Medical imaging and telemedicine - from medical data production, to processing, storing, and sharing: a short outlook.
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Database Management Systems↗
Biomedical subjects
Jyh-Cheng Chen
Publications and source records attributed to Jyh-Cheng Chen.
Evaluation of the quantitative capability of a home-made cone-beam micro computed tomography system.
Quantitative computed tomography provides the most accurate form of bone mineral density measurement. It is very useful in several applications when used with micro computed tomography (microCT). The objective of this study is to evaluate the quantitative capability of iterative and analytic reconstruction with and without energy-based beam hardening calibration using a home-made microCT. Due to the fact that the source of X-rays in the microCT is poly-energetic and the linear attenuation coefficient varies with the energy of the X-ray photons, a specific correction is presented in this study that resolves the poly-energetic effect. Then, a 3D distribution of the linear attenuation coefficient is reconstructed from the ordered subsets using the maximum likelihood and T-FDK algorithms. These algorithms were both developed for cone-beam microCT. The images reconstructed by the two algorithms with/without correction are presented. A region of interest analysis is used to evaluate the results from two algorithms and their advantages and disadvantages are discussed. The quantitative capability is better when the image is reconstructed using the iterative method along with a beam hardening correction.
Algorithms↗
In vitro evaluation of herpes simplex virus type 1 thymidine kinase reporter system in dynamic studies of transcriptional gene regulation.
The herpes simplex virus type 1 thymidine kinase (HSV1-TK) reporter system is being used to directly and indirectly monitor therapeutic gene expression, immune cell trafficking and protein-protein interactions in various living animals. However, the issues of HSV1-TK enzyme stability in living cells and whether this reporter system is optimal for dynamic studies of gene expression events in genetic imaging have not be addressed. The purpose of the present study was to evaluate the application of this reporter system in dynamic studies of transcriptional gene regulation. To achieve this purpose, we established two tetracycline-inducible murine sarcoma cell lines, tetracycline-turn-off HSV1-tk-expressing cell line (NG4TL4/tet-off-HSV1-tk) and tetracycline-turn-off Luc-expressing cell line (NG4TL4/tet-off-Luc), to create an artificially regulated gene expression model in vitro. The dynamic transcriptional events mediating a series of doxycycline (Dox) inductions were monitored by HSV1-TK or by the firefly luciferase reporter gene using HSV1-TK enzyme activity assay and luciferase assay, respectively. The results of dynamic gene expression studies showed that the luciferase gene is an optimal reporter gene for monitoring short-timescale, dynamic transcriptional events mediating a series of Dox inductions, whereas the HSV1-tk is not optimal to achieve this purpose. Furthermore, the enzyme half-life of HSV1-TK in NG4TL4 cells is about 35 h after cycloheximide-induced protein inhibition. On the other hand, the results of an efflux assay of [(131)I] FIAU and [(3)H] GCV revealed that the molecular probe phosphorylated by HSV1-TK can be trapped long term within HSV1-TK stably transformed cells. Therefore, a long half-life radionuclide is not suitable for dynamic gene expression studies. Based on these results, we suggest that the HSV1-TK reporter system is not optimal for monitoring short-timescale dynamic processes such as kinetic gene expression controlled by inducible promoters or a less stable protein with a more rapid turnover due to the limitations of the half-life of the HSV1-TK enzyme and the cellular retention time of their phosphorylated molecular probes.
Arabinofuranosyluracil↗
Disposable electrochemical sensor for determination of nitroaromatic compounds by a single-run approach.
Environmental and security applications have generated major demands for effective field-deployable tools for detecting nitroaromatic compounds, such as chloramphenicol (an antibiotic), parathion (an organophosphate nerve agent), and TNT (2,4,6-trinitrotoluene, an explosive) in a fast, simple, sensitive, reliable, and cost-effective manner. We report here a single-run approach for such a purpose. The reduction potential of different nitroaromatic compounds was found to systematically shift with the substituent group at an electrochemically preanodized screen-printed carbon electrode. The preanodization treatment makes the peak sharp and hence provides a precise way to identify the substituent effect on nitroaromatic compounds. By using potential shifts as analytical characteristics of nitroaromatic compounds, a suitable internal standard can be chosen based on the criteria of well-separated peak potential and rarely found in the real sample of interest. Simply by measuring the ratio of peak currents between analytes of interest and internal standard, the analysis can be done in a single-run measurement. Both the matrix effect and the variation of electrode during the preparation process can be canceled out in this approach and thus allows for a high-precision analysis. Just by placing a 20-microL drop on a single-use amperometric sensor strip incorporating a three-electrode configuration is enough for rapid and sensitive detection of nitroaromatic compounds by square-wave voltammetry. For example, the linear detection range can be up to 100 microM with a detection limit of 0.42 microM (S/N = 3) in the detection of chloramphenicol. This approach was successfully demonstrated in real sample analysis to verify the applicability of the method. The promising performances open new possibilities for rapid determination of nitroaromatic compounds in environmental and biological samples.
