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Poststroke neuroinflammation exacerbates disease progression. [ 11 C]PK11195-positron emission tomography (PET) imaging has been used to visualize neuroinflammation; however, its short half-life of 20 min limits its clinical use. [ 123 I]CLINDE has a longer half-life (13h); therefore, [ 123 I]CLINDE-single-photon emission computed tomography (SPECT) imaging is potentially more practical than [ 11 C]PK11195-PET imaging in clinical settings. The objectives of this study were to 1) validate neuroinflammation imaging using [ 123 I]CLINDE and 2) investigate the mechanisms underlying stroke in association with neuroinflammation using multimodal techniques, including magnetic resonance imaging (MRI), gas-PET, and histological analysis, in a rat model of ischemic stroke, that is, permanent middle cerebral artery occlusion (pMCAo). At 6 days post-pMCAo, [ 123 I]CLINDE-SPECT considerably corresponded to the immunohistochemical images stained with the CD68 antibody (a marker for microglia/microphages), comparable to the level observed in [ 11 C]PK11195-PET images. In addition, the [ 123 I]CLINDE-SPECT images corresponded well with autoradiography images. Rats with severe infarcts, as defined by MRI, exhibited marked neuroinflammation in the peri-infarct area and less neuroinflammation in the ischemic core, accompanied by a substantial reduction in the cerebral metabolic rate of oxygen (CMRO 2 ) in 15 O-gas-PET. Rats with moderate-to-mild infarcts exhibited neuroinflammation in the ischemic core, where CMRO 2 levels were mildly reduced. This study demonstrates that [ 123 I]CLINDE-SPECT imaging is suitable for neuroinflammation imaging and that the distribution of neuroinflammation varies depending on the severity of infarction., Competing Interests: Declaration of competing interest, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The Cingulate Island Sign score (CIScore) by rCBF SPECT is used in the differentiation between Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) but has some false-positive AD cases. To resolve the problem, we developed new differential diagnosing method incorporating occipital lobe and para-hippocampal rCBF., Materials and Methods: In 27 DLB and 31 AD cases undertaken Tc-99 m-ECD SPECT, we evaluated the mean Z score in the bilateral superior, middle, inferior occipital gyri, cuneus, amygdala, hippocampus, and para-hippocampus. One criterion of DLB was defined as the case with CIScore lower than 0.27. The other criteria were the cases of following either or both two conditions were satisfied. (1) The number of occipital gyri with mean Z score higher than 1 is three or more. (2) The number of hippocampal regions with mean Z score higher than 1 is one or less. We compared the differential diagnostic ability among these four criterions., Results: The diagnostic accuracy by CIscore was 69% and that of the occipital gyri analysis 84%, para-hippocampal regions analysis 76% and combined occipital gyri and para-hippocampal regions analysis 93%., Conclusion: The new method by combined rCBF analysis of occipital gyri and para-hippocampal regions showed best diagnostic ability in differentiating DLB from AD.

Purpose: Quantitative estimates of dopamine transporter availability, determined with [(123)I]FP-CIT SPECT, depend on the SPECT equipment, including both hardware and (reconstruction) software, which limits their use in multicentre research and clinical routine. This study tested a dedicated reconstruction algorithm for its ability to reduce camera-specific intersubject variability in [(123)I]FP-CIT SPECT. The secondary aim was to evaluate binding in whole brain (excluding striatum) as a reference for quantitative analysis., Methods: Of 73 healthy subjects from the European Normal Control Database of [(123)I]FP-CIT recruited at six centres, 70 aged between 20 and 82 years were included. SPECT images were reconstructed using the QSPECT software package which provides fully automated detection of the outer contour of the head, camera-specific correction for scatter and septal penetration by transmission-dependent convolution subtraction, iterative OSEM reconstruction including attenuation correction, and camera-specific "to kBq/ml" calibration. LINK and HERMES reconstruction were used for head-to-head comparison. The specific striatal [(123)I]FP-CIT binding ratio (SBR) was computed using the Southampton method with binding in the whole brain, occipital cortex or cerebellum as the reference. The correlation between SBR and age was used as the primary quality measure., Results: The fraction of SBR variability explained by age was highest (1) with QSPECT, independently of the reference region, and (2) with whole brain as the reference, independently of the reconstruction algorithm., Conclusion: QSPECT reconstruction appears to be useful for reduction of camera-specific intersubject variability of [(123)I]FP-CIT SPECT in multisite and single-site multicamera settings. Whole brain excluding striatal binding as the reference provides more stable quantitative estimates than occipital or cerebellar binding.

Purpose: A recently developed technique which reconstructs quantitative images from original projection data acquired using existing single-photon emission computed tomography (SPECT) devices enabled quantitative assessment of cerebral blood flow (CBF) at rest and after acetazolamide challenge. This study was intended to generate a normal database and to investigate its inter-institutional consistency., Methods: The three institutions carried out a series of SPECT scanning on 32 healthy volunteers, following a recently proposed method that involved dual administration of (123)I-iodoamphetamine during a single SPECT scan. Intra-institute and inter-institutional variations of regional CBF values were evaluated both at rest and after acetazolamide challenge. Functional images were pooled for both rest and acetazolamide CBF, and inter-institutional difference was evaluated among these images using two independent software programs., Results: Quantitative assessment of CBF images at rest and after acetazolamide was successfully achieved with the given protocol in all institutions. Intra-institutional variation of CBF values at rest and after acetazolamide was consistent with previously reported values. Quantitative CBF values showed no significant difference among institutions in all regions, except for a posterior cerebral artery region after acetazolamide challenge in one institution which employed SPECT device with lowest spatial resolution. Pooled CBF images at rest and after acetazolamide generated using two software programs showed no institutional differences after equalization of the spatial resolution., Conclusions: SPECT can provide reproducible images from projection data acquired using different SPECT devices. A common database acquired at different institutions may be shared among institutions, if images are reconstructed using a quantitative reconstruction program, and acquired by following a standardized protocol.

Objectives: Thallium-201 ((201)Tl) single photon emission computed tomography (SPECT) is an important tool in the diagnosis of ischemic heart disease. Absolute quantification of myocardial blood flow (MBF) has the potential to provide more useful information on myocardial perfusion than semi-quantitative assessments. This study aimed to validate the quantification of MBF using (201)Tl cardiac SPECT based on a population-averaged input function (STD-IF) and one-point blood sample technique., Methods: (201)Tl emission and computed tomography (CT)-based attenuation scans were performed on 11 healthy volunteers at rest using a SPECT/CT scanner. Individual input functions (IND-IFs) during the emission scans were based on arterial blood samples. The STD-IF technique was validated as follows: (1) optimal time to calibrate a STD-IF was determined to minimize differences between the calibrated STD-IF and the IND-IFs. (2) Tissue time-activity curves (TTACs) were generated based on a single-tissue compartment model for MBFtrue = 0.5, 1.0, 1.5, and 2.0 mL/min/g, a constant distribution volume of 45 mL/mL, and IND-IFs. The pseudo STD-IF for each subject was generated using the leave-one-out technique. Using the optimal calibration time and the pseudo STD-IFs, MBF values were estimated on the TTACs with an autoradiography method. Optimal mid-scan time (MST) with a fixed duration of 20 min was determined to minimize intersubject variation in estimated MBF errors, and (3) Global and regional MBF values estimated with pseudo STD-IFs were compared to those with IND-IFs using the optimal calibration time and MST., Results: The optimal calibration time and MST were both 20 min after (201)Tl injection. Global MBF determined using both IND-IFs and pseudo STD-IF showed significant correlations with rate-pressure products, R (2) = 0.645; p < 0.01 and R (2) = 0.303; p < 0.05, respectively. The mean percent error in regional MBF using pseudo STD-IFs was 0.69 ± 7.80 % (-12.80 to 14.25 %). No significant difference was observed between regional MBF values using IND-IFs and pseudo STD-IFs., Conclusion: This study demonstrated that the proposed technique based on a STD-IF and one-point blood sample provided hemodynamically reasonable global MBF values and the regional MBF values comparable to those with IND-IFs.

