Time of flight dual photon emission computed tomography.

Time-of-flight dual photon emission computed tomography (TOF-DuPECT) is an imaging system that can obtain radionuclide distributions using time information recorded from two cascade-decay photons. The potential decay locations in the image space, a hyperbolic response curve, can be determined via time-difference-of-arrival (TDOA) estimations from two instantaneous coincidence photons. In this feasibility study, Monte Carlo simulations were performed to generate list-mode coincidence data. A full-ring positron emission tomography-like detection system geometry was built in the simulation environment. A contrast phantom and a Jaszczak-like phantom filled with Selenium-75 (Se-75) were used to evaluate the image quality. A TOF-DuPECT system with varying coincidence time resolution (CTR) was then evaluated. We used the stochastic origin ensemble (SOE) algorithm to reconstruct images from the recorded list-mode data. The results indicate that the SOE method can be successfully employed for the TOF-DuPECT system and can achieve acceptable image quality when the CTR is less than 100 ps. Therefore, the TOF-DuPECT imaging system is feasible. With the improvement of the detector with time, future implementations and applications of TOF-DuPECT are promising. Further quantitative imaging techniques such as attenuation and scatter corrections for the TOF-DuPECT system will be developed in future.

A noise smoothing origin ensemble algorithm based on local filtering.

An origin ensemble (OE) image reconstruction algorithm can be used for the fast reconstruction of unconventional geometrical images, e.g. in a Compton camera (CC) system. Due to the low-count rate in the emission data, the reconstructed image is often noisy and inhomogeneous in density. In this study, we propose a way to smooth out the noise in the OE algorithm. During the OE reconstruction, the algorithm stochastically modifies the current location to a random new voxel along the probable corresponding curve of each event depending on the relative event density of the new and old locations. In the original OE technique, the event density is simply the number of events in the voxel. In the proposed method, the event density is estimated from the filtering of a kernel window centered on the voxel. Incorporating the regional filtering is similar to performing an OE algorithm on a smoothed image at each iteration and enables the reconstruction of a smoother image. A Flangeless Esser PET phantom and a multi-activity phantom are used to study the property of the new reconstruction algorithm. The results indicate that the proposed method performs better than a conventional OE algorithm in terms of normalized mean square error (NMSE) and structural similarity (SSIM). Both contrast noise ratio (CNR) and reconstruction accuracy of the new method are better than the conventional OE algorithm and their performances improve with the increase of object size. The median-OE possesses the highest overall image quality and recovery rate among the three filter-OE algorithms and is the method of choice for image reconstruction. Comparing to conventional post-smoothing OEs, the NMSE of median-OE improves 57.6% (46.9%) and the SSIM increased by 73.2% (51.1%) for the Esser (multi-activity) phantom. The proposed OE algorithm is simple and efficient for noise smoothing without complex calculations and highly suited for low-count cases.

Accuracy of using high-energy prompt gamma to verify proton beam range with a Compton camera: A Monte Carlo simulation study.

Prompt gamma (PG) rays emitted during proton therapy has been used for proton range verification. Because high-energy PG emission is well correlated to the Bragg peak (BP), high-energy PG rays are well-suited for proton range verification. However, the low production and detection of high-energy PG rays often lead to inaccurate BP position estimates. The aim of this study is to improve the BP position estimates obtained from high-energy PG rays. We propose a BP position estimation method based on the local maximum closest to the distal fall-off region. We present the results of Monte Carlo simulations in which a water phantom was irradiated with a proton beam. Our results show that the BP position estimated from the 6.13 MeV PG rays can be improved using the proposed position estimation method. Moreover, the 6.92 and 7.12 MeV PG rays can be used for predicting the BP position. However, the accuracy of the BP position estimation decreases with decreasing tissue oxygen levels. We also found that the subtraction of the PG images of 6.13 MeV from those of 6.92 and 7.12 MeV can be used to predict the BP position with a mean accuracy of < 2 mm. The accurate estimation of the BP position can be achieved using different high-energy PG rays, but factors including position estimation, irradiated tissue and event selection should be carefully taken into account.

A low-count reconstruction algorithm for Compton-based prompt gamma imaging.

