Image contrast assessment of metal-based nanoparticles as applications for image-guided radiation therapy
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ABSTRACT:
SUBMITTER: Nakayama M
PROVIDER: S-EPMC8626564 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Selective killing of cancer cells while minimizing damage to healthy tissues is the goal of clinical radiation therapy. This therapeutic ratio can be improved by image-guided radiation delivery and selective radiosensitization of cancer cells. Here, we have designed and tested a novel trimodal theranostic nanoparticle made of bismuth and gadolinium for on-site radiosensitization and image contrast enhancement to improve the efficacy and accuracy of radiation therapy. We demonstrate in vivo magnetic resonance (MR), computed tomography (CT) contrast enhancement, and tumor suppression with prolonged survival in a non-small cell lung carcinoma model during clinical radiation therapy. Histological studies show minimal off-target toxicities due to the nanoparticles or radiation. By mimicking existing clinical workflows, we show that the bismuth-gadolinium nanoparticles are highly compatible with current CT-guided radiation therapy and emerging MR-guided approaches. This study reports the first in vivo proof-of-principle for image-guided radiation therapy with a new class of theranostic nanoparticles.
| S-EPMC5505266 | biostudies-literature
Project description:Nanoradiosensitizers have been developed to enhance localization and precision of therapeutic radiation delivery. A specific volume of comprising surface atoms is known to be the radiosensitizing region. However, the shape-dependent local dose enhancement of nanoparticles is often underestimated and rarely reported. Here, a noble metal nanostructure, inspired by the photoperiodic day-flowers, was synthesized by metal reduction with bile acid molecules. The impact of high surface area of day-flower mimicking metallic nanoparticles (D-NP) on radiosensitizing effect was demonstrated with assays for ROS generation, cellular apoptosis, and clonogenic survival of human liver cancer cells (HepG2) cells. In comparison with lower-surface-area spherical night-flower mimicking metallic nanoparticles (N-NP), exposure of our D-NP to external beam radiation doses led to a significant increase in reactive oxygen species (ROS) production and radiosensitizing cell cycle synchronization, resulting in an enhanced cancer-cell-killing effect. In clonogenic survival studies, dose-enhancing factor (DEF) of D-NP was 16.5-fold higher than N-NP. Finally, we demonstrated in vivo feasibility of our D-NP as a potent nanoradiosensitizer and CT contrast agent for advanced image-guided radiation therapy.
| S-EPMC7047606 | biostudies-literature
Project description:PURPOSE:To develop and validate a technique for radiation therapy gating using slow (?1 frame per second) magnetic resonance imaging (MRI) and a motion model. Proposed uses of the technique include radiation therapy gating using T2-weighted images and conducting additional imaging studies during gated treatments. METHODS AND MATERIALS:The technique uses a physiologically guided breathing motion model to interpolate deformed target position between 2-dimensional (2D) MRI images acquired every 1 to 3 seconds. The model is parameterized by a 1-dimensional respiratory bellows surrogate and is continuously updated with the most recently acquired 2D images. A phantom and 8 volunteers were imaged with a 0.35T MRI-guided radiation therapy system. A balanced steady-state free precession sequence with a 2D frame rate of 3 frames per second was used to evaluate the technique. The accuracy and beam-on positive predictive value (PPV) of the model-based gating decisions were evaluated using the gating decisions derived from imaging as a ground truth. A T2-weighted gating offline proof-of-concept study using a half-Fourier, single-shot, turbo-spin echo sequence is reported. RESULTS:Model-interpolated gating accuracy, beam-on PPV, and median absolute distances between model and image-tracked target centroids were, on average, 98.3%, 98.4%, and 0.33 mm, respectively, in the balanced steady-state free precession phantom studies and 93.7%, 92.1%, and 0.86 mm, respectively, in the volunteer studies. T2 model-interpolated gating in 6 volunteers yielded an average accuracy and PPV of 94.3% and 92.5%, respectively, and the mean absolute median distance between modeled and imaged target centroids was 0.86 mm. CONCLUSIONS:This work demonstrates the concept of model-interpolated gating for MRI-guided radiation therapy. The technique was found to be potentially sufficiently accurate for clinical use. Further development is needed to accommodate out-of-plane motion and the use of an internal MR-based respiratory surrogate.
