Polymer gel dosimetry using x-ray computed tomography: a feasibility study

A new three-dimensional dosimetry technique using x-ray computed tomography (CT) to analyse polymer gels is proposed. The CT imaging is sensitive to radiation-induced density changes that occur within irradiated polyacrylamide gel (PAG). In this preliminary study, a CT imaging protocol is developed to optimize CT images of PAG; the response of PAG CT number to dose (N(CT)-dose response) and the reproducibility of the response are investigated, and the use of CT to analyse PAG is compared with MRI. Experiments were conducted using two 1.5 l cylindrical PAG phantoms (3% acrylamide, 3% bis and 5% gelatin by weight), one irradiated with four intersecting 10 MV photon beams and the other with 10 sets of 6 MV parallel opposed circular radiosurgery fields. The final imaging protocol involves using optimum CT parameters (120 kVp and 200 mAs for our GE HiSpeed CT/i scanner), image averaging and background subtraction. The N(CT)-dose response is reproducible, linear up to 800-1000 cGy and is relatively insensitive to the gel temperature during imaging. The dose resolution is approximately 50 cGy for an image thickness of 10 mm. Despite the low dose resolution, preliminary results indicate that this CT technique provides accurate localization of high dose gradients such as those observed in stereotactic radiosurgery. Thus, given the availability and speed of CT scanners, the technique has the potential to be a valuable and practical 3D dose verification tool in radiation therapy.     

Limited-angle x-ray luminescence tomography: methodology and feasibility study

X-ray luminescence tomography (XLT) has recently been proposed as a new imaging modality for biological imaging applications. This modality utilizes phosphor nanoparticles which luminesce near-infrared light when excited by x-ray photons. The advantages of this modality are that it uniquely combines the high sensitivity of radioluminescent nanoparticles and the high spatial localization of collimated x-ray beams. Currently, XLT has been demonstrated using x-ray spatial encoding to resolve the imaging volume. However, there are applications where the x-ray excitation may be limited by geometry, where increased temporal resolution is desired, or where a lower dose is mandatory. This paper extends the utility of XLT to meet these requirements by incorporating a photon propagation model into the reconstruction algorithm in an x-ray limited-angle (LA) geometry. This enables such applications as image-guided surgery, where the ability to resolve lesions at depths of several centimeters can be the key to successful resection. The hybrid x-ray/diffuse optical model is first formulated and then demonstrated in a breast-sized phantom, simulating a breast lumpectomy geometry. Both numerical and experimental phantoms are tested, with lesion-simulating objects of various sizes and depths. Results show localization accuracy with median error of 2.2 mm, or 4% of object depth, for small 2-14 mm diameter lesions positioned from 1 to 4.5 cm in depth. This compares favorably with fluorescence optical imaging, which is not able to resolve such small objects at this depth. The recovered lesion size has lower size bias in the x-ray excitation direction than the optical direction, which is expected due to the increased optical scatter. However, the technique is shown to be quite invariant in recovered size with respect to depth, as the standard deviation is less than 2.5 mm. Sensitivity is a function of dose; radiological doses are found to provide sufficient recovery for μg ml(-1) concentrations, while therapy dosages provide recovery for ng ml(-1) concentrations. Experimental phantom results agree closely with the numerical results, with positional errors recovered within 8.6% of the effective depth for a 5 mm object, and within 5.2% of the depth for a 10 mm object. Object-size median error is within 2.3% and 2% for the 5 and 10 mm objects, respectively. For shallow-to-medium depth applications where optical and radio-emission imaging modalities are not ideal, such as in intra-operative procedures, LAXLT may be a useful tool to detect molecular signatures of disease.     

Transcostal high-intensity-focused ultrasound: ex vivo adaptive focusing feasibility study

Ex vivo experiments have been conducted through excised pork rib with bone, cartilage, muscle and skin. The aberrating effect of the ribcage has been experimentally evaluated. Adaptive ultrasonic focusing through ribs has been studied at low power. Without any correction, the pressure fields in the focal plane were both affected by inhomogeneous attenuation and phase distortion and three main effects were observed: a mean 2 mm shift of the main lobe, a mean 1.25 mm spreading of the half width of the main lobe and up to 20 dB increase of the secondary lobe level. Thanks to time-reversal focusing, a 5 dB decrease in the secondary lobes was obtained and the ratio between the energy deposited at the target location and the total amount of energy emitted by the therapeutic array was six times higher than that without correction. Time-reversal minimizes the heating of the ribs by automatically sonicating between the ribs, as demonstrated by temperature measurements using thermocouples placed at different locations on the ribcage. It is also discussed how this aberration correction process could be achieved non-invasively for clinical application.     

