High-resolution Single Photon Emission Computed Tomography Research Articles

Integration of nano- and biotechnology for beta-cell and islet transplantation in type-1 diabetes treatment.

Regenerative medicine using human or porcine β‐cells or islets has an excellent potential to become a clinically relevant method for the treatment of type‐1 diabetes. High‐resolution imaging of the function and faith of transplanted porcine pancreatic islets and human stem cell–derived beta cells in large animals and patients for testing advanced therapy medicinal products (ATMPs) is a currently unmet need for pre‐clinical/clinical trials. The iNanoBIT EU H2020 project is developing novel highly sensitive nanotechnology‐based imaging approaches allowing for monitoring of survival, engraftment, proliferation, function and whole‐body distribution of the cellular transplants in a porcine diabetes model with excellent translational potential to humans. We develop and validate the application of single‐photon emission computed tomography (SPECT) and optoacoustic imaging technologies in a transgenic insulin‐deficient pig model to observe transplanted porcine xeno‐islets and in vitro differentiated human beta cells. We are progressing in generating new transgenic reporter pigs and human‐induced pluripotent cell (iPSC) lines for optoacoustic imaging and testing them in transplantable bioartificial islet devices. Novel multifunctional nanoparticles have been generated and are being tested for nuclear imaging of islets and beta cells using a new, high‐resolution SPECT imaging device. Overall, the combined multidisciplinary expertise of the project partners allows progress towards creating much needed technological toolboxes for the xenotransplantation and ATMP field, and thus reinforces the European healthcare supply chain for regenerative medicinal products.

Obstructive sleep apnea during REM sleep and daytime cerebral functioning: A regional cerebral blood flow study using high-resolution SPECT

Obstructive sleep apnea (OSA) predominantly during rapid eye movement (REM) sleep may have impacts on brain health, even in milder OSA cases. Here, we evaluated whether REM sleep OSA is associated with abnormal daytime cerebral functioning using high-resolution single-photon emission computed tomography (SPECT). We tested 96 subjects (25 F, age: 65.2 ± 6.4) with a wide range of OSA severity from no OSA to severe OSA (apnea–hypopnea index: 0–97 events/h). More respiratory events during REM sleep were associated with reduced daytime regional cerebral blood flow (rCBF) in the bilateral ventromedial prefrontal cortex and in the right insula extending to the frontal cortex. More respiratory events during non-REM (NREM) sleep were associated with reduced daytime rCBF in the left sensorimotor and temporal cortex. In subjects with a lower overall OSA severity (apnea–hypopnea index<15), more respiratory events during REM sleep were also associated with reduced daytime rCBF in the insula and extending to the frontal cortex. Respiratory events that characterized OSA during NREM versus REM sleep are associated with distinct patterns of daytime cerebral perfusion. REM sleep OSA could be more detrimental to brain health, as evidenced by reduced daytime rCBF in milder forms of OSA.

Capabilities of the Monte Carlo Simulation Codes for Modeling of a Small Animal SPECT Camera.

This study aims to compare Monte Carlo-based codes' characteristics in the determination of the basic parameters of a high-resolution single photon emission computed tomography (HiReSPECT) scanner. The geometry of this dual-head gamma camera equipped with a pixelated CsI(Na) scintillator and lead hexagonal hole collimator were accurately described in the GEANT4 Application for the Tomographic Emission (GATE), Monte Carlo N-particle extended (MCNP-X), and simulation of imaging nuclear detectors (SIMIND) codes. We implemented simulation procedures similar to the experimental test for calculation of the energy spectra, spatial resolution, and sensitivity of HiReSPECT by using 99mTc sources. The energy resolutions simulated by SIMIND, MCNP-X, and GATE were 17.53, 19.24, and 18.26%, respectively, while it was calculated at 19.15% in experimental test. The average spatial resolutions of the HiReSPECT camera at 2.5cm from the collimator surface simulated by SIMIND, MCNP-X, and GATE were 3.18, 2.9, and 2.62mm, respectively, while this parameter was reported at 2.82mm in the experiment test. The sensitivities simulated by SIMIND, MCNP-X, and GATE were 1.44, 1.27, and 1.38cps/μCi, respectively, on the collimator surface. Comparison between simulation and experimental results showed that among these MC codes, GATE enabled to accurately model realistic SPECT system and electromagnetic physical processes, but it required more time and hardware facilities to run simulations. SIMIND was the most flexible and user-friendly code to simulate a SPECT camera, but it had limitations in defining the non-conventional imaging device. The most important characteristics like time and speed of simulation, preciseness of results, and user-friendliness should be considered during simulations.

