Quantitative computed tomography (CT) is helpful to diagnosis and to correction for attenuation i... more Quantitative computed tomography (CT) is helpful to diagnosis and to correction for attenuation in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) images. Calibration factors, which are measured from scans of known-density phantoms, are used to convert plain CT numbers into quantitative radiodensity values (usually represented in the Hounsfield units, or HU). Even in the same CT system, the calibration factors may largely vary with different acquisition and reconstruction settings. It is not trivial for software or researchers to always apply the correct calibration factors to images. To simplify this procedure, we proposed a practical self-calibration method for small-animal CT based on image histograms. Two peaks can be found in the histogram of a small-animal CT image (Figure 1), one of which is associated with air and the other with dominating material of an animal (mainly contributed by soft tissues and muscles and hereinafter referred ...
Application of focusing pinhole geometries can result in improved resolution and reduced noise in... more Application of focusing pinhole geometries can result in improved resolution and reduced noise in small-animal SPECT studies. Attenuation of photon flux between object voxels and pinholes affects quantitative accuracy of reconstructed images. Although photon attenuation plays a much smaller role in small-animal SPECT than in clinical SPECT, correction for attenuation together with correction for scatter and distance-dependent sensitivity of pinhole collimators is desirable when high quantitative accuracy is required. Previously we proposed a 3D iterative correction method that deals with the pinhole sensitivity and scatter. Here we propose and validate a first-order method for attenuation correction in focusing pinhole SPECT, which is combined with 3D iterative reconstruction. The method has the advantage that no new system matrix has to be calculated for each scan. Instead of using X-ray CT data, optical photos made by webcams integrated in the SPECT system are used to estimate the...
OBJECTIVES: Pre-clinical SPECT images are typically much less degraded by attenuation than clinic... more OBJECTIVES: Pre-clinical SPECT images are typically much less degraded by attenuation than clinical SPECT images because of smaller body dimensions. It means that first-order attenuation-correction could be sufficient for quantitative pre-clinical studies. Here we developed and validated a practical Chang-based method based on animal body contours to perform attenuation correction for multi-pinhole SPECT that does not require CT data. METHODS: Optical images from the top and both sides of the animals prior to scanning were obtained and displayed on a dedicated graphical user interface. This allows the users to quickly draw 2D contours of each animal on the sagittal and coronal optical images, and then creates a 3D surface based on widths measured on the 2D contours at each transverse slice of the animal. With the 3D surfaces, uniform attenuation-coefficient maps were generated and a first-order Chang algorithm was carried out on reconstructed images. The method is combined with scat...
ABSTRACT Gamma cameras based on Charge Coupled Devices (CCDs) and micro-columnar CsI scintillator... more ABSTRACT Gamma cameras based on Charge Coupled Devices (CCDs) and micro-columnar CsI scintillators can reach high spatial resolutions. However, the gamma interaction probability of these scintillators is low (typically ≪30% at 141 keV) due to the limited thickness of presently available micro-columnar scintillators. Continuous scintillators can improve the interaction probability but suffer from increased light spread compared to columnar scintillators. In addition, for both types of scintillators gamma photons incident at an oblique angle reduce the spatial resolution due to the variable depth of interaction (DOI). To improve spatial resolution and spectral characteristics of these detectors, we have developed a fast analytic scintillation detection algorithm that makes use of a depth-dependent light spread model and as a result is able to determine the DOI in the scintillator. This algorithm, performing multi-scale frame analysis, was tested for an Electron Multiplying CCD (EM-CCD) optically coupled to CsI(Tl) scintillators of different thicknesses. For a 2.6 mm thick scintillator a spatial resolution of 148 μm Full Width Half Maximum (FWHM) was obtained with an energy resolution of 46% FWHM for gamma photons incident perpendicularly (interaction probability 61% at 141 keV). The multi-scale algorithm improves the spatial resolution up to 11 %, and the energy resolution up to 36 % compared to a previously implemented algorithm that did not model the depth-dependent light spread. In addition, the multi-scale algorithm can accurately approximate DOI. As a result, degradation of the spatial resolution due to the variable DOI for gamma photons incident at a 47° angle was improved from 2600 μm to 508 μm FWHM for a 3 mm thick scintillator. We conclude that the multi-scale algorithm significantly improves CCD based gamma cameras as can be applied in future SPECT systems.
