Dosimetry of a portable in vivo x-ray fluorescence system using EBT3 radiochromic film.

PURPOSE: In vivo x-ray fluorescence is a non-invasive analytical technique for determining trace and toxic element exposures. In this work we measure the dose for a portable handheld x-ray system (pXRF). MATERIALS AND METHODS: We used EBT3 radiochromic film calibrated with a clinical orthovoltage unit for absolute dose measurement. Films were placed on a human phantom and irradiated with the Tracer III-SD pXRF at tube potentials of 40 and 45 kVp with various levels of filtration. RESULTS: Using settings that result in the best detection limits, the highest absorbed point dose to the skin was 0.3 Gy, the equivalent dose to a 1 cm2 area was 54 mSv, and the whole-body effective dose was less than 1 µSv for a standard 3-min in vivo measurement of strontium or lead. Recent work has demonstrated that 1 s and 30 s measurements are feasible for bone strontium measurements, which would lead to significantly lower doses. CONCLUSIONS: Our results are in agreement with a previous dosimetry study of another portable x-ray device and indicate that it is safe for in vivo measurements of elements such as strontium and lead, only after appropriate dose validation and with appropriate beam filtration in place.

Pure hydroxyapatite phantoms for the calibration of in vivo X-ray fluorescence systems of bone lead and strontium quantification.

Plaster of Paris [poP, CaSO4·(1)/(2) H2O] is the standard phantom material used for the calibration of in vivo X-ray fluorescence (IVXRF)-based systems of bone metal quantification (i.e bone strontium and lead). Calibration of IVXRF systems of bone metal quantification employs the use of a coherent normalization procedure which requires the application of a coherent correction factor (CCF) to the data, calculated as the ratio of the relativistic form factors of the phantom material and bone mineral. Various issues have been raised as to the suitability of poP for the calibration of IVXRF systems of bone metal quantification which include its chemical purity and its chemical difference from bone mineral (a calcium phosphate). This work describes the preparation of a chemically pure hydroxyapatite phantom material, of known composition and stoichiometry, proposed for the purpose of calibrating IVXRF systems of bone strontium and lead quantification as a replacement for poP. The issue with contamination by the analyte was resolved by preparing pure Ca(OH)2 by hydroxide precipitation, which was found to bring strontium and lead levels to <0.7 and <0.3 µg/g Ca, respectively. HAp phantoms were prepared from known quantities of chemically pure Ca(OH)2, CaHPO4·2H2O prepared from pure Ca(OH)2, the analyte, and a HPO4(2-) containing setting solution. The final crystal structure of the material was found to be similar to that of the bone mineral component of NIST SRM 1486 (bone meal), as determined by powder X-ray diffraction spectrometry.

Predicting head and neck cancer treatment outcomes with pre-treatment quantitative ultrasound texture features and optimising machine learning classifiers with texture-of-texture features.

Aim: Cancer treatments with radiation present a challenging physical toll for patients, which can be justified by the potential reduction in cancerous tissue with treatment. However, there remain patients for whom treatments do not yield desired outcomes. Radiomics involves using biomedical images to determine imaging features which, when used in tandem with retrospective treatment outcomes, can train machine learning (ML) classifiers to create predictive models. In this study we investigated whether pre-treatment imaging features from index lymph node (LN) quantitative ultrasound (QUS) scans parametric maps of head & neck (H&N) cancer patients can provide predictive information about treatment outcomes. Methods: 72 H&N cancer patients with bulky metastatic LN involvement were recruited for study. Involved bulky neck nodes were scanned with ultrasound prior to the start of treatment for each patient. QUS parametric maps and related radiomics texture-based features were determined and used to train two ML classifiers (support vector machines (SVM) and k-nearest neighbour (k-NN)) for predictive modeling using retrospectively labelled binary treatment outcomes, as determined clinically 3-months after completion of treatment. Additionally, novel higher-order texture-of-texture (TOT) features were incorporated and evaluated in regards to improved predictive model performance. Results: It was found that a 7-feature multivariable model of QUS texture features using a support vector machine (SVM) classifier demonstrated 81% sensitivity, 76% specificity, 79% accuracy, 86% precision and an area under the curve (AUC) of 0.82 in separating responding from non-responding patients. All performance metrics improved after implementation of TOT features to 85% sensitivity, 80% specificity, 83% accuracy, 89% precision and AUC of 0.85. Similar trends were found with k-NN classifier. Conclusion: Binary H&N cancer treatment outcomes can be predicted with QUS texture features acquired from index LNs. Prediction efficacy improved by implementing TOT features following methodology outlined in this work.

