Plasma and intracerebral pharmacokinetics and pharmacodynamics modeling for the acetylcholine releasing effect of ginsenoside Rg1 in mPFC of Aß model rats.

Ginsenoside Rg1 is a major bioactive component of ginseng. Limited information is available regarding Rg1 concentrations in the central neural system and the corresponding relationship of plasma/intracerebral concentrations, and intracerebral effects of Rg1. Awake Aß model rats received a single subcutaneous administration of Rg1. Concentrations of unbound Rg1 and acetylcholine in the brain extracellular fluid and Rg1 in plasma were then determined. An Emax-two compartment pharmacokinetic/pharmacodynamics (PK/PD) model without effect compartment was finally obtained by evaluating three mechanism-based models. The corresponding relationship between the plasma PK and PD of Rg1 can be described as E = 119.05•C/(73.42 + C).[Formula: see text].

Pharmacokinetics of ginsenoside Rg1 in rat medial prefrontal cortex, hippocampus, and lateral ventricle after subcutaneous administration.

The present study aimed to investigate pharmacokinetics of Rg1 in rat medial prefrontal cortex (mPFC), hippocampus (HIP), and lateral ventricle (LV) after subcutaneous injection. For the first time, intracerebral pharmacokinetics of Rg1 was studied in freely moving rats by microdialysis technique. Rg1 concentrations in dialysates were detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and were revised using in vivo probe-recovery in HIP and LV. The pharmacokinetic parameters were then determined using non-compartmental models. Since the in vivo recoveries remained stable in HIP and LV during 9 h dialysis, average recoveries were used to revise dialysate concentrations. After dosing, Rg1 was soon detected in brain extracellular fluid (bECF) and cerebrospinal fluid (CSF). The elimination of Rg1 was significantly slower in mPFC than in HIP and LV, and significantly greater AUC was obtained in mPFC than in HIP. Rg1 kinetics in bECF and CSF indicate that Rg1 can go across the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), and then immediately distribute to learning and memory-related regions in brain, which may lead to rapid pharmacological onset. There may be active transport and target-mediated disposition of Rg1 in the CNS, which need to be further clarified.

Unsupervised deep learning framework for data-driven gating in positron emission tomography.

BACKGROUND: Physiological motion, such as respiratory motion, has become a limiting factor in the spatial resolution of positron emission tomography (PET) imaging as the resolution of PET detectors continue to improve. Motion-induced misregistration between PET and CT images can also cause attenuation correction artifacts. Respiratory gating can be used to freeze the motion and to reduce motion induced artifacts. PURPOSE: In this study, we propose a robust data-driven approach using an unsupervised deep clustering network that employs an autoencoder (AE) to extract latent features for respiratory gating. METHODS: We first divide list-mode PET data into short-time frames. The short-time frame images are reconstructed without attenuation, scatter, or randoms correction to avoid attenuation mismatch artifacts and to reduce image reconstruction time. The deep AE is then trained using reconstructed short-time frame images to extract latent features for respiratory gating. No additional data are required for the AE training. K-means clustering is subsequently used to perform respiratory gating based on the latent features extracted by the deep AE. The effectiveness of our proposed Deep Clustering method was evaluated using physical phantom and real patient datasets. The performance was compared against phase gating based on an external signal (External) and image based principal component analysis (PCA) with K-means clustering (Image PCA). RESULTS: The proposed method produced gated images with higher contrast and sharper myocardium boundaries than those obtained using the External gating method and Image PCA. Quantitatively, the gated images generated by the proposed Deep Clustering method showed larger center of mass (COM) displacement and higher lesion contrast than those obtained using the other two methods. CONCLUSIONS: The effectiveness of our proposed method was validated using physical phantom and real patient data. The results showed our proposed framework could provide superior gating than the conventional External method and Image PCA.

Pharmacokinetic Study of Enteric-Coated Sustained-Release Aspirin Tablets in Healthy Chinese Participants.

