Evaluating the Targeting of a Staphylococcus-aureus-Infected Implant with a Radiolabeled Antibody In Vivo.

Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide evidence of the specificity and biodistribution of S.-aureus-targeting antibodies in a mouse implant infection model. The monoclonal antibody 4497-IgG1 targeting wall teichoic acid in S. aureus was labeled with indium-111 using CHX-A"-DTPA as a chelator. Single Photon Emission Computed Tomography/computed tomographyscans were performed at 24, 72 and 120 h after administration of the 111In-4497 mAb in Balb/cAnNCrl mice with a subcutaneous implant that was pre-colonized with S. aureus biofilm. The biodistribution of this labelled antibody over various organs was visualized and quantified using SPECT/CT imaging, and was compared to the uptake at the target tissue with the implanted infection. Uptake of the 111In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm3 at 24 h to 9.22 %ID/cm3 at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm3, whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm3 at 120 h. The effective half-life of 111In-4497 mAbs was determined to be 59 h. In conclusion, 111In-4497 mAbs were found to specifically detect S. aureus and its biofilm with excellent and prolonged accumulation at the site of the colonized implant. Therefore, it has the potential to serve as a drug delivery system for the diagnostic and bactericidal treatment of biofilm.

Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach.

PURPOSE: Atherosclerotic plaque development and progression signifies a complex inflammatory disease mediated by a multitude of proinflammatory leukocyte subsets. Using single photon emission computed tomography (SPECT) coupled with computed tomography (CT), this study tested a new dual-isotope acquisition protocol to assess each radiotracer's capability to identify plaque phenotype and inflammation levels pertaining to leukocytes expressing leukocyte function-associated antigen-1 (LFA-1) and the leukocyte subset of proinflammatory macrophages expressing somatostatin receptor subtype-2 (SST2). Individual radiotracer uptake was quantified and the presence of corresponding immunohistological cell markers was assessed. METHODS: Human symptomatic carotid plaque segments were obtained from endarterectomy. Segments were incubated in dual-isotope radiotracers [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt) and [99mTc]Tc-[N0-14,Asp0,Tyr3]-octreotate ([99mTc]Tc-Demotate 2) before scanning with SPECT/CT. Plaque phenotype was classified as pathological intimal thickening, fibrous cap atheroma or fibrocalcific using histology sections based on distinct morphological characteristics. Plaque segments were subsequently immuno-stained with LFA-1 and SST2 and quantified in terms of positive area fraction and compared against the corresponding SPECT images. RESULTS: Focal uptake of co-localising dual-radiotracers identified the heterogeneous distribution of inflamed regions in the plaques which co-localised with positive immuno-stained regions of LFA-1 and SST2. [111In]In-Danbirt and [99mTc]Tc-Demotate 2 uptake demonstrated a significant positive correlation (r = 0.651; p = 0.001). Fibrous cap atheroma plaque phenotype correlated with the highest [111In]In-Danbirt and [99mTc]Tc-Demotate 2 uptake compared with fibrocalcific plaques and pathological intimal thickening phenotypes, in line with the immunohistological analyses. CONCLUSION: A dual-isotope acquisition protocol permits the imaging of multiple leukocyte subsets and the pro-inflammatory macrophages simultaneously in atherosclerotic plaque tissue. [111In]In-Danbirt may have added value for assessing the total inflammation levels in atherosclerotic plaques in addition to classifying plaque phenotype.

SPECT/CT Imaging of Pluronic Nanocarriers with Varying Poly(ethylene oxide) Block Length and Aggregation State.

