Fabrication and Testing of Microfluidic Optomechanical Oscillators

Cavity optomechanics experiments that parametrically couple the phonon modes and photon modes have been investigated in various optical systems including microresonators. However, because of the increased acoustic radiative losses during direct liquid immersion of optomechanical devices, almost all published optomechanical experiments have been performed in solid phase. This paper discusses a recently introduced hollow microfluidic optomechanical resonator. Detailed methodology is provided to fabricate these ultra-high-Q microfluidic resonators, perform optomechanical testing, and measure radiation pressure-driven breathing mode and SBS-driven whispering gallery mode parametric vibrations. By confining liquids inside the capillary resonator, high mechanical- and optical- quality factors are simultaneously maintained.     

The three Endonuclease III variants of Deinococcus radiodurans possess distinct and complementary DNA repair activities

Endonuclease III (EndoIII) is a bifunctional DNA glycosylase that removes oxidized pyrimidines from DNA. The genome of Deinococcus radiodurans encodes for an unusually high number of DNA glycosylases, including three EndoIII enzymes (drEndoIII1-3). Here, we compare the properties of these enzymes to those of their well-studied homologues from E. coli and human. Our biochemical and mutational data, reinforced by MD simulations of EndoIII-DNA complexes, reveal that drEndoIII2 exhibits a broad substrate specificity and a catalytic efficiency surpassing that of its counterparts. In contrast, drEndoIII1 has much weaker and uncoupled DNA glycosylase and AP-lyase activities, a characteristic feature of eukaryotic DNA glycosylases, and was found to present a relatively robust activity on single-stranded DNA substrates. To our knowledge, this is the first report of such an activity for an EndoIII. In the case of drEndoIII3, no catalytic activity could be detected, but its ability to specifically recognize lesion-containing DNA using a largely rearranged substrate binding pocket suggests that it may play an alternative role in genome maintenance. Overall, these findings reveal that D. radiodurans possesses a unique set of DNA repair enzymes, including three non-redundant EndoIII variants with distinct properties and complementary activities, which together contribute to genome maintenance in this bacterium.     

Multicellular dosimetric chain for molecular radiotherapy exemplified with dose simulations on 3D cell spheroids

PurposeAbsorbed radiation dose-response relationships are not clear in molecular radiotherapy (MRT). Here, we propose a voxel-based dose calculation system for multicellular dosimetry in MRT. We applied confocal microscope images of a spherical cell aggregate i.e. a spheroid, to examine the computation of dose distribution within a tissue from the distribution of radiopharmaceuticals.MethodsA confocal microscope Z-stack of a human hepatocellular carcinoma HepG2 spheroid was segmented using a support-vector machine algorithm and a watershed function. Heterogeneity in activity uptake was simulated by selecting a varying amount of the cell nuclei to contain ¹¹¹In, ¹²⁵I, or ¹⁷⁷Lu. Absorbed dose simulations were carried out using vxlPen, a software application based on the Monte Carlo code PENELOPE.ResultsWe developed a schema for radiopharmaceutical dosimetry. The schema utilizes a partially supervised segmentation method for cell-level image data together with a novel main program for voxel-based radiation dose simulations. We observed that for ¹⁷⁷Lu, radiation cross-fire enabled full dose coverage even if the radiopharmaceutical had accumulated to only 60% of the spheroid cells. This effect was not found with ¹¹¹In and ¹²⁵I. Using these Auger/internal conversion electron emitters seemed to guarantee that only the cells with a high enough activity uptake will accumulate a lethal amount of dose, while neighboring cells are spared.ConclusionsWe computed absorbed radiation dose distributions in a 3D-cultured cell spheroid with a novel multicellular dosimetric chain. Combined with pharmacological studies in different tissue models, our cell-level dosimetric calculation method can clarify dose-response relationships for radiopharmaceuticals used in MRT.     