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Project description:To investigate the undesired irradiations outside of the treatment field by electron streams in air (air-electron-stream) during magnetic-resonance image-guided radiation therapy (MR-IGRT). A custom-made support phantom adjusting angles between the beam central axis (CAX) and the phantom surface (termed phantom-angles), were used. Using the ViewRay system, a rectangular parallelepiped phantom placed on the support phantom, was irradiated with field sizes of 6.3 cm × 6.3 cm (FS6.3) and 12.6 cm × 12.6 cm (FS12.6) at gantry angles of 0°, 30°, and 330°, and phantom-angles of 10°, 20°, and 30°. For each beam delivery, the isocenter was located at the center of mass of the phantom and 3 Gy was delivered to the isocenter (prescription dose = 3 Gy). The doses given by the air-electron-streams were measured using the EBT3 films on the panels placed orthogonal to the direction of the magnetic field at distances of 10 and 17 cm from CAX. Two dose distributions per irradiation were measured on the panel facing the phantom surface of the incident beam (front panel) and on the panel facing the phantom surface of the beam exit (end panel). We investigated the doses by the air-electron-streams by calculating the average doses inside the circles drawn around a point of the maximum dose with radii of x cm (DRx) from the dose distributions on the panels (x = 1-5 cm). The largest value of DRx was DR1 (1.64 Gy, 55% of the prescription dose) at 10 cm distance from CAX, with FS12.6, at 30° phantom-angle and 330° gantry angle. The average difference of the DR1 at the end panels (FS12.6) between the calculations and measurements was 1.36 Gy. The average global gamma passing rate with 3%/3 mm on the dose distributions at the end panels (FS12.6) was 40.3%. The calculated dose distributions on both panels were not coincident with the measured dose distributions. The Spearman's rank correlation coefficients between the projected areas and the DRx values were always higher than 0.75 (all with p < 0.001). The doses by the air-electron-streams increased with the projected areas of the cross-sections of the treatment beams on the panels.
| S-EPMC6519819 | biostudies-literature
Project description:Cone beam CT (CBCT) in image-guided radiotherapy (IGRT) offers a tremendous advantage for treatment guidance. The associated imaging dose is a clinical concern. One unique feature of CBCT-based IGRT is that the same patient is repeatedly scanned during a treatment course, and the contents of CBCT images at different fractions are similar. The authors propose a progressive dose control (PDC) scheme to utilize this temporal correlation for imaging dose reduction.A dynamic CBCT scan protocol, as opposed to the static one in the current clinical practice, is proposed to gradually reduce the imaging dose in each treatment fraction. The CBCT image from each fraction is processed by a prior-image based nonlocal means (PINLM) module to enhance its quality. The increasing amount of prior information from previous CBCT images prevents degradation of image quality due to the reduced imaging dose. Two proof-of-principle experiments have been conducted using measured phantom data and Monte Carlo simulated patient data with deformation.In the measured phantom case, utilizing a prior image acquired at 0.4 mAs, PINLM is able to improve the image quality of a CBCT acquired at 0.2 mAs by reducing the noise level from 34.95 to 12.45 HU. In the synthetic patient case, acceptable image quality is maintained at four consecutive fractions with gradually decreasing exposure levels of 0.4, 0.1, 0.07, and 0.05 mAs. When compared with the standard low-dose protocol of 0.4 mAs for each fraction, an overall imaging dose reduction of more than 60% is achieved.PINLM-PDC is able to reduce CBCT imaging dose in IGRT utilizing the temporal correlations among the sequence of CBCT images while maintaining the quality.