Purpose: To study and compare the pharmacokinetic characteristics of enteric-coated sustained-release (EcSr) aspirin tablets with enteric-coated (Ec) aspirin tablets (Bayer S.p.A) in healthy Chinese participants. Patients and Methods: In this open, randomized, single-dose, three-way, crossover study, 18 healthy participants randomly received 100 mg EcSr tablets pre-prandially (a.c.), EcSr tablets post-prandially (p.c.), or Ec tablets a.c. in each period. The concentrations of acetylsalicylic acid (ASA) and salicylic acid (SA) in plasma were determined by the LC-MS/MS method, and the pharmacokinetic parameters were calculated using WinNonlin (version 8.1). Results: The essential PK parameters under the three treatment conditions (ie Ec a.c., EcSr a.c. and EcSr p.c.) were as follows: Cmax, ASA: 758.38±455.34, 222.77±98.04 and 194.54±61.19 ng, Tmax, ASA: 6.75(2,16), 4.5(2,11) and 8.25(5,11) h, T1/2, ASA: 0.43±0.08, 1.44±0.59 and 4.32±10.04 h, AUC0-t, ASA: 1008.88±452.27, 918.04±238.40 and 845.55±183.25 h·ng/mL; Cmax, SA: 6409.38±2098.52, 2863.53±679.73 and 2913.75±853.27ng/mL, Tmax, SA: 7.25(2,24), 10(3.5-14) and 10(7,14) h, T1/2, SA: 2.21±0.46, 2.69±0.72 and 3.51±2.06h, AUC0-t, SA: 29,131.41±9376.23, 27,243.97±7465.16, 27,240.25±7444.67 h·ng/mL. When taking EcSr aspirin tablets, the 90% confidence intervals of the geometric mean ratios (pre-prandial/post-prandial) of AUC0-t, ASA and AUC0-∞, ASA, Cmax, SA, AUC0-t, SA and AUC0-∞, SA were within the range of 80.00%-125.00%. Conclusion: EcSr aspirin tablets showed less inter-individual variation in release and absorption than Ec aspirin tablets, which was well reflected by comparing essential PK parameters. Furthermore, meals had no significant effect on the pharmacokinetics of EcSr aspirin tablets.

The Comparative Bioavailability of Fluticasone and Azelastine Delivered as a Single Fixed Dose Combination (MP-AzeFlu) in Comparison to Two Different Formulations of Azelastine and Fluticasone Propionate Following Intranasal Administration in Healthy Chinese Volunteers.

Objective: Two studies (Study I and Study II) were conducted in healthy Chinese volunteers to confirm that there was no pharmacokinetic drug interaction between AZE and FLU in MP-AzeFlu. The secondary objective was to evaluate the pharmacokinetic parameters of MP-AzeFlu compared with the commercially available mono-components. Methods: Both studies were a randomized, open-label, three-period, six-sequence, single-dose cross-over trial (William's design) conducted at Beijing Hospital (Beijing, China) in September and October of 2019 in 30 healthy adult male and female volunteers. The natural log transformed parameters: AUC0-tlast, AUC0-∞ and Cmax were analyzed. Results: The comparison of PK parameters between MP-AzeFlu and Aze (commercially available) showed that the LS mean ratios (90% CI) values for, AUC0-tlast, AUC 0-∞ and Cmax were 100.29% (94.31-106.66%), 100.76% (94.60-107.32%) and 93.14% (81.47-106.48%). The comparison of PK parameters between MP-AzeFlu and Flu (commercially available) for the bioavailability evaluation showed that the LS mean ratios (90% CI) values for, AUC0-tlast, AUC 0-∞ and Cmax were 83.48% (69.81-99.82%), 100.19% (87.34-114.94%) and 81.91% (68.50-97.95%). Conclusion: The study results confirm that neither the FLU or the AZE component in the combination product (MP-AzeFlu), nor the existing qualitative and quantitative differences in the formulation between the currently marketed AZE and FLU mono-product, display significant potential to impact the systemic exposure of AZE or FLU in Chinese subjects.

