Quantitative image reconstruction for small-animal SPECT imaging including resolution recovery, scatter correction and attenuation correction.

This study assessed the impact of scatter and attenuation corrections on the estimated activity delivered to whole body and liver in five patients included in a radioimmunotherapy clinical trial. Before injection of the radiopharmaceutical, transmission images were acquired with the Transmission Attenuation Correction - Whole-body (SMVi-GEMS) prototype. Emission images were obtained in energy-indexed list mode at least four times after injection. 20% window and scatter-corrected images (Dual Energy Window-DEW and Triple Energy Window-TEW) were generated. Whole-body activity was calculated 1-h after injection (and compared with injected activity). Cumulated activities in whole body and liver were determined according to the geometric mean approach. The mean relative error made in estimations of whole-body activity at 1-h was 6.9+/-10.3% without corrections. Taking scatter into account led to underestimation, but reduced the influence of patient morphotype (-40.0+/-7.6% and -43.3+/-6.2% for DEW and TEW). Attenuation correction led to a large overestimation, whether used alone (155.2+/-39.0%) or associated with scatter correction (39.6+/-10.4% and 35.9+/-10.2% for DEW and TEW). Compared to the geometric mean alone, scatter correction led to a reduction of cumulated activities of around 45% for whole body and less than 30% for liver. Attenuation correction had a more marked impact, particularly for liver where estimated cumulated activity increased from 150 to 300%. Preliminary scatter correction limited the increase to 100% for DEW and 150% for TEW in liver and to 25% for both DEW and TEW in whole body. Although this would probably be different at the organ level, the calculation of whole-body activity without scatter and attenuation correction gave the lowest biases. But from a scientific point of view, this cannot be a satisfactory method. Attenuation correction has a greater impact than scatter correction. The association of both corrections is not sufficient to obtain accurate absolute quantification. Other factors limit planar quantification with iodine-131, notably auto-absorption of sources, septal penetration of high-energy photons through the collimator and superimposition of sources.

Scatter correction improves concordance in SPECT MPI with a dedicated cardiac SPECT solid-state camera

BackgroundNoninvasive multimodality imaging is essential for preclinical evaluation of the biodistribution and pharmacokinetics of radionuclide therapy and for monitoring tumor response. Imaging with nonstandard positron-emission tomography [PET] isotopes such as 124I is promising in that context but requires accurate activity quantification. The decay scheme of 124I implies an optimization of both acquisition settings and correction processing. The PET scanner investigated in this study was the Inveon PET/CT system dedicated to small animal imaging.MethodsThe noise equivalent count rate [NECR], the scatter fraction [SF], and the gamma-prompt fraction [GF] were used to determine the best acquisition parameters for mouse- and rat-sized phantoms filled with 124I. An image-quality phantom as specified by the National Electrical Manufacturers Association NU 4-2008 protocol was acquired and reconstructed with two-dimensional filtered back projection, 2D ordered-subset expectation maximization [2DOSEM], and 3DOSEM with maximum a posteriori [3DOSEM/MAP] algorithms, with and without attenuation correction, scatter correction, and gamma-prompt correction (weighted uniform distribution subtraction).ResultsOptimal energy windows were established for the rat phantom (390 to 550 keV) and the mouse phantom (400 to 590 keV) by combining the NECR, SF, and GF results. The coincidence time window had no significant impact regarding the NECR curve variation. Activity concentration of 124I measured in the uniform region of an image-quality phantom was underestimated by 9.9% for the 3DOSEM/MAP algorithm with attenuation and scatter corrections, and by 23% with the gamma-prompt correction. Attenuation, scatter, and gamma-prompt corrections decreased the residual signal in the cold insert.ConclusionsThe optimal energy windows were chosen with the NECR, SF, and GF evaluation. Nevertheless, an image quality and an activity quantification assessment were required to establish the most suitable reconstruction algorithm and corrections for 124I small animal imaging.