A case of radiation-induced bullous morphea/lichen sclerosus overlap in a breast cancer patient

Radiation induced morphea (RIM) is an increasingly common complication of radiation treatment for malignancy as early detection has made more patients eligible for non-surgical treatment options. In many cases, the radiation oncologist is the first person to learn of the initial skin changes, often months before a dermatologist sees them. In this paper we present a breast cancer patient who developed a rare bullous variant of RIM, which delayed her diagnosis and subsequent treatment. It is imperative to diagnose RIM early as it carries significant morbidity and permanent deformity if left untreated. The lesions typically present within 1 year of radiation therapy and extend beyond the radiated field. RIM is often mistaken for radiation dermatitis or cellulitis. Bullae, when present, are often hemorrhagic in appearance, which can serve as another clinical clue. It is important to refer these patients for a full gynecologic exam as there can be concurrent anogenital lichen sclerosus et atrophicus which is both debilitating and carries a long term risk for squamous cell carcinoma. Treatment with systemic agents is often necessary, and can be managed by a dermatologist. The most proven regimen in the literature appears to be methotrexate, with our without concurrent narrow band UVB phototherapy.     

Evaluating the accuracy of geometrical distortion correction of magnetic resonance images for use in intracranial brain tumor radiotherapy

AimDetermine the 1) effectiveness of correction for gradient-non-linearity and susceptibility effects on both QUASAR GRID^3D and CIRS phantoms; and 2) the magnitude and location of regions of residual distortion before and after correction.BackgroundUsing magnetic resonance imaging (MRI) as a primary dataset for radiotherapy planning requires correction for geometrical distortion and non-uniform intensity.Materials and MethodsPhantom Study: MRI, computed tomography (CT) and cone beam CT images of QUASAR GRID^3D and CIRS head phantoms were acquired. Patient Study: Ten patients were MRI-scanned for stereotactic radiosurgery treatment. Correction algorithm: Two magnitude and one phase difference image were acquired to create a field map. A MATLAB program was used to calculate geometrical distortion in the frequency encoding direction, and 3D interpolation was applied to resize it to match 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images. MPRAGE images were warped according to the interpolated field map in the frequency encoding direction. The corrected and uncorrected MRI images were fused, deformable registered, and a difference distortion map generated.ResultsMaximum deviation improvements: GRID^3D, 0.27 mm y-direction, 0.07 mm z-direction, 0.23 mm x-direction. CIRS, 0.34 mm, 0.1 mm and 0.09 mm at 20-, 40- and 60-mm diameters from the isocenter. Patient data show corrections from 0.2 to 1.2 mm, based on location. The most-distorted areas are around air cavities, e.g. sinuses.ConclusionsThe phantom data show the validity of our fast distortion correction algorithm. Patient-specific data are acquired in <2 min and analyzed and available for planning in less than a minute.     

Quality control in cone-beam computed tomography (CBCT) EFOMP-ESTRO-IAEA protocol (summary report)

The aim of the guideline presented in this article is to unify the test parameters for image quality evaluation and radiation output in all types of cone-beam computed tomography (CBCT) systems. The applications of CBCT spread over dental and interventional radiology, guided surgery and radiotherapy. The chosen tests provide the means to objectively evaluate the performance and monitor the constancy of the imaging chain. Experience from all involved associations has been collected to achieve a consensus that is rigorous and helpful for the practice.The guideline recommends to assess image quality in terms of uniformity, geometrical precision, voxel density values (or Hounsfield units where available), noise, low contrast resolution and spatial resolution measurements. These tests usually require the use of a phantom and evaluation software. Radiation output can be determined with a kerma-area product meter attached to the tube case. Alternatively, a solid state dosimeter attached to the flat panel and a simple geometric relationship can be used to calculate the dose to the isocentre. Summary tables including action levels and recommended frequencies for each test, as well as relevant references, are provided.If the radiation output or image quality deviates from expected values, or exceeds documented action levels for a given system, a more in depth system analysis (using conventional tests) and corrective maintenance work may be required.     

Effectiveness of different accelerated partial breast irradiation techniques for the treatment of breast cancer patients: Systematic review using indirect comparisons of randomized clinical trials

