The reactive oxygen species (ROS)-mediated mechanism is the major cause underlying the efficacy of photodynamic therapy (PDT). The PDT procedure is based on the cascade of synergistic effects between light, a photosensitizer (PS) and oxygen, which greatly favors the spatiotemporal control of the treatment. This procedure has also evoked several unresolved challenges at different levels including (i) the limited penetration depth of light, which restricts traditional PDT to superficial tumours; (ii) oxygen reliance does not allow PDT treatment of hypoxic tumours; (iii) light can complicate the phototherapeutic outcomes because of the concurrent heat generation; (iv) specific delivery of PSs to sub-cellular organelles for exerting effective toxicity remains an issue; and (v) side effects from undesirable white-light activation and self-catalysation of traditional PSs. Recent advances in nanotechnology and nanomedicine have provided new opportunities to develop ROS-generating systems through photodynamic or non-photodynamic procedures while tackling the challenges of the current PDT approaches. In this review, we summarize the current status and discuss the possible opportunities for ROS generation for cancer therapy. We hope this review will spur pre-clinical research and clinical practice for ROS-mediated tumour treatments.

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

Spectroscopic Tagging Lucas A. Lane,† Ximei Qian,† and Shuming Nie*,†,‡ †Departments of Biomedical Engineering and Chemistry, Emory University and Georgia Institute of Technology, Health Sciences Research Building, Room E116, 1760 Haygood Drive, Atlanta, Georgia 30322, United States ‡College of Engineering and Applied Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu Province 210093, China

SERS Nanoparticles in Medicine: From Label-Free Detection to Spectroscopic Tagging.

Physics of Radiology

The Monte Carlo (MC) method has been shown through many research studies to calculate accurate dose distributions for clinical radiotherapy, particularly in heterogeneous patient tissues where the effects of electron transport cannot be accurately handled with conventional, deterministic dose algorithms. Despite its proven accuracy and the potential for improved dose distributions to influence treatment outcomes, the long calculation times previously associated with MC simulation rendered this method impractical for routine clinical treatment planning. However, the development of faster codes optimized for radiotherapy calculations and improvements in computer processor technology have substantially reduced calculation times to, in some instances, within minutes on a single processor. These advances have motivated several major treatment planning system vendors to embark upon the path of MC techniques. Several commercial vendors have already released or are currently in the process of releasing MC algorithms for photon and/or electron beam treatment planning. Consequently, the accessibility and use of MC treatment planning algorithms may well become widespread in the radiotherapy community. With MC simulation, dose is computed stochastically using first principles; this method is therefore quite different from conventional dose algorithms. Issues such as statistical uncertainties, the use of variance reduction techniques, theability to account for geometric details in the accelerator treatment head simulation, and other features, are all unique components of a MC treatment planning algorithm. Successful implementation by the clinical physicist of such a system will require an understanding of the basic principles of MC techniques. The purpose of this report, while providing education and review on the use of MC simulation in radiotherapy planning, is to set out, for both users and developers, the salient issues associated with clinical implementation and experimental verification of MC dose algorithms. As the MC method is an emerging technology, this report is not meant to be prescriptive. Rather, it is intended as a preliminary report to review the tenets of the MC method and to provide the framework upon which to build a comprehensive program for commissioning and routine quality assurance of MC-based treatment planning systems.

Report of the AAPM Task Group No. 105 : Issues associated with clinical implementation of Monte Carlo-based photon and electron external beam treatment planning

This feature article covers the recent applications of metal-organic framework nanoparticles (MOF NPs) in photodynamic therapy (PDT) of cancer. It aims at giving the reader an overview about these two current research fields, i. e., MOF and PDT, and at highlighting the potential synergistic effect that could result from their association. After describing the general photophysics and photochemistry that underlie PDT, the relationship between photosensitizer (PS) properties and PDT requirements is discussed throughout the PSs historical development. This development reveals the advantages of using nanotechnology platforms for the creation of the ideal PS and leads us to define the fourth generation of PSs, which includes NPs built from the PS itself as porphysomes or PS-based MOF NPs. Especially, the precise spatial control over the PS assembly into well-defined MOF NPs, which keeps the PS in its monomeric form and prevents PS self-quenching, appears as a notable feature to solve PS solubility and aggregation issues and therefore improves the PDT efficiency. Finally, we discuss the future perspectives of MOF NPs in PDT and shed light on how promising these nanomaterials are.

