and a Gibbs prior on the image. Reconstructions obtained from point source data using the accurate system model demonstrate a potential for near-isotropic FWHM resolution of approximately 1.2 mm at the center of the field of view compared with approximately 2 mm when using an analytic 3D reprojection (3DRP) method with a ramp filter. These results also show the ability of the accurate system model to compensate for resolution loss due to crystal penetration producing nearly constant radial FWHM resolution of 1 mm out to a 4 mm radius. Studies with a point source in a uniform cylinder indicate that as the resolution of the image is reduced to control noise propagation the resolution obtained using the accurate system model is superior to that obtained using 3DRP at matched background noise levels. Additional studies using pie phantoms with hot and cold cylinders of diameter 1-2.5 mm and 18FDG animal studies appear to confirm this observation.     

Maximum a posteriori estimation with Good's roughness for three-dimensional optical-sectioning microscopy

The three-dimensional image-reconstruction problem solved here for optical-sectioning microscopy is to estimate the fluorescence intensity lambda(x), where x epsilon R3, given a series of Poisson counting process measurements [Mj(dx)]jJ = 1, each with intensity [formula: see text] with [formula: see text] being the point spread of the optics focused to the jth plane and sj(y) the detection probability for detector point y at focal depth j. A maximum a posteriori reconstruction generated by inducing a prior distribution on the space of images via Good's three-dimensional rotationally invariant roughness penalty [formula: see text] It is proven that the sequence of iterates that is generated by using the expectation maximization algorithm is monotonically increasing in posterior probability, with stable points of the iteration satisfying the necessary maximizer conditions of the maximum a posteriori solution. The algorithms were implemented on the DECmpp-SX, a 64 x 64 parallel processor, running at < 2 s/(64(3), 3-D iteration). Results are demonstrated from simulated as well as amoebae and volvox data. We study performance comparisons of the algorithms for the missing-data problems corresponding to fast data collection for rapid motion studies in which every other focal plane is removed and for imaging with limited detector areas and efficiency.     

Dual-slice spiral versus single-slice spiral scanning: comparison of the physical performance of two computed tomography scanners

In this paper we deal with two types of spiral scanners; one is a single-slice spiral scanner, while the other employs dual-slice technology into spiral scanning. Physical performance parameters, including image noise, contrast resolution, spatial resolution (transversal and longitudinal), and radiation exposure are measured. Computer simulations based on two interpolation methods (180 degrees and 360 degrees linear interpolation) are also used in evaluating the slice-sensitivity profile (SSP) and noise. The results show that the noise behaves in the same way for both types of scanners. The noise change, relative to that of the standard scan with the same scanning parameters, depends solely on the interpolation algorithm. Table speed and scanner geometry (either single slice or dual slice) have no effect on the noise value. For the given table speed, as well as individual detector collimation (slice width) the dual-slice scan results in better longitudinal resolution (SSP) compared to a single-slice scan if the scan is obtained with nonoverlapping slices (pitch greater than 2). This is because the dual-slice scan obtains twice the number of nonoverlapped projections for the same length, which reduces the degradation of the slice profile by using more densely arranged projections (in the longitudinal direction) for the interpolation. In the dual-slice scanner the workable scan rate is extended up to pitch 4 compared to a pitch of 2 for the single-slice scanner. Therefore, the dual-slice spiral scanner is preferred in applications requiring an increased scan rate with comparative image quality.     

Combined constraints for efficient algebraic regularized methods in fully 3D reconstruction

SPECT systems incorporate the use of one or more rotating gamma cameras which can be equipped with cone-beam collimators to improve the trade-off between spatial resolution and sensitivity. The geometry of the cone-beam collimators implies that a specific 3D reconstruction algorithm must be applied. Algebraic methods provide the possibility of including the physical characteristics, such as attenuation, Compton scatter and detector response, in the reconstruction process. However, the reconstruction problem is an ill-posed problem which should be regularized. This paper presents a 3D algebraic method that combines three regularizing constraints. These constraints deal respectively with penalizing negative voxels, local noise smoothing and missing data compensation. The results presented were obtained from imaging simulations, phantom data and from a thyroid clinical study of a normal volunteer.     

Model-free reconstruction of three-dimensional myocardial strain from planar tagged MR images

A technique is presented for reconstructing a three-dimensional myocardial strain map from a set of parallel-tagged MR images. Radial strains were reconstructed from in vivo data from an anesthetized dog with values between .05 and .1 with a precision of +/- .003 for a tag detection accuracy of .1 mm and a tag spacing of 2.5 mm. The reconstruction spatial resolution was demonstrated by reconstructing a localized displacement abnormality. In the circumferential direction, the abnormality that resulted in 50% displacement attenuation had a full width at half maximum of 5.4 +/- .4 mm (mean +/- SD). Graphs are presented showing the relationship between the size of an abnormality and the ability of the method to reconstruct that abnormality. The combination of high resolution parallel-tagged MR images and the model-free, coordinate system-free strain reconstruction technique presented in this paper is capable of producing accurate, high resolution strain maps of the myocardium.     