Single photon emission computed tomography (SPECT) is used widely in clinical studies. However, the technique requires image reconstruction and the methods for correcting scattered radiation and absorption are not standardized among SPECT procedures. Therefore, quantitation of cerebral blood flow (CBF) may not be constant across SPECT models. The quantitative SPECT (QSPECT) software package has been developed for standardization of CBF. Using the QSPECT/dual-table autoradiographic (DTARG) method, CBF and cerebral vascular reactivity (CVR) at rest and after acetazolamide challenge can be evaluated using (123)I-iodoamphetamine in a single SPECT session. In this study, we examined the reproducibility of quantitative regional CBF and CVR in QSPECT/DTARG using different SPECT models at two facilities. The subjects were nine patients with chronic cerebral ischemic disease who underwent QSPECT/DTARG at both facilities with use of different γ-cameras and collimators. There were significant correlations for CBF at rest and after acetazolamide challenge measured at the two facilities. The consistency of the CBFs of the patients measured at the two facilities were good in all cases. Our results show that CBF measured by QSPECT/DTARG in the same patients is reproducible in different SPECT models. This indicates that standardized evaluation of CBF can be performed in large multicenter studies.

Objective: In a typical single photon emission computed tomography (SPECT) system, intrinsic spatial resolution depends on the accuracy of the identification of an interacting point, which is dominated by propagation of the scintillation photons in the detector block. This study was intended to establish a Monte Carlo simulation-based evaluation tool taking into account the propagation of scintillation photons to estimate the intrinsic spatial and energy resolutions of the position-sensitive scintillator block in a SPECT detector., Methods: We employed Geant4 Monte Carlo simulation library which incorporated the optical photon processes for two different designs of the position-sensitive scintillator blocks. The validation of the simulation code was performed for a monolithic NaI(Tl) scintillator (251 × 147 × 6.4 mm(3)) coupled to 15 flat-panel type multi-anode photo multiplier tubes (PMT) (H8500: Hamamatsu) and results were compared with those obtained experimentally. The code was then applied to a LaBr(3)(Ce) scintillator of 120 mm square with varied thicknesses for designing high-resolution detector., Results: The simulation resulted in 2.6 mm full width at half maximum (FWHM) of spatial resolution and 9.0% FWHM of energy resolution for the NaI(Tl)-based detector, which were in a good agreement of the experimental results, i.e., 2.7 mm and 10%, respectively. These findings suggest that Geant4 simulation including optical photon processes enables to predict the spatial and energy resolutions of a SPECT detector block accurately. The simulation also demonstrated that 2 mm spatial resolution can be obtained for a 6 mm thickness of the LaBr(3)(Ce), which is a significant improvement in performance as compared to existing gamma camera system that employs the scintillation detector fitted with PMTs., Conclusions: The Monte Carlo simulation-based evaluation tool was established to estimate the intrinsic spatial and energy resolutions of SPECT detector with position sensitive PMTs. This simulation may be useful to provide an optimal design of a SPECT detector without physical experiments.

The aim of this study is to develop a non-invasive procedure for quantitative assessment of regional cerebral blood flow using IMP and SPECT. A technique to utilize a population-based standardized arterial input function has been evaluated for the normal data base obtained from 3 institutions, which employed different SPECT device configurations. In total, data from 39 subjects were analyzed. Due to the unique feature of the QSPECT reconstruction software program, images are quantitative providing units of Bq/ml. Thus, the well counter values can be converted to absolute radioactivity concentration. The blood-to-whole-body average partition coefficient was 343.8 +/- 65.0 and did not show significant difference among the three institutions. The estimated blood counts agreed with those assessed by the well counter in all institutions, thus the arterial input function can be estimated with the unique conversion factor for all institutions. This feature may allow a large scale multi-center investigation, which may contribute to improve the non-invasive protocol.

Introduction: This study is intended to evaluate the feasibility of using a high-resolution pinhole SPECT system and iodine-123-N-isopropyl-4-iodoamphetamine ((123)I-IMP) for three-dimensional (3D) absolute quantitation of regional cerebral blood flow (rCBF) in mice., Methods: The pinhole SPECT system consists of a rotating stage and a pinhole collimator attached to a clinical gamma camera. The collimator's focal length is 251 mm. Phantom studies were performed to evaluate sensitivity and full-width half-maximum (FWHM) spatial resolution. The aperture-to-object distance was 15 mm. Six mice were studied. Cerebral infarctions were induced by ligating and disconnecting the distal portion of the left middle cerebral artery. Ex vivo SPECT studies were performed using harvested brains and skulls. The CBF volumetric image was computed using the standardized input function., Results: Excellent spatial resolution of 0.9-mm FWHM and uniform sensitivity throughout the 3D volume were demonstrated in the phantom experiments. The CBF images showed a defect in the infarcted areas and a reduction of CBF values in the infarcted region as compared with the control region., Conclusions: This study demonstrated the feasibility of the 3D quantitation of rCBF in mice using a high-resolution pinhole SPECT system and (123)I-IMP., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: The aim of this work was to evaluate a pixelated semiconductor detector and non-pixelated scintillation detector in a pinhole SPECT system for small animal imaging., Methods: We assumed two pixelated CdTe semiconductor detectors (a monolithic type and a modular type) and two non-pixelated NaI(Tl) scintillation detectors (a conventional type and a large detector field type). For the monolithic semiconductor detector we assumed that the size of a pixel was 1.0 × 1.0 mm², the thickness 1 mm, and an effective detector field 128 × 128 mm². For the modular-type semiconductor detector we assumed that the size of a pixel was 2.5 × 2.5 mm², the thickness 5 mm, and an effective detector field 320 × 320 mm². For the two scintillation detectors we assumed that the size of a pixel was 1.4 × 1.4 mm² and the intrinsic spatial resolution 4.0 mm FWHM, and the thickness 9 mm. For the conventional scintillation detector we assumed that the effective detector field was 179.2 × 179.2 mm², and for the large field scintillation detector 358.2 × 358.2 mm² and the magnification factor two. In the simulation we used a pinhole collimator with a pinhole size of 0.3 mm. We reconstructed SPECT images of hot-rod and cold-channel phantoms with projection data calculated with a Monte Carlo method assuming a fixed data acquisition time, and evaluated the image quality with respect to contrast and spatial resolution. In addition, we calculated the scatter fraction to compare the amount of scattered photons between the pixelated and non-pixelated detectors., Results: The image quality of the modular-type pixelated detector was similar to that of the non-pixelated detector operated with a twofold magnified data acquisition. The scattered photons and the parallax effect in the pixelated detector were small and similar to those in the non-pixelated detector., Conclusions: The performance of a modular-type pixelated semiconductor detector was almost the same as that of a non-pixelated scintillation detector with a magnified data acquisition in a small animal pinhole SPECT system.

Unlabelled: SPECT can provide valuable diagnostic and treatment response information in large-scale multicenter clinical trials. However, SPECT has been limited in providing consistent quantitative functional parametric values across the centers, largely because of a lack of standardized procedures to correct for attenuation and scatter. Recently, a novel software package has been developed to reconstruct quantitative SPECT images and assess cerebral blood flow (CBF) at rest and after acetazolamide challenge from a single SPECT session. This study was aimed at validating this technique at different institutions with a variety of SPECT devices and imaging protocols., Methods: Twelve participating institutions obtained a series of SPECT scans on physical phantoms and clinical patients. The phantom experiments included the assessment of septal penetration for each collimator used and of the accuracy of the reconstructed images. Clinical studies were divided into 3 protocols, including intrainstitutional reproducibility, a comparison with PET, and rest-rest study consistency. The results from 46 successful studies were analyzed., Results: Activity concentration estimation (Bq/mL) in the reconstructed SPECT images of a uniform cylindric phantom showed an interinstitution variation of ±5.1%, with a systematic underestimation of concentration by 12.5%. CBF values were reproducible both at rest and after acetazolamide on the basis of repeated studies in the same patient (mean ± SD difference, -0.4 ± 5.2 mL/min/100 g, n = 44). CBF values were also consistent with those determined using PET (-6.1 ± 5.1 mL/min/100 g, n = 6)., Conclusion: This study demonstrates that SPECT can quantitatively provide physiologic functional images of rest and acetazolamide challenge CBF, using a quantitative reconstruction software package.

