Quantitative SPECT/CT imaging of actinium-225 for targeted alpha therapy of glioblastomas.

BACKGROUND: A new, alternative option for patients with recurrent glioblastoma is targeted alpha therapy (TAT), in the form of a local administration of substance P (neurokinin type 1 receptor ligand, NK-1) labelled with 225Ac. The purpose of the study was to confirm the feasibility of quantitative SPECT imaging of 225Ac, in a model reproducing specific conditions of TAT. In particular, to present the SPECT calibration methodology used, as well as the results of validation measurements and their accuracy. Additionally, to discuss the specific problems related to high noise in the presented case. MATERIALS AND METHODS: All SPECT/CT scans were conducted using the Symbia T6 equipped with HE collimators, and acquired with multiple energy windows (three main windows: 440 keV, 218 keV, and 78 keV, with three lower scatter energy windows). A Jaszczak phantom with fillable cylindrical sources of various sizes was used to investigate quantitative SPECT/CT imaging characteristics. The planar sensitivity of the camera, an imaging calibration factor, and recovery coefficients were determined. Additionally, the 3D printed model of the glioblastoma tumour was developed and imaged to evaluate the accuracy of the proposed protocol. RESULTS: Using the imaging calibration factor and recovery coefficients obtained with the Jaszczak phantom, we were able to quantify the activity in a 3D-printed model of a glioblastoma tumour with uncertainty of no more than 10% and satisfying accuracy. CONCLUSIONS: It is feasible to perform quantitative 225Ac SPECT/CT imaging. However, there are still many more challenges that should be considered for further research on this topic (among others: accurate determination of ICF in the case of high background noise, better method of background estimation for recovery coefficient calculations, other methods for scatter correction than the dual-energy window scatter-compensation method used in this study).

Isodoses-a set theory-based patient-specific QA measure to compare planned and delivered isodose distributions in photon radiotherapy.

BACKGROUND: The gamma index and dose-volume histogram (DVH)-based patient-specific quality assurance (QA) measures commonly applied in radiotherapy planning are unable to simultaneously deliver detailed locations and magnitudes of discrepancy between isodoses of planned and delivered dose distributions. By exploiting statistical classification performance measures such as sensitivity or specificity, compliance between a planned and delivered isodose may be evaluated locally, both for organs-at-risk (OAR) and the planning target volume (PTV), at any specified isodose level. Thus, a patient-specific QA tool may be developed to supplement those presently available in clinical radiotherapy. MATERIALS AND METHODS: A method was developed to locally establish and report dose delivery errors in three-dimensional (3D) isodoses of planned (reference) and delivered (evaluated) dose distributions simultaneously as a function the dose level and of spatial location. At any given isodose level, the total volume of delivered dose containing the reference and the evaluated isodoses is locally decomposed into four subregions: true positive-subregions within both reference and evaluated isodoses, true negative-outside of both of these isodoses, false positive-inside the evaluated isodose but not the reference isodose, and false negatives-inside the reference isodose but not the evaluated isodose. Such subregions may be established over the whole volume of delivered dose. This decomposition allows the construction of a confusion matrix and calculation of various indices to quantify the discrepancies between the selected planned and delivered isodose distributions, over the complete range of values of dose delivered. The 3D projection and visualization of the spatial distribution of these discrepancies facilitates the application of the developed method in clinical practice. RESULTS: Several clinical photon radiotherapy plans were analyzed using the developed method. In some plans at certain isodose levels, dose delivery errors were found at anatomically significant locations. These errors were not otherwise highlighted-neither by gamma analysis nor by DVH-based QA measures. A specially developed 3D projection tool to visualize the spatial distribution of such errors against anatomical features of the patient aids in the proposed analysis of therapy plans. CONCLUSIONS: The proposed method is able to spatially locate delivery errors at selected isodose levels and may supplement the presently applied gamma analysis and DVH-based QA measures in patient-specific radiotherapy planning.

Are gamma passing rate and dose-volume histogram QA metrics correlated?

