Low-Dose CT Image Synthesis for Domain Adaptation Imaging Using a Generative Adversarial Network With Noise Encoding Transfer Learning.

Deep learning (DL) based image processing methods have been successfully applied to low-dose x-ray images based on the assumption that the feature distribution of the training data is consistent with that of the test data. However, low-dose computed tomography (LDCT) images from different commercial scanners may contain different amounts and types of image noise, violating this assumption. Moreover, in the application of DL based image processing methods to LDCT, the feature distributions of LDCT images from simulation and clinical CT examination can be quite different. Therefore, the network models trained with simulated image data or LDCT images from one specific scanner may not work well for another CT scanner and image processing task. To solve such domain adaptation problem, in this study, a novel generative adversarial network (GAN) with noise encoding transfer learning (NETL), or GAN-NETL, is proposed to generate a paired dataset with a different noise style. Specifically, we proposed a method to perform noise encoding operator and incorporate it into the generator to extract a noise style. Meanwhile, with a transfer learning (TL) approach, the image noise encoding operator transformed the noise type of the source domain to that of the target domain for realistic noise generation. One public and two private datasets are used to evaluate the proposed method. Experiment results demonstrated the feasibility and effectiveness of our proposed GAN-NETL model in LDCT image synthesis. In addition, we conduct additional image denoising study using the synthesized clinical LDCT data, which verified the merit of the proposed synthesis in improving the performance of the DL based LDCT processing method.

Comparison of organ and effective dose estimations from different Monte Carlo simulation-based software methods in infant CT and comparison with direct phantom measurements.

PURPOSE: Computational dosimetry software is routinely used to evaluate the organ and effective doses from computed tomography (CT) examinations. Studies have shown a significant variation in dose estimates between software in adult cohorts, and few studies have evaluated software for pediatric dose estimates. This study aims to compare the primary organ and effective doses estimated by four commercially available CT dosimetry software to thermoluminescent dosimeter (TLD) measurements in a 1-year-old phantom. METHODS: One hundred fifteen calibrated LiF (Mg, Cu, P)-TLD 100-H chips were embedded within an anthropomorphic phantom representing a 1-year-old child at positions that matched the approximate location of organs within an infant. The phantom was scanned under three protocols, each with whole-body coverage. The mean absorbed doses from 25 radiosensitive organs and skeletal tissues were determined from the TLD readings. Effective doses for each of the protocols were subsequently calculated using ICRP 103 formalism. Dose estimates by the four Monte Carlo-based dose calculation systems were determined and compared to the directly measured doses. RESULTS: Most organ doses determined by computation dosimetry software aligned to phantom measurements within 20%. Additionally, comparisons between effective doses are calculated using computational and direct measurement methods aligned within 20% across the three protocols. Significant variances were found in bone surface dose estimations among dosimetry methods, likely caused by differences in bone tissue modeling. CONCLUSION: All four-dosimetry software evaluated in this study provide adequate primary organ and effective dose estimations. Users should be aware, however, of the possible estimated uncertainty associated with each of the programs.

A review of current imaging techniques used for the detection of occult bony fractures in young children suspected of sustaining non-accidental injury.

Non-accidental injuries remain a leading cause of preventable morbidity and mortality in young children. The accurate identification of the full spectrum of injuries in children presenting with suspected abuse is essential to ensure the appropriate protective intervention is taken. The identification of occult bone fractures in this cohort is important as it raises the level of concern about the mechanism of injury and maintaining the child's safety. Radiographic imaging remains the modality of choice for skeletal assessment; however, current studies report concerns regarding the ability of radiographs to detect certain fractures in the acute stage. As such, alternative modalities for the detection of fractures have been proposed. This article reviews the current literature regarding fracture detectability and radiation dose burden of imaging modalities currently used for the assessment of occult bony injury in young children in whom non-accidental injury is suspected.

Characterisation of out-of-field dose at shallow depths for external beam radiotherapy: implications for eye lens dose.

