Quantitative imaging for targeted radionuclide therapy dosimetry : technical review

Targeted radionuclide therapy (TRT) is a promising technique for cancer therapy. However, in order to deliver the required dose to the tumor, minimize potential toxicity in normal organs, as well as monitor therapeutic effects, it is important to assess the individualized internal dosimetry based on patient-specific data. Advanced imaging techniques, especially radionuclide imaging, can be used to determine the spatial distribution of administered tracers for calculating the organ-absorbed dose. While planar scintigraphy is still the mainstream imaging method, SPECT, PET and bremsstrahlung imaging have promising properties to improve accuracy in quantification. This article reviews the basic principles of TRT and discusses the latest development in radionuclide imaging techniques for different theranostic agents, with emphasis on their potential to improve personalized TRT dosimetry

Development and implementation of efficient noise suppression methods for emission computed tomography

In PET and SPECT imaging, iterative reconstruction is now widely used due to its capability of incorporating into the reconstruction process a physics model and Bayesian statistics involved in photon detection. Iterative reconstruction methods rely on regularization terms to suppress image noise and render radiotracer distribution with good image quality. The choice of regularization method substantially affects the appearances of reconstructed images, and is thus a critical aspect of the reconstruction process. Major contributions of this work include implementation and evaluation of various new regularization methods. Previously, our group developed a preconditioned alternating projection algorithm (PAPA) to optimize the emission computed tomography (ECT) objective function with the non-differentiable total variation (TV) regularizer. The algorithm was modified to optimize the proposed reconstruction objective functions. First, two novel TV-based regularizers—high-order total variation (HOTV) and infimal convolution total variation (ICTV)—were proposed as alternative choices to the customary TV regularizer in SPECT reconstruction, to reduce “staircase” artifacts produced by TV. We have evaluated both proposed reconstruction methods (HOTV-PAPA and ICTV-PAPA), and compared them with the TV regularized reconstruction (TV-PAPA) and the clinical standard, Gaussian post-filtered, expectation-maximization reconstruction method (GPF-EM) using both Monte Carlo-simulated data and anonymized clinical data. Model-observer studies using Monte Carlo-simulated data indicate that ICTV-PAPA is able to reconstruct images with similar or better lesion detectability, compared with clinical standard GPF-EM methods, but at lower detected count levels. This implies that switching from GPF-EM to ICTV-PAPA can reduce patient dose while maintaining image quality for diagnostic use. Second, the 1 norm of discrete cosine transform (DCT)-induced framelet regularization was studied. We decomposed the image into high and low spatial-frequency components, and then preferentially penalized the high spatial-frequency components. The DCT-induced framelet transform of the natural radiotracer distribution image is sparse. By using this property, we were able to effectively suppress image noise without overly compromising spatial resolution or image contrast. Finally, the fractional norm of the first-order spatial gradient was introduced as a regularizer. We implemented 2/3 and 1/2 norms to suppress image spatial variability. Due to the strong penalty of small differences between neighboring pixels, fractional-norm regularizers suffer from similar cartoon-like artifacts as with the TV regularizer. However, when penalty weights are properly selected, fractional-norm regularizers outperform TV in terms of noise suppression and contrast recovery

Segmented field electron conformal therapy with an electron multi-leaf collimator

Purpose: The purpose of this work was to investigate the potential of a prototype electron multi-leaf collimator (eMLC) to deliver segmented-field electron conformal therapy (ECT) and to improve dose homogeneity to the planning target volume (PTV) by feathering the abutting edge of the higher energy electron fields. Methods: Software was developed to define the eMLC leaf positions that most closely fit a general field shape. Electron beams (6-20 MeV) using a prototype eMLC were commissioned for the pencil beam dose algorithm in the Pinnacle treatment planning system. A discrete (5-step) Gaussian edge spread function was used to match electron dose penumbras of differing energies at a specified depth in a water phantom. The effect of 1D edge feathering on dose homogeneity was computed and measured for segmented-field ECT treatment plans for three 2D PTVs in a water phantom (depths varied along axis parallel to leaf motion) and one 3D PTV (depth varied along both axes normal to beam). Additionally, the effect of 2D edge feathering was computed for the 3D PTV. Results: 1D discrete Gaussian edge feathering reduced the standard deviation of dose in the 2D PTVs by 34, 34, and 39%. In the 3D PTV, 1D discrete Gaussian edge feathering reduced the standard deviation of dose by 19%. The physical constraints (1-cm leaf width) of the eMLC hindered the 2D application of the feathering solution to the 3D PTV, and the standard deviation of dose increased by 10%. However, 2D discrete Gaussian edge feathering with a smooth-aperture (infinitesimal leaf width) reduced the standard deviation of dose in the 3D PTV by 33%. Conclusions: A 5-step discrete Gaussian edge spread function applied in 2D improves the abutment dosimetry but requires an eMLC leaf resolution better than 1 cm

Theory of longitudinal emission computed tomography and the practical application to cardiac imaging

