High Resolution Small Animal Research Articles

Effect of depth of interaction resolution on the spatial resolution of SIAT aPET

Objective. Spatial resolution is a crucial parameter for a positron emission tomography (PET) scanner. The spatial resolution of a high-resolution small animal PET scanner is significantly influenced by the effect of depth of interaction (DOI) uncertainty. The aim of this work is to investigate the impact of DOI resolution on the spatial resolution of a small animal PET scanner called SIAT aPET and determine the required DOI resolution to achieve nearly uniform spatial resolution within the field of view (FOV). Approach. The SIAT aPET detectors utilize 1.0 × 1.0 × 20 mm3 crystals, with an average DOI resolution of ∼2 mm. A default number of 16 DOI bins are used during data acquisition. First, a Na-22 point source was scanned in the center of the axial FOV with different radial offsets. Then, a Derenzo phantom was scanned at radial offsets of 0 and 15 mm in the center axial FOV. The measured DOI information was rebinned to 1, 2, 4 and 8 DOI bins to mimic different DOI resolutions of the detectors during image reconstruction. Main results. Significant artifacts were observed in images obtained from both the point source and Derenzo phantom when using only one DOI bin. When accurate measurement of DOI is not achieved, degradation in spatial resolution is more pronounced in the radial direction compared to tangential and axial directions for large radial offsets. The radial spatial resolutions at a 30 mm radial offset are 5.05, 2.62, 1.24, 0.86 and 0.78 mm when using 1, 2, 4, 8, or 16 DOI bins, respectively. The axial spatial resolution improved from ∼1.3 to 0.7 mm as the number of DOI bins increased from 1 to 16 at radial offsets from 0 to 25 mm. Two DOI bins are required to obtain images without significant artifacts. The required DOI resolution is about three times the crystal width of SIAT aPET to achieve a uniform submillimeter spatial resolution within the central 60 mm FOV and resolve the 1 mm rods of the Derenzo phantom at both positions.

A CNN-based four-layer DOI encoding detector using LYSO and BGO scintillators for small animal PET imaging

Objective. We propose a novel four-layer depth-of-interaction (DOI) encoding phoswich detector using lutetium–yttrium oxyothosilicate (LYSO) and bismuth germanate (BGO) scintillator crystal arrays for high sensitivity and high spatial resolution small animal PET imaging. Approach. The detector was comprised of a stack of four alternating LYSO and BGO scintillator crystal arrays coupled to an 8 × 8 multi-pixel photon counter (MPPC) array and read out by a PETsys TOFPET2 application specific integrated circuit. The four layers from the top (gamma ray entrance) to the bottom (facing the MPPC) consisted of a 24 × 24 array of 0.99 × 0.99 × 6 mm3 LYSO crystals, a 24 × 24 array of 0.99 × 0.99 × 6 mm3 BGO crystals, a 16 × 16 array of 1.53 × 1.53 × 6 mm3 LYSO crystals and a 16 × 16 array of 1.53 × 1.53 × 6 mm3 BGO crystals. Main results. Events that occurred in the LYSO and BGO layers were first separated by measuring the pulse energy (integrated charge) and duration (time over threshold (ToT)) from the scintillation pulses. Convolutional neural networks (CNNs) were then used to distinguish between the top and lower LYSO layers and between the upper and bottom BGO layers. Measurements with the prototype detector showed that our proposed method successfully identified events from all four layers. The CNN models achieved a classification accuracy of 91% for distinguishing the two LYSO layers and 81% for distinguishing the two BGO layers. The measured average energy resolution was 13.1% ± 1.7% for the top LYSO layer, 34.0% ± 6.3% for the upper BGO layer, 12.3% ± 1.3% for the lower LYSO layer, and 33.9% ± 6.9% for the bottom BGO layer. The timing resolution between each individual layer (from the top to the bottom) and a single crystal reference detector was 350 ps, 2.8 ns, 328 ps, and 2.1 ns respectively. Significance. In conclusion, the proposed four-layer DOI encoding detector achieved high performance and is an attractive choice for next-generation high sensitivity and high spatial resolution small animal positron emission tomography systems.