Re-evaluation of the eye lens radio-sensitivity by the ICRP in 2011 resulted in a significant reduction of the threshold for lens opacities from 8 Gy to 0.5 Gy. This has led to an increase in concern for eye lens doses from treatment sites further from the eye than previously considered. The aim of this study was to examine the out-of-field dose far from the field edge and develop an effective method to accurately characterise the constituent components of this dose at varying depths. Dose profile scans using a 0.6 cm3 cylindrical ionisation chamber in a motorised water tank were compared with previous studies and displayed good agreement. At points more than 20 cm from the field edge patient scatter becomes insignificant, and the dose is dominated by head leakage and collimator scatter. Point depth-dose measurements made with a Roos parallel plate chamber in solid water at distances of 52 cm and 76 cm from central axis showed that the highest dose is at the surface. Since the sensitive region of the eye can be as shallow as 3 mm, in vivo measurements carried out with a detector with buildup more than 3 mm water equivalent thickness may be underestimating the dose to the lens. It is therefore recommended that for in vivo measurements for the eye lens further than 20 cm from the field edge the detector should have only 3 mm build-up material over the effective point of measurement.

Characterization of prompt gamma ray emission for in vivo range verification in particle therapy: A simulation study.

In this paper we investigate the emission and detection characteristics of prompt gamma (PG) rays for in vivo range verification during hadron therapy, using Geant4 simulations. Proton, 4He and 12C beams of varying energy are incident on water phantoms. The PG production yield, energy spectral characteristics and spatial correlation with the Bragg Peak (BP) have been quantified. Further, the angular distributions for PG detection with respect to a point-of-reference on the phantom surface have been explored. The temporal properties of PG emission and time-of-flight (TOF) of PG detection have also been investigated in correlation with the changing particle beam range. Our results show that the primary PG rays from nuclear interactions of the primary beam exhibit the closest correlation to the beam range but its signal is significantly masked by the concurrent secondary PG rays, particularly for heavier ions such as carbon ion beams. The PG TOF spectroscopy encodes the essential information of the beam range but requires high time resolution measurements to retrieve it. A hybrid PG detection system to utilize the energy, timing and spatial characteristics of PG rays is desirable for BP tracking in real-time.

Characterization of prompt gamma-ray emission with respect to the Bragg peak for proton beam range verification: A Monte Carlo study.

In this paper we report a Geant4 simulation study to investigate the characteristic prompt gamma (PG) emission in a water phantom for real-time monitoring of the Bragg peak (BP) during proton beam irradiation. The PG production, emission spatial correlation with the BP, and position preference for detection with respect to the BP have been quantified in different PG energy windows as a function of proton pencil-beam energy from 100 to 200MeV. The PG response to small BP shifts was evaluated using a 2cm-thick slab with different human body materials embedded in a water phantom. Our results show that the prominent characteristic PG emissions of 4.44, 5.21 and 6.13MeV exhibit distinctive correlation with the dose deposition curve. The accuracy in BP position identification using these characteristic PG rays is highly consistent as the beam energy increases from 100 to 200MeV. There exists a position preference for PG detection with respect to the BP position, which has a strong dependence on the proton beam energy and PG energies. It was also observed that a submillimeter shift of the BP position can be realized by using PG signals. These results indicate that the characteristic PG signal is sensitive and reliable for BP tracking. Although the maximization of the PG measurement associated with the BP is difficult, it can be optimized with energy and detection position preferences.

Therapeutic analysis of high-dose-rate (192)Ir vaginal cuff brachytherapy for endometrial cancer using a cylindrical target volume model and varied cancer cell distributions.

