A Monte Carlo investigation of the spatial resolution performance of a small-animal PET scanner designed for mouse brain imaging studies

Our laboratory has developed PET detectors with depth-encoding accuracy of ∼2 mm based on finely pixelated crystals with a tapered geometry, readout at both ends with position-sensitive avalanche photodiodes (PSAPDs). These detectors are currently being used in our laboratory to build a one-ring high resolution PET scanner for mouse brain imaging studies. Due to the inactive areas around the PSAPDs, large gaps exist between the detector modules which can degrade the image spatial resolution obtained using analytical reconstruction with filtered backprojection (FBP). In this work, the Geant4-based GATE Monte Carlo package was used to assist in determining whether gantry rotation was necessary and to assess the expected spatial resolution of the system. The following factors were investigated: rotating vs. static gantry modes with and without compensation of missing data using the discrete cosine transform (DCT) method, two levels of depth-encoding, and positron annihilation effects for ¹⁸F. Our results indicate that while the static scanner produces poor quality FBP images with streak and ring artifacts, the image quality was greatly improved after compensation of missing data. The simulation indicates that the expected FWHM system spatial resolution is 0.70 ± 0.05 mm, which approaches the predicted limit of 0.5 mm FWHM due to positron range, photon non-colinearity and physical detector element size effects. We conclude that excellent reconstructed resolution without gantry rotation is possible even using FBP if the gaps are appropriately handled and that this design can approach the resolution limits set by positron annihilation physics.     

Experimental evaluation of depth-of-interaction correction in a small-animal positron emission tomography scanner

Human and small-animal positron emission tomography (PET) scanners with cylindrical geometry and conventional detectors exhibit a progressive reduction in radial spatial resolution with increasing radial distance from the geometric axis of the scanner. This "depth-of-interaction" (DOI) effect is sufficiently deleterious that many laboratories have devised novel schemes to reduce the magnitude of this effect and thereby yield PET images of greater quantitative accuracy. Here we examine experimentally the effects of a particular DOI correction method (dual-scintillator phoswich detectors with pulse shape discrimination) implemented in a small-animal PET scanner by comparing the same phantom and same mouse images with and without DOI correction. The results suggest that even this relatively coarse, two-level estimate of radial gamma ray interaction position significantly reduces the DOI parallax error. This study also confirms two less appreciated advantages of DOI correction: a reduction in radial distortion and radial source displacement as a source is moved toward the edge of the field of view and a resolution improvement detectable in the central field of view likely owing to improved spatial sampling.     

Impact of high energy resolution detectors on the performance of a PET system dedicated to breast cancer imaging

We are developing a high resolution, high sensitivity PET camera dedicated to breast cancer imaging. We are studying two novel detector technologies for this imaging system: a scintillation detector comprising layers of small lutetium oxyorthosilicate (LSO) crystals coupled to new position sensitive avalanche photodiodes (PSAPDs), and a pure semiconductor detector comprising cadmium zinc telluride (CZT) crystal slabs with thin anode and cathode strips deposited in orthogonal directions on either side of each slab. Both detectors achieve 1 mm spatial resolution with 3–5 mm directly measured photon interaction depth resolution, which promotes uniform reconstructed spatial resolution throughout a compact, breast-size field of view. Both detector types also achieve outstanding energy resolution (<3% and <12%, respectively for LSO-PSAPD and CZT at 511 keV). This paper studies the effects that this excellent energy resolution has on the expected system performance. Results indicate the importance that high energy resolution and narrow energy window settings have in reducing background random as well as scatter coincidences without compromising statistical quality of the dedicated breast PET data. Simulations predict that using either detector type the excellent performance and novel arrangement of these detectors proposed for the system facilitate ∼20% instrument sensitivity at the system center and a peak noise-equivalent count rate of >4 kcps for 200 microCi in a simulated breast phantom.     