Pre- and intraoperative diagnostic techniques facilitating tumor staging are of paramount importa... more Pre- and intraoperative diagnostic techniques facilitating tumor staging are of paramount importance in colorectal cancer surgery. The urokinase receptor (uPAR) plays an important role in the development of cancer, tumor invasion, angiogenesis, and metastasis and over-expression is found in the majority of carcinomas. This study aims to develop the first clinically relevant anti-uPAR antibody-based imaging agent that combines nuclear (111In) and real-time near-infrared (NIR) fluorescent imaging (ZW800-1). Conjugation and binding capacities were investigated and validated in vitro using spectrophotometry and cell-based assays. In vivo, three human colorectal xenograft models were used including an orthotopic peritoneal carcinomatosis model to image small tumors. Nuclear and NIR fluorescent signals showed clear tumor delineation between 24h and 72h post-injection, with highest tumor-to-background ratios of 5.0 ± 1.3 at 72h using fluorescence and 4.2 ± 0.1 at 24h with radioactivity. 1-...
Objective: Attenuation of photon flux on trajectories between the source and pinhole apertures af... more Objective: Attenuation of photon flux on trajectories between the source and pinhole apertures affects the quantitative accuracy of reconstructed single-photon emission computed tomography (SPECT) images. Attenuation maps can be employed, e.g. from registered X-ray CT images, to correct for attenuation post-reconstruction, showing highly accurate quantification. Here we investigate effects of CT image inaccuracies (misregistration and errors in attenuation coefficients) to quantitative accuracy. Methods: A rat cadaver containing 12 small artificial Tc-99m sources with known activities was scanned in a U-SPECT-II/CT system. An attenuation map was derived from the CT image (as a gold standard), and then the map was shifted up to 3 mm or the attenuation coefficients in the maps were globally altered by 10%. A Chang-based first-order method was employed for post-reconstruction attenuation correction. Quantitative differences of the artificial sources in the SPECT images obtained after c...
CT can be used for creating attenuation maps for quantitative SPECT. Generally, CT calibration wi... more CT can be used for creating attenuation maps for quantitative SPECT. Generally, CT calibration with known-density phantoms is needed to translate arbitrary units into physical units, usually Hounsfield units (HU). However, phantom variables and non-uniform artifacts in phantom images are responsible for a measurable degradation in accuracy of CT calibration. Here we present a histogram-based method for small-animal CT calibration without phantoms. Two peaks in histograms of total-body small-animal CT images could be found, one of which is corresponded to air (= −1000 HU) and the other one is contributed mainly by muscles. An uncalibrated CT image could be calibrated by assigning HU values of air and muscles to voxel values at the two peaks in the histogram and rescaling rest voxel values linearly. To find an proper HU value for the muscle peak of rats, and to evaluate the acceptability of using this method for attenuation correction in quantitative micro-SPECT, four rats with small ...