Calibration↗
Development of wavelet de-noising technique for PET images.
Positron emission tomography (PET) imaging provides the functional information and precise physiological uptake of radioactivity in a patient's body. But the shortcoming of PET is low signal to noise ratio (SNR) due to photon noise. The noise may influence image quality, and cause the mistake of clinical interpretation. The purpose of this research is to develop a wavelet de-noising technique to reduce the noise of PET images. By processing the image through the optimum wavelet parameters we selected, we keep the resolution and contrast but reduce almost half of coefficient of variation in the region of interest of PET images.
Humans↗
Evaluation of F-18-labeled amino acid derivatives and [18F]FDG as PET probes in a brain tumor-bearing animal model.
UNLABELLED: 2-Deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) has been extensively used as positron emission tomography (PET) tracer in clinical tumor imaging. This study compared the pharmacokinetics of two (18)F-labeled amino acid derivatives, O-2-[(18)F]fluoroethyl-l-tyrosine (l-[(18)F]FET) and 4-borono-2-[(18)F]fluoro-l-phenylalanine-fructose (l-[(18)F]FBPA-Fr), to that of [(18)F]FDG in an animal brain tumor model. METHODS: A self-modified automated PET tracer synthesizer was used to produce no-carrier-added (nca) l-[(18)F]FET. The cellular uptake, biodistribution, autoradiography and microPET imaging of l-[(18)F]FET, l-[(18)F]FBPA-Fr and [(18)F]FDG were performed with F98 glioma cell culture and F98 glioma-bearing Fischer344 rats. RESULTS: The radiochemical purity of l-[(18)F]FET was >98% and the radiochemical yield was 50% in average of 16 runs. The uptake of l-[(18)F]FET and l-[(18)F]FBPA-Fr in the F98 glioma cells increased rapidly for the first 5 min and reached a steady-state level after 10 min of incubation, whereas the cellular uptake of [(18)F]FDG kept increasing during the study period. The biodistribution of l-[(18)F]FET, l-[(18)F]FBPA-Fr and [(18)F]FDG in the brain tumors was 1.26+/-0.22, 0.86+/-0.08 and 2.77+/-0.44 %ID/g at 60 min postinjection, respectively, while the tumor-to-normal brain ratios of l-[(18)F]FET (3.15) and l-[(18)F]FBPA-Fr (3.44) were higher than that of [(18)F]FDG (1.44). Both microPET images and autoradiograms of l-[(18)F]FET and l-[(18)F]FBPA-Fr exhibited remarkable uptake with high contrast in the brain tumor, whereas [(18)F]FDG showed high uptake in the normal brain and gave blurred brain tumor images. CONCLUSION: Both l-[(18)F]FET and l-[(18)F]FBPA-Fr are superior to [(18)F]FDG for the brain tumor imaging as shown in this study with microPET.
Animals↗
Quantification method in [18F]fluorodeoxyglucose brain positron emission tomography using independent component analysis.
OBJECTIVE: To extract accurate image-derived input functions from dynamic brain positron emission tomography images (DBPIs) using independent component analysis (ICA). METHODS: A modified linear model with haematocrit correction was used to improve the accuracy of input functions estimated by independent component analysis and to reduce the error of quantitative analysis. Two types of material were examined: (1) a simulated dynamic phantom with a three-compartment, four-parameter model; (2) clinical 2-h DBPIs with a standard plasma sampling procedure. The input function was extracted from DBPIs using independent component analysis. The modified linear model with haematocrit correction was used to obtain the independent component analysis-estimated input function (Iica). For comparison, the input function derived from the last three blood samples (Iest) was used. The image-derived input functions (Iica and Iest) were compared with the input function from blood sampling (Itp). The mean percentage error of the metabolic rate of [F]-2-fluoro-2-deoxy-D-glucose (MRFDG) was calculated for both Iica and Iest against that of Itp. RESULTS: In simulated studies, the mean percentage errors of MRFDG between true simulated and estimated values of Iest and Iica were 8.2% and 4.2%, respectively. In clinical studies, six clinical cases were collected. The mean percentage errors and standard deviations of MRFDG with Iest and Iica were 12.6+/-7.5% and 7.7+/-3.3%, respectively. CONCLUSIONS: We have proposed a technique for estimating image-derived input functions using independent component analysis without blood sampling. The results of our method were highly correlated with those from standard blood sampling, and more accurate than those of other methods proposed previously.
Algorithms↗
Evaluation of pharmacokinetics of 4-borono-2-(18)F-fluoro-L-phenylalanine for boron neutron capture therapy in a glioma-bearing rat model with hyperosmolar blood-brain barrier disruption.
