[123I]CLINDE SPECT as a neuroinflammation imaging approach in a rat model of stroke.

Poststroke neuroinflammation exacerbates disease progression. [11C]PK11195-positron emission tomography (PET) imaging has been used to visualize neuroinflammation; however, its short half-life of 20 min limits its clinical use. [123I]CLINDE has a longer half-life (13h); therefore, [123I]CLINDE-single-photon emission computed tomography (SPECT) imaging is potentially more practical than [11C]PK11195-PET imaging in clinical settings. The objectives of this study were to 1) validate neuroinflammation imaging using [123I]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, [123I]CLINDE-SPECT considerably corresponded to the immunohistochemical images stained with the CD68 antibody (a marker for microglia/microphages), comparable to the level observed in [11C]PK11195-PET images. In addition, the [123I]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 (CMRO2) in 15O-gas-PET. Rats with moderate-to-mild infarcts exhibited neuroinflammation in the ischemic core, where CMRO2 levels were mildly reduced. This study demonstrates that [123I]CLINDE-SPECT imaging is suitable for neuroinflammation imaging and that the distribution of neuroinflammation varies depending on the severity of infarction.

123I-Labeled oxLDL Is Widely Distributed Throughout the Whole Body in Mice.

PURPOSE: Oxidized low-density lipoprotein (oxLDL) plays a key role in endothelial dysfunction, vascular inflammation, and atherogenesis. The aim of this study was to assess blood clearance and in vivo kinetics of radiolabeled oxLDL in mice. METHODS: We synthesized 123I-oxLDL by the iodine monochloride method, and performed an uptake study in CHO cells transfected with lectin-like oxLDL receptor-1 (LOX-1). In addition, we evaluated the consistency between the 123I-oxLDL autoradiogram and the fluorescence image of DiI-oxLDL after intravenous injection for both spleen and liver. Whole-body dynamic planar images were acquired 10 min post injection of 123I-oxLDL to generate regional time-activity curves (TACs) of the liver, heart, lungs, kidney, head, and abdomen. Regional radioactivity for those excised tissues as well as the bladder, stomach, gut, and thyroid were assessed using a gamma counter, yielding percent injected dose (%ID) and dose uptake ratio (DUR). The presence of 123I-oxLDL in serum was assessed by radio-HPLC. RESULTS: The cellular uptakes of 123I-oxLDL were identical to those of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited consistent distributions. TACs after injection of 123I-oxLDL demonstrated extremely fast kinetics. The radioactivity uptake at 10 min post-injection was highest in the liver (40.8 ± 2.4% ID). Notably, radioactivity uptake was equivalent throughout the rest of the body (39.4 ± 2.7% ID). HPLC analysis revealed no remaining 123I-oxLDL or its metabolites in the blood. CONCLUSION: 123I-OxLDL was widely distributed not only in the liver, but also throughout the whole body, providing insight into the pathophysiological effects of oxLDL.

Multi-pinhole fluorescent x-ray computed tomography for molecular imaging.

We propose a multi-pinhole fluorescent x-ray computed tomography (mp-FXCT) technique for preclinical molecular imaging that can provide the complete data necessary to produce 3-D tomographic images during anaesthesia. In this method, multiple projections are simultaneously acquired through a multi-pinhole collimator with a 2-D detector and full-field volumetric beam to accelerate the data acquisition process and enhance the signal-to-noise ratios of the projections. We constructed a 15-pinhole mp-FXCT imaging system at beamline ARNE-7A at KEK and performed preliminary experiments to investigate its imaging properties using physical phantoms and a non-radioactive I imaging agent. The mp-FXCT system could detect an I concentration of 0.038 mg/ml, the minimum required for in-vivo imaging, at a spatial resolution of about 0.3 mm during a data acquisition time of 90 min, which is less than the time for which anaesthesia is effective and suggests that preclinical molecular imaging is feasible with mp-FXCT.

Dual-energy fluorescent x-ray computed tomography system with a pinhole design: Use of K-edge discontinuity for scatter correction.

We propose a pinhole-based fluorescent x-ray computed tomography (p-FXCT) system with a 2-D detector and volumetric beam that can suppress the quality deterioration caused by scatter components. In the corresponding p-FXCT technique, projections are acquired at individual incident energies just above and below the K-edge of the imaged trace element; then, reconstruction is performed based on the two sets of projections using a maximum likelihood expectation maximization algorithm that incorporates the scatter components. We constructed a p-FXCT imaging system and performed a preliminary experiment using a physical phantom and an I imaging agent. The proposed dual-energy p-FXCT improved the contrast-to-noise ratio by a factor of more than 2.5 compared to that attainable using mono-energetic p-FXCT for a 0.3 mg/ml I solution. We also imaged an excised rat's liver infused with a Ba contrast agent to demonstrate the feasibility of imaging a biological sample.

