Using micro-synchrotron radiation x-ray fluorescence (µ-SRXRF) for trace metal imaging in the development of MRI contrast agents for prostate cancer imaging.

BACKGROUND: Contrast agents (CA) are administered in magnetic resonance imaging (MRI) clinical exams to measure tissue perfusion, enhance image contrast between adjacent tissues, or provide additional biochemical information in molecular MRI. The efficacy of a CA is determined by the tissue distribution of the agent and its concentration in the extracellular space of all tissues. METHODS: In this work, micro-synchrotron radiation x-ray fluorescence (µ-SRXRF) was used to examine and characterize a gadolinium-based zinc-sensitive agent (GdL2) currently under development for detection of prostate cancer (PCa) by MRI. Prostate tissue samples were collected from control mice and mice with known PCa after an MRI exam that included injection of GdL2. The samples were raster scanned to investigate trends in Zn, Gd, Cu, Fe, S, P, and Ca. RESULTS: Significant Zn and Gd co-localization was observed in both healthy and malignant tissues. In addition, a marked decrease in Zn was found in the lateral lobe of the prostate obtained from mice with PCa. CONCLUSION: We demonstrate here that µ-SRXRF is a useful tool for monitoring the distribution of several elements including Zn and Gd in animal models of cancer. The optimized procedures for tissue preparation, processing, data collection, and analysis are described.

Experimental determination of Gd dose enhancement and Gd dose sparing by 192Ir brachytherapy source with Gafchromic EBT3 dosimeter.

This work evaluates experimentally the dose enhancement factor (DEF) and dose sparing factor (DSF) due to radiation self-shielding, produced by Gd infused in tumor phantom irradiated with brachytherapy HDR 192Ir source by Gafchromic EBT3 dosimeter. The phantom was made of a set of solid water slabs (30 × 30 × 1.0) cm3 and three acrylic slabs of (30 × 30 × 0.5) cm3 machined to contain in the central axis acrylics vials of (1 × 1 × 5) cm3. The first and second acrylic vials were filled with an identical Gd solution of 0, 10 and 20 mg/ml, simulating Gd-doped and undoped tumor, and the third vial was filled in all the measurement only with water, representing an organ at risk. Additional solid water slabs were used to complete a phantom of (30 × 30 × 16) cm3. In the phantom center an acrylic slab was machined to introduce the 2.5 mm flexible guide tube of GammaMed plus iX equipment and positioning the 192Ir source in the phantom central part. EBT3 fragments of (0.9 × 4) cm2 were placed on the inner edge of the second and third vials to measure dose enhancement and dose sparing simultaneously. Phantom CT images were acquired for planning and to prescribe a dose of 6.0 Gy at 2.0 cm of the source, achieving an isodose curve of 44.5% at 3.0 cm (positions of the EBT3 films). Additionally, Monte Carlo simulation of the identical experimental setup was implemented to compare measurement values. The results showed the feasibility of measuring a DEF of 1.15 ± 0.05 in 20 mg/ml of Gd concentration consistent with the Monte Carlo DEF of 1.112 ± 0.005 for the same concentration. DEF value for concentration of 10 mg/ml would not be detected (1.00 ± 0.04) by an expected under measurement of the EBT3 films associated with the non-detection of photoelectrons and Auger electrons of very low energy that cannot reach the radiosensitive substrate.

Taylor Dispersion Analysis Coupled to Inductively Coupled Plasma-Mass Spectrometry for Ultrasmall Nanoparticle Size Measurement: From Drug Product to Biological Media Studies.

During past decade, special focus has been laid on ultrasmall nanoparticles for nanomedicine and eventual clinical translation. To achieve such translation, a lot of challenges have to be solved. Among them, size determination is a particularly tricky one. In this aim, we have developed a simple hyphenation between Taylor dispersion analysis and inductively coupled plasma-mass spectrometry (ICP-MS). This method was proven to allow the determination of the hydrodynamic radius of metal-containing nanoparticles, even for sizes under 5 nm, with a relative standard deviation below 10% (with a 95% confidence interval) and at low concentrations. Moreover, its specificity provides the opportunity to perform measurements in complex biological media. This was applied to the characterization of an ultrasmall gadolinium-containing nanoparticle used as a theranostic agent in cancer diseases. Hydrodynamic radii measured in urine, cerebrospinal fluid, and undiluted serum demonstrated the absence of interaction between the particle and biological compounds such as proteins.

Detection and imaging of gadolinium accumulation in human bone tissue by micro- and submicro-XRF.