Effects of Magnetic Fields of up to 9.4 T on Resolution and Contrast of PET Images as Measured with an MR-BrainPET

Simultaneous, hybrid MR-PET is expected to improve PET image resolution in the plane perpendicular to the static magnetic field of the scanner. Previous papers have reported this either by simulation or experiment with simple sources and detector arrangements. Here, we extend those studies using a realistic brain phantom in a recently installed MR-PET system comprising a 9.4 T MRI-scanner and an APD-based BrainPET insert in the magnet bore. Point and line sources and a 3D brain phantom were filled with ¹⁸F (low-energy positron emitter), ⁶⁸Ga (medium energy positron emitter) or ¹²⁰I, a non-standard positron emitter (high positron energies of up to 4.6 MeV). Using the BrainPET insert, emission scans of the phantoms were recorded at different positions inside and outside the magnet bore such that the magnetic field was 0 T, 3 T, 7 T or 9.4 T. Brain phantom images, with the ‘grey matter’ compartment filled with ¹⁸F, showed no obvious resolution improvement with increasing field. This is confirmed by practically unchanged transaxial FWHM and ‘grey/white matter’ ratio values between at 0T and 9.4T. Field-dependent improvements in the resolution and contrast of transaxial PET images were clearly evident when the brain phantom was filled with ⁶⁸Ga or ¹²⁰I. The grey/white matter ratio increased by 7.3% and 16.3%, respectively. The greater reduction of the FWTM compared to FWHM in ⁶⁸Ga or ¹²⁰I line-spread images was in agreement with the improved contrast of ⁶⁸Ga or ¹²⁰I images. Notwithstanding elongations seen in the z-direction of ⁶⁸Ga or ¹²⁰I point source images acquired in foam, brain phantom images show no comparable extension. Our experimental study confirms that integrated MR-PET delivers improved PET image resolution and contrast for medium- and high-energy positron emitters even though the positron range is reduced only in directions perpendicular to the magnetic field.     

Acoustic resolution photoacoustic microscopy based on microelectromechanical systems scanner

Photoacoustic microscopy (PAM) can be classified as optical resolution (OR)‐PAM and acoustic resolution (AR)‐PAM depending on the type of resolution achieved. Using microelectromechanical systems (MEMS) scanner, high‐speed OR‐PAM system was developed earlier. Depth of imaging limits the use of OR‐PAM technology for many preclinical and clinical imaging applications. Here, we demonstrate the use of a high‐speed MEMS scanner for AR‐PAM imaging. Lateral resolution of 84 μm and an axial resolution of 27 μm with ~2.7 mm imaging depth was achieved using a 50 MHz transducer‐based AR‐PAM system. Use of a higher frequency transducer at 75 MHz has further improved the resolution characteristics of the system with a reduction in imaging depth and a lateral resolution of 53 μm and an axial resolution of 18 μm with ~1.8 mm imaging depth was achieved. Using the two‐axis MEMS scanner a 2 × 2 .5 mm² area was imaged in 3 seconds. The capability of achieving acoustic resolution images using the MEMS scanner makes it beneficial for the development of high‐speed miniaturized systems for deeper tissue imaging.      

Small-animal imaging using clinical positron emission tomography/computed tomography and super-resolution

Considering the high cost of dedicated small-animal positron emission tomography/computed tomography (PET/CT), an acceptable alternative in many situations might be clinical PET/CT. However, spatial resolution and image quality are of concern. The utility of clinical PET/CT for small-animal research and image quality improvements from super-resolution (spatial subsampling) were investigated. National Electrical Manufacturers Association (NEMA) NU 4 phantom and mouse data were acquired with a clinical PET/CT scanner, as both conventional static and stepped scans. Static scans were reconstructed with and without point spread function (PSF) modeling. Stepped images were postprocessed with iterative deconvolution to produce super-resolution images. Image quality was markedly improved using the super-resolution technique, avoiding certain artifacts produced by PSF modeling. The 2 mm rod of the NU 4 phantom was visualized with high contrast, and the major structures of the mouse were well resolved. Although not a perfect substitute for a state-of-the-art small-animal PET/CT scanner, a clinical PET/CT scanner with super-resolution produces acceptable small-animal image quality for many preclinical research studies.     