Validity of using a 3-dimensional PET scanner during inhalation of 15O-labeled oxygen for quantitative assessment of regional metabolic rate of oxygen in man.

Use of 15O labeled oxygen (15O2) and positron emission tomography (PET) allows quantitative assessment of the regional metabolic rate of oxygen (CMRO2) in vivo, which is essential to understanding the pathological status of patients with cerebral vascular and neurological disorders. The method has, however, been challenging, when a 3D PET scanner is employed, largely attributed to the presence of gaseous radioactivity in the trachea and the inhalation system, which results in a large amount of scatter and random events in the PET assessment. The present study was intended to evaluate the adequacy of using a recently available commercial 3D PET scanner in the assessment of regional cerebral radioactivity distribution during an inhalation of 15O2. Systematic experiments were carried out on a brain phantom. Experiments were also performed on a healthy volunteer following a recently developed protocol for simultaneous assessment of CMRO2 and cerebral blood flow, which involves sequential administration of 15O2 and C15O2. A particular intention was to evaluate the adequacy of the scatter-correction procedures. The phantom experiment demonstrated that errors were within 3% at the practically maximum radioactivity in the face mask, with the greatest radioactivity in the lung. The volunteer experiment demonstrated that the counting rate was at peak during the 15O gas inhalation period, within a verified range. Tomographic images represented good quality over the entire FOV, including the lower part of the cerebral structures and the carotid artery regions. The scatter-correction procedures appeared to be important, particularly in the process to compensate for the scatter originating outside the FOV. Reconstructed images dramatically changed if the correction was carried out using inappropriate procedures. This study demonstrated that accurate reconstruction could be obtained when the scatter compensation was appropriately carried out. This study also suggested the feasibility of using a state-of-the-art 3D PET scanner in the quantitative PET imaging during inhalation of 15O labeled oxygen.

Quantification of myocardial blood flow using (201)Tl SPECT and population-based input function.

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.

Adequacy of a compartment model for CMRO2 quantitation using ¹5O-labeled oxygen and PET: a clearance measurement of ¹5O-radioactivity following intracarotid bolus injection of ¹5O-labeled oxyhemoglobin on Macaca fascicularis.

We aimed at evaluating the adequacy of the commonly employed compartmental model for quantitation of cerebral metabolic rate of oxygen (CMRO2) using (15)O-labeled oxygen ((15)O2) and positron emission tomography (PET). Sequential PET imaging was carried out on monkeys following slow bolus injection of blood samples containing (15)O2-oxyhemoglobin ((15)O2-Hb), (15)O-labeled water (H2(15)O), and C(15)O-labeled hemoglobin (C(15)O-Hb) into the internal carotid artery (ICA). Clearance slopes were assessed in the middle cerebral artery territory of the injected hemisphere. The time-activity curves were bi-exponential for both (15)O2-Hb and H2(15)O. Single exponential fitting to the early (5 to 40 seconds) and late (80 to 240 seconds) periods after the peak was performed and the (15)O2-Hb and H2(15)O results were compared. It was found that a significant difference between the clearance rates of the (15)O2-Hb and H2(15)O injections is unlikely, which supports the mathematical model that is widely used to describe the kinetics of (15)O2-Hb and H2(15)O in cerebral tissues and is the basis of recent approaches to simultaneously assess CMRO2 and cerebral blood flow in a single PET session. However, it should be noted that more data are necessary to unequivocally confirm the result.

The feasibility study on 3-dimensional fluorescent x-ray computed tomography using the pinhole effect for biomedical applications.

We propose a 3-dimensional fluorescent x-ray computed tomography (CT) pinhole collimator, aimed at providing molecular imaging with quantifiable measures and sub-millimeter spatial resolution. In this study, we demonstrate the feasibility of this concept and investigate imaging properties such as spatial resolution, contrast resolution and quantifiable measures, by imaging physical phantoms using a preliminary imaging system developed with monochromatic synchrotron x rays constructed at the BLNE-7A experimental line at KEK, Japan.

Three-dimensional brain phantom containing bone and grey matter structures with a realistic head contour.