Right Ventricular Function Assessment Using Gated Blood-Pool SPECT Ventriculography in Patients with Advanced Heart Failure

Assessment of right ventricular (RV) function and volumes is critical for planning of advanced heart failure (HF) therapies, but it is often difficult and imprecise, particularly in HF patients after left ventricular assist device (LVAD) implantation. The goal of the study was to test performance of quantitative 3-dimensional gated blood-pool single photon emission computed tomography (SPECT) imaging of the right ventricle using novel high-resolution SPECT camera.

Altered brain perfusion patterns in wakefulness and slow-wave sleep in sleepwalkers.

The present study assessed brain perfusion patterns with single-photon emission computed tomography (SPECT) during sleepwalkers' post-sleep deprivation slow-wave sleep (SWS) and resting-state wakefulness. Following a 24 hr period of sleep deprivation, 10 sleepwalkers and 10 sex- and age-matched controls were scanned with a high-resolution SPECT scanner. Participants were injected with 99mTc-ethylene cysteinate dimer after 2 min of stable SWS within their first sleep cycle as well as during resting-state wakefulness, both after a subsequent 24 hr period of sleep deprivation. When compared with controls' brain perfusion patterns during both SWS and resting-state wakefulness, sleepwalkers showed reduced regional cerebral perfusion in several bilateral frontal regions, including the superior frontal, middle frontal, and medial frontal gyri. Moreover, reduced regional cerebral perfusion was also found in sleepwalkers' left postcentral gyrus, insula, and superior temporal gyrus during SWS compared with controls. During resting-state wakefulness compared with controls, reduced cerebral perfusion was also found in parietal and temporal regions of sleepwalkers' left hemisphere, whereas the right parahippocampal gyrus showed increased regional cerebral perfusion. Our results reveal patterns of reduced regional cerebral perfusion in sleepwalkers' frontal and parietal areas when compared with controls, regions previously associated with SWS generation and episode occurrence. Additionally, reduced perfusion in the dorsolateral prefrontal cortex and insula during recovery SWS is consistent with the clinical features of somnambulistic episodes, including impaired awareness and reduced pain perception. Altered regional cerebral perfusion patterns during sleepwalkers' resting-state wakefulness may be related to daytime functional anomalies in this population.

Performance comparison of finely pixelated LYSO- and GAGG-based Si-PM gamma cameras for high resolution SPECT

Although Lu-based scintillators, including Ce-doped Lu1.8Y0.2SiO5 (LYSO) scintillators, are often used for positron emission tomography (PET) detectors, they are not commonly used in gamma cameras for single-photon emission computed tomography (SPECT) because background counts due to contamination of the natural radioisotope in Lu are detected. However, several studies report that deterioration in image contrast due to background counts of the natural radioisotope is not critical and thus LYSO is promising for use in SPECT detectors. Meanwhile, a new scintillator, the Ce-doped Gd3Al2Ga3O12 (GAGG) with a high light yield and no natural radioisotope, has been developed and is also thought to be a promising scintillator. Thus, we compared the performance of LYSO with that of GAGG to determine which is more appropriate for a silicon photomultiplier (Si-PM)-based high-resolution small field-of-view (FOV) gamma camera for SPECT. We used finely pixelated LYSO and GAGG plates that were optically coupled to Si-PM arrays to form gamma cameras and measured the basic performance for 122-keV gamma photons. The energy resolutions of the LYSO- and GAGG-based Si-PM gamma cameras were 30% and 23% full width at half maximum (FWHM), respectively. The intrinsic spatial resolution of the GAGG (∼0.5mm FWHM) based gamma camera was better than that of the LYSO (∼0.6mm FWHM). The background counts of the LYSO-based gamma camera were 28 times larger than that of the GAGG. Based on these results, we conclude that GAGG is more appropriate than LYSO for the development of a Si-PM based gamma camera for high resolution SPECT.