Optimal biodistribution and prolonged circulation of nanocarriers improve diagnostic and therapeutic effects of enhanced permeability and retention-based nanomedicines. Despite extensive use of Pluronics in polymer-based pharmaceuticals, the influence of different poly(ethylene oxide) (PEO) block length and aggregation state on the biodistribution of the carriers is rather unexplored. In this work, we studied these effects by evaluating the biodistribution of Pluronic unimers and cross-linked micelles with different PEO block size. In vivo biodistribution of (111)In-radiolabeled Pluronic nanocarriers was investigated in healthy mice using single photon emission computed tomography. All carriers show fast uptake in the organs from the reticuloendothelial system followed by a steady elimination through the hepatobiliary tract and renal filtration. The PEO block length affects the initial renal clearance of the compounds and the overall liver uptake. The aggregation state influences the long-term accumulation of the nanocarriers in the liver. We showed that the circulation time and elimination pathways can be tuned by varying the physicochemical properties of Pluronic copolymers. Our results can be beneficial for the design of future Pluronic-based nanomedicines.

Development of a Hybrid Tracer for SPECT and Optical Imaging of Bacterial Infections.

In trauma and orthopedic surgery, infection of implants has a major impact on the outcome for patients. Infections may develop either during the initial implantation or during the lifetime of an implant. Both infections, as well as aseptic loosening of the implant, are reasons for revision of the implants. Therefore, discrimination between aseptic-mechanical-loosening and septic-bacterial-loosening of implants is critical during selection of a patient-tailored treatment policy. Specific detection and visualization of infections is a challenge because it is difficult to discriminate infections from inflammation. An imaging tracer that facilitates bacterial identification in a pre- and intraoperative setting may aid the workup for patients suspicious of bacterial infections. In this study we evaluated an antimicrobial peptide conjugated to a hybrid label, which contains both a radioisotope and a fluorescent dye. After synthesis of DTPA-Cy5-UBI29-41 and-when necessary-radiolabeling with (111)In (yield 96.3 ± 2.7%), in vitro binding to various bacterial strains was evaluated using radioactivity counting and confocal fluorescence microscopy. Intramuscular bacterial infections (S. aureus or K. pneumoniae) were also visualized in vivo using a combined nuclear and fluorescence imaging system. The indium-111 was chosen as label as it has a well-defined coordination chemistry, and in pilot studies labeling DTPA-Cy5-UBI29-41 with technetium-99m, we encountered damage to the Cy5 dye after the reduction with SnCl2. As a reference, we used the validated tracer (99m)Tc-UBI29-41. Fast renal excretion of (111)In-DTPA-Cy5-UBI29-41 was observed. Target to nontarget (T/NT) ratios were highest at 2 h post injection: radioactivity counting yielded T/NT ratios of 2.82 ± 0.32 for S. aureus and 2.37 ± 0.05 for K. pneumoniae. Comparable T/NT ratios with fluorescence imaging of 2.38 ± 0.09 for S. aureus and 3.55 ± 0.31 for K. pneumoniae were calculated. Ex vivo confocal microscopy of excised infected tissues showed specific binding of the tracer to bacteria. Using a combination of nuclear and fluorescence imaging techniques, the hybrid antimicrobial peptide conjugate DTPA-Cy5-UBI29-41 was shown to specifically accumulate in bacterial infections. This hybrid tracer may facilitate integration of noninvasive identification of infections and their extent as well as real-time fluorescence guidance during surgical resection of infected areas.

Influence of respiratory gating, image filtering, and animal positioning on high-resolution electrocardiography-gated murine cardiac single-photon emission computed tomography.

Cardiac 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 differences (> 5%) in EDV and ESV were found with regard to different positioning of animals. A linear relationship (p < .001) was found between the EDV or ESV and the kernel size of the gaussian filter. In short, respiratory gating did not significantly affect the cardiac parameters of mice obtained with ultra-high-resolution SPECT, whereas the position of the animals and the image filters should be the same in a comparative study with multiple scans to avoid systematic differences in measured cardiac parameters.

Quarter-millimeter-resolution molecular mouse imaging with U-SPECT⁺.