QS2. High Frequency Spectral Ultrasound Imaging Detects Early Post Traumatic Muscle Fibrosis in Rodents

Purpose: Muscle fibrosis is a devastating condition that can occur following traumatic injury leading to loss of function and poor outcomes. Limited noninvasive modalities exist to diagnose and characterize the extent of muscle damage. Here we investigate spectral ultrasound imaging (SUSI), a quantitative imaging technique which detects tissue parameters based on intrinsic structure and composition, to identify early muscle fibrosis based on fibrotic changes established in a rat model. We hypothesize that SUSI will detect early traumatic muscle fibrosis in a clinically translational rat muscle injury model. Methods: Adult male Sprague Dawley rats were sedated, prepped, and underwent a soft tissue crush injury that generated 20lbs/in2 of pressure using a digital force gauge. A superficial 1.5 cm incisional wound was then made over the quadriceps and closed. Injured and contralateral uninjured hind limbs were collected and fixed for SUSI imaging. Imaging was performed with a VisualSonics VEVO770 high resolution small animal ultrasound imaging system, using a 30 MHz center frequency single element transducer. Injured muscles were imaged at the crush injury and the corresponding place on the contralateral limb. Analysis of radiofrequency data was done as previously described in literature and SUSI parameters were calculated using the average acoustic concentration (AAC) of the fibrotic region and the corresponding region in the contralateral muscle. AAC values were grouped by time point and tissue type for statistical comparison using unpaired t tests. Results: In our rodent model, SUSI identified muscle fibrosis as early as 7 days post injury. The average AAC of injured fibrotic versus uninjured muscle was significantly increased at post injury day 7 (36.33 vs 18.36 db/mm3, injured versus uninjured, p = 0.003) and day 28 (54.64 vs 28.29 db/mm3, injured versus uninjured, p<0.0001). Though not statistically significant at day 14 (38.69 vs 27.61 db/mm3, injured vs uninjured, p=0.14) the fibrotic muscle did trend toward a higher AAC value. These results indicate that at day 7 and 28, the SUSI measurement AAC can be used to distinguish injured fibrotic muscle from uninjured muscle. Conclusions: SUSI offers a portable, non-invasive, and safe diagnostic modality to detect muscle fibrosis, making it an ideal modality for post traumatic injuries. Here, we show SUSI distinguishes muscle fibrosis from healthy tissue at day 7 and 28 post injury in our model allowing for early treatment. Unlike qualitative grayscale imaging, SUSI determines unique parameters of the tissue based on a calibrated spectrum related to the inherent properties of the tissue, making it less user-dependent and more reproducible.

Upregulation of miR-335 reduces myocardial injury following myocardial infarction via targeting MAP3K2.

Acute myocardial infarction (AMI) is a serious cardiovascular disease with a high incidence worldwide and the main cause of sudden cardiac death. The aim of this article was to study the protective role of miR-335 in myocardial infarction (MI) and the underlying molecular mechanism. Thirty Sprague Dawley (SD) rats were randomly divided into sham group, MI + NC group and MI + agomiR-335 group. The expression of miR-335 in rat myocardium was detected by quantitative Real Time-Polymerase Chain Reaction (RT-PCR). Western blot was performed to detect the expression of TNF-α, IL-6, IL-1β, Caspase-3, Cleaved Caspase-3 (C-Caspase-3) and MAP3K2 in rat myocardium. On the 7th day of the establishment of the rat MI model, a high-resolution small animal ultrasound system was utilized to detect the cardiac function of the rats, and the heart tissues and blood samples of the rats were collected. The corresponding kits were purchased to detect the contents of LDH, CK-MB, MDA and SOD in rat serum, and HE staining was employed to observe the morphology of rat myocardial tissue. The expression of miR-335 in myocardial infarcted zones and border zones of MI rats decreased significantly. The upregulation of miR-335 remarkably inhibited myocardial inflammation and apoptosis after MI, thus improving the cardiac function of MI rats. Compared with the sham group, the MAP3K2 expression in the MI + NC group was observably increased, while the overexpression of miR-335 could inhibit the expression of this protein. Through the Luciferase reporter gene experiment, we found that miR-335 could directly target MAP3K2. The expression of miR-335 decreased in myocardial tissue after MI, and the overexpression of miR-335 reduced myocardial damage by inhibiting oxidative stress, inflammation, and apoptosis via targeting MAP3K2, thereby improving the cardiac function of MI rats.

Role of Nuclear Imaging to Understand the Neural Substrates of Brain Disorders in Laboratory Animals: Current Status and Future Prospects.