We evaluated a novel normal database (NDB) generated using single photon emission computed tomography (SPECT) data obtained from healthy brains by using a SPECT/CT system, analyzed using a resolution recovery (RR) technique applied to the three-dimensional stereotactic surface projection (3D-SSP) technique. We used a three-dimensional ordered subset expectation maximization method (3D-OSEM) with applied scatter correction (SC), attenuation correction, and RR to reconstruct the data. We verified the accuracy of the novel NDB's values (Z, extent, and error scores), and compared the novel NDB to the 3D-SSP technique by using simulated misery perfusion-related patient data from a conventional NDB. In addition, Z, extent, and error scores at the precuneus, cuneus, and posterior cingulate were compared under different reconstruction conditions by using the patient data. In the simulation, Z scores decreased when using the novel NDB corrected using computed tomography-based attenuation correction (CTAC), SC, and RR. The extent scores of the posterior cingulate increased using the novel NDB, relative to the other NDBs. The error score with the novel NDB without RR decreased by 15% compared to that of the conventional NDB. Z scores generated from patient data decreased in the novel NDB with RR. The extent scores tended to decrease in the novel NDB with RR. The extent scores in the novel NDB with RR improved at the posterior cingulate, compared to the scores with the other NDBs. However, applying RR to the novel NDB conferred no advantage because the cut-off of the current Z score must be reconsidered when using the additive RR technique.

Low energy (LE) collimator is generally used in I-123 SPECT imaging. However, the septal penetration and scattering of photons emitted with energy above 159 keV will affect the image contrast and quantitative accuracy of images. To reduce this effect, medium energy (ME) collimator has been used with the cost of lower counting statistics and spatial resolution. The effects of collimator dependency on the quantitative accuracy of attenuation corrected (AC) I-123 SPECT images using X-ray-based attenuation map was investigated. Both brain and heart/thorax phantoms were used to evaluate different degree of attenuation effect between brain and thorax. Experiments were performed at different target-to-background ratios to simulate different object contrast. Both photopeak and scatter projections were collected for dual-energy window scatter correction (SC). Images were reconstructed and compared using different reconstruction methods, which included FBP (filtered backprojection), and OSEM (ordered subset expectation maximization) without corrections, with AC, with SC, and with AC and SC. In both phantom studies, the image contrast and quantitative accuracy were both improved with the use of CT-based transmission map for AC. The image contrast provided by ME collimator was better than that of LE collimator, especially in the region with void activity of thorax phantom. From the results of phantom studies, medium energy collimator with CT-based transmission map showed improvements in image contrast and quantitative accuracy of I-123 SPECT images.

This study aimed to develop deep learning (DL) models for CT-free attenuation correction and Monte Carlo-based scatter correction in 99mTc-macroagregated albumin (99mTc-MAA) SPECT imaging, with the goal of enhancing quantitative accuracy for improved treatment planning and pre-therapy dosimetry in 90Y-selctive internal radiation therapy (SIRT). Data from 222 patients who underwent 99mTc-MAA SPECT imaging prior to 90Y-SIRT were included in this study. Uncorrected SPECT images (without attenuation and/or scatter correction) were used as input to a modified 3D shifted-window UNet Transformer (Swin UNETR) architecture. Three separate models were trained to predict attenuation corrected (AC), scatter corrected (SC), and joint attenuation and scatter corrected (ASC) SPECT images. The dataset was split into a training set (~ 80%) and an independent test set (~ 20%). Model training was performed using a five-fold cross-validation framework, with final evaluation conducted on the blind test set. To clinically assess model performance, 3D voxel-wise dosimetry was performed on the test set using the local energy deposition method, assuming 99mTc-MAA as a surrogate for 90Y distribution. Quantitative evaluation included organ- and voxel-level metrics, along with Gamma analysis using three combinations of distance-to-agreement (DTA, mm) and dose-difference (DD, %) criteria. The average (± SD) of the voxel-wise mean error (ME) was ≤ 0.003Gy for all tasks. The Relative Error (RE (%)) for AC, SC, and ASC tasks were 4.64 ± 7.52%, 8.99 ± 26.35%, and 16.45 ± 25.83%, respectively. Voxel-level Gamma evaluations within the whole body using three different criteria sets, including "DTA: 4.79mm, DD: 1%"; "DTA: 10mm, DD: 5%"; and "DTA: 15mm, DD: 10%" yielded pass rates of over 99.60%. The mean absolute error (MAE) for lesions, normal liver and lungs across all tasks were 3.16 ± 3.39, 0.35 ± 0.36, 0.41 ± 0.47Gy for AC, 1.97 ± 2.79, 0.19 ± 0.16, 0.22 ± 0.20Gy, for SC and 5.16 ± 7.10, 0.45 ± 0.51, and 0.34 ± 0.37Gy for ASC, respectively. Multiple models were developed for key SPECT quantification tasks, with potential value in clinical setting lacking reliable CT data or sufficient computational resources for Monte Carlo simulations. The models look promising for potential clinical translation and integration into commercial reconstruction software.