Portable optical fiber probe-based spectroscopic scanner for rapid cancer diagnosis: a new tool for intraoperative margin assessment

There continues to be a significant clinical need for rapid and reliable intraoperative margin assessment during cancer surgery. Here we describe a portable, quantitative, optical fiber probe-based, spectroscopic tissue scanner designed for intraoperative diagnostic imaging of surgical margins, which we tested in a proof of concept study in human tissue for breast cancer diagnosis. The tissue scanner combines both diffuse reflectance spectroscopy (DRS) and intrinsic fluorescence spectroscopy (IFS), and has hyperspectral imaging capability, acquiring full DRS and IFS spectra for each scanned image pixel. Modeling of the DRS and IFS spectra yields quantitative parameters that reflect the metabolic, biochemical and morphological state of tissue, which are translated into disease diagnosis. The tissue scanner has high spatial resolution (0.25 mm) over a wide field of view (10 cm × 10 cm), and both high spectral resolution (2 nm) and high spectral contrast, readily distinguishing tissues with widely varying optical properties (bone, skeletal muscle, fat and connective tissue). Tissue-simulating phantom experiments confirm that the tissue scanner can quantitatively measure spectral parameters, such as hemoglobin concentration, in a physiologically relevant range with a high degree of accuracy (<5% error). Finally, studies using human breast tissues showed that the tissue scanner can detect small foci of breast cancer in a background of normal breast tissue. This tissue scanner is simpler in design, images a larger field of view at higher resolution and provides a more physically meaningful tissue diagnosis than other spectroscopic imaging systems currently reported in literatures. We believe this spectroscopic tissue scanner can provide real-time, comprehensive diagnostic imaging of surgical margins in excised tissues, overcoming the sampling limitation in current histopathology margin assessment. As such it is a significant step in the development of a platform technology for intraoperative management of cancer, a clinical problem that has been inadequately addressed to date.     

X线、CT、SPECT、PET在评估小鼠的骨成像中的作用

目的利用各种影像诊断设备对正常小鼠的骨进行成像,观察其在小鼠骨成像中最佳成像参数。方法分别使用X线、CT、SPECT、PET对小鼠的骨进行拍摄成像。结果X线和CT均可以清楚地对小鼠的骨组织成像,而SPECT、PET由于其分辨率和特异性不高,成像较模糊。结论X线和CT检查对小鼠的骨成像明显,对小鼠疾病的观察有重要意义。而SPECT、PET对诊断小鼠的骨疾病意义不是很大。     

Full field spatially-variant image-based resolution modelling reconstruction for the HRRT

Accurate characterisation of the scanner's point spread function across the entire field of view (FOV) is crucial in order to account for spatially dependent factors that degrade the resolution of the reconstructed images. The HRRT users' community resolution modelling reconstruction software includes a shift-invariant resolution kernel, which leads to transaxially non-uniform resolution in the reconstructed images. Unlike previous work to date in this field, this work is the first to model the spatially variant resolution across the entire FOV of the HRRT, which is the highest resolution human brain PET scanner in the world. In this paper we developed a spatially variant image-based resolution modelling reconstruction dedicated to the HRRT, using an experimentally measured shift-variant resolution kernel. Previously, the system response was measured and characterised in detail across the entire FOV of the HRRT, using a printed point source array. The newly developed resolution modelling reconstruction was applied on measured phantom, as well as clinical data and was compared against the HRRT users' community resolution modelling reconstruction, which is currently in use. Results demonstrated improvements both in contrast and resolution recovery, particularly for regions close to the edges of the FOV, with almost uniform resolution recovery across the entire transverse FOV. In addition, because the newly measured resolution kernel is slightly broader with wider tails, compared to the deliberately conservative kernel employed in the HRRT users' community software, the reconstructed images appear to have not only improved contrast recovery (up to 20% for small regions), but also better noise characteristics.     