Objective: The aim of this work was to evaluate an ultra-high spatial resolution SPECT system with a semiconductor detector and a high-resolution parallel-hole collimator or a pinhole collimator for small animal imaging., Methods: We evaluated an ultra-high spatial resolution SPECT system with a high-resolution parallel-hole collimator attached to a cadmium telluride (CdTe) semiconductor detector for small animal imaging. The sizes of an active area and a pixel in the semiconductor detector were 44 x 44 and 0.5 x 0.5 mm(2), respectively. In the high-resolution parallel-hole collimator the size of a hole was 0.4 x 0.4 mm(2), the thickness of a septum 0.1 mm, and the hole-length 30 mm. We also used a high-resolution pinhole collimator with a hole size of 0.3 or 0.5 mmvarphi. The physical performance of this SPECT system was evaluated with some experiments with phantoms filled with (99m)Tc-pertechnatate solution. In addition ideal performance and limitations of the system were evaluated with Monte Carlo simulations under the same geometrical conditions as in the experiments. In the evaluation for small animal imaging, we used mice that were administered with (99m)Tc-MDP. We also conducted an ultra-high resolution X-ray CT of the mice to verify the accumulated location of (99m)Tc-MDP using the bone CT images of the mice., Results: The results of the phantom experiments showed that we could resolve 1 mmvarphi hot-channels and 1.6 mmvarphi cold-rods with the high-resolution parallel-hole collimator and pinhole collimators. We could image 0.3 mmvarphi hot-channels with the high-resolution pinhole collimators. The results of the simulations showed that the resolution limit in the pinhole imaging was about 0.6 mm FWHM. And the results of experiments with mice showed that we could reconstruct high-resolution images of (99m)Tc-MDP. Furthermore, the distribution of (99m)Tc-MDP in a mouse was found to correspond closely to the location of the bones of the mouse in reconstructions made with the ultra-high resolution X-ray CT system., Conclusions: Our results demonstrated that the ultra-high spatial resolution SPECT system was feasible for small animal imaging allowing a relatively long data acquisition time.

Objective: The quality of single-photon emission computed tomography (SPECT) imaging is hampered by attenuation, collimator blurring, and scatter. Correction for all of these three factors is required for accurate reconstruction, but unfortunately, reconstruction-based compensation often leads to clinically unacceptable long reconstruction times. Especially, efficient scatter correction has proved to be difficult to achieve. The objective of this article was to extend the well-known transmission-dependent convolution subtraction (TDCS) scatter-correction approach into a rapid reconstruction-based scatter-compensation method and to include it into a fast 3D reconstruction algorithm with attenuation and collimator-blurring corrections., Methods: Ordered subsets expectation maximization algorithm with attenuation, collimator blurring, and accelerated transmission-dependent scatter compensation were implemented. The new reconstruction method was compared with TDCS-based scatter correction and with one other transmission-dependent scatter-correction method using Monte Carlo simulated projection data of (99m)Tc-ECD and (123)I-FP-CIT brain studies., Results: The new reconstruction-based scatter compensation outperformed the other two scatter-correction methods in terms of quantitative accuracy and contrast measured with normalized mean-squared error, gray-to-white matter and striatum-to-background ratios, and also in visual quality. Highest accuracy was achieved when all the corrections (i.e., attenuation, collimator blurring, and scatter) were applied., Conclusions: The developed 3D reconstruction algorithm with transmission-dependent scatter compensation is a promising alternative to accurate and efficient SPECT reconstruction.

Single proton emission computed tomography (SPECT) images are degraded by photon scatter making scatter compensation essential for accurate reconstruction. Reconstruction-based scatter compensation with Monte Carlo (MC) modelling of scatter shows promise for accurate scatter correction, but it is normally hampered by long computation times. The aim of this work was to accelerate the MC-based scatter compensation using coarse grid and intermittent scatter modelling. The acceleration methods were compared to un-accelerated implementation using MC-simulated projection data of the mathematical cardiac torso (MCAT) phantom modelling (99m)Tc uptake and clinical myocardial perfusion studies. The results showed that when combined the acceleration methods reduced the reconstruction time for 10 ordered subset expectation maximization (OS-EM) iterations from 56 to 11 min without a significant reduction in image quality indicating that the coarse grid and intermittent scatter modelling are suitable for MC-based scatter compensation in cardiac SPECT.

Purpose: 201Tl has been extensively used for myocardial perfusion and viability assessment. Unlike 99mTc-labelled agents, such as 99mTc-sestamibi and 99mTc-tetrofosmine, the regional concentration of 201Tl varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of 201Tl using dynamic SPECT., Methods: Dynamic SPECT was carried out on 20 normal canines after the intravenous administration of 201Tl using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time-activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant (K(1)) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments., Results: Regional time-activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBF(SPECT)) correlated well with the MBF values obtained by the radio-labelled microspheres (MBF(MS)) (MBF(SPECT) = -0.067 + 1.042 x MBF(MS), p < 0.001). The three-compartment model provided better fit than the two-compartment model, but the difference in MBF values between the two methods was small and could be accounted for with a simple linear regression., Conclusion: Absolute quantitation of regional MBF, for a wide physiological flow range, appears to be feasible using 201Tl and dynamic SPECT.

Background: The resolution of a gamma camera is depth-dependent and worsens with increasing distance to the camera resulting in a loss of fine details in SPECT images. A common approach to reduce the effects of this resolution loss is to utilize body-contour acquisition orbits. Even though body-contour orbits can improve resolution of reconstructed images their effect on lesion detection is not well known., Objective: To investigate whether body-contour orbits offer better defect detection performance than circular orbits in cardiac SPECT., Methods: The mathematical cardiac torso (MCAT) phantom was used to model Tc-sestamibi uptake. A total of four phantoms (two male and two female) with eight defects (four locations and two sizes) were generated and projection data were simulated using an analytical projector with attenuation, scatter, collimator response and acquisition orbit modelling. The circular and body-contour projections were reconstructed using the OSEM algorithm with/without collimator response compensation. Defect detection performance was assessed by calculating area under the receiver operating characteristic (ROC) curve for channelized Hotelling observer., Results: The defect detection performance of circular and body-contour acquisition was very similar and the difference in the area under the ROC curve between the orbits was not statistically significant with or without collimator response compensation. The collimator response compensation, on the other hand, was noticed to be valuable and it provided significantly better defect detection performance than reconstruction without it regardless of the acquisition orbit type., Conclusions: We conclude that by replacing circular orbit with more complex body-contour orbit will not lead to statistically significant increase in defect detection performance in cardiac SPECT.

Objective: A conventional pinhole single-photon emission computed tomography (SPECT) with a single circular orbit has limitations associated with non-uniform spatial resolution or axial blurring. Recently, we demonstrated that three-dimensional (3D) images with uniform spatial resolution and no blurring can be obtained by complete data acquired using two-circular orbit, combined with the 3D ordered subsets expectation maximization (OSEM) reconstruction method. However, a long computation time is required to obtain the reconstruction image, because of the fact that 3D-OSEM is an iterative method and two-orbit acquisition doubles the size of the projection data. To reduce the long reconstruction time, we parallelized the two-orbit pinhole 3D-OSEM reconstruction process by using a Beowulf personal computer (PC) cluster., Methods: The Beowulf PC cluster consists of seven PCs connected to Gbit Ethernet switches. Message passing interface protocol was utilized for parallelizing the reconstruction process. The projection data in a subset are distributed to each PC. The partial image forward- and back-projected in each PC is transferred to all PCs. The current image estimate on each PC is updated after summing the partial images. The performance of parallelization on the PC cluster was evaluated using two independent projection data sets acquired by a pinhole SPECT system with two different circular orbits., Results: Parallelization using the PC cluster improved the reconstruction time with increasing number of PCs. The reconstruction time of 54 min by the single PC was decreased to 10 min when six or seven PCs were used. The speed-up factor was 5.4. The reconstruction image by the PC cluster was virtually identical with that by the single PC., Conclusions: Parallelization of 3D-OSEM reconstruction for pinhole SPECT using the PC cluster can significantly reduce the computation time, whereas its implementation is simple and inexpensive.