A quantitative study of motion estimation methods on 4D cardiac gated SPECT reconstruction.

PURPOSE: Motion-compensated temporal processing can have a major impact on improving the image quality in gated cardiac single photon emission computed tomography (SPECT). In this work, we investigate the effect of different optical flow estimation methods for motion-compensated temporal processing in gated SPECT. In particular, we explore whether better motion estimation can substantially improve reconstructed image quality, and how the estimated motion would compare to the ideal case of known motion in terms of reconstruction. METHODS: We consider the following three methods for obtaining the image motion in 4D reconstruction: (1) the Horn-Schunck optical flow equation (OFE) method, (2) a recently developed periodic OFE method, and (3) known cardiac motion derived from the NURBS-based cardiac-torso (NCAT) phantom. The periodic OFE method is used to exploit the inherent periodic nature in cardiac gated images. In this method, the optical flow in a sequence is modeled by a Fourier harmonic representation, which is then estimated from the image data. We study the impact of temporal processing on 4D reconstructions when the image motion is obtained with the different methods above. For quantitative evaluation, we use simulated imaging with multiple noise realizations from the NCAT phantom, where different patient geometry and lesion sizes are also considered. To quantify the reconstruction results, we use the following measures of reconstruction accuracy and defect detection in the myocardium: (1) overall error level in the myocardium, (2) regional accuracy of the left ventricle (LV) wall, (3) accuracy of regional time activity curves of the LV, and (4) perfusion defect detectability with a channelized Hotelling observer (CHO). In addition, we also examine the effect of noise on the distortion in the reconstructed LV wall shape by detecting its contours. As a preliminary demonstration, these methods are also tested on two sets of clinical acquisitions. RESULTS: For the different quantitative measures considered, the periodic OFE further improved the reconstruction accuracy of the myocardium compared to OFE in 4D reconstruction; its improvement in reconstruction almost matched that of the known motion. Specifically, the overall mean-squared error in the myocardium was reduced by over 20% with periodic OFE; with noise level fixed at 10%, the regional bias on the LV was reduced from 20% (OFE) to 14% (periodic OFE), compared to 11% by the known motion. In addition, the CHO results show that there was also improvement in lesion detectability with the periodic OFE. The regional time activity curves obtained with the periodic OFE were also observed to be more consistent with the reference; in addition, the contours of the reconstructed LV wall with the periodic OFE were demonstrated to show less degree of variations among different noise realizations. Such improvements were also consistent with the results obtained from the clinical acquisitions. CONCLUSIONS: Use of improved optical flow estimation can further improve the accuracy of reconstructed images in 4D. The periodic OFE method not only can achieve improvements over the traditional OFE, but also can almost match that of the known motion in terms of the several quality measures considered.

Deep Learning Based Joint PET Image Reconstruction and Motion Estimation.

Respiratory motion is one of the main sources of motion artifacts in positron emission tomography (PET) imaging. The emission image and patient motion can be estimated simultaneously from respiratory gated data through a joint estimation framework. However, conventional motion estimation methods based on registration of a pair of images are sensitive to noise. The goal of this study is to develop a robust joint estimation method that incorporates a deep learning (DL)-based image registration approach for motion estimation. We propose a joint estimation framework by incorporating a learned image registration network into a regularized PET image reconstruction. The joint estimation was formulated as a constrained optimization problem with moving gated images related to a fixed image via the deep neural network. The constrained optimization problem is solved by the alternating direction method of multipliers (ADMM) algorithm. The effectiveness of the algorithm was demonstrated using simulated and real data. We compared the proposed DL-ADMM joint estimation algorithm with a monotonic iterative joint estimation. Motion compensated reconstructions using pre-calculated deformation fields by DL-based (DL-MC recon) and iterative (iterative-MC recon) image registration were also included for comparison. Our simulation study shows that the proposed DL-ADMM joint estimation method reduces bias compared to the ungated image without increasing noise and outperforms the competing methods. In the real data study, our proposed method also generated higher lesion contrast and sharper liver boundaries compared to the ungated image and had lower noise than the reference gated image.