UNLABELLED: This study evaluated the pharmacokinetics and biodistribution of 4-borono-2-(18)F-fluoro-l-phenylalanine ((18)F-FBPA) after intracarotid injection and with blood-brain barrier disruption (BBB-D) in F98 glioma-bearing F344 rats. The pharmacokinetics of l-p-boronophenylalanine (BPA) and (18)F-FBPA following different administration routes were compared to demonstrate the optimal delivery route and the time period for thermal neutron irradiation. METHODS: F98 glioma-bearing rats were injected intravenously or intracarotidly with (18)F-FBPA and BPA and with or without mannitol-induced hyperosmotic BBB-D. The boron concentration and (18)F radioactivity in tissues were determined by invasive (inductively coupled plasma mass spectroscopy, gamma-counting) and noninvasive PET methods. RESULTS: The biodistributions of (18)F-FBPA and BPA in F98 glioma-bearing rats were similar after intracarotid administration with BBB-D. The accumulation of BPA and (18)F-FBPA in brain tumor and the tumor-to-ipsilateral brain ratios were the highest after intracarotid injection with BBB-D, whereas the retention of boron drugs in contralateral brains exhibited only nonsignificant differences compared with those after intracarotid injection without BBB-D and intravenous injection. The high boron concentration in brain tumor (76.6 mug/g) and the high tumor-to-ipsilateral brain ratio (6.3) may afford enough radiation doses to destroy the tumor cells while sparing the normal tissues in boron neutron capture therapy. The pharmacokinetic parameters of k(el), k(12), k(21), and V(1) for intracarotid injection of (18)F-FBPA with BBB-D derived from the open 2-compartment model are 0.0206 +/- 0.0018 min(-1), 0.0260 +/- 0.0016 min(-1), 0.0039 +/- 0.0003 min(-1), and 3.1 +/- 0.1 mL, respectively. The effect of BBB-D varied depending on the anesthetic agents used and the anesthetic conditions. A smaller degree of BBB-D and, thus, lower boron concentrations in tumor and ipsilateral brain were observed under isoflurane anesthesia than under ketamine anesthesia. The k(12)/k(21) ratio may serve as a good indication for evaluating the extent of BBB-D, tumor uptake, and tumor-to-brain ratio after intracarotid injection of boron compounds. CONCLUSION: Our findings provide important information for establishing an optimal treatment protocol when intracarotid injection with BPA after BBB-D is applied in clinical boron neutron capture therapy.
Animals↗
Development and evaluation of MRI based Bayesian image reconstruction methods for PET.
A maximum a posteriori algorithm, which incorporates correlated magnetic resonance images into the processing of positron emission tomography reconstruction with the aim of improving image quality was developed. The line site map from MRI a priori is made up of a modified Markov random field or Canny edge detector with Gaussian smoothing filter. It is used in the MAP algorithm by a weighted line site method. We evaluate and compare the performance of these reconstruction methods. The results show that the Bayesian methods produce reconstructed images with less noise and better spatial resolution than those produced by the maximum likelihood-expectation maximization method.
Algorithms↗
Microautoradiography of [123I]ADAM in mice treated with fluoxetine and serotonin reuptake inhibitors.
A radiopharmaceutical, (123)I-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ([(123)I]ADAM), has been developed recently for evaluation of how serotonin transporters (SERT) function in the brain. However, the detailed biodistribution and specific binding in certain brain areas are not well investigated. In this study, both phosphor plate imaging and microautoradiography were applied to explore the binding characteristics of [(123)I]ADAM in SERT neurons. The effect of two psychotropics and one narcotic on the binding of [(123)I]ADAM to SERT was also studied. Fluoxetine and desipramine, both are psychotropics and specific SERT ligands and decreased the affinity of [(123)I]ADAM, while p-chloroamphetamine (PCA), a narcotic, destroyed most of serotonergic neurons, as well as reducing the concentration of serotonin and the number of SERT in the brain as shown by the biodistribution of [(123)I]ADAM. Significant and selective accumulation of [(123)I]ADAM in the areas from midbrain to brain stem in normal mice with maximum target-to-background ratio was found at 90 minutes postinjection. A rapid clearance of [(131)I]ADAM at 120 minutes postinjection was found in the CA1, CA3 and ThN brain areas. In addition, the inhibition effect on binding ability of [(123)I]ADAM to SERT by the psychotropics and the narcotic was found to have the order of: PCA > fluoxetine > desipramine.
Adrenergic Uptake Inhibitors↗
In vivo quantification by SPECT of [123I] ADAM bound to serotonin transporters in the brains of rabbits.
