Biomedical subjects

Lei Xing

Publications and source records attributed to Lei Xing.

At least 19 recordsLinked to original sources

PubMed2026

Leveraging Interradiomic Feature Relationships for Enhanced Prediction of Distant Metastasis and Characterization of Heterogeneity in Head and Neck Cancer.

PURPOSE: Distant metastasis remains a major cause of treatment failure in head and neck (HN) cancer, highlighting the need for more accurate early risk stratification. This study developed and validated a deep radiomics framework to characterize tumor heterogeneity from pretreatment computed tomography (CT) images and improve prediction of distant metastasis-free survival (DMFS). METHODS AND MATERIALS: This multicenter study included 3421 patients with HN cancer from 4 cohorts across 12 institutions. Radiomics features were extracted from primary tumors and transformed into OmicsMaps, a structured representation that spatially organizes interfeature relationships to facilitate learning of complex prognostic patterns. A convolutional neural network was trained to derive prognostic signatures, which were integrated with key clinical variables to construct an OmicsMap-clinical fusion model for patient risk stratification. Model performance was assessed using the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) in the CT Images from Large Head and Neck Cohort (RADCURE), HEAD-NECK-RADIOMICS-HN1 (HN1), and Head-Neck-Positron Emission Tomography-Computed Tomography (HN-PET-CT) cohorts. Radiogenomic analyses using RNA-seq data were conducted in the Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) cohort to investigate biological characteristics associated with the imaging-defined risk groups. RESULTS: The OmicsMap achieved C-index values of 0.742, 0.768, and 0.671 in the RADCURE, HN1, and HN-PET-CT cohorts, outperforming the conventional radiomics approach by 5.40%-6.37%. Incorporating clinical variables further improved generalizability, yielding a C-index of 0.864 (HN1) and 0.730 (HN-PET-CT), with time-dependent AUC of 0.727-0.895. The fusion model consistently stratified patients into distinct high- and low-risk groups for both DMFS and overall survival across cohorts (P <.01). Radiogenomic analyses revealed enrichment of immune-related pathways in the low-risk group, whereas the high-risk group exhibited a more aggressive phenotype enriched for proliferation, hypoxia, and epithelial-mesenchymal transition pathways, along with a fibrosis-prone tumor microenvironment characterized by extracellular matrix remodeling. CONCLUSIONS: Modeling interradiomic feature relationships using the OmicsMap representation substantially improves CT-based prediction of DMFS and characterization of tumor heterogeneity in HN cancer, supporting precision risk stratification in clinical oncology.

Journal Article↗

PubMed2026

Perturbation of genes linked to common schizophrenia risk variants identifies cilia programs.

Schizophrenia (SCZ) is a common psychiatric disorder characterized by psychosis, emotional withdrawal, and cognitive deficits. Most SCZ risk variants reside in non-coding regions of the genome and are thought to influence disease risk by modulating gene regulation. However, the target genes, biological pathways, and cell types through which these variants exert their effects remain poorly understood. To address this gap, we employed in vivo CRISPR droplet sequencing (CROP-seq) in the postnatal mouse neocortex. We perturbed 12 SCZ risk genes previously linked to functionally validated risk variants, followed by single-cell RNA sequencing. We identified 3,031 differentially expressed genes (DEGs) that recapitulate transcriptional alterations observed in postmortem SCZ brains. Integrative analysis using DEG clustering, factor analysis, and gene regulatory network inference uncovered convergent gene programs with distinct biological functions and cell type specificity. Notably, ciliary transcriptional programs consistently emerged across analytical frameworks. The primary cilium is a neurocircuit modulating signaling organelle in neurons and glia that remains understudied in SCZ. Perturbation of key contributors to the ciliary transcriptional programs led to significant alterations in ciliary structure, suggesting that SCZ genetic risk factors may influence how brain cells sense and transduce extracellular signals through synapse-independent mechanisms. Together, this study provides the first in vivo characterization of the functional consequence of common variant architecture in SCZ and implicates ciliary dysfunction as a convergent downstream mechanism.

Journal Article↗

PubMed2026

A dual-reporter mouse for therapeutic discovery in Angelman syndrome.