Therapy region monitoring based on PET using 478 keV single prompt gamma ray during BNCT: A Monte Carlo simulation study

We confirmed the feasibility of using our proposed system to extract two different kinds of functional images from a positron emission tomography (PET) module by using an insertable collimator during boron neutron capture therapy (BNCT). Coincidence events from a tumor region that included boron particles were identified by a PET scanner before BNCT; subsequently, the prompt gamma ray events from the same tumor region were collected after exposure to an external neutron beam through an insertable collimator on the PET detector. Five tumor regions that contained boron particles and were located in the water phantom and in the BNCT system with the PET module were simulated with Monte Carlo simulation code. The acquired images were quantitatively analyzed. Based on the receiver operating characteristic (ROC) curves in the five boron regions, A, B, C, D, and E, the PET and single-photon images were 10.2%, 11.7%, 8.2% (center region), 12.6%, and 10.5%, respectively. We were able to acquire simultaneously PET and single prompt photon images for tumor regions monitoring by using an insertable collimator without any additional isotopes.     

Five-year experience of quality control for a 3D LSO-based whole-body PET scanner: Results and considerations

PET scanners require routine monitoring and quality control (QC) to ensure proper scanner performance. QC helps to ensure that PET equipment performs as specified by the manufacturer and that there have not been significant changes in the system response since acceptance. In this work we describe the maintenance history and we report on the results obtained from the PET system QC testing program over 5 years at two centers, both utilizing a Siemens Biograph 16 HiRez PET/CT system. QC testing programs were based on international standards and included the manufacturer’s daily QC, monthly uniformity and sensitivity, quarterly cross-calibration and annual resolution and image quality.For the Winnipeg and Novara sites, two and one PET detector blocks have been replaced, respectively. Neither system has had other significant PET system related hardware replacements. The manufacturer’s suggested daily QC was sensitive to detecting problems in the function of PET detector elements. The same test was not sensitive for detecting long term drifts in the systems: the Novara system observed a significant deterioration over five years of testing in the sensitivity which exhibited a decrease of 16% as compared to its initial value measured at system installation. The measure of the energy spectrum, showed that the 511 keV photopeak had shifted to a position of 468 keV. This shift was corrected by having service personnel perform a complete system calibration and detector block setup.We recommend including tests of system energy response and of sensitivity as part of a QC program since they can provide useful information on the actual performance of the scanner. A modification of the daily QC test by the manufacturer is suggested to monitor the long term stability of the system. Image quality and spatial resolution tests have proven to be of limited value for monitoring the system over time.     

Fluorescence data analysis on gel-based biochips

A series of biochip readers developed for gel-based biochips includes three imaging models and a novel nonimaging biochip scanner. The imaging readers, ranging from a research-grade versatile reader to a simple portable one, use wide-field objectives and 12-bit digital large-coupled device cameras for parallel addressing of multiple array elements. This feature is valuable for monitoring the kinetics of sample interaction with immobilized probes. Depending on the model and the label used, the sensitivity of these readers approaches 0.3 amol of a labeled sample per gel element. In the selective scanner, both the spot size of the excitation laser beam and the detector field of view match the size of the biochip array elements so that the whole row of the array can be read in a single scan. The portable version reads 50-mm long, 150-element, one-dimensional arrays in 5 s. With a dynamic range of 4000:1, a sensitivity of 1-5 amol of a labeled sample per gel element, and a data format facilitating online processing, the scanner is an attractive, inexpensive solution for biomedical diagnostics. Fluorophores for sample labeling were compared experimentally in terms of detection sensitivity, influence on duplex stability, and suitability for multilabel analysis and thermodynamic studies. Texas Red and tetracarboxyphenylporphyn proved to be the best choice for two-wavelength analysis using the imaging readers.     

Performance and limitations of positron emission tomography (PET) scanners for imaging very low activity sources

Emerging applications for positron emission tomography (PET) may require the ability to image very low activity source distributions in the body. The performance of clinical PET scanners in the regime where activity in the field of view is <1 MBq has not previously been explored. In this study, we compared the counting rate performance of two clinical PET/CT scanners, the Siemens Biograph Reveal 16 scanner which is based on lutetium oxyorthosilicate (LSO) detectors and the GE Discovery-ST scanner which is based on bismuth germanate (BGO) detectors using a modified National Electrical Manufacturers Association (NEMA) NU 2-2007 protocol. Across the activity range studied (2–100 kBq/mL in a 5.5 mL line source in the NEMA scatter phantom), the BGO-based scanner significantly outperformed the LSO-based scanner. This was largely due to the effect of background counts emanating from naturally occurring but radioactive ¹⁷⁶Lu within the LSO detector material, which dominates the observed counting rate at the lowest activities. Increasing the lower energy threshold from 350 keV to 425 keV in an attempt to reduce this background did not significantly improve the measured NECR performance. The measured singles rate due to ¹⁷⁶Lu emissions within the scanner energy window was also found to be dependent on temperature, and to be affected by the operation of the CT component, making approaches to correct or compensate for the background more challenging. We conclude that for PET studies in a very low activity range, BGO-based scanners are likely to have better performance because of the lack of significant background.     