PURPOSE: To evaluate high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT) in the treatment of endometrial cancer in a cylindrical target volume with either a varied or a constant cancer cell distributions using the linear quadratic (LQ) model. METHODS: A Monte Carlo (MC) technique was used to calculate the 3D dose distribution of HDR VCBT over a variety of cylinder diameters and treatment lengths. A treatment planning system (TPS) was used to make plans for the various cylinder diameters, treatment lengths, and prescriptions using the clinical protocol. The dwell times obtained from the TPS were fed into MC. The LQ model was used to evaluate the therapeutic outcome of two brachytherapy regimens prescribed either at 0.5 cm depth (5.5 Gy × 4 fractions) or at the vaginal mucosal surface (8.8 Gy × 4 fractions) for the treatment of endometrial cancer. An experimentally determined endometrial cancer cell distribution, which showed a varied and resembled a half-Gaussian distribution, was used in radiobiology modeling. The equivalent uniform dose (EUD) to cancer cells was calculated for each treatment scenario. The therapeutic ratio (TR) was defined by comparing VCBT with a uniform dose radiotherapy plan in term of normal cell survival at the same level of cancer cell killing. Calculations of clinical impact were run twice assuming two different types of cancer cell density distributions in the cylindrical target volume: (1) a half-Gaussian or (2) a uniform distribution. RESULTS: EUDs were weakly dependent on cylinder size, treatment length, and the prescription depth, but strongly dependent on the cancer cell distribution. TRs were strongly dependent on the cylinder size, treatment length, types of the cancer cell distributions, and the sensitivity of normal tissue. With a half-Gaussian distribution of cancer cells which populated at the vaginal mucosa the most, the EUDs were between 6.9 Gy × 4 and 7.8 Gy × 4, the TRs were in the range from (5.0)(4) to (13.4)(4) for the radiosensitive normal tissue depending on the cylinder size, treatment lengths, prescription depth, and dose as well. However, for a uniform cancer cell distribution, the EUDs were between 6.3 Gy × 4 and 7.1 Gy × 4, and the TRs were found to be between (1.4)(4) and (1.7)(4). For the uniformly interspersed cancer and radio-resistant normal cells, the TRs were less than 1. The two VCBT prescription regimens were found to be equivalent in terms of EUDs and TRs. CONCLUSIONS: HDR VCBT strongly favors cylindrical target volume with the cancer cell distribution following its dosimetric trend. Assuming a half-Gaussian distribution of cancer cells, the HDR VCBT provides a considerable radiobiological advantage over the external beam radiotherapy (EBRT) in terms of sparing more normal tissues while maintaining the same level of cancer cell killing. But for the uniform cancer cell distribution and radio-resistant normal tissue, the radiobiology outcome of the HDR VCBT does not show an advantage over the EBRT. This study strongly suggests that radiation therapy design should consider the cancer cell distribution inside the target volume in addition to the shape of target.

Fluorine-18 labeling by click chemistry: multiple probes in one pot.

Click chemistry has been widely applied in drug development including radiopharmaceuticals and has shown great advantages. Here we reported a novel strategy for rapid preparation of multiple (18)F labeled PET probes in one pot using the 'Click Reaction' of Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition of terminal alkynes and organic azides (CuAAC). Preliminary results showed its high efficiency and potential for speeding up the preclinical screening of PET probes.

Radiolabeling of RGD peptide and preliminary biological evaluation in mice bearing U87MG tumors.

2-[(18)F]Fluoroethyl azide ([(18)F]FEA) and terminal alkynyl modified propioloyl RGDfK were selected in this study. [(18)F]FEA was prepared by nucleophilic radiofluorination of 2-azidoethyl 4-toluenesulfonate with radiochemical yield of 71 ± 4% (n = 5, decay-corrected). We assessed the various conditions of the CuAAC reaction between [(18)F]FEA and propioloyl RGDfK, which included peptide concentration, reaction time, temperature and catalyst dosage. The (18)F-labeled-RGD peptide ([(18)F]F-RGDfK) could be obtained in 60 min by a two-step radiochemical synthesis route, with total radiochemical yield of 60 ± 2% (n = 3, decay-corrected) through click chemistry. [(18)F]F-RGDfK showed high stability in phosphate buffered saline and new-born calf serum. Micro-PET imaging at 1 h post injection of [(18)F]F-RGDfK showed medium concentration of radioactivity in tumors while much decreased concentration in tumors in the blocking group. These results showed that [(18)F]F-RGDfK obtained by click chemistry maintained the affinity and specificity of the RGDfK peptide to integrin α(v)ß(3). This study provided useful information for peptide radiofluorination by using click chemistry.

Comparison of 16 mm OSU-Nag and COMS eye plaques.

OSU-NAG eye plaques use fewer sources than COMS-plaques of comparable size, and do not employ a Silastic seed carrier insert. Monte Carlo modeling was used to calculate 3D dose distributions for a 16 mm OSU-NAG eye plaque and a 16 mm COMS eye plaque loaded with either Iodine-125 or Cesium-131 brachytherapy sources. The OSU-NAG eye plaque was loaded with eight sources forming two squares, whereas the COMS eye plaque was loaded with thirteen sources approximating three isocentric circles. A spherical eyeball 24.6 mm in diameter and an ellipsoid-like tumor 6 mm in height and 12 mm in the major and minor axes were used to evaluate the doses delivered. To establish a fair comparison, a water seed carrier was used instead of the Silastic seed carrier designed for the traditional COMS eye plaque. Calculations were performed on the dose distributions along the eye plaque axis and the DVHs of the tumor, as well as the 3D distribution. Our results indicated that, to achieve a prescription dose of 85 Gy at 6 mm from the inner sclera edge for a six-day treatment, the OSU-NAG eye plaque will need 6.16 U/source and 6.82U/source for 125I and 131Cs, respectively. The COMS eye plaque will require 4.02 U/source and 4.43 U/source for the same source types. The dose profiles of the two types of eye plaques on their central axes are within 9% difference for all applicable distances. The OSU-NAG plaque delivers about 10% and 12% more dose than the COMS for 125I and 131Cs sources, respectively, at the inner sclera edge, but 6% and 3% less dose at the opposite retina. The DVHs of the tumor for two types of plaques were within 6% difference. In conclusion, the dosimetric quality of the OSU-NAG eye plaque used in eye plaque brachytherapy is comparable to the COMS eye plaque.