0738 EFFECTS OF SLEEP DEPRIVATION ON BRAIN PERFUSION PATTERNS IN SLEEPWALKERS’ WAKEFULNESS AND SLOW WAVE SLEEP

Several EEG-based studies have documented anomalies in the slow wave sleep (SWS) of adult sleepwalkers. Moreover, previous imaging studies have identified specific brain perfusion patterns in sleepwalkers during post sleep deprivation wakefulness as well as during a somnambulistic episode. However, neuroimaging has yet to be used to investigate sleepwalkers’ SWS. The present study measured regional cerebral blood flow (rCBF) with single photon emission computed tomography (SPECT) during sleepwalkers’ post sleep deprivation SWS and resting-state wakefulness. Following 24 hr period of sleep deprivation, 10 sleepwalkers (7F, 3M; mean age: 28.2 ± 6.9 years) and 10 sex and age-matched controls were injected with a unidose of 99mTc-ECD after 2 minutes of stable SWS within their first sleep cycle as well as during resting-state wakefulness. Participants were scanned after each injection with a high-resolution SPECT. Between group differences in rCBF were assessed using two-sample t-tests separately for SWS and wakefulness. Significance was set at p<0.005 at the voxel level uncorrected for multiple comparisons combined with >100 contiguous voxels by cluster. When compared to controls’ rCBF observed during SWS and resting-state wakefulness, sleepwalkers showed significant decreases in several bilateral frontal regions, including the superior frontal, middle frontal and medial frontal gyri. Most of these regions are included in the dorsolateral prefrontal cortex (DLPFC). During SWS, decreased rCBF was also found in sleepwalkers’ left postcentral gyrus, insula and superior temporal gyrus. During waking resting-state, decreased rCBF was also found in parietal and temporal regions of sleepwalkers’ left hemisphere. This study was the first to use neuroimaging to investigate sleepwalkers’ SWS. Decreased rCBF was found in sleepwalkers’ DLPFC and insula, two regions involved in consciousness and in the generation of slow wave activity. The data also reveal altered rCBF patterns during sleepwalkers’ resting-state wakefulness. These findings suggest that prefrontal and insular regions may be implicated in the pathophysiology of sleepwalking. This research was supported by a research grant from the Canadian Institutes of Health Research (CIHR).

Simulation study of a novel target oriented SPECT design using a variable pinhole collimator.