Blood lead levels and cumulative blood lead index (CBLI) as predictors of late neurodevelopment in lead poisoned children.

OBJECTIVE: To find the best lead exposure assessment marker for children. METHODS: We recruited 11 children, calculated a cumulative blood lead index (CBLI) for the children, measured their concurrent BLL, assessed their development, and measured their bone lead level. RESULTS: Nine of 11 children had clinically significant neurodevelopment problems. CBLI and current blood lead level, but not the peak lead level, were significantly or marginally negatively associated with the full-scale IQ score. CONCLUSION: Lead exposure at younger age significantly impacts a child's later neurodevelopment. CBLI may be a better predictor of neurodevelopment than are current or peak blood lead levels.

Investigating coherent normalization and dosimetry for the 241Am-La K XRF system.

OBJECTIVES: Lanthanum (La) retention in bone has been shown to occur in individuals who are orally administered lanthanum carbonate (LaC), a drug to treat hyperphosphatemia. The breakdown of LaC in the gastrointestinal tract into La3+ and carbonate ions results in residual quantities of La being deposited in bone. We previously reported on a non-invasive x-ray fluorescence (XRF) system that was developed to quantify bone La concentrations and applied it to a series of excised cadaver tibiae. However, given interpatient variability in bone shape and size, differential signal attenuation that occurs in bone and tissue, patient movement and overlying tissue thickness at the measurement site, quantifying bone La concentrations during in vivo measurements in live subjects needs to be investigated further along with the radiation dose associated with the measurement. APPROACH: Coherent normalization was investigated as a function of overlying tissue thickness, source-subject distance and bone radius through Monte Carlo simulation and experimental work. This was accomplished by observing the ratio of the net La K x-ray peak area to the coherently scattered peak area at 59.5 keV. In addition, the dose delivered during a 2000 s measurement was determined using radiochromic film. MAIN RESULTS: The coherent normalization of the La x-ray signal was shown to be independent of overlying tissue thickness, source-subject movement and bone radius, which indicates that this normalization procedure can correct for these factors. The equivalent skin dose and effective dose were 18.0 mSv and 3.2 µSv, respectively for a five-year-old. SIGNIFICANCE: While coherent normalization for the bone lead (Pb) and bone gadolinium (Gd) systems has been shown to be successful, we also report that this normalization procedure can correct for these interpatient variabilities in the in vivo 241Am-La K XRF system.

Postimplant Dosimetry of Permanent Prostate Brachytherapy: Comparison of MRI-Only and CT-MRI Fusion-Based Workflows.

PURPOSE: The current magnetic resonance imaging-computed tomography (MRI-CT) fusion-based workflow for postimplant dosimetry of low-dose-rate (LDR) prostate brachytherapy takes advantage of the superior soft tissue contrast of MRI, but still relies on CT for seed visualization and detection. Recently an MR-only workflow has been proposed that employs standard MR sequences and visualizes conventional implanted seed with positive contrast solely through MR postprocessing. In this work, the novel MR-only based workflow is compared with the clinical CT-MRI fusion approach. METHODS AND MATERIALS: Twenty-four prostate patients with a total of 1775 implanted LDR seeds were scanned using a 3-dimensional multiecho gradient echo sequence on a 3 Tesla MR scanner within 30 days after implantation. Quantitative susceptibility mapping was used for seed visualization. Seeds were automatically segmented and localized on the quantitative susceptibility mapping using convolutional neural network and k-means clustering, respectively. To assess the MR-only seed localization error, CT and MR-derived seed positions were coregistered, and ultimately, the resulting dose-volume histograms were compared. RESULTS: The MR-based seed visualization, segmentation, and localization generated comparable results to the CT-MR registration approach. The accuracy of the MRI-only based seed identification was 99.1%. After a rigid registration between the MR and CT-derived seed centroids, the average localization error was 0.8 ± 0.8 mm. The average prostate D90, V100, V150, and V200 for MRI-only and CT-MR fusion based dosimetry were 114.3 ± 12.5% versus 113.9 ± 11.9%, 95.1 ± 3.7% versus 95.3 ± 3.8%, 54.5 ± 14.5% versus 55.0 ± 13.2% and 22.9 ± 6.8% versus 23.2 ± 6.7%, respectively. No significant differences were observed in 3-dimensional seed positions and dosimetric parameters between MR-only and CT-MR fusion-based workflows (P > 0.2). CONCLUSIONS: The MRI-only LDR postimplant dosimetry is feasible and has very good potential to eliminate the need for CT-based seed identification.