Gadolinium-based contrast agents (GBCAs) are frequently used in patients undergoing magnetic resonance imaging. In GBCAs gadolinium (Gd) is present in a bound chelated form. Gadolinium is a rare-earth element, which is normally not present in human body. Though the blood elimination half-life of contrast agents is about 90 minutes, recent studies demonstrated that some tissues retain gadolinium, which might further pose a health threat due to toxic effects of free gadolinium. It is known that the bone tissue can serve as a gadolinium depot, but so far only bulk measurements were performed. Here we present a summary of experiments in which for the first time we mapped gadolinium in bone biopsy from a male patient with idiopathic osteoporosis (without indication of renal impairment), who received MRI 8 months prior to biopsy. In our studies performed by means of synchrotron radiation induced micro- and submicro-X-ray fluorescence spectroscopy (SR-XRF), gadolinium was detected in human cortical bone tissue. The distribution of gadolinium displays a specific accumulation pattern. Correlation of elemental maps obtained at ANKA synchrotron with qBEI images (quantitative backscattered electron imaging) allowed assignment of Gd structures to the histological bone structures. Follow-up beamtimes at ESRF and Diamond Light Source using submicro-SR-XRF allowed resolving thin Gd structures in cortical bone, as well as correlating them with calcium and zinc.

Nephrogenic Systemic Fibrosis Risk Assessment and Skin Biopsy Quantification in Patients with Renal Disease following Gadobenate Contrast Administration.

BACKGROUND AND PURPOSE: Nephrogenic systemic fibrosis following administration of intravenous gadobenate during MR imaging is rare. This study aimed to analyze any nephrogenic systemic fibrosis-related risks and quantify skin gadolinium levels in patients with impaired renal function but without nephrogenic systemic fibrosis who had received gadobenate. MATERIALS AND METHODS: In this retrospective study with a prospective skin biopsy phase, patients with estimated glomerular filtration rates of <60 mL/min/1.73 m2 undergoing contrast-enhanced MR imaging from July 2007 through June 2014 were screened for nephrogenic systemic fibrosis using a questionnaire. This was highly sensitive but not specific and reliably excluded nephrogenic systemic fibrosis if responses to at least 6 of the 8 questions were negative. If no nephrogenic systemic fibrosis was detected, a skin biopsy was requested. RESULTS: Of 2914 patients who met these criteria, 1988 were excluded for various reasons. Of the remaining 926 patients, 860 were screened negative for nephrogenic systemic fibrosis. Of these, 17 (2%) had estimated glomerular filtration rates of <15 mL/min/1.73 m2, 51 (6%) had levels of 15 < 30 mL/min/1.73 m2, 234 (27%) had levels of 30 < 45 mL/min/1.73 m2, and 534 (62%) had levels of 45 < 60 mL/min/1.73 m2. Of the 66 who were not cleared of nephrogenic systemic fibrosis by the questionnaire, 6 patients were evaluated by a dermatologist and confirmed not to have nephrogenic systemic fibrosis (no biopsy required). CONCLUSIONS: A diagnosis of nephrogenic systemic fibrosis was excluded in 860 patients with impaired renal function who were followed up and received gadobenate during MR imaging. In 14 such patients who underwent at least 1 gadobenate-enhanced MR imaging examination and did not have nephrogenic systemic fibrosis, gadolinium levels in the skin were exceedingly low.

Accurate and Real-Time Temperature Monitoring during MR Imaging Guided PTT.

Photothermal therapy (PTT) is an efficient approach for cancer treatment. However, accurately monitoring the spatial distribution of photothermal transducing agents (PTAs) and mapping the real-time temperature change in tumor and peritumoral normal tissue remain a huge challenge. Here, we propose an innovative strategy to integrate T1-MRI for precisely tracking PTAs with magnetic resonance temperature imaging (MRTI) for real-time monitoring temperature change in vivo during PTT. NaBiF4: Gd@PDA@PEG nanomaterials were synthesized with favorable T1-weighted performance to target tumor and localize PTAs. The extremely weak susceptibility (1.04 × 10-6 emu g-1 Oe1-) of NaBiF4: Gd@PDA@PEG interferes with the local phase marginally, which maintains the capability of MRTI to dynamically record real-time temperature change in tumor and peritumoral normal tissue. The time resolution is 19 s per frame, and the detection precision of temperature change is approximately 0.1 K. The approach achieving PTT guided by multimode MRI holds significant potential for the clinical application.