In the past decade, demands for organ specific (target oriented) single-photon emission computed tomography (SPECT) is increasing, and several groups have conducted studies on developing clinical dedicated SPECT with pinhole collimator to improve the spatial resolution. However, acceptance angle of the collimator cannot be adjusted to fit the different ROIs of target objects because the shape of pinhole could not be changed, and the magnifying factor cannot be maximized as the collimator-to-detector distance is fixed. Furthermore, those dedicated pinhole SPECTs are typically made for a single purpose and therefore possess a drawback in that it cannot be utilized for any other purpose. In this study, we propose a novel SPECT system using variable pinhole collimator (VP SPECT) whose parameters are flexible. The proposed variable pinhole collimator is modeled on conventional pinhole by piling several tungsten layers of different apertures. Depending on the combination of the holes in each layer, a variety of hole diameters and acceptance angles of the pinhole can be made. In addition, VP SPECT system allows attaching the collimator to the object as close as possible to maximize the sensitivity and adjust the distance of the pinhole from the scintillation detector to optimize the system resolution for each rotation angle, automatically. For quantitative measurement, we compared the sensitivity and spatial resolution of VP SPECT with those of conventional pinhole SPECT. To determine the possibility of the clinical and preclinical use of proposed system, a digital mouse whole-body (MOBY) phantom is used for simulating the live mouse model. The result of simulation using ultra-micro hot spot phantom shows that the sensitivity of the proposed VP SPECT system is about 297% of that of the conventional system. While hot rods of diameter 0.6mm can be distinguished in the image with the proposed VP SPECT system, 1.2-mm hot rods are barely discernible in the conventional pinhole SPECT image. According to the result of MOBY phantom simulation, heart walls separated by 3mm were not distinguished in conventional pinhole SPECT images, but were clearly discerned in VP SPECT images. In this study, we designed a novel pinhole collimator for SPECT and presented preliminary results of target oriented imaging with a simulation study. Currently, we are pursuing strategies to realize the proposed system, with the goal to apply the technology into a high-sensitivity and high-resolution preclinical SPECT. Should VP SPECT be applied to the clinical setting, we anticipate a high-sensitivity, high-resolution system for applications such as heart dedicated SPECT or related fields.

SPECT Imaging of 2-D and 3-D Distributed Sources with Near-Field Coded Aperture Collimation: Computer Simulation and Real Data Validation.

The imaging of distributed sources with near-field coded aperture (CA) remains extremely challenging and is broadly considered unsuitable for single-photon emission computerized tomography (SPECT). This study proposes a novel CA SPECT reconstruction approach and evaluates the feasibilities of imaging and reconstructing distributed hot sources and cold lesions using near-field CA collimation and iterative image reconstruction. Computer simulations were designed to compare CA and pinhole collimations in two-dimensional radionuclide imaging. Digital phantoms were created and CA images of the phantoms were reconstructed using maximum likelihood expectation maximization (MLEM). Errors and the contrast-to-noise ratio (CNR) were calculated and image resolution was evaluated. An ex vivo rat heart with myocardial infarction was imaged using a micro-SPECT system equipped with a custom-made CA module and a commercial 5-pinhole collimator. Rat CA images were reconstructed via the three-dimensional (3-D) MLEM algorithm developed for CA SPECT with and without correction for a large projection angle, and 5-pinhole images were reconstructed using the commercial software provided by the SPECT system. Phantom images of CA were markedly improved in terms of image quality, quantitative root-mean-squared error, and CNR, as compared to pinhole images. CA and pinhole images yielded similar image resolution, while CA collimation resulted in fewer noise artifacts. CA and pinhole images of the rat heart were well reconstructed and the myocardial perfusion defects could be clearly discerned from 3-D CA and 5-pinhole SPECT images, whereas 5-pinhole SPECT images suffered from severe noise artifacts. Image contrast of CA SPECT was further improved after correction for the large projection angle used in the rat heart imaging. The computer simulations and small-animal imaging study presented herein indicate that the proposed 3-D CA SPECT imaging and reconstruction approaches worked reasonably well, demonstrating the feasibilities of achieving high sensitivity and high resolution SPECT using near-field CA collimation.

High-resolution brain SPECT imaging by combination of parallel and tilted detector heads.

