Optimization and performance evaluation of the microPET II scanner for in vivo small-animal imaging

MicroPET II is a newly developed PET (positron emission tomography) scanner designed for high-resolution imaging of small animals. It consists of 17,640 LSO crystals each measuring 0.975 x 0.975 x 12.5 mm3, which are arranged in 42 contiguous rings, with 420 crystals per ring. The scanner has an axial field of view (FOV) of 4.9 cm and a transaxial FOV of 8.5 cm. The purpose of this study was to carefully evaluate the performance of the system and to optimize settings for in vivo mouse and rat imaging studies. The volumetric image resolution was found to depend strongly on the reconstruction algorithm employed and averaged 1.1 mm (1.4 microl) across the central 3 cm of the transaxial FOV when using a statistical reconstruction algorithm with accurate system modelling. The sensitivity, scatter fraction and noise-equivalent count (NEC) rate for mouse- and rat-sized phantoms were measured for different energy and timing windows. Mouse imaging was optimized with a wide open energy window (150-750 keV) and a 10 ns timing window, leading to a sensitivity of 3.3% at the centre of the FOV and a peak NEC rate of 235,000 cps for a total activity of 80 MBq (2.2 mCi) in the phantom. Rat imaging, due to the higher scatter fraction, and the activity that lies outside of the field of view, achieved a maximum NEC rate of 24,600 cps for a total activity of 80 MBq (2.2 mCi) in the phantom, with an energy window of 250-750 keV and a 6 ns timing window. The sensitivity at the centre of the FOV for these settings is 2.1%. This work demonstrates that different scanner settings are necessary to optimize the NEC count rate for different-sized animals and different injected doses. Finally, phantom and in vivo animal studies are presented to demonstrate the capabilities of microPET II for small-animal imaging studies.     

Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging.

We are currently developing a small animal positron emission tomography (PET) scanner with a design goal of 1 microlitre (1 mm3) image resolution. The detectors consist of a 12 x 12 array of 1 x 1 x 10 mm lutetium oxyorthosilicate (LSO) scintillator crystals coupled to a 64-channel photomultiplier tube (PMT) via 5 cm long optical fibre bundles. The optical fibre connection allows a high detector packing fraction despite the dead space surrounding the active region of the PMT. Optical fibre bundles made from different types of glass were tested for light transmission, and also their effects on crystal identification and energy resolution, and compared to direct coupling of the LSO arrays to the PMTs. We also investigated the effects of extramural absorber (EMA) in the fibre bundles. Based on these results, fibre bundles manufactured from F2 glass were selected. We built three pairs of prototype detectors (directly coupled LSO array, fibre bundle without EMA and fibre bundle with EMA) and measured flood histograms, energy resolution, intrinsic spatial resolution and timing resolution. The results demonstrated an intrinsic spatial resolution (FWHM) of 1.12 mm (directly coupled), 1.23 mm (fibre bundle without EMA coupling) and 1.27 mm (fibre bundle with EMA coupling) using an approximately 500 microm diameter Na-22 point source. Using a 330 microm outer diameter steel needle line source filled with F-18, spatial resolution for the detector with the EMA optical fibre bundle improved to 1.05 mm. The respective timing and energy FWHM values were 1.96 ns, 21% (directly coupled), 2.20 ns, 23% (fibre bundle without EMA) and 2.99 ns, 30% (fibre bundle with EMA). The peak-to-valley ratio in the flood histograms was better with EMA (5:1) compared to the optical fibre bundle without EMA (2.5:1), due to the decreased optical cross-talk. In comparison to the detectors used in our current generation microPET scanner, these detectors substantially improve on the spatial resolution, preserve the timing resolution and provide adequate energy resolution for a modern high-resolution animal PET tomograph.     

A flat-panel detector based micro-CT system: performance evaluation for small-animal imaging

A dedicated small-animal x-ray micro computed tomography (micro-CT) system has been developed to screen laboratory small animals such as mice and rats. The micro-CT system consists of an indirect-detection flat-panel x-ray detector with a field-of-view of 120 x 120 mm2, a microfocus x-ray source, a rotational subject holder and a parallel data processing system. The flat-panel detector is based on a matrix-addressed photodiode array fabricated by a CMOS (complementary metal-oxide semiconductor) process coupled to a CsI:T1 (thallium-doped caesium iodide) scintillator as an x-ray-to-light converter. Principal imaging performances of the micro-CT system have been evaluated in terms of image uniformity, voxel noise and spatial resolution. It has been found that the image non-uniformity mainly comes from the structural non-uniform sensitivity pattern of the flat-panel detector and the voxel noise is about 48 CT numbers at the voxel size of 100 x 100 x 200 microm3 and the air kerma of 286 mGy. When the magnification ratio is 2, the spatial resolution of the micro-CT system is about 14 1p/mm (line pairs per millimetre) that is almost determined by the flat-panel detector showing about 7 1p/mm resolving power. Through low-contrast phantom imaging studies, the minimum resolvable contrast has been found to be less than 36 CT numbers at the air kerma of 95 mGy. Some laboratory rat imaging results are presented.     