Longitudinal Emission Computed Tomography (LECT) is a radioisotope imaging technique which has found particular use in cardiac investigations. However, its clinical use has revealed Imaging problems which show themselves as reconstruction artefacts or false defects. The basis for the imaging problem of LECT is established theoretically using a simple analysis which shows that the reconstruction will predict that activity lies outside the object volume. The volume of the reconstruction lying outside the object volume is considered as an error volume, by using simple, unmodified back projection. This is the first time such a concept has been developed and it is used to calculate an error volume index (EVI). This index is shown to be useful for assessing and comparing LECT systems. It is used to examine the reduction of the error volume by modifications to LECT systems. Thallium-201 perfusion imaging for ischaemic heart disease and infarct detection using a rotating slant hole (RSH) LECT system is compared to conventional planar imaging and X-ray contrast arteriography. RSHLECT is shown not to improve the diagnostic performance of planar imaging. The tomograms suffer from artefacts which appear as defects in the myocardium. Although the presence of these artefacts have been demonstrated by other workers this study shows that they have a significant affect on the diagnostic performance of the technique. A computer simulation and experimental studies using a simulated cardiac chamber are used to study the source of the problem. The origin of the artefacts is demonstrated for the first time. The problem of the error volume in reconstructing the cardiac blood pool is considered. Three techniques to correct the reconstruction volume are examined and one is recommended which will reduce the error volume. Computer simulation and experimental studies with a simulated blood pool are used to examine this problem. It is shown that it is not possible to correct the reconstruction volume when an iterative least squares reconstruction technique is used together with the assumption of a uniform activity distribution; this implies the need for an alternative predictive function. The Inability to correct the reconstruction volume for a simple uniform activity distribution show that, for Thallium-201 perfusion Imaging where the distribution is non-uniform, there is a need for an imaging system modified to reduce the error volume. This work concerning a blood pool LECT reconstruction and correction of the reconstruction volume is original. For the clinical trial of Thallium-201 perfusion imaging and the experimental work with a simulated cardiac chamber, a rotating slant hole LECT system was used. The physical performance of this system was measured and compared with other LECT systems. In doing this a relationship between plane density in the reconstruction and inter-planar resolution is demonstrated for the first time

Use of an Effective Attenuation Coefficient Value and Material Filter Technique for Scatter Correction in Tc-99m SPECT

Accuracy in the diagnosis of disease in Tc-99m Single Photon Emission Computed Tomography is reduced due to the presence of scattered gamma photons in the image data. A range of scatter correction techniques exist, however, none is considered as the standard. The objective of this study is to apply a flat sheet of Aluminum 0.3mm thick as an absorber for the removal of scattered gamma photons and compare the image quality with those images obtained by using effective attenuation coefficient value. Data were acquired with the gamma camera (Philip ADAC Forte dual head) installed with LEHR collimator. A cylindrical phantom with cold and hot regions insert was scanned. Tc-99m radioactive material was introduced into the phantom. Images were reconstructed by using filtered back projection method. Perceived image quality and contrast of cold and hot regions, whereas, count profile and standard deviation in the count density of uniform region was measured. Quantitative analysis of all image quality parameters investigated show fair improvement with material filter. In conclusion, 0.3mm thickness of aluminum material filter may have some advantage over the use of effective attenuation coefficient value for scatter compensation when applied by scanning other ECT phantoms using Tc-99m radionuclide

Virtual Compton Scattering and the Generalized Polarizabilities of the Proton at Q^2=0.92 and 1.76 GeV^2

Virtual Compton Scattering (VCS) on the proton has been studied at Jefferson Lab using the exclusive photon electroproduction reaction (e p --> e p gamma). This paper gives a detailed account of the analysis which has led to the determination of the structure functions P_LL-P_TT/epsilon and P_LT, and the electric and magnetic generalized polarizabilities (GPs) alpha_E(Q^2) and beta_M(Q^2) at values of the four-momentum transfer squared Q^2= 0.92 and 1.76 GeV^2. These data, together with the results of VCS experiments at lower momenta, help building a coherent picture of the electric and magnetic GPs of the proton over the full measured Q^2-range, and point to their non-trivial behavior.Comment: version 2: modified according to PRC Editor's and Referee's recommendations. Archival paper for the E93-050 experiment at JLab Hall A. 28 pages, 23 figures, 5 cross-section tables. To be submitted to Phys.Rev.