A comprehensive validation of data acquired by different myocardial perfusion imaging (MPI) systems was performed to evaluate contrast, self-attenuation properties, and perfusion detection capability. An anthropomorphic phantom with a myocardial insert and perfusion defect was used to simulate 99mTc-tetrofosmin distribution. Different MPI systems were evaluated: a SPECT system with iterative reconstruction algorithms and resolution recovery (IRR) with/without scatter correction (SPECT-IRR-SC and SPECT-IRR), and a cardio-centric IQ SPECT/CT system with IRR, with/without scatter and attenuation corrections (IQ-IRR-SC-AC and IQ-IRR). The image quality was assessed through physical descriptors: the contrast between the left ventricular (LV) wall and LV inner chamber (CLV/LVIC), intrinsic contrast (IC), and net contrast (NC). CLV/LVIC was found to be superior for IQ-IRR-SC-AC. The IC results showed non-uniformity of the signal intensity in the LV wall for the SPECT systems. The lowest IC values were obtained for IQ-IRR-SC-AC, except for septal position, where an underestimation of the signal intensity was revealed. The NC was found to be the highest for IQ-IRR-SC-AC and SPECT-IRR-SC. Additionally, for IQ-IRR-SC-AC, the NC increased in posterior and septal positions compared to IQ-IRR, enabling better perfusion detection capability over short-axis images. IQ-IRR showed performances comparable to SPECT-IRR. The characterization and evaluation perfusion detection capability of the MPI systems enabled the investigation of the systems’ performance and limitations.

N-isopropyl-p-123I-iodoamphetamine brain perfusion SPECT has been used with various attenuation coefficients (μ-values); however, optimization is required. This study aimed to determine the optimal μ-value (μopt-value) for Chang attenuation correction (AC) using clinical data by comparing the Chang method and CT-based AC. Methods: We used 100 patients (reference group, 60; disease group, 40) who underwent N-isopropyl-p-123I-iodoamphetamine SPECT. SPECT images of the reference group were obtained to calculate the AC using the Chang method (μ-values, 0.07-0.20; 0.005 interval) and the CT-based method, both without scatter correction (SC) and with SC. The μopt-value with the smallest mean percentage error for the brain regions of the reference group was calculated. Agreement between the Chang and CT-based methods applying the μopt-value was evaluated using Bland-Altman analysis. Additionally, the percentage error in the region of hypoperfusion in the diseased group was compared with the percentage error in the same region in the reference group when the μopt-value was applied. Results: The μopt-values were 0.140 for Chang without SC and 0.160 for Chang with SC. In the Chang method, with the μopt-value applied, fixed and proportional biases were observed in the Bland-Altman analysis (both P < 0.05), and there was a tendency for the percentage error to be underestimated in the limbic regions and overestimated in the central brain regions. There was no significant difference between the disease group and the reference group in the region of hypoperfusion in either Chang without SC or Chang with SC. Conclusion: The present study revealed that the μopt-values of the Chang method are 0.140 without SC and 0.160 with SC.