Molecular imaging, which allows the real-time visualization, characterization and measurement of biological processes, is becoming increasingly used in neuroscience research. Scintigraphy techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) provide qualitative and quantitative measurement of brain activity in both physiological and pathological states. Laboratory animals, and rodents in particular, are essential in neuroscience research, providing plenty of models of brain disorders. The development of innovative high-resolution small animal imaging systems together with their radiotracers pave the way to the study of brain functioning and neurotransmitter release during behavioral tasks in rodents. The assessment of local changes in the release of neurotransmitters associated with the performance of a given behavioral task is a turning point for the development of new potential drugs for psychiatric and neurological disorders. This review addresses the role of SPECT and PET small animal imaging systems for a better understanding of brain functioning in health and disease states. Brain imaging in rodent models faces a series of challenges since it acts within the boundaries of current imaging in terms of sensitivity and spatial resolution. Several topics are discussed, including technical considerations regarding the strengths and weaknesses of both technologies. Moreover, the application of some of the radioligands developed for small animal nuclear imaging studies is discussed. Then, we examine the changes in metabolic and neurotransmitter activity in various brain areas during task-induced neural activation with special regard to the imaging of opioid, dopaminergic and cannabinoid receptors. Finally, we discuss the current status providing future perspectives on the most innovative imaging techniques in small laboratory animals. The challenges and solutions discussed here might be useful to better understand brain functioning allowing the translation of preclinical results into clinical applications.

A GPU-accelerated fully 3D OSEM image reconstruction for a high-resolution small animal PET scanner using dual-ended readout detectors

In this work, a GPU-accelerated fully 3D ordered-subset expectation maximization (OSEM) image reconstruction with point spread function (PSF) modeling was developed for a small animal PET scanner with a long axial field of view (FOV). Dual-ended readout detectors that provided high depth of interaction (DOI) resolution were used for the small animal PET scanner to simultaneously achieve uniform high spatial resolution and high sensitivity. First, we developed a novel sinogram generation method, in which the dimension of the sinogram was determined first and then an event was assigned to a few neighboring sinogram elements by using weights that are inversely proportional to the distance from the measured line of response (LOR) to the LOR of the sinogram elements. System geometric symmetry, precomputation of LOR-driven ray-tracing and texture memory were applied to accelerate the GPU-based reconstruction. We developed a spatially variant PSF model where the PSF parameters were obtained by using point source images measured at 18 positions in the FOV and a spatial invariant PSF model where the PSF parameters were obtained by using only one image measured at the center FOV. The performance of the image reconstruction method was evaluated by using simulated phantom data as well as phantom and in-vivo mouse data acquired on the scanner. The results showed that the proposed reconstruction method provided better spatial resolution, a higher contrast recovery coefficient and lower noise than the OSEM reconstruction and was more than 1000 times faster than the CPU-based reconstruction. The spatially variant PSF model did not result in any spatial resolution improvement compared to the spatial invariant PSF model, and thus, the latter that is much easier to implement in image reconstruction and can be used in a small animal PET scanner using detectors with very high DOI resolution. A whole body 18F-FDG mouse image with high resolution and a high contrast to noise ratio was obtained by using the proposed reconstruction method.

Design and performance of SIAT aPET: a uniform high-resolution small animal PET scanner using dual-ended readout detectors

In this work, a small animal PET scanner named SIAT aPET was developed using dual-ended readout depth encoding detectors to simultaneously achieve high spatial resolution and high sensitivity. The scanner consists of four detector rings with 12 detector modules per ring; the ring diameter is 111 mm and the axial field of view (FOV) is 105.6 mm. The images are reconstructed using an ordered subset expectation maximization (OSEM) algorithm. The spatial resolution of the scanner was measured by using a 22Na point source at the center axial FOV with different radial offsets. The sensitivity of the scanner was measured at center axis of the scanner with different axial positions. The count rate performance of the system was evaluated by scanning mouse-sized and rat-sized phantoms. An ultra-micro hot-rods phantom and two mice injected with 18F-NaF and 18F-FDG were scanned on the scanner. An average depth of interaction (DOI) resolution of 1.96 mm, energy resolution of 19.1% and timing resolution of 1.20 ns were obtained for the detector. Average spatial resolutions of 0.82 mm and 1.16 mm were obtained up to a distance of 30 mm radially from the center of the FOV when reconstructing a point source in 1% and 10% warm backgrounds, respectively, using OSEM reconstruction with 16 subsets and 10 iterations. Sensitivities of 16.0% and 11.9% were achieved at center of the scanner for energy windows of 250–750 keV and 350–750 keV respectively. Peak noise equivalent count rates (NECRs) of 324 kcps and 144 kcps were obtained at an activity of 26.4 MBq for the mouse-sized and rat-sized phantoms. Rods of 1.0 mm diameter can be visually resolved from the image of the ultra-micro hot-rods phantom. The capability of the scanner was demonstrated by high quality in-vivo mouse images.