Angelman syndrome is a neurodevelopmental disorder caused by loss of the maternal UBE3A allele, the sole source of UBE3A in mature neurons owing to epigenetic silencing of the paternal allele. Although emerging therapies are being developed to restore UBE3A expression by activating the dormant paternal UBE3A allele, existing mouse models for such preclinical studies have limited throughput and utility, creating bottlenecks for both in vitro therapeutic screening and in vivo characterization. To address this, we developed the Ube3a-INSG dual-reporter knockin mouse, in which an IRES-Nanoluciferase-T2A-Sun1-sfGFP (INSG) cassette was inserted downstream of the endogenous Ube3a stop codon. The INSG model preserves UBE3A protein levels and function while enabling 2 complementary allele-specific readouts: Sun1-sfGFP and Nanoluciferase. We show that Sun1-sfGFP, a nuclear envelope-localized reporter, enables single-cell fluorescence analysis, whole-brain light-sheet imaging, and nuclear quantification by flow cytometry. Further, Nanoluciferase supports high-throughput luminescence assays for sensitive pharmacological profiling in cultured neurons and noninvasive in vivo bioluminescence imaging for pharmacodynamic assessment. By combining scalable screening, cellular analysis, and real-time in vivo monitoring in a single model, the Ube3a-INSG dual-reporter mouse provides a powerful platform to accelerate therapeutic development centered on UBE3A.

Animals↗

PubMed2007

Evaluation of on-board kV cone beam CT (CBCT)-based dose calculation.

On-board CBCT images are used to generate patient geometric models to assist patient setup. The image data can also, potentially, be used for dose reconstruction in combination with the fluence maps from treatment plan. Here we evaluate the achievable accuracy in using a kV CBCT for dose calculation. Relative electron density as a function of HU was obtained for both planning CT (pCT) and CBCT using a Catphan-600 calibration phantom. The CBCT calibration stability was monitored weekly for 8 consecutive weeks. A clinical treatment planning system was employed for pCT- and CBCT-based dose calculations and subsequent comparisons. Phantom and patient studies were carried out. In the former study, both Catphan-600 and pelvic phantoms were employed to evaluate the dosimetric performance of the full-fan and half-fan scanning modes. To evaluate the dosimetric influence of motion artefacts commonly seen in CBCT images, the Catphan-600 phantom was scanned with and without cyclic motion using the pCT and CBCT scanners. The doses computed based on the four sets of CT images (pCT and CBCT with/without motion) were compared quantitatively. The patient studies included a lung case and three prostate cases. The lung case was employed to further assess the adverse effect of intra-scan organ motion. Unlike the phantom study, the pCT of a patient is generally acquired at the time of simulation and the anatomy may be different from that of CBCT acquired at the time of treatment delivery because of organ deformation. To tackle the problem, we introduced a set of modified CBCT images (mCBCT) for each patient, which possesses the geometric information of the CBCT but the electronic density distribution mapped from the pCT with the help of a BSpline deformable image registration software. In the patient study, the dose computed with the mCBCT was used as a surrogate of the 'ground truth'. We found that the CBCT electron density calibration curve differs moderately from that of pCT. No significant fluctuation was observed in the calibration over the period of 8 weeks. For the static phantom, the doses computed based on pCT and CBCT agreed to within 1%. A notable difference in CBCT- and pCT-based dose distributions was found for the motion phantom due to the motion artefacts which appeared in the CBCT images (the maximum discrepancy was found to be approximately 3.0% in the high dose region). The motion artefacts-induced dosimetric inaccuracy was also observed in the lung patient study. For the prostate cases, the mCBCT- and CBCT-based dose calculations yielded very close results (<2%). Coupled with the phantom data, it is concluded that the CBCT can be employed directly for dose calculation for a disease site such as the prostate, where there is little motion artefact. In the prostate case study, we also noted a large discrepancy between the original treatment plan and the CBCT (or mCBCT)-based calculation, suggesting the importance of inter-fractional organ movement and the need for adaptive therapy to compensate for the anatomical changes in the future.

Biophysical Phenomena↗

PubMed2007

Evaluation of patterns of failure and subjective salivary function in patients treated with intensity modulated radiotherapy for head and neck squamous cell carcinoma.