Noninvasive imaging of vascular permeability to predict the risk of rupture in abdominal aortic aneurysms using an albumin-binding probe.

Abdominal aortic aneurysm (AAA) remains a fatal disease. Its development encompasses a complex interplay between hemodynamic stimuli on and changes in the arterial wall. Currently available biomarkers fail to predict the risk of AAA rupture independent of aneurysm size. Therefore, novel biomarkers for AAA characterization are needed. In this study, we used a mouse model of AAA to investigate the potential of magnetic resonance imaging (MRI) with an albumin-binding probe to assess changes in vascular permeability at different stages of aneurysm growth. Two imaging studies were performed: a longitudinal study with follow-up and death as endpoint to predict rupture risk and a week-by-week study to characterize AAA development. AAAs, which eventually ruptured, demonstrated a significantly higher in vivo MR signal enhancement from the albumin-binding probe (p = 0.047) and a smaller nonenhancing thrombus area compared to intact AAAs (p = 0.001). The ratio of albumin-binding-probe enhancement of the aneurysm wall to size of nonenhancing-thrombus-area predicted AAA rupture with high sensitivity/specificity (100%/86%). More advanced aneurysms with higher vascular permeability demonstrated an increased uptake of the albumin-binding-probe. These results indicate that MRI with an albumin-binding probe may enable noninvasive assessment of vascular permeability in murine AAAs and prediction of rupture risk.

The role of gadolinium in magnetic resonance imaging for early prostate cancer diagnosis: A diagnostic accuracy study.

OBJECTIVE: Prostate lesions detected with multiparametric magnetic resonance imaging (mpMRI) are classified for their malignant potential according to the Prostate Imaging-Reporting And Data System (PI-RADS™2). In this study, we evaluate the diagnostic accuracy of the mpMRI with and without gadolinium, with emphasis on the added diagnostic value of the dynamic contrast enhancement (DCE). MATERIALS AND METHODS: The study was retrospective for 286 prostate lesions / 213 eligible patients, n = 116/170, and 49/59% malignant for the peripheral (Pz) and transitional zone (Tz), respectively. A stereotactic MRI-guided prostate biopsy served as the histological ground truth. All patients received a mpMRI with DCE. The influence of DCE in the prediction of malignancy was analyzed by blinded assessment of the imaging protocol without DCE and the DCE separately. RESULTS: Significant (CSPca) and insignificant (IPca) prostate cancers were evaluated separately to enhance the potential effects of the DCE in the detection of CSPca. The Receiver Operating Characteristics Area Under Curve (ROC-AUC), sensitivity (Se) and specificity (Spe) of PIRADS-without-DCE in the Pz was 0.70/0.47/0.86 for all cancers (IPca and CSPca merged) and 0.73/0.54/0.82 for CSPca. PIRADS-with-DCE for the same patients showed ROC-AUC/Se/Spe of 0.70/0.49/0.86 for all Pz cancers and 0.69/0.54/0.81 for CSPca in the Pz, respectively, p>0.05 chi-squared test. Similar results for the Tz, AUC/Se/Spe for PIRADS-without-DCE was 0.75/0.61/0.79 all cancers and 0.67/0.54/0.71 for CSPca, not influenced by DCE (0.66/0.47/0.81 for all Tz cancers and 0.61/0.39/0.75 for CSPca in Tz). The added Se and Spe of DCE for the detection of CSPca was 88/34% and 78/33% in the Pz and Tz, respectively. CONCLUSION: DCE showed no significant added diagnostic value and lower specificity for the prediction of CSPca compared to the non-enhanced sequences. Our results support that gadolinium might be omitted without mitigating the diagnostic accuracy of the mpMRI for prostate cancer.

Evaluation of Early Gadolinium Enhancement (EGE) and Cardiac Functional Parameters in Cine-Magnetic Resonance Imaging (MRI) on Artificial Intelligence in Patients with Acute Myocarditis: A Case-Controlled Observational Study.

