Measuring circular dichroism in a capillary cell using the b23 synchrotron radiation CD beamline at diamond light source

Synchrotron radiation circular dichroism (SRCD) is a well-established method in structural biology. The first UV-VIS beamline dedicated to circular dichroism at Diamond Light Source, a third generation synchrotron facility in South Oxfordshire, has recently become operational and it is now available for the user community. Herein we present an important application of SRCD: the CD measurement of protein solutions in fused silica rectangular capillary cells. This was achieved without the use of any lens between the photoelastic modulator and the photomultiplier tube detectors by exploiting the high photon flux of the collimated beam that can be as little as half a millimeter squared. Measures to minimize or eliminate vacuum-UV protein denaturation effects are discussed. The CD spectra measured in capillaries is a proof of principle to address CD measurements in microdevice systems using the new B23 SRCD beamline.     

Canadian macromolecular crystallography facility: a suite of fully automated beamlines

The Canadian light source is a 2.9 GeV national synchrotron radiation facility located on the University of Saskatchewan campus in Saskatoon. The small-gap in-vacuum undulator illuminated beamline, 08ID-1, together with the bending magnet beamline, 08B1-1, constitute the Canadian Macromolecular Crystallography Facility (CMCF). The CMCF provides service to more than 50 Principal Investigators in Canada and the United States. Up to 25% of the beam time is devoted to commercial users and the general user program is guaranteed up to 55% of the useful beam time through a peer-review process. CMCF staff provides "Mail-In" crystallography service to users with the highest scored proposals. Both beamlines are equipped with very robust end-stations including on-axis visualization systems, Rayonix 300 CCD series detectors and Stanford-type robotic sample auto-mounters. MxDC, an in-house developed beamline control system, is integrated with a data processing module, AutoProcess, allowing full automation of data collection and data processing with minimal human intervention. Sample management and remote monitoring of experiments is enabled through interaction with a Laboratory Information Management System developed at the facility.     

A focused scanning vertical beam for charged particle irradiation of living cells with single counted particles

The Surrey vertical beam is a new facility for targeted irradiation of cells in medium with singly counted ions. A duo-plasmatron ion source and a 2 MV Tandem? accelerator supply a range of ions from protons to calcium for this beamline and microscope endstation, with energy ranges from 0.5 to 12 MeV. A magnetic quadrupole triplet lens is used to focus the beam of ions. We present the design of this beamline, and early results showing the capability to count single ions with 98% certainty on CR-39 track etch. We also show that the beam targeting accuracy is within 5 μm and selectively target human fibroblasts with a <5 μm carbon beam, using γ-H2AX immunofluorescence to demonstrate which cell nuclei were irradiated. We discuss future commissioning steps necessary to achieve submicron targeting accuracy with this beamline.     

Beamline characterization of a dielectric-filled reentrant cavity resonator as beam current monitor for a medical cyclotron facility

At PSI (Paul Scherrer Institute), Switzerland, a superconducting cyclotron called “COMET” delivers proton beam of 250 MeV pulsed at 72.85 MHz for proton radiation therapy. Measuring proton beam currents (0.1–10nA) is of crucial importance for the treatment safety and is usually performed with invasive monitors such as ionisation chambers (ICs) which degrade the beam quality. A new non-invasive beam current monitor working on the principle of electromagnetic resonance is built to replace ICs in order to preserve the beam quality delivered. The fundamental resonance frequency of the resonator is tuned to 145.7 MHz, which is the second harmonic of the pulse rate, so it provides signals proportional to beam current. The cavity resonator installed in the beamline of the COMET is designed to measure beam currents for the energy range 238–70 MeV. Good agreement is reached between expected and measured resonator response over the energy range of interest. The resonator can deliver beam current information down to 0.15 nA for a measurement integration time of 1 s. The cavity resonator might be applied serving as a safety monitor to trigger interlocks within the existing domain of proton radiation therapy. Low beam currents limit the abilities to detect sufficiently, however, with the potential implementation of FLASH proton therapy, the application of cavity resonator as an online beam-monitoring device is feasible.     