A new method has been developed for diffusible tracers, to quantify CBF at rest and after pharmacological stress from a single session of dynamic scans with dual bolus administration of a radiotracer. The calculation process consisted of three steps, including the procedures of incorporating background radioactivity contaminated from the previous scan. Feasibility of this approach was tested on clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart, were carried out on each subject, after each of two split-dose administrations of 111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the second IMP injection. Additional PET scans were also carried out on 6 subjects on a separate day, at rest and after acetazolamide administration. The other 5 subjects were scanned only at rest during the whole study period. Quantitative CBF obtained by this method was in a good agreement with those determined with PET (y(ml/100 g/min)=1.07x(ml/100 g/min)-1.14, r=0.94). Vasareactivity was approximately 40% over the whole cerebral area on healthy controls, which was consistent with a literature value. Reproducibility of CBF determined in the rest-rest study was 1.5+/-5.7%. Noise enhancement of CBF images, particularly the second CBF, was reduced, providing reasonable image quality. Repeat assessment of quantitative CBF from a single session of scans with split-dose IMP is accurate, and may be applied to clinical research for assessing vascular reactivity in patients with chronic cerebral vascular disease.

Background and Objectives: Statistical reconstruction methods allow resolution recovery in tomographic reconstruction. Even though resolution recovery has the potential to improve overall image quality, pinhole SPECT images are still often reconstructed using simplified models of the acquisition geometry in order to reduce reconstruction time. This paper investigates the benefits of two resolution recovery methods, multi-ray and point-spread function based, in pinhole SPECT by comparing them to uncorrected reconstruction., Methods: Resolution recovery was incorporated into ordered subsets expectation maximization reconstruction algorithm. The first of the correction methods used a simple but very fast multiple projection ray approach, whereas the second, much slower, method modelled the acquisition geometry more accurately using the analytical point-spread function of the pinhole collimator. Line source, Jaszczak and contrast phantom studies were performed and used for comparison., Results: Resolution recovery improved resolution, contrast and visual quality of the images when compared to reconstructions without it. The method based on the point-spread function performed slightly better, but was almost 50 times slower than the much simpler multi-ray approach., Conclusion: The multiple projection ray approach is a promising method for very fast and easy resolution recovery in pinhole SPECT. It has a profound effect on image quality and can markedly improve the resolution-sensitivity trade-off.

Objectives: Pinhole SPECT which permits in vivo high resolution 3D imaging of physiological functions in small animals facilitates objective assessment of pharmaceutical development and regenerative therapy in pre-clinical trials. For handiness and mobility, the miniature size of the SPECT system is useful. We developed a small animal SPECT system based on a compact high-resolution gamma camera fitted to a pinhole collimator and an object-rotating unit. This study was aimed at evaluating the basic performance of the detection system and the feasibility of small animal SPECT imaging., Methods: The gamma camera consists of a 22 x 22 pixellated scintillator array of 1.8 mm x 1.8 mm x 5 mm NaI(Tl crystals with 0.2-mm gap between the crystals coupled to a 2" flat panel position-sensitive photomultiplier tube (Hamamatsu H8500) with 64 channels. The active imaging region of the camera was 43.8 mm x 43.8 mm. Data acquisition is controlled by a personal computer (Microsoft Windows) through the camera controller. Projection data over 360 degrees for SPECT images are obtained by synchronizing with the rotating unit. The knife-edge pinhole collimators made of tungsten are attached on the camera and have 0.5-mm and 1.0-mm apertures. The basic performance of the detection system was evaluated with 99mTc and 201Tl solutions. Energy resolution, system spatial resolution and linearity of count rate were measured. Rat myocardial perfusion SPECT scans were sequentially performed following intravenous injection of 201TlCl. Projection data were reconstructed using a previously validated pinhole 3D-OSEM method., Results: The energy resolution at 140 keV was 14.8% using a point source. The system spatial resolutions were 2.8-mm FWHM and 2.5-mm FWHM for 99mTc and 201Tl line sources, respectively, at 30-mm source distance (magnification factor of 1.3) using a 1.0-mm pinhole. The linearity between the activity and count rate was good up to 10 kcps. In a rat study, the left ventricular walls were clearly visible in all scans., Conclusions: We developed a compact SPECT system using compact gamma camera for small animals and evaluated basic physical performances. The present system may be of use for quantitation of biological functions such as myocardial blood flow in small animals.

Purpose: An image-based scatter correction (IBSC) method was developed to convert scatter-uncorrected into scatter-corrected SPECT images. The purpose of this study was to validate this method by means of phantom simulations and human studies with 99mTc-labeled tracers, based on comparison with the conventional triple energy window (TEW) method., Methods: The IBSC method corrects scatter on the reconstructed image I(mub)AC with Chang's attenuation correction factor. The scatter component image is estimated by convolving I(mub)AC with a scatter function followed by multiplication with an image-based scatter fraction function. The IBSC method was evaluated with Monte Carlo simulations and 99mTc-ethyl cysteinate dimer SPECT human brain perfusion studies obtained from five volunteers. The image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were compared., Results: Using data obtained from the simulations, the image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were found to be nearly identical for both gray and white matter. In human brain images, no significant differences in image contrast were observed between the IBSC and TEW methods., Conclusion: The IBSC method is a simple scatter correction technique feasible for use in clinical routine.

Pinhole single-photon emission computed tomography (SPECT) is able to provide information on the biodistribution of several radioligands in small laboratory animals, but has limitations associated with non-uniform spatial resolution or axial blurring. We have hypothesised that this blurring is due to incompleteness of the projection data acquired by a single circular pinhole orbit, and have evaluated a new strategy for accurate image reconstruction with better spatial resolution uniformity. A pinhole SPECT system using two circular orbits and a dedicated three-dimensional ordered subsets expectation maximisation (3D-OSEM) reconstruction method were developed. In this system, not the camera but the object rotates, and the two orbits are at 90 degrees and 45 degrees relative to the object's axis. This system satisfies Tuy's condition, and is thus able to provide complete data for 3D pinhole SPECT reconstruction within the whole field of view (FOV). To evaluate this system, a series of experiments was carried out using a multiple-disk phantom filled with 99mTc solution. The feasibility of the proposed method for small animal imaging was tested with a mouse bone study using 99mTc-hydroxymethylene diphosphonate. Feldkamp's filtered back-projection (FBP) method and the 3D-OSEM method were applied to these data sets, and the visual and statistical properties were examined. Axial blurring, which was still visible at the edge of the FOV even after applying the conventional 3D-OSEM instead of FBP for single-orbit data, was not visible after application of 3D-OSEM using two-orbit data. 3D-OSEM using two-orbit data dramatically reduced the resolution non-uniformity and statistical noise, and also demonstrated considerably better image quality in the mouse scan. This system may be of use in quantitative assessment of bio-physiological functions in small animals.

The purpose of this study was to assess the utility of a new single-photon emission tomography ligand, [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), to measure regional nAChR binding in human brain. Six healthy nonsmoker subjects (two men and four women, age 33 +/- 15 years) participated in both a bolus (dose: 317 +/- 42 MBq) and a bolus plus constant infusion (dose of bolus: 98 +/- 32 MBq, B/I=6.7 +/- 2.6 h, total dose: 331 +/- 55 MBq) study. The study duration was 5-8 h and 14 h in the former and the latter, respectively. Nonlinear least-squares compartmental analysis was applied to bolus studies to calculate total (VT') and specific (VS') distribution volumes. A two-tissue compartment model was applied to identify VS'. VT' was also calculated in B/I studies. In bolus studies, VT' was well identified by both one- and two-tissue compartment models, with a coefficient of variation of less than 5% in most regions. The two-compartment model gave VT' values of 51, 22, 27, 32, 20, 19, 20, and 17 ml cm(-3) in thalamus, cerebellum, putamen, pons, and frontal, parietal, temporal, and occipital cortices, respectively. The two-compartment model did not identify VS' well. B/I studies provided poor accuracy of VT' measurement, possibly due to deviations from equilibrium conditions. These results demonstrate the feasibility of quantifying high-affinity type nAChRs using [123I]5-I-A-85380 in humans and support the use of VT' measured by bolus studies.