INTRODUCTION: A physical 3-dimensional phantom that simulates PET/SPECT images of static regional cerebral blood flow in grey matter with a realistic head contour has been developed. This study examined the feasibility of using this phantom for evaluating PET/SPECT images. METHODS: The phantom was constructed using a transparent, hydrophobic photo-curable polymer with a laser-modelling technique. The phantom was designed to contain the grey matter, the skull, and the trachea spaces filled with a radioactive solution, a bone-equivalent solution of K(2)HPO(4), and air, respectively. The grey matter and bone compartments were designed to establish the connectivity. A series of experiments was performed to confirm the accuracy and reproducibility of the phantom using X-ray CT, SPECT, and PET. RESULTS: The total weight was 1997 ± 2 g excluding the inner liquid, and volumes were 563 ± 1 and 306 ± 2 mL, corresponding to the grey matter and bone compartments, respectively. The apparent attenuation coefficient averaged over the whole brain was 0.168 ± 0.006 cm(-1) for Tc-99 m, which was consistent with the previously reported value for humans (0.168 ± 0.010 cm(-1)). Air bubbles were well removed from both grey-matter and bone compartments, as confirmed by X-ray CT. The phantom was well adapted to experiments using PET and SPECT devices. CONCLUSION: The 3-dimensional brain phantom constructed in this study may be of use for evaluating the adequacy of SPECT/PET reconstruction software programs.

Quantitative assessment of regional cerebral blood flow by dynamic susceptibility contrast-enhanced MRI, without the need for arterial blood signals.

In dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI), an arterial input function (AIF) is usually obtained from a time-concentration curve (TCC) of the cerebral artery. This study was aimed at developing an alternative technique for reconstructing AIF from TCCs of multiple brain regions. AIF was formulated by a multi-exponential function using four parameters, and the parameters were determined so that the AIF curves convolved with a model of tissue response reproduced the measured TCCs for 20 regions. Systematic simulations were performed to evaluate the effects of possible error sources. DSC-MRI and positron emission tomography (PET) studies were performed on 14 patients with major cerebral artery occlusion. Cerebral blood flow (CBF) images were calculated from DSC-MRI data, using our novel method alongside conventional AIF estimations, and compared with those from (15)O-PET. Simulations showed that the calculated CBF values were sensitive to variations in the assumptions regarding cerebral blood volume. Nevertheless, AIFs were reasonably reconstructed for all patients. The difference in CBF values between DSC-MRI and PET was -2.2 ± 7.4 ml/100 g/min (r = 0.55, p < 0.01) for our method, versus -0.2 ± 8.2 ml/100 g/min (r = 0.47, p = 0.01) for the conventional method. The difference in the ratio of affected to unaffected hemispheres between DSC-MRI and PET was 0.07 ± 0.09 (r = 0.82, p < 0.01) for our method, versus 0.07 ± 0.09 (r = 0.83, p < 0.01) for the conventional method. The contrasts in CBF images from our method were the same as those from the conventional method. These findings suggest the feasibility of assessing CBF without arterial blood signals.

Breath-hold CT attenuation correction for quantitative cardiac SPECT.

BACKGROUND: Attenuation correction of a single photon emission computed tomography (SPECT) image is possible using computed tomography (CT)-based attenuation maps with hybrid SPECT/CT. CT attenuation maps acquired during breath holding can be misaligned with SPECT, generating artifacts in the reconstructed images. The purpose of this study was to investigate the effects of respiratory phase during breath-hold CT acquisition on attenuation correction of cardiac SPECT imaging. METHODS: A series of 201Tl-emission and 99mTc-based transmission computed tomography (TCT) scans was carried out along with CT-attenuation scans on 11 young normal volunteers using a hybrid SPECT/CT scanner. The CT scans were performed at three respiratory phases: end-inspiration (INS), end-expiration (EXP), and the midpoint (MID) between these phases. Using alignment parameters between attenuation maps and SPECT images without attenuation or scatter corrections, quantitative SPECT images were reconstructed, including corrections for attenuation and scatter. Regional radioactivity concentrations normalized by the subjects' weights were compared between CT- and TCT-based attenuation correction techniques. RESULTS: SPECT images with CT attenuation maps at the EXP phase showed significant differences in regional weight-normalized radioactivity concentrations relative to the images using the other attenuation maps (p < 0.05), as well as systematic positive bias errors, compared to TCT-based images for all myocardial segments, 5.7% ± 2.7% (1.9% to 10.0%). No significant differences in regional weight-normalized radioactivity concentrations were observed between images with CT attenuation maps at MID and INS phases or between these and the TCT-based images, but regional tendencies were found: for anterior to anterolateral segment, positive bias of 5.0% ± 2.2% (1.3% to 8.1%) and 5.6% ± 1.9% (2.6% to 8.5%) and for inferior to inferoseptal segment, negative bias of -5.3% ± 2.6% (-9.1% to -1.7%) and -4.6% ± 2.5% (-8.8% to -1.5%) for the MID and INS phases, respectively. CONCLUSIONS: Use of breath-hold CT attenuation maps at INS and MID phases for attenuation and scatter corrections demonstrated accurate quantitative images that would prove beneficial in cardiac SPECT/CT studies.

