Whole-Body [18F]-Fluoride PET SUV Imaging to Monitor Response to Dasatinib Therapy in Castration-Resistant Prostate Cancer Bone Metastases: Secondary Results from ACRIN 6687.

ACRIN 6687, a multi-center clinical trial evaluating differential response of bone metastases to dasatinib in men with metastatic castration-resistant prostate cancer (mCRPC), used [18F]-fluoride (NaF) PET imaging. We extend previous ACRIN 6687 dynamic imaging results by examining NaF whole-body (WB) static SUV PET scans acquired after dynamic scanning. Eighteen patients underwent WB NaF imaging prior to and 12 weeks into dasatinib treatment. Regional VOI analysis of the most NaF avid bone metastases and an automated whole-body method using Quantitative Total Bone Imaging software (QTBI; AIQ Solutions, Inc., Madison, WI, USA) were used. We assessed differences in tumor and normal bone, between pre- and on-treatment dasatinib, and evaluated parameters in association with PFS and OS. Significant decrease in average SUVmax and average SUVpeak occurred in response to dasatinib. Univariate and multivariate analysis showed NaF uptake had significant association with PFS. Pharmacodynamic changes with dasatinib in tumor bone can be identified by WB NaF PET in men with mCRPC. WB PET has the benefit of examining the entire body and is less complicated than single FOV dynamic imaging.

Feasibility and sensitivity study of helical tomotherapy for dose painting plans.

Important limitations for dose painting are due to treatment planning and delivery constraints. The purpose of this study was to develop a methodology for creating voxel-based dose painting plans that are deliverable using the clinical TomoTherapy Hi-Art II treatment planning system (TPS). Material and methods. Uptake data from a head and neck patient who underwent a [(61)Cu]Cu-ATSM (hypoxia surrogate) PET/CT scan was retrospectively extracted for planning. Non-uniform voxel-based prescriptions were converted to structured-based prescriptions for compatibility with the Hi-Art II TPS. Optimized plans were generated by varying parameters such as dose level, structure importance, prescription point normalization, DVH volume, min/max dose, and dose penalty. Delivery parameters such as pitch, jaw width and modulation factor were also varied. Isodose distributions, quality volume histograms and planning target volume percentage receiving planned dose within 5% of the prescription (Q(0.95-1.05)) were used to evaluate plan conformity. Results. In general, the conformity of treatment plans to dose prescriptions was found to be adequate for delivery of dose painting plans. The conformity was better as the dose levels increased from three to nine levels (Q(0.95-1.05): 69% to 93%), jaw decreased in width from 5.0cm to 1.05cm (Q(0.95-1.05): 81% to 93%), and modulation factor increased up to 2.0 (Q(0.95-1.05): 36% to 92%). The conformity was invariant to changes in pitch. Plan conformity decreased as the prescription DVH constraint (Q(0.95-1.05): 93% vs. 89%) or the normalization point (Q(0.95-1.05): 93% vs. 90%) deviated from the means. Conclusion. This investigation demonstrated the ability of the Hi-Art II TPS to create voxel-based dose painting plans. Results indicated that agreement in prescription dose and planned dose distributions for all plans were sensitive to physical delivery parameter changes in jaw width and modulation factors, but insensitive to changes in pitch. Tight constraints on target structures also resulted in decreased plan conformity while under a relaxed set of optimization parameters, plan conformity was increased.

Exploring Spatial-Temporal Changes in 18F-Sodium Fluoride PET/CT and Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide.