BACKGROUND: Our aim was to correlate patterns of failure with target volume delineations in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiation therapy (IMRT) and to report subjective xerostomia outcomes after IMRT as compared with conventional radiation therapy (CRT). METHODS: Between January 2000 and April 2005, 69 patients with newly diagnosed nonmetastatic HNSCC underwent curative parotid-sparing IMRT at Stanford University. Sites included were oropharynx (n = 39), oral cavity (n = 8), larynx (n = 8), hypopharynx (n = 8), and unknown primary (n = 6). Forty-six patients received definitive IMRT (66 Gy, 2.2 Gy/fraction), and 23 patients received postoperative IMRT (60.2 Gy, 2.15 Gy/fraction). Fifty-one patients also received concomitant chemotherapy. Posttreatment salivary gland function was evaluated by a validated xerostomia questionnaire in 29 IMRT and 75 matched CRT patients >6 months after completing radiation treatment. RESULTS: At a median follow-up of 25 months for living patients (range, 10-60), 7 locoregional failures were observed, 5 in the gross target or high-risk postoperative volume, 1 in the clinical target volume, and 1 at the junction of the IMRT and supraclavicular fields. The 2-year Kaplan-Meier estimates for locoregional control and overall survival were 92% and 74% for definitive IMRT and 87% and 87% for postoperative IMRT patients, respectively. The mean total xerostomia questionnaire score was significantly better for IMRT than for CRT patients (p = .006). CONCLUSIONS: The predominant pattern of failure in IMRT-treated patients is in the gross tumor volume. Parotid sparing with IMRT resulted in less subjective xerostomia and may improve quality of life in irradiated HNSCC patients.

Carcinoma, Squamous Cell↗

PubMed2006

Optimizing 4D cone-beam CT acquisition protocol for external beam radiotherapy.

PURPOSE: Four-dimensional cone-beam computed tomography (4D-CBCT) imaging is sensitive to parameters such as gantry rotation speed, number of gantry rotations, X-ray pulse rate, and tube current, as well as a patient's breathing pattern. The aim of this study is to optimize the image acquisition on a patient-specific basis while minimizing the scan time and the radiation dose. METHODS AND MATERIALS: More than 60 sets of 4D-CBCT images, each with a temporal resolution of 10 phases, were acquired using multiple-gantry rotation and slow-gantry rotation techniques. The image quality was quantified with a relative root mean-square error (RE) and correlated with various acquisition settings; specifically, varying gantry rotation speed, varying both the rotation speed and the number of rotations, and varying both the rotation speed and tube current to keep the radiation exposure constant. These experiments were repeated for three different respiratory periods. RESULTS: With similar radiation dose, 4D-CBCT images acquired with low current and low rotation speed have better quality over images obtained with high current and high rotation speed. In general, a one-rotation low-speed scan is superior to a two-rotation double-speed scan, even though they provide the same number of projections. Furthermore, it is found that the image quality behaves monotonically with the relative speed as defined by the gantry rotation speed and the patient respiratory period. CONCLUSIONS: The RE curves established in this work can be used to predict the 4D-CBCT image quality before a scan. This allows the acquisition protocol to be optimized individually to balance the desired quality with the associated scanning time and patient radiation dose.

Humans↗

PubMed2006

Combination of integrin siRNA and irradiation for breast cancer therapy.

Up-regulation of integrin alpha(v)beta(3) has been shown to play a key role in tumor angiogenesis and metastasis. In this study, we evaluated the role of integrin alpha(v)beta(3) in breast cancer cell resistance to ionizing irradiation (IR) and tested the anti-tumor efficacy of combining integrin alpha(v) siRNA and IR. Colonogenic survival assay, cell proliferation, apoptosis, and cell cycle analysis were carried out to determine the treatment effect of siRNA, IR, or combination of both on MDA-MB-435 cells (integrin alpha(v)beta(3)-positive). Integrin alpha(v)beta(3)-negative MCF-7 cells exert more radiosensitivity than MDA-MB-435 cells. IR up-regulates integrin alpha(v)beta(3) expression in MDA-MB-435 cells and integrin alpha(v) siRNA can effectively reduce both alpha(v) and alpha(v)beta(3) integrin expression, leading to increased radiosensitivity. Integrin alpha(v) siRNA also promotes IR-induced apoptosis and enhances IR-induced G2/M arrest in cell cycle progression. This study, with further optimization, may provide a simple and highly efficient treatment strategy for breast cancer as well as other integrin alpha(v)beta(3)-positive cancer types.