Pharmacokinetics, Pharmacodynamics, and Tolerability of Opicapone in Healthy Chinese and Caucasian Subjects: An Open-Label, Single-Center, Phase 1 Study.

INTRODUCTION: This study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple doses of opicapone (OPC) in healthy Chinese and Caucasian subjects. METHODS: In this open-label, single-center, phase 1 study, eligible Chinese subjects received one of three OPC doses (25, 50, or 100 mg), and Caucasian subjects received either 25 or 50 mg of OPC. All subjects were administered a single dose of OPC, whereas subjects in the 50-mg OPC group continued to receive once-daily doses of 50 mg OPC for 10 days. The primary endpoint was to evaluate and compare the plasma concentrations and PK parameters of OPC and its main metabolite, and erythrocyte-soluble catechol-O-methyltransferase (S-COMT) activity in Chinese subjects with that of Caucasian subjects. The secondary endpoint was to evaluate the safety of OPC in Chinese subjects. The estimated results for geometric mean ratios (GMRs) were evaluated with the standard bioequivalence (BE) limits between 80% and 125% to evaluate the ethnic differences. All statistical analyses were performed using SAS version 9.4. RESULTS: In total, 70 subjects (45 Chinese, 25 Caucasian) were enrolled; the majority of them were male (85.7%). The plasma exposure of both OPC and BIA 9-1103 increased in an approximately dose-proportional manner in both populations. Maximum S-COMT inhibition ranged from 79% to 95% after a single dose and was about 94% after a 10-day once-daily regimen in both populations. The point estimates of GMRs (Chinese/Caucasian) and 90% CI, except Cmax in 25-mg and 50-mg OPC groups, for PK and PD parameters were within 80% to 125%. Furthermore, no new risks or safety concerns associated with OPC were identified, indicating a tolerable safety profile in healthy Chinese subjects. CONCLUSION: Ethnicity had no significant impact on PK and PD parameters after single or multiple doses of OPC, and OPC was safe and tolerable in healthy Chinese subjects. TRIAL REGISTRATION: ChiCTR number, CTR20192230.

Sensitive detection of Shiga Toxin 2 and some of its variants in environmental samples by a novel immuno-PCR assay.

Shiga toxin-producing Escherichia coli (STEC) in the environment has been reported frequently. However, robust detection of STEC in environmental samples remains difficult because the numbers of bacteria in samples are often below the detection threshold of the method. We developed a novel and sensitive immuno-PCR (IPCR) assay for the detection of Shiga toxin 2 (Stx2) and Stx2 variants. The assay involves immunocapture of Stx2 at the B subunit and real-time PCR amplification of a DNA marker linked to a detection antibody recognizing the Stx2 A subunit. The qualitative detection limit of the assay is 0.1 pg/ml in phosphate-buffered saline (PBS), with a quantification range of 10 to 100,000 pg/ml. The IPCR method was 10,000-fold more sensitive than an analogue conventional enzyme-linked immunosorbent assay (ELISA) in PBS. Although the sensitivity of the IPCR for detection of Stx2 was affected by environmental sample matrices of feces, feral swine colons, soil, and water from watersheds, application of the IPCR assay to 23 enriched cultures of fecal, feral swine colon, soil, and watershed samples collected from the environment revealed that the IPCR detected Stx2 in all 15 samples that were shown to be STEC positive by real-time PCR and culture methods, demonstrating a 100% sensitivity and specificity. The modification of the sandwich IPCR we have described in this study will be a sensitive and specific screening method for evaluating the occurrence of STEC in the environment.

A pilot study for colorectal carcinoma screening by instant metabolomic profiles using conductive polymer spray ionization mass spectrometry.

