Small Animal Imaging Applications Research Articles

Analytical Modeling of a Slit Collimator and Optimization for Small Animal Imaging Applications

Purpose: The collimator design and optimization are essential in small animal molecular imaging for preclinical studies. In this study, a mathematical model was derived and used to optimize the slit collimator for small animal imaging applications. Materials and Methods: The geometric efficiency was formulated as a source-to-detector distance for a certain amount of the collimator resolution ( ). The first-order derivative of the derived formula gives the optimized parameters. The detector performance was modeled in terms of intrinsic resolution . Furthermore, the edge penetration effect was considered using the validated model. Results: Optimum source-to-detector distance was found as . For an ideal detector, optimal , geometric efficiency and slit aperture width were found as , and , respectively. Where and are the source-to-collimator distance and detector length, respectively. For the fixed resolution of 1.0 mm, the sensitivity for different source-to-collimator distances of 50.0, 100.0, and 150.0 mm was calculated as , , and , respectively. In addition, for a sub-millimeter resolution of 0.5 mm at 15.0, 30.0, and 50.0 mm, the geometric efficiency was calculated as, , , and . For a typical source-to-collimator distance (15.0 mm), the optimal geometric efficiencies are , , , , and for the resolutions of 0.25, 0.50, 1.0, 1.5, and 2.0 mm, respectively. Conclusion: Based on the analytic model predictions, the performance characteristics of the slit collimator in terms of geometric efficiency and resolution were extracted. The importance of the proposed model lies both in its speed and ease of application.

A Prototype VP-PET Imaging System Based on Highly Pixelated CdZnTe Detectors.

We investigated a prototype virtual-pinhole positron emission tomography (PET) system for small-animal imaging applications. The PET detector modules were made up of 1.3 mm lutetium-yttrium oxyorthosilicate (LYSO) arrays, and the insert detectors consisted of 0.6 mm pixelated cadmium zinc telluride (CdZnTe). To validate the imaging experiment, we did a Monte Carlo simulation for the virtual-pinhole PET (VP-PET) system in the Geant4 Application for Emission Tomography (GATE). For a point source of 22Na with a 0.5 mm diameter, the filtered back-projection algorithm-reconstructed PET image showed a resolution of 0.7 mm full-width-at-half-maximum. The system sensitivity was 0.46 cps/kBq at the center of the field view of the PET system with a source activity of 0.925 MBq and an energy window of 350 to 650 keV. A rod source phantom and a Derenzo phantom with 18F were also simulated to investigate the PET imaging ability. GATE simulation indicated that sources with 0.5 mm diameter could be clearly detected using 0.6 mm pixelated CdZnTe detectors as insert devices in a VP-PET system.

Generic high resolution PET detector block using 12 × 12 SiPM array

With the advancement of the Silicon Photomultiplier (SiPM) technology, these devices are becoming the mainstream for use in high resolution PET detectors especially where the compatibility with magnetic field is critical. Large-area SiPM arrays are now widely used in high resolution PET detector modules. The challenges are emerged in the readout and timing circuitry by the increase of pixel density in the area. The application-specific integrated circuits (ASICs) are developed to readout arrays with standard anode/cathode outputs. SiPM detection principle, which produces dark current noise in the inactive pixels, makes the multiplexing techniques more challenging rather than the PMT signals. In this work a new generic PET detector block using SiPM arrays with three outputs (anode, cathode, and fast) is presented which is suitable for applications in small animal, brain, and clinical PET imaging. The block detector accepts a 12 × 12 array with both standard and fast output signals with an overall detector dimension of 50 × 50 mm2. A new version of the scrambled crosswire readout (SCR) method was implemented to reduce 144 ‘fast outputs’ to 9 tile signals and 144 standard outputs to 16 energy channels. The tile signals are also used to generate time pickoff information for timing resolution. We implemented time-to-digital converter (TDC) in Xilinx’s SPARTAN6 field programmable gate array (FPGA) by using the 64-tap delay line. This low cost chip performs all required processes for position, energy, time, and interface architecture. The attached 24 × 24 LYSO:Ce array with 2 × 2 × 10 mm3 pixels is imaged and pixels are resolved clearly in the room temperature. The measured energy resolution of the detector block after calibration for all crystal pixels is 12.4% at 511 keV. Also, the coincidence resolving time for two identical modules was measured at 1.85 ns.