Limited spatial resolution of preclinical positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has slowed down applications of molecular imaging in small animals. Here we present the latest-generation U-SPECT system (U-SPECT⁺, MILabs, Utrecht, the Netherlands) enabling radionuclide imaging of mice with quarter-millimeter resolution. The system was equipped with the newest high-resolution collimator with 0.25 mm diameter circular pinholes. It was calibrated with technetium-99 m point source measurements from which the system matrix was calculated. Images were reconstructed using pixel-based ordered subset expectation maximization (OSEM). Various phantoms and mouse SPECT scans were acquired. The reconstructed spatial resolution (the smallest visible capillary diameter in a hot-rod resolution phantom) was 0.25 mm. Knee joint images show tiny structures such as the femur epicondyle sulcus, as well as a clear separation between cortical and trabecular bone structures. In addition, time-activity curves of the lumbar spine illustrated that tracer dynamics in tiny tissue amounts could be measured. U-SPECT⁺ allows discrimination between molecular concentrations in adjacent volumes of as small as 0.015 µL, which is significantly better than can be imaged by any existing SPECT or PET system. This increase in the level of detail makes it more and more attractive to replace ex vivo methods and allows monitoring biological processes in tiny parts of organs in vivo.

The role of preclinical SPECT in oncological and neurological research in combination with either CT or MRI.

Preclinical imaging with SPECT combined with CT or MRI is used more and more frequently and has proven to be very useful in translational research. In this article, an overview of current preclinical research applications and trends of SPECT combined with CT or MRI, mainly in tumour imaging and neuroscience imaging, is given and the advantages and disadvantages of the different approaches are described. Today SPECT and CT systems are often integrated into a single device (commonly called a SPECT/CT system), whereas at present combined SPECT and MRI is almost always carried out with separate systems and fiducial markers to combine the separately acquired images. While preclinical SPECT/CT is most widely applied in oncology research, SPECT combined with MRI (SPECT/MRI when integrated in one system) offers the potential for both neuroscience applications and oncological applications. Today CT and MRI are still mainly used to localize radiotracer binding and to improve SPECT quantification, although both CT and MRI have additional potential. Future technology developments may include fast sequential or simultaneous acquisition of (dynamic) multimodality data, spectroscopy, fMRI along with high-resolution anatomic MRI, advanced CT procedures, and combinations of more than two modalities such as combinations of SPECT, PET, MRI and CT all together. This will all strongly depend on new technologies. With further advances in biology and chemistry for imaging molecular targets and (patho)physiological processes in vivo, the introduction of new imaging procedures and promising new radiopharmaceuticals in clinical practice may be accelerated.

NaI gamma camera performance for high energies: Effects of crystal thickness, photomultiplier tube geometry and light guide thickness.

BACKGROUND: Gamma camera imaging, including single photon emission computed tomography (SPECT), is crucial for research, diagnostics, and radionuclide therapy. Gamma cameras are predominantly based on arrays of photon multipliers tubes (PMTs) that read out NaI(Tl) scintillation crystals. In this way, standard gamma cameras can localize É£-rays with energies typically ranging from 30 to 360 keV. In the last decade, there has been an increasing interest towards gamma imaging outside this conventional clinical energy range, for example, for theragnostic applications and preclinical multi-isotope positron emission tomography (PET) and PET-SPECT. However, standard gamma cameras are typically equipped with 9.5 mm thick NaI(Tl) crystals which can result in limited sensitivity for these higher energies. PURPOSE: Here we investigate to what extent thicker scintillators can improve the photopeak sensitivity for higher energy isotopes while attempting to maintain spatial resolution. METHODS: Using Monte Carlo simulations, we analyzed multiple PMT-based configurations of gamma detectors with monolithic NaI (Tl) crystals of 20 and 40 mm thickness. Optimized light guide thickness together with 2-inch round, 3-inch round, 60 × 60 mm2 square, and 76 × 76 mm2 square PMTs were tested. For each setup, we assessed photopeak sensitivity, energy resolution, spatial, and depth-of-interaction (DoI) resolution for conventional (140 keV) and high (511 keV) energy É£ using a maximum-likelihood algorithm. These metrics were compared to those of a "standard" 9.5 mm-thick crystal detector with 3-inch round PMTs. RESULTS: Estimated photopeak sensitivities for 511 keV were 27% and 53% for 20 and 40 mm thick scintillators, which is respectively, 2.2 and 4.4 times higher than for 9.5 mm thickness. In most cases, energy resolution benefits from using square PMTs instead of round ones, regardless of their size. Lateral and DoI spatial resolution are best for smaller PMTs (2-inch round and 60 × 60 mm2 square) which outperform the more cost-effective larger PMT setups (3-inch round and 76 × 76 mm2 square), while PMT layout and shape have negligible (< 10%) effect on resolution. Best spatial resolution was obtained with 60 × 60 mm2 PMTs; for 140 keV, lateral resolution was 3.5 mm irrespective of scintillator thickness, improving to 2.8 and 2.9 mm for 511 keV with 20 and 40 mm thick crystals, respectively. Using the 3-inch round PMTs, lateral resolutions of 4.5 and 3.9 mm for 140 keV and of 3.5 and 3.7 mm for 511 keV were obtained with 20 and 40 mm thick crystals respectively, indicating a moderate performance degradation compared to the 3.5 and 2.9 mm resolution obtained by the standard detector for 140 and 511 keV. Additionally, DoI resolution for 511 keV was 7.0 and 5.6 mm with 20 and 40 mm crystals using 60 × 60 mm2 square PMTs, while with 3-inch round PMTs 12.1 and 5.9 mm were obtained. CONCLUSION: Depending on PMT size and shape, the use of thicker scintillator crystals can substantially improve detector sensitivity at high gamma energies, while spatial resolution is slightly improved or mildly degraded compared to standard crystals.