Pinhole collimation can be used to improve spatial resolution in SPET. However, the resolution improvement is achieved at the cost of reduced sensitivity, which leads to projection images with poor statistics. Images reconstructed from these projections using the maximum likelihood expectation maximization (ML-EM) algorithms, which have been used to reduce the artefacts generated by the filtered backprojection (FBP) based reconstruction, suffer from noise/bias trade-off: noise contaminates the images at high iteration numbers, whereas early abortion of the algorithm produces images that are excessively smooth and biased towards the initial estimate of the algorithm. To limit the noise accumulation we propose the use of the pinhole median root prior (PH-MRP) reconstruction algorithm. MRP is a Bayesian reconstruction method that has already been used in PET imaging and shown to possess good noise reduction and edge preservation properties. In this study the PH-MRP algorithm was accelerated with the ordered subsets (OS) procedure and compared to the FBP, OS-EM and conventional Bayesian reconstruction methods in terms of noise reduction, quantitative accuracy, edge preservation and visual quality. The results showed that the accelerated PH-MRP algorithm was very robust. It provided visually pleasing images with lower noise level than the FBP or OS-EM and with smaller bias and sharper edges than the conventional Bayesian methods.

We evaluated an autoradiographic (ARG) method to calculate regional cerebral blood flow (rCBF) sequentially before and after an acetazolamide (ACZ) challenge in a single session of single-photon emission tomography (SPET) with two injections of N-isopropyl-[(123)I] p-iodoamphetamine (IMP). The method uses a table look-up method with a fixed distribution volume (Vd) and a standard input function of IMP. To calculate rCBF after an ACZ challenge, two look-up tables (a dual-table) are used to reflect the effect of radioactivity in the brain from the first dose of IMP. We performed simulation studies to evaluate errors attributable to (a) a change in rCBF induced by an ACZ challenge during the scan and (b) a fixed Vd value that might be different from an individual one, along with the effect of (c) scan length. Thirty-three patients were studied by dynamic SPET with two injections of IMP and frequent arterial blood sampling, and the data were analysed using the dual-table ARG method. Twenty-four of the 33 patients received an injection of ACZ 10 min before the second dose of IMP. We generated a standard input function by averaging individual input functions. The optimal method to calibrate a standard input function was determined so that the SD of differences between rCBF calculated by using a calibrated standard input function (F(SIF)) and that calculated by using an individual input function (F(IIF)) was minimised. Reliability of the method was evaluated by comparing F(SIF) with gold standard rCBF (F(REF)) obtained by two-compartment model analysis of dynamic SPET data and an individual input function with a non-linear least squares fitting method. Errors caused by (a) were less than 4% for a first rCBF ranging between 20 and 60 ml 100 g(-1) min(-1) and an rCBF change of between -25% and 50%. Errors caused by (b) were relatively large compared with those caused by (a), and were affected by (c) with an increasing error in a longer scan. In the patient study with a proposed scan protocol of 25 min for the first and 15 min for the second measurement, the error attributable to the standard input function was smaller when calibrated with a continuously drawn arterial blood sample (random error of 3.8% for continuous 10-min arterial blood sampling after the second dose of IMP) than with a single arterial blood sample (random error of 9.0% at 5 min after the second dose of IMP). Systematic and random errors of F(SIF) compared with F(REF) were 0.0% and 6.3%, respectively. The dual-table ARG method can be reliably used to quantify rCBF before and after an ACZ challenge with a 40-min scan protocol and continuous arterial blood sampling for several minutes.

Unlabelled: The use of nitrates is reported to be effective in viability detection in scintigraphic perfusion imaging. The purpose of the study was to evaluate the effect of nitroglycerin (NTG) on myocardial blood flow (MBF) and coronary vascular resistance (CVR) in various segments characterized by rest-redistribution (201)Tl SPECT., Methods: Twenty-three patients with coronary artery disease underwent rest-redistribution (201)Tl SPECT and (15)O-labeled water PET at rest and after NTG spray (0.3 mg). In addition, 11 healthy volunteers were also studied using PET., Results: NTG did not change global MBF in the volunteers or in the patients. In segments with normal (201)Tl uptake and in those with a severe irreversible (201)Tl defect, NTG significantly reduced MBF without changing CVR. NTG reduced CVR in segments with a reversible (201)Tl defect (141 +/- 50 to 114 +/- 29 mm Hg/[mL/min/g], P = 0.004) and in those with a mild-to-moderate irreversible (201)Tl defect (165 +/- 64 to 149 +/- 60 mm Hg/[mL/min/g], P = 0.003), while maintaining MBF., Conclusion: NTG preferentially reduces CVR in the viable myocardium with ischemia. After NTG, tracer uptake in the ischemic myocardium will be relatively increased compared with that in the nonviable and nonischemic myocardium, leading to improvements in viability detection.

In quantitative pinhole SPECT, photon penetration through the collimator edges (penetration), and photon scattering by the object (object scatter) and collimator (collimator scatter) have not been investigated rigorously. Monte Carlo simulation was used to evaluate these three physical processes for different tungsten knife-edge pinhole collimators using uniform, hotspot and donut phantoms filled with 201Tl, 99mTc, 123I and 131I solutions. For the hotspot phantom, the penetration levels with respect to total counts for a 1 mm pinhole aperture were 78%, 28% and 23% for 131I, 123I and 99mTc, respectively. For a 2 mm aperture, these values were 65% for 131I, 16% for 123I and 12% for 99mTc. For all pinholes, 201Tl penetration was less than 4%. The evaluated scatter (from object and collimator) with a hotspot phantom for the 1 mm pinhole was 24%, 16%, 18% and 13% for 201Tl, 99mTc, 123I and 131I, respectively. Summation of the object and collimator scatter for the uniform phantom was approximately 20% higher than that for the hotspot phantom. Significant counts due to penetration and object and collimator scatter in the reconstructed image were observed inside the core of the donut phantom. The collimator scatter can be neglected for all isotopes used in this study except for 131I. Object scatter correction for all radionuclides used in this study is necessary and correction for the penetration contribution is necessary for all radionuclides but 201Tl.

Unlabelled: Correction of scatter and attenuation is essential for quantitative SPECT. In this work, we evaluated the accuracy gained from a method of transmission-dependent convolution subtraction (TDCS) in the quantitation of activity that is highly concentrated in the striatum (STR)., Methods: SPECT data were acquired from an (123)I-containing phantom with a constant activity in the STR but differing background (BKG) activities, so as to simulate various STR/BKG ratios (19.7:1, 9.7:1, 4.8:1, 1.9:1, and 1:1). In a study of healthy humans (n = 6), a transmission scan followed by an emission scan was performed 24 h after injection of (123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane ((123)I-beta-CIT). All SPECT data was reconstructed with ordered-subset expectation maximization. TDCS was applied for scatter correction. Values of activity in the STR and occipital lobe (for BKG) were used to calculate binding potential V(3)" (= [STR - BKG]/BKG). The effect of SPECT collimator dependency on scatter correction was also evaluated for 6 collimators from 3 different SPECT cameras in the phantom experiment., Results: Scatter correction in the phantom experiment increased the measured values of STR activity (36.2%), resulting in a substantial increase in V(3)" (66.1%). Scatter and attenuation corrections with recovery correction showed an overall bias of -7.3% for the STR, -4.0% for BKG activity, and -7.8% for V(3)". TDCS corrections of phantom activities were relatively uniform for the 6 different collimators, with variabilities of <5.5% for the STR and <3.0% for BKG activities. TDCS correction of human (123)I-beta-CIT images was of a similar, although slightly larger, magnitude than for the phantom data, with increased V(3)" values of 9.4 +/- 2.3 and 4.9 +/- 0.6, with and without scatter correction, respectively., Conclusion: The TDSC method significantly improved the accuracy of SPECT images with a nonuniform distribution of activity highly concentrated in central regions. The value of V(3)" was significantly increased in phantom and human data, with most of the improvement derived from an increase in STR activity. This scatter correction method was approximately equally useful with data from the 6 different collimators and is recommended for more accurate quantitation of nonuniformly distributed brain activities.