BACKGROUND: The rapid and accurate discrimination of colorectal carcinoma (CRC) and polyps at the molecular level enables early intervention of CRC, which can greatly improve the 5-year survival rate of patients. Here we reported the potential of conductive polymer spray ionization mass spectrometry (CPSI-MS) in successfully screening CRC according to the serum metabolic profile. METHODS: Trace intravenous blood (50 µL) was collected from 60 colorectal carcinoma (CRC) and 60 polyp patients, respectively. After centrifugation, serum (2 µL) was loaded onto the tip of conductive polymer to form a dried serum spot. When the 5 µL methanol-water (1:1, v/v) extraction solvent was spiked onto the dried serum spot followed with +4.5 kV high voltage applied on the polymer tip, the extracted components will be ionized and carried into the MS system for direct metabolic profiling. FINDINGS: There were 51 metabolites discovered to be significantly changed in CRC serum compared to polyps. Combining these metabolites as the characteristic panel, the ideal diagnostic performance was achieved by Lasso regression model with the accuracy of 88.3%. INTERPRETATION: This pilot study demonstrated the potential of CPSI-MS as a cost-effective tool in large-scale CRC screening in the high-risk population.

Anatomically aided PET image reconstruction using deep neural networks.

PURPOSE: The developments of PET/CT and PET/MR scanners provide opportunities for improving PET image quality by using anatomical information. In this paper, we propose a novel co-learning three-dimensional (3D) convolutional neural network (CNN) to extract modality-specific features from PET/CT image pairs and integrate complementary features into an iterative reconstruction framework to improve PET image reconstruction. METHODS: We used a pretrained deep neural network to represent PET images. The network was trained using low-count PET and CT image pairs as inputs and high-count PET images as labels. This network was then incorporated into a constrained maximum likelihood framework to regularize PET image reconstruction. Two different network structures were investigated for the integration of anatomical information from CT images. One was a multichannel CNN, which treated PET and CT volumes as separate channels of the input. The other one was multibranch CNN, which implemented separate encoders for PET and CT images to extract latent features and fed the combined latent features into a decoder. Using computer-based Monte Carlo simulations and two real patient datasets, the proposed method has been compared with existing methods, including the maximum likelihood expectation maximization (MLEM) reconstruction, a kernel-based reconstruction and a CNN-based deep penalty method with and without anatomical guidance. RESULTS: Reconstructed images showed that the proposed constrained ML reconstruction approach produced higher quality images than the competing methods. The tumors in the lung region have higher contrast in the proposed constrained ML reconstruction than in the CNN-based deep penalty reconstruction. The image quality was further improved by incorporating the anatomical information. Moreover, the liver standard deviation was lower in the proposed approach than all the competing methods at a matched lesion contrast. CONCLUSIONS: The supervised co-learning strategy can improve the performance of constrained maximum likelihood reconstruction. Compared with existing techniques, the proposed method produced a better lesion contrast versus background standard deviation trade-off curve, which can potentially improve lesion detection.

Safety, Tolerability, and Pharmacokinetics of Ibuprofenamine Hydrochloride Spray (NSAIDs), a New Drug for Rheumatoid Arthritis and Osteoarthritis, in Healthy Chinese Subjects.

BACKGROUND: Ibuprofenamine hydrochloride spray is novel transdermal nonsteroidal anti-inflammatory drugs (NSAIDs), under clinical development for the treatment of Rheumatoid Arthritis and Osteoarthritis as a novel transdermal drug. METHODS: A single and multiple ascending dose study investigated the safety, tolerability and pharmacokinetics of ibuprofenamine hydrochloride in healthy Chinese subjects. A total of 34 subjects (single-dose study: 34 subjects and multiple-dose study: 20 subjects) were involved in the trial. In the single-dose study, subjects were assigned to one of the four groups received 35, 70, 140, 280 mg. In the 70 mg and 140 mg treatment groups, subjects received one dose on the first day and twice a day from day 6 to 12. The starting dose was determined considering the no observed adverse effect level based on preclinical studies, and the dose escalations in subsequent cohorts were decided based on safety, tolerability, and pharmacokinetic data from previous dose cohorts. RESULTS: After a single dose, both ibuprofenamine and ibuprofen plasma exposure showed a more than dose-proportional increase across a dose range of 35-280 mg. After multiple dosing, both ibuprofenamine and ibuprofen steady-state exposure increased obviously more than dose-proportional manner across the evaluated dose range (twice a day for 7 days) resulted in obvious accumulation. Single or multiple doses of ibuprofenamine hydrochloride were generally well tolerated and no obvious skin irritation was observed. CONCLUSION: Ibuprofenamine hydrochloride exhibited a safety and pharmacokinetic profile that supports its future investigation as a potential therapeutic for Rheumatoid Arthritis and Osteoarthritis.