PURPOSE: Intrapatient treatment response heterogeneity is under-recognized. Quantitative total bone imaging (QTBI) using 18F-NaF positron emission tomography/computed tomography (PET/CT) scans is a tool that allows characterization of interlesional treatment response heterogeneity in bone. Understanding spatial-temporal response is important to identify individuals who may benefit from treatment beyond progression. PATIENTS AND METHODS: Men with progressive metastatic castration-resistant prostate cancer (mCRPC) with at least two lesions on bone scintigraphy were enrolled and treated with enzalutamide 160 mg daily (ClinicalTrials.gov identifier: NCT02384382). 18F-NaF PET/CT scans were obtained at baseline (PET1), week 13 (PET2), and at the time of prostate-specific antigen (PSA) progression, standard radiographic or clinical progression, or at 2 years without progression (PET3). QTBI was used to determine lesion-level response. The primary end point was the proportion of men with at least one responding bone lesion on PET3 using QTBI. RESULTS: Twenty-three men were enrolled. Duration on treatment ranged from 1.4 to 34.1 months. In general, global standardized uptake value (SUV) metrics decreased while on enzalutamide (PET2) and increased at the time of progression (PET3). The most robust predictor of PSA progression was change in SUVhetero (PET1 to PET3; hazard ratio, 3.88; 95% CI, 1.24 to 12.1). Although overall functional disease burden improved during enzalutamide treatment, an increase in total burden (SUVtotal) was seen at the time of progression, as measured by 18F-NaF PET/CT. All (22/22) evaluable men had at least one responding bone lesion at PET3 using QTBI. CONCLUSION: We found that the proportion of progressing lesions was low, indicating that a substantial number of lesions appear to continue to benefit from enzalutamide beyond progression. Selective targeting of nonresponding lesions may be a reasonable approach to extend benefit.

Response-to-repeatability of quantitative imaging features for longitudinal response assessment.

Quantitative imaging biomarkers (QIBs) are often selected and ranked based on their repeatability performance. In the context of treatment response assessment, however, one must also consider how sensitive a QIB is to measuring changes in the tumour. This work introduces response-to-repeatability ratio (R/R), which weighs the ability of a QIB to detect significant changes with respect to its measurement repeatability and applies it to the case of PET texture features. R/R is evaluated as the proportion of measurable changes from baseline to follow-up for each candidate QIB. We analyse 47 texture features extracted from lesions in bone-metastatic prostate cancer patients who received double baseline and/or baseline to treatment follow-up 18F-NaF PET/CT scans. R/R evaluates the proportion of follow-up changes outside of the 95% limits of agreement (LOA) defined by test-retest values. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) are calculated for each feature. Relationship between ICC and R/R are evaluated with the Spearman's correlation coefficient. R/R varied significantly across texture features: 41/47 (87%) features demonstrated R/R > 5%; 21/47 (45%) features demonstrated R/R > 10%, and 11/47 (23%) features demonstrated R/R > 20%. LOA of features ranged from [0.998, 1.001] to [0.22, 4.86]. Repeatability alone did not qualify a feature for its efficacy at detecting measurable change at follow-up, as shown by weak correlations between R/R and both CV and ICC (ρ = 0.23 and ρ = 0.40, respectively). Three features demonstrated excellent ICC (ICC > 0.75) and R/R greater than that of SUVmax (R/R = 41.8%): skewness (ICC = 0.92, R/R = 75.4%), kurtosis (ICC = 0.88, R/R = 47.0%) and diagonal moment (ICC = 0.88, R/R = 45.5%). R/R characterizes the sensitivity of candidate QIBs to detect measurable changes at follow-up. R/R supplements existing precision performance metrics (e.g. CV, ICC, and LOA) as an index to assess the utility of QIBs for response assessment.