Positron emission tomography detector performance with different crystal pitches

In this work, we evaluated the performance of three pitches positron emission tomography (PET) detectors for building a high-resolution small-animal PET imaging experimental platform. The evaluation of PET detectors includes two-dimensional crystal identification, energy resolution, and crystal look-up table. The nuclear instrumentation module and PXI data acquisition (DAQ) system were both used to obtain flood images. The energy spectrum of the Na-22 source was measured. PET detectors of 2.0 and 1.6 mm pitches used in our present experiment were composed of lutetium yttrium oxyorthosilicate (LYSO) crystals directly coupled to position-sensitive photomultiplier tubes (PSPMTs). The 1.3-mm pitch detector comprises a LYSO crystal, a tapered light-guide, and a PSPMT. The crystal sizes of the detectors were a $$10 \times 10$$ array of $$2.0 \times 2.0 \times 10\,\hbox {mm}^{3}$$ crystals, a $$10 \times 10$$ array of $$1.6 \times 1.6 \times 10\,\hbox {mm}^3$$ crystals, and an $$18 \times 18$$ array of $$1.3 \times 1.3 \times 10\,\hbox {mm}^3$$ crystals, respectively. Due to the lower sampling frequency of the DAQ system, a spline interpolation algorithm was introduced in the signal waveform to reconstruct the peak values. The experimental results indicated that all three PET detector crystals could be clearly identified. A detailed analysis demonstrated that the key characteristic full width at half maximum (FWHM) values of the crystals profile could reach $$0.46\pm 0.03$$ , $$0.32\pm 0.03$$ , and $$0.21\pm 0.02\,\hbox {mm}$$ , while the crystal average energy resolutions were $$16.8\%\pm 1.76\%$$ , $$20.1\%\pm 2.24\%$$ , and $$31.5\%\pm 3.76\%$$ , which correspond to pitches of 2.0-, 1.6-, and 1.3-mm, respectively. The PET detector modules of LYSO crystal arrays could be potentially used in the small-animal PET imaging applications and are promising to achieve sub-millimeter PET images.

A compact 3 T all HTS cryogen-free MRI system

We have designed and built a passively shielded, cryogen-free 3 T 160 mm bore bismuth strontium calcium copper oxide HTS magnet with shielded gradient coils suitable for use in small animal imaging applications. The magnet is cooled to approximately 16 K using a two-stage cryocooler and is operated at 200 A. The magnet has been passively shimmed so as to achieve ±10 parts per million (ppm) homogeneity over a 60 mm diameter imaging volume. We have demonstrated that B0 temporal stability is fit-for-purpose despite the magnet operating in the driven mode. The system has produced good quality spin-echo and gradient echo images. This compact HTS-MRI system is emerging as a true alternative to conventional low temperature superconductor based cryogen-free MRI systems, with much more efficient cryogenics since it operates entirely from a single phase alternating current electrical supply.