The present study aimed to quantify which image reconstruction conditions for normal databases and patients affect statistical brain function image analysis using an easy z score imaging system (eZIS) and 3-dimensional stereotactic surface projections (3D-SSP). We constructed normal databases based on cerebral perfusion SPECT images obtained from 15 healthy individuals. Each normal database was created with the following unique conditions: a variable Butterworth filter cutoff frequency (fc) with and without scatter and attenuation corrections. To simulate patient data, we selected 1 dataset from among those created from the 15 healthy individuals. The simulated patient data were designed to include hypoperfused regions with prespecified volumes. Using 3D-SSP and eZIS, we compared how the above processing conditions affect the distribution of SD in normal database images and the accuracy of detecting specific regions. The SD for the SPECT images increased with the fc of the Butterworth filter. The z score decreased by 30% for 3D-SSP and by 14% for eZIS, indicating that the prefilter significantly affected z scores. The accuracy of detecting the hypoperfused regions was significantly influenced by the fc; 3D-SSP decreased by 7.51%, and eZIS decreased by 55.34%. The detection accuracy with eZIS, which involves a smoothing process, was significantly decreased. The error of the area of hypoperfused regions was minimized when normal database and patient data were both corrected for scatter and attenuation. When the reconstruction conditions (fc, scatter correction, and attenuation correction) at normal database creation differed from those at patient data processing, the z scores widely underestimated the analytic results because the SD varied according to the reconstruction conditions. The accuracy of brain function image analysis can be improved by considering the reconstruction conditions and correcting for scatter and attenuation on both normal databases and patient data.

The purpose of this study was to demonstrate the feasibility of accurate quantification in pinhole SPECT using micro-CT information. Pinhole SPECT scans were performed using a clinical dual-head gamma camera. Each pinhole SPECT scan was followed by a micro-CT acquisition. Functional and anatomical images were coregistered using six point sources visible with both modalities. Pinhole SPECT images were reconstructed iteratively. Attenuation correction was based on micro-CT information. Scatter correction was based on dual and triple-energy window methods. Phantom and animal experiments were performed. A phantom containing nine vials was filled with different concentrations of (99m)Tc. Three vials were also filled with CT contrast agent to increase attenuation. Activity concentrations measured on the pinhole SPECT images were compared with activity concentrations measured by the dose calibrator. In addition, 11 mice were injected with (99m)Tc-labelled Nanobodies. After acquiring functional and anatomical images, the animals were killed and the liver activity was measured using a gamma-counter. Activity concentrations measured on the reconstructed images were compared with activity concentrations measured with the gamma counter. The phantom experiments demonstrated an average error of -27.3 +/- 15.9% between the activity concentrations measured on the uncorrected pinhole SPECT images and in the dose calibrator. This error decreased significantly to -0.1 +/- 7.3% when corrections were applied for nonuniform attenuation and scatter. The animal experiment revealed an average error of -18.4 +/- 11.9% between the activity concentrations measured on the uncorrected pinhole SPECT images and measured with the gamma counter. This error decreased to -7.9 +/- 10.4% when attenuation and scatter correction was applied. Attenuation correction obtained from micro-CT data in combination with scatter correction allows accurate quantification in pinhole SPECT.

Human-observer receiver-operating characteristic (ROC) results with clinical patient studies indicate that ordered-subset expectation-maximization (OSEM) reconstructions with a combination of corrections for attenuation, scatter, and distance-dependent resolution (DDR) significantly improves perfusion defect detection accuracy over filtered back-projection (FBP) images with no compensation. A recent Monte Carlo study has also shown that for scatter correction (SC) in particular, selection of an appropriate strategy can impact cardiac uniformity. The spatial domain based effective source scatter estimation (ESSE) technique was shown to provide more robust performance in improving cardiac uniformity than the triple-energy window (TEW) method. In this work, we investigate if further improvements in observer performance could be obtained by using the ESSE method of SC instead of the currently employed TEW SC, in combination with attenuation correction (AC) and resolution compensation (RC). We evaluated the effectiveness of the ESSE method to provide additional improvements in image quality objectively by using human-observer ROC studies on clinically acquired patient acquisitions. Results indicate that both ESSE and TEW SC in combination with AC and RC provide significantly higher detection accuracy than FBP with no compensation for the overall detection of coronary artery disease (CAD) as well as in localizing perfusion defects in the left anterior descending (LAD) and left circumflex (LCx) territories. Comparing, the two implementations of SC evaluated in this study, we note that the ESSE method resulted in larger aggregate areas under the ROC curve (A/sub z/) in each case. However, a statistically significant improvement over TEW correction was only observed in the LAD territory. This indicates that SC implemented with the ESSE and TEW methods were close in terms of their improvement in detection accuracy for perfusion defects in the clinical images of this investigation, with the ESSE method arguably being slightly better. However, the clinical implementation of ESSE will be hampered by its longer computing time.

