A gantry-based tri-modality system for bioluminescence tomography.
Ontology highlight
ABSTRACT:
SUBMITTER: Yan H
PROVIDER: S-EPMC3350538 | biostudies-other | 2012 Apr
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Photoacoustic microscopy (PAM) and optical coherence tomography (OCT) are sensitive to optical absorption and scattering characteristics, respectively. As such, the integration of these two modalities in order to combine important complementary information has garnered much attention. Due to the relatively low axial resolution of PAM, PAM and OCT dual modality systems generally have a large resolution gap, especially for reflection mode systems. In this study, based on a wide-band transparent pure-optical ultrasonic detector, we developed a dual modality system (PAM-OCT system) in which PAM has a similar spatial resolution (i.e. several micrometers in both the lateral and axial directions) to OCT. In addition, due to the optical transparency advantage, the integrated system works in reflection mode, which is ideal for in vivo biomedical imaging. We successfully imaged the skin of a mouse hindlimb, which cannot be done by a transmission mode dual modality system. Our work demonstrates this dual modality system has potential in biomedical studies with complementary imaging contrasts.
| S-EPMC7300161 | biostudies-literature
Project description:In preclinical radiation research, it is challenging to localize soft tissue targets based on cone beam computed tomography (CBCT) guidance. As a more effective method to localize soft tissue targets, we developed an online bioluminescence tomography (BLT) system for small-animal radiation research platform (SARRP). We demonstrated BLT-guided radiation therapy and validated targeting accuracy based on a newly developed reconstruction algorithm.The BLT system was designed to dock with the SARRP for image acquisition and to be detached before radiation delivery. A 3-mirror system was devised to reflect the bioluminescence emitted from the subject to a stationary charge-coupled device (CCD) camera. Multispectral BLT and the incomplete variables truncated conjugate gradient method with a permissible region shrinking strategy were used as the optimization scheme to reconstruct bioluminescent source distributions. To validate BLT targeting accuracy, a small cylindrical light source with high CBCT contrast was placed in a phantom and also in the abdomen of a mouse carcass. The center of mass (CoM) of the source was recovered from BLT and used to guide radiation delivery. The accuracy of the BLT-guided targeting was validated with films and compared with the CBCT-guided delivery. In vivo experiments were conducted to demonstrate BLT localization capability for various source geometries.Online BLT was able to recover the CoM of the embedded light source with an average accuracy of 1 mm compared to that with CBCT localization. Differences between BLT- and CBCT-guided irradiation shown on the films were consistent with the source localization revealed in the BLT and CBCT images. In vivo results demonstrated that our BLT system could potentially be applied for multiple targets and tumors.The online BLT/CBCT/SARRP system provides an effective solution for soft tissue targeting, particularly for small, nonpalpable, or orthotopic tumor models.
| S-EPMC4814325 | biostudies-literature
Project description:Bioluminescence-based imaging of living cells has become an important tool in biological and medical research. However, many bioluminescence imaging applications are limited by the requirement of an externally provided luciferin substrate and the low bioluminescence signal which restricts the sensitivity and spatiotemporal resolution. The bacterial bioluminescence system is fully genetically encodable and hence produces autonomous bioluminescence without an external luciferin, but its brightness in cell types other than bacteria has, so far, not been sufficient for imaging single cells. We coexpressed codon-optimized forms of the bacterial luxCDABE and frp genes from multiple plasmids in different mammalian cell lines. Our approach produces high luminescence levels that are comparable to firefly luciferase, thus enabling autonomous bioluminescence microscopy of mammalian cells.