Bone manganese as a biomarker of manganese exposure: a feasibility study.

BACKGROUND: There is a need for a diagnostic tool with the ability to measure cumulative exposure to manganese (Mn) in the workplace. Measuring bone Mn levels with in vivo neutron activation analysis (IVNAA) could serve as a biomarker of past exposure. Bone Mn levels of welders were measured and compared to the levels found in subjects without exposure to the element. METHOD: Forty subjects (30 welders and 10 controls) were recruited. An occupational history was obtained and subjects underwent IVNAA bone Mn measurements. RESULTS: The mean bone Mn levels were (2.9 +/- 0.4) and (0.1 +/- 0.7) microg Mn/g Ca for welders and controls, respectively (P < 0.05). CONCLUSIONS: This project, the first of its kind, reports differences in bone Mn between Mn-exposed welders and non-occupationally exposed subjects. It appears that bone Mn levels do reflect differences in the occupational exposure of welders.

Ex vivo quantification of lanthanum and gadolinium in post-mortem human tibiae with estimated barium and iodine concentrations using K x-ray fluorescence.

OBJECTIVES: Lanthanum (La) and gadolinium (Gd) are known to deposit in bone of exposed populations, namely those who are orally administered lanthanum carbonate (LaC, La2(CO3)3) or are injected with Gd-based contrast agents, respectively. In this work, bone La and Gd concentrations from the environment and diet were measured using x-ray fluorescence in ten post-mortem human tibiae. As a secondary objective, bone barium (Ba) and iodine concentrations were estimated. APPROACH: Two calibration lines were produced for La and Gd and the minimum detection limits (MDLs) of the system were determined using a 180° irradiation-detection geometry. MAIN RESULTS: The MDLs of the system were 0.4 µg La g-1 bone mineral and 0.5 µg Gd g-1 bone mineral. The mean concentrations were -0.02 ± 0.1 µg La g-1 bone mineral and 0.1 ± 0.2 µg Gd g-1 bone mineral in tibiae. The average Ba and iodine concentrations estimated from the experimental La calibration line and Monte-Carlo derived sensitivity factors were determined to be 3.4 ± 0.8 µg Ba g-1 bone mineral and -0.5 ± 0.3 µg iodine g-1 bone mineral. Since it was discovered that four donors previously received an iodine-based contrast agent, the mean concentrations in these donors was 27.8 ± 28.4 µg iodine g-1 bone mineral. SIGNIFICANCE: The XRF system has determined baseline concentrations of these four heavy metals in trace quantities from natural exposure pathways (with the exception of iodine in four donors). This indicates that the system can measure low levels in ex vivo tibiae samples and can potentially be further developed for in vivo studies involving live subjects who are directly exposed to these metals.

Potential applications of the quantitative susceptibility mapping (QSM) in MR-guided radiation therapy.

Magnetic resonance-guided radiation therapy (MR-GRT) offers great potential to improve radiation treatment outcomes by providing more accurate and patient-tailored therapy. Despite superior soft tissue contrast in MRI, one of the challenges towards MRI-only workflows is that the process often requires some sort of 'MR-invisible' metal-based devices. In this study, the feasibility of quantitative susceptibility mapping (QSM) for visualization of some MR-invisible radiation therapy devices was studied. Our recently proposed QSM-based algorithm for brachytherapy seed visualization was modified and the feasibility of the optimized algorithm for visualization of different devices including: brachytherapy seeds, plastic interstitial needles, CT-markers and obturators, and different types of fiducial markers in agar, prostate and meat phantoms were studied. All phantoms were scanned using 3T MR scanner with a 3D multi-echo gradient recalled echo (ME-GRE) pulse sequence. The QSM results in all phantoms were compared to CT images for spatial accuracy of the QSM. The applied post-processing algorithm was found to be insensitive to the seeds' type; also, presence of nearby calcifications had no effect on seed visualization. QSM successfully generated positive contrast for both types of investigated fiducial markers with high spatial accuracy compared to CT. Interstitial needles containing both aluminum-based CT-maker and titanium-based obturators were accurately depicted on the QSM. The proposed QSM-based technique relies on the standard MR pulse sequences and visualize the conventional MR-invisible metallic devices with CT-like positive contrast solely through post-processing. Upon in vivo validation of the technique, QSM may have the potential to replace CT for an MR-only guided radiation therapy.