A scanning focus nuclear microscope with multi-pinhole collimation.

Microscopic nuclear imaging down to spatial resolutions of a few hundred microns can already be achieved using low-energy gamma emitters (e.g.125I, ∼30 keV) and a basic single micro-pinhole gamma camera. This has been applied toin vivomouse thyroid imaging, for example. For clinically used radionuclides such as99mTc, this approach fails due to penetration of the higher-energy gamma photons through the pinhole edges. To overcome these resolution degradation effects, we propose a new imaging approach: scanning focus nuclear microscopy (SFNM). We assess SFNM using Monte Carlo simulations for clinically used isotopes. SFNM is based on the use of a 2D scanning stage with a focused multi-pinhole collimator containing 42 pinholes with narrow pinhole aperture opening angles to reduce photon penetration. All projections of different positions are used to iteratively reconstruct a three-dimensional image from which synthetic planar images are generated. SFNM imaging was tested using a digital Derenzo resolution phantom and a mouse ankle joint phantom containing99mTc (140 keV). The planar images were compared with those obtained using a single-pinhole collimator, either with matched pinhole diameter or with matched sensitivity. The simulation results showed an achievable99mTc image resolution of 0.04 mm and detailed99mTc bone images of a mouse ankle with SFNM. SFNM has strong advantages over single-pinhole imaging in terms of spatial resolution.

Glymphatic-assisted perivascular brain delivery of intrathecal small gold nanoparticles.

Nanoparticles are ultrafine particulate matter having considerable potential for treatment of central nervous system (CNS) disorders. Despite their tiny size, the blood-brain barrier (BBB) restricts their access to the CNS. Their direct cerebrospinal fluid (CSF) administration bypasses the BBB endothelium, but still fails to give adequate brain uptake. We present a novel approach for efficient CNS delivery of 111In-radiolabelled gold nanoparticles (AuNPs; 10-15 nm) via intra-cisterna magna administration, with tracking by SPECT imaging. To accelerate CSF brain influx, we administered AuNPs intracisternally in conjunction with systemic hypertonic saline, which dramatically increased the parenchymal AuNP uptake, especially in deep brain regions. AuNPs entered the CNS along periarterial spaces as visualized by MRI of gadolinium-labelled AuNPs and were cleared from brain within 24 h and excreted through the kidneys. Thus, the glymphatic-assisted perivascular network augment by systemic hypertonic saline is a pathway for highly efficient brain-wide distribution of small AuNPs.

Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro and in vivo biofilm.