用于波长色散X射线荧光光谱仪的闪烁计数器及信号处理系统的研制

闪烁计数器(SC)是波长色散X射线荧光光谱仪(WDXRF)常用的探测器。相较于传统的闪烁计数器,通过反复试验,采用100μm的Be片作为屏蔽材料与闪烁体一体化封装,采用石英玻璃作为NaI晶体的封装材料,改善了NaI晶体的封装工艺,实现了NaI晶体的良好密封,提高了探测器的探测效率;通过电子器件定制选型,实现了对闪烁计数器输出的微弱信号的有效提取及放大,提高了探测器的能量分辨率;采用数字可调信号放大技术,实现了阳极脉冲信号放大倍数的连续可调,提高了探测器的探测范围。将上述闪烁计数器用于顺序式波长色散X射线荧光光谱仪,依照国家计量检定规程JJG 810—1993对整机进行了精密度、稳定性、探测器分辨率的测定实验。其结果为:纯铜块样品的CuKα计数值的精密度指标为0.078%,铬镍不锈钢圆块样品的NiKα计数值的稳定性指标为0.238%,探测器能量分辨率指标为39.73%,均达到该检定规程中A级指标要求。     

A rotating PET scanner using BGO block detectors: design, performance and applications

Recent advances in fully three-dimensional reconstruction for multi-ring PET scanners have led us to explore the potential of a prototype scanner based on the rotation of two opposing arrays of BGO block detectors. The prototype contains only one-third of the number of detectors in the equivalent full ring scanner, resulting in reduced cost. With a lower energy threshold at 250 keV, the absolute efficiency of the scanner is 0.5% and the scatter fraction is 35% for a 20-cm cylinder. Transaxial and axial spatial resolution is about 6 mm. The maximum noise equivalent count rate estimated for a 15-cm diameter cylinder is 36,000 cps at a concentration of 26 kBq/ml. The minimum scan time for a 18F-fluoro-2-deoxyglucose (FDG) brain study is 55 sec. The camera has been validated for clinical applications using both FDG and 82Rb.     

Technical bases and acquisition conditions of electron-beam computed tomography

PURPOSE: In this review the technical principle and scanner characteristics of electron beam computer tomography (EBCT) are discussed. METHODS: In contrast to conventional CT, image acquisition in EBCT is achieved without mechanically moving parts. This construction allows for short acquisition times in investigating given anatomical regions (100 ms per slice) or up to 8 levels without table movement and short interscan delays (50 ms per slice). RESULTS: Depending on the nature of the investigation, the scanner can be used in the single slice, continuous volume scanning and multi slice mode. The single slice mode is used for detection and quantification of coronary calcifications and for CT angiography of the coronary vessels. Equivalent to the spiral mode in conventional CT, continuous volume scanning may be used for routine investigation of the chest and abdomen. Functional investigations of the heart and perfusion measurement of different organs can be performed in multi slice mode. Because of the geometry of the electron beam scanner, radiation exposure for certain investigations is above the exposure with conventional CT. CONCLUSION: Future developments will focus on dose efficient radiation collimation, high resolution detector systems and artefact reducing reconstruction kernels.     

Pre-processing variance reducing techniques in multispectral positron emission tomography

Stochastic fluctuations and systematic errors severely restrict the potential of multispectral acquisition to improve scatter correction by energy-dependent processing in high-resolution positron emission tomography (PET). To overcome this limitation, three pre-processing approaches which reduce stochastic fluctuations and systematic errors without degrading spatial resolution were investigated: statistical variance was reduced by smoothing acquired data in energy space, systematic errors due to nonuniform detector efficiency were minimized by normalizing the data in the spatial domain and the overall variance was further reduced by selecting an optimal pre-processing sequence. Selection of the best protocol to reduce stochastic fluctuations entailed comparisons between four smoothing algorithms (prior constrained (PC) smoothing, weighted smoothing (WS), ideal low-pass filtering (ILF) and mean median (MM) smoothing) and permutations of three pre-processing procedures (smoothing, normalization and subtraction of random events). Results demonstrated that spectral smoothing by WS, ILF and MM efficiently reduces the statistical variance in both the energy and spatial domains without observable spatial resolution loss. The ILF algorithm was found to be the most convenient in terms of simplicity and efficiency. Regardless of the position of subtraction of randoms in the sequence, reduction of the systematic errors by normalization followed by spectral smoothing to suppress statistical noise produced the best results. However, subtraction of random events first in the sequence reduces computation load by half since the need to pre-process this distribution before subtraction is removed. In summary, normalizing data in the spatial domain and smoothing data in energy space are essential steps required to reduce systematic errors and statistical variance independently without degrading spatial resolution of multispectral PET data.