Conceptual Design and Simulation Study of an ROI-Focused Panel-PET Scanner

Positron emission tomography (PET) is an important imaging modality for clincial use. Conventionally, the PET scanner is generally built to provide a roomy enough transverse field-of-view (FOV) for imaging most adults’ torsos. However, in many cases, the region-of-interest (ROI) for imaging is usually a small area inside the human body. Therefore, to fulfill a PET system which provides an FOV comparable in size to the target ROI seems appealing and more cost effective. Meanwhile, such a PET system has the potential for portable or bedside application with the reduced system size. In this work, we have investigated the feasibility of using dual-headed panel-detectors to build an ROI-focused PET scanner. A novel windowed list-mode ordered subset expectation maximization method was developed to perform the ROI image reconstruction. With this method, the ROI of the object can be reconstructed from the coincidences whose position determined by time-of-flight (TOF) measurements was inside the ROI. Monte Carlo simulation demonstrates the feasibility of detecting lesions not less than 1 cm in diameter, with a 300 ps full width at half maximum timing resolution. As a critical system performance, the impact of TOF information on image quality has been studied and the required TOF capability was assessed. With enhanced timing resolution, the distortions and artifacts were reduced effectively. The further improved TOF capability also shows a noticeable improvement of detection performance for low uptake lesions, as well as the recovery speed of lesion contrast, which is of practical significance in the lesion detection task.     

The use of PET/CT scanning technique for 3D visualization and quantification of real-time soil/plant interactions

Aims

Conventional methodology using destructive sampling, which is laborious and has poor spatial and temporal resolution, has limited our understanding of soil-plant interactions. New non-invasive tomographic techniques have the potential to significantly improve our knowledge. In this study we demonstrated the simultaneous use of PET (positron emission tomography) and CT (X-ray computed tomography) to (a) non-destructively image a whole plant growing in sand, and (b) to link the observed morphology with recently assimilated C. The PET scanner was used to detect and visualize the location of the short-lived radioisotope ¹¹C (with a half-life of 20.4?min) taken up by the plant through ¹¹C-labelled CO₂. This provided information on carbon translocation and the metabolism of photo-assimilates in the plant as well as root structure. The CT scanners yielded data on soil and root structure.

Methods

A medical PET/CT scanner was used to scan a fodder radish plant growing in a pot with test soil composed of homogenous sand. We constructed an air-plant-soil controller system (APS) to control the environmental conditions, such as CO₂, temperature and light during the experiment. The plant was allowed to assimilate ¹¹CO₂ for 90?min before PET scanning was initiated. We carried out PET scanning for 60?min. Subsequently, the aerial parts of the plant was cut off and the pot was rescanned using a micro-CT scanner to obtain more detailed information on structure of the root system and the growth medium structure.

Results

The acquired PET and CT images gave images clearly visualizing the architecture and morphology of root and soil. Using a CT scanner, we were able to detect the main taproot located at 0 to 30?mm depth. With the PET scanner, we were able to measure a signal down to 82?mm below the surface of the sand. We found the highest concentration of ¹¹C at the position of the main root. The PET images, at different time intervals, showed the translocation and metabolisation of photo-assimilates from top to root. Using the micro-CT scanner (voxel size of 90?μm), we were able to detect roots down to 100?mm depth. These findings correlated the PET signals measured down to 82?mm depth.

Conclusions

We conclude that the simultaneous use of PET and CT technologies was successfully applied for soil-plant studies. The combined PET/CT technology has potential to provide new fundamental insight into soil-plant interactions and especially into the effect of abiotic stresses in spite of the limitation due to spatial resolution.     