To improve the spatial resolution of brain single-photon emission computed tomography (SPECT), we propose a new brain SPECT system in which the detector heads are tilted towards the rotation axis so that they are closer to the brain. In addition, parallel detector heads are used to obtain the complete projection data set. We evaluated this parallel and tilted detector head system (PT-SPECT) in simulations. In the simulation study, the tilt angle of the detector heads relative to the axis was 45°. The distance from the collimator surface of the parallel detector heads to the axis was 130 mm. The distance from the collimator surface of the tilted detector heads to the origin on the axis was 110 mm. A CdTe semiconductor panel with a 1.4 mm detector pitch and a parallel-hole collimator were employed in both types of detector head. A line source phantom, cold-rod brain-shaped phantom, and cerebral blood flow phantom were evaluated. The projection data were generated by forward-projection of the phantom images using physics models, and Poisson noise at clinical levels was applied to the projection data. The ordered-subsets expectation maximization algorithm with physics models was used. We also evaluated conventional SPECT using four parallel detector heads for the sake of comparison. The evaluation of the line source phantom showed that the transaxial FWHM in the central slice for conventional SPECT ranged from 6.1 to 8.5 mm, while that for PT-SPECT ranged from 5.3 to 6.9 mm. The cold-rod brain-shaped phantom image showed that conventional SPECT could visualize up to 8-mm-diameter rods. By contrast, PT-SPECT could visualize up to 6-mm-diameter rods in upper slices of a cerebrum. The cerebral blood flow phantom image showed that the PT-SPECT system provided higher resolution at the thalamus and caudate nucleus as well as at the longitudinal fissure of the cerebrum compared with conventional SPECT. PT-SPECT provides improved image resolution at not only upper but also at central slices of the cerebrum.

A high resolution SPECT detector based on thin continuous LYSO

Single-photon emission computed tomography (SPECT) detectors with improved spatial resolution can be used to build multi-pinhole SPECT systems that have a higher sensitivity or a higher spatial resolution. In order to improve the spatial resolution we investigate the performance of a 2 mm thick continuous Lutetium Yttrium Orthosilicate (LYSO) scintillator and compare it to the performance of a 5 mm thick continuous NaI(Tl) scintillator. The advantages of LYSO are its high stopping power and its non-hygroscopicity. Drawbacks are the lower light output and the intrinsic radioactivity. The hypothesis of this study is that such a thin LYSO scintillator will have a small light spread and, as a consequence, will also have an improved spatial resolution when coupled to a Hamamatsu H8500 position sensitive photomultiplier tube. To optimize the spatial resolution and the useful detector area we used a mean nearest neighbor event-positioning method. Beam source measurements (99mTc, 140 keV) were done to investigate the energy resolution and the spatial resolution of both detectors. The effect of the intrinsic radioactivity of the LYSO scintillator in the energy window was quantified. The mean energy resolution is 9.3% for the NaI(Tl) scintillator and 21.3% for the LYSO scintillator. The LYSO spectrum shows an X-ray escape peak which decreases the detection efficiency with 9.1%. The spatial resolution of the LYSO detector (0.93 mm full width at half maximum (FWHM)) is superior to the spatial resolution of the NaI(Tl) detector (1.37 mm FWHM). The intrinsic radioactivity in the energy window (42% window centered at 140 keV) is low (125.6 cps, 0.024 cps mm−3). LYSO is a promising scintillator for small-animal SPECT imaging, where spatial resolution is more important than energy resolution.

Reduction in regional cerebral blood flow in obstructive sleep apnea during wakefulness: A high-resolution SPECT study

Introduction Obstructive sleep apnea (OSA) is characterized by recurrent respiratory pauses that cause hypoxemia and sleep fragmentation. OSA is known to be associated with daytime sleepiness, cognitive deficits, and altered brain functioning. The objective of this study is to investigate changes in regional cerebral blood flow (rCBF) at rest using a high- resolution single photon emission computed tomography (SPECT) system in patients with OSA, compared to healthy subjects. Materials and methods rCBF of 9 OSA patients (apnea- hypopnea index (AHI): 39.7 ± 16.9; age: 66.1 ± 7.8 years) and 9 control subjects (AHI 2.5 ± 1.8; age: 67.9 ± 9.0 years) matched for body mass index were evaluated with 99Tc-HMPAO SPECT. Hypoperfusions in OSA subjects were compared to control subjects using statistical parametric mapping with independent t-tests with a significance threshold of 0.05 corrected for multiple comparisons for clusters and 0.001 uncorrected for peaks. Results OSA subjects showed significant reductions of rCBF in bilateral inferior parietal lobules (Brodmann area (BA): 40), left superior temporal gyrus (BA: 39) and left medial frontal gyrus (BA: 6) compared to control subjects. Conclusion These preliminary results show that OSA is associated with reduction of rCBF in several cortical regions that are known to be part of the default mode network. This network is a set of associative structures involved in internal cognition (e.g. planning and episodic memory). Altered rCBF in this network could be associated with cognitive deficits generally observed in OSA or with early signs of neurodegenerative disorders, but further studies with larger samples will be needed to investigate this relationship. Acknowledgements Supported by the Canadian Institutes of Health Research and the COPSE of the Faculty of Medicine of Universite de Montreal.