Preliminary biological evaluation of ¹²5I-labeled anti-carbonic anhydrase IX monoclonal antibody in the mice bearing HT-29 tumors.

OBJECTIVE: To evaluate ¹²5I-labeled anti-carbonic anhydrase IX monoclonal antibody (¹²5I-MAb) as a novel single-photon emission computed tomography tracer for imaging carbonic anhydrase IX in the mice bearing HT-29 tumors. METHODS: Anti-carbonic anhydrase IX monoclonal antibody was labeled with iodine-125 by the iodogen method. The radiochemical purity of ¹²5I-MAb was measured by radio-thin-layer chromatography. The in-vitro stability of ¹²5I-MAb was determined in PBS (0.05 mol/l, pH 7.4) or new-born calf serum at 37°C, and analyzed by radio-thin-layer chromatography. A biodistribution study and planar imaging were carried out in the mice bearing HT-29 tumors. The expression of CA IX in HT-29 tumors was analyzed by immunohistochemistry. RESULTS: ¹²5I-MAb was obtained with a radiolabeling efficiency of 98%, and showed high stability in PBS and new-born calf serum. Furthermore, the biodistribution study showed specific tumor uptake in the mice bearing HT-29 tumors, and planar imaging with ¹²5I-MAb 48 h post injection showed a high concentration of radioactivity in tumors and a much decreased concentration in tumors in the blocking group. An immunohistochemical analysis showed the expression of CA IX in HT-29 tumors. CONCLUSION: The preliminary biodistribution study and results from planar imaging showed the potential of ¹²5I-MAb as an agent for tumor diagnosis and encouraged further investigation.

Radiosynthesis, biodistribution and micro-SPECT imaging study of dendrimer-avidin conjugate.

Partially acetylated generation five polyamidoamine (PAMAM) dendrimer (G5-Ac) was reacted with biotin and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetria minepentaacetic acid (1B4M-DTPA), respectively to form the complex Bt-G5-Ac-1B4M which was further conjugated with avidin to give the conjugate Av-G5-Ac-1B4M. Then both of the conjugates were radiolabeled with technetium-99m ((99m)Tc), respectively. Their in vitro cellular uptake study shows that the conjugate of Av-G5-Ac-1B4M-(99m)Tc exhibits much higher cellular uptake in HeLa cells than that of Bt-G5-Ac-1B4M-(99m)Tc. Accordingly the following evaluation such as in vitro/in vivo stability, biodistribution and micro-SPECT imaging was observed only for the conjugate of Av-G5-Ac-1B4M-(99m)Tc.

Study on retinal dopamine transporter in form deprivation myopia using the radiopharmaceutical tracer 99mTc-TRODAT-1.

PURPOSE: To investigate the distributions and changes in dopamine transporters (DATs) using Tc-TRODAT-1 ([Tc-(2((2-(((3-(4-chlorophenyl)-8-methyl-8-azabicyclo(3,2,1)-oct-2-yl)-methyl)(2-mercaptoethyl)amino)ethyl)amino)ethane-thiolato(3-)-N2,N2',S2,S2)oxo-(1R-(exo-exo)))]) in form deprivation myopia retina. METHODS: Pigmented guinea pigs aged 3 weeks were randomly assigned into two groups: form-deprivation myopia and normal control group. The test group wore a translucent goggle covering randomly for 4 weeks, and both groups underwent biometric measurement before and after the experiment. Both Micro-single-photon emission computed tomography (SPECT) imaging and ex-vivo autoradiography were performed with the injection of Tc-TRODAT-1 on the 4th week for all the guinea pigs. RESULTS: The retinas were clearly resolved with Tc-TRODAT-1 in both Micro-SPECT imaging and ex-vivo autoradiography. In Micro-SPECT imaging, the ratio of Tc-TRODAT-1 uptake in the myopic retinas (11.55+/-2.80) was 3.64+/-1.40 lower than that in the normal control eyes (15.20+/-1.98, P=0.026, F=2.94, t=2.605), and 2.35+/-1.05 lower than that in the fellow eyes (13.90+/-2.04, P=0.003, t=5.476). In ex-vivo autoradiography, the ratio of Tc-TRODAT-1 uptake in the myopic retina (95.52+/-12.04) was 18.54+/-5.86 lower than in the normal control eyes (114.06+/-7.81, P=0.01, F=0.331, t=3.164), and was 16.95+/-5.78 lower than in the fellow eyes (112.47+/-15.67, P=0.001, t=7.179). CONCLUSION: Tc-TRODAT-1 can be used to trace the distributions and changes in DAT in the retina. DATs in the myopic retinas were lower than that in the fellow and normal control eyes. Radionuclide tracing may provide a new approach in vivo for further studies on the dopamine system in myopia.