The Compton camera is an imaging device which has been proposed to detect prompt gammas (PGs) produced by proton-nuclear interactions within tissue during proton beam irradiation. Compton-based PG imaging has been developed to verify proton ranges because PG rays, particularly characteristic ones, have strong correlations with the distribution of the proton dose. However, accurate image reconstruction from characteristic PGs is challenging because the detector efficiency and resolution are generally low. Our previous study showed that point spread functions can be incorporated into the reconstruction process to improve image resolution. In this study, we proposed a low-count reconstruction algorithm to improve the image quality of a characteristic PG emission by pooling information from other characteristic PG emissions. PGs were simulated from a proton beam irradiated on a water phantom, and a two-stage Compton camera was used for PG detection. The results show that the image quality of the reconstructed characteristic PG emission is improved with our proposed method in contrast to the standard reconstruction method using events from only one characteristic PG emission. For the 4.44 MeV PG rays, both methods can be used to predict the positions of the peak and the distal falloff with a mean accuracy of 2 mm. Moreover, only the proposed method can improve the estimated positions of the peak and the distal falloff of 5.25 MeV PG rays, and a mean accuracy of 2 mm can be reached.

PSF reconstruction for Compton-based prompt gamma imaging.

Compton-based prompt gamma (PG) imaging has been proposed for in vivo range verification in proton therapy. However, several factors degrade the image quality of PG images, some of which are due to inherent properties of a Compton camera such as spatial resolution and energy resolution. Moreover, Compton-based PG imaging has a spatially variant resolution loss. In this study, we investigate the performance of the list-mode ordered subset expectation maximization algorithm with a shift-variant point spread function (LM-OSEM-SV-PSF) model. We also evaluate how well the PG images reconstructed using an SV-PSF model reproduce the distal falloff of the proton beam. The SV-PSF parameters were estimated from simulation data of point sources at various positions. Simulated PGs were produced in a water phantom irradiated with a proton beam. Compared to the LM-OSEM algorithm, the LM-OSEM-SV-PSF algorithm improved the quality of the reconstructed PG images and the estimation of PG falloff positions. In addition, the 4.44 and 5.25 MeV PG emissions can be accurately reconstructed using the LM-OSEM-SV-PSF algorithm. However, for the 2.31 and 6.13 MeV PG emissions, the LM-OSEM-SV-PSF reconstruction provides limited improvement. We also found that the LM-OSEM algorithm followed by a shift-variant Richardson-Lucy deconvolution could reconstruct images with quality visually similar to the LM-OSEM-SV-PSF-reconstructed images, while requiring shorter computation time.

Use of a LYSO-based Compton camera for prompt gamma range verification in proton therapy.

PURPOSE: A Compton camera (CC), which measures prompt gammas (PGs) emitted during proton therapy, is a potentially useful imaging device for proton range verification. The aim of this study was to evaluate how well the reconstructed PG images obtained from various two-stage CC configurations reproduce the distal falloff of the PG emission. METHODS: We conducted Monte Carlo simulations to evaluate different two-stage CCs positioned orthogonal to a proton pencil beam irradiating a water phantom. The results were compared with those obtained for a three-stage CC. In particular, all detectors were made of lutetium-yttrium orthosilicate (LYSO) crystals. RESULTS: We found that: (a) the position resolution of the detector led to more uncertainty in predicting the depth of maximum emission and distal falloff positions than did the energy resolution of the detector; (b) reducing the thickness of the absorber detector reduces the effect of position resolution on the quality of reconstructed images and improves falloff position estimates; (c) incomplete absorption of PGs can be filtered by restricting incident gamma energies to known PG energy spectral peaks; and (d) there is greater bias and less accuracy in predicting distal falloff positions with the three-stage CC compared with the two-stage CC. CONCLUSIONS: This study demonstrates the feasibility of using various CC designs and event selection methods to improve the imaging of PG rays. In our designed two-stage CCs, the thin LYSO-based absorber can provide better predictions of the distal falloff positions than the thick one. Compared to three-stage CCs, two-stage CCs are less biased and provide more accurate range verification.

Noninvasive measurement of radiopharmaceutical time-activity data using external thermoluminescent dosimeters (TLDs).