Breast Neoplasms↗

PubMed2006

Indirect MR lymphangiography of the head and neck using conventional gadolinium contrast: a pilot study in humans.

PURPOSE: To evaluate indirect magnetic resonance lymphangiography (MR-LAG) using interstitial injection of conventional gadolinium contrast (gadoteridol and gadopentetate dimeglumine) for delineating the primary lymphatic drainage of head-and-neck sites. METHODS AND MATERIALS: We performed head-and-neck MR-LAG in 5 healthy volunteers, with injection of dermal and mucosal sites. We evaluated the safety of the procedure, the patterns of enhancement categorized by injection site and nodal level, the time course of enhancement, the optimal concentration and volume of contrast, and the optimal imaging sequence. RESULTS: The worst side effects of interstitial contrast injection were brief, mild pain and swelling at the injected sites that were self-limited. MR-LAG resulted in consistent visualization of the primary lymphatic drainage pattern specific to each injected site, which was reproducible on repeated examinations. The best enhancement was obtained with injection of small volumes (0.3-0.5 mL) of either agent diluted, imaging within 5-15 min of injection, and a three-dimensional fast spoiled gradient echo sequence with magnetization transfer. CONCLUSIONS: We found head-and-neck MR-LAG to be a safe, convenient imaging method that provides functional information about the lymphatic drainage of injected sites. Applied to head-and-neck cancer, it has the potential to identify sites at highest risk of occult metastatic spread for radiotherapy or surgical planning, and possibly to visualize micrometastases.

Adult↗

PubMed2006

Multiprotein complexes of the survival of motor neuron protein SMN with Gemins traffic to neuronal processes and growth cones of motor neurons.

Spinal muscular atrophy (SMA), a progressive neurodegenerative disease affecting motor neurons, is caused by mutations or deletions of the SMN1 gene encoding the survival of motor neuron (SMN) protein. In immortalized non-neuronal cell lines, SMN has been shown to form a ribonucleoprotein (RNP) complex with Gemin proteins, which is essential for the assembly of small nuclear RNPs (snRNPs). An additional function of SMN in neurons has been hypothesized to facilitate assembly of localized messenger RNP complexes. We have shown that SMN is localized in granules that are actively transported into neuronal processes and growth cones. In cultured motor neurons, SMN granules colocalized with ribonucleoprotein Gemin proteins but not spliceosomal Sm proteins needed for snRNP assembly. Quantitative analysis of endogenous protein colocalization in growth cones after three-dimensional reconstructions revealed a statistically nonrandom association of SMN with Gemin2 (40%) and Gemin3 (48%). SMN and Gemin containing granules distributed to both axons and dendrites of differentiated motor neurons. A direct interaction between SMN and Gemin2 within single granules was indicated by fluorescence resonance energy transfer analysis of fluorescently tagged and overexpressed proteins. High-speed dual-channel imaging of live neurons depicted the rapid and bidirectional transport of the SMN-Gemin complex. The N terminus of SMN was required for the recruitment of Gemin2 into cytoplasmic granules and enhanced Gemin2 stability. These findings provide new insight into the molecular composition of distinct SMN multiprotein complexes in neurons and motivation to investigate deficiencies of localized RNPs in SMA.

Animals↗

PubMed2006

Image interpolation in 4D CT using a BSpline deformable registration model.