Skeletal muscle satellite cell migration to injured tissue measured with111In-oxine and high-resolution SPECT imaging

The delivery of adult skeletal muscle stem cells, called satellite cells, to several injured muscles via the circulation would be useful, however, an improved understanding of cell fate and biodistribution following their delivery is important for this goal to be achieved. The objective of this study was to evaluate the ability of systemically delivered satellite cells to home to injured skeletal muscle using single-photon emission computed tomography (SPECT) imaging of (111)In-labeled satellite cells. Satellite cells labeled with (111)In-oxine and green fluorescent protein (GFP) were injected intravenously after bupivicaine-induced injury to the tibialis anterior muscle. Animals were imaged with a high-resolution SPECT system called FastSPECT II for up to 7 days after transplantation. In vivo FastSPECT II imaging demonstrated a three to five-fold greater number of transplanted satellite cells in bupivicaine-injured muscle as compared to un-injured muscle after transplantation; a finding that was verified through autoradiograph analysis and quantification of GFP expression. Satellite cells also accumulated in other organs including the lung, liver, and spleen, as determined by biodistribution measurements. These data support the ability of satellite cells to home to injured muscle and support the use of SPECT and autoradiograph imaging techniques to track systemically transplanted (111)In labeled satellite cells in vivo, and suggest their homing may be improved by reducing their entrapment in filter organs.

Performance assessment of the single photon emission microscope: high spatial resolution SPECT imaging of small animal organs

The single photon emission microscope (SPEM) is an instrument developed to obtain high spatial resolution single photon emission computed tomography (SPECT) images of small structures inside the mouse brain. SPEM consists of two independent imaging devices, which combine a multipinhole collimator, a high-resolution, thallium-doped cesium iodide [CsI(Tl)] columnar scintillator, a demagnifying/intensifier tube, and an electron-multiplying charge-coupling device (CCD). Collimators have 300- and 450-µm diameter pinholes on tungsten slabs, in hexagonal arrays of 19 and 7 holes. Projection data are acquired in a photon-counting strategy, where CCD frames are stored at 50 frames per second, with a radius of rotation of 35 mm and magnification factor of one. The image reconstruction software tool is based on the maximum likelihood algorithm. Our aim was to evaluate the spatial resolution and sensitivity attainable with the seven-pinhole imaging device, together with the linearity for quantification on the tomographic images, and to test the instrument in obtaining tomographic images of different mouse organs. A spatial resolution better than 500 µm and a sensitivity of 21.6 counts·s-1·MBq-1 were reached, as well as a correlation coefficient between activity and intensity better than 0.99, when imaging 99mTc sources. Images of the thyroid, heart, lungs, and bones of mice were registered using 99mTc-labeled radiopharmaceuticals in times appropriate for routine preclinical experimentation of <1 h per projection data set. Detailed experimental protocols and images of the aforementioned organs are shown. We plan to extend the instrument's field of view to fix larger animals and to combine data from both detectors to reduce the acquisition time or applied activity.