Impact of Anatomic Location of Bone Metastases on Prognosis in Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Whole-body assessments of 18F-NaF positron emission tomography (PET)/computed tomography (CT) provide promising quantitative imaging biomarkers of metastatic castration-resistant prostate cancer (mCRPC). This study investigated whether the distribution of metastases across anatomic regions is prognostic of progression-free survival. PATIENTS AND METHODS: Fifty-four mCRPC patients with osseous metastases received baseline NaF PET/CT. Patients received chemotherapy (n = 16) or androgen receptor pathway inhibitors (n = 38). Semiautomated analysis using Quantitative Total Bone Imaging software extracted imaging metrics for the whole, axial, and appendicular skeleton as well as 11 skeletal regions. Five PET metrics were extracted for each region: number of lesions (NL), standardized maximum uptake value (SUVmax), average uptake (SUVmean), sum of uptake (SUVtotal), and diseased fraction of the skeleton (volume fraction). Progression included that discovered by clinical, biochemical, or radiographic means. Univariate and multivariate Cox proportional hazard regression analyses were performed between imaging metrics and progression-free survival, and were assessed according to their hazard ratios (HR) and concordance (C)-indices. RESULTS: The strongest univariate models of progression-free survival were pelvic NL and SUVmax with HR = 1.80 (NL: false discovery rate adjusted P = .001, SUVmax: adjusted P = .001). Three other region-specific metrics (axial NL: HR = 1.59, adjusted P = .02, axial SUVmax: HR = 1.61, adjusted P = .02, and skull SUVmax: HR = 1.58, adjusted P = .04) were found to be stronger prognosticators relative to their whole-body counterparts. Multivariate model including region-specific metrics (C-index = 0.727) outperformed that of whole-body metrics (C-index = 0.705). The best performance was obtained when region-specific and whole-body metrics were included (C-index = 0.742). CONCLUSION: Quantitative characterization of metastatic spread by anatomic location on NaF PET/CT enhances potential prognostication. Further study is warranted to optimize the prognostic and predictive value of NaF PET/CT in mCRPC patients.

Quantification of bone flare on 18F-NaF PET/CT in metastatic castration-resistant prostate cancer.

BACKGROUND: Bone flare has been observed on 99mTc-MDP bone scans of patients with metastatic castration-resistant prostate cancer (mCRPC). This exploratory study investigates bone flare in mCRPC patients receiving androgen receptor (AR) inhibitors using 18F-NaF PET/CT. METHODS: Twenty-nine mCRPC patients undergoing AR-inhibiting therapy (abiraterone, orteronel, enzalutamide) received NaF PET/CT scans at baseline, week 6, and week 12 of treatment. SUV metrics were extracted globally for each patient (SUV) and for each individual lesion (iSUV). Bone flare was defined as increasing SUV metrics or lesion number at week 6 followed by subsequent week 12 decrease. Differences in metrics across timepoints were compared using Wilcoxon tests. Cox proportional hazard regression was conducted between global metrics and progression-free survival (PFS). RESULTS: Total SUV was most sensitive for flare detection and was identified in 14/23 (61%) patients receiving CYP17A1-inhibitors (abiraterone, orteronel), and not identified in any of six patients receiving enzalutamide. The appearance of new lesions did not account for initial increases in SUV metrics. iSUV metrics followed patient-level trends: bone flare positive patients showed a median of 72% (range: 0-100%) of lesions with total iSUV flare. Increasing mean SUV at week 6 correlated with extended PFS (HR = 0.58, p = 0.02). CONCLUSION: NaF PET bone flare was present on 61% of mCRPC patients in the first 6 weeks of treatment with CYP17A1-inhibitors. Characterization provided in this study suggests favorable PFS in patients showing bone flare. This characterization of NaF flare is important for guiding treatment assessment schedules to better distinguish between patients showing bone flare and those truly progressing, and should be performed for all emerging mCRPC treatments and imaging agents.

A statistically optimized regional thresholding method (SORT) for bone lesion detection in 18F-NaF PET/CT imaging.