Development and initial characterization of a high-resolution PET detector module with DOI

Organ-dedicated PET scanners are becoming more prevalent because of their advantages in higher sensitivity, improved image quality, and lower cost. Detectors utilized in these scanners have finer pixel size with depth of interaction (DOI) capability. This work presents a LYSO(Ce) detector module with DOI capability which has the potential to be scaled up to a high-resolution small animal or organ-dedicated PET system. For DOI capability, a submodule with one LYSO block detector utilizing PETsys TOFPET2 application-specific integrated circuit (ASIC) was previously developed in our lab. We scaled up the submodule and optimized the configuration to allow for a compact housing of the dual-readout boards in one side of the blocks by designing a high-speed dual-readout cable to maintain the original pin-to-pin relationship between the Samtec connectors. The module size is 53.8 × 57.8 mm2. Each module has 2 × 2 LYSO blocks, each LYSO block consists of 4 × 4 LYSO units, and each LYSO unit contains a 6 × 6 array of 1 × 1 × 20 mm3 LYSO crystals. The four lateral surfaces of LYSO crystal were mechanically ground to W14, and the two end surfaces were polished. Two ends of the LYSO crystal are optically connected to SiPM for DOI measurement. Eight LYSO blocks performance including energy, timing, and DOI resolution is characterized with a single LYSO slab. The in-panel and orthogonal-panel spatial resolution of the two modules with 107.4 mm distance between each other are measured at 9 positions within the field of view (FOV) with a 22Na source. Results show that the average energy, timing, and DOI resolution of all LYSO blocks are 16.13% ± 1.01% at 511 keV, 658.03 ± 15.18 ps, and 2.62 ± 0.06 mm, respectively. The energy and timing resolution of two modules are 16.35% and 0.86 ns, respectively. The in-panel and orthogonal-panel spatial resolution of the two modules at the FOV center are 1.9 and 4.4 mm respectively.

Cross-Species Physiological Assessment of Brain Estrogen Receptor Expression Using 18F-FES and 18F-4FMFES PET Imaging.

A retrospective analysis was performed of preclinical and clinical data acquired during the evaluation of the estrogen receptor (ER) PET tracer 4-fluoro-11β-methoxy-16α-[18F]-fluoroestradiol (4FMFES) and its comparison with 16α-[18F]-fluoroestradiol (FES) in mice, rats, and humans with a focus on the brain uptake. Breast cancer tumor-bearing female BALB/c mice from a previous study and female Sprague-Dawley rats (control and ovariectomized) were imaged by 4FMFES or FES-PET imaging. Immediately after, low-dose CT was performed in the same bed position. Semi-quantitative analysis was conducted to extract %ID/g data. Small cohorts of mice and rats were imaged with 4FMFES in an ultra-high-resolution small animal PET scanner prototype (LabPET II). Rat brains were dissected and imaged separately with both PET and autoradiography. In parallel, 31 breast cancer patients were enrolled in a clinical phase II study to compare 4FMFES with FES for oncological assessment. Since the head was included in the field of view, brain uptake of discernable foci was measured and reported as SUVMax. Regardless of the species studied, 4FMFES and FES uptake were relatively uniform in most regions of the brain, except for bilateral foci at the base of the skull, at the midsection of the brain. Anatomical localization of the PET signal using CT image fusion indicates thatthe signal origins from the pituitary in all studied species. 4FMFES yielded lower pituitary uptake than FES in patients, but an inverse trend was observed in rodents. 4FMFES pituitary contrast was higher than FES in all assessed groups. High-resolution small animal imaging of the brain of rats and mice revealed a supplemental signal anterior to the pituitary, which is likely to be the medial preoptic area. Dissection data further confirmed those findings and revealed additional signals corresponding to the arcuate and ventromedial nuclei, along with the medial and cortical amygdala. 4FMFES allowed visualization of ER expression in the pituitary in humans and two different rodent species with better contrast than FES. Improvement in clinical spatial resolution might allow visualization and analysis of other ER-rich brain areas in humans. Further work is now possible to link 4FMFES pituitary uptake to cognitive functions.