Group cognitive behavioral therapy for bipolar disorder: a feasibility and effectiveness study

BACKGROUND: Bipolar disorder (BD) is a common disorder that results in significant psychosocial impairment, including diminished quality of life and functioning, despite aggressive pharmacotherapy. Psychosocial interventions that target functional factors could be beneficial for this population, and we hypothesized that the addition of group cognitive behavioral therapy (CBT) to maintenance pharmacotherapy would improve functioning and quality of life. METHODS: Patients diagnosed (by SCID) with bipolar disorder attending an outpatient clinic of a mood disorders program participated in the study. All patients were on maintenance mood stabilizers, and were required to have controlled symptoms before entering the study. Mood symptoms were assessed with the Hamilton Depression Rating scale and Young Mania scale at baseline and 14 weeks. Objective and subjective functioning was rated at the same interval using the Global Assessment of Functioning scale and the Medical Outcomes Survey SF-36. Treatment was provided via a specific manual based on CBT principles that could be applied to this population. RESULTS: Forty nine patients participated in this open trial, and 38 patients completed treatment. Objective and subjective indices of impairment showed improvement after 14 weeks. Both GAF and MOS scores increased significantly by the end of treatment. LIMITATIONS: This study was an open trial, and lack of control groups limits the interpretation of results. Because the study concerned effectiveness, the results do not clarify whether the improvement represents the normal course of illness or whether it is the result of the CBT intervention. CONCLUSIONS: The addition of group CBT to standard pharmacological treatment was acceptable to patients, and nearly 80% of patients complied with treatment. Despite the fact that mood symptoms were controlled at entry into the study, psychosocial functioning increased significantly at the end of treatment. Adjunctive CBT should be further investigated in this population.     

Interaction vertex imaging (IVI) for carbon ion therapy monitoring: a feasibility study

Proton imaging can be seen as a powerful technique for online monitoring of ion range during carbon ion therapy irradiations. Indeed, a large number of secondary protons are created during nuclear reactions, and many of these protons are likely to escape from the patient even for deep-seated tumors, carrying accurate information on the reaction vertex position. Two detection techniques have been considered: (i) double-proton detection by means of two forward-located trackers and (ii) single-proton detection in coincidence with the incoming carbon ion detected by means of a beam hodoscope. Geant4 simulations, validated by proton yield measurements performed at GANIL and GSI, show that ion-range monitoring is accessible on a pencil-beam basis with the single-proton imaging technique. Millimetric precision on the Bragg peak position is expected in the ideal case of homogeneous targets. The uncertainties in more realistic conditions should be investigated, in particular the influence of tissue heterogeneity in the very last part of the ion path (about 20?mm).     

Particle selection for laser-accelerated proton therapy feasibility study

In this paper we present calculations for the design of a particle selection system for laser-accelerated proton therapy. Laser-accelerated protons coming from a thin high-density foil have broad energy and angular spectra leading to dose distributions that cannot be directly used for therapeutic applications. Our solution to this problem is a compact particle selection and collimation device that delivers small pencil beams of protons with desired energy spectra. We propose a spectrometer-like particle selection and beam modulation system in which the magnetic field will be used to spread the protons spatially according to their energies and emitting angles. Subsequently, an aperture will be used to select the protons within a therapeutic window of energy (energy modulation). It will be shown that for the effective proton spatial differentiation, the primary collimation device should be used, which will collimate protons to the desired angular distribution and limit the spatial mixing of different energy protons once they have traveled through the magnetic system. Due to the angular proton distribution, the spatial mixing of protons of different energies will always be present and it will result in a proton energy spread with the width depending on the energy. For 250 MeV protons, the width (from the maximum to the minimum energy) is found to be 50 MeV for the magnetic field configuration used in our calculations. As the proton energy decreases, its energy width decreases as well, and for 80 MeV protons it equals 9 MeV. The presence of the energy width in the proton energy distribution will modify the depth dose curves needed for the energy modulation calculation. The matching magnetic field setup will ensure the refocusing of the selected protons and the final beam will be collimated by the secondary collimator. The calculations presented in this article show that the dose rate that the selection system can yield is on the order of D=260 Gy/min for a field size of 1 x 1 cm2.     