Uncertainty quantification analysis and optimization for proton therapy beam lines

Since many years proton therapy is an effective treatment solution against deep-seated tumors. A precise quantification of sources of uncertainty in each proton therapy aspect (e.g. accelerator, beam lines, patient positioning, treatment planning) is of profound importance to increase the accuracy of the dose delivered to the patient. Together with Monte Carlo techniques, a new research field called Uncertainty Quantification (UQ) has been recently introduced to verify the robustness of the treatment planning. In this work we present the first application of UQ as a method to identify typical errors in the transport lines of a cyclotron-based proton therapy facility and analyze their impact on the properties of the therapeutic beams. We also demonstrate the potential of UQ methods in developing optimized beam optics solutions for high-dimensional problems. Sensitivity analysis and surrogate models offer a fast way to exclude unimportant parameters frcomplex optimization problems such as the design of a superconducting gantry performed at Paul Scherrer Institute in Switzerland.     

BMIT facility at the Canadian Light Source: Advances in X-ray phase-sensitive imaging

The BioMedical Imaging and Therapy (BMIT) facility [1,2] located at the Canadian Light Source, provides synchrotron-specific imaging and radiation therapy capabilities. There are two separate beamlines used for experiments: the bending magnet (05B1-1) and the insertion device (05ID-2) beamline.The bending magnet beamline provides access to monochromatic beam spanning a spectral range of 15–40 keV, and the beam is 240 mm wide in the POE-2 experimental hutch. Users can also perform experiments with polychromatic (pink) beam.The insertion device beamline was officially opened for general user program in 2015. The source for the ID beamline is a multi-pole, superconducting 4.3 T wiggler. The high field gives a critical energy over 20 keV. The optics hutches prepare a beam that is 220 mm wide in the last experimental hutch SOE-1. The monochromatic spectral range spans 25–150+ keV. Several different X-ray detectors are available for both beamlines, with resolutions ranging from 2 μm to 200 μm.BMIT provides a number of imaging techniques including standard absorption X-ray imaging, K-edge subtraction imaging (KES), in-line phase contrast imaging (also known as propagation based imaging, PBI) and Diffraction Enhanced Imaging/Analyzer Based Imaging (DEI/ABI), all in either projection or CT mode. PBI and DEI/ABI are particularly important tools for BMIT users since these techniques enable visualization of soft tissue and allow for low dose imaging.     

Fabrication and Characterization of Disordered Polymer Optical Fibers for Transverse Anderson Localization of Light

We develop and characterize a disordered polymer optical fiber that uses transverse Anderson localization as a novel waveguiding mechanism. The developed polymer optical fiber is composed of 80,000 strands of poly (methyl methacrylate) (PMMA) and polystyrene (PS) that are randomly mixed and drawn into a square cross section optical fiber with a side width of 250 μm. Initially, each strand is 200 μm in diameter and 8-inches long. During the mixing process of the original fiber strands, the fibers cross over each other; however, a large draw ratio guarantees that the refractive index profile is invariant along the length of the fiber for several tens of centimeters. The large refractive index difference of 0.1 between the disordered sites results in a small localized beam radius that is comparable to the beam radius of conventional optical fibers. The input light is launched from a standard single mode optical fiber using the butt-coupling method and the near-field output beam from the disordered fiber is imaged using a 40X objective and a CCD camera. The output beam diameter agrees well with the expected results from the numerical simulations. The disordered optical fiber presented in this work is the first device-level implementation of 2D Anderson localization, and can potentially be used for image transport and short-haul optical communication systems.     