AimThis systematic review was conducted to compare the effectiveness of different accelerated partial breast irradiation (APBI) techniques for the treatment of breast cancer patients.BackgroundNumerous (APBI) techniques are available for clinical practice.Methods and materialsSystematic review of randomized controlled trials of APBI versus whole breast irradiation (WBI). The data from APBI studies were extracted for the analyses. Indirect comparisons were used to compare different APBI techniques.ResultsTen studies fulfilled the inclusion criteria. A total of 4343 patients were included, most of them with tumor stage T1-T2 and N0. Regarding APBI techniques, six trials used external beam radiation therapy; one intraoperative electrons; one intraoperative low-energy photons; one brachytherapy; and one external beam radiation therapy or brachytherapy. The indirect comparisons related to 5-years local control and 5-years overall survival were not significantly different between APBI techniques.ConclusionsBased on indirect comparisons, no differences in clinical outcomes were observed among diverse APBI techniques in published clinical trials that formally compared WBI to APBI. However wide confidence intervals and high risk of inconsistency precluded a sound conclusion. Further head-to-head clinical trials comparing different APBI techniques are required to confirm our findings. Studies comparing different techniques using individual participant data and/or real-life data from population-based studies/registries could also provide more robust results.     

Cost-benefit analysis of establishing and operating radiation oncology services in Fiji

BackgroundRising demand for services of cancer patients has been recognised by the Government of Fiji as a national health priority. Increasing attention has been paid to the lack of service of radiation therapy or radiotherapy in Fiji.ObjectiveThis study aims to estimate and compare the costs and benefits of introducing radiation oncology services in Fiji from the societal perspective.MethodsTime horizon for cost-benefit analysis (CBA) was 15 years from 2021 to 2035. The benefits and costs were converted to the present values of 2016. Estimates for the CBA model were taken from previous studies and expert opinions and data obtained from field visits to Fiji in January 2016. Sensitivity analyses with changing assumptions were undertaken.ResultsThe estimated net benefit, applying the national minimum wage (NMW) to measure monetary value for life-year gained, was −31,624,421 FJD with 0.69 of benefit-cost (B/C) ratio. If gross national income (GNI) per capita was used for the value of life years, net benefit was 3,975,684 FJD (B/C ratio: 1.04). With a pessimistic scenario, establishing the center appeared to be not cost-beneficial, and the net benefit was −53,634,682 FJD (B/C ratio: 0.46); net benefit with an optimistic scenario was estimated 23,178,189 FJD (B/C ratio: 1.20).ConclusionsBased on the CBA results from using GNI per capita instead of the NMW, this project would be cost-beneficial. Introducing a radiation oncology center in Fiji would have potential impacts on financial sustainability, financial protection, and accessibility and equity of the health system.     

Real-time patient radiation dosimeter for use in interventional radiology

There is currently no effective real-time patient dosimeter available for use in interventional radiology (IR). We conducted a feasibility study in a clinical setting to investigate the use of the new dosimeter using photoluminescence sensors during procedures. Reference dosimeters were set at almost the same position of the prototype dosimeter sensors.We found excellent correlations between the reference measurements and those of the prototype dosimeter (r² = 0.950). The sensor of the new dosimeter does not interfere with the IR procedure. The new dosimeter will be an effective tool for the real-time measurement of patient skin doses during IR.     

Condensed-history Monte-Carlo simulation for charged particles: what can it do for us?

Condensed-history (CH) Monte-Carlo (MC) groups together the vast number of individual charged-particle collisions using multiple scattering theory for elastic angular changes and stopping power for energy losses. CH codes such as EGS4 have been enormously successful in simulating the transport of electrons, for example, in radiotherapy. MC-derived values of the water-to-air stopping-power ratio, s _w/air, are used in all modern codes of practice for absolute dose determination in radiotherapy clinics. MC can also directly yield the dose ratio D _med/D _det for a dosimeter in a medium, and Correlated Sampling has been exploited to increase the efficiency, e. g., the central electrode in an ion chamber (aluminium vs. graphite). The extremely low density of the gas in an ion chamber poses problems for CH codes. However, multiple scattering can now be combined with single scattering and is expected to finally resolve important chamber perturbation effects. An exciting application of CH MC in radiotherapy is the computation of dose distributions in patients. Currently one can achieve an uncertainty around 1% (1 SD) in mm-sized voxels in several minutes for an electron beam and in around an hour for a photon treatment plan on hardware costing less than $20,000, and thus avoid all the various approximations conventionally used to account for inhomogeneities. In the microdosimetry/track structure field, CH codes have shown that the fluence (dΦ/dE) per unit dose at low electron energies is virtually independent of incident particle energy or depth, which simply explains the negligible RBE variation. Received: 1 April 1999 / Accepted in revised form: 1 July 1999