Ho-166 is a combined beta–gamma emitter of which the betas can be used therapeutically. From the 81 keV gammas of Ho-166, SPECT images can be obtained, which give opportunities to guide Ho-166 therapy. Accurate reconstruction of Ho-166 images is currently hampered by photopeak-scatter in the patient, down-scatter in the detector, collimator and patient caused by the 1.4 MeV photons and by bremsstrahlung. We developed and validated a method for quantitative SPECT of Ho-166 that involves correction for both types of scatter plus non-uniform attenuation correction using attenuation maps. Photopeak-scatter (S) is compensated for by a rapid 3D Monte Carlo (MC) method that is incorporated in ordered subset (OS) reconstruction of the emission data, together with simultaneous correction for attenuation (A) and detector response (D); this method is referred to as OS-ADS. Additionally, for correction of down-scatter, we use a 14 keV wide energy window centred at 118 keV (OS-ADSS). Due to a limited number of available energy windows, the same 118 keV energy window was used for down-scatter correction of the simultaneously acquired Gd-153 transmission data. Validations were performed using physical phantom experiments carried out on a dual-head SPECT system; Gd-153 transmission line sources were used for acquiring attenuation maps. For quantitative comparison of OS-ADS and OS-ADSS, bottles filled with Ho-166 were placed in both a cylindrical phantom and an anthropomorphic thorax phantom. Both OS-ADS and OS-ADSS were compared with an ordered subset reconstruction without any scatter correction (OS-AD). Underestimations of about 20% in the attenuation map were reduced to a few per cent after down-scatter correction. The average deviation from the true activity contained in the bottles was +72% with OS-AD. Using OS-ADS, this average overestimation was reduced to +28% and with OS-ADSS the deviation was further reduced to 16%. With OS-AD and OS-ADS, these numbers were more sensitive to the choice of volumes of interest than with OS-ADSS. For the reconstructed activity distributions, erroneous background activity found with OS-AD was reduced by a factor of ∼2 by applying OS-ADS and reduced by a factor of ∼4 by applying OS-ADSS. The combined attenuation, photopeak-scatter and down-scatter correction framework proposed here greatly enhanced the quantitative accuracy of Ho-166 imaging, which is of the uppermost importance for image-guided therapies. It is expected that the method, with adapted window settings, also can be applied to other isotopes with high energy peaks that contaminate the photopeak data, such as I-131 or In-111.

Detector blurring and non-ideal collimation decrease the spatial resolution of the single-photon emission computed tomography (SPECT) images. Iterative reconstruction algorithms such as ordered subsets expectation maximization (OSEM) can incorporate degrading factors during reconstruction. We investigated the quantitative errors associated with poor SPECT resolution and evaluated the importance of two-dimensional (2D) and three-dimensional (3D) resolution recovery by modelling system response during iterative image reconstruction. Different phantoms consisted of the NURBS-based cardiac-torso (NCAT) liver phantom with small tumors, the Zubal brain phantom and the NCAT heart phantom were used in this study. Monte Carlo simulation was used to create SPECT projections. Gaussian functions were used to model collimator detector response (CDR). Modeled CDRs were applied during OSEM. Both noise-free and noisy projections were created. Even with noise-free projections, conventional OSEM algorithm provided limited quantitative accuracy compared to both 2D and 3D resolution recovery. The 3D implementation of resolution recovery, however, yielded superior results compared to its 2D implementation. For the liver phantom, the ability to distinguish small tumors in both transverse and axial planes was improved. For the brain phantom, gray to white matter activity ratio was increased from 3.14 ± 0.04 in simple OSEM to 3.84 ± 0.06 in 3D OSEM. For the NCAT heart phantom, 3D resolution recovery, results in images with thinner wall and higher contrast for different noise levels. There are considerable quantitative errors associated with CDR, especially when the size of the target is comparable with the spatial resolution of the system. Between different reconstruction algorithms, 3D OSEM that consider the 3D nature of CDR, improve both the visual quality and the quantitative accuracy of any SPECT studies.