PURPOSE: To develop a method for deriving the phase-binned four-dimensional computed tomography (4D CT) image sets through interpolation of the images acquired at some known phases. METHODS AND MATERIALS: Four-dimensional computed tomography data sets for 3 patients were acquired. For each patient, the correlation between inhale and exhale phases was studied and quantified using a BSpline deformable model. Images at an arbitrary phase were deduced by an interpolation of the deformation coefficients. The accuracy of the proposed scheme was assessed by comparing marker trajectories and by checkerboard/difference display of the interpolated and acquired images. RESULTS: The images at intermediate phases could be derived by an interpolation of the deformation field. An analysis of marker movements indicated that 3 mm accuracy is achievable by the interpolation. The subtraction of image analysis indicated a similar level of success. The proposed technique was useful also for automatically mapping the organ contours in a known phase to other phases, and for designing patient-specific margins in the presence of respiratory motion. Finally, the technique led to a 90% reduction in the acquired data, because in the BSpline model, a lattice of only a few thousand values is sufficient to describe a CT data set of 25 million pixels. CONCLUSIONS: Organ deformation can be well modeled by using a BSpline model. The proposed technique may offer useful means for radiation dose reduction, binning artifacts removal, and disk storage improvement in 4D imaging.

Algorithms↗

PubMed2006

Detection of nitric oxide in culture media and studies on nitric oxide formation by marine microalgae.

BACKGROUND: Multiple functions of nitric oxide (NO) in organisms and its special function and role in the atmosphere were investigated. In this study, marine microalga culture-medium NO concentrations were detected and studied in order to find the laws governing NO release by marine microalgae and relevant material was collected for discussion on the production mechanisms. MATERIAL/METHODS: NO concentrations in culture media of the marine microalgae Platymonas subcordiformis, Skeletonema costatum, and Gymnodinium sp. were detected and other media parameters, such as nutrients concentrations, Chl-a, alga cell density, and pH, were also measured concurrently. RESULTS: The NO concentrations in culture media of the marine microalgae Platymonas subcordiformis, Skeletonema costatum, and Gymnodinium sp. were detected and found to be about 10(-8)-10(-9) mol/l. The relationships between NO and nutrients and NO and pH were discussed. It was found that "NO" could serve as the message factor of microalga growth status. Experiments showed that factors affecting alga growth, such as trace elements, light, temperature, and salinity, all affected the culture-medium NO concentration. At the same time, an environmental stimulus could give rise to sudden NO peaks, with NO being a signal molecule of marine microalga stress response. CONCLUSIONS: These results indicated that low concentrations of NO were produced by marine phytoplankton (microalgae) under the condition of normal growth. NO is a message factor of microalga growth and is also a signal molecule of stress response.

Animals↗

PubMed2006

Overview of image-guided radiation therapy.

Radiation therapy has gone through a series of revolutions in the last few decades and it is now possible to produce highly conformal radiation dose distribution by using techniques such as intensity-modulated radiation therapy (IMRT). The improved dose conformity and steep dose gradients have necessitated enhanced patient localization and beam targeting techniques for radiotherapy treatments. Components affecting the reproducibility of target position during and between subsequent fractions of radiation therapy include the displacement of internal organs between fractions and internal organ motion within a fraction. Image-guided radiation therapy (IGRT) uses advanced imaging technology to better define the tumor target and is the key to reducing and ultimately eliminating the uncertainties. The purpose of this article is to summarize recent advancements in IGRT and discussed various practical issues related to the implementation of the new imaging techniques available to radiation oncology community. We introduce various new IGRT concepts and approaches, and hope to provide the reader with a comprehensive understanding of the emerging clinical IGRT technologies. Some important research topics will also be addressed.

Humans↗

PubMed2006

Image registration with auto-mapped control volumes.