| S-EPMC6936394 | biostudies-literature
Project description:PurposeThe cone-beam computed tomography (CBCT)-guided small animal radiation research platform (SARRP) has provided unique opportunities to test radiobiologic hypotheses. However, CBCT is less adept to localize soft tissue targets growing in a low imaging contrast environment. Three-dimensional bioluminescence tomography (BLT) provides strong image contrast and thus offers an attractive solution. We introduced a novel and efficient BLT-guided conformal radiation therapy and demonstrated it in an orthotopic glioblastoma (GBM) model.Methods and materialsA multispectral BLT system was integrated with SARRP for radiation therapy (RT) guidance. GBM growth curve was first established by contrast CBCT/magnetic resonance imaging (MRI) to derive equivalent sphere as approximated gross target volume (aGTV). For BLT, mice were subject to multispectral bioluminescence imaging, followed by SARRP CBCT imaging and optical reconstruction. The CBCT image was acquired to generate anatomic mesh for the reconstruction and RT planning. To ensure high accuracy of the BLT-reconstructed center of mass (CoM) for target localization, we optimized the optical absorption coefficients ?a by minimizing the distance between the CoMs of BLT reconstruction and contrast CBCT/MRI-delineated GBM volume. The aGTV combined with the uncertainties of BLT CoM localization and target volume determination was used to generate estimated target volume (ETV). For conformal irradiation procedure, the GBM was first localized by the predetermined ETV centered at BLT-reconstructed CoM, followed by SARRP radiation. The irradiation accuracy was qualitatively confirmed by pathologic staining.ResultsDeviation between CoMs of BLT reconstruction and contrast CBCT/MRI-imaged GBM is approximately 1 mm. Our derived ETV centered at BLT-reconstructed CoM covers >95% of the tumor volume. Using the second-week GBM as an example, the ETV-based BLT-guided irradiation can cover 95.4% ± 4.7% tumor volume at prescribed dose. The pathologic staining demonstrated the BLT-guided irradiated area overlapped well with the GBM location.ConclusionsThe BLT-guided RT enables 3-dimensional conformal radiation for important orthotopic tumor models, which provides investigators a new preclinical research capability.
| S-EPMC7007925 | biostudies-literature
Project description:PurposeWidely used cone beam computed tomography (CBCT)-guided irradiators in preclinical radiation research are limited to localize soft tissue target because of low imaging contrast. Knowledge of target volume is a fundamental need for radiation therapy (RT). Without such information to guide radiation, normal tissue can be overirradiated, introducing experimental uncertainties. This led us to develop high-contrast quantitative bioluminescence tomography (QBLT) for guidance. The use of a 3-dimensional bioluminescence signal, related to cell viability, for preclinical radiation research is one step toward biology-guided RT.Methods and materialsOur QBLT system enables multiprojection and multispectral bioluminescence imaging to maximize input data for the tomographic reconstruction. Accurate quantification of spectrum and dynamic change of in vivo signal were also accounted for the QBLT. A spectral-derivative method was implemented to eliminate the modeling of the light propagation from animal surface to detector. We demonstrated the QBLT capability of guiding conformal RT using a bioluminescent glioblastoma (GBM) model in vivo. A threshold was determined to delineate QBLT reconstructed gross target volume (GTVQBLT), which provides the best overlap between the GTVQBLT and CBCT contrast labeled GBM (GTV), used as the ground truth for GBM volume. To account for the uncertainty of GTVQBLT in target positioning and volume delineation, a margin was determined and added to the GTVQBLT to form a QBLT planning target volume (PTVQBLT) for guidance.ResultsThe QBLT can reconstruct in vivo GBM with localization accuracy within 1 mm. A 0.5-mm margin was determined and added to GTVQBLT to form PTVQBLT, largely improving tumor coverage from 75.0% (0 mm margin) to 97.9% in average, while minimizing normal tissue toxicity. With the goal of prescribed dose 5 Gy covering 95% of PTVQBLT, QBLT-guided 7-field conformal RT can effectively irradiate 99.4 ± 1.0% of GTV.ConclusionsThe QBLT provides a unique opportunity for investigators to use biologic information for target delineation, guiding conformal irradiation, and reducing normal tissue involvement, which is expected to increase reproducibility of scientific discovery.