Implant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and potential treatment of biofilm-related infections. Here, we show that mAbs targeting common surface components of S. aureus can recognize clinically relevant biofilm types. The mAbs were also shown to bind a collection of clinical isolates derived from different biofilm-associated infections (endocarditis, prosthetic joint, catheter). We identify two groups of antibodies: one group that uniquely binds S. aureus in biofilm state and one that recognizes S. aureus in both biofilm and planktonic state. Furthermore, we show that a mAb recognizing wall teichoic acid (clone 4497) specifically localizes to a subcutaneously implanted pre-colonized catheter in mice. In conclusion, we demonstrate the capacity of several human mAbs to detect S. aureus biofilms in vitro and in vivo.

Targeted multi-pinhole SPECT.

PURPOSE: Small-animal single photon emission computed tomography (SPECT) with focused multi-pinhole collimation geometries allows scanning modes in which large amounts of photons can be collected from specific volumes of interest. Here we present new tools that improve targeted imaging of specific organs and tumours, and validate the effects of improved targeting of the pinhole focus. METHODS: A SPECT system with 75 pinholes and stationary detectors was used (U-SPECT-II). An XYZ stage automatically translates the animal bed with a specific sequence in order to scan a selected volume of interest. Prior to stepping the animal through the collimator, integrated webcams acquire images of the animal. Using sliders, the user designates the desired volume to be scanned (e.g. a xenograft or specific organ) on these optical images. Optionally projections of an atlas are overlaid semiautomatically to locate specific organs. In order to assess the effects of more targeted imaging, scans of a resolution phantom and a mouse myocardial phantom, as well as in vivo mouse cardiac and tumour scans, were acquired with increased levels of targeting. Differences were evaluated in terms of count yield, hot rod visibility and contrast-to-noise ratio. RESULTS: By restricting focused SPECT scans to a 1.13-ml resolution phantom, count yield was increased by a factor 3.6, and visibility of small structures was significantly enhanced. At equal noise levels, the small-lesion contrast measured in the myocardial phantom was increased by 42%. Noise in in vivo images of a tumour and the mouse heart was significantly reduced. CONCLUSION: Targeted pinhole SPECT improves images and can be used to shorten scan times. Scan planning with optical cameras provides an effective tool to exploit this principle without the necessity for additional X-ray CT imaging.

Convolutional neural network based attenuation correction for123I-FP-CIT SPECT with focused striatum imaging.

SPECT imaging with123I-FP-CIT is used for diagnosis of neurodegenerative disorders like Parkinson's disease. Attenuation correction (AC) can be useful for quantitative analysis of123I-FP-CIT SPECT. Ideally, AC would be performed based on attenuation maps (µ-maps) derived from perfectly registered CT scans. Suchµ-maps, however, are most times not available and possible errors in image registration can induce quantitative inaccuracies in AC corrected SPECT images. Earlier, we showed that a convolutional neural network (CNN) based approach allows to estimate SPECT-alignedµ-maps for full brain perfusion imaging using only emission data. Here we investigate the feasibility of similar CNN methods for axially focused123I-FP-CIT scans. We tested our approach on a high-resolution multi-pinhole prototype clinical SPECT system in a Monte Carlo simulation study. Three CNNs that estimateµ-maps in a voxel-wise, patch-wise and image-wise manner were investigated. As the added value of AC on clinical123I-FP-CIT scans is still debatable, the impact of AC was also reported to check in which cases CNN based AC could be beneficial. AC using the ground truthµ-maps (GT-AC) and CNN estimatedµ-maps (CNN-AC) were compared with the case when no AC was done (No-AC). Results show that the effect of using GT-AC versus CNN-AC or No-AC on striatal shape and symmetry is minimal. Specific binding ratios (SBRs) from localized regions show a deviation from GT-AC≤2.5% for all three CNN-ACs while No-AC systematically underestimates SBRs by 13.1%. A strong correlation (r≥0.99) was obtained between GT-AC based SBRs and SBRs from CNN-ACs and No-AC. Absolute quantification (in kBq ml-1) shows a deviation from GT-AC within 2.2% for all three CNN-ACs and of 71.7% for No-AC. To conclude, all three CNNs show comparable performance in accurateµ-map estimation and123I-FP-CIT quantification. CNN-estimatedµ-map can be a promising substitute for CT-basedµ-map.