Extracting material parameters from x-ray attenuation: a CT feasibility study using kilovoltage synchrotron x-rays incident upon low atomic number absorbers

The work reported here is a feasibility study of the extraction of material parameters from measurements of the linear x-ray attenuation coefficient of low atomic number absorbers. Computed tomography (CT) scans of small samples containing several liquids and solids were carried out with synchrotron radiation at the Australian National Beamline Facility (BL 20B) in Japan. Average values of the x-ray linear attenuation coefficient were extracted for each material for x-ray energies ranging from 11 keV to 20.5 keV. The electron density was estimated by applying results derived from a parametrization of the x-ray linear attenuation coefficient first developed by Jackson and Hawkes and extended for this work. Average estimates for the electron density of triethanolamine and acetic acid were made to within +5.3% of the actual value. Other materials examined included furfuraldehyde, perspex and teflon, for which average estimates of the electron density were less than 10% in excess of the calculated value.     

MRI-guided interstitial ultrasound thermal therapy of the prostate: a feasibility study in the canine model

The feasibility of MRI-guided interstitial ultrasound thermal therapy of the prostate was evaluated in an in vivo canine prostate model. MRI compatible, multielement interstitial ultrasound applicators were developed using 1.5 mm diameter cylindrical piezoceramic transducers (7 to 8 MHz) sectored to provide 180 degrees of angular directional heating. Two in vivo experiments were performed in canine prostate. The first using two interstitial ultrasound applicators, the second using three ultrasound applicators in conjunction with rectal and urethral cooling. In both experiments, the applicators were inserted transperineally into the prostate with the energy directed ventrally, away from the rectum. Electrical power levels of 5-17 W per element (approximately 1.6-5.4 W acoustic output power) were applied for heating periods of 18 and 48 min. Phase-sensitive gradient-echo MR imaging was used to monitor the thermal treatment in real-time on a 0.5 T interventional MRI system. Contrast-enhanced T1-weighted images and vital-stained serial tissue sections were obtained to assess thermal damage and correlate to real-time thermal contour plots and calculated thermal doses. Results from these studies indicated a large volume of ablated (nonstained) tissue within the prostate, extending 1.2 to 2.0 cm from the applicators to the periphery of the gland, with the dorsal margin of coagulation well-defined by the applicator placement and directionality. The shape of the lesions correlated well to the hypointense regions visible in the contrast-enhanced T1-weighted images, and were also in good agreement with the contours of the 52 degrees C threshold temperature and t43 > 240 min. This study demonstrates the feasibility of using directional interstitial ultrasound in conjunction with MRI thermal imaging to monitor and possibly control thermal coagulation within a targeted tissue volume while potentially protecting surrounding tissue, such as rectum, from thermal damage.     

A biodegradable vascularizing membrane: a feasibility study

Regenerative medicine and in vivo biosensor applications require the formation of mature vascular networks for long-term success. This study investigated whether biodegradable porous membranes could induce the formation of a vascularized fibrous capsule and, if so, the effect of degradation kinetics on neovascularization. Poly(l-lactic acid) (PLLA) and poly(dl-lactic-co-glycolic) acid (PLGA) membranes were created by a solvent casting/salt leaching method. Specifically, PLLA, PLGA 75:25 and PLGA 50:50 polymers were used to vary degradation kinetics. The membranes were designed to have an average 60mum pore diameter, as this pore size has been shown to be optimal for inducing blood vessel formation around nondegradable polymer materials. Membrane samples were imaged by scanning electron microscopy at several time points during in vitro degradation to assess any changes in pore structure. The in vivo performance of the membranes was assessed in Sprague-Dawley rats by measuring vascularization within the fibrous capsule that forms adjacent to implants. The vascular density within 100microm of the membranes was compared with that seen in normal tissue, and to that surrounding the commercially available vascularizing membrane TheraCyte. The hemoglobin content of tissue containing the membranes was measured by four-dimensional elastic light scattering as a novel method to assess tissue perfusion. Results from this study show that slow-degrading membranes induce greater amounts of neovascularization and a thinner fibrous capsule relative to fast degrading membranes. These results may be due both to an initially increased number of macrophages surrounding the slower degrading membranes and to the maintenance of their initial pore structure.     