PURPOSE: The quality of a measured distribution of dose delivered against its corresponding radiotherapy plan is routinely assessed by gamma index (GI) and dose-volume histogram (DVH) metrics. Any correlation between error detection rates, as based on either of these approaches, while argued, has never been convincingly demonstrated. The dependence of the strength of correlation between the GI passing rate ( γ P ) and DVH quality assurance (QA) metrics on various elements of the therapy plan has not been systematically investigated. METHODS: A formal analysis of the relation between γ P and DVH metrics has been undertaken, leading to a relationship which may partly approximate γ P with respect to the DVH. This relationship was further validated by studying examples of simulated clinical radiotherapy plans and by studying the correlation between γ P and the derived relationship using a simple two-dimensional representations of the planning target volume (PTV) and organs at risk (OAR), where penumbra regions, distance-to-agreement tolerances and dose delivery errors were systematically varied. RESULTS: It is shown formally that there cannot be any correlation between γ P and other commonly applied DVH-derived QA measures. However, γ P may be partly approximated given the planned and measured DVH. The derived γ P approximation (the " γ -slope indicator") may be clinically useful in some practical cases of radiotherapy plan QA. CONCLUSIONS: In formal terms, there cannot be any correlation between γ P and any common DVH-calculated patient-specific measures, with respect to PTV or OAR. However, as demonstrated analytically and further confirmed in our simulation studies, the γ P approximation derived in this study (the " γ -slope indicator") may in some cases offer a degree of correlation between γ P and the PTV and OAR DVH QA metrics in measured and planned patient-specific dose distributions-which may be potentially useful in clinical practice.

On the optimization of bone SPECT/CT in terms of image quality and radiation dose.

INTRODUCTION: The purpose of this study was to present the optimization process of CT parameters to reduce patient exposure during bone SPECT/CT without affecting the quality of SPECT images with attenuation correction (AC). MATERIAL AND METHODS: A fillable phantom reflecting realistic bone scintigraphy conditions was developed and acquired on an AnyScan SC. SPECT/CT scans were carried out with different x-ray tube current values (10, 20, 30, 40, 50, 60, 70, 90, 110, 130, 150, and 200 mA) at three different high-voltage values (80, 100, and 120 kV). The contrast (C) and coefficients of variation (CV) in the SPECT images as well as the signal-to-noise ratio (SNR) and noise (SDCT ) in the CT images with CTDIvol were measured. An optimal acquisition protocol that obtained SPECT/CT images with no artifacts on both CT and SPECT images, acceptable C, SNR, CV, and SDCT values, and the largest reduction in patient exposure compared to the reference acquisition procedure was sought. RESULTS: The optimal set of parameters for bone SPECT/CT was determined based on a phantom study. It has been implemented in clinical practice. Two groups of patients were examined according to the baseline and optimized protocols, respectively. The new SPECT/CT protocol substantially reduced patients' radiation exposure compared to the old protocol while maintaining the required diagnostic quality of SPECT and CT images. CONCLUSIONS: In the study, we present a methodology that finds a compromise between diagnostic information and patient exposure during bone SPECT/CT procedures.

Statistical approach to the selection of the tolerances for distance to agreement improves the quality control of the dose delivery in radiotherapy.

In the study, a local approach to setting reference tolerance values for the distance-to-agreement (DTA) component of the gamma index is proposed. The reference tolerance values are calculated in simulations, following a dose delivery model presented in a previous work. An analytical model for determining the quantiles of DTA distribution is also proposed and verified. It is shown that the distributions of DTA values normalized with either quantiles or standard deviation of DTA distributions are universal over analyzed plans and points within a single plan. This enables statistically sound inference about the quality of dose delivery. In particular, based on the normalized distributions the comparison of planned and delivered doses can be formulated within the framework of statistical inference as a problem of multiple statistical testing. For every evaluated point P of a plan, one may formulate and test a null hypothesis that there is no delivery error against an alternative hypothesis that there is a delivery error in P. It is also shown that the proposed approach is more sensitive than the current standard approach to shift errors in high dose gradient regions.

A simulation-based method for evaluating geometric tests of a linac c-arm in quality control in radiotherapy.

PURPOSE: Assessment of the accuracy of geometric tests of a linac used in external beam therapy is crucial for ensuring precise dose delivery. In this paper, a new simulation-based method for assessing accuracy of such geometric tests is proposed and evaluated on a set of testing procedures. METHODS: Linac geometry testing methods used in this study are based on an established design of a two-module phantom. Electronic portal imaging device (EPID) images of fiducial balls contained in these modules can be used to automatically reconstruct linac geometry. The projection of the phantom modules fiducial balls onto the EPID detector plane is simulated for assumed nominal geometry of a linac. Then, random errors are added to the coordinates of the projections of the centers of the fiducial balls and the linac geometry is reconstructed from these data. RESULTS: Reconstruction is performed for a set of geometric test designs and it is shown how the dispersion of the reconstructed values of geometric parameters depends on the design of a geometric test. Assuming realistic accuracy of EPID image analysis, it is shown that for selected testing plans the reconstruction accuracy of geometric parameters can be significantly better than commonly used action thresholds for these parameters. CONCLUSIONS: Proposed solution has the potential to improve geometric testing design and practice. It is an important part of a fully automated geometric testing solution.