Metal-Organic Framework Nanoparticles in Photodynamic Therapy: Current Status and Perspectives

Monte Carlo (MC) dose calculations are performed on patient geometries derived from computed tomography (CT) images. For most available MC codes, the Hounsfield units (HU) in each voxel of a CT image have to be converted into mass density (rho) and material type. This is typically done with a (HU; rho) calibration curve which may lead to mis-assignment of media. In this work, an improved material segmentation using dual-energy CT-based material extraction is presented. For this purpose, the differences in extracted effective atomic numbers Z and the relative electron densities rho(e) of each voxel are used. Dual-energy CT material extraction based on parametrization of the linear attenuation coefficient for 17 tissue-equivalent inserts inside a solid water phantom was done. Scans of the phantom were acquired at 100 kVp and 140 kVp from which Z and rho(e) values of each insert were derived. The mean errors on Z and rho(e) extraction were 2.8% and 1.8%, respectively. Phantom dose calculations were performed for 250 kVp and 18 MV photon beams and an 18 MeV electron beam in the EGSnrc/DOSXYZnrc code. Two material assignments were used: the conventional (HU; rho) and the novel (HU; rho, Z) dual-energy CT tissue segmentation. The dose calculation errors using the conventional tissue segmentation were as high as 17% in a mis-assigned soft bone tissue-equivalent material for the 250 kVp photon beam. Similarly, the errors for the 18 MeV electron beam and the 18 MV photon beam were up to 6% and 3% in some mis-assigned media. The assignment of all tissue-equivalent inserts was accurate using the novel dual-energy CT material assignment. As a result, the dose calculation errors were below 1% in all beam arrangements. Comparable improvement in dose calculation accuracy is expected for human tissues. The dual-energy tissue segmentation offers a significantly higher accuracy compared to the conventional single-energy segmentation.

https://iopscience.iop.org/article/10.1088/0031-9155/53/9/015/pdf

Dual-energy CT-based material extraction for tissue segmentation in Monte Carlo dose calculations

Computed tomography (CT) images of patients having metallic implants or dental fillings exhibit severe streaking artifacts. These artifacts may disallow tumor and organ delineation and compromise dose calculation outcomes in radiotherapy. We used a sinogram interpolation metal streaking artifact correction algorithm on several phantoms of exact-known compositions and on a prostate patient with two hip prostheses. We compared original CT images and artifact-corrected images of both. To evaluate the effect of the artifact correction on dose calculations, we performed Monte Carlo dose calculation in the EGSnrc/DOSXYZnrc code. For the phantoms, we performed calculations in the exact geometry, in the original CT geometry and in the artifact-corrected geometry for photon and electron beams. The maximum errors in 6 MV photon beam dose calculation were found to exceed 25% in original CT images when the standard DOSXYZnrc/CTCREATE calibration is used but less than 2% in artifact-corrected images when an extended calibration is used. The extended calibration includes an extra calibration point for a metal. The patient dose volume histograms of a hypothetical target irradiated by five 18 MV photon beams in a hypothetical treatment differ significantly in the original CT geometry and in the artifact-corrected geometry. This was found to be mostlymore » due to miss-assignment of tissue voxels to air due to metal artifacts. We also developed a simple Monte Carlo model for a CT scanner and we simulated the contribution of scatter and beam hardening to metal streaking artifacts. We found that whereas beam hardening has a minor effect on metal artifacts, scatter is an important cause of these artifacts.« less

Correction of CT artifacts and its influence on Monte Carlo dose calculations.