| S-EPMC8602741 | biostudies-literature
Project description:PurposeIn proton therapy, the potential of using high-dose rates in the cancer treatment is being explored. High-dose rates could improve efficiency and throughput in standard clinical practice, allow efficient utilization of motion mitigation techniques for moving targets, and potentially enhance normal tissue sparing due to the so-called FLASH effect. However, high-dose rates are difficult to reach when lower energy beams are applied in cyclotron-based proton therapy facilities, because they result in large beam sizes and divergences downstream of the degrader, incurring large losses from the cyclotron to the patient position (isocenter). In current facilities, the emittance after the degrader is reduced using circular collimators; however, this does not provide an optimal matching to the acceptance of the following beamline, causing a low transmission for these energies. We, therefore, propose to use a collimation system, asymmetric in both beam size and divergence, resulting in symmetric emittance in both beam transverse planes as required for a gantry system. This new emittance selection, together with a new optics design for the following beamline and gantry, allows a better matching to the beamline acceptance and an improvement of the transmission.MethodsWe implemented a custom method to design the collimator sizes and shape required to select high emittance, to be transported by the following beamline using new beam optics (designed with TRANSPORT) to maximize acceptance matching. For predicting the transmission in the new configuration (new collimators + optics), we used Monte Carlo simulations implemented in BDSIM, implementing a model of PSI Gantry 2 which we benchmarked against measurements taken in the current clinical scenario (circular collimators + clinical optics).ResultsFrom the BDSIM simulations, we found that the new collimator system and matching beam optics results in an overall transmission from the cyclotron to the isocenter for a 70 MeV beam of 0.72%. This is an improvement of almost a factor of 6 over the current clinical performance (0.13% transmission). The new optics satisfies clinical beam requirements at the isocenter.ConclusionsWe developed a new emittance collimation system for PSI's PROSCAN beamline which, by carefully selecting beam size and divergence asymmetrically, increases the beam transmission for low-energy beams in current state-of-the-art cyclotron-based proton therapy gantries. With these improvements, we could predict almost 1% transmission for low-energy beams at PSI's Gantry 2. Such a system could easily be implemented in facilities interested in increasing dose rates for efficient motion mitigation and FLASH experiments alike.
| S-EPMC9298197 | biostudies-literature
Project description:Two novel imaging agents trastuzumab-Cy5.5-CHX-A''1 and cetuximab-Cy7-CHX-A''2, bearing both a chelating moiety (CHX-A'') for sequestering metallic radionuclides ((86)Y or (111)In) and the near infrared dye Cy5.5/Cy7, were prepared by a novel modular synthetic strategy as examples of dual-labeled, antibody-based imaging probe library. Fluorescent microscopy illustrated that 1 and 2 strongly bind to HER2-expressing cancer cells (e.g., NIH3T3-HER2(+), SKOV-3) and to EGFR-expressing cancer cells (e.g., A431), respectively, thereby demonstrating that the functionality of the targeting moiety is conserved. Hence, the described novel synthesis strategy can be applied to engineer other tumor-targeted monoclonal antibody based probes for multimodality imaging.
| S-EPMC2759299 | biostudies-literature
Project description:PurposeTo assess clinically relevant image quality metrics (IQMs) of helical fan beam kilovoltage (kV) fan beam computed tomography (CT).Methods and materialskVCT IQMs were evaluated on an Accuray Radixact unit equipped with helical fan beam kVCT to assess the capabilities of this newly available modality. kVCT IQMs were evaluated and compared to a kVCT simulator and linear accelerator-based cone beam CTs (CBCT) using a commercial CBCT image quality phantom. kVCTs were acquired on the Accuray Radixact for all combinations of kVp and mAs in fine mode using a 440-mm field of view (FOV). Evaluated IQMs were spatial resolution, overall uniformity, subject contrast, contrast-to-noise ratio (CNR), and effective slice thickness. Imaging dose was assessed for planar kV imaging.ResultsOn this kVCT system spatial resolution and contrast were consistent across all settings with 0.28 ± 0.03 lp/mm and 9.8% ± 0.7% (both 95% confidence interval). CNR strongly depended on selected mode (views per rotation) and body size (mA per view) and ranged between 7.9 and 34.9. Overall uniformity was greater than 97% for all settings. Large FOV was not found to substantially affect the IQMs whereas small FOV affected IQMs due to its effect on pitch. Technique-matched CT simulator scans were comparable for uniformity and contrast, while spatial resolution was higher (0.43 ± 0.06 lp/mm), and CNR was between 4% (140 kVp) and 51% (100 kVp) lower. For kV-CBCT, spatial resolutions ranging from 0.37 to 0.44 lp/mm were achieved with comparable contrast, CNR, and uniformity to kVCT. All kVCT scans exhibit imaging artifacts due to helical acquisition. Clinical acquisitions of megavoltage (MV) CT, kV-CBCT, and kVCT on the same patient showed improved and comparable image quality of kVCT compared to MVCT and kV-CBCT, respectively.ConclusionsHelical fan beam kVCT allows for daily image guidance for localization and setup verification with comparable performance to existing kV-CBCT systems. Scan parameters must be selected carefully to maximize image quality for the desired tasks. Due to the large effective slice thicknesses for all parameter combinations, kVCT scans should not be used for simulation or planning of stereotactic procedures. Finally, improved image quality over MVCT has the potential to greatly improve manual and automated adaptive monitoring and planning.