Automatic attenuation map estimation from SPECT data only for brain perfusion scans using convolutional neural networks.

In clinical brain SPECT, correction for photon attenuation in the patient is essential to obtain images which provide quantitative information on the regional activity concentration per unit volume (kBq.[Formula: see text]). This correction generally requires an attenuation map ([Formula: see text] map) denoting the attenuation coefficient at each voxel which is often derived from a CT or MRI scan. However, such an additional scan is not always available and the method may suffer from registration errors. Therefore, we propose a SPECT-only-based strategy for [Formula: see text] map estimation that we apply to a stationary multi-pinhole clinical SPECT system (G-SPECT-I) for 99mTc-HMPAO brain perfusion imaging. The method is based on the use of a convolutional neural network (CNN) and was validated with Monte Carlo simulated scans. Data acquired in list mode was used to employ the energy information of both primary and scattered photons to obtain information about the tissue attenuation as much as possible. Multiple SPECT reconstructions were performed from different energy windows over a large energy range. Locally extracted 4D SPECT patches (three spatial plus one energy dimension) were used as input for the CNN which was trained to predict the attenuation coefficient of the corresponding central voxel of the patch. Results show that Attenuation Correction using the Ground Truth [Formula: see text] maps (GT-AC) or using the CNN estimated [Formula: see text] maps (CNN-AC) achieve comparable accuracy. This was confirmed by a visual assessment as well as a quantitative comparison; the mean deviation from the GT-AC when using the CNN-AC is within 1.8% for the standardized uptake values in all brain regions. Therefore, our results indicate that a CNN-based method can be an automatic and accurate tool for SPECT attenuation correction that is independent of attenuation data from other imaging modalities or human interpretations about head contours.

Efficient Monte-Carlo based system modelling for image reconstruction in preclinical pinhole SPECT.

The use of multi-pinhole collimation has enabled ultra-high-resolution imaging of SPECT and PET tracers in small animals. Key for obtaining high-quality images is the use of statistical iterative image reconstruction with accurate energy-dependent photon transport modelling through collimator and detector. This can be incorporated in a system matrix that contains the probabilities that a photon emitted from a certain voxel is detected at a specific detector pixel. Here we introduce a fast Monte-Carlo based (FMC-based) matrix generation method for pinhole imaging that is easy to apply to various radionuclides. The method is based on accelerated point source simulations combined with model-based interpolation to straightforwardly change or combine photon energies of the radionuclide of interest. The proposed method was evaluated for a VECTor PET-SPECT system with (i) a HE-UHR-M collimator and (ii) an EXIRAD-3D 3D autoradiography collimator. Both experimental scans with99mTc,111In, and123I, and simulated scans with67Ga and90Y were performed for evaluation. FMC was compared with two currently used approaches, one based on a set of point source measurements with99mTc (dubbed traditional method), and the other based on an energy-dependent ray-tracing simulation (ray-tracing method). The reconstruction results show better image quality when using FMC-based matrices than when applying the traditional or ray-tracing matrices in various cases. FMC-based matrices generalise better than the traditional matrices when imaging radionuclides with energies deviating too much from the energy used in the calibration and are computationally more efficient for very-high-resolution imaging than the ray-tracing matrices. In addition, FMC has the advantage of easily combining energies in a single matrix which is relevant when imaging radionuclides with multiple photopeak energies (e.g.67Ga and111In) or with a continuous energy spectrum (e.g.90Y). To conclude, FMC is an efficient, accurate, and versatile tool for creating system matrices for ultra-high-resolution pinhole SPECT.

3D-printed saw guides for lower arm osteotomy, a comparison between a synthetic CT and CT-based workflow.