Identification of individual lesions on 18F-NaF PET bone scans is a time-consuming and often subjective process that makes accurate characterization of disease burden challenging. Current automated methods either underestimate disease or struggle with high false positive rates. We developed a statistically optimized regional thresholding (SORT) method that optimizes detection of bone lesions. This study assessed 18F-NaF PET/CT scans of 37 bone metastatic prostate cancer patients. Each PET image was divided into 19 skeletal regions. Areas of disease in each skeletal region were identified by an experienced nuclear medicine physician. A region of interest (ROI) was placed at each disease location and local maxima were extracted for both healthy and diseased ROIs. Secondary physician review was performed after identification of suspicious local maxima. Region-specific SUV thresholds were determined based on receiver operating characteristic (ROC) analysis optimized for detection of malignant disease. The detection performance of the SORT thresholds were compared to commonly used SUV > 10 g ml-1 (SUV10) and SUV > 15 g ml-1 (SUV15) global thresholds. The sensitivity of the SORT thresholds to various factors was evaluated, such as the number of subjects evaluated or image reconstruction settings. 1751 lesions were manually identified by the nuclear medicine physician. SORT identified different thresholds in each skeletal region (SUV range: 3-13 g ml-1). Region-specific SORT thresholding resulted in higher sensitivity (95.8%) than commonly used global thresholds (82.8% for SUV10 and 58.4% for SUV15) while maintaining a high specificity (97.1%, compared to 97.3% for SUV10 and 100.0% for SUV15). Factors, such as reconstruction settings, had minimal impact on threshold optimization, resulting in an average change of 10% (range: 2%-17%) in thresholds for each factor. Region-specific SUV thresholding of NaF PET images for bone lesion detection in metastatic prostate patients was found to be superior to current global thresholding methods.

Automated classification of benign and malignant lesions in 18F-NaF PET/CT images using machine learning.

PURPOSE: 18F-NaF PET/CT imaging of bone metastases is confounded by tracer uptake in benign diseases, such as osteoarthritis. The goal of this work was to develop an automated bone lesion classification algorithm to classify lesions in NaF PET/CT images. METHODS: A nuclear medicine physician manually identified and classified 1751 bone lesions in NaF PET/CT images from 37 subjects with metastatic castrate-resistant prostate cancer, 14 of which (598 lesions) were analyzed by three additional physicians. Lesions were classified on a five-point scale from definite benign to definite metastatic lesions. Classification agreement between physicians was assessed using Fleiss' κ. To perform fully automated lesion classification, three different lesion detection methods based on thresholding were assessed: SUV > 10 g ml-1, SUV > 15 g ml-1, and a statistically optimized regional thresholding (SORT) algorithm. For each ROI in the image, 172 different imaging features were extracted, including PET, CT, and spatial probability features. These imaging features were used as inputs into different machine learning algorithms. The impact of different deterministic factors affecting classification performance was assessed. RESULTS: The factors that most impacted classification performance were the machine learning algorithm and the lesion identification method. Random forests (RF) had the highest classification performance. For lesion segmentation, using SORT (AUC = 0.95 [95%CI = 0.94-0.95], sensitivity = 88% [86%-90%], and specificity = 0.89 [0.87-0.90]) resulted in superior classification performance (p < 0.001) compared to SUV > 10 g ml-1 (AUC = 0.87) and SUV > 15 g ml-1 (AUC = 0.86). While there was only moderate agreement between physicians in lesion classification (κ = 0.53 [95% CI = 0.52-0.53]), classification performance was high using any of the four physicians as ground truth (AUC range: 0.91-0.93). CONCLUSION: We have developed the first whole-body automatic disease classification tool for NaF PET using RF, and demonstrated its ability to replicate different physicians' classification tendencies. This enables fully-automated analysis of whole-body NaF PET/CT images.

Quantitative Assessment of Early [18F]Sodium Fluoride Positron Emission Tomography/Computed Tomography Response to Treatment in Men With Metastatic Prostate Cancer to Bone.