MicroCT scanner performance and considerations for vascular specimen imaging

Obtaining three-dimensional geometrical data of vascular systems is of major importance to a number of research areas in medicine and biology. Examples are the characterization of tumor vasculature, modeling blood flow, or genetic effects on vascular development. The performance of the General Electric Medical Systems MS8 microCT scanner is examined in the context of these applications. The system is designed to acquire high-resolution images of specimens up to 5 cm in diameter. A maximum resolution of 38 lp/mm at the 10% modulation transfer function level or 22 microm full width at half maximum of the plane spread function can be achieved with 8.5 microm voxels and a 17 mm field of view. Three different contrast agents are discussed and applied for imaging of small animal vasculature: corrosion casting material Batson's No. 17 with an added lead pigment, silicon rubber MICROFIL MV122, and a suspension of barium sulfate (Baritop) in gelatin. Contrast for all of these agents was highly variable in different vessels as well as within the same vessel. Imaging of PMMA tubing filled with MICROFIL shows that even vessels below 20 microm in diameter are detectable and that diameter estimation of vessels based on thresholding is possible with a precision of 2-3 pixels.     

Evaluation of transmission methodology and attenuation correction for the microPET Focus 220 animal scanner

An accurate, low noise estimate of photon attenuation in the subject is required for quantitative microPET studies of molecular tracer distributions in vivo. In this work, several transmission-based measurement techniques were compared, including coincidence mode with and without rod windowing, singles mode with two different energy sources ((68)Ge and (57)Co), and postinjection transmission scanning. In addition, the effectiveness of transmission segmentation and the propagation of transmission bias and noise into the emission images were examined. The (57)Co singles measurements provided the most accurate attenuation coefficients and superior signal-to-noise ratio, while (68)Ge singles measurements were degraded due to scattering from the object. Scatter correction of (68)Ge transmission data improved the accuracy for a 10 cm phantom but over-corrected for a mouse phantom. (57)Co scanning also resulted in low bias and noise in postinjection transmission scans for emission activities up to 20 MBq. Segmentation worked most reliably for transmission data acquired with (57)Co but the minor improvement in accuracy of attenuation coefficients and signal-to-noise may not justify its use, particularly for small subjects. We conclude that (57)Co singles transmission scanning is the most suitable method for measured attenuation correction on the microPET Focus 220 animal scanner.     

Good design practice for medical devices and equipment,Part II: design for validation

Medical devices and their associated process equipment must be reliable and fit for purpose. In light of the recent changes to the medical device regulations, manufacturers must now take an integrated approach to design, development and validation. Good design practice encourages this integrated approach while ensuring fitness for purpose within commercial reality. A review of current literature related to good design practice carried out in Part I of this paper showed that there is inadequate guidance regarding the integration of validation with design. This paper proposes a practical approach to design for validation aimed at making devices easier and more economic to validate. The approach comes in the form of a model of design for validation that illustrates the basic relationship between design, development and validation and a series of design tactics that were formulated in order to help designers take a more proactive approach to validation during design.     

Low-cost multifrequency electrical impedance-based system (MFEIBS) for clinical imaging: design and performance evaluation

Electrical impedance tomography (EIT) is an upcoming and capable imaging modality used for clinical imaging. It is non-invasive, non-ionising and an inexpensive technique. This paper explains the designing and the analysis of a low-cost multifrequency electrical impedance-based system (MFEIBS) having a flexible mechanism of interfacing up to 32 electrodes, suitable for 1?kHz–2?MHz. Various indicators to check the performance of the EIT system were evaluated and presented here. The performance of VCO and VCCS was measured up to 2?MHz. SNR was measured with saline phantom and its mean value is 74?dB for the complete bandwidth. Different combinations of resistors and capacitors were used to find the accuracy of the system, and relative error was less than 0.55% for the entire range. CMRR of the system was calculated and it was found to be maximum 85?dB at 1?kHz frequency. A 16-electrode circular plastic phantom having a diameter of 18?cm was established and connected with a simple MFEIBS. Obtained surface potential was applied to the computer used for image formation using NI USB-6259, 16-bit, 1.25?MS/s M Series High-speed DAQ. Images reconstructed using the system presented in this paper was generated from a 16-electrode plastic phantom filled with NaCl up to 1.2?cm height.     

Segmented crystalline scintillators: an initial investigation of high quantum efficiency detectors for megavoltage x-ray imaging