In this study, we present a new method for estimating the time-activity data using serial timely measurements of thermoluminescent dosimeters (TLDs). The approach is based on the combination of the measurement of surface dose using TLD and Monte Carlo (MC) simulation to estimate the radiopharmaceutical time-activity data. It involves four steps: (1) identify the source organs and outline their contours in computed tomography images; (2) compute the S values on the body surface for each source organ using a MC code; (3) obtain a serial measurement of the dose with numerous TLDs placed on the body surface; (4) solve the dose-activity equation to generate organ cumulative activity for each period of measurement. The activity of each organ at the time of measurement is simply the cumulative activity divided by the timespan between measurements. The usefulness of this method was studied using a MC simulation based on an Oak Ridge National Laboratory mathematical phantom with 18F-FDG filled in six source organs. Numerous TLDs were placed on different locations of the surface and were repeatedly read and replaced. The time-activity curves (TACs) of all organs were successfully reconstructed. Experiments on a physical phantom were also performed. Preliminary results indicate that it is an effective, robust, and simple method for assessing the TAC. The proposed method holds great potential for a range of applications in areas such as targeted radionuclide therapy, pharmaceutical research, and patient-specific dose estimation.

Recovering the triple coincidence of non-pure positron emitters in preclinical PET.

Non-pure positron emitters, with their long half-lives, allow for the tracing of slow biochemical processes which cannot be adequately examined by the commonly used short-lived positron emitters. Most of these isotopes emit high-energy cascade gamma rays in addition to positron decay that can be detected and create a triple coincidence with annihilation photons. Triple coincidence is discarded in most scanners, however, the majority of the triple coincidence contains true photon pairs that can be recovered. In this study, we propose a strategy for recovering triple coincidence events to raise the sensitivity of PET imaging for non-pure positron emitters. To identify the true line of response (LOR) from a triple coincidence, a framework utilizing geometrical, energy and temporal information is proposed. The geometrical criterion is based on the assumption that the LOR with the largest radial offset among the three sub pairs of triple coincidences is least likely to be a true LOR. Then, a confidence time window is used to test the valid LOR among those within triple coincidence. Finally, a likelihood ratio discriminant rule based on the energy probability density distribution of cascade and annihilation gammas is established to identify the true LOR. An Inveon preclinical PET scanner was modeled with GATE (GEANT4 application for tomographic emission) Monte Carlo software. We evaluated the performance of the proposed method in terms of identification fraction, noise equivalent count rates (NECR), and image quality on various phantoms. With the inclusion of triple coincidence events using the proposed method, the NECR was found to increase from 11% to 26% and 19% to 29% for I-124 and Br-76, respectively, when 7.4-185 MBq of activity was used. Compared to the reconstructed images using double coincidence, this technique increased the SNR by 5.1-7.3% for I-124 and 9.3-10.3% for Br-76 within the activity range of 9.25-74 MBq, without compromising the spatial resolution or contrast. We conclude that the proposed method can improve the counting statistics of PET imaging for non-pure positron emitters and is ready to be implemented on current PET systems.

Investigation of Readout RF Pulse Impact on the Chemical Exchange Saturation Transfer Spectrum.

Chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) is capable of both microenvironment and molecular imaging. The optimization of scanning parameters is important since the CEST effect is sensitive to factors such as saturation power and field homogeneity. The aim of this study was to determine if the CEST effect would be altered by changing the length of readout RF pulses. Both theoretical computer simulation and phantom experiments were performed to examine the influence of readout RF pulses. Our results showed that the length of readout RF pulses has unremarkable impact on the Z-spectrum and CEST effect in both computer simulation and phantom experiment. Moreover, we demonstrated that multiple refocusing RF pulses used in rapid acquisition with relaxation enhancement (RARE) sequence induced no obvious saturation transfer contrast. Therefore, readout RF pulse has negligible effect on CEST Z-spectrum and the optimization of readout RF pulse length can be disregarded in CEST imaging protocol.

Efficient simulation of voxelized phantom in GATE with embedded SimSET multiple photon history generator.