The use of planar bone scintigraphy and HiSPECT for diagnosis of primary and concomitant flexor enthesopathy in the canine elbow

To investigate the possibilities and limitations of planar bone scintigraphy and high resolution single photon emission computed tomography (HiSPECT) to diagnose flexor enthesopathy and to distinguish primary flexor enthesopathy from the concomitant form. A prospective study of 46 dogs with primary flexor enthesopathy, concomitant flexor enthesopathy, medial coronoid disease, and normal elbows was performed. All dogs underwent planar bone scintigraphy and HiSPECT imaging. The obtained images were visually scored for increased radiopharmaceutical uptake in the medial humeral epicondylar and medial coronoid process region using a score from 1-3. Planar bone scintigraphy demonstrated increased radiopharmaceutical uptake in all diseased elbow joints, except for one. HiSPECT demonstrated increased radiopharmaceutical uptake of the medial humeral epicondyle in nearly all clinically affected joints with primary and concomitant flexor enthesopathy. Additional uptake of the medial coronoid process was recorded in all clinically affected joints with concomitant flexor enthesopathy and in six out of 18 with primary flexor enthesopathy. No difference in intensity of the uptake was noticed. Planar bone scintigraphy allows the attribution of lameness to the elbow joint in cases of primary flexor enthesopathy with minimal or even absent radiographic changes. The more detailed HiSPECT enables the localization of pathology within the elbow joint and is a sensitive technique to detect flexor enthesopathy. However HiSPECT is insufficient to distinguish primary from concomitant flexor enthesopathy.

A Low-Dose High-Resolution SPECT System with CdTe for Small-Animal Imaging Applications: A GATE Simulation Study

Dedicated single-photon emission computed tomography (SPECT) systems based on pixelated semiconductors are being developed for studying small animal models of human disease. To clarify the possibility of using a SPECT system with CdTe for a high resolution low-dose small animal imaging, we compared the quality of reconstructed images from pixelated CdTe detector to those from a small SPECT system with NaI(Tl). The CdTe detector was 44.8×44.8 mm and the pixels were 0.35×0.35×5 mm. The intrinsic resolution of the detector was 0.35 mm, which is equal to the pixel size. GATE simulations were performed to assess the image quality of both SPECT systems. The spatial resolutions and sensitivities for both systems were evaluated using a 10 MBq 99m Tc point source. The quantitative comparison with different injected dose was performed using a voxelized MOBY phantom, and the absorbed doses for each organ were evaluated. The spatial resolution of the SPECT with NaI(Tl) was about 1.54 mm FWHM, while that of the SPECT with a CdTe detector was about 1.32 mm FWHM at 30 mm. The sensitivity of NaI(Tl) based SPECT was 83 cps/MBq, while that of the CdTe detector based SPECT was 116 cps/MBq at 30 mm. The image statistics were evaluated by calculating the CNR of the image from both systems. When the injected activity for the striatum in the mouse brain was 160 Bq/voxel, the CNR of CdTe based SPECT was 2.30 while that of NaI(Tl) based SPECT was 1.85. The CNR of SPECT with CdTe was overall higher than that of the NaI(Tl) based SPECT. In addition, the absorbed dose was higher from SPECT with CdTe than those from NaI(Tl) based SPECT to acquire the same quantitative values. Our simulation results indicated that the SPECT with CdTe detector showed overall high performance compared to the SPECT with NaI(Tl). Even though the validation study is needed, the SPECT system with CdTe detector appeared to be feasible for high resolution low-dose small animal imaging.

Myocardial Infarction Area Quantification using High-Resolution SPECT Images in Rats

BackgroundImaging techniques enable in vivo sequential assessment of the morphology and function of animal organs in experimental models. We developed a device for high-resolution single photon emission computed tomography (SPECT) imaging based on an adapted pinhole collimator. ObjectiveTo determine the accuracy of this system for quantification of myocardial infarct area in rats. MethodsThirteen male Wistar rats (250 g) underwent experimental myocardial infarction by occlusion of the left coronary artery. After 4 weeks, SPECT images were acquired 1.5 hours after intravenous injection of 555 MBq of 99mTc-Sestamibi. The tomographic reconstruction was performed by using specially developed software based on the Maximum Likelihood algorithm. The analysis of the data included the correlation between the area of perfusion defects detected by scintigraphy and extent of myocardial fibrosis assessed by histology. ResultsThe images showed a high target organ/background ratio with adequate visualization of the left ventricular walls and cavity. All animals presenting infarction areas were correctly identified by the perfusion images. There was no difference of the infarct area as measured by SPECT (21.1 ± 21.2%) and by histology (21.7 ± 22.0%; p=0.45). There was a strong correlation between individual values of the area of infarction measured by these two methods. ConclusionThe developed system presented adequate spatial resolution and high accuracy for the detection and quantification of myocardial infarction areas, consisting in a low cost and versatile option for high-resolution SPECT imaging of small rodents.