Performance evaluation of a compact PET/SPECT/CT tri-modality system for small animal imaging applications

PET, SPECT and CT imaging techniques are widely used in preclinical small animal imaging applications. In this paper, we present a compact small animal PET/SPECT/CT tri-modality system. A dual-functional, shared detector design is implemented which enables PET and SPECT imaging with a same LYSO ring detector. A multi-pinhole collimator is mounted on the system and inserted into the detector ring in SPECT imaging mode. A cone-beam CT consisting of a micro focus X-ray tube and a CMOS detector is implemented. The detailed design and the performance evaluations are reported in this paper. In PET imaging mode, the measured NEMA based spatial resolution is 2.12mm (FWHM), and the sensitivity at the central field of view (CFOV) is 3.2%. The FOV size is 50mm (∅)×100mm (L). The SPECT has a spatial resolution of 1.32mm (FWHM) and an average sensitivity of 0.031% at the center axial, and a 30mm (∅)×90mm (L) FOV. The CT spatial resolution is 8.32lp/mm @10%MTF, and the contrast discrimination function value is 2.06% with 1.5mm size cubic box object. In conclusion, a compact, tri-modality PET/SPECT/CT system was successfully built with low cost and high performance.

Fully Digital FPGA-Based Data Acquisition System for Dual Head PET Detectors

We present the development of a new fully digital, flexible, cost-efficient data acquisition system (DAQ) suitable for dual head Positron Emission Tomography (PET) scanners for small animal imaging applications. A free-running 12 bit octal channel Analog to Digital Converter (ADC), with 65 MHz sampling rate, was used for the digitization of the detector signals. The digitized data were fed into a Spartan 6 Field Programmable Gate Array (FPGA) for event processing. An embedded system was developed for the acquisition, using Xilinx’s Embedded Development Kit (EDK) and Microblaze processor. A digital version of the Constant Fraction Discriminator (CFD) method was implemented in the FPGA, in order to achieve higher time resolution than the ADC sampling period, eliminating the need of an external mixed-signal device. The obtained information using FPGA includes: event timing, energy determination-discrimination, position determination and coincidence processing. The online processing of potential coincident events, significantly reduces the amount of data that will be transmitted to the computer. Coincident events are written temporarily to an external memory provided on a development board and are transferred to a Personal Computer (PC), via Ethernet link, for image reconstruction. Minimal post processing of the data is required prior to reconstruction. A small detector pair consisting of a BGO array coupled to a Position Sensitive Photomultiplier Tube (PSPMT) was used for the evaluation of the readout system. Obtained results prove that the proposed architecture can be used for the readout of dual head PET detectors for small animal imaging applications.

A Gaseous Compton Camera using a 2D-sensitive gaseous photomultiplier for Nuclear Medical Imaging

A new Compton Camera (CC) concept based on a High Pressure Scintillation Chamber coupled to a position-sensitive Gaseous PhotoMultiplier for Nuclear Medical Imaging applications is proposed. The main goal of this work is to describe the development of a ϕ25×12cm3 cylindrical prototype, which will be suitable for scintimammography and for small-animal imaging applications. The possibility to scale it to an useful human size device is also in study. The idea is to develop a device capable to compete with the standard Anger Camera. Despite the large success of the Anger Camera, it still presents some limitations, such as: low position resolution and fair energy resolutions for 140keV. The CC arises a different solution as it provides information about the incoming photon direction, avoiding the use of a collimator, which is responsible for a huge reduction (10−4) of the sensitivity. The main problem of the CC's is related with the Doppler Broadening which is responsible for the loss of angular resolution. In this work, calculations for the Doppler Broadening in Xe, Ar, Ne and their mixtures are presented. Simulations of the detector performance together with discussion about the gas choice are also included .

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.

Investigation of crystal surface finish and geometry on single LYSO scintillator detector performance for depth-of-interaction measurement with silicon photomultipliers