Effects of electron-beam irradiation on volatile flavor compounds of salmon fillets by the molecular sensory science technique.

Vacuum-packed salmon was treated by electron beam irradiation preservation technology, to study the effects of electron-beam irradiation on odor active compounds of salmon by two types of methods for extraction: headspace-solid phase micro extraction (HS-SPME) and solvent assisted flavor evaporation (SAFE). Volatile flavor compounds examined by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-olfactometry (GC-O), combined with aroma extract dilution method (AEDA) and odor activity value (OAV) for identification of important odorants. In addition, the correlation between sensory attributes and volatile compounds of salmon irradiated at different doses was analyzed by partial least squares regression (PLSR). The results showed that after SPME and SAFE extraction, a total of 49 and 70 volatile flavor compounds were detected in salmon before and after electron beam irradiation. AEDA and OAV were further identified, among which 10 odorants were considered as important volatile flavor compounds and played an important role in the formation of aroma contours such as meaty, fatty, and grassy in salmon. In addition, methanethiol, 3-methyl butyraldehyde, 3-methyl propyl aldehyde, dimethyl disulfide, dimethyl trisulfide, and 2-pentyl furan were identified as the important volatile flavor compounds in salmon irradiated with 4 kGy, and were also the unique compounds that constituted irradiation off-odor. In general, salmon irradiated with 1 kGy showed the best aroma profile. PRACTICAL APPLICATION: SPME and SAFE were used as two types of extraction methods for volatile compounds of salmon, which complemented each other. Additionally, combined with AEDA and OAV, characteristic flavor compounds were identified. Furthermore, the odor fingerprint of salmon with E-beam irradiation was established for the first time.

The Impact of ABCB1 and CES1 Polymorphisms on Dabigatran Pharmacokinetics in Healthy Chinese Subjects.

Dabigatran is a novel direct oral anticoagulant agent, whose plasma concentration is closely related to bleeding risk. Genetic polymorphisms can affect the level of plasma dabigatran. The purpose of this study was to understand the relationship between dabigatran-related genes and the plasma level of dabigatran in healthy Chinese subjects after taking a single oral dose. This study was performed with a single-center, single-dose, randomized, open-label, and four-period crossover trial design under both fasting and fed conditions. A total of 106 eligible healthy subjects were enrolled in the study and 104 were genotyped. One-way analysis of variance (ANOVA) was used to compare pharmacokinetic parameters among different genotypes and linear regression was applied to explore the multiplicative interaction between variables. In this study, we found that the genotype frequencies of CES1 rs2244613 and CES1 rs8192935 were significantly different between Chinese and Caucasians, but the genotype frequencies of ABCB1 rs1045642 and ABCB1 rs4148738 were similar in both populations. CES1 rs8192935 were associated with the peak concentration of dabigatran. There was no significant gender difference in the exposure level of dabigatran. Furthermore, food significantly delayed the absorption of dabigatran but had little effect on Cmax and AUC0-∞.

Pharmacokinetics of Opicapone and Its Metabolites in Healthy White and Chinese Subjects.