Assessment of the neutron dose field around a biomedical cyclotron: FLUKA simulation and experimental measurements

In the planning of a new cyclotron facility, an accurate knowledge of the radiation field around the accelerator is fundamental for the design of shielding, the protection of workers, the general public and the environment.Monte Carlo simulations can be very useful in this process, and their use is constantly increasing. However, few data have been published so far as regards the proper validation of Monte Carlo simulation against experimental measurements, particularly in the energy range of biomedical cyclotrons.In this work a detailed model of an existing installation of a GE PETtrace 16.5 MeV cyclotron was developed using FLUKA. An extensive measurement campaign of the neutron ambient dose equivalent H¹(10) in marked positions around the cyclotron was conducted using a neutron rem-counter probe and CR39 neutron detectors. Data from a previous measurement campaign performed by our group using TLDs were also re-evaluated.The FLUKA model was then validated by comparing the results of high-statistics simulations with experimental data. In 10 out of 12 measurement locations, FLUKA simulations were in agreement within uncertainties with all the three different sets of experimental data; in the remaining 2 positions, the agreement was with 2/3 of the measurements.Our work allows to quantitatively validate our FLUKA simulation setup and confirms that Monte Carlo technique can produce accurate results in the energy range of biomedical cyclotrons.     

An improved optical technique for monitoring plant cell concentration

 An improved optical method was developed to determine cell weight concentrations using a micro-plate reader. Light absorbance was measured by a vertical light beam, which can minimize the cell settling effect found in traditional optical measurements with a horizontal light beam. The use of well plates not only requires very small sample sizes, but also handles a large number of samples at the same time. Absorbance measurements were linearly related to cell weight over the full range of batch culture growth. Received: 4 Jannuary 1999 / Revision received: 23 March 1999 / Accepted: 14 April 1999     

Polarization-modulated second harmonic generation in collagen

Collagen possesses a strong second-order nonlinear susceptibility, a nonlinear optical property characterized by second harmonic generation in the presence of intense laser beams. We present a new technique involving polarization modulation of an ultra-short pulse laser beam that can simultaneously determine collagen fiber orientation and a parameter related to the second-order nonlinear susceptibility. We demonstrate the ability to discriminate among different patterns of fibrillar orientation, as exemplified by tendon, fascia, cornea, and successive lamellar rings in an intervertebral disc. Fiber orientation can be measured as a function of depth with an axial resolution of approximately 10 microm. The parameter related to the second-order nonlinear susceptibility is sensitive to fiber disorganization, oblique incidence of the beam on the sample, and birefringence of the tissue. This parameter represents an aggregate measure of tissue optical properties that could potentially be used for optical imaging in vivo.     

On the influence of Alfvén resonance on ion cyclotron resonance heating

Physical processes determining the excitation of RF electromagnetic fields in a plasma column in a magnetic field are analyzed. The Alfvén resonance plays an important role at frequencies close to the ion cyclotron frequency. It leads to the enhancement of the RF electric field and transformation of Alfvén oscillations with a predominantly transverse polarization of the electric field into lower hybrid ones, which have a significant longitudinal component of the electric field. Lower hybrid oscillations efficiently interact with electrons causing their heating. Difficulties in the implementation of ion cyclotron resonance heating by the magnetic beach method are outlined. The processes considered in this work can be important for the VASIMR plasma engine.     

DICOM-RT Ion interface to utilize MC simulations in routine clinical workflow for proton pencil beam radiotherapy

To adopt Monte Carlo (MC) simulations as an independent dose calculation method for proton pencil beam radiotherapy, an interface that converts the plan information in DICOM format into MC components such as geometries and beam source is a crucial element. For this purpose, a DICOM-RT Ion interface (https://github.com/topasmc/dicom-interface) has been developed and integrated into the TOPAS MC code to perform such conversions on-the-fly. DICOM-RT objects utilized in this interface include Ion Plan (RTIP), Ion Beams Treatment Record (RTIBTR), CT image, and Dose. Beamline geometries, gantry and patient coordinate systems, and fluence maps are determined from RTIP and/or RTIBTR. In this interface, DICOM information is processed and delivered to a MC engine in two steps. A MC model, which consists of beamline geometries and beam source, to represent a treatment machine is created by a DICOM parser of the interface. The complexities from different DICOM types, various beamline configurations and source models are handled in this step. Next, geometry information and beam source are transferred to TOPAS on-the-fly via the developed TOPAS extensions. This interface with two treatment machines was successfully deployed into our automated MC workflow which provides simulated dose and LET distributions in a patient or a water phantom automatically when a new plan is identified. The developed interface provides novel features such as handling multiple treatment systems based on different DICOM types, DICOM conversions on-the-fly, and flexible sampling methods that significantly reduce the burden of handling DICOM based plan or treatment record information for MC simulations.     