Automated multiple-cell karyotyping: a clinical feasibility study

In order to increase the efficiency of the Magiscan metaphase location and karyotyping system, its software and mode of operation have been changed. In the new multiple-cell karyotyping method, interactions by the operator are only required for relocation and counting of metaphases, but not for karyotyping. Metaphases are located and their coordinates recorded automatically as before. The first metaphase in the list is relocated, displayed on the screen, and counted by the operator. It is then karyotyped automatically while the operator relocates and counts the next metaphase in the list. This procedure continues until an appropriate number of metaphases have been counted and karyotyped. Finally a composite karyotype is printed out. Each karyotype is represented by a column of 23 chromosome pairs (1-22 and XX or XY) and all columns are lined up next to each other. Most chromosomes are correctly classified into the composite karyotype. Minor structural abnormalities are detected by comparing pairs of homologues. Overlapped, close touching, and grossly abnormal chromosomes are often misclassified or rejected and shown beneath the classified chromosomes. A trained cytotechnician can easily detect even small chromosome abnormalities on the composite karyotype. A clinical feasibility study indicates that the procedure can be used for routine cytogenetic analysis.     

The feasibility of polychromatic cone-beam x-ray fluorescence computed tomography (XFCT) imaging of gold nanoparticle-loaded objects: a Monte Carlo study

A recent study investigated the feasibility to develop a bench-top x-ray fluorescence computed tomography (XFCT) system capable of determining the spatial distribution and concentration of gold nanoparticles (GNPs) in vivo using a diagnostic energy range polychromatic (i.e. 110 kVp) pencil-beam source. In this follow-up study, we examined the feasibility of a polychromatic cone-beam implementation of XFCT by Monte Carlo (MC) simulations using the MCNP5 code. In the current MC model, cylindrical columns with various sizes (5-10 mm in diameter) containing water loaded with GNPs (0.1-2% gold by weight) were inserted into a 5 cm diameter cylindrical polymethyl methacrylate phantom. The phantom was then irradiated by a lead-filtered 110 kVp x-ray source, and the resulting gold fluorescence and Compton-scattered photons were collected by a series of energy-sensitive tallies after passing through lead parallel-hole collimators. A maximum-likelihood iterative reconstruction algorithm was implemented to reconstruct the image of GNP-loaded objects within the phantom. The effects of attenuation of both the primary beam through the phantom and the gold fluorescence photons en route to the detector were corrected during the image reconstruction. Accurate images of the GNP-containing phantom were successfully reconstructed for three different phantom configurations, with both spatial distribution and relative concentration of GNPs well identified. The pixel intensity of regions containing GNPs was linearly proportional to the gold concentration. The current MC study strongly suggests the possibility of developing a bench-top, polychromatic, cone-beam XFCT system for in vivo imaging.     

Motion in radiotherapy: particle therapy

Charged particle beam radiotherapy requires dedicated measures to compensate for the dosimetric influence of inter- and intra-fractional target motion. Independent of the delivery technique, these measures have to incorporate the strong influence of the radiological depth on the delivered dose. For scanned beam delivery, interference effects of target motion and scanned beam can further cause under-dosage of the clinical target volume despite using margins. Within the scope of this review, published data with respect to motion management in scattered as well as scanned beam treatment delivery will be summarized. Based on a section covering the dosimetric impact of organ motion, motion management during treatment planning, patient positioning, treatment delivery and treatment validation will be summarized. For scattered beam delivery, the concepts and data are often based on clinical usage since treatment of moving tumors has been performed for several years. In the field of scanned beam delivery, the report focuses on the results of research on countermeasures of the interference effect. Clinical application of these techniques can be expected in the near future.     