Many image registration algorithms rely on the use of homologous control points on the two input image sets to be registered. In reality, the interactive identification of the control points on both images is tedious, difficult, and often a source of error. We propose a two-step algorithm to automatically identify homologous regions that are used as a priori information during the image registration procedure. First, a number of small control volumes having distinct anatomical features are identified on the model image in a somewhat arbitrary fashion. Instead of attempting to find their correspondences in the reference image through user interaction, in the proposed method, each of the control regions is mapped to the corresponding part of the reference image by using an automated image registration algorithm. A normalized cross-correlation (NCC) function or mutual information was used as the auto-mapping metric and a limited memory Broyden-Fletcher-Goldfarb-Shanno algorithm (L-BFGS) was employed to optimize the function to find the optimal mapping. For rigid registration, the transformation parameters of the system are obtained by averaging that derived from the individual control volumes. In our deformable calculation, the mapped control volumes are treated as the nodes or control points with known positions on the two images. If the number of control volumes is not enough to cover the whole image to be registered, additional nodes are placed on the model image and then located on the reference image in a manner similar to the conventional BSpline deformable calculation. For deformable registration, the established correspondence by the auto-mapped control volumes provides valuable guidance for the registration calculation and greatly reduces the dimensionality of the problem. The performance of the two-step registrations was applied to three rigid registration cases (two PET-CT registrations and a brain MRI-CT registration) and one deformable registration of inhale and exhale phases of a lung 4D CT. Algorithm convergence was confirmed by starting the registration calculations from a large number of initial transformation parameters. An accuracy of approximately 2 mm was achieved for both deformable and rigid registration. The proposed image registration method greatly reduces the complexity involved in the determination of homologous control points and allows us to minimize the subjectivity and uncertainty associated with the current manual interactive approach. Patient studies have indicated that the two-step registration technique is fast, reliable, and provides a valuable tool to facilitate both rigid and nonrigid image registrations.

Algorithms↗

PubMed2006

Model-based image reconstruction for four-dimensional PET.

Positron emission tonography (PET) is useful in diagnosis and radiation treatment planning for a variety of cancers. For patients with cancers in thoracic or upper abdominal region, the respiratory motion produces large distortions in the tumor shape and size, affecting the accuracy in both diagnosis and treatment. Four-dimensional (4D) (gated) PET aims to reduce the motion artifacts and to provide accurate measurement of the tumor volume and the tracer concentration. A major issue in 4D PET is the lack of statistics. Since the collected photons are divided into several frames in the 4D PET scan, the quality of each reconstructed frame degrades as the number of frames increases. The increased noise in each frame heavily degrades the quantitative accuracy of the PET imaging. In this work, we propose a method to enhance the performance of 4D PET by developing a new technique of 4D PET reconstruction with incorporation of an organ motion model derived from 4D-CT images. The method is based on the well-known maximum-likelihood expectation-maximization (ML-EM) algorithm. During the processes of forward- and backward-projection in the ML-EM iterations, all projection data acquired at different phases are combined together to update the emission map with the aid of deformable model, the statistics is therefore greatly improved. The proposed algorithm was first evaluated with computer simulations using a mathematical dynamic phantom. Experiment with a moving physical phantom was then carried out to demonstrate the accuracy of the proposed method and the increase of signal-to-noise ratio over three-dimensional PET. Finally, the 4D PET reconstruction was applied to a patient case.

Algorithms↗

PubMed2006

Reducing respiratory motion artifacts in positron emission tomography through retrospective stacking.

Respiratory motion artifacts in positron emission tomography (PET) imaging can alter lesion intensity profiles, and result in substantially reduced activity and contrast-to-noise ratios (CNRs). We propose a corrective algorithm, coined "retrospective stacking" (RS), to restore image quality without requiring additional scan time. Retrospective stacking uses b-spline deformable image registration to combine amplitude-binned PET data along the entire respiratory cycle into a single respiratory end point. We applied the method to a phantom model consisting of a small, hot vial oscillating within a warm background, as well as to 18FDG-PET images of a pancreatic and a liver patient. Comparisons were made using cross-section visualizations, activity profiles, and CNRs within the region of interest. Retrospective stacking was found to properly restore the lesion location and intensity profile in all cases. In addition, RS provided CNR improvements up to three-fold over gated images, and up to five-fold over ungated data. These phantom and patient studies demonstrate that RS can correct for lesion motion and deformation, while substantially improving tumor visibility and background noise.

Algorithms↗

PubMed2006

Four-dimensional cone-beam computed tomography using an on-board imager.