BACKGROUND The diagnosis of myocarditis is challenging, and the treatment is generally delayed due to misdiagnosis or missed diagnosis. Endomyocardial biopsy (EMB) is not a specific or sensitive method. A case-controlled observational study was conducted to evaluate early gadolinium enhancement (EGE) and left ventricular functional parameters on Artificial Intelligence in cine-MRI in patients with acute myocarditis. MATERIAL AND METHODS We selected 21 patients with pathologically proven acute myocarditis. We analyzed the EGE findings (total/serial number and location of positive-segments using the 17-segment model according to the American Heart Association) and clinical characteristics (symptoms, arrhythmias in ECG, coronary angiography, and EMB). All patients were divided into positive EGE and negative EGE groups to analyze left ventricular functional parameters (LVEF, FS, LVEDD, LVEDV, LVESV, LVMM, LVSV, CO, and CI) on Artificial Intelligence. RESULTS We enrolled 21 patients (11 males) with a mean age of 32.6±9.8 years (range, 16 to 51 years). Abnormalities on EGE were found in 2/3 of patients, involving 41 segments among multiple locations on the myocardium. The differences in LVEF (40.2±10.2% vs. 51.3±3.6%), LVESV (69.0±16.1ml vs. 52.5±10.6ml) and LVSV (42.6±11.4 vs. 52.8±2.8 ml) on Artificial Intelligence was statistically significant between the positive EGE and negative EGE groups (p<0.05). CONCLUSIONS Our results suggest a significant role of EGE on the basis of Lake Louise criteria in evaluating patients with clinical suspicion of acute myocarditis. Parameters, including LVEF, LVESV, and LVSV, on Artificial Intelligence, may be useful independent predictors for capillary leakage and microcirculatory disturbance in myocarditis.

A high-sensitivity and low dose energy-dispersive X-ray fluorescence system for identification of gadolium accumulations in planar X-ray fluorescence images.

A new technique, based on in-vivo energy dispersive X-ray fluorescence (EDXRF), has been developed to gadolinium (Gd) concentrations identification in planar X-ray fluorescence (XRF) images. Higher signal-to-noise (SNR) ratios while keeping a low radiation dose were achieved. Experimental validation was performed using tissue equivalent phantoms under two different data acquisition criteria. The first criteria consisted on acquiring the energy spectra from different experimental narrow spectrum beam (FWHM = 2.5 keV) with peak central energy above the L edge energy and determining the spectrum which producing Lowest-Limit-of-Detection (Lowest-LoD) for a specific acquisition time. This also provided the minimum dose expected under the condition of minimum irradiation time. The second criteria consisted on measuring the surface dose required to obtain a specific LoD by different narrow spectrum beam, providing the Lowest-Dose setting. Surface (2D) Gd-doped tissue-equivalent phantoms scanning were performed according to optimized scenarios: Lowest-LoD setting (obtaining to central energy of 10.9 keV) and Lowest-Dose setting (obtaining to central energy 12.9 keV). 625 pixel images were acquired in two different conditions: a pre-defined time (5 s) per pixel was set in the first approach, whereas a pre-defined total surface dose (4 mGy) was set to the second approach. According to the results obtained for the first approach, a 58 times reduction was observed when comparing SNR between the Lowest-LoD and Lowest-Dose settings. On the other hand, for the second approach pre-defining total dose during the whole examination, the best SNR was obtained for the Lowest-Dose configuration exhibiting a 42% of increment respecting to the Lowest-LoD configuration and 47 times higher when compared with the limit case of no optimization.

Preparation of gadolinium doped carbon dots for enhanced MR imaging and cell fluorescence labeling.

Gadolinium doped carbon dots (Gd-CDs) were prepared as a dual-modal imaging agent for enhanced MR imaging and cell fluorescence imaging. The Gd-CDs were synthesized via one-step solvent free technique with Gd-DTPA and l-arginine as the Gd and carbon sources with a quantum yield of 57.78%. The Gd-CDs exhibited good crystal structure, excellent aqueous dispersity, high colloidal stability, intense fluorescence and low cytotoxicity. The bio-TEM images revealed that the Gd-CDs could be easily internalized by cancer cells and escape from the endosomes. Furthermore, the Gd-CDs demonstrated wonderful multi-color fluoresence cell labeling ability at various excitation wavelength and much better MR contrast effect compared with commercial Gd-DTPA with a high r1 relaxivity value 6.27 mM-1s-1. In addition, Gd-CDs exhibited brighter MR signal than Gd-DTPA in the animal MR imaging test. Finally, the Gd-CDs also indicated low long-term toxicity by the serum biochemistry analysis. Thus, these results indicated that Gd-CDs would be an excellent dual-modal imaging probe for enhanced MR imaging and fluorescence imaging.

Exploring the tumour extracellular matrix by in vivo Fast Field Cycling relaxometry after the administration of a Gadolinium-based MRI contrast agent.