GEANT4 Application for Tomographic Emission (GATE) is a powerful Monte Carlo simulator that combines the advantages of the general-purpose GEANT4 simulation code and the specific software tool implementations dedicated to emission tomography. However, the detailed physical modelling of GEANT4 is highly computationally demanding, especially when tracking particles through voxelized phantoms. To circumvent the relatively slow simulation of voxelized phantoms in GATE, another efficient Monte Carlo code can be used to simulate photon interactions and transport inside a voxelized phantom. The simulation system for emission tomography (SimSET), a dedicated Monte Carlo code for PET/SPECT systems, is well-known for its efficiency in simulation of voxel-based objects. An efficient Monte Carlo workflow integrating GATE and SimSET for simulating pinhole SPECT has been proposed to improve voxelized phantom simulation. Although the workflow achieves a desirable increase in speed, it sacrifices the ability to simulate decaying radioactive sources such as non-pure positron emitters or multiple emission isotopes with complex decay schemes and lacks the modelling of time-dependent processes due to the inherent limitations of the SimSET photon history generator (PHG). Moreover, a large volume of disk storage is needed to store the huge temporal photon history file produced by SimSET that must be transported to GATE. In this work, we developed a multiple photon emission history generator (MPHG) based on SimSET/PHG to support a majority of the medically important positron emitters. We incorporated the new generator codes inside GATE to improve the simulation efficiency of voxelized phantoms in GATE, while eliminating the need for the temporal photon history file. The validation of this new code based on a MicroPET R4 system was conducted for (124)I and (18)F with mouse-like and rat-like phantoms. Comparison of GATE/MPHG with GATE/GEANT4 indicated there is a slight difference in energy spectra for energy below 50 keV due to the lack of x-ray simulation from (124)I decay in the new code. The spatial resolution, scatter fraction and count rate performance are in good agreement between the two codes. For the case studies of (18)F-NaF ((124)I-IAZG) using MOBY phantom with 1  ×  1 × 1 mm(3) voxel sizes, the results show that GATE/MPHG can achieve acceleration factors of approximately 3.1 × (4.5 ×), 6.5 × (10.7 ×) and 9.5 × (31.0 ×) compared with GATE using the regular navigation method, the compressed voxel method and the parameterized tracking technique, respectively. In conclusion, the implementation of MPHG in GATE allows for improved efficiency of voxelized phantom simulations and is suitable for studying clinical and preclinical imaging.

Monitoring of 2-deoxy-2-[18F]fluoro-D-glucose uptake in tumor-bearing mice using high-sensitivity projection imaging: compared with PET imaging.

OBJECTIVE: To investigate the feasibility of using high-sensitivity projection [F]fluoro-deoxyglucose imaging to monitor chemotherapeutic efficacy in BALB/c mice bearing CT-26 tumor implants. METHODS: A planar positron imaging system (PPIS)-4800 and a microPET R4 were used for projection and tomographic imaging, respectively. Six disks filled with different volumes of F-FDG solution were scanned by PPIS for calibration check. Tumor-bearing mice were treated with saline (control) or cyclophosphamide by intraperitoneal injections. Tumor responses were evaluated by both PPIS and microPET imaging. RESULTS: The disk-activity ratios obtained from PPIS were 1.00: 1.30: 1.98: 2.48: 2.73: 3.53 with corresponding volume ratios of 1.0: 1.5: 2.0: 2.5: 3.0: 3.5. PPIS imaging in tumor-bearing mice showed that the tumor/non-tumor ratios were 1.62, 2.12, 3.03, 4.46, and 3.61 on days 7, 10, 13, 17, and 20, respectively, after tumor inoculation. In addition, PPIS was used to monitor the chemotherapeutic effect of cyclophosphamide on tumor-bearing mice. The correlation coefficients between the tumor sizes and tumor/non-tumor ratios for microPET and PPIS were 0.63 and 0.72, respectively, in the control group, and were 0.98 and 0.81, respectively, in the cyclophosphamide-treated group. CONCLUSION: This study showed that PPIS imaging is a feasible modality for monitoring tumor responses. These results suggest that PPIS, a potential high-throughput screening imaging system, may be used for the preclinical evaluation of tumor response to new anticancer drugs using murine tumor models.

Receptor-binding, biodistribution, dosimetry, and micro-SPECT/CT imaging of 111In-[DTPA(1), Lys(3), Tyr(4)]-bombesin analog in human prostate tumor-bearing mice.