Computed tomography with energy-resolved detection: a feasibility study

The feasibility of computed tomography (CT) with energy-resolved x-ray detection has been investigated. A breast CT design with multi slit multi slice (MSMS) data acquisition was used for this study. The MSMS CT includes linear arrays of photon counting detectors separated by gaps. This CT configuration allows for efficient scatter rejection and 3D data acquisition. The energy-resolved CT images were simulated using a digital breast phantom and the design parameters of the proposed MSMS CT. The phantom had 14 cm diameter and 50/50 adipose/glandular composition, and included carcinoma, adipose, blood, iodine and CaCO3 as contrast elements. The x-ray technique was 90 kVp tube voltage with 660 mR skin exposure. Photon counting, charge (energy) integrating and photon energy weighting CT images were generated. The contrast-to-noise (CNR) improvement with photon energy weighting was quantified. The dual energy subtracted images of CaCO3 and iodine were generated using a single CT scan at a fixed x-ray tube voltage. The x-ray spectrum was electronically split into low- and high-energy parts by a photon counting detector. The CNR of the energy weighting CT images of carcinoma, blood, adipose, iodine, and CaCO3 was higher by a factor of 1.16, 1.20, 1.21, 1.36 and 1.35, respectively, as compared to CT with a conventional charge (energy) integrating detector. Photon energy weighting was applied to CT projections prior to dual energy subtraction and reconstruction. Photon energy weighting improved the CNR in dual energy subtracted CT images of CaCO3 and iodine by a factor of 1.35 and 1.33, respectively. The combination of CNR improvements due to scatter rejection and energy weighting was in the range of 1.71-2 depending on the type of the contrast element. The tilted angle CZT detector was considered as the detector of choice. Experiments were performed to test the effect of the tilting angle on the energy spectrum. Using the CZT detector with 20 degrees tilting angle decreased the tailing of the measured x-ray spectrum as compared to a conventional CZT detector. It was concluded that the energy-resolved MSMS CT with tilted angle CZT detector is potentially feasible and could provide a unique combination of photon counting, energy weighting, scatter rejection and single kVp dual energy subtraction CT imaging.     

Phase contrast enhancement of x-ray mammography: a design study

This paper explores the application to mammography of phase contrast produced by variations in x-ray refractive index. As a spatially coherent x-ray beam propagates through an x-ray transparent medium, the phase of the incident wavefront becomes modified in a manner related to the electron density of the medium. The resulting phase gradient across the wavefront is equivalent to a small change in direction of the propagation of the wave. For a general object, the change in propagation direction will vary from point to point depending on the structures within the object. The net effect can be recorded in a radiographic image using an appropriate geometry to produce the visual appearance of edge enhancement at interfaces between materials with differing x-ray refractive indices. Normally these materials will also have differences in attenuation coefficient, so the overall effect is to increase the visibility of interfaces between materials. It is proposed that mammographic images can be subtly enhanced by the use of phase contrast information to overcome some of the known limitations of the imaging process whilst leaving the gross radiological appearance of the images substantially unchanged. The design trade-offs required to utilize phase contrast information were investigated using a conventional mammographic x-ray generator and film-screen system. The Leeds TORMAM mammographic image quality test object was then used to demonstrate a considerable improvement in image quality for the phase contrast enhanced images over those produced in the conventional geometry with no increase in radiation dose to the patient. The results are discussed in terms of their possible practical application.     

Alumina as a filler for bone cement: a feasibility study

A composite bone cement of Alcoa A-10 Alumina and very finely ground poly(methyl methacrylate) beads (PMMA) was fabricated. It was tested in an attempt to improve on the conventionally used pure PMMA bone cement.

By knowing the densities of the powders and their volumes, the mass of each was calculated for the most efficient packing of PMMA and Al₂O₃ powders and a 65% PMMA: 35% Al₂O₃ ratio by weight composition was determined. This was tested, as well as the pure cement so comparisons could be made. Cylinders for the strength tests were also made of silane treated Al₂O₃.

The compositions were tested for compressive and tensile strengths. The pure PMMA, composite and silane treated composite had compressive strengths of 79.64 ± 13.0, 83.17 ± 4.8, and 71.52±8.6 MPa and the tensile strengths were 6.69 ±0.6, 5.12 ±0.3, and 7.12±0.5 MPa respectively. Also the 65%–35% PMMA-Al₂O₃ composite required 64% less monomer for mixing than did the pure cement which is thought to be better for tissue healing. The maximum temperature attained from room temperature was 110°–115°C for both cements. The composite took 6.5 min longer to reach its peak temperature than did the pure cement. The bone cements were implanted for one week in a rabbit and both compositions seemed acceptable by the tissue.     

Modelization of a self-opening peripheral neural interface: a feasibility study

In this paper a self-opening intrafascicular neural interface (SELINE) has been modeled using both a theoretical approach and a Finite Element (FE) analysis. This innovative self opening interface has several potential advantages such as: higher selectivity due to its three-dimensional structure and efficient anchorage system. Mechanical, structural and micro-technological issues have been considered to obtain an effective design of the electrode, as a feasibility study of the self-opening approach. A simple framework has been provided to model the insertion and partial retraction into peripheral nerves, resulting in the opening of wings.This integrated approach results in a rational procedure to optimize kinematics, geometry, and structural properties of peripheral interfaces. The design and feasibility study carried out in this work can potentially assure a correct behavior and dimensioning of the neural interface: in this way anomalous breakage should be avoided while mechanical and geometrical biocompatibility should increase.