Surgical Resection With Radiation Treatment Planning of Spinal Tumors.

BACKGROUND: The clinical paradigm for spinal tumors with epidural involvement is challenging considering the rigid dose tolerance of the spinal cord. One effective approach involves open surgery for tumor resection, followed by stereotactic body radiotherapy (SBRT). Resection extent is often determined by the neurosurgeon's clinical expertise, without considering optimal subsequent post-operative SBRT treatment. OBJECTIVE: To quantify the effect of incremental epidural disease resection on tumor coverage for spine SBRT in an effort to working towards integrating radiotherapy planning within the operating room. METHODS: Ten patients having undergone spinal separation surgery with postoperative SBRT were retrospectively reviewed. Preoperative magnetic resonance imaging was coregistered to postoperative planning computed tomography to delineate the preoperative epidural disease gross tumor volume (GTV). The GTV was digitally shrunk by a series of fixed amounts away from the cord (up to 6 mm) simulating incremental tumor resection and reflecting an optimal dosimetric endpoint. The dosimetric effect on simulated GTVs was analyzed using metrics such as minimum biologically effective dose (BED) to 95% of the simulated GTV (D95) and compared to the unresected epidural GTV. RESULTS: Epidural GTV D95 increased at an average rate of 0.88 ± 0.09 Gy10 per mm of resected disease up to the simulated 6 mm limit. Mean BED to D95 was 5.3 Gy10 (31.2%) greater than unresected cases. All metrics showed strong positive correlations with increasing tumor resection margins (R2: 0.989-0.999, P < .01). CONCLUSION: Spine separation surgery provides division between the spinal cord and epidural disease, facilitating better disease coverage for subsequent post-operative SBRT. By quantifying the dosimetric advantage prior to surgery on actual clinical cases, targeted surgical planning can be implemented.

Feasibility of an MRI-only workflow for postimplant dosimetry of low-dose-rate prostate brachytherapy: Transition from phantoms to patients.

PURPOSE: The lack of positive contrast from brachytherapy seeds in conventional MR images remains a major challenge toward an MRI-only workflow for postimplant dosimetry of low-dose-rate brachytherapy. In this work, the feasibility of our recently proposed MRI-only workflow in clinically relevant scenarios is investigated and the necessary modifications in image acquisition and processing pipeline are proposed for transition to the clinic. METHODS AND MATERIALS: Four prostate phantoms with a total of 321 I-125 implanted dummy seeds and three patients with a total of 168 implanted seeds were scanned using a gradient echo sequence on 1.5 T and 3T MR scanners. Quantitative susceptibility mapping (QSM) was performed for seed visualization. Before QSM, the seed-induced distortion correction was performed followed by edge enhancement. Seed localization was performed using spatial clustering algorithms and was compared with CT. In addition, feasibility of the proposed method on detection of prostatic calcifications was studied. RESULTS: The proposed susceptibility-based algorithm generated consistent positive contrast for the seeds in phantoms and patients. All the 321 seeds in the four phantoms were correctly identified; the MR-derived seeds centroids agreed well with CT-derived positions (average error = 0.5 ± 0.3 mm). The proposed algorithm for seed visualization was found to be orientation invariant. In patient cases, all seeds were visualized and correctly localized (average error = 1.2 ± 0.9 mm); no significant differences between dose volume histogram parameters were found. Prostatic calcifications were depicted with negative contrast on QSM and spatially agreed with CT. CONCLUSIONS: The proposed MRI-based approach has great potential to replace the current CT-based practices. Additional patient studies are necessary to further optimize and validate the workflow.

Assessment of the effect of strontium, lead, and aluminum in bone on dual-energy x-ray absorptiometry and quantitative ultrasound measurements: A phantom study.