BACKGROUND: A novel radioiodine ligand [(123)I] ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine) has been suggested as a promising serotonin transporter (SERT) imaging agent for the central nervous system. In this study, the biodistribution of SERTs in the rabbit brain was investigated using [(123)I] ADAM and mapping images of the same animal produced by both single-photon emission computed tomography (SPECT) and microautoradiography. A semiquantification method was adopted to deduce the optimum time for SPECT imaging, whereas the input for a simple fully quantitative tracer kinetic model was provided from arterial blood sampling data. METHODS: SPECT imaging was performed on female rabbits postinjection of 185 MBq [(123)I] ADAM. The time-activity curve obtained from the SPECT images was used to quantify the SERTs, for which the binding potential was calculated from the kinetic modeling of [(123)I] ADAM. The kinetic data were analyzed by the nonlinear least squares method. The effects of the selective serotonin reuptake inhibitors fluoxetine and p-chloroamphetamine (PCA) on rabbits were also evaluated. After scanning, the same animal was sacrificed and the brain was removed for microautoradiography. Regions-of-interest were analyzed using both SPECT and microautoradiography images. The SPECT images were coregistered manually with the corresponding microautoradiography images for comparative study. RESULTS: During the time interval 90-100 min postinjection, the peak specific binding levels in different brain regions were compared and the brain stem was shown to have the highest activity. The target-to-background ratio was 1.89+/-0.02. Similar studies with fluoxetine and PCA showed a background level for SERT occupation. Microautoradiography demonstrated a higher level of anatomical details of the [(123)I] ADAM distribution than that obtained by SPECT imaging of the rabbit brain. CONCLUSION: SPECT imaging of the rabbit brain with [(123)I] ADAM showed high affinity, high specificity, and favorable kinetics. The time-activity curve showed that the accumulation of the [(123)I] ADAM in the brain stem reached a maximum between 90 and 100 min postinjection. The microautoradiography provides high-resolution images of the rabbit brain. Our results for the [(123)I] ADAM biodistribution in the rabbit brains demonstrate that this new radioligand is suitable as a selective SPECT imaging agent for SERTs.
Algorithms↗
Evaluation of 4-borono-2-18F-fluoro-L-phenylalanine-fructose as a probe for boron neutron capture therapy in a glioma-bearing rat model.
UNLABELLED: L-p-Boronophenylalanine (BPA) has been applied as a potential boron carrier for the treatment of malignant glioma in clinical boron neutron capture therapy (BNCT) since 1994. To provide the pharmacokinetics of BPA for clinical use of BNCT in Taiwan, 4-borono-2-(18)F-fluoro-L-phenylalanine-fructose ((18)F-FBPA-Fr) was synthesized and the biologic characteristics of this radiotracer in glioma-bearing rats were investigated. METHODS: Radiolabeled (18)F-F(2) was produced via the (20)Ne(d,alpha)(18)F reaction, and (18)F-acetyl hypofluorite ((18)F-AcOF) was generated by passing (18)F-F(2) through a column filled with tightly packed KOAc/HOAc powder. The effluent containing (18)F-AcOF was bubbled into BPA in trifluoroacetic acid, then purified by high-performance liquid chromatography, and further composited with fructose to afford (18)F-FBPA-Fr. Male Fischer 344 rats bearing F98 glioma in the left brain were used for biologic studies. The biodistribution of BPA-Fr and (18)F-FBPA-Fr was determined, and the microautoradiography and PET imaging of (18)F-FBPA-Fr were performed, on the 13th day after tumor inoculation. RESULTS: The radiochemical purity of (18)F-FBPA-Fr was >97% and the radiochemical yield of (18)F-FBPA-Fr was 20%-25%. In glioma-bearing rats, the accumulation ratios of B-10 for glioma-to-normal brain were 2.05, 1.86, 1.24, and 1.10 at 0.5, 1, 2, and 4 h, respectively, after administration of 43 mg BPA-Fr via the tail vein. The accumulation ratios of (18)F-FBPA-Fr for glioma-to-normal brain were 3.45, 3.13, 2.61, and 2.02, whereas the tumor-to-heart blood ratios were 1.72, 2.61, 2.00, and 1.93, respectively, for the same time points. The uptake characteristics of BPA-Fr and (18)F-FBPA-Fr in F98 glioma were similar with a maximum at 1 h after the drugs' administration. The results obtained from the biodistribution studies indicated that 0.5-1 h after BPA-Fr injection would be the optimal time for BNCT. Biodistribution, PET images, and brain microautoradiography of (18)F-FBPA-Fr all confirmed this finding. CONCLUSION: (18)F-FBPA-Fr showed specific tumor uptake in F98 glioma-bearing rats and could be used as a probe for BPA-Fr in BNCT. This study provides useful information for the future clinical application of BNCT in brain tumor therapy.
Animals↗