Brown-Roberts-Wells stereotactic frame modifications to accomplish magnetic resonance imaging guidance in three planes

The Brown-Roberts-Wells (BRW) computer tomography (CT) stereotactic guidance system has been modified to accommodate magnetic resonance imaging (MRI). A smaller head ring, which fits in standard MRI head coils, is constructed of a non-ferromagnetic aluminum ring that is split to prevent eddy currents and anodized to prevent MRI image distortion and resolution degradation. A new localizing device has been designed in a box configuration, which allows BRW stereotactic coordinates to be calculated from coronal and sagittal MRI images, in addition to axial images. The system was tested utilizing a phantom and T1- and T2-weighted images. Using 5-mm MRI scan slices, targets were localized accurately to a 5-mm cube in three combined planes. Optimized calibration of both low field strength (0.3 T) and high field strength (1.5 T) MRI systems is necessary to obtain thin slice (5 mm) images with acceptable image resolution. To date, 10 patients have had MRI stereotactic localization of brain lesions that were better defined by MRI than CT.     

A fusion PET-MRI system with a high-resolution research tomograph-PET and ultra-high field 7.0 T-MRI for the molecular-genetic imaging of the brain

We have developed a positron emission tomography (PET) and magnetic resonance imaging (MRI) fusion system for the molecular-genetic imaging (MGI) of the in vivo human brain using two high-end imaging devices: the HRRT-PET, a high-resolution research tomograph dedicated to brain imaging on the molecular level, and the 7.0 T-MRI, an ultra-high field version used for morphological imaging. HRRT-PET delivers high-resolution molecular imaging with a resolution down to 2.5 mm full width at half maximum (FWHM), which allows us to observe the brain's molecular changes using the specific reporter genes and probes. On the other front, the 7.0 T-MRI, with submillimeter resolution images of the cortical areas down to 250 mum, allows us to visualize the fine details of the brainstem areas as well as the many cortical and subcortical areas. The new PET-MRI fusion imaging system will provide many answers to the questions on neurological diseases as well as cognitive neurosciences. Some examples of the answers are the quantitative visualization of neuronal functions by clear molecular and genetic bases, as well as diagnoses of many neurological diseases such as Parkinson's and Alzheimer's. The salient point of molecular-genetic imaging and diagnosis is the fact that they precede the morphological manifestations, and hence, the early and specific diagnosis of certain diseases, such as cancers.     

ClearPEM,un TEP dédié au sein

Conventional breast imaging (mammography, ultrasound, MRI) relies on the analysis of anatomical characteristics. Whole-body positron emission tomography (PET) allows for the acquisition of a metabolic image, yet is limited by its poor spatial resolution. The Crystal Clear Collaboration developed a PET dedicated for breast imaging, the ClearPEM, in order to offer a high-resolution nuclear imaging technique. The patient is installed in the prone position on the exam bed, with two detector plates rotating around to breast to acquire a 3-dimensional image. Two prototypes were built and installed in hospitals. We summarize the technical solutions necessary for the development of this system and present a summary of its performances as well as an outlook on preclinical and clinical tests.     

Simultaneous PET-MRI: a new approach for functional and morphological imaging

Noninvasive imaging at the molecular level is an emerging field in biomedical research. This paper introduces a new technology synergizing two leading imaging methodologies: positron emission tomography (PET) and magnetic resonance imaging (MRI). Although the value of PET lies in its high-sensitivity tracking of biomarkers in vivo, it lacks resolving morphology. MRI has lower sensitivity, but produces high soft-tissue contrast and provides spectroscopic information and functional MRI (fMRI). We have developed a three-dimensional animal PET scanner that is built into a 7-T MRI. Our evaluations show that both modalities preserve their functionality, even when operated isochronously. With this combined imaging system, we simultaneously acquired functional and morphological PET-MRI data from living mice. PET-MRI provides a powerful tool for studying biology and pathology in preclinical research and has great potential for clinical applications. Combining fMRI and spectroscopy with PET paves the way for a new perspective in molecular imaging.