Imaging Salt Uptake Dynamics in Plants Using PET

Soil salinity is a global environmental challenge for crop production. Understanding the uptake and transport properties of salt in plants is crucial to evaluate their potential for growth in high salinity soils and as a basis for engineering varieties with increased salt tolerance. Positron emission tomography (PET), traditionally used in medical and animal imaging applications for assessing and quantifying the dynamic bio-distribution of molecular species, has the potential to provide useful measurements of salt transport dynamics in an intact plant. Here we report on the feasibility of studying the dynamic transport of 22Na in millet using PET. Twenty-four green foxtail (Setaria viridis L. Beauv.) plants, 12 of each of two different accessions, were incubated in a growth solution containing 22Na+ ions and imaged at 5 time points over a 2-week period using a high-resolution small animal PET scanner. The reconstructed PET images showed clear evidence of sodium transport throughout the whole plant over time. Quantitative region-of-interest analysis of the PET data confirmed a strong correlation between total 22Na activity in the plants and time. Our results showed consistent salt transport dynamics within plants of the same variety and important differences between the accessions. These differences were corroborated by independent measurement of Na+ content and expression of the NHX transcript, a gene implicated in sodium transport. Our results demonstrate that PET can be used to quantitatively evaluate the transport of sodium in plants over time and, potentially, to discern differing salt-tolerance properties between plant varieties. In this paper, we also address the practical radiation safety aspects of working with 22Na in the context of plant imaging and describe a robust pipeline for handling and incubating plants. We conclude that PET is a promising and practical candidate technology to complement more traditional salt analysis methods and provide insights into systems-level salt transport mechanisms in intact plants.

Design and performance evaluation of high resolution small animal PET scanner based on monolithic crystal: a simulation study

Dedicated small-animal PET scanners functionality can be optimized by improving the sensitivity and spatial resolution of the scanner. Approximately most of the developed and commercially available small-animal PET scanners are equipped with pixelated scintillators; therefore, their spatial resolution is limited to the crystal pixel size. Complex fabrication, low-sensitivity, and disability in depth of interaction calculation (DOI) are the major disadvantages of pixelated crystals. However, monolithic scintillator crystals are known as one of the most commonly used substitutions, as they have higher sensitivity, DOI recognition, and lower cost. We already designed and implemented a dedicated small-animal PET scanner based on pixelated scintillator crystals and silicon photomultiplier (SiPM). In this study, we plan to present a new optimized design based on the monolithic crystal, with similar performance by the previous scanner. Then we would optimize the thickness of the monolithic crystals for animal PET scanners as a function of sensitivity and spatial resolution. All simulations were performed based on GEANT4, a validated Monte Carlo toolkit. We simulated a recently fabricated scanner with pixelated crystals and compared it with a simulated scanner based on an optimized monolithic crystal. The experimental setup used for comparison and validation is a small Animal PET consisting of ten pixelated modules. This study anticipates that by replacing a pixelated crystal (consist of 24 × 24 LYSO elements, and 2 × 2 ×10 mm3 crystal size) with a monolithic crystal (with 8 mm thickness and 50.2 × 50.2 entrance area), the average spatial resolution stays the same and sensitivity grows ∼ 17% in the center of AFOV and also the fabrication cost dives remarkably. Simulation reveals that although the depth of interaction DOI was not taken into consideration, the crystals with 6 mm thickness have acceptable spatial resolution (∼ 1.3 mm FWHM at the centre of the AFOV) and relatively good absolute sensitivity (∼ 1.6%).

Toxicity-efficacy converting of ginseng combined with Fuzi Banxia incompatibility in heart failure stage of cor pulmonale

ObjectiveFuzi Banxia is one of eighteen antagonisms, previous studies have shown that the incompatibility could play special effects in the specific condition of diseases and appropriate compatible environment. The present study aims to evaluate the toxicity-efficacy of ginseng combined with Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale and to explore its mechanism. MethodsMonocrotaline (MCT)-induced cor pulmonale were used in this study. Ultra high-resolution small animal ultrasound real-time imaging system and the right heart catheterization were used to estimate cardiac function. Semi automatic biochemical analyzer was used to test myocardial enzyme LDH, CK, and CK-MB in serum. The heart tissues were stained with HE, and TUNEL assay was used to assess the pathomorphological changes and myocardial apoptosis. The expression of hypertrophy and apoptosis associated genes: ANP, BNP, β-MHC, Bax, and Bcl-2 in the right ventricle were determined by RT-PCR. ResultsFuzi Banxia combined with ginseng obviously attenuated mortality, decreased RVHI, and increased cardiac index; RVSP and mPAP were significantly reduced, and EF and FS were raised obviously; Myocardial enzymes LDH, CK, and CK-MB were pronounced attenuated; heart diameter reduced, right ventricular dilatation was significantly decreased, inflammatory cell infiltration notably reduced, and cardiac apoptosis rate was decreased obviously. Meanwhile, the expression of hypertrophy-related ANP, BNP, and β-MHC mRNA were up-regulated, the expression of apoptosis-related Bax mRNA was down-regulated, and the expression of anti-apoptosis-related Bcl-2 mRNA and Bcl-2/Bax ratio were up-regulated. ConclusionGinseng compatible environment could attenuate cardiac toxicity of Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale, and improve cardiac function, which may be related to the expression of hypertrophy and apoptosis associated genes, and thus delay the occurrence and development of heart failure.