AbstractCardiac parameters obtained from single-photon emission computed tomographic (SPECT) imag... more AbstractCardiac parameters obtained from single-photon emission computed tomographic (SPECT) images can be affected by respiratory motion, image filtering, and animal positioning. We investigated the influence of these factors on ultra-high-resolution murine myocardial perfusion SPECT. Five mice were injected with 99m technetium (99mTc)-tetrofosmin, and each was scanned in supine and prone positions in a U-SPECT-II scanner with respiratory and electrocardiographic (ECG) gating. ECG-gated SPECT images were created without applying respiratory motion correction or with two different respiratory motion correction strategies. The images were filtered with a range of three-dimensional gaussian kernels, after which end-diastolic volumes (EDVs), end-systolic volumes (ESVs), and left ventricular ejection fractions were calculated. No significant differences in the measured cardiac parameters were detected when any strategy to reduce or correct for respiratory motion was applied, whereas big...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
SPECT with submegabecquerel amounts of tracer or subsecond time resolution would enable a wide ra... more SPECT with submegabecquerel amounts of tracer or subsecond time resolution would enable a wide range of new imaging protocols such as screening tracers with initially low yield or labeling efficiency, imaging low receptor densities, or even performing SPECT outside regular radiation laboratories. To this end we developed dedicated ultra-high-sensitivity pinhole SPECT. A cylindric collimator with 54 focused 2.0-mm-diameter conical pinholes was manufactured and mounted in a stationary small-animal SPECT system. The system matrix for image reconstruction was calculated via a hybrid method based on both (99m)Tc point source measurements and ray-tracing analytic modeling. SPECT images were reconstructed using pixel-based ordered-subsets expectation maximization. Performance was evaluated with phantoms and low-dose bone, dynamic kidney, and cardiac mouse scans. The peak sensitivity reached 1.3% (13,080 cps/MBq). The reconstructed spatial resolution (rod visibility in a micro-Jaszczak phan...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2007
Recently, we launched a stationary SPECT system (U-SPECT-I) dedicated to small-animal imaging. A ... more Recently, we launched a stationary SPECT system (U-SPECT-I) dedicated to small-animal imaging. A cylinder with 75 gold micropinhole apertures that focus on a mouse organ was used to maximize the detection yield of gamma-photons. Image resolutions of approximately 0.45 and 0.35 mm could be achieved with 0.6- and 0.3-mm pinholes, respectively. Here, we present a combined acquisition and reconstruction strategy that allowed us to perform full-body imaging with U-SPECT-I. The bed was stepped in the axial and transaxial directions so that the pinholes collected photons from the entire animal (scanning focus method, or SFM). Next, a maximum-likelihood expectation maximization algorithm exploited all projections simultaneously to reconstruct the entire volume sampled. The memory required for image reconstruction was dramatically reduced by using the same transition submatrix for each of the bed positions. This use of the same submatrix was possible because the submatrix acted on subvolumes...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 5, 2014
PET imaging of rodents is increasingly used in preclinical research, but its utility is limited b... more PET imaging of rodents is increasingly used in preclinical research, but its utility is limited by spatial resolution and signal-to-noise ratio of the images. A recently developed preclinical PET system uses a clustered-pinhole collimator, enabling high-resolution, simultaneous imaging of PET and SPECT tracers. Pinhole collimation strongly departs from traditional electronic collimation achieved via coincidence detection in PET. We investigated the potential of such a design by direct comparison to a traditional PET scanner. Two small-animal PET scanners, 1 with electronic collimation and 1 with physical collimation using clustered pinholes, were used to acquire data from Jaszczak (hot rod) and uniform phantoms. Mouse brain imaging using (18)F-FDG PET was performed on each system and compared with quantitative ex vivo autoradiography as a gold standard. Bone imaging using (18)F-NaF allowed comparison of imaging in the mouse body. Images were visually and quantitatively compared usin...