Effects of patient movement on measurements of myocardial blood flow and viability in resting ¹5O-water PET studies.

BACKGROUND: Patient movement has been considered an important source of errors in cardiac PET. This study was aimed at evaluating the effects of such movement on myocardial blood flow (MBF) and perfusable tissue fraction (PTF) measurements in intravenous ¹5O-water PET. METHODS: Nineteen ¹5O-water scans were performed on ten healthy volunteers and three patients with severe cardiac dysfunction under resting conditions. Motions of subjects during scans were estimated by monitoring locations of markers on their chests using an optical motion-tracking device. Each sinogram of the dynamic emission frames was corrected for subject motion. Variation of regional MBF and PTF with and without the motion corrections was evaluated. RESULTS: In nine scans, motions during ¹5O-water scan (inter-frame (IF) motion) and misalignments relative to the transmission scan (inter-scan (IS) motion) larger than the spatial resolution of the PET scanner (4.0 mm) were both detected by the optical motion-tracking device. After correction for IF motions, MBF values changed from 0.845 ± 0.366 to 0.780 ± 0.360 mL/minute/g (P < .05). In four scans with only IS motion detected, PTF values changed significantly from 0.465 ± 0.118 to 0.504 ± 0.087 g/mL (P< .05), but no significant change was found in MBF values. CONCLUSIONS: This study demonstrates that IF motion during ¹5O-water scan at rest can be source of error in MBF measurement. Furthermore, estimated MBF is less sensitive than PTF values to misalignment between transmission and ¹5O-water emission scans.

Monte Carlo simulation of scintillation photons for the design of a high-resolution SPECT detector dedicated to human brain.

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.

Three-dimensional quantitation of regional cerebral blood flow in mice using a high-resolution pinhole SPECT system and 123I-iodoamphetamine.

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.

Experimental pig model of old myocardial infarction with long survival leading to chronic left ventricular dysfunction and remodeling as evaluated by PET.

UNLABELLED: A pig model of reduced left ventricular (LV) function and remodeling or chronic heart failure with long survival after myocardial infarction (MI) has not been established. The aim of this study was to evaluate the pathophysiologic status of a pig model of old MI using a series of PET studies. METHODS: Twenty-seven male farm pigs were divided into 2 groups: 7 animals in the control group and 20 animals that underwent a proximal coronary artery (CA) occlusion using an ameroid constrictor after distal CA ligation. A series of PET examinations was performed to assess LV volumes, LV functions, myocardial perfusion response to adenosine, and viability as water-perfusable tissue index. RESULTS: The distal CA ligation inhibited arrhythmia during and after the operation, and a transmural anteroseptal MI, with an infarction area of 27% ± 5% of the whole left ventricle, was generated with a survival rate of 75% at 4 mo. Wall motion evaluated by (18)F-FDG PET was diffusely reduced, including the noninfarcted wall. Global LV ejection fraction as assessed by gated C(15)O PET was reduced (39% ± 16%) in the group undergoing occlusion, compared with the control group (66% ± 16%, P < 0.05). LV end-systolic (31.4 ± 9.2 cm(3)) and end-diastolic (52.7 ± 10.2 cm(3)) volumes were increased, compared with controls (15.2 ± 9.4 cm(3), P < 0.01, and 41.7 ± 11.5 cm(3), P < 0.05, respectively). Histology showed hypertrophy and development of microscopic fibrosis in noninfarcted myocardium. PET demonstrated the reduced myocardial perfusion response to adenosine and also reduced water-perfusable tissue index in remote segments. CONCLUSION: The pig model of old MI generated by the chronic proximal CA obstruction after distal ligation was characterized by LV dysfunction and remodeling, with a high survival rate.

Multicenter evaluation of a standardized protocol for rest and acetazolamide cerebral blood flow assessment using a quantitative SPECT reconstruction program and split-dose 123I-iodoamphetamine.

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.

Absolute quantitation of myocardial blood flow with (201)Tl and dynamic SPECT in canine: optimisation and validation of kinetic modelling.

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.

Accelerated 3D-OSEM image reconstruction using a Beowulf PC cluster for pinhole 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.

Comparison of multi-ray and point-spread function based resolution recovery methods in pinhole SPECT reconstruction.

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.

Use of a compact pixellated gamma camera for small animal pinhole SPECT imaging.

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.