Echocardiographic Evaluation of Coronary Abnormalities and Cardiac Function in a Murine Model of Kawasaki Disease Using High-frequency Ultrasound.

Background:Murine model of coronary arterial inflammation has been widely accepted as an animal model of and used in Kawasaki disease (KD). This study sought to evaluate the developmental changes of coronary arteries and cardiac function in a murine model of KD with a high-frequency ultrasound system and to provide evidence for the preparation of the model of KD.Methods:Lactobacillus casei cell wall extract was prepared and injected into C57BL/6 mice intraperitoneally (i.p.) to induce KD. A total of 120 mice were grouped into three groups. The intravenous immunoglobulin (IVIG) treatment group was i.p. injected with IVIG (2 g/kg), while the KD model and normal control groups were i.p. injected with 0.5 ml of phosphate buffered solution on day 5. All high-resolution echocardiography detection of mouse heart was performed by the same senior technician. Animal echocardiography was performed by measuring the coronary artery dimensions and cardiac function on days 0, 7, 14, 28, and 56 (high-resolution small animal ultrasound [Vevo770 pattern; VisualSonic, Canada] with broadband probe [RMVTM707B; frequency, 30 mHz; depth of focus, 1.2 cm]) which were measured and analyzed with Vevo770 software.Results:Pathological studies revealed focal inflammatory infiltrate asymmetrically distributed around the coronary artery trunk in the KD model group. Echocardiographic study including coronary dimension and cardiac function measurements was successfully performed in all subjects. The KD model and IVIG treatment groups showed left coronary artery dilation on days 7, 14, 28, and 56. The diameter of left coronary artery in the KD model group (0.53 ± 0.09 mm; 0.36 ± 0.07 mm; 0.34 ± 0.05 mm; 0.34 ± 0.04 mm) was significantly larger than those of IVIG treatment group (0.22 ± 0.02 mm; 0.28 ± 0.03 mm; 0.26 ± 0.03 mm; 0.27 ± 0.05 mm; 0.26 ± 0.03 mm; all P < 0.01) and the normal control group (0.21 ± 0.02 mm; 0.22 ± 0.03 mm; 0.22 ± 0.02 mm; 0.23 ± 0.02 mm; 0.27 ± 0.04 mm; all P < 0.01) on days 7, 14, 28, and 56. No significant differences were observed in the measurements of cardiac function among the groups on days 0, 7, 14, 28, and 56 (all P > 0.05).Conclusions:Echocardiography could identify the consecutive changes of coronary artery in KD mice. Echocardiography is more convenient and direct in evaluating the coronary abnormalities in this animal model.

MR-compatibility of a high-resolution small animal PET insert operating inside a 7 T MRI

A full-ring PET insert consisting of 16 PET detector modules was designed and constructed to fit within the 114 mm diameter gradient bore of a Bruker 7 T MRI. The individual detector modules contain two silicon photomultiplier (SiPM) arrays, dual-layer offset LYSO crystal arrays, and high-definition multimedia interface (HDMI) cables for both signal and power transmission. Several different RF shielding configurations were assessed prior to construction of a fully assembled PET insert using a combination of carbon fibre and copper foil for RF shielding. MR-compatibility measurements included field mapping of the static magnetic field (B0) and the time-varying excitation field (B1) as well as acquisitions with multiple pulse sequences: spin echo (SE), rapid imaging with refocused echoes (RARE), fast low angle shot (FLASH) gradient echo, and echo planar imaging (EPI). B0 field maps revealed a small degradation in the mean homogeneity (+0.1 ppm) when the PET insert was installed and operating. No significant change was observed in the B1 field maps or the image homogeneity of various MR images, with a 9% decrease in the signal-to-noise ratio (SNR) observed only in EPI images acquired with the PET insert installed and operating. PET detector flood histograms, photopeak amplitudes, and energy resolutions were unchanged in individual PET detector modules when acquired during MRI operation. There was a small baseline shift on the PET detector signals due to the switching amplifiers used to power MRI gradient pulses. This baseline shift was observable when measured with an oscilloscope and varied as a function of the gradient duty cycle, but had no noticeable effect on the performance of the PET detector modules. Compact front-end electronics and effective RF shielding led to minimal cross-interference between the PET and MRI systems. Both PET detector and MRI performance was excellent, whether operating as a standalone system or a hybrid PET/MRI.