Considerations for laboratory animal imaging center design and setup

In vivo animal imaging is an outstanding noninvasive tool to study the pathophysiology of disease or response to therapy; additionally, serial imaging reduces the required number of experimental animals. Because of the tremendous capital investment, we recommend the imaging center be a shared resource to facilitate innovative and productive cross-disciplinary scientific collaborations. A shared center also enables a broader range of imaging, as equipment is often cost prohibitive for smaller facilities. A multitude of factors will determine the architectural design, facility efficiency, and functionality. Important considerations to determine during the planning stages include the types of animals to be imaged, types of imaging studies to be performed, types of imaging equipment and related services to be offered, and the location of the imaging center. Architects must work closely with manufacturers to accommodate equipment-related building specifications; facility planners and veterinarians can provide a practical logistical design that will ensure efficient functionality. Miscellaneous considerations include biosecurity levels, use of radioisotopes, and personnel safety in the imaging environment. The ideal imaging center will include space to house animals and perform necessary preimaging procedures, state-of-the-art in vivo imaging devices and the most up-to-date anesthesia, physiological support, and monitoring equipment. The center staff should include imaging specialists for technical development and data analysis. As it is difficult to provide a comprehensive manual for setting up an in vivo animal imaging center, we offer advice based on our experiences with the National Institutes of Health Mouse Imaging Facility. Because magnetic resonance imaging (MRI) is the most expensive imaging tool, requires specific building design considerations, and poses unique occupational health and safety risks, we focus on MRI as the foundation for an imaging facility design.     

Linear behaviour in the aperture pupil of single photoreceptors: Consequences related to the degree of inhomogeneity

An exact treatment of the initial field falling on the entrance face of a photoreceptor, so that the scattered field far from the latter vanishes, is presented. Its physical interest and some consequences are discussed. By establishing certain similarities between the behaviour of the photoreceptor as light penetrates into and propagates along, and an optical linear system, it is possible to define a spatial transverse impulse response containing information on the diffraction capability of each individual receptor. The distribution of this function across a transverse plane depends upon the particular form of the refractive index in the photoreceptor. Thus, certain differences are seen to occur between the case of an homogeneous receptor and an inhomogeneous one, for particular values in the degree of inhomogeneity. This fact allows to interpret the presence of inhomogeneities in the photoreceptor structure.     

Estimation of the electron density and radiative energy losses in a calcium plasma source based on an electron cyclotron resonance discharge

The parameters of a calcium plasma source based on an electron cyclotron resonance (ECR) discharge were calculated. The analysis was performed as applied to an ion cyclotron resonance system designed for separation of calcium isotopes. The plasma electrons in the source were heated by gyrotron microwave radiation in the zone of the inhomogeneous magnetic field. It was assumed that, in such a combined trap, the energy of the extraordinary microwave propagating from the high-field side was initially transferred to a small group of resonance electrons. As a result, two electron components with different transverse temperatures—the hot resonance component and the cold nonresonance component—were created in the plasma. The longitudinal temperatures of both components were assumed to be equal. The entire discharge space was divided into a narrow ECR zone, where resonance electrons acquired transverse energy, and the region of the discharge itself, where the gas was ionized. The transverse energy of resonance electrons was calculated by solving the equations for electron motion in an inhomogeneous magnetic field. Using the law of energy conservation and the balance condition for the number of hot electrons entering the discharge zone and cooled due to ionization and elastic collisions, the density of hot electrons was estimated and the dependence of the longitudinal temperature T _e∥ of the main (cold) electron component on the energy fraction β lost for radiation was obtained.     