Objectives: Accurate mu maps are important for quantitative image reconstruction in SPECT. The Compton scatter energy window (CSW) technique has been proposed to define the outline of objects. In this technique, a lower energy window image is acquired in addition to the main photo-peak energy window. The image of the lower energy window is used to estimate the edge of the scanned object to produce a constant attenuation map. The aim of this study was to investigate the dependency of CSW on the spatial and energy distribution of radioisotope to predict the edges of objects., Methods: Two particular cases of brain study were considered, namely uniform distribution and non-uniform distribution using Monte Carlo simulation and experiments with uniform cylindrical phantom and hotspot phantom. The phantoms were filled with water and a radioactive solution of 99mTc. For each phantom, 20%, 30%, 40% and 50% thresholds of the mean profile were applied to estimate Ewt, the energy window for minimum difference between the estimated and true edge of objects., Results: The Ewt's were 100-120 keV with a 40% threshold and 92-114 keV with a 30% threshold for uniform and hotspot phantoms, respectively., Conclusions: Edge of the objects with CSW technique varies with energy window and thresholds. Careful setting of the energy window is required to use the CSW technique.

Unlabelled: Use of a standard arterial input function and calibrating it by a single blood sample or a continuous arterial blood sample has been researched for a repeat CBF assessment with split-dose administration of N-isopropyl-p[123I]iodoamphetamine (IMP)., Methods: The study population consisted of 5 normal volunteers and 5 patients with cerebrovascular disease. IMP was injected twice (111 MBq/2 ml each) into the anti-cubital vein at a constant infusion speed for 1 min. The arterial input function was monitored during the study including a continuous measurement of radioactivity concentration of both the whole-blood and the octanol-soluble component (Real-Input Function, RIF). Standard input function was determined, and was calibrated either by a single blood sample or a continuous blood sample to estimate the Estimated-Input Function (EIF). Area-Under-the Curve (AUC) was then compared between RIF and EIF., Results: In case EIF was estimated with a single blood sample, the minimum error of estimated AUC was obtained when calibrated at 7 minutes after either the 1st or 2nd injections. Deviation of AUC for [0, 30] was +/- 6.6%, and +/- 5.0%, respectively. If calibrated with a continuous blood sample, the minimum error of AUC with the continuous blood sampling period of 10 min for [0, 30] and [30, 60] was +/- 5.3% and +/- 4.0%, respectively., Conclusions: AUC of EIF with either a single or continuous blood sampling appeared to have reasonably small errors, suggesting the validity of the use of standardized input function in the split-dose IMP SPECT.

Purpose: The aim of this study was to investigate the clinical value of coregistration of interictal SPECT and magnetic resonance imaging (MRI) in patients with partial epilepsy., Materials and Methods: Seventeen patients with partial epilepsy were examined with I-123 IMP or Tc-99m ethyl cysteinate dimer SPECT during the interictal phase. The SPECT images were automatically coregistered to axial T1 weighted MRIs. Asymmetry indexes (AIs) were calculated in both nonregistered images and coregistered images., Results: SPECT images showed areas of decreased tracer uptake in 12 patients. In two patients, the relation between the tumor and the extent of decreased uptake became more accurate in the coregistered images. In five cases, the coregistered images clearly showed that the decreased uptake was located in the sulcus. The AIs were significantly reduced from 14.29 +/- 7.23 to 5.86 +/- 3.48 (P < 0.001) after the images were coregistered in these cases. In five cases, the coregistered images indicated that the decreased areas were in agreement with the cortical findings. No significant differences in the AIs were observed in these cases (16.50 +/- 6.19 versus 17.83 +/- 4.45). Thus, the coregistered images were useful not only to differentiate actual hypoperfusion from artificial hypoperfusion resulting from partial volume effects but also to improve the accuracy of AIs., Conclusion: The coregistration of interictal perfusion SPECT and MRI is useful not only to provide precise functional and anatomic mapping but also to improve the accuracy of calculations of the semiquantitative analysis of regional cerebral blood flow parameters during the interictal state of epilepsy.

To evaluate the usefulness of a combination of linearization and scatter-attenuation correction on 99mTc-bicisate (ECD)-single photon emission tomographic (SPECT) images, both cerebral blood flow (CBF)-positron emission tomographic (PET) images and ECD-SPECT images from fifteen patients with chronic cerebral infarction were acquired. We measured radioactivity counts in regions of interest (ROIs) on all sets of both images and obtained a 2D scattered graph between ECD-SPECT and CBF-PET data. To evaluate diagnostic accuracy, the sensitivity, specificity and accuracy of ECD-SPECT images were calculated by means of discriminant analysis. The same analysis was also performed on the ECD-SPECT images corrected by a combination of linearization and scatter-attenuation correction. An overall nonlinear relationship was observed between ECD-SPECT and CBF-PET. The sensitivity, specificity, and accuracy of ECD-SPECT images were 69.6%, 91.4% and 73.0%, and those of ECD images corrected by the combination of linearization and scatter-attenuation correction were 79.5%, 95.7% and 82.0% respectively. The clinically diagnostic accuracy of ECD-SPECT images corrected by the combined method apparently increased. So that the linearization with the scatter-attenuation method is useful for improving the diagnostic accuracy of ECD-SPECT images.

A multicenter cooperation phantom study was conducted to evaluate the accuracy of a triple energy window scatter correction technique in combination with various attenuation correction methods for 99mTc single photon emission computed tomography (SPECT) imaging. Six centers participated in this research and the data obtained with seven SPECT instruments were analyzed. The phantom used in the experiment was a 20 x 10 cm cylinder filled with homogeneous 99mTc solution, containing two kinds of cold spots (cold rod phantoms). One had a water-filled cylinder 5.5 cm in diameter positioned 2.5 cm from the center. The other contained 6 water-filled cylinders of various sizes. Contrasts of cold regions were in the range from 74% to 120% (true 100%). Another phantom had the shape of a pie-chart divided into six chambers symmetrically positioned in a cylinder 20 cm in diameter and 10 cm in height. Each chamber had volume of 480 ml and contained homogeneous 99mTc solution of different concentrations. This phantom was used to test for linearity between the radio activity concentration and reconstructed count density (linearity phantom). The intercept of the regression line obtained from the linearity phantom was 8.4 kBq ml-1 without scatter correction and -6.8 kBq ml-1 with scatter correction. Contrast was in the range from 78% to 132% (true 100%). The mean relative error for the measured activity concentration was 4.9% +/- 3.5% (mean +/- sd).

Unlabelled: Use of a standardized arterial input function and calibrating it by a single blood sample has been proposed to assess quantitatively cerebral blood flow using N-isopropyl-p[123I]iodoamphetamine (IMP) and single-photon emission computed tomography. This study was intended to validate this approach using a larger number of measured arterial radioactivity curves in the clinical setting., Method: Arterial input function was measured for 50 patients at rest following the i.v. IMP, and its inter-subject variation was assessed. Difference between smokers and non-smokers in addition to effects of acetazolamide administration were particularly investigated. We also evaluated the accuracy of the calibration procedures by means of either a single blood sample or a continuous arterial blood withdrawal sampling for an early period., Results: Inter-subject variation of the observed arterial input function appeared not to show large variations among the 50 patients, thus suggesting the validity of using the standardized arterial input function for the IMP SPECT study. There was a significant difference in the shape of the arterial input function between the smokers and non-smokers, but the calibration at an optimized sampling time provided the area-under-the curve (AUC) that was not significantly different between the two groups. The arterial input function after the acetazolamide showed no significant difference as compared with the shape at rest. The calibration of the standardized input function by means of the early integration of individual curve did not show better accuracy except for a short period of AUC (i.e., < 20 min) for longer integration period > 10 min., Conclusion: Thus, use of the standardized arterial input function has been validated for the IMP SPECT study. The single blood sampling procedure for calibrating the standardized input function has also been validated, and has been shown to provide better accuracy compared with the continuous withdrawal procedure.

The transmission dependent convolution subtraction method which is one of the methods for scatter correction of SPECT was applied to the assessment of CBF using SPECT and I-123-IMP. The effects of scatter correction on regional distribution of CBF were evaluated on a pixel by pixel basis by means of an anatomic standardization technique. SPECT scan was performed on six healthy men. Image reconstruction was carried out with and without the scatter correction. All reconstructed images were globally normalized for the radioactivity of each pixel, and transformed into a standard brain anatomy. After anatomic standardization, the average SPECT images were calculated for scatter corrected and uncorrected groups, and these groups were compared on pixel by pixel basis. In the scatter uncorrected group, a significant overestimation of CBF was observed in the deep cerebral white matter, pons, thalamus, putamen, hippocampal region and cingulate gyrus as compared with scatter corrected group. A significant underestimation was observed in all neocortical regions, especially in the occipital and parietal lobes, and the cerebellar cortex. The regional distribution of CBF obtained by scatter corrected SPECT was similar to that obtained by O-15 water PET. The scatter correction is needed for the assessment of CBF using SPECT.