Opicapone (OPC) is a third-generation catechol-O-methyltransferase inhibitor developed to treat Parkinson disease and motor fluctuations. This open-label, single-center, phase 1 study aimed to evaluate the pharmacokinetics (PK) of OPC and its metabolites when administered as single and multiple doses in healthy White and Chinese subjects. The study enrolled a total of 30 White and Chinese healthy subjects, equally balanced among groups. The first dose of OPC was administered orally as a single dose of 50 mg on day 1, followed by a 10-day once-daily treatment from day 5 to day 14. Plasma concentrations of OPC and its metabolites were measured at 0 to 72 and 0 to 144 hours after dosing for single dose and multiple dose, respectively. Moreover, urine concentrations of OPC and its metabolite were measured 0 to 24 hours after dosing. PK parameters were derived from noncompartmental analysis. Geometric mean ratios and 90% confidence intervals for the main PK parameters were conducted to evaluate the ethnic difference between White and Chinese subjects. The plasma and urine exposure of OPC and its metabolites in Chinese subjects were similar to those in White subjects. These results indicated that ethnicity had no significant impact on PK of OPC between White and Chinese subjects.

Motion correction of respiratory-gated PET images using deep learning based image registration framework.

Artifacts caused by patient breathing and movement during PET data acquisition affect image quality. Respiratory gating is commonly used to gate the list-mode PET data into multiple bins over a respiratory cycle. Non-rigid registration of respiratory-gated PET images can reduce motion artifacts and preserve count statistics, but it is time consuming. In this work, we propose an unsupervised non-rigid image registration framework using deep learning for motion correction. Our network uses a differentiable spatial transformer layer to warp the moving image to the fixed image and uses a stacked structure for deformation field refinement. Estimated deformation fields were incorporated into an iterative image reconstruction algorithm to perform motion compensated PET image reconstruction. We validated the proposed method using simulation and clinical data and implemented an iterative image registration approach for comparison. Motion compensated reconstructions were compared with ungated images. Our simulation study showed that the motion compensated methods can generate images with sharp boundaries and reveal more details in the heart region compared with the ungated image. The resulting normalized root mean square error (NRMS) was 24.3 ± 1.7% for the deep learning based motion correction, 31.1 ± 1.4% for the iterative registration based motion correction, and 41.9 ± 2.0% for ungated reconstruction. The proposed deep learning based motion correction reduced the bias compared with the ungated image without increasing the noise level and outperformed the iterative registration based method. In the real data study, both motion compensated images provided higher lesion contrast and sharper liver boundaries than the ungated image and had lower noise than the reference gate image. The contrast of the proposed method based on the deep neural network was higher than the ungated image and iterative registration method at any matched noise level.

Generative adversarial network based regularized image reconstruction for PET.

Positron emission tomography (PET) is an ill-posed inverse problem and suffers high noise due to limited number of detected events. Prior information can be used to improve the quality of reconstructed PET images. Deep neural networks have also been applied to regularized image reconstruction. One method is to use a pretrained denoising neural network to represent the PET image and to perform a constrained maximum likelihood estimation. In this work, we propose to use a generative adversarial network (GAN) to further improve the network performance. We also modify the objective function to include a data-matching term on the network input. Experimental studies using computer-based Monte Carlo simulations and real patient datasets demonstrate that the proposed method leads to noticeable improvements over the kernel-based and U-net-based regularization methods in terms of lesion contrast recovery versus background noise trade-offs.

Motion-compensated image reconstruction vs postreconstruction correction in respiratory-binned SPECT with standard and reduced-dose acquisitions.