Non-invasive beam profile monitor for medical accelerators

A beam profile monitor based on a supersonic gas-curtain is currently under development for transverse profile diagnostics of electron and proton beams in the High Luminosity LHC. This monitor uses a thin supersonic gas curtain that crosses the primary beam to be characterized under an angle of 45 degrees. The fluorescence caused by the interaction between the beam and gas-curtain is detected using a specially designed imaging system to determine the 2D transverse profile of the primary beam. Another prototype monitor based on beam induced ionization is installed at The Cockcroft Institute. This paper presents the design features of both the monitors, the gas-jet curtain formation and various experimental tests, including profile measurements of an electron beam, using helium, nitrogen and neon as gases. Such a non-invasive online beam profile monitor would be highly desirable also for medical LINAC’s and storage rings as it can characterize the beam without stopping machine operation. The paper discusses opportunities for simplifying the monitor design for integration into a medical accelerator and expected monitor performance.     

Quasilinear theory of the inversionless generation of electron cyclotron radiation

A study is made of the parametric generation of cyclotron radiation by a modulated electron ensemble that is stable against the generation of a monochromatic field—the classical effect characteristic of an inversionless maser. A quasilinear theory of inversionless cyclotron instability is developed. It is shown that, during quasilinear diffusion, the system of a modulated electron beam and an electromagnetic field relaxes to a certain steady state.     

The impact of treatment parameter variation on secondary neutron spectra in high-energy electron beam radiotherapy

High-energy electron treatment procedures in radiotherapy pose a potential iatrogenic cancer risk as well as a critical health risk to patients with cardiac implantable electronic devices due to the generation of secondary neutrons in the linac head, the treatment room, and the patient. It may be argued that the neutron production from photons is well characterized, but the same is not true for electrons. Therefore, to assess the risk involved in an electron treatment, one must determine the neutron flux spectrum generated by the treatment procedure. The neutron spectrum depends on the treatment parameters used and therefore it is crucial to study its dependence on these parameters. In this work, eight experiments were devised to analyze how eight electron treatment parameters impacted the neutron spectrum. The parameters we considered were the electron beam energy, location of measurement, cutout size, collimator size, applicator size, collimator angle, choice of treatment room, and the presence or absence of a solid water phantom. For each experiment, we used a Nested Neutron Spectrometer™ (NNS) to measure the neutron flux spectra for multiple settings of the treatment parameter of interest. The resulting spectra were plotted and compared. We found that the electron beam energy and the location of measurement had the most impact on the neutron flux spectra, while the other parameters had a smaller or insignificant impact. This report may serve as a reference tool for medical physicists to help estimate the risk associated with a particular high-energy electron treatment procedure.     

Heat generation in laser irradiated tissue

Many medical applications involving lasers rely upon the generation of heat within the tissue for the desired therapeutic effect. Determination of the absorbed light energy in tissue is difficult in many cases. Although UV wavelengths of the excimer laser and 10.6 microns wavelength of the CO2 laser are absorbed within the first 20 microns of soft tissue, visible and near infrared wavelengths are scattered as well as absorbed. Typically, multiple scattering is a significant factor in the distribution of light in tissue and the resulting heat source term. An improved model is presented for estimating heat generation due to the absorption of a collimated (axisymmetric) laser beam and scattered light at each point r and z in tissue. Heat generated within tissue is a function of the laser power, the shape and size of the incident beam and the optical properties of the tissue at the irradiation wavelength. Key to the calculation of heat source strength is accurate estimation of the light distribution. Methods for experimentally determining the optical parameters of tissue are discussed in the context of the improved model.