1 H Fast Field Cycling NMR (FFC-NMR) relaxometry is proposed as a powerful method to investigate tumour stroma in vivo upon the administration of a Gd-based contrast agent. To perform this study, an FFC-NMR equipment endowed with a wide bore magnet was used for the acquisition of Nuclear Magnetic Resonance Dispersion profiles on healthy muscle and tumour tissue in living mice. At magnetic field strengths < of ca. 1 MHz, the differences in the relaxation rates of the intra and extracellular compartment become of the same order of magnitude of the exchange rate across the cellular membranes. Under this condition, the water exchange rate between the two compartments yields to a biexponential magnetization recovery that can be analysed by fitting the experimental data with the two-Site eXchange (2SX) model. Using this model, it was possible to obtain, for the two compartments, both relaxation properties and water kinetic constants for water exchange across cell membranes. The method allowed us to determine the effect of the "matrix" on the water proton relaxation times and, in turn, to get some insights of the composition of this compartment, till now, largely unknown.

LA-ICP-MS/MS improves limits of detection in elemental bioimaging of gadolinium deposition originating from MRI contrast agents in skin and brain tissues.

A novel analytical method to detect the retention of gadolinium from contrast agents for magnetic resonance imaging (MRI) in tissue samples of patients is presented. It is based on laser ablation - inductively coupled plasma - triple quadrupole - mass spectrometry (LA-ICP-MS/MS). Both Gd and P were monitored with a mass shift of +16, corresponding to mono-oxygenated species, as well as Zn, Ca, and Fe on-mass. This method resulted in a significantly reduced background and improved limits of detection not only for phosphorus, but also for gadolinium. These improvements were essential to perform elemental bioimaging with improved resolution of 5 µm x 5 µm, allowing the detection of small Gd deposits in fibrotic skin and brain tumour tissue with diameters of approximately 50 µm. Detailed analyses of these regions revealed that most Gd was accompanied with P and Ca, indicating co-precipitation.

Physicians' awareness of gadolinium retention and MRI timing practices in the longitudinal management of pituitary tumors: a "Pituitary Society" survey.

PURPOSE: In view of mounting attention related to possible brain retention of gadolinium-based contrast agents (GBCAs) in patients with normal renal function, our purpose was to detail results from a survey of pituitary experts to assess: 1) the timing interval and frequency of pituitary magnetic resonance imaging (MRI) following surgical and/or medical and/or radiation therapy of pituitary tumors, 2) awareness of the types of GBCAs used and their possible safety issues. METHODS: The Pituitary Society Education Committee composed a survey with 12 multiple choice questions, 8 of which specifically addressed the time interval and frequency of MRI in the longitudinal management of pituitary tumors. The survey was distributed at two meetings; the International Pituitary Neurosurgeons Society conference in San Diego, CA, on February 18th, 2018, and the Pituitary Society Membership and Career Development Forum, Chicago, IL on March 18th, 2018. RESULTS: There is consensus among pituitary endocrinologists and neurosurgeons that long-term repeated imaging is recommended in most pituitary tumors, although the precise strategy of timing varied depending on the specialist group and the specific clinical context of the adenoma. The data also suggest that International Pituitary Neurosurgeons Society neurosurgeons, as well as Pituitary Society neuroendocrinologists, are sometimes unaware of which contrast agents are used by their institution, and many are also unaware that evidence of long-term brain retention has been reported with the use of GBCAs in patients with normal function. CONCLUSIONS: International pituitary endocrinologists and pituitary neurosurgeons experts suggest ongoing MRIs for the management of pituitary tumors; strategies vary based on clinical context, but also on individual experience and practice.

Small Gd(III) Tags for Gd(III)-Gd(III) Distance Measurements in Proteins by EPR Spectroscopy.

The C7-Gd and C8-Gd tags are compact hydrophilic cyclen-based lanthanide tags for conjugation to cysteine residues in proteins. The tags are enantiomers, which differ in the configuration of the 2-hydroxylpropyl pendant arms coordinating the lanthanide ion. Here, we report the electron paramagnetic resonance (EPR) performance of the C7-Gd ( S configuration) and C8-Gd ( R configuration) tags loaded with Gd(III) on two mutants of the homodimeric ERp29 protein. The W-band EPR spectra were found to differ between the tags in the free state and after conjugation to the protein. In addition, the spectra were sensitive to the labeling position, which may originate from an environment-dependent charge density on the Gd(III)-coordinating oxygens. This is in agreement with previous NMR experiments with different lanthanide ions, which suggested sensitivity to H-bonding. W-band 1H-ENDOR (electron-electron double resonance) experiments detected effects from orientation selection in the central transition, due to a relatively narrow distribution in the ZFS parameters as indicated by simulations. In contrast, the distance distributions derived from DEER (double electron-electron resonance) measurements were insensitive to the R or S configuration of the tags and did not exhibit any orientation selection effects. The DEER measurements faithfully reflected the different widths of the distance distributions at the different protein sites in agreement with previous DEER measurements using other Gd(III) tags. Due to their small size, short tether to the protein, and a broad central EPR transition, the C7-Gd and C8-Gd tags are attractive Gd(III) tags for measurements of relatively short (<4 nm) distances by EPR spectroscopy.