Synthesis, biodistribution, and microsingle photon emission computed tomography (SPECT) imaging study of technetium-99m labeled PEGylated dendrimer poly(amidoamine) (PAMAM)-folic acid conjugates.

Three conjugates based on dendrimer PAMAM generation five were synthesized and radiolabeled successfully. To investigate their tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and micro-SPECT imaging were evaluated, respectively. The conjugate of (99m)Tc labeled PEGylated dendrimer PAMAM folic acid conjugate ((99m)Tc-G5-Ac-pegFA-DTPA) shows much higher uptake in KB cancer cells and accumulated more in the tumor area than that of the other two conjugates. The uptake in KB cells depends on the incubation time. The results of in vivo biodistribution agree with the data obtained from micro-SPECT imaging. These studies show that PEGylation of PAMAM dendrimer folic acid conjugate improves the tumor targeting. Folate-conjugated dendrimer maybe developed to be potential radiopharmaceuticals and targeted drug delivery systems.

Radiosynthesis and micro-SPECT imaging of 99mTc-dendrimer poly(amido)-amine folic acid conjugate.

Acetylated (Ac) dendrimer poly(amido)-amine (PAMAM) generation 5 (G5) reacted with folic acid (FA), followed by reacting with 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetria minepentaacetic acid (1B4M DTPA) to form the conjugate of Ac-G5-FA-1B4M DTPA which was further radiolabeled with (99m)Tc. The radiochemical yield is up to 98.9% with excellent in vitro/in vivo stability, rapid blood clearance and certain tumor accumulation which was further confirmed by micro-SPECT imaging study.

Radioactive synthesis and biodistribution study of beta-elemene-99mTc(CO)3 conjugates.

Beta-elemene, (5S,7R,10S)-(-)-(1-methyl-1-vinyl-2,4-diisopropenylcyclohexane), is an anticancer agent from traditional Chinese herbal medicine. Three novel (99m)Tc(CO)(3)-beta-elemene conjugates were synthesized successfully, and compared with beta-elemene exhibited improved water solubility. A biodistribution and micro single photon emission computed tomography image study showed there is a visible accumulation in Lewis lung cancer tumors.

Optimized Collimator Designs for Small Animal SPECT Imaging With a Compact Gamma Camera.

The aim of this study to design optimized pinhole and parallel-hole collimators for the development of a high-resolution microSPECT system using a compact pixelleted scintillation detector. The detector has a field-of-view of 11cm with pixellated crystal elements of 1.0mm pixel size and 1.12mm pixel pitch. The relative resolution and sensitivity advantages of pinhole and parallel-hole collimators for mice and rats imaging were investigated using analytic formulations and Monte Carlo simulations. The optimized collimator designs were obtained by maximizing the system detection efficiency for a given object resolution. The collimator designs were optimized for 140 keV incident gamma photons. Our results indicate that this small field-of-view compact detector fitted with a conventional high-resolution parallel-hole collimator with 4cm hole-length and 1.2mm hex hole-size couldn't provide better than 2 mm resolution for mice and rats imaging. However, a pinhole collimator with 10cm focal length and 1.0mm aperture size with keel-edge design of 0.5mm channel-height can provide the desired resolutions for imaging mice and rats. The relative efficiency is about 2 times higher than that of the parallel-hole collimator for imaging mice at the distance of 3cm from the collimator. In conclusion, pinhole collimator is superior to parallel-hole collimator and requires sophisticated optimal designs with high-resolution compact gamma camera for small animal imaging.