| S-EPMC8749200 | biostudies-literature
Project description:BACKGROUND:Although tri-modality therapy is an acceptable standard of care in patients with locally advanced esophageal cancer, data regarding patterns of failure is lacking. We report bi-institutional patterns of failure experience treating patients using tri-modality therapy. MATERIALS AND METHODS:We retrospectively reviewed patients who underwent chemoradiation followed by esophagectomy between 2006 and 2011 at two NCI-designated cancer centers. First failure sites were categorized as local, regional nodal, or distant. Statistical analysis was performed using Fisher's exact test, non-parametric Wilcoxon rank-sum test, and multiple logistic regression. Kaplan-Meier curves were generated for relapse-free survival (RFS) and overall survival. RESULTS:A total of 132 patients met the inclusion criteria with a median age of 62 (range 36-80) and median follow-up of 28 months (range 4-128). There were a total of six (4.5%) local, 13 (10%) regional nodal, and 32 (23.5%) distant failures. Local failure was correlated with fewer lymph nodes (LN) assessed (p?=?0.01) and close/positive margins (p?<?0.01). Regional nodal failure was correlated with fewer LN assessed (p?<?0.01) and larger pretreatment tumor size (p?=?0.04). Patients with??13 LN evaluated had an inferior locoregional RFS versus patients with?>13 LN evaluated (p?=?0.003). Distant recurrence was correlated with higher pathologic nodal stage (p?<?0.001), ulceration (p?=?0.017), perineural invasion (p?=?0.029), residual disease (p?=?0.004), and higher post-treatment PET SUV max (p?=?0.049). Patients with a pathologic complete response (OR 0.19, 95% CI 0.05-0.68) were less likely to experience distant recurrence. CONCLUSION:Tumor and treatment factors may predict for failure in patients undergoing tri-modality therapy for locally advanced esophageal cancer. Further data is needed to identify patterns of failure in these patients.
| S-EPMC6854665 | biostudies-literature
Project description:Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, affects 8-10 million people worldwide and represents a major public health challenge. There is no effective treatment or vaccine to control the disease that is characterized by a mild acute phase followed by a chronic life-long infection. Approximately 30% of chronically infected individuals develop cardiac and/or digestive pathologies. T. cruzi can invade a wide variety of nucleated cells, but only persists at specific tissues in the host. However, the mechanisms that determine tissue tropism and the progression of the infection have not been fully described. Identification of infection niches in animal models has been difficult due to the limited quantity of parasite-infected cells and their focal distribution in tissues during the chronic phase. To better understand the course of chronic infections and parasite dissemination, we developed a bioluminescence imaging system based on the use of transgenic T. cruzi Colombiana strain parasites expressing nanoluciferase. Swiss Webster mice were infected with luminescent trypomastigotes and monitored for 126 days. Whole animal in vivo imaging showed parasites predominantly distributed in the abdominal cavity and surrounding areas throughout the infection. Bioluminescence signal reached a peak between 14 to 21 days post infection (dpi) and decreased progressively over time. Total animal luminescence could still be measured 126 dpi while parasites remained undetectable in blood by microscopy in most animals. Ex vivo imaging of specific tissues and organs dissected post-mortem at 126 dpi revealed a widespread parasite distribution in the skeletal muscle, heart, intestines and mesenteric fat. Parasites were also detected in lungs and liver. This noninvasive imaging model represents a novel tool to study host-parasite interactions and to identify parasite reservoirs of chronic Chagas Disease.
| S-EPMC5908157 | biostudies-literature