BACKGROUND: Three-dimensional (3D)-printed saw guides are frequently used to optimize osteotomy results and are usually designed based on computed tomography (CT), despite the radiation burden, as radiation-less alternatives like magnetic resonance imaging (MRI) have inferior bone visualization capabilities. This study investigated the usability of MR-based synthetic-CT (sCT), a novel radiation-less bone visualization technique for 3D planning and design of patient-specific saw guides. METHODS: Eight human cadaveric lower arms (mean age: 78y) received MRI and CT scans as well as high-resolution micro-CT. From the MRI scans, sCT were generated using a conditional generative adversarial network. Digital 3D bone surface models based on the sCT and general CT were compared to the surface model from the micro-CT that was used as ground truth for image resolution. From both the sCT and CT digital bone models saw guides were designed and 3D-printed in nylon for one proximal and one distal bone position for each radius and ulna. Six blinded observers placed these saw guides as accurately as possible on dissected bones. The position of each guide was assessed by optical 3D-scanning of each bone with positioned saw guide and compared to the preplanning. Eight placement errors were evaluated: three translational errors (along each axis), three rotational errors (around each axis), a total translation (∆T) and a total rotation error (∆R). RESULTS: Surface models derived from micro-CT were on average smaller than sCT and CT-based models with average differences of 0.27 ± 0.30 mm for sCT and 0.24 ± 0.12 mm for CT. No statistically significant positioning differences on the bones were found between sCT- and CT-based saw guides for any axis specific translational or rotational errors nor between the ∆T (p = .284) and ∆R (p = .216). On Bland-Altman plots, the ∆T and ∆R limits of agreement (LoA) were within the inter-observer variability LoA. CONCLUSIONS: This research showed a similar error for sCT and CT digital surface models when comparing to ground truth micro-CT models. Additionally, the saw guide study showed equivalent CT- and sCT-based saw guide placement errors. Therefore, MRI-based synthetic CT is a promising radiation-less alternative to CT for the creation of patient-specific osteotomy surgical saw guides.

Small field-of-view dedicated cardiac SPECT systems: impact of projection truncation.

PURPOSE: Small field-of-view (FOV) dedicated cardiac SPECT systems suffer from truncated projection data. This results in (1) neglect of liver activity that otherwise could be used to estimate (and subsequently correct) the amount of scatter in the myocardium by model-based scatter correction, and (2) distorted attenuation maps. In this study, we investigated to what extent truncation impacts attenuation correction and model-based scatter correction in the cases of (99m)Tc, (201)Tl, and simultaneous (99m)Tc/(201)Tl studies. In addition, we evaluated a simple correction method to mitigate the effects of truncation. METHODS: Digital thorax phantoms of different sizes were used to simulate the full FOV SPECT projections for (99m)Tc, (201)Tl, and simultaneous (99m)Tc/(201)Tl studies. Small FOV projections were obtained by artificially truncating the full FOV projections. Deviations from ideal heart positioning were simulated by axially shifting projections resulting in more severe liver truncation. Effects of truncation on SPECT images were tested for ordered subset (OS) expectation maximization reconstruction with (1) attenuation correction and detector response modelling (OS-AD), and (2) with additional Monte-Carlo-based scatter correction (OS-ADS). To correct truncation-induced artefacts, we axially extended truncated projections on both sides by duplicating pixel values on the projection edge. RESULTS: For both (99m)Tc and (201)Tl, differences in the reconstructed myocardium between full FOV and small FOV projections were negligible. In the nine myocardial segments, the maximum deviations of the average pixel values were 1.3% for OS-AD and 3.5% for OS-ADS. For the simultaneous (99m)Tc/(201)Tl studies, reconstructed (201)Tl SPECT images from full FOV and small FOV projections showed clearly different image profiles due to truncation. The maximum deviation in defected segments was found to be 49% in the worst-case scenario. However, artificially extending projections reduced deviations in defected segments to a few percent. CONCLUSION: Our results indicate that, for single isotope studies, using small FOV systems has little impact on attenuation correction and model-based scatter correction. For simultaneous (99m)Tc/(201)Tl studies, artificial projection extension almost fully eliminates the adverse effects of projection truncation.

Absolute quantitative total-body small-animal SPECT with focusing pinholes.