Electronic portal imaging devices (EPIDs) based on indirect detection, active matrix flat panel imagers (AMFPIs) have become the technology of choice for geometric verification of patient localization and dose delivery in external beam radiotherapy. However, current AMFPI EPIDs, which are based on powdered-phosphor screens, make use of only approximately 2% of the incident radiation, thus severely limiting their imaging performance as quantified by the detective quantum efficiency (DQE) (approximately 1%, compared to approximately 75% for kilovoltage AMFPIs). With the rapidly increasing adoption of image-guided techniques in virtually every aspect of radiotherapy, there exist strong incentives to develop high-DQE megavoltage x-ray imagers, capable of providing soft-tissue contrast at very low doses in megavoltage tomographic and, potentially, projection imaging. In this work we present a systematic theoretical and preliminary empirical evaluation of a promising, high-quantum-efficiency, megavoltage x-ray detector design based on a two-dimensional matrix of thick, optically isolated, crystalline scintillator elements. The detector is coupled with an indirect detection-based active matrix array, with the center-to-center spacing of the crystalline elements chosen to match the pitch of the underlying array pixels. Such a design enables the utilization of a significantly larger fraction of the incident radiation (up to 80% for a 6 MV beam), through increases in the thickness of the crystalline elements, without loss of spatial resolution due to the spread of optical photons. Radiation damage studies were performed on test samples of two candidate scintillator materials, CsI(Tl) and BGO, under conditions relevant to radiotherapy imaging. A detailed Monte Carlo-based study was performed in order to examine the signal, spatial spreading, and noise properties of the absorbed energy for several segmented detector configurations. Parameters studied included scintillator material, septal wall material, detector thickness, and the thickness of the septal walls. The results of the Monte Carlo simulations were used to estimate the upper limits of the modulation transfer function, noise power spectrum and the DQE for a select number of configurations. An exploratory, small-area prototype segmented detector was fabricated by infusing crystalline CsI(Tl) in a 2 mm thick tungsten matrix, and the signal response was measured under radiotherapy imaging conditions. Results from the radiation damage studies showed that both CsI(Tl) and BGO exhibited less than approximately 15% reduction in light output after 2500 cGy equivalent dose. The prototype CsI(Tl) segmented detector exhibited high uniformity, but a lower-than-expected magnitude of signal response. Finally, results from Monte Carlo studies strongly indicate that high scintillator-fill-factor configurations, incorporating high-density scintillator and septal wall materials, could achieve up to 50 times higher DQE compared to current AMFPI EPIDs.     

Technical development of PubMed Interact: an improved interface for MEDLINE/PubMed searches

Background  

The project aims to create an alternative search interface for MEDLINE/PubMed that may provide assistance to the novice user and added convenience to the advanced user. An earlier version of the project was the 'Slider Interface for MEDLINE/PubMed searches' (SLIM) which provided JavaScript slider bars to control search parameters. In this new version, recent developments in Web-based technologies were implemented. These changes may prove to be even more valuable in enhancing user interactivity through client-side manipulation and management of results.     

Monte Carlo modelling of the performance of a rotating slit-collimator for improved planar gamma-camera imaging.

Planar imaging with a gamma camera is currently limited by the performance of the collimator. Spatial resolution and sensitivity trade off against each other; it is not possible with conventional parallel-hole collimation to have high geometric sensitivity and at the same time excellent spatial resolution unless field-of-view is sacrificed by using fan- or cone-beam collimators. We propose a rotating slit-collimator which collects one-dimensional projections from which the planar image may be reconstructed by the theory of computed tomography. The performance of such a collimator is modelled by Monte Carlo methods and images are reconstructed by a convolution and backprojection technique. The performance is compared with that of a conventional parallel-hole collimator and it is shown that higher spatial resolution with increased sensitivity is possible with the slit-collimator. For a point source a spatial resolution of some 6 mm at a distance of 100 mm from the collimator with a x7 sensitivity compared with a parallel-hole collimator was achieved. Applications to bone scintigraphy are modelled and an improved performance in hot-spot imaging is demonstrated. The expected performance in cold-spot imaging is analytically investigated. The slit-collimator is not expected to improve cold-spot imaging. Practical design considerations are discussed.     

Pitfalls of the synthetic lethality screen in Saccharomyces cerevisiae: an improved design

The colony color assay in yeast enables the visual identification of plasmid-loss events. In combination with a plasmid-dependence assay, it is commonly used to identify synthetic interactions between functionally related genes. Frequently, the plasmid carries the ADE3 gene and mutants are recognized as red colonies that fail to produce sectors. In these assays, a high percentage of false-positives is obtained, most of which result from synthetic lethality with the ade3 mutation. Here, we study the nature of these mutants. We report that mutations in the HIP1 and SHM1 genes exhibit synthetic lethality with ade3 deletions. A similar interaction is found between the fur1 and ura3 mutations. Lethality in the absence of the mitochondrial Shm1 and the cytoplasmic Ade3 enzymes indicates that, under certain circumstances, these cellular compartments cooperate in carrying out essential metabolic processes. In addition, we report the identification of a truncated ADE3 allele with a unique coloration phenotype and show that it can be used to improve synthetic lethal screens.     

An improved reflective photoplethysmograph probe design for detection of an arterial blood flow

The current work presents the design and development of an improved probe for arterial blood flow measurement. The probe was designed as a reflective photoplethysmograph. Photoplethysmographs are optical detectors by which it is possible to indicate the volume of blood within or passing through tissue. In order to develop and test the probe performances, four different locations--the brachial, carotid, femoral and temporal arteries--were used as photoplethysmographic sites. In addition, a new simple method to eliminate electromagnetic noise and to reduce moving artefacts is also presented.