Depth of Interaction (DOI) information can improve quality of reconstructed images acquired from Positron Emission Tomography (PET), especially in high resolution and compact scanners dedicated for breast, brain, or small animal imaging applications. Additionally, clinical scanners with time of flight capability can also benefit from DOI information. One of the most promising methods of determining DOI in a crystal involves reading the signal from two ends of a scintillation crystal, and calculating the signal ratio between the two detectors. This method is known to deliver a better DOI resolution with rough crystals compared to highly polished crystals. However, what is still not well studied is how much of a tradeoff is involved between spatial, energy, temporal, and DOI resolutions as a function of the crystal surface treatment and geometry with the use of Silicon Photomultipliers (SiPM) as the photo detectors. This study investigates the effects of different crystal surface finishes and geometries on energy, timing and DOI resolutions at different crystal depths. The results show that for LYSO scintillators of 1.5×1.5×20mm3 and 2×2×20mm3 with their surfaces finished from 0.5 to 30μm roughness, almost the same energy and coincidence timing resolutions were maintained, around 15% and 2.4ns, respectively across different crystal depths, while the DOI resolutions were steadily improved from worse than 5mm to better than 2mm. They demonstrate that crystal roughness, with proper surface preparing, does not have a significant effect on the energy and coincidence timing resolutions in the crystals examined, and there does not appear to be a tradeoff between improving DOI resolution and degrading other detector performances. These results will be valuable to guide the selection of crystal surface conditions for developing a DOI measurable PET detector with a full array of LYSO scintillators coupled to SiPM arrays.

A multifunctional, reconfigurable pulse generator for high-frequency ultrasound imaging

High-frequency (>20 MHz) ultrasound (HFUS) imaging systems have made it possible to image small structures with fine spatial resolution. They find a variety of biomedical applications in dermatology, ophthalmology, intravascular imaging, and small-animal imaging. One critical technical challenge of HFUS is to generate high-voltage, high-frequency pulsed signals to effectively excite the transducer for a high SNR. This paper presents the development of a multifunctional, reconfigurable pulse generator for HFUS imaging. The pulse generator can produce a high-voltage unipolar pulse, a bipolar pulse, or arbitrary pulses for B-mode imaging, Doppler measurement, and modulated excitation imaging. The characteristics of the pulses, such as timing, waveform, and frequency are reconfigurable by a high-speed field-programmable gate array (FPGA). Customized software was developed to interface with the FPGA through a USB connector for pulse selection, and easy, flexible, real-time pulse management. The hardware was implemented in a compact, printed circuit board (PCB)-based scheme using state-of-the-art electronics for costeffectiveness and fully digital control. Testing results show that the unipolar pulse can reach over 165 Vpp with a 6-dB bandwidth of 70 MHz, and the bipolar pulse and arbitrary pulses can reach 150 and 60 Vpp with central frequencies of 60 and 120 MHz, respectively.

Near-infrared molecular probes for in vivo imaging.

Cellular and tissue imaging in the near-infrared (NIR) wavelengths between 700 and 900 nm is advantageous for in vivo imaging because of the low absorption of biological molecules in this region. This unit presents protocols for small animal imaging using planar and fluorescence lifetime imaging techniques. Included is an overview of NIR fluorescence imaging of cells and small animals using NIR organic fluorophores, nanoparticles, and multimodal imaging probes. The development, advantages, and application of NIR fluorescent probes that have been used for in vivo imaging are also summarized. The use of NIR agents in conjunction with visible dyes and considerations in selecting imaging agents are discussed. We conclude with practical considerations for the use of these dyes in cell and small animal imaging applications.

Ultra-high-resolution SPECT with CdTe for small-animal imaging applications: A Monte Carlo simulation study using a voxelized phantom

