Ernesto Amato

Can Contrast Media Increase Organ Doses in CT Examinations? A Clinical Study

OBJECTIVE The purpose of this article is to quantify the CT radiation dose increment in five organs resulting from the administration of iodinated contrast medium. MATERIALS AND METHODS Forty consecutive patients who underwent both un-enhanced and contrast-enhanced thoracoabdominal CT were included in our retrospective study. The dose increase between CT before and after contrast agent administration was evaluated in the portal phase for the thyroid, liver, spleen, pancreas, and kidneys by applying a previously validated method. RESULTS An increase in radiation dose was noted in all organs studied. Average dose increments were 19% for liver, 71% for kidneys, 33% for spleen and pancreas, and 41% for thyroid. Kidneys exhibited the maximum dose increment, whereas the pancreas showed the widest variance because of the differences in fibro-fatty involution. Finally, thyroids with high attenuation values on unenhanced CT showed a lower Hounsfield unit increase and, thus, a smaller increment in the dose. CONCLUSION Our study showed an increase in radiation dose in several parenchymatous tissues on contrast-enhanced CT. Our method allowed us to evaluate the dose increase from the change in attenuation measured in Hounsfield units. Because diagnostic protocols require multiple acquisitions after the contrast agent administration, such a dose increase should be considered when optimizing these protocols.

Kidney Dosimetry in 177Lu and 90Y Peptide Receptor Radionuclide Therapy: Influence of Image Timing, Time-Activity Integration Method, and Risk Factors

Kidney dosimetry in 177Lu and 90Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with 177Lu DOTATATE and 30 with 177Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for 177Lu therapy and 70 h for 90Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05).

Use of diffusion-weighted, intravoxel incoherent motion, and dynamic contrast-enhanced MR imaging in the assessment of response to radiotherapy of lytic bone metastases from breast cancer.

RATIONALE AND OBJECTIVES To investigate the value of diffusion-weighted (DW), perfusion-sensitive, and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) techniques in assessing the response of bone metastases from breast cancer to radiotherapy, with particular emphasis on the role of intravoxel incoherent motion (IVIM)-DW parameters as a potential valuable imaging marker of tumor response. MATERIALS AND METHODS Fifteen women having breast cancer and bone metastases underwent MRI before and after radiotherapy (3 weeks [time 1], 2 months [time 2], and 4 months [time 3]), consisting of DW, perfusion-sensitive (IVIM), and DCE acquisitions. MR-based DW and perfusion parameters, including water diffusivity (D), perfusion fraction (f), pseudodiffusion (D*), total apparent diffusion coefficient (ADC-total), fractionated ADCs (ADC-high and ADC-low), and initial area under the gadolinium concentration curve after the first 60 seconds (IAUGC60), were determined. The morphologic MRI findings were also recorded. A one-way repeated measures analysis of variance was used to compare the value of MR-based parameters at the different time points. RESULTS A significant variation between pretreatment (time 0) and post-treatment (times 1, 2, and 3) was found for ADC-total and D parameters (P < .001). A statistically significant reduction was also found for IAUGC60 values between times 0 and 3 (P < .001). A significant change across the different time points was observed for D* and IAUGC60 parameters (P < .001). On the contrary, there was no statistically significant change over time for parameters ADC-total, D, f, and IAUGC60 comparing response between each metastasis, that is, the response to therapy was similar for each metastasis. CONCLUSIONS DW, IVIM, and DCE-MRI techniques show effectiveness in assessing the response to radiotherapy in bone metastases from breast cancer.

Gold nanoparticles as a sensitising agent in external beam radiotherapy and brachytherapy: a feasibility study through Monte Carlo simulation

In recent years, gold nanoparticles (GNP) have been proposed as sensitising agents in radiotherapy. Several studies, performed both through Monte Carlo simulation of dosimetric and microdosimetric enhancement in presence of GNPs and through in–vitro experiments, have clearly shown the powerfulness of such a technique in radiotherapy. Aim of the present work is to estimate the dose enhancement during external beam radiotherapy and brachytherapy in tissues loaded with different GNP concentrations. We developed two Monte Carlo simulations in GEANT4: one reproducing a medical Linac operating at 6 MV, irradiating a volume of soft tissue containing GNP–doped sub–volumes at various depths; the second one representing an 192Ir source irradiating a cylindrical cavity, in presence of a shallow volume distribution of GNPs. The Linac simulation yielded relative percent dose increases ranging from 1.6% for GNP concentrations of 1% in weight to 18% for 10% GNP concentrations, while the high–energy brachytherapy 192Ir source gave 6% of relative dose increase at 1% of concentration up to more than 70% increase at 10% of GNP concentration. Such dose enhancements are mainly due to the increased photoelectron and characteristic X–ray production from the GNPs and, at a lower percentage, to the Auger electrons escaping from the GNPs. These scarcely penetrating radiations induce relevant microdosimetric intensifications in the surrounding of each GNP, leading to a biological damage at cellular and sub–cellular level, which depends on the biological distribution of GNPs within the target cells.

Differences in 3D dose distributions due to calculation method of voxel S-values and the influence of image blurring in SPECT.

This study compares 3D dose distributions obtained with voxel S values (VSVs) for soft tissue, calculated by several methods at their current state-of-the-art, varying the degree of image blurring. The methods were: 1) convolution of Dose Point Kernel (DPK) for water, using a scaling factor method; 2) an analytical model (AM), fitting the deposited energy as a function of the source-target distance; 3) a rescaling method (RSM) based on a set of high-resolution VSVs for each isotope; 4) local energy deposition (LED). VSVs calculated by direct Monte Carlo simulations were assumed as reference. Dose distributions were calculated considering spheroidal clusters with various sizes (251, 1237 and 4139 voxels of 3 mm size), uniformly filled with (131)I, (177)Lu, (188)Re or (90)Y. The activity distributions were blurred with Gaussian filters of various widths (6, 8 and 12 mm). Moreover, 3D-dosimetry was performed for 10 treatments with (90)Y derivatives. Cumulative Dose Volume Histograms (cDVHs) were compared, studying the differences in D95%, D50% or Dmax (ΔD95%, ΔD50% and ΔDmax) and dose profiles.For unblurred spheroidal clusters, ΔD95%, ΔD50% and ΔDmax were mostly within some percents, slightly higher for (177)Lu with DPK (8%) and RSM (12%) and considerably higher for LED (ΔD95% up to 59%). Increasing the blurring, differences decreased and also LED yielded very similar results, but D95% and D50% underestimations between 30-60% and 15-50%, respectively (with respect to 3D-dosimetry with unblurred distributions), were evidenced. Also for clinical images (affected by blurring as well), cDVHs differences for most methods were within few percents, except for slightly higher differences with LED, and almost systematic for dose profiles with DPK