Systematic evaluation of 99mTc-tetrofosmin versus 99mTc-sestamibi to study murine myocardial perfusion in small animal SPECT/CT

BackgroundThe “back-translation” of clinically available protocols to measure myocardial perfusion to preclinical imaging in mouse models of human disease is attractive for basic biomedical research. With respect to single-photon emission computed tomography (SPECT) approaches, clinical myocardial perfusion imaging protocols are established with different 99mTc-labeled perfusion tracers; however, studies evaluating and optimizing protocols for these tracers in high-resolution pinhole SPECT in mice are lacking. This study aims at evaluating two clinically available 99mTc-labeled myocardial perfusion tracers (99mTc-sestamibi vs. 99mTc-Tetrofosmin) in mice using four different imaging protocols.MethodsAdult C57BL/6 male mice were injected with 99mTc-sestamibi (MIBI) or 99mTc-Tetrofosmin (TETRO) (4 MBq/g body weight) either intravenously through the tail vein (n = 5) or retroorbitally (n = 5) or intraperitoneally (i.p.) under anesthesia (n = 3) or i.p. in an awake state (n = 3) at rest. Immediately after injection, a multi-frame single-photon emission computed tomography/computed tomography (SPECT/CT) acquisition was initiated with six subsequent time frames of 10 min each. Reconstructed images of the different protocols were assessed and compared by visual analysis by experts and by time-activity-curves generated from regions-of-interest for various organs (normalized uptake values).ResultsVisually assessing overall image quality, the best image quality was found for MIBI for both intravenous injection protocols, whereas TETRO only had comparable image quality after retroorbital injections. These results were confirmed by quantitative analysis where left ventricular (LV) uptake of MIBI after tail vein injections was found significantly higher for all time points accompanied with a significantly slower washout of 16% for MIBI vs. 33% for TETRO (p = 0.009) from 10 to 60 min post injection (PI). Interestingly, LV washout from 10 to 60 min PI was significantly higher for TETRO when applied by tail vein injections when compared to retroorbital injections (22%, p = 0.008). However, liver uptake was significant and comparable for both tracers at all time points. Radioactivity concentration in the lungs was negligible for all time points and both tracers.ConclusionIntravenous MIBI injection (both tail vein and retroorbital) results in the best image quality for assessing myocardial perfusion of the murine heart by SPECT/CT. TETRO has a comparable image quality only for the retroorbital injection route.

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

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

High-Resolution Versus High-Sensitivity SPECT Imaging With Geometric Blurring Compensation for Various Parallel-Hole Collimation Geometries

Recent studies have shown that trading efficiency for improved resolution may be a good choice for small lesion detection, but utilizing collimator with high efficiency may be more favorable for cardiac single photon emission computed tomography (SPECT). This paper investigates the tradeoffs of geometric-blurring compensation for high-resolution (HR) and high-sensitivity (HS) SPECT imaging with various parallel-hole collimators in terms of noise reduction and resolution recovery. Five types of collimators were investigated and compared with a general all purpose collimator using computer simulations. It is shown that less noisy SPECT images can be achieved with unchanged spatial resolution using large collimator holes with blurring compensation. The optimal collimator hole found in the computer simulation is the one with a hole acceptance angle in the range from 6.3 degrees to 9.4 degrees. Phantom experiments with two cardiac-insert phantoms show that the resolution of the image obtained using the HS collimator can be successfully recovered by blurring compensation, and the image is less noisy compared to the one obtained using the HR collimator.