The Axxent developed by Xoft Inc. is a novel electronic brachytherapy system capable of generating x-rays up to 50 keV. These low energy photon-emitting sources merit attention not only because of their ability to vary the dosimetric properties of the radiation, but also because of the radiobiological effects of low energy x-rays. The objective of this study is to characterize the x-ray source and to model it using the Geant4 Monte Carlo code. Spectral and attenuation curve measurements are performed at various peak voltages and angles and the source is characterized in terms of spectrum and half-value layers (HVLs). Also, the effects of source variation and source aging are quantified. Bremsstrahlung splitting, phase-space scoring and particle-tagging features are implemented in the Geant4 code, which is bench-marked against BEAMnrc simulations. HVLs from spectral measurements, attenuation curve measurements and Geant4 simulations mostly agree within uncertainty. However, there are discrepancies between measurements and simulations for photons emitted on the source transverse plane (90°).

https://iopscience.iop.org/article/10.1088/0031-9155/53/1/004/pdf

Spectroscopic characterization of a novel electronic brachytherapy system.

This work provides a comprehensive Monte Carlo study of X-ray fluorescence computed tomography (XFCT) and K-edge imaging system, including the system design, the influence of various imaging components, the sensitivity and resolution under various conditions. We modified the widely used EGSnrc/DOSXYZnrc code to simulate XFCT images of two acrylic phantoms loaded with various concentrations of gold nanoparticles and Cisplatin for a number of XFCT geometries. In particular, reconstructed signal as a function of the width of the detector ring, its angular coverage and energy resolution were studied. We found that XFCT imaging sensitivity of the modeled systems consisting of a conventional X-ray tube and a full 2-cm-wide energy-resolving detector ring was 0.061% and 0.042% for gold nanoparticles and Cisplatin, respectively, for a dose of ~10cGy. Contrast-to-noise ratio (CNR) of XFCT images of the simulated acrylic phantoms was higher than that of transmission K-edge images for contrast concentrations below 0.4%.

Investigation of X-ray Fluorescence Computed Tomography (XFCT) and K-Edge Imaging

Simultaneous imaging of multiple probes or biomarkers represents a critical step toward high specificity molecular imaging In this work, we propose to utilize the element-specific nature of the X-ray fluorescence (XRF) signal for imaging multiple elements simultaneously (multiplexing) using XRF computed tomography (XFCT) A 5-mm-diameter pencil beam produced by a polychromatic X-ray source (150 kV, 20 mA) was used to stimulate emission of XRF photons from 2% (weight/volume) gold (Au), gadolinium (Gd), and barium (Ba) embedded within a water phantom The phantom was translated and rotated relative to the stationary pencil beam in a first-generation CT geometry The X-ray energy spectrum was collected for 18 s at each position using a cadmium telluride detector The spectra were then used to isolate the K shell XRF peak and to generate sinograms for the three elements of interest The distribution and concentration of the three elements were reconstructed with the iterative maximum likelihood expectation maximization algorithm The linearity between the XFCT intensity and the concentrations of elements of interest was investigated We found that measured XRF spectra showed sharp peaks characteristic of Au, Gd, and Ba The narrow full-width at half-maximum (FWHM) of the peaks strongly supports the potential of XFCT for multiplexed imaging of Au, Gd, and Ba (FWHMAu,Kα1 = 0619 keV, FWHMAu,Kα2=1371 keV , FWHMGd,Kα=1297 keV, FWHMGd,Kβ=0974 keV , FWHMBa,Kα=0852 keV, and FWHMBa,Kβ=0594 keV ) The distribution of Au, Gd, and Ba in the water phantom was clearly identifiable in the reconstructed XRF images Our results showed linear relationships between the XRF intensity of each tested element and their concentrations (R2Au=0944 , RGd2=0986, and RBa2=0999), suggesting that XFCT is capable of quantitative imaging Finally, a transmission CT image was obtained to show the potential of the approach for providing attenuation correction and morphological information In conclusion, XFCT is a promising modality for multiplexed imaging of high atomic number probes

Magdalena Bazalova

Papers

Dual-energy CT-based material extraction for tissue segmentation in Monte Carlo dose calculations

Correction of CT artifacts and its influence on Monte Carlo dose calculations.

Spectroscopic characterization of a novel electronic brachytherapy system.

Investigation of X-ray Fluorescence Computed Tomography (XFCT) and K-Edge Imaging

First Demonstration of Multiplexed X-Ray Fluorescence Computed Tomography (XFCT) Imaging