Accuracy and limitation of energy-window based scatter correction techniques have been evaluated for myocardial 201Tl SPECT by means of Monte Carlo simulation. In particular, projection view-dependency of energy distribution of the scattered photons was evaluated. Two geometrical configurations were simulated: namely a homogeneous cylindrical radioactivity located asymmetrically in a homogeneous cylindrical phantom, and a homogeneous ring radioactivity positioned at the myocardial region of a human thorax phantom. Energy spectra were recorded for each projection, and accuracy of the triple-energy window (TEW) method was then evaluation for both phantoms. The energy distribution of the scattered photons was apparently dependent on the projection view. TEW also demonstrated systematic overcorrection for the scatter because of multiple photo peaks around 80 KeV, and more importantly, the error was highly dependent on the projection view. The error reached to 35-38% for the view that is the closest to the 201Tl radioactivity (anterior view in case of the myocardial ring phantom), and was approximately 20% in the opposite view. This view-dependency of the error remained for other energy window settings, and was found to cause significant artifact in the reconstructed myocardial images, typically causing a defect in the anterior myocardial wall. Thus, this study demonstrated the need for optimizing the window settings for each projection view in all energy window-based scatter correction methods.

To measure regional cerebral blood flow (rCBF) by blood sampling using 99mTc-ECD we devised a method of measuring the radioactive concentration in arterial blood sample with a gamma camera. In this method the head and a blood sample are placed within the same visual field to record the SPECT data of both specimens simultaneously. The results of an evaluation of the counting rate performance, applying the 30 hours decaying method using 99mTc solution showed that this method is not comparable to the well-type scintillation counter and in clinical cases the active concentration in arterial blood sample remained well within the dynamic range. In addition, examination of the influence of scattered radiation from the brain by the dilution method showed that it was negligible at a distance of more than 7.5 cm between the brain and the arterial blood sample. In the present study we placed a head-shaped phantom next to the sample. The results of the examinations suggested that this method is suitable for clinical application, and because it does not require a well-type scintillation counter, it is expected to find wide application.

With the recent development in scatter and attenuation correction algorithms, dynamic single photon emission computerized tomography (SPECT) can potentially yield physiological parameters, with tracers exhibiting suitable kinetics such as thallium-201 (Tl-201). A systematic way is proposed to investigate the minimum data acquisition times and sampling requirements for estimating physiological parameters with quantitative dynamic SPECT. Two different sampling schemes were investigated with Monte Carlo simulations: 1) Continuous data collection for total study duration ranging from 30-240 min. 2) Continuous data collection for first 10-45 min followed by a delayed study at approximately 3 h. Tissue time activity curves with realistic noise were generated from a mean plasma time activity curve and rate constants (K1 - k4) derived from Tl-201 kinetic studies in 16 dogs. Full dynamic sampling schedules (DynSS) were compared to optimum sampling schedules (OSS). We found that OSS can reliably estimate the blood flow related K1 and Vd comparable to DynSS. A 30-min continuous collection was sufficient if only K1 was of interest. A split session schedule of a 30-min dynamic followed by a static study at 3 h allowed reliable estimation of both K1 and Vd avoiding the need for a prolonged (>60-min) continuous dynamic acquisition. The methodology developed should also be applicable to optimizing sampling schedules for other SPECT tracers.

Thallium-201 has been used extensively as a myocardial perfusion agent and to assess myocardial viability. Unlike other 99mTc-labeled agents such as 99mTc-sestamibi and 99mTc-tetrofosmine, the regional concentration of 201Tl varies with time, and its kinetics make it a potential candidate for estimating absolute physiologic parameters with kinetic model analysis. This article outlines a strategy for quantitative assessment of regional myocardial blood flow in man using 201Tl and dynamic single photon emission computed tomography (SPECT). Quantitatively accurate SPECT images that are proportional to the true radioactivity distribution are prerequisites for model-based kinetic analysis. Our technique for quantitative SPECT includes ordered-subset maximum likelihood-expectation maximization (ML-EM) reconstruction with transmission data-based attenuation correction and transmission-dependent convolution subtraction scatter correction. A three-compartment model was found to reproduce the observed regional time-activity curves well, and dog experiments demonstrated that influx rate constant (K1) values estimated from the dynamic SPECT data correlated well with absolute myocardial blood flow determined by in vitro microspheres for a physiologically wide range of flows. Several possible strategies for simplifying the study procedures, without compromising accuracy, are also presented, which should make absolute quantitation of regional myocardial blood flow feasible using 201Tl and a conventional SPECT camera in a clinical setting.

Unlabelled: Appropriate corrections for scatter and attenuation correction are prerequisites for quantitative SPECT studies. However, in most cerebral SPECT studies, uniform attenuation in the head is assumed, and scatter is usually neglected. This study evaluated the effect of attenuation correction and scatter correction on quantitative values and image contrast., Methods: Studies were performed in six normal volunteers (ages 22-26 yr) following intravenous 123I-IMP administration using a rotating, dual-head gamma camera. A transmission scan was acquired with a 99mTc rod source (74 MBq) placed at the focus of a symmetrical fanbeam collimator. Data were reconstructed using two attenuation coefficient (mu) maps: quantitative mu map from the transmission scan and a uniform mu map generated by edge detection of the reconstructed images. Narrow and broad beam mu values were used with and without scatter correction, respectively. Scatter was corrected with transmission-dependent convolution subtraction and triple-energy window techniques. Quantitative rCBF images were calculated by the previously validated IMP-autoradiographic technique, and they were compared with those obtained by (15)O-water and PET. SPECT and PET images were registered to MRI studies, and rCBF values were compared in 39 ROIs selected on MRI., Results: Clear differences were observed in rCBF images between the measured and constant mu maps in the lower slices due to the airways and in the higher slices due to increased skull attenuation. However, differences were < 5% in all cerebral tissue regions, thus assumption of uniform mu introduces little bias. The scatter correction was found to increase the image contrast significantly, i.e., rCBF increased by 20%-30% in gray matter and decreased in white matter regions by 10%-20% after scatter correction, increasing gray-to-white ratio to be close to that of PET measurement. The rCBF values from the two scatter correction were not significantly different, but the triple-energy window technique suffered from increased noise. After scatter correction, rCBF values were in good agreement with those measured by PET., Conclusion: This study shows little loss in accuracy results from assuming uniform mu map. However, scatter correction is required for the quantitative rCBF values and gray-to-white ratios to approach those of PET.

Scatter correction is a prerequisite for quantitative SPECT, but potentially increases noise. Monte Carlo simulations (EGS4) and physical phantom measurements were used to compare accuracy and noise properties of two scatter correction techniques: the triple-energy window (TEW), and the transmission dependent convolution subtraction (TDCS) techniques. Two scatter functions were investigated for TDCS: (i) the originally proposed mono-exponential function (TDCSmono) and (ii) an exponential plus Gaussian scatter function (TDCSGauss) demonstrated to be superior from our Monte Carlo simulations. Signal to noise ratio (S/N) and accuracy were investigated in cylindrical phantoms and a chest phantom. Results from each method were compared to the true primary counts (simulations), or known activity concentrations (phantom studies). 99mTc was used in all cases. The optimized TDCS(Gauss) method overall performed best, with an accuracy of better than 4% for all simulations and physical phantom studies. Maximum errors for TEW and TDCS(mono) of -30 and -22%, respectively, were observed in the heart chamber of the simulated chest phantom. TEW had the worst S/N ratio of the three techniques. The S/N ratios of the two TDCS methods were similar and only slightly lower than those of simulated true primary data. Thus, accurate quantitation can be obtained with TDCS(Gauss), with a relatively small reduction in S/N ratio.