Purpose [18F]Sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) is a promising radiotracer for quantitative assessment of bone metastases. This study assesses changes in early NaF PET/CT response measures in metastatic prostate cancer for correlation to clinical outcomes. Patients and Methods Fifty-six patients with metastatic castration-resistant prostate cancer (mCRPC) with osseous metastases had NaF PET/CT scans performed at baseline and after three cycles of chemotherapy (n = 16) or androgen receptor pathway inhibitors (n = 40). A novel technology, Quantitative Total Bone Imaging, was used for analysis. Global imaging metrics, including maximum standardized uptake value (SUVmax) and total functional burden (SUVtotal), were extracted from composite lesion-level statistics for each patient and tracked throughout treatment. Progression-free survival (PFS) was calculated as a composite end point of progressive events using conventional imaging and/or physician discretion of clinical benefit; NaF imaging was not used for clinical evaluation. Cox proportional hazards regression analyses were conducted between imaging metrics and PFS. Results Functional burden (SUVtotal) assessed midtreatment was the strongest univariable PFS predictor (hazard ratio, 1.97; 95% CI, 1.44 to 2.71; P < .001). Classification of patients based on changes in functional burden showed stronger correlation to PFS than did the change in number of lesions. Various global imaging metrics outperformed baseline clinical markers in predicting outcome, including SUVtotal and SUVmean. No differences in imaging response or PFS correlates were found for different treatment cohorts. Conclusion Quantitative total bone imaging enables comprehensive disease quantification on NaF PET/CT imaging, showing strong correlation to clinical outcomes. Total functional burden assessed after three cycles of hormonal therapy or chemotherapy was predictive of PFS for men with mCRPC. This supports ongoing development of NaF PET/CT-based imaging biomarkers in mCRPC to bone.

Molecular image-directed biopsies: improving clinical biopsy selection in patients with multiple tumors.

Site selection for image-guided biopsies in patients with multiple lesions is typically based on clinical feasibility and physician preference. This study outlines the development of a selection algorithm that, in addition to clinical requirements, incorporates quantitative imaging data for automatic identification of candidate lesions for biopsy. The algorithm is designed to rank potential targets by maximizing a lesion-specific score, incorporating various criteria separated into two categories: (1) physician-feasibility category including physician-preferred lesion location and absolute volume scores, and (2) imaging-based category including various modality and application-specific metrics. This platform was benchmarked in two clinical scenarios, a pre-treatment setting and response-based setting using imaging from metastatic prostate cancer patients with high disease burden (multiple lesions) undergoing conventional treatment and receiving whole-body [18F]NaF PET/CT scans pre- and mid-treatment. Targeting of metastatic lesions was robust to different weighting ratios and candidacy for biopsy was physician confirmed. Lesion ranked as top targets for biopsy remained so for all patients in pre-treatment and post-treatment biopsy selection after sensitivity testing was completed for physician-biased or imaging-biased scenarios. After identifying candidates, biopsy feasibility was evaluated by a physician and confirmed for 90% (32/36) of high-ranking lesions, of which all top choices were confirmed. The remaining cases represented lesions with high anatomical difficulty for targeting, such as proximity to sciatic nerve. This newly developed selection method was successfully used to quantitatively identify candidate lesions for biopsies in patients with multiple lesions. In a prospective study, we were able to successfully plan, develop, and implement this technique for the selection of a pre-treatment biopsy location.

Repeatability of Quantitative 18F-NaF PET: A Multicenter Study.

18F-NaF, a PET radiotracer of bone turnover, has shown potential as an imaging biomarker for assessing the response of bone metastases to therapy. This study aimed to evaluate the repeatability of 18F-NaF PET-derived SUV imaging metrics in individual bone lesions from patients in a multicenter study. METHODS: Thirty-five castration-resistant prostate cancer patients with multiple metastases underwent 2 whole-body (test-retest) 18F-NaF PET/CT scans 3 ± 2 d apart from 1 of 3 imaging sites. A total of 411 bone lesions larger than 1.5 cm3 were automatically segmented using an SUV threshold of 15 g/mL. Two levels of analysis were performed: lesion-level, in which measures were extracted from individual-lesion regions of interest (ROI), and patient-level, in which all lesions within a patient were grouped into a patient ROI for analysis. Uptake was quantified with SUVmax, SUVmean, and SUVtotal Test-retest repeatability was assessed using Bland-Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation, critical percentage difference, and repeatability coefficient. The 95% limit of agreement (LOA) of the ratio between test and retest measurements was calculated. RESULTS: At the lesion level, the coefficient of variation for SUVmax, SUVmean, and SUVtotal was 14.1%, 6.6%, and 25.5%, respectively. At the patient level, it was slightly smaller: 12.0%, 5.3%, and 18.5%, respectively. ICC was excellent (>0.95) for all SUV metrics. Lesion-level 95% LOA for SUVmax, SUVmean, and SUVtotal was (0.76, 1.32), (0.88, 1.14), and (0.63, 1.71), respectively. Patient-level 95% LOA was slightly narrower, at (0.79, 1.26), (0.89, 1.10), and (0.70, 1.44), respectively. We observed significant differences in the variance and sample mean of lesion-level and patient-level measurements between imaging sites. CONCLUSION: The repeatability of SUVmax, SUVmean, and SUVtotal for 18F-NaF PET/CT was similar between lesion- and patient-level ROIs. We found significant differences in lesion-level and patient-level distributions between sites. These results can be used to establish 18F-NaF PET-based criteria for assessing treatment response at the lesion and patient levels. 18F-NaF PET demonstrates repeatability levels useful for clinically quantifying the response of bone lesions to therapy.