PURPOSE: Dual-energy X-ray absorptiometry (DXA) is the gold standard technique to measure areal bone mineral density (aBMD) for the diagnosis of osteoporosis. Because DXA relies on the attenuation of photon to estimate aBMD, deposition of bone-seeking metallic elements such as strontium, lead, and aluminum that differ in atomic numbers from calcium can cause inaccurate estimation of aBMD. Quantitative ultrasound (QUS) is another technique available to assess bone health by measuring broadband ultrasound attenuation (BUA), speed of sound (SOS), and an empirically derived quantity called stiffness index (SI). Because the acoustic properties are not prone to significant change due to changes in microscopic atomic composition of bone, it is hypothesized that QUS is unaffected by the presence of bone-seeking elements in the bone. The objective of this study was to investigate the effect of strontium, lead, and aluminum on DXA-derived aBMD and QUS parameters using bone-mimicking phantoms compatible with both techniques. METHODS: Bone-mimicking phantoms were produced by homogeneously mixing finely powdered hydroxyapatite compounds that contain varying concentrations of strontium, lead, or aluminum with porcine gelatin solution. Seven strontium-substituted phantoms were produced with varying molar ratio of Sr/(Sr + Ca) ranging from 0% to 2%. Four lead-doped phantoms and four aluminum-doped phantoms were constructed with the respective analyte concentrations ranging from 50 to 200 ppm. An additional 0 ppm phantom was produced to be used as a baseline for the lead and aluminum phantom measurements. All phantoms had uniform volumetric bone mineral density (vBMD) of 200 mg/cm3 , and were assessed using a Hologic Horizon® DXA device and a Hologic Sahara® QUS device. Furthermore, theoretical aBMD bias for mol/mol% substitution of calcium with the three bone-seeking elements was calculated. RESULTS: Strong positive linear relationship was found between aBMD measured by DXA and strontium concentration (P < 0.001, r = 0.995). From the measurement of lead and aluminum phantoms using DXA, no statistically significant relationship was observed between aBMD and the analyte concentrations. For the QUS system, with an exception of BUA and lead concentration that exhibited statistically significant relationship (P < 0.038, r = 0.899), no statistically significant change was observed in all QUS parameters with respect to the clinically relevant concentration of all three elements. The calculated theoretical aBMD bias induced by 1 mol/mol% substitution of calcium with strontium, lead, and aluminum were 10.8%, 4.6%, and -0.7%, respectively. CONCLUSION: aBMD measured by DXA was prone to overestimation in the presence of strontium, but acoustic parameters measured by QUS are independent of strontium concentration. The deviation in aBMD induced by the clinically relevant concentrations of lead and aluminum under 200 ppm could not be detected using the Hologic Horizon® DXA device. Furthermore, the SI measured by the QUS system was not affected by lead or aluminum concentrations used in this study.

MRI-based automated detection of implanted low dose rate (LDR) brachytherapy seeds using quantitative susceptibility mapping (QSM) and unsupervised machine learning (ML).

BACKGROUND AND PURPOSE: Permanent seed brachytherapy is an established treatment option for localized prostate cancer. Currently, post-implant dosimetry is performed on CT images despite challenging target delineation due to limited soft tissue contrast. This work aims to develop an MRI-only workflow for post-implant dosimetry of prostate brachytherapy seeds. MATERIAL AND METHODS: A prostate mimicking phantom containing twenty stranded I-125 dummy seeds and calcifications was constructed. A three-dimensional gradient-echo MR sequence was employed on 3T and 1.5T MR scanners. An optimized quantitative susceptibility mapping (QSM) technique was applied to generate positive contrast for the seeds and calcifications. Seed numbers, centroids, and orientations were determined using unsupervised machine learning algorithms (K-means and K-medoids clustering). The geometrical seed positions and the resulting dose distribution were compared to the clinical CT-based approach. RESULTS: The optimized QSM-based method generated high quality positive contrast for the seeds that were significantly different from that for calcifications and could be easily differentiated by thresholding. The estimated seed centroids from both 3T and 1.5T MR data were in perfect agreement with the standard CT-based seed detection algorithm (maximum difference of 0.7 mm). The estimated seed orientations were highly correlated with the actual orientations (R > 0.98). CONCLUSIONS: The proposed MRI-based workflow enabling an accurate and robust means to localize the seeds (position and orientation) upon validation on complex seed configurations, has the potential to replace the current widely practiced CT-based workflow.

Calibration of the 125I-induced x-ray fluorescence spectrometry-based system of in vivo bone strontium determinations using hydroxyapatite as a phantom material: a simulation study.