Molecular imaging has emerged as a powerful approach for studying drug interactions with cellular... more Molecular imaging has emerged as a powerful approach for studying drug interactions with cellular targets noninvasively in animal models and humans. Most large pharmaceutical companies are now building capacity for molecular imaging or seeking partnerships with research facilities. Therefore, it is timely to review the features and capabilities of the key technologies - single photon emission computed tomography (SPECT), positron emission tomography (PET) and magnetic resonance imaging (MRI). Owing to the differences in the information they convey and the time scales on which they are able to measure the kinetics of labelled drugs, they form a highly complementary set of technologies.:
Quantitative computed tomography (CT) is helpful to diagnosis and to correction for attenuation i... more Quantitative computed tomography (CT) is helpful to diagnosis and to correction for attenuation in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) images. Calibration factors, which are measured from scans of known-density phantoms, are used to convert plain CT numbers into quantitative radiodensity values (usually represented in the Hounsfield units, or HU). Even in the same CT system, the calibration factors may largely vary with different acquisition and reconstruction settings. It is not trivial for software or researchers to always apply the correct calibration factors to images. To simplify this procedure, we proposed a practical self-calibration method for small-animal CT based on image histograms. Two peaks can be found in the histogram of a small-animal CT image (Figure 1), one of which is associated with air and the other with dominating material of an animal (mainly contributed by soft tissues and muscles and hereinafter referred ...
Application of focusing pinhole geometries can result in improved resolution and reduced noise in... more Application of focusing pinhole geometries can result in improved resolution and reduced noise in small-animal SPECT studies. Attenuation of photon flux between object voxels and pinholes affects quantitative accuracy of reconstructed images. Although photon attenuation plays a much smaller role in small-animal SPECT than in clinical SPECT, correction for attenuation together with correction for scatter and distance-dependent sensitivity of pinhole collimators is desirable when high quantitative accuracy is required. Previously we proposed a 3D iterative correction method that deals with the pinhole sensitivity and scatter. Here we propose and validate a first-order method for attenuation correction in focusing pinhole SPECT, which is combined with 3D iterative reconstruction. The method has the advantage that no new system matrix has to be calculated for each scan. Instead of using X-ray CT data, optical photos made by webcams integrated in the SPECT system are used to estimate the...
OBJECTIVES: Pre-clinical SPECT images are typically much less degraded by attenuation than clinic... more OBJECTIVES: Pre-clinical SPECT images are typically much less degraded by attenuation than clinical SPECT images because of smaller body dimensions. It means that first-order attenuation-correction could be sufficient for quantitative pre-clinical studies. Here we developed and validated a practical Chang-based method based on animal body contours to perform attenuation correction for multi-pinhole SPECT that does not require CT data. METHODS: Optical images from the top and both sides of the animals prior to scanning were obtained and displayed on a dedicated graphical user interface. This allows the users to quickly draw 2D contours of each animal on the sagittal and coronal optical images, and then creates a 3D surface based on widths measured on the 2D contours at each transverse slice of the animal. With the 3D surfaces, uniform attenuation-coefficient maps were generated and a first-order Chang algorithm was carried out on reconstructed images. The method is combined with scat...
ABSTRACT Gamma cameras based on Charge Coupled Devices (CCDs) and micro-columnar CsI scintillator... more ABSTRACT Gamma cameras based on Charge Coupled Devices (CCDs) and micro-columnar CsI scintillators can reach high spatial resolutions. However, the gamma interaction probability of these scintillators is low (typically ≪30% at 141 keV) due to the limited thickness of presently available micro-columnar scintillators. Continuous scintillators can improve the interaction probability but suffer from increased light spread compared to columnar scintillators. In addition, for both types of scintillators gamma photons incident at an oblique angle reduce the spatial resolution due to the variable depth of interaction (DOI). To improve spatial resolution and spectral characteristics of these detectors, we have developed a fast analytic scintillation detection algorithm that makes use of a depth-dependent light spread model and as a result is able to determine the DOI in the scintillator. This algorithm, performing multi-scale frame analysis, was tested for an Electron Multiplying CCD (EM-CCD) optically coupled to CsI(Tl) scintillators of different thicknesses. For a 2.6 mm thick scintillator a spatial resolution of 148 μm Full Width Half Maximum (FWHM) was obtained with an energy resolution of 46% FWHM for gamma photons incident perpendicularly (interaction probability 61% at 141 keV). The multi-scale algorithm improves the spatial resolution up to 11 %, and the energy resolution up to 36 % compared to a previously implemented algorithm that did not model the depth-dependent light spread. In addition, the multi-scale algorithm can accurately approximate DOI. As a result, degradation of the spatial resolution due to the variable DOI for gamma photons incident at a 47° angle was improved from 2600 μm to 508 μm FWHM for a 3 mm thick scintillator. We conclude that the multi-scale algorithm significantly improves CCD based gamma cameras as can be applied in future SPECT systems.