Gastrin-releasing peptide receptors (GRPRs) are overexpressed on a variety of human tumors, such as prostate, breast, and lung cancer. Bombesin (BN) is a 14-amino-acid peptide with high affinity for these GRPRs. We synthesized DTPA-Q-K-Y-G-N-Q-W-A-V-G-H-L-M, a 13-amino-acid peptide chelated with diethylenetriaminepentaacetic acid (DTPA), and radiolabeled this BN analog with 111InCl(3). Biologic activity of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was evaluated in PC-3 prostate tumor-bearing severely compromised immunodeficient (SCID) mice. The purity of synthesized [DTPA(1), Lys(3), Tyr(4)]-BN was greater than 95%. The radiolabeling efficiency of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was 96.9% +/- 2.46%. The IC(50) and K(i) of [DTPA(1), Lys(3), Tyr(4)]-BN in the human bombesin 2 receptor were 1.05 +/- 0.46 and 0.83 +/- 0.36 nM, respectively. The K(d) of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN in GRPR-expressing PC-3 tumor cells was 22.9 +/- 6.81 nM. Both biodistribution and micro-SPECT/CT (single-photon emission computed tomography/computed tomography) imaging studies with 111In-[DTPA(1), Lys(3), Tyr(4)]-BN demonstrated the highest uptake at 8 hours postinjection. The Pearson correlation analysis showed a positive correlation of tumor uptake between biodistribution and micro-SPECT/CT semiquantification imaging analysis (r = 0.832). Our results revealed 111In-[DTPA(1), Lys(3), Tyr(4)]-BN has high affinity with BN type 2 receptor. The results demonstrated a good uptake in the GRPR-overexpression of PC-3 tumor-bearing SCID mice. 111In-[DTPA(1), Lys(3), Tyr(4)]-BN is a potential agent for imaging GRPR-positive tumors in humans.

Imaging of regional metabolic activity by (18)F-FDG/PET in rats with transient cerebral ischemia.

Changes in regional metabolic activities induced by middle cerebral artery occlusion (MCAO) can influence patient outcome. Our aim was to demonstrate in a rat model that (18)F-FDG with positron emission tomography (PET) imaging is a quantitative, reproducible approach for identifying acute and sub-acute metabolic variations in infarct regions. We found that imaging with (18)F-FDG/PET enabled detection and quantification of ischemia-induced metabolic deficits and provided a sensitive and reliable means of assessing cerebral ischemic lesions compared with conventional neurological scoring systems in rodents.

A Lower-Cost High-Resolution LYSO Detector Development for Positron Emission Mammography (PEM).

In photomultiplier-quadrant-sharing (PQS) geometry for positron emission tomography applications, each PMT is shared by four blocks and each detector block is optically coupled to four round PMTs. Although this design reduces the cost of high-resolution PET systems, when the camera consists of detector panels that are made up of square blocks, half of the PMT's sensitive window remains unused at the detector panel edge. Our goal was to develop a LYSO detector panel which minimizes the unused portion of the PMTs for a low-cost, high-resolution, and high-sensitivity positron emission mammography (PEM) camera. We modified the PQS design by using elongated blocks at panel edges and square blocks in the inner area. For elongated blocks, symmetric and asymmetrical reflector patterns were developed and PQS and PMT-half-sharing (PHS) arrangements were implemented in order to obtain a suitable decoding. The packing fraction was 96.3% for asymmetric block and 95.5% for symmetric block. Both of the blocks have excellent decoding capability with all crystals clearly identified, 156 for asymmetric and 144 for symmetric and peak-to-valley ratio of 3.0 and 2.3 respectively. The average energy resolution was 14.2% for the asymmetric block and 13.1% for the symmetric block. Using a modified PQS geometry and asymmetric block design, we reduced the unused PMT region at detector panel edges, thereby increased the field-of-view and the overall detection sensitivity and minimized the undetected breast region near the chest wall. This detector design and using regular round PMT allowed building a lower-cost, high-resolution and high-sensitivity PEM camera.

Longitudinal microSPECt/CT imaging and pharmacokinetics of synthetic luteinizing hormone-releasing hormone (LHRH) vaccine in rats.