| S-EPMC3669143 | biostudies-other
Project description:Tumor tissue that remains undetected at the primary surgical site can cause tumor recurrence, repeat surgery, and treatment strategy alterations that impose a significant patient and healthcare burden. Intraoperative near infrared fluorescence (NIRF) imaging is one potential method to identify remaining tumor by visualization of NIR fluorophores that are preferentially localized to the tumor. This requires development of fluorophores that consistently identify tumor tissue in different patients and tumor types. In this study we examined a panel of NIRF contrast agents consisting of polymeric nanoparticle (NP) formulations derived from hyaluronic acid (HA), with either physically entrapped indocyanine green (ICG) or covalently conjugated Cy7.5. Using orthotopic human breast cancer MDA-MB-231 xenografts in nude mice we identified two lead formulations. One, NanoICGPBA, with physicochemically entrapped ICG, showed 2.3-fold greater tumor contrast than ICG alone at 24 h (p < 0.01), and another, NanoCy7.5100-H, with covalently conjugated Cy7.5, showed 74-fold greater tumor contrast than Cy7.5 alone at 24 h (p < 0.0001). These two lead formulations were then tested in immune competent BALB/c mice bearing orthotopic 4T1 breast cancer tumors. NanoICGPBA showed 2.2-fold greater contrast than ICG alone (p < 0.0001), and NanoCy7.5100-H showed 14.8-fold greater contrast than Cy7.5 alone (p < 0.0001). Furthermore, both NanoICGPBA and NanoCy7.5100-H provided strong tumor enhancement using image-guided surgery in mice bearing 4T1 tumors. These studies demonstrate the efficacy of a panel of HA-derived NPs in delineating tumors in vivo, and identifies promising formulations that can be used for future in vivo tumor removal efficacy studies.
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Project description:Noninvasive dynamic positron emission tomography (PET) imaging was used to investigate the balance between renal clearance and tumor uptake behaviors of polyethylene glycol (PEG)-modified porphyrin nanoparticles (TCPP-PEG) with various molecular weights. TCPP-PEG10K nanoparticles with clearance behavior would be a good candidate for PET image-guided photodynamic therapy.
| S-EPMC5687274 | biostudies-literature
Project description:The development of synthetic computed tomography (CT) (synCT) derived from magnetic resonance (MR) images supports MR-only treatment planning. We evaluated the accuracy of synCT and synCT-generated digitally reconstructed radiographs (DRRs) relative to CT and determined their performance for image guided radiation therapy (IGRT).Magnetic resonance simulation (MR-SIM) and CT simulation (CT-SIM) images were acquired of an anthropomorphic skull phantom and 12 patient brain cancer cases. SynCTs were generated using fluid attenuation inversion recovery, ultrashort echo time, and Dixon data sets through a voxel-based weighted summation of 5 tissue classifications. The DRRs were generated from the phantom synCT, and geometric fidelity was assessed relative to CT-generated DRRs through bounding box and landmark analysis. An offline retrospective analysis was conducted to register cone beam CTs (n=34) to synCTs and CTs using automated rigid registration in the treatment planning system. Planar MV and KV images (n=37) were rigidly registered to synCT and CT DRRs using an in-house script. Planar and volumetric registration reproducibility was assessed and margin differences were characterized by the van Herk formalism.Bounding box and landmark analysis of phantom synCT DRRs were within 1 mm of CT DRRs. Absolute planar registration shift differences ranged from 0.0 to 0.7 mm for phantom DRRs on all treatment platforms and from 0.0 to 0.4 mm for volumetric registrations. For patient planar registrations, the mean shift differences were 0.4 ± 0.5 mm (range, -0.6 to 1.6 mm), 0.0 ± 0.5 mm (range, -0.9 to 1.2 mm), and 0.1 ± 0.3 mm (range, -0.7 to 0.6 mm) for the superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) axes, respectively. The mean shift differences in volumetric registrations were 0.6 ± 0.4 mm (range, -0.2 to 1.6 mm), 0.2 ± 0.4 mm (range, -0.3 to 1.2 mm), and 0.2 ± 0.3 mm (range, -0.2 to 1.2 mm) for the S-I, L-R, and A-P axes, respectively. The CT-SIM and synCT derived margins were <0.3 mm different.DRRs generated by synCT were in close agreement with CT-SIM. Planar and volumetric image registrations to synCT-derived targets were comparable with CT for phantom and patients. This validation is the next step toward MR-only planning for the brain.