The effect of gadolinium-based contrast agents on rat testis.

Previous studies have reported that repeated administrations of linear gadolinium-based contrast agents lead to their accumulation in the brain and other tissues in individuals with normal renal functions. The purpose of this prospective animal study was to investigate the effect of multiple administrations of macrocyclic ionic (gadoteric acid) and linear nonionic (gadodiamide) gadolinium-based contrast agents (GBCAs) on rat testis tissue and to compare these molecules in terms of tissue damage. Thirty-two male Sprague-Dawley rats were kept without drugs for 5 weeks after administration of 0.1 mmol mg-1 kg-1 (0.2 ml/kg) gadodiamide and gadoteric acid for 4 days over 5 weeks. Biochemical, histopathological and immunohistochemical changes in testis tissue were evaluated at the end of 10 weeks. When used in repeated clinical doses, gadolinium was observed to increase apoptosis in the Leydig cells of the rat testis, and to increase serum Ca+2 levels and reduce testosterone levels (p < .05). Although the difference was not statistically significant, a greater loss of spermatozoa and immature germinal cell accumulation were observed in the seminiferous tubule lumen in the GBCA groups compared with the control and saline groups (p > .05). Both linear and macrocyclic contrast agents have toxic effects on testis tissue, irrespective of the type of drug.

Targeted gadofullerene for sensitive magnetic resonance imaging and risk-stratification of breast cancer.

Molecular imaging of cancer biomarkers is critical for non-invasive accurate cancer detection and risk-stratification in precision healthcare. A peptide-targeted tri-gadolinium nitride metallofullerene, ZD2-Gd3N@C80, is synthesised for sensitive molecular magnetic resonance imaging of extradomain-B fibronectin in aggressive tumours. ZD2-Gd3N@C80 has superior r 1 and r 2 relaxivities of 223.8 and 344.7 mM-1 s-1 (1.5 T), respectively. It generates prominent contrast enhancement in aggressive MDA-MB-231 triple negative breast cancer in mice at a low dose (1.7 µmol kg-1, 1 T), but not in oestrogen receptor-positive MCF-7 tumours. Strong tumour contrast enhancement is consistently observed in other triple negative breast cancer models, but not in low-risk slow-growing tumours. The dose of the contrast agent for effective molecular MRI is only slightly lower than that of ZD2-Cy5.5 (0.5 µmol kg-1) in fluorescence imaging. These results demonstrate that high-sensitivity molecular magnetic resonance imaging with ZD2-Gd3N@C80 may provide accurate detection and risk-stratification of high-risk tumours for precision healthcare of breast cancer.Molecular MRI is a powerful clinical tool for non-invasive detection of cancer biomarkers. Here, the authors develop a targeted peptide gadofullerene contrast agent that can sensitively distinguish between breast cancers of different aggressiveness.

Confirming improved detection of gadolinium in bone using in vivo XRF.

The safety of using Gd in MRI contrast agents has recently been questioned, due to recent evidence of the retention of Gd in individuals with healthy renal function. Bone has proven to be a storage site for Gd, as unusually high concentrations have been measured in femoral heads of patients undergoing hip replacement surgery, as well as in autopsy samples. All previous measurements of Gd in bone have been invasive and required the bone to be removed from the body. X-ray fluorescence (XRF) offers a non-invasive and non-destructive method for carrying out in vivo measurements of Gd in humans. An updated XRF system provides improved detection limits in a short measurement time of 30-min. A new four-detector system and higher activity Cd-109 excitation source of 5GBq results in minimum detection limits (MDLs) of 1.64-1.72µgGd/g plaster for an average overlaying tissue thickness of the tibia. These levels are well within the range of previous in vitro Gd measurements. Additional validation through comparison with ICP-MS measurements has confirmed the ability of the XRF system for detecting Gd further, proving it is a feasible system to carry out human measurements.