First Results From a High-Resolution Small Animal SiPM PET Insert for PET/MR Imaging at 7T

We present the initial results from a small animal PET insert designed to be operated inside a 7T MRI. The insert fits within the 114 mm inner diameter of the Bruker BGA-12S gradient coil while accommodating the Bruker 35 mm volume RF coil (outer diameter 60 mm), both used in the Bruker 70/20 MRI systems. The PET insert is a ring comprising 16 detectors. Each detector has a dual-layer offset (DLO) lutetium-yttrium oxyorthsilicate (LYSO) scintillator array read out by two SensL SPMArray4B SiPM arrays. The DLO scintillator has bottom (top) layers of: $22\times 10$ ( $21 \times 9$ ) crystals of size $1.2 \times 1.2 \times 6$ (4) mm3 for a total of 409 crystals per block, providing an axial extent of 28.17 mm. The detector outputs are multiplexed to four signals using a custom readout board and digitized using the OpenPET data acquisition platform. The detector flood images successfully resolve over 99% of the crystals, with average energy resolution of 12.5 ± 2.0% at 511 keV. Testing of the PET system inside the MRI showed that the PET insert had no effect on MRI image homogeneity and only a small effect on echo planar images (EPI) signal to noise ratio (SNR) (-9%), with neither PET nor MRI images showing obvious artefacts. These acquisitions used the OpenPET operating in “oscilloscope mode” with USB2.0 interface, allowing a maximum total singles event rate of 280 kcps, strongly limiting the count rate capabilities of the system. The PET radial spatial resolution (as measured with a 22Na point source and FBP-3DRP reconstruction) is 1.17 mm at the centre, degrading to 1.86 mm at a 15 mm radial offset. Simultaneous phantom and mouse PET/MR imaging produced good quality images that were free of any obvious artefacts.

A new virtual ring-based system matrix generator for iterative image reconstruction in high resolution small volume PET systems

A common approach to improving the spatial resolution of small animal PET scanners is to reduce the size of scintillation crystals and/or employ high resolution pixellated semiconductor detectors. The large number of detector elements results in the system matrix—an essential part of statistical iterative reconstruction algorithms—becoming impractically large. In this paper, we propose a methodology for system matrix modelling which utilises a virtual single-layer detector ring to greatly reduce the size of the system matrix without sacrificing precision. Two methods for populating the system matrix are compared; the first utilises a geometrically-derived system matrix based on Siddon’s ray tracer method with the addition of an accurate detector response function, while the second uses Monte Carlo simulation to populate the system matrix. The effectiveness of both variations of the proposed technique is demonstrated via simulations of PETiPIX, an ultra high spatial resolution small animal PET scanner featuring high-resolution DoI capabilities, which has previously been simulated and characterised using classical image reconstruction methods. Compression factors of and are achieved using this methodology for the system matrices produced using the geometric and Monte Carlo-based approaches, respectively, requiring a total of 0.5–1.2 GB of memory-resident storage. Images reconstructed from Monte Carlo simulations of various point source and phantom models, produced using system matrices generated via both geometric and simulation methods, are used to evaluate the quality of the resulting system matrix in terms of achievable spatial resolution and the CRC, CoV and CW-SSIM index image quality metrics. The Monte Carlo-based system matrix is shown to provide the best image quality at the cost of substantial one-off computational effort and a lower (but still practical) compression factor. Finally, a straightforward extension of the virtual ring method to a three dimensional virtual cylinder is demonstrated using a 3D DoI PET scanner.

First results from a high-resolution small animal PET insert for PET/MRI imaging.