Recently, two methods have been proposed for regional cerebral blood flow (rCBF) quantitation using [123I]iodoamphetamine (IMP) and single-photon emission computed tomography (SPECT). The table look-up (TLU) method has been shown to provide both rCBF and volume of distribution, Vd, images from two SPECT scans, while a single-scan autoradiographic (ARG) technique provided rCBF using a fixed and assumed Vd. In both methods, a single blood sample was referred to calibrate the previously determined standard input function. The present multicenter project was designed to evaluate the accuracy of both methods for use as clinical investigative tools. Ten independent institutions performed [123I]IMP-SPECT studies according to both methods in 76 subjects (10 normal volunteers, 32 patients with cerebrovascular disease, and 34 patients with other diseases). Calculated rCBF values were compared with those obtained by the following reference methods available in the participating institutions; [15O] H2O positron emission tomography (PET) (five institutions), [133Xe]SPECT (four institutions), and the [123I]IMP microsphere method (three institutions). Both ARG and TLU methods provided rCBF values that were significantly correlated with those measured by the [15O] H2O PET technique (p < 0.001 for all subjects; overall regression equation, y = 15.14 + 0.54x) and those measured by the [123I]IMP-microsphere method (p < 0.001 for all subjects: y = 2.0 + 0.80x). Significant correlation (p < 0.05) was observed in 18 of 24 subjects studied with the [133Xe] SPECT reference technique (overall regression equation, y = 15.0 + 0.55x). Mean cortical gray matter rCBF in a group of normal subject was 43.9 +/- 3.3 and 43.4 +/- 2.0 ml/min/100 g for the ARG and TLU methods, respectively. Regional Vd of [123I]IMP estimated by the TLU method was 45 ml/ml +/- 20% in the normal cortical region. Close agreement between ARG and TLU rCBF values was observed (y = -3.21 + 1.07x, r = 0.97), confirming the validity of assuming a fixed Vd in the ARG method. Results of this study demonstrate that both the ARG and TLU methods accurately and reliably estimate rCBF in a variety of clinical settings.

Effects of Compton scatter has been investigated for quantitative single-photon emission computed tomography. Using a technique proposed by Ichihara and Ogawa (triple-energy window method) as a gold standard, effects of correcting the scatter has been evaluated for 5 different phantom configurations, as well as a clinical cerebral blood flow study with use of 123I-IMP. Without the scatter correction but with a correction for attenuation, a conventional reconstruction provided a non-uniform distribution for uniform phantom configurations, and the quantitative pixel counts being highly dependent on size and shape of the objects. On the other hand, a uniform distribution and quantitative pixel counts that were independent of size or shape of the object were obtained by applying the scatter correction using a conventional attenuation correction technique with use of a theoretical mu value of 0.146 cm-1, thus suggesting importance of the scatter correction. Similar results were observed without the scatter correction, if an empirical value of mu of 0.07 cm-1 was used in the attenuation correction. However, this procedure was found to decrease the image contrast between the high count and low count regions. Significant underestimation of 20-30% was caused in cortical gray matter regions, and overestimation of 20% in the white matter regions. In practical clinical studies, magnitude of the error is still unknown, and is probably dependent on shape, size and radioactivity distribution of the object. A further systematic study is required in order to investigate significance of the scatter correction in real clinical studies.

To estimate regional cerebral blood flow (rCBF) and distribution volume (Vd) using N-isopropyl-p-[123]iodoamphetamine (IMP) and two SPECT data (early and delayed data) measured at two discrete time points, three fast algorithms are implemented, which are the table look-up method (TLU), the linear least-squares fitting method (LLSF), and the linear search method (LS). A two-compartment model was used as the IMP kinetic model. These algorithms were applied to the early and delayed data measured by the two scan protocols, t1 = 12 min, t2 = 54 min (scan A) and t1 = 12 min, t2 = 85 min (scan B). The estimated rCBF and Vd values using the present three algorithms were in good agreement with those using the nonlinear least-squares fitting technique and dynamic SPECT data. The quantitative value and signal to noise (S/N) ratio of rCBF images by TLU was not changed whether scan A or scan B was used. However, the S/N of the Vd image by TLU using scan B improved over that using scan A. The same tendency was observed in the results of LLSF and LS. The CPU times for the parametric imaging of CBF and Vd images for one slice (64 x 64 matrix) were 0.04, 0.09, and 0.14 s using TLU, LLSF, and LS, respectively. In conclusion, the present three algorithms gave reasonably accurate estimates of rCBF and Vd using two SPECT data, and are well suited for parametric imaging because of their good statistical properties and high computational efficiency.

While N-isopropyl-p-[123I]iodoamphetamine (IMP) is commonly used as a flow tracer, significant clearance from the brain causes underestimation of CBF as compared with true CBF when conventional microsphere model analysis is applied. We previously reported a simple "table look-up" method for CBF measurement using IMP taking into account this clearance effect. The method is based on a two-compartment model, the K1 (corresponding to CBF) and k2 constants being obtained from a table from the ratio of the 1st SPECT (40 min) to the 2nd SPECT (180 min) counts. Arterial input data used were obtained by one point blood sampling 10 min after IMP infusion against the standard input function. In the present study, this approach was compared with conventional microsphere model analysis. For 30 subjects, the latter method entailed 8 min continuous arterial blood sampling after IMP infusion and the use of SPECT data at the end of this period, calibrated by a count ratio of 8 min/40 min planar images of whole brains. A good correlation was observed between the two methods (r = 0.88), but an overestimation of table look-up method CBF as compared with microsphere model CBF was observed contrary to theoretical predictions. Limitations in the estimation of SPECT data at 8 min, obtained with SPECT data at 40 min for calibration of the count ratio of 8 min/40 min whole brain planar images, might be responsible for this.

Unlabelled: Iodine-123-iodoamphetamine (IMP) is commonly used as a flow tracer for SPECT due to its large first-pass extraction fraction. Significant clearance from the brain, however, causes changes in distribution and underestimation of CBF values when a conventional microsphere model is applied to prolonged data acquisition. We have developed a rapid method to calculate CBF images in which clearance effects are taken into account., Methods: A dynamic SPECT scan was obtained from five subjects (four patients with cerebral infarctions and one healthy volunteer) following intravenous injection of IMP lasting 1 min. The arterial input function was obtained by frequent blood sampling and measurement of the octanol extraction ratio. The dynamic images were weighted and integrated so that the look-up table procedures yielded values of CBF and distribution volume (Vd) simultaneously., Results: Calculated values for CBF and Vd were consistent with those determined by nonlinear least squares fitting [CBF: Y = 1.03X-0.30 (ml/100 ml/min), r = 0.998, p < 0.001; Vd: Y = 0.99X-0.11 (ml/ml), r = 0.99, p < 0.001] and calculated CBF correlated significantly with CBF measured by PET [Y = 0.85X-0.15 (ml/100 ml/min), r = 0.92, p < 0.001]., Conclusion: This technique is valid for estimating CBF.

Recently, a method has been proposed to measure quantitative regional cerebral blood flow (rCBF) in man using N-isopropyl-p-[123I]-iodoamphetamine (IMP) and single photon emission tomography (SPECT). In this method (IMP-ARG method), a functional map of rCBF was calculated from a single SPECT scan data set, in which effects of the clearance of IMP from the brain was taken into account by employing the 2 compartment model. To avoid the procedures of frequent and/or continuous sampling of the arterial blood that was required in determination of the input function, use of a standard input function and calibrating it by one blood sampling were validated. The present study was intended to investigate the sensitivity to various sources of errors in the IMP-ARG method such as (1) effects of individual difference of the arterial input function, (2) effects of ambiguity of the regional distribution volume (Vd) of IMP, and (3) effects of inaccuracy of the SPECT measurement. It was shown in the present simulation study that errors in the calculated rCBF values were dependent on the SPECT mid-scan time (MST), and that the minimum error corresponded to the MST of approximately 30 min after the IMP infusion. With this optimal MST, errors in rCBF due to the individual difference of the input function was approximately 10%, and the errors due to the ambiguity of the Vd were approximately 8%. The total accuracy of the calculated rCBF in the IMP-ARG method was, therefore, estimated as approximately 13%. Although a relatively large error was expected at a high rCBF area, this study strongly suggested the IMP-ARG method being useful and accurate for providing the quantitative rCBF map for a clinical use.