Use of statistical approaches to improve the quality control of the dose delivery in radiotherapy.

The gamma index is a measure used routinely for the quality control of dose delivery in radiotherapy, implemented in commercial systems for the verification of treatment plans. It involves comparison of the difference between planned and delivered doses to a single reference. The same reference value is selected for all points in the plan that can potentially hide dose delivery errors, especially in medium and low dose areas. In this study, a receiver operating characteristic analysis is used to demonstrate the limits of the performance of the global gamma index as a method for detecting dose delivery errors. The performance of a global gamma index is compared with two approaches based on statistical tests for outlier detection. Two statistical approaches are considered: according to the first, the distribution of the delivered doses is estimated based on an appropriate calibration procedure. According to the second, the distribution of the delivered doses is estimated based on the detection of relatively homogeneous regions of a plan and analyzing the distributions of planned doses within these regions. The performance of the three approaches is compared based on analytical considerations and in simulations in which errors are intentionally introduced to the plan delivery and noise related to dose delivery is modeled. We have shown that a statistics-based approach to gamma analysis generally leads to better detection of true delivery errors. The results of analytical consideration coincide with the simulations. In simulations, we observe that both statistical approaches are better detectors of true delivery errors than the global method for the gamma-index passing rate in the range from 0.9-1.0. It is shown that the global gamma index is a weak detector of dose delivery errors, which in some circumstances behaves only slightly better than a purely random classifier.

INVESTIGATION OF SECONDARY MIXED RADIATION FIELD AROUND A MEDICAL LINEAR ACCELERATOR.

The aim of this study is to investigate secondary mixed radiation field around linac, as the first part of an overall assessment of out-of-field contribution of neutron dose for new advanced radiation dose delivery techniques. All measurements were performed around Varian Clinic 2300 C/D accelerator at Maria Sklodowska-Curie Memorial, Cancer Center and Institute of Oncology, Krakow Branch. Recombination chambers REM-2 and GW2 were used for recombination index of radiation quality Q4 determination (as an estimate of quality factor Q), measurement of total tissue dose Dt and calculation of gamma and neutron components to Dt. Estimation of Dt and Q4 allowed for the ambient dose equivalent H*(10) per monitor unit (MU) calculations. Measurements around linac were performed on the height of the middle of the linac's head (three positions) and on the height of the linac's isocentre (five positions). Estimation of secondary radiation level was carried out for seven different configurations of upper and lower jaws position and multileaf collimator set open or closed in each position. Study includes the use of two photon beam modes: 6 and 18 MV. Spatial distribution of ambient dose equivalent H*(10) per MU on the height of the linac's head and on the standard couch height for patients during the routine treatment, as well as relative contribution of gamma and neutron secondary radiation inside treatment room were evaluated.

A generic multimodule phantom for testing geometry of a linac c-arm as a part of quality control in radiotherapy.

PURPOSE: To develop an assumption-free methodology for testing geometry of linacs. METHODS: The problem of projecting a fiducial positioned in a predefined point in a 3D space and attached rigidly to a treatment table of a radiotherapeutic device onto an imaging plane with unknown characteristics from a source with unknown coordinates is formulated. The problem of determining these unknowns is formulated as an optimization problem. The problem of determining the gantry/the collimator rotation axis and angle from projection of additional fiducials is also formulated and solved. Analytical methodology is developed for determining isocenter position and an error of estimating isocenter position. The developed methodology is tested in simulations. RESULTS: Very good agreement between preset and calculated values of quantities of interest was found in the simulations. In all cases, the proposed schemes enabled determination of the geometric characteristics of a radiotherapeutic device with accuracy better than one hundredth of a millimeter and one hundredth of a degree. CONCLUSIONS: A concept of a multimodule multifiducial phantom has been introduced. Analytical framework has been developed to extract geometric characteristics of radiotherapy devices from projection images of a phantom. The phantom design and the methodology developed have been tested in simulations.