The single photon emission computed tomography (SPECT) based on pixelated Cadmium Telluride (CdTe) detector has been promising for high resolution small animal imaging. For the feasibility of our ultra-high resolution SPECT system with CdTe, we compared the quality of the reconstructed image of our SPECT system to that of a conventional small animal SPECT system with NaI(Tl) detector. The pixel size of CdTe detector was 0.35 mm × 0.35 mm which was available for a real detector (PID350, AJAT, Finland). The detector size was 44.8 × 44.8 mm with 128 × 128 pixels and the thickness of this detector was 1 mm. The intrinsic resolution of CdTe detector and that of NaI(Tl) detector were 0.35 mm and 2.3 mm, respectively. The height parallel hole collimator made of lead was 25 mm and that of a septum was 0.2 mm. The shape of that parallel hole collimator and its radius were hexagonal and 0.5 mm, respectively. A SPECT liver scan was simulated for both SPECT with CdTe and conventional SPECT system using voxelized MOBY phantom. All SPECT images were obtained using 120 projection views acquired from 0° to 360° with a 3°. Slices were reconstructed using an Ordered Subsets Expectation Maximization (OS-EM) and 5 iterations with 4 subsets. We compared the quality of images for two systems in terms of spatial resolution (FWHM), sensitivity, signal-to-noise ratio (SNR), and contrast-to-noise (CNR). Our simulation results indicated that the reconstructed SPECT images obtained with CdTe detector showed higher resolution compared to those with the conventional scintillation detector. These results demonstrated that the SPECT imaging based on pixelated CdTe detector can improve the performance of SPECT system for small animal imaging.

In vivo Cerenkov luminescence imaging: a new tool for molecular imaging

Cerenkov radiation is a phenomenon where optical photons are emitted when a charged particle moves faster than the speed of light for the medium in which it travels. Recently, we and others have discovered that measurable visible light due to the Cerenkov effect is produced in vivo following the administration of β-emitting radionuclides to small animals. Furthermore, the amounts of injected activity required to produce a detectable signal are consistent with small-animal molecular imaging applications. This surprising observation has led to the development of a new hybrid molecular imaging modality known as Cerenkov luminescence imaging (CLI), which allows the spatial distribution of biomolecules labelled with β-emitting radionuclides to be imaged in vivo using sensitive charge-coupled device cameras. We review the physics of Cerenkov radiation as it relates to molecular imaging, present simulation results for light intensity and spatial distribution, and show an example of CLI in a mouse cancer model. CLI allows many common radiotracers to be imaged in widely available in vivo optical imaging systems, and, more importantly, provides a pathway for directly imaging β(-)-emitting radionuclides that are being developed for therapeutic applications in cancer and that are not readily imaged by existing methods.

Carbon nanotube based X-ray sources: Applications in pre-clinical and medical imaging

Field emission offers an alternate method of electron production for Bremsstrahlung based X-ray tubes. Carbon nanotubes (CNTs) serve as very effective field emitters, allowing them to serve as electron sources for X-ray sources, with specific advantages over traditional thermionic tubes. CNT derived X-ray sources can create X-ray pulses of any duration and frequency, gate the X-ray pulse to any source and allow the placement of many sources in close proximity. We have constructed a number of micro-CT systems based on CNT X-ray sources for applications in small animal imaging, specifically focused on the imaging of the heart and lungs. This paper offers a review of the pre-clinical applications of the CNT based micro-CT that we have developed. We also discuss some of the current and potential clinical applications of the CNT X-ray sources.

Statistical Approach for Optoacoustic Image Reconstruction in the Presence of Strong Acoustic Heterogeneities

A method is presented to reduce artefacts produced in optoacoustic tomography images due to internal reflection or scattering of the acoustic waves. It is based on weighting the tomographic contribution of each detector with the probability that a signal affected by acoustic mismatches is measured at that position. The correction method does not require a priori knowledge of the acoustic or optical properties of the imaged sample. Performance tests were made with agar phantoms that included air gaps for mimicking strong acoustic reflections as well as with an acoustically heterogeneous adult Zebrafish. The results obtained with the method proposed show a clear reduction of the artefacts with respect to the original images reconstructed with filtered back-projection algorithm. This performance is directly related to in vivo small animal imaging applications involving imaging in the presence of bones, lungs, and other highly mismatched organs.