| S-EPMC5450663 | biostudies-literature
Project description:PURPOSE:This study reported long-term outcomes of patients with cervical cancer who were treated with intensity modulated radiation therapy and 3-dimensional (3D) image-guided adapted brachytherapy (IMRT/3D-IGABT) compared with those treated with 2-dimensional (2D) external irradiation and 2D brachytherapy (2D EBRT/BT). METHODS AND MATERIALS:This study included patients with newly diagnosed cervical cancer and pretreatment fluorodeoxyglucose positron emission tomography scans who were treated with curative-intent irradiation from 1997 to 2013. The treatment policy changed from using 2D EBRT/BT to IMRT/3D-IGABT in 2005. Patterns of recurrence, cancer-specific survival (CSS), and overall survival (OS) were evaluated. Late gastrointestinal and genitourinary toxicity were scored with National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS:The median follow-up for patients alive at the time of last follow-up in the 2D EBRT/BT group (n = 300) was 15.3 years (range, 10.8-20.5 years). In the IMRT/3D-IGABT group (n = 300), it was 7 years (range, 5-12.4 years). According to the International Federation of Gynecology and Obstetrics, 33% of tumors were stage IB1 to IB2, 41% were stage IIA to IIB, and 26% were stage IIIA to IVA. The results after 5 years for patients treated with 2D EBRT/BT showed that freedom from relapse (FFR) was 57%, CSS was 62%, and OS was 57%. For the IMRT/3D-IGABT group, the 5-year results showed that FFR was 65% (P = .04), CSS was 69% (P = .01), and OS was 61% (P = .04). When stratified by lymph node status according to positron emission tomography scan results, disease control was most improved with IMRT/3D-IGABT versus 2D EBRT/BT in patients with positive pelvic lymph nodes only (P = .02). Cumulatively, 88 of 600 patients (15%) had grade ?3 late bowel/bladder toxicity. The 2D EBRT/BT group had 55 patients (18%), and the IMRT/3D-IGABT group had 33 patients (11%; P = .02). CONCLUSIONS:IMRT/3D-IGABT was associated with improved survival and decreased gastrointestinal and genitourinary toxicity in patients with cervical cancer compared with those who received 2D EBRT/BT.
| S-EPMC7065668 | biostudies-literature
Project description:This paper reports on the commissioning of an Elekta cone-beam computed tomography (CT) system at one of the first U.S. sites to install a "regular," off-the-shelf Elekta Synergy (Elekta, Stockholm, Sweden) accelerator system. We present the quality assurance (QA) procedure as a guide for other users. The commissioning had six elements: (1) system safety, (2) geometric accuracy (agreement of megavoltage and kilovoltage beam isocenters), (3) image quality, (4) registration and correction accuracy, (5) dose to patient and dosimetric stability, and (6) QA procedures. The system passed the safety tests, and agreement of the isocenters was found to be within 1 mm. Using a precisely moved skull phantom, the reconstruction and alignment algorithm was found to be accurate within 1 mm and 1 degree in each dimension. Of 12 measurement points spanning a 9x9x15-cm volume in a Rando phantom (The Phantom Laboratory, Salem, NY), the average agreement in the x, y, and z coordinates was 0.10 mm, -0.12 mm, and 0.22 mm [standard deviations (SDs): 0.21 mm, 0.55 mm, 0.21 mm; largest deviations: 0.6 mm, 1.0 mm, 0.5 mm] respectively. The larger deviation for the y component can be partly attributed to the CT slice thickness of 1 mm in that direction. Dose to the patient depends on the machine settings and patient geometry. To monitor dose consistency, air kerma (output) and half-value layer (beam quality) are measured for a typical clinical setting. Air kerma was 6.3 cGy (120 kVp, 40 mA, 40 ms per frame, 360-degree scan, S20 field of view); half value layer was 7.1 mm aluminum (120 kV, 40 mA). We suggest performing items 1, 2, and 3 monthly, and 4 and 5 annually. In addition, we devised a daily QA procedure to verify agreement of the megavoltage and kilovoltage isocenters using a simple phantom containing three small steel balls. The frequency of all checks will be reevaluated based on data collected during about 1 year.
| S-EPMC5722599 | biostudies-literature