The rapid growth and usage of small-animal positron emission tomography (PET) in molecular imaging research has led to increased demand on PET scanner's time. One potential solution to increase throughput is to scan multiple rodents simultaneously. However, this is achieved at the expense of deterioration of image quality and loss of quantitative accuracy owing to enhanced effects of photon attenuation and Compton scattering. The purpose of this work is, first, to characterize the magnitude and spatial distribution of the scatter component in small-animal PET imaging when scanning single and multiple rodents simultaneously and, second, to assess the relevance and evaluate the performance of scatter correction under similar conditions. The LabPET™-8 scanner was modelled as realistically as possible using Geant4 Application for Tomographic Emission Monte Carlo simulation platform. Monte Carlo simulations allow the separation of unscattered and scattered coincidences and as such enable detailed assessment of the scatter component and its origin. Simple shape-based and more realistic voxel-based phantoms were used to simulate single and multiple PET imaging studies. The modelled scatter component using the single-scatter simulation technique was compared to Monte Carlo simulation results. PET images were also corrected for attenuation and the combined effect of attenuation and scatter on single and multiple small-animal PET imaging evaluated in terms of image quality and quantitative accuracy. A good agreement was observed between calculated and Monte Carlo simulated scatter profiles for single- and multiple-subject imaging. In the LabPET™-8 scanner, the detector covering material (kovar) contributed the maximum amount of scatter events while the scatter contribution due to lead shielding is negligible. The out-of field-of-view (FOV) scatter fraction (SF) is 1.70, 0.76, and 0.11% for lower energy thresholds of 250, 350, and 400 keV, respectively. The increase in SF ranged between 25 and 64% when imaging multiple subjects (three to five) of different size simultaneously in comparison to imaging a single subject. The spill-over ratio (SOR) increases with increasing the number of subjects in the FOV. Scatter correction improved the SOR for both water and air cold compartments of single and multiple imaging studies. The recovery coefficients for different body parts of the mouse whole-body and rat whole-body anatomical models were improved for multiple imaging studies following scatter correction. The magnitude and spatial distribution of the scatter component in small-animal PET imaging of single and multiple subjects simultaneously were characterized, and its impact was evaluated in different situations. Scatter correction improves PET image quality and quantitative accuracy for single rat and simultaneous multiple mice and rat imaging studies, whereas its impact is insignificant in single mouse imaging.

The purpose of this study was to evaluate the effects of voxel size and iterative reconstruction parameters on the radial and tangential resolution for 99mTc SPECT as a function of radial distance from isocenter. SPECT/CT scans of eight coplanar point sources of size smaller than 1 mm3 containing high concentration 99mTc solution were acquired on a SPECT/CT system with 5/8 inch NaI(Tl) detector and low-energy, high-resolution collimator. The tomographic projection images were acquired in step-and-shoot mode for 360 views over 360° with 250,000 counts per view, a zoom of 2.67, and an image matrix of 256 × 256 pixels that resulted in a 0.9 × 0.9 × 0.9 mm3 SPECT voxel size over 230 mm field-of-view. The projection images were also rebinned to image matrices of 128 × 128 and 64 × 64 to yield SPECT voxel sizes of 1.8 × 1.8 × 1.8 and 3.6 × 3.6 × 3.6 mm3, respectively. The SPECT/CT datasets were reconstructed using the vendor-supplied iterative reconstruction software that incorporated collimator-specific resolution recovery, CT-based attenuation correction, and dual-energy window-based scatter correction using different combinations of iterations and subsets. SPECT spatial resolution was estimated as the full width at half maximum of the radial and tangential profiles through the center of each point source in reconstructed SPECT images. Both radial and tangential resolution improved with higher iterations and subsets, and with smaller voxel sizes. Both radial and tangential resolution also improved with radial distance further away from isocenter. The magnitude of variation decreased for smaller voxel sizes and for higher number of iterations and subsets. Tangential resolution was found not to be equal to the radial resolution, and the nature of the anisotropy depended on the distribution of the radionuclide and on the reconstruction parameters used. The tangential resolution converged faster than the radial resolution, with higher iterations and subsets. SPECT resolution was isotropic and independent of radial distance when reconstructed using filtered back-projection. SPECT spatial resolution and therefore quantification of SPECT uptake via partial-volume correction in clinical images were found to depend on the nature of activity distribution within the SPECT field-of-view and on the specific choice of iterative reconstruction parameters.