Near‐field radiofrequency thermoacoustic tomography with impulse excitation

Imaging performance of radiofrequency and microwave-based thermoacoustic tomography systems is mainly determined by the ability to deposit a substantial amount of electromagnetic energy within ultrashort time duration. Pulses of nanosecond-range duration that can carry hundreds of millijoules energy are ideal for obtaining good signal-to-noise and spatial resolution in many biological imaging applications. However, existing implementations are based on modulated-carrier-frequency amplification solutions, which are generally costly and cannot achieve ultrahigh-peak-power requirements essential for optimal thermoacoustic signal generation. Herein the authors suggest and experimentally validate a near-field radiofrequency tomography (NRT) method for high resolution imaging of biological tissues using ultrashort electromagnetic impulses. The solution includes a low-cost pulsing system while the imaged objects are placed in the near field of the energy-emitting aperture for improved coupling using nonradiative fields. In the current design, the authors were able to achieve excitation impulse energies of hundreds of millijoules with durations in the order of a few nanoseconds, corresponding to peak power levels of multiple megawatts. The phantom imaging experiments demonstrated image features with characteristic sizes of around 170 microm, but the impulse durations used herein allow in principle spatial resolutions in the order of a few tens of microns when using an appropriate ultrasonic detection bandwidth. The proposed NRT method makes it possible to attain very high spatial resolution without compromising the thermoacoustic signal strength. This makes the imaging performance to be limited by the available bandwidth of the ultrasonic detector rather than by the microwave pulse duration. It is overall expected that the combination of pulsed near-field coupling with optimal choice of energy dissipation elements will generate a practical modality that can scale its application to small and larger volumes alike, while optimally adjusting the resolution to match the acoustic resolution possible. Such an approach should find several applications in small animal and clinical imaging.

Self-demodulation of high-frequency ultrasound

High-frequency (>10 MHz) ultrasound is used in, e.g., small animal imaging or intravascular applications. Currently available ultrasound contrast agents (UCAs) have a suboptimal response for high frequencies. This study therefore investigates the nonlinear propagation effects in a high-frequency ultrasound field (25 MHz) and its use for standard UCA and diagnostic frequencies (1-3 MHz). Nonlinear mixing of two high-frequency carrier waves produces a low-frequency wave, known as the self-demodulation or parametric array effect. Hydrophone experiments showed that the self-demodulated field of a focused 25 MHz transducer (850 kPa source pressure) has an amplitude of 45 kPa at 1.5 MHz in water. Such pressure level is sufficient for UCA excitation. Experimental values are confirmed by numerical simulations using the Khokhlov-Zabolotskaya-Kuznetsov equation on a spatially convergent grid.

二维稳态辐射传输方程的有限差分求解法

A novel finite difference method (FDM) solution to the 2-dimensional time-independent radiative transfer equation (RTE) is proposed for small-animal imaging applications, which is based on the real physics of 3-dimensional scattering of a photon in turbid medium. The influences of the angular discretization and the spatially meshing grids on the accuracy of FDM-RTE solution are investigated and a comparison is made between the FDM-RTE calculations to the relevant Monte-Carlo simulation ones for a validation of the proposed method. The comparison shows that, as the number of the discretized solid angles is over 80, the accuracy of the FDM-RTE calculated forward photon density is insensitive to the spatially meshing grids on the transmission and side surfaces but on the reflection surface. This study provides a viable methodology to the development of the RTE-based Diffuse Optical Tomography(DOT) technology.

Feasibility of in vivo imaging of fluorescent proteins using lifetime contrast

We show that fluorescence lifetime is a powerful contrast mechanism that can enhance the whole-body imaging of fluorescent proteins (FPs), in the presence of background tissue autofluorescence (AF). The nonexponential AF decay is characterized from time-domain (TD) measurements on multiple nude mice and separated from the FP fluorescence using a linear fit to a priori basis functions. We illustrate this approach using an orthotopic mouse tumor model of breast adenocarcinoma. We also report that four commonly used FPs show distinct lifetimes, indicating their suitability for in vivo lifetime multiplexing. These results suggest the potential for exploiting fluorescence lifetime for imaging FPs for a variety of whole-body small-animal imaging applications.