BACKGROUND: Luteinizing hormone-releasing hormone (LHRH)-derived decapeptide-based vaccines have been used in studies of immunocastration and immunotherapy of prostate cancer, but no image data are available on the kinetics of vaccines post injection (p.i.). Therefore, an 131I radiolabeled LHRH-derived immunogen was developed to visualize and evaluate the retention of LHRH-derived vaccines in rats. MATERIALS AND METHODS: The LHRH immunogens, which contained equal moles of 131I-p607E, p667 and p500, were formulated with an equal volume of an adjuvant, Montanide ISA50. MicroSPECT/CT imaging was performed to visualize the retention of the radiolabeled immunogen up to 30 days after intramuscular inoculation of 25 microg immunogens. The pharmacokinetics, distribution and excretion were also evaluated. RESULTS: The radiochemical purity of 131I-p607E was 97.85+/-2.12%. The longitudinal microSPECT/CT imaging revealed that most 131I-p607E was retained at the injected muscle site until 30 days p.i.. Biodistribution showed that 34.56+/-4.27% of radioactivity remained at the injected muscle site at 28 days p.i.. The cumulative radioactivity excreted via urine was 30.02+/-3.82% up to day 28 p.i.. The elimination half-life (t1/2), Tmax and Cmax were 158.67 h, 24 h, and 0.026 percentage of injected dose per gram (%ID/g), respectively. CONCLUSION: The LHRH immunogen, 131I-p607E, was mainly retained at the intramuscular injection site during the whole study period. The microSPECTICT imaging modality can be used to monitor the location and distribution of the LHRH immunogen, 131I-p607E, in a rat model.

Imaging the availability of serotonin transporter in rat brain with 123I-ADAM and small-animal SPECT.

BACKGROUND: Imaging serotonin transporters during antidepressant treatment in small animals is a useful tool for preclinical study during drug development. In this work, we aimed to demonstrate the feasibility of using 123I-ADAM and small-animal SPECT to monitor serotonin transporter availabilities in rat brains prior to and after administration of a selective serotonin re-uptake inhibitor. METHODS: Male Sprague-Dawley rats with and without administration of citalopram (4 mg x kg body weight) were examined in this study. During the process rat brains were scanned using a double-headed microSPECT system equipped with pinhole collimators. SPECT tomographic images and X-ray computed tomography (CT) were acquired after introducing 123I-ADAM via the tail vein. The 123I-ADAM specific binding was assessed by SPECT/CT fused image to draw regions of interest in the midbrain and cerebellum. Ex-vivo autoradiography was carried out as a parallel investigation to validate the SPECT technique. RESULTS: SPECT images displayed specific binding ratio in midbrain to be 0.91+/-0.30 averaged from three rats. Drug occupancies (95.47+/-1.56)% were shown after administration of citalopram in a dosage of 4 mg x kg. CONCLUSION: This study demonstrated that the serotonin transporter availability during antidepressant treatment in small animals can be assessed semi-quantitatively by using 123I-ADAM and SPECT.

Scatter correction for 3D PET using beam stoppers combined with dual-energy window acquisition: a feasibility study.

Fully three-dimensional (3D) positron emission tomography (PET) can achieve high sensitivity of coincidence events, but the absence of inter-slice septa inevitably leads to increased scattered events. The scattered events can represent as much as 50% of the total detected events. In this research, we proposed a scatter correction method for 3D PET based on beam stoppers and dual-energy window acquisition. The beam stoppers were placed surrounding the object to attenuate primary beams. The scatter fractions were directly estimated at those blocked lines of response and then the entire scatter fraction distribution was recovered using the dual-energy window ratio as reference. The performance was evaluated by using Monte Carlo simulations of various digital phantoms. For the Utah phantom study, the proposed method accurately estimated the scatter fraction distribution, and improved image contrast and quantification based on four different quality indices as performance measures. For the non-homogeneous Zubal phantom, the simulated results also demonstrated that the proposed method achieved a better restoration of image contrast than the dual-energy window method. We conclude that the proposed scatter correction method could effectively suppress various kinds of scattered events, including multiple scatter and scatter from outside the field of view.

Coincidence planar imaging for dynamic [18F]FDG uptake in nude mice with tumors and inflammation: correlated with histopathology and micro-autoradiography.