Confirmation, refinement, and extension of a study in intrafraction motion interplay with sliding jaw motion.

The interplay between a constant scan speed and intrafraction oscillatory motion produces interesting fluence intensity modulations along the axis of motion that are sensitive to the motion function, as originally shown in a classic paper by Yu et al. [Phys. Med. Biol. 43, 91-104 (1998)]. The fluence intensity profiles are explored in this note for an intuitive understanding, then compared with Yu et al., and finally further explored for the effects of low scan speed and random components of both intrafraction and interfraction motion. At slow scan speeds typical of helical tomotherapy, these fluence intensity modulations are only a few percent. With the addition of only a small amount of cycle-to-cycle randomness in frequency and amplitude, the fluence intensity profiles change dramatically. It is further shown that after a typical 30-fraction treatment, the sensitivities displayed in the single fraction fluence intensity profiles greatly diminish.

Optimizing an 18F-NaF and 18F-FDG cocktail for PET assessment of metastatic castration-resistant prostate cancer.

BACKGROUND: PET/computed tomography (CT) imaging with the sodium-(F)-fluoride/2-(F)-fluoro-2-deoxy-D-glucose (F-NaF/F-FDG) cocktail has been proposed for patients with osseous metastases. This work aimed to optimize the cocktail composition for patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: The study was carried out on six patients with mCRPC, with a total of 26 analyzed lesions. The patients were injected with F-NaF and F-FDG at separate time points. Dynamic PET/CT imaging recorded the uptake time course for both the tracers into osseous metastases. F-NaF and F-FDG uptakes were decoupled by kinetic analysis, which enabled calculation of F-NaF and F-FDG standardized uptake values (SUVs) images. Peak, mean, and total SUVs were evaluated for both tracers and all visible lesions. The F-NaF/F-FDG cocktail was optimized under the assumption that the contribution of both tracers to image formation is equal. SUV images from PET/CT imaging with a combination of F-NaF and F-FDG were generated for cocktail compositions with an F-NaF : F-FDG ratio varying from 1 : 8 to 1 : 2. RESULTS: The F-NaF peak and mean SUVs were on average four to five times higher than the F-FDG peak and mean SUVs, with an interlesion coefficient of variations of 20%. The total SUV for F-NaF was on average seven times higher than that for F-FDG. When the F-NaF : F-FDG ratio changed from 1 : 8 to 1 : 2, the typical SUV on the generated PET images increased by 50%, whereas the change in the uptake visual pattern was hardly noticeable. CONCLUSION: F-NaF and F-FDG in the cocktail contribute equally to image formation when the F-NaF : F-FDG ratio is 1 : 5. Therefore, we propose this ratio as the optimal cocktail composition for mCRPC patients. We also urge to strictly control the cocktail composition during any F-NaF/F-FDG cocktail PET/CT examination.

Comparison of NaF and FDG PET/CT for assessment of treatment response in castration-resistant prostate cancers with osseous metastases.

BACKGROUND: Assessment of skeletal metastases' response to therapy is a highly relevant but unresolved clinical problem. The main goal of this work was to compare pharmacodynamic responses to therapy assessed with positron emission tomography-computed tomography (PET/CT) using fluorine-18 sodium fluoride (NaF) and fluorine-18 fluorodeoxyglucose (FDG) as the tracers. MATERIALS AND METHODS: Patients with prostate cancer with known osseous metastases were treated with zibotentan (ZD4054) and imaged with combined dynamic NaF/FDG PET/CT before therapy (baseline), after 4 weeks of therapy (week 4), and after 2 weeks of treatment break (week 6). Kinetic analysis allowed comparison of the voxel-based tracer uptake rate parameter Ki, the vasculature parameters K1 (measuring perfusion/permeability) and Vb (measuring vasculature fraction in the tissue), and the standardized uptake values (SUVs). RESULTS: Correlations were high for the NaF and FDG peak uptake parameters (Ki and SUV correlations ranged from 0.57 to 0.88) and for vasculature parameters (K1 and Vb correlations ranged from 0.61 to 0.81). Correlation was low between the NaF and FDG week 4 Ki responses (ρ = 0.35; P = .084) but was higher for NaF and FDG week 6 Ki responses (ρ = 0.72; P < .0001). Correlations for vasculature responses were always low (ρ < 0.35). NaF and FDG uptakes in the osseous metastases were spatially dislocated, with overlap in the range from 0% to 80%. CONCLUSION: This study found that late NaF and FDG uptake responses are consistently correlated but that earlier uptake responses and all vasculature responses can be unrelated. This study also confirmed that FDG and NaF uptakes are spatially dislocated. Although treatment responses assessed with NaF and FDG may be correlated, using both tracers provides additional information.

Image reconstruction and the effect on dose calculation for hip prostheses.

High atomic number inserts, such as hip prostheses and dental fillings, cause streak artifacts on computed tomography (CT) images when filtered back-projection (FBP) methods are used. These streak artifacts severely degrade our ability to differentiate the tumor volume. Also, incorrect Hounsfield numbers yield incorrect electron density information that may lead to erroneous dose calculations, and, as a result, compromise clinical outcomes. The aim of this research was to evaluate the dosimetric consequences of artifacts during radiotherapy planning of a prostate patient containing a hip prosthesis. The CT numbers corresponding to an iron prosthesis were inserted into the right femoral head of an existing CT image set. This artifact-free image was used as the standard image set. CT projections through the image set formed the sinogram, from which filtered back projection and iterative deblurring methods were used to create reconstructed image sets. These reconstructed image sets contained artifacts. Prostate treatment plans were then calculated using a Monte Carlo system for the standard and reconstructed CT image sets. Close to the prosthesis, the CT numbers between the reconstructed and standard image sets differed substantially. However, because the CT number differences covered only a small area, the dose distributions on the reconstructed and standard image sets were not significantly different. The dose-volume histograms for the prostate, rectum, and bladder were virtually identical. Our results indicate that even though CT image artifacts restrict our ability to differentiate tumors and critical structures, the dose distributions for a prostate plan containing a hip prosthesis, calculated on both artifact-free image sets and image sets containing artifacts, are not significantly different.

Confirmation, refinement, and extension of a study in intrafraction motion interplay with sliding jaw motion.

The interplay between a constant scan speed and intrafraction oscillatory motion produces interesting fluence intensity modulations along the axis of motion that are sensitive to the motion function, as originally shown in a classic paper by Yu et al. [Phys. Med. Biol. 43, 91-104 (1998)]. The fluence intensity profiles are explored in this note for an intuitive understanding, then compared with Yu et al., and finally further explored for the effects of low scan speed and random components of both intrafraction and interfraction motion. At slow scan speeds typical of helical tomotherapy, these fluence intensity modulations are only a few percent. With the addition of only a small amount of cycle-to-cycle randomness in frequency and amplitude, the fluence intensity profiles change dramatically. It is further shown that after a typical 30-fraction treatment, the sensitivities displayed in the single fraction fluence intensity profiles greatly diminish.