PURPOSE: In pinhole SPECT, attenuation of the photon flux on trajectories between source and pinholes affects quantitative accuracy of reconstructed images. Previously we introduced iterative methods that compensate for image degrading effects of detector and pinhole blurring, pinhole sensitivity and scatter for multi-pinhole SPECT. The aim of this paper is (1) to investigate the accuracy of the Chang algorithm in rodents and (2) to present a practical Chang-based method using body outline contours obtained with optical cameras. METHODS: Here we develop and experimentally validate a practical method for attenuation correction based on a Chang first-order method. This approach has the advantage that it is employed after, and therefore independently from, iterative reconstruction. Therefore, no new system matrix has to be calculated for each specific animal. Experiments with phantoms and animals were performed with a high-resolution focusing multi-pinhole SPECT system (U-SPECT-II, MILabs, The Netherlands). This SPECT system provides three additional optical camera images of the animal for each SPECT scan from which the animal contour can be estimated. RESULTS: Phantom experiments demonstrated that an average quantification error of -18.7% was reduced to -1.7% when both window-based scatter correction and Chang correction based on the body outline from optical images were applied. Without scatter and attenuation correction, quantification errors in a sacrificed rat containing sources with known activity ranged from -23.6 to -9.3%. These errors were reduced to values between -6.3 and +4.3% (with an average magnitude of 2.1%) after applying scatter and Chang attenuation correction. CONCLUSION: We conclude that the modified Chang correction based on body contour combined with window-based scatter correction is a practical method for obtaining small-animal SPECT images with high quantitative accuracy.

Small-animal SPECT and SPECT/CT: application in cardiovascular research.

Preclinical cardiovascular research using noninvasive radionuclide and hybrid imaging systems has been extensively developed in recent years. Single photon emission computed tomography (SPECT) is based on the molecular tracer principle and is an established tool in noninvasive imaging. SPECT uses gamma cameras and collimators to form projection data that are used to estimate (dynamic) 3-D tracer distributions in vivo. Recent developments in multipinhole collimation and advanced image reconstruction have led to sub-millimetre and sub-half-millimetre resolution SPECT in rats and mice, respectively. In this article we review applications of microSPECT in cardiovascular research in which information about the function and pathology of the myocardium, vessels and neurons is obtained. We give examples on how diagnostic tracers, new therapeutic interventions, pre- and postcardiovascular event prognosis, and functional and pathophysiological heart conditions can be explored by microSPECT, using small-animal models of cardiovascular disease.

Model of the point spread function of monolithic scintillator PET detectors for perpendicular incidence.

PURPOSE: Previously, we demonstrated the potential of positron emission tomography detectors consisting of monolithic scintillation crystals read out by arrays of solid-state light sensors. We reported detector spatial resolutions of 1.1-1.3 mm full width at half maximum (FWHM) with no degradation for angles of incidence up to 30 degrees, energy resolutions of approximately 11% FWHM, and timing resolutions of approximately 2 ns FWHM, using monolithic LYSO:Ce3+ crystals coupled to avalanche photodiode (APD) arrays. Here we develop, validate, and demonstrate a simple model of the detector point spread function (PSF) of such monolithic scintillator detectors. METHODS: A PSF model was developed that essentially consists of two convolved components, one accounting for the spatial distribution of the energy deposited by annihilation photons within the crystal, and the other for the influences of statistical signal fluctuations and electronic noise. The model was validated through comparison with spatial resolution measurements on a detector consisting of an LYSO:Ce3+ crystal read out by two APD arrays. RESULTS: The model is shown to describe the measured detector spatial response well at the noise levels found in the experiments. In addition, it is demonstrated how the model can be used to correct the measured spatial response for the influence of the finite diameter of the annihilation photon beam used in the experiments, thus obtaining an estimate of the intrinsic detector PSF. CONCLUSIONS: Despite its simplicity, the proposed model is an accurate tool for analyzing the detector PSF of monolithic scintillator detectors and can be used to estimate the intrinsic detector PSF from the measured one.