We have recently completed construction of a high resolution small animal PET insert designed for operation inside a Bruker 7T MRI. The PET insert is designed to achieve a 1 mm spatial resolution in the centre of its field of view (FOV) and fit within the 114 mm inner diameter of the Bruker BGA-12S gradient coil while accommodating the Bruker 35 mm volume RF coil (outer diameter 60 mm). The PET insert is a ring geometry with a single ring of 16 detectors. Each detector uses a dual layer offset (DLO) LYSO scintillator array (bottom/top layer: 22x10/21x9 of 1.2x1.2x6/4 mm crystals, 409 crystals per block), with total axial extent of 28.3 mm, readout by two SensL SPMArray4B SiPM arrays. The detector outputs are multiplexed to four signals using a custom readout board and digitized using the OpenPET data acquisition platform. Detector flood image quality is sufficient to resolve >99% of the crystals in the system. The average energy resolution of the 6544 crystals is 11.94%+/-1.77% at 511keV. MR compatibility testing of the complete PET system conducted with a 7T Bruker Avance III MRI showed that the operating PET insert had no effect on MRI image homogeneity and only a small effect on EPI signal to noise ratio (SNR) (-15%). Initial PET data were collected using a Ge68 line source with the PET system on the benchtop. For this first acquisition, the OpenPET system was operating in oscilloscope mode, limiting the total singles event rate to 18kcps. The sinogram and initial reconstructed images showed no obvious artefacts. We have recently implemented an OpenPET firmware upgrade that will support a singles rate of 280kcps; this will allow us to acquire first simultaneous phantom and mouse PET/MR images.

Assessment of a fully 3D Monte Carlo reconstruction method for preclinical PET with iodine-124

Iodine-124 is a radionuclide well suited to the labeling of intact monoclonal antibodies. Yet, accurate quantification in preclinical imaging with I-124 is challenging due to the large positron range and a complex decay scheme including high-energy gammas. The aim of this work was to assess the quantitative performance of a fully 3D Monte Carlo (MC) reconstruction for preclinical I-124 PET. The high-resolution small animal PET Inveon (Siemens) was simulated using GATE 6.1. Three system matrices (SM) of different complexity were calculated in addition to a Siddon-based ray tracing approach for comparison purpose. Each system matrix accounted for a more or less complete description of the physics processes both in the scanned object and in the PET scanner. One homogeneous water phantom and three heterogeneous phantoms including water, lungs and bones were simulated, where hot and cold regions were used to assess activity recovery as well as the trade-off between contrast recovery and noise in different regions. The benefit of accounting for scatter, attenuation, positron range and spurious coincidences occurring in the object when calculating the system matrix used to reconstruct I-124 PET images was highlighted. We found that the use of an MC SM including a thorough modelling of the detector response and physical effects in a uniform water-equivalent phantom was efficient to get reasonable quantitative accuracy in homogeneous and heterogeneous phantoms. Modelling the phantom heterogeneities in the SM did not necessarily yield the most accurate estimate of the activity distribution, due to the high variance affecting many SM elements in the most sophisticated SM.

Denoising of high resolution small animal 3D PET data using the non-subsampled Haar wavelet transform

PET allows functional imaging of the living tissue. However, one of the most serious technical problems affecting the reconstructed data is the noise, particularly in images of small animals. In this paper, a method for high-resolution small animal 3D PET data is proposed with the aim to reduce the noise and preserve details. The method is based on the estimation of the non-subsampled Haar wavelet coefficients by using a linear estimator. The procedure is applied to the volumetric images, reconstructed without correction factors (plane reconstruction). Results show that the method preserves the structures and drastically reduces the noise that contaminates the image.

Accuracy of ultrasound-guided intra-articular injections in guinea pig knees.

Objective Dunkin Hartley guinea pigs, a commonly used animal model of osteoarthritis, were used to determine if high frequency ultrasound can ensure intra-articular injections are accurately positioned in the knee joint.MethodsA high-resolution small animal ultrasound system with a 40 MHz transducer was used for image-guided injections. A total of 36 guinea pigs were anaesthetised with isoflurane and placed on a heated stage. Sterile needles were inserted directly into the knee joint medially, while the transducer was placed on the lateral surface, allowing the femur, tibia and fat pad to be visualised in the images. B-mode cine loops were acquired during 100 µl. We assessed our ability to visualise 1) important anatomical landmarks, 2) the needle and 3) anatomical changes due to the injection. ResultsFrom the ultrasound images, we were able to visualise clearly the movement of anatomical landmarks in 75% of the injections. The majority of these showed separation of the fat pad (67.1%), suggesting the injections were correctly delivered in the joint space. We also observed dorsal joint expansion (23%) and patellar tendon movement (10%) in a smaller subset of injections.ConclusionThe results demonstrate that this image-guided technique can be used to visualise the location of an intra-articular injection in the joints of guinea pigs. Future studies using an ultrasound-guided approach could help improve the injection accuracy in a variety of anatomical locations and animal models, in the hope of developing anti-arthritic therapies.Cite this article: Bone Joint Res 2015;4:1–5.