Pre- and intraoperative diagnostic techniques facilitating tumor staging are of paramount importa... more Pre- and intraoperative diagnostic techniques facilitating tumor staging are of paramount importance in colorectal cancer surgery. The urokinase receptor (uPAR) plays an important role in the development of cancer, tumor invasion, angiogenesis, and metastasis and over-expression is found in the majority of carcinomas. This study aims to develop the first clinically relevant anti-uPAR antibody-based imaging agent that combines nuclear (111In) and real-time near-infrared (NIR) fluorescent imaging (ZW800-1). Conjugation and binding capacities were investigated and validated in vitro using spectrophotometry and cell-based assays. In vivo, three human colorectal xenograft models were used including an orthotopic peritoneal carcinomatosis model to image small tumors. Nuclear and NIR fluorescent signals showed clear tumor delineation between 24h and 72h post-injection, with highest tumor-to-background ratios of 5.0 ± 1.3 at 72h using fluorescence and 4.2 ± 0.1 at 24h with radioactivity. 1-...
Objective: Attenuation of photon flux on trajectories between the source and pinhole apertures af... more Objective: Attenuation of photon flux on trajectories between the source and pinhole apertures affects the quantitative accuracy of reconstructed single-photon emission computed tomography (SPECT) images. Attenuation maps can be employed, e.g. from registered X-ray CT images, to correct for attenuation post-reconstruction, showing highly accurate quantification. Here we investigate effects of CT image inaccuracies (misregistration and errors in attenuation coefficients) to quantitative accuracy. Methods: A rat cadaver containing 12 small artificial Tc-99m sources with known activities was scanned in a U-SPECT-II/CT system. An attenuation map was derived from the CT image (as a gold standard), and then the map was shifted up to 3 mm or the attenuation coefficients in the maps were globally altered by 10%. A Chang-based first-order method was employed for post-reconstruction attenuation correction. Quantitative differences of the artificial sources in the SPECT images obtained after c...
CT can be used for creating attenuation maps for quantitative SPECT. Generally, CT calibration wi... more CT can be used for creating attenuation maps for quantitative SPECT. Generally, CT calibration with known-density phantoms is needed to translate arbitrary units into physical units, usually Hounsfield units (HU). However, phantom variables and non-uniform artifacts in phantom images are responsible for a measurable degradation in accuracy of CT calibration. Here we present a histogram-based method for small-animal CT calibration without phantoms. Two peaks in histograms of total-body small-animal CT images could be found, one of which is corresponded to air (= −1000 HU) and the other one is contributed mainly by muscles. An uncalibrated CT image could be calibrated by assigning HU values of air and muscles to voxel values at the two peaks in the histogram and rescaling rest voxel values linearly. To find an proper HU value for the muscle peak of rats, and to evaluate the acceptability of using this method for attenuation correction in quantitative micro-SPECT, four rats with small ...