The Institute of Nuclear Energy Research of Taiwan has developed a dynamic coincidence detection device for positron emitted radiotracer pharmacodynamic study in small mice models. In this study, we set up an experimental paradigm by determining [fluorine-18]-2-deoxy-2-fluoro-D-glucose ([18F]FDG) dynamic uptake in tumors and inflammations in nude mice as the foundation for future applications in therapy development. Histopathology and micro-autoradiography of these tumors and inflammations were obtained for confirmation. Dynamic coincidence planar images of six tumors and two inflammations in nude mice were acquired over 4 hours immediately after injection of 25.9 MBq of [18F]FDG into the right thigh of each animal. After image reconstruction, the lesion-to-background ratios were calculated in regions of interest over the lesion and contralateral thigh to determine the equilibrium status of the radiotracer. All mice were sacrificed for histopathologic examination and six of the mice were examined with micro-autoradiography. [18F]FDG uptake in tumors and inflammations both reached equilibrium about 3 hours after injection. At equilibrium, [18F]FDG uptake into tumors was two to four times higher than the background. Uptake into the 4-day and 8-day inflammations was 2.3 and 5.5 times higher than the background, respectively. Histopathology showed macrophage and neutrophil infiltration around the tumors and in the inflammations. Micro-autoradiography showed dense silver grains in the granulation tissue surrounding the tumors and inflammations. The preliminary results suggested that dynamic [18F]FDG coincidence planar imaging can help in determining the suitable time for static [18F]FDG imaging in nude mice models. The optimal time for static [18F]FDG positron emission tomography imaging was around 3 hours after injection. The paradigm for determining a dynamic [18F]FDG uptake pattern was demonstrated for future new therapeutic drug experimental use.

A maximum likelihood expectation maximization algorithm with thresholding.

The maximum likelihood expectation maximization (MLEM) algorithm has several advantages over the conventional filtered back-projection (FBP) for image reconstruction. However, the slow convergence and the high computational cost for its practical implementation have limited its clinical applications. This study proposes the incorporation of a thresholding technique in both the MLEM and ordered subsets EM (OSEM) algorithm to accelerate convergence. The threshold is set to c*m, where m is the mean pixel value of the whole image. The reconstruction time is proportional to the total number of pixels, so a thresholding technique that nullifies the value of a pixel if it falls below a threshold, can effectively remove the non-active pixels and substantially accelerate reconstruction. Preliminary tests on simulated PET data reveal that the thresholding technique accelerates the convergence rate and reduce error in the reconstructed image. The reconstruction performance improves with the increase of the threshold level and the MSE reaches minimum for c value equals to about 1.

A three-dimensional registration method for automated fusion of micro PET-CT-SPECT whole-body images.

Micro positron emission tomography (PET) and micro single-photon emission computed tomography (SPECT), used for imaging small animals, have become essential tools in developing new pharmaceuticals and can be used, among other things, to test new therapeutic approaches in animal models of human disease, as well as to image gene expression. These imaging techniques can be used noninvasively in both detection and quantification. However, functional images provide little information on the structure of tissues and organs, which makes the localization of lesions difficult. Image fusion techniques can be exploited to map the functional images to structural images, such as X-ray computed tomography (CT), to support target identification and to facilitate the interpretation of PET or SPECT studies. Furthermore, the mapping of two functional images of SPECT and PET on a structural CT image can be beneficial for those in vivo studies that require two biological processes to be monitored simultaneously. This paper proposes an automated method for registering PET, CT, and SPECT images for small animals. A calibration phantom and a holder were used to determine the relationship among three-dimensional fields of view of various modalities. The holder was arranged in fixed positions on the couches of the scanners, and the spatial transformation matrix between the modalities was held unchanged. As long as objects were scanned together with the holder, the predetermined matrix could register the acquired tomograms from different modalities, independently of the imaged objects. In this work, the PET scan was performed by Concorde's microPET R4 scanner, and the SPECT and CT data were obtained using the Gamma Medica's X-SPECT/CT system. Fusion studies on phantoms and animals have been successfully performed using this method. For microPET-CT fusion, the maximum registration errors were 0.21 mm +/- 0.14 mm, 0.26 mm +/- 0.14 mm, and 0.45 mm +/- 0.34 mm in the X (right-left), Y (upper lower), and Z (rostral-caudal) directions, respectively; for the microPET-SPECT fusion, they were 0.24 mm +/- 0.14 mm, 0.28 mm +/- 0.15 mm, and 0.54 mm +/- 0.35 mm in the X, Y, and Z directions, respectively. The results indicate that this simple method can be used in routine fusion studies.