On-board cone-beam computed tomography (CBCT) has recently become available to provide volumetric information of a patient in the treatment position, and holds promises for improved target localization and irradiation dose verification. The design of currently available on-board CBCT, however, is far from optimal. Its quality is adversely influenced by many factors, such as scatter, beam hardening, and intra-scanning organ motion. In this work we quantitatively study the influence of organ motion on CBCT imaging and investigate a strategy to acquire high quality phase-resolved [four-dimensional (4D)] CBCT images based on phase binning of the CBCT projection data. An efficient and robust method for binning CBCT data according to the patient's respiratory phase derived in the projection space was developed. The phase-binned projections were reconstructed using the conventional Feldkamp algorithm to yield 4D CBCT images. Both phantom and patient studies were carried out to validate the technique and to optimize the 4D CBCT data acquisition protocol. Several factors that are important to the clinical implementation of the technique, such as the image quality, scanning time, number of projections, and radiation dose, were analyzed for various scanning schemes. The general references drawn from this study are: (i) reliable phase binning of CBCT projections is accomplishable with the aid of external or internal marker and simple analysis of its trace in the projection space, and (ii) artifact-free 4D CBCT images can be obtained without increasing the patient radiation dose as compared to the current 3D CBCT scan.

Algorithms↗

PubMed2006

18F-labeled bombesin analogs for targeting GRP receptor-expressing prostate cancer.

UNLABELLED: The gastrin-releasing peptide receptor (GRPR) is found to be overexpressed in a variety of human tumors. The aim of this study was to develop 18F-labeled bombesin analogs for PET of GRPR expression in prostate cancer xenograft models. METHODS: [Lys3]Bombesin ([Lys3]BBN) and aminocaproic acid-bombesin(7-14) (Aca-BBN(7-14)) were labeled with 18F by coupling the Lys3 amino group and Aca amino group, respectively, with N-succinimidyl-4-18F-fluorobenzoate (18F-SFB) under slightly basic condition (pH 8.5). Receptor-binding affinity of FB-[Lys3]BBN and FB-Aca-BBN(7-14) was tested in PC-3 human prostate carcinoma cells. Internalization and efflux of both radiotracers were also evaluated. Tumor-targeting efficacy and in vivo kinetics of both radiotracers were examined in male athymic nude mice bearing subcutaneous PC-3 tumors by means of biodistribution and dynamic microPET imaging studies. 18F-FB-[Lys3]BBN was also tested for orthotopic PC-3 tumor delineation. Metabolic stability of 18F-FB-[Lys3]BBN was determined in mouse blood, urine, liver, kidney, and tumor homogenates at 1 h after injection. RESULTS: The typical decay-corrected radiochemical yield was about 30%-40% for both tracers, with a total reaction time of 150 +/- 20 min starting from 18F-. 18F-FB-[Lys3]BBN had moderate stability in the blood and PC-3 tumor, whereas it was degraded rapidly in the liver, kidneys, and urine. Both radiotracers exhibited rapid blood clearance. 18F-FB-[Lys3]BBN had predominant renal excretion. 18F-FB-Aca-BBN(7-14) exhibited both hepatobiliary and renal clearance. Dynamic microPET imaging studies revealed that the PC-3 tumor uptake of 18F-FB-[Lys3]BBN in PC-3 tumor was much higher than that of 18F-FB-Aca-BBN(7-14) at all time points examined (P < 0.01). The receptor specificity of 18F-FB-[Lys3]BBN in vivo was demonstrated by effective blocking of tumor uptake in the presence of [Tyr4]BBN. No obvious blockade was found in PC-3 tumor when 18F-FB-Aca-BBN(7-14) was used as radiotracer under the same condition. 18F-FB-[Lys3]BBN was also able to visualize orthotopic PC-3 tumor at early time points after tracer administration, at which time minimal urinary bladder activity was present to interfere with the receptor-mediated tumor uptake. CONCLUSION: This study demonstrates that 18F-FB-[Lys3]BBN and PET are suitable for detecting GRPR-positive prostate cancer in vivo.

Animals↗

PubMed2005

Experimental investigation of an inhomogeneous loss and its influence on multiwavelength fiber lasers.

Inhomogeneous loss generated by multimode laser linewidth broadening in an optical fiber is experimentally studied. With this mechanism, multiwavelength lasing is achieved by use of either fiber Raman gain or erbium-doped fiber gain. Through various pump powers and optical filter bandwidths, the relationship between inhomogeneous loss and the performance of a multiwavelength fiber laser is studied, and a physical explanation is provided.

Journal Article↗