Verification and Evaluation of a Passive Intensity Modulation Device for Bolus Conformal Therapy

Purpose: Bolus electron conformal therapy (BECT) provides effective radiation treatment for superficial cancers and other diseases close to the skin surface, but can have as great as a 30% planning target volume (PTV) dose heterogeneity due to scattering from the irregular proximal bolus surface. Intensity modulated (IM) BECT can improve PTV dose homogeneity, but is not currently available. This study fabricated patient-specific passive intensity modulators and validated their delivering planned dose distributions calculated by a modified pencil beam redefinition algorithm (PBRA). Methods: Two test-patterns and four patient-specific intensity modulators were designed, fabricated, and tested. Dose plans were generated using a research version of p.d (.decimal LLC, Sanford, FL), which contained an intensity modulation operator. Dose distributions under intensity modulators were measured using a water phantom and scanning diode. The PBRA was modified to calculate dose in the presence of island blocks (tungsten pins of varying diameters) embedded in a low-density, machinable foam contained within an electron cutout. Results: Dose under island blocks with axes parallel to central axis was greater than expected, believed due to electrons scattered from island blocks, hence island blocks with axes along rays diverging from the virtual source were recommended. The PBRA modeled machineable foam by shifting R90 0.1 cm shallower and scaling σθx by 1.5, calculating dose distributions under foam with an accuracy equal to that without foam; however, foam increased the penumbra indicating it beneficial to reduce its thickness (g×cm2). PBRA modifications for island blocks yielded doses within 3% of measurements for IRF \u3e75%, indicating the need to model scatter from and into island blocks for lower IRFs. For all four patient-specific intensity modulators, measured doses were within 3%/3mm of calculated doses for ≥99.5% of points having dose \u3e10%, proving the hypothesis. Conclusions: Results showed that patient intensity modulators could deliver dose (fluence) within 3%/3mm of that planned, indicating the PBRA was sufficiently accurate for the patients studied and that .decimal can fabricate intensity modulators capable of delivering planned dose distributions. Comparison of dose distributions measured with a dose matrix for additional patient plans having greater intensity modulation is needed to establish future QA criteria

A Measurement of the Parity-Violating Asymmetry in Aluminum and its Contribution to A Measurement of the Proton\u27s Weak Charge

The Qweak experiment, which ran at the Thomas Je↵erson National Accelerator Facility, made a precision measurement of the proton’s weak charge, Q_p^W . The weak charge is extracted via a measurement of the parity-violating asymmetry in elastic electron-proton scattering from hydrogen at low momentum transfer (Q^2=0.025 GeV^2). This result is directly related to the electroweak mixing angle, sin2 (theta_W ), a fundamental parameter in the Standard Model of particle physics. This provides a precision test sensitive to new, as yet unknown, fundamental physics. This dissertation focuses on two central corrections to the Qweak measurement: the target window contribution and sub-percent determination of the electron beam polarization. The aluminum target windows contribute approximately 30% of the measured asymmetry. Removal of this background requires precise measurements of both the elastic electron-aluminum scattering rate and its parity-violating asymmetry. The results reported here are the most precise measurement of the Qweak target dilution and asymmetry to date. The parity-violating asymmetry for the aluminum alloy was found to be 1.6174 ± 0.0704 (stat.) ± 0.0113 (sys.) parts-per-million. The first sub-percent precision polarization measurements made from the Hall C Møller polarimeter are also reported, with systematic uncertainties of 0.84%

Small Animal X-ray Irradiator Characterisation

The aim of this project is to characterise an X-RAD 320 x-ray irradiator in the low energy spectrum range of 50-320kVp and develop methods for real-time 2d imaging of low energy x-rays using a MagicPlate-512 detector. The dose characteristics measured were the Output factor, depth dose, dose rate, and dose profile. The irradiator was characterised using the ‘American Association of Physicists in Medicine protocol for 40-300kV x-ray beam dosimetry’ (TG-61 protocol) to describe dose. First, the response was measured with a farmer chamber, using the TG-61 protocol the response was converted into dose. Using the farmer chamber the effect of different quantities on dose absorbed was tested including X-ray tube voltage, field size, SSD, and depth in water phantom. The ionisation chamber data allowed for the development of formula for dose absorbed by the MagicPlate-512 detector. EBT3 radiochromic film was used to compare the 2d dose imaging quality of the MagicPlate- 512. An attempt was made to develop a Geant4 Monte Carlo based simulation for comparison against detector materials, unfortunately the simulations did not show a similar relationship in dose deposited when compared to any of the other detector results. Other than the adjustable square collimator a 1cm (at 50cm SSD) pencil beam collimator was tested and found to be significantly rotationally unsymmetrical. To reduce electric noise the MagicPlate-512 detector was covered in aluminium tape, the tape and the detector housing was then connected to ground. To reduce the dose rate dependence, the detector was irradiated with 3Mrad, which improved the equalization of pixel response, comprehensive testing was not possible due to restricted lab access. When compared to a previous study by Rezvan which also used the X-RAD 320, once the difference in SSD and accounting for the backscatter factor the dose rate found experimentally using the farmer chamber was larger than Rezvan’s dose rate (21.2273mGy/s estimated at 50cm SSD compared to the 14.8333mGy/s found by Rezvan). Though this difference is significant the larger field size (24cm compared to 20cm) support that Rezvan’s dose should be lower. The MagicPlate-512 response illogically increased with depth in water phantom, at this low energy range the penetrating power of the x-rays should be relatively low meaning that the dose should be deposited at low depths