PURPOSE: Cardiac perfusion images in single-photon emission computed tomography (SPECT) can suffer from respiratory motion blur. We investigated a reconstruction approach for correcting respiratory motion in respiratory-binned acquisitions and assessed the benefit of this approach in both standard dose and reduced dose. METHODS: We modeled the acquired data from different respiratory bins by a joint probability distribution which was parameterized with respect to a common reference bin. The acquired data from all the respiratory bins were then utilized simultaneously for determining the source distribution in the reference bin using maximum a posteriori (MAP) estimation. We evaluated this approach with simulated imaging data and ten sets of clinical acquisitions, and compared it with a postreconstruction motion correction approach developed previously. We quantified the accuracy of the reconstruction results both at standard dose and with imaging dose reduced by 50% and 75%, respectively. RESULTS: The proposed motion-compensated reconstruction (MCR) approach led to improved reconstruction of the myocardium in terms of both noise level and LV wall resolution. Compared to traditional acquisition (without motion correction), the proposed approach reduced the mean squared error of the image intensity in the myocardium by 27.59%, 20.59%, and 12.05% at full, half-, and quarter dose, respectively; the LV resolution, quantified by the full width at half-maximum (FWHM), was improved by 17.34%, 14.35%, and 12.95% at full, half-, and quarter dose, respectively; in addition, the proposed approach also improved the perfusion defect detectability at both full dose and reduced dose. Furthermore, with motion correction, the reconstruction results obtained at half-dose were comparable to that obtained at full dose without correction. Similar improvements were also demonstrated in the clinical acquisitions at different dose levels. CONCLUSIONS: Respiratory motion correction in perfusion SPECT can improve the reconstruction of the myocardium at both standard and reduced dose. At half-dose, the results obtained with motion correction are comparable to that of traditional reconstruction obtained at full dose. MCR can be more accurate than postreconstruction correction.

Determination of quetiapine in human plasma by LC-MS/MS and its application in a bioequivalence study.

A selective, sensitive and simple high performance liquid chromatography tandem mass spectrometric (HPLC-MS/MS) method for determining quetiapine in human plasma was developed and validated. One-step protein precipitation with acetonitrile was used to pretreat plasma samples. Carbamazepine was used as internal standard. An automated liquid handling workstation with 96-well protein precipitate plate was used to facilitate the process. The chromatographic separation was achieved on a Waters Xbridge C18 column (3.5µm, 2.1mm×50mm). Gradient elution was set with a mobile phase of acetonitrile/water (containing 10mM ammonium acetate and 0.1% formic acid).The flow rate was 0.4mL/min and total analytical run time was 3min. The analysis was conducted using a triple quadrupole tandem mass spectrometer with an electrospray ionization source operating in positive ion mode. The multiple reaction monitoring of transition were m/z 384.2→253.1 for quetiapine and m/z 237.0→194.0 for carbamazepine, respectively. The linear concentration range for the standard curve of quetiapine was 0.5-400ng/mL for a 5µL injection of the pretreated sample (original plasma sample, 50µL). The intra-day and inter-day accuracy and precision were all less than 15%. The method was successfully used in a bioequivalence study comparing two quetiapine extended-release tablets in Chinese volunteers.

4-D Reconstruction With Respiratory Correction for Gated Myocardial Perfusion SPECT.

Cardiac single photon emission computed tomography (SPECT) images are known to suffer from both cardiac and respiratory motion blur. In this paper, we investigate a 4-D reconstruction approach to suppress the effect of respiratory motion in gated cardiac SPECT imaging. In this approach, the sequence of cardiac gated images is reconstructed with respect to a reference respiratory amplitude bin in the respiratory cycle. To combat the challenge of inherent high-imaging noise, we utilize the data counts acquired during the entire respiratory cycle by making use of a motion-compensated scheme, in which both cardiac motion and respiratory motion are taken into account. In the experiments, we first use Monte Carlo simulated imaging data, wherein the ground truth is known for quantitative comparison. We then demonstrate the proposed approach on eight sets of clinical acquisitions, in which the subjects exhibit different degrees of respiratory motion blur. The quantitative evaluation results show that the 4-D reconstruction with respiratory correction could effectively reduce the effect of motion blur and lead to a more accurate reconstruction of the myocardium. The mean-squared error of the myocardium is reduced by 22%, and the left ventricle (LV) resolution is improved by 21%. Such improvement is also demonstrated with the clinical acquisitions, where the motion blur is markedly improved in the reconstructed LV wall and blood pool. The proposed approach is also noted to be effective on correcting the spill-over effect in the myocardium from nearby bowel or liver activities.