AbstractCardiac parameters obtained from single-photon emission computed tomographic (SPECT) imag... more AbstractCardiac parameters obtained from single-photon emission computed tomographic (SPECT) images can be affected by respiratory motion, image filtering, and animal positioning. We investigated the influence of these factors on ultra-high-resolution murine myocardial perfusion SPECT. Five mice were injected with 99m technetium (99mTc)-tetrofosmin, and each was scanned in supine and prone positions in a U-SPECT-II scanner with respiratory and electrocardiographic (ECG) gating. ECG-gated SPECT images were created without applying respiratory motion correction or with two different respiratory motion correction strategies. The images were filtered with a range of three-dimensional gaussian kernels, after which end-diastolic volumes (EDVs), end-systolic volumes (ESVs), and left ventricular ejection fractions were calculated. No significant differences in the measured cardiac parameters were detected when any strategy to reduce or correct for respiratory motion was applied, whereas big...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
SPECT with submegabecquerel amounts of tracer or subsecond time resolution would enable a wide ra... more SPECT with submegabecquerel amounts of tracer or subsecond time resolution would enable a wide range of new imaging protocols such as screening tracers with initially low yield or labeling efficiency, imaging low receptor densities, or even performing SPECT outside regular radiation laboratories. To this end we developed dedicated ultra-high-sensitivity pinhole SPECT. A cylindric collimator with 54 focused 2.0-mm-diameter conical pinholes was manufactured and mounted in a stationary small-animal SPECT system. The system matrix for image reconstruction was calculated via a hybrid method based on both (99m)Tc point source measurements and ray-tracing analytic modeling. SPECT images were reconstructed using pixel-based ordered-subsets expectation maximization. Performance was evaluated with phantoms and low-dose bone, dynamic kidney, and cardiac mouse scans. The peak sensitivity reached 1.3% (13,080 cps/MBq). The reconstructed spatial resolution (rod visibility in a micro-Jaszczak phan...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2007
Recently, we launched a stationary SPECT system (U-SPECT-I) dedicated to small-animal imaging. A ... more Recently, we launched a stationary SPECT system (U-SPECT-I) dedicated to small-animal imaging. A cylinder with 75 gold micropinhole apertures that focus on a mouse organ was used to maximize the detection yield of gamma-photons. Image resolutions of approximately 0.45 and 0.35 mm could be achieved with 0.6- and 0.3-mm pinholes, respectively. Here, we present a combined acquisition and reconstruction strategy that allowed us to perform full-body imaging with U-SPECT-I. The bed was stepped in the axial and transaxial directions so that the pinholes collected photons from the entire animal (scanning focus method, or SFM). Next, a maximum-likelihood expectation maximization algorithm exploited all projections simultaneously to reconstruct the entire volume sampled. The memory required for image reconstruction was dramatically reduced by using the same transition submatrix for each of the bed positions. This use of the same submatrix was possible because the submatrix acted on subvolumes...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 5, 2014
PET imaging of rodents is increasingly used in preclinical research, but its utility is limited b... more PET imaging of rodents is increasingly used in preclinical research, but its utility is limited by spatial resolution and signal-to-noise ratio of the images. A recently developed preclinical PET system uses a clustered-pinhole collimator, enabling high-resolution, simultaneous imaging of PET and SPECT tracers. Pinhole collimation strongly departs from traditional electronic collimation achieved via coincidence detection in PET. We investigated the potential of such a design by direct comparison to a traditional PET scanner. Two small-animal PET scanners, 1 with electronic collimation and 1 with physical collimation using clustered pinholes, were used to acquire data from Jaszczak (hot rod) and uniform phantoms. Mouse brain imaging using (18)F-FDG PET was performed on each system and compared with quantitative ex vivo autoradiography as a gold standard. Bone imaging using (18)F-NaF allowed comparison of imaging in the mouse body. Images were visually and quantitatively compared usin...
Molecular imaging has emerged as a powerful approach for studying drug interactions with cellular... more Molecular imaging has emerged as a powerful approach for studying drug interactions with cellular targets noninvasively in animal models and humans. Most large pharmaceutical companies are now building capacity for molecular imaging or seeking partnerships with research facilities. Therefore, it is timely to review the features and capabilities of the key technologies - single photon emission computed tomography (SPECT), positron emission tomography (PET) and magnetic resonance imaging (MRI). Owing to the differences in the information they convey and the time scales on which they are able to measure the kinetics of labelled drugs, they form a highly complementary set of technologies.:
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Papers by Freek Beekman