OBJECTIVE: The calibration of in vivo x-ray fluorescence systems of bone strontium quantification, based on 125I excitation, is dependent on a coherent normalization procedure. Application of this procedure with the use of plaster of Paris (poP) as a phantom material requires the application of a coherent conversion factor (CCF) to make the calibration functions transferable between the phantom material and human bone. In this work we evaluate, with the use of Monte Carlo simulation, the potential benefit of employing a newly developed hydroxyapatite phantom material into the calibration protocol. APPROACH: Simulations being performed on bare bone phantoms, as the emission spectrum in this case is equivalent to an emission spectrum of an adequately corrected measurement for soft tissue attenuation of emitted strontium signal. We report that the application of hydroxyapatite phantoms does in fact remove the need for a coherent correction factor (CCF). MAIN RESULTS: The newly developed phantoms can thus be used for the calibration of in vivo bone strontium systems removing one step of the calibration protocol. Calibration is, however, limited to cases in which the concentration is relative to the amount of calcium in the specimen, which is, the most useful quantity in a clinical sense. Determining concentrations on a per-mass-of-material basis, that is, a concentration not normalized to the calcium content of the phantom/bone, results in large biases in estimated bone strontium content. SIGNIFICANCE: The use of an HAp phantom material was found to remove the need for a CCF. It was also found that in the case of an incomplete conversion ratio when preparing the phantom material that there would be little effect on the differential coherent cross-section and thereby the coherent normalization-based calibration protocol.

The feasibility of in vivo detection of lanthanum using a 241Am K x-ray fluorescence system.

OBJECTIVE: Lanthanum (La) is commonly used in phosphate binders in the form of lanthanum carbonate in patients with end-stage kidney disease undergoing hemodialysis treatments. With this administration, there is the potential for La storage in the body with bone being the main site of concern. However, the long-term effects of residual La in the body on bone health are not yet known. In this work, we investigate the feasibility of using a K x-ray fluorescence (K-XRF) spectroscopy system to measure bone La in vivo. APPROACH: A series of hydroxyapatite (HAp) bone mineral phantoms were created to represent human bone. A 1.09 GBq 241Am source was used to excite the HAp phantoms doped with various known concentrations of La placed in a 90° geometry relative to the photon source and high-purity germanium (HPGe) detector. MAIN RESULTS: For a detector live time of 2000 s, the minimum detection limit was calculated to be 1.7 µg La g-1 Ca or 0.7 µg La g-1 HAp and is comparable to previously reported in vivo bone La concentrations. SIGNIFICANCE: The technique developed in this study shows promising results and provides an alternative method to invasive biopsy sampling techniques to monitor the accumulation of bone La. To the best of our knowledge, this is the first reported work that seeks to non-invasively measure bone La via in vivo XRF.

Technical Note: Bone mineral density measurements of strontium-rich trabecular bone-mimicking phantoms using quantitative ultrasound.

PURPOSE: Bone quantity, as determined by the current gold standard, dual energy X-ray absorptiometry (DXA), through measured areal bone mineral density (aBMD), is subject to positive biases if bone strontium levels are high. This is of particular concern for populations administered strontium-based compounds for the treatment of osteoporosis. This study investigated the dependence of bone mineral density (BMD) determinations, and associated ultrasound-determined indices, obtained by quantitative ultrasound (QUS), on bone strontium content using a new generation of trabecular bone-mimicking phantoms. METHODS: A new generation of bone-mimicking phantoms, consisting of hydroxyapatite (HA) and gelatin, was developed. Castor oil layers were included in these phantoms to create a multilayer bone-mimicking phantom. These phantoms were prepared using a bone mineral fraction consisting of varying strontium concentrations in the range of 0-2.5% mol/mol as strontium-substituted HA. The effect of varying bone strontium content on determined quality indices was evaluated based on determined speed of sound (SOS), broadband ultrasound attenuation (BUA) and determined quantitative ultrasound index (QUI) for phantoms with varying BMD values and varying strontium concentration using two QUS systems: a clinical Sahara® system and an in-house research system with two identical transducers with center frequency of 1 MHz. The two QUS systems were also compared through a Bland-Altman analysis. RESULTS: Both the clinical system and the research QUS systems showed a strong dependency between BMD and BUA, indicating a potential for QUS to be used as a means of estimating BMD (p = 0.001). SOS was found to have no correlation to BMD (p = 0.546). There was no correlation observed between BUA and increasing bone strontium concentrations for the research (p = 0.749) and clinical (p = 0.609) QUS systems. Similarly, no dependency was observed between the SOS and bone strontium levels up to 2.5 mol/mol [Sr/(Sr+Ca)]% for the research (p = 0.862) and clinical (p = 0.481) QUS systems. No effect on the QUI values was observed with changing strontium levels with either research (p = 0.939) or clinical QUS systems (p = 0.931). A Bland-Altman analysis showed that there was a clear offset in determined QUI values for both systems but they are in agreement with one another. CONCLUSIONS: Bone quality can be assessed through the use of QUS while increasing bone strontium concentration was found to have no effect on QUS-determined quality indices. This study concludes that QUS can potentially be used for the determination of bone quality without introducing biases due to bone strontium levels as is known to be the case with DXA determined aBMD.

Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain Metastases.

PURPOSE: To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). METHODS: Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. RESULTS: Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. CONCLUSION: Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio.

Monitoring bone strontium intake in osteoporotic females self-supplementing with strontium citrate with a novel in-vivo X-ray fluorescence based diagnostic tool.

Ten female volunteers were recruited as part of the Ryerson and McMaster University Strontium (Sr) in Bone Research Study to have their bone Sr levels measured as they self-supplemented with Sr supplements of their choice. Of the ten volunteers, nine were suffering from osteopenia and/or osteoporosis. Non-invasive bone Sr measurements were performed using an in vivo x-ray fluorescence (IVXRF) I-125 based system. Thirty minute measurements were taken at the finger and ankle, representing primarily cortical and trabecular bone, respectively. For analysis, the 14.2keV Sr K-alpha peak normalized to the Coherent peak at 35.5keV was used. Baseline readings, representing natural bone Sr levels were acquired since all volunteers had no previous intake of Sr based supplements or medications. Once Sr supplements were started, a 24h reading was taken, followed by frequent measurements ranging from weekly, biweekly to monthly. The longest volunteer participation was 1535days. The mean baseline Sr signal observed for the group was 0.42±0.13 and 0.39±0.07 for the finger and ankle, respectively. After 24h, the mean Sr signal rose to 1.43±1.12 and 1.17±0.51, for the finger and ankle, respectively, representing a statistically significant increase (p=0.0043 & p=0.000613). Bone Sr levels continued to increase throughout the length of the study. However the Sr signal varied widely between the individuals such that after three years, the highest Sr signal observed was 28.15±0.86 for the finger and 26.47±1.22 for the ankle in one volunteer compared to 3.15±0.15 and 4.46±0.36, for the finger and ankle, respectively in another. Furthermore, while it was previously reported by our group, that finger bone Sr levels may plateau within two years, these results suggest otherwise, indicating that bone Sr levels will continue to rise at both bone sites even after 4years of Sr intake.

Accumulation of bone strontium measured by in vivo XRF in rats supplemented with strontium citrate and strontium ranelate.

Strontium ranelate is an approved pharmacotherapy for osteoporosis in Europe and Australia, but not in Canada or the United States. Strontium citrate, an alternative strontium salt, however, is available for purchase over-the-counter as a nutritional supplement. The effects of strontium citrate on bone are largely unknown. The study's objectives were 1) to quantify bone strontium accumulation in female Sprague Dawley rats administered strontium citrate (N=7) and compare these levels to rats administered strontium ranelate (N=6) and vehicle (N=6) over 8 weeks, and 2) to verify an in vivo X-ray fluorescence spectroscopy (XRF) system for measurement of bone strontium in the rat. Daily doses of strontium citrate and strontium ranelate were determined with the intention to achieve equivalent amounts of elemental strontium. However, post-hoc analyses of each strontium compound conducted using energy dispersive spectrometry microanalysis revealed a higher elemental strontium concentration in strontium citrate than strontium ranelate. Bone strontium levels were measured at baseline and 8 weeks follow-up using a unique in vivo XRF technique previously used in humans. XRF measurements were validated against ex vivo measurements of bone strontium using inductively coupled plasma mass spectrometry. Weight gain in rats in all three groups was equivalent over the study duration. A two-way ANOVA was conducted to compare bone strontium levels amongst the three groups. Bone strontium levels in rats administered strontium citrate were significantly greater (p<0.05) than rats administered strontium ranelate and vehicle. ANCOVA analyses were performed with Sr dose as a covariate to account for differences in strontium dosing. The ANCOVA revealed differences in bone strontium levels between the strontium groups were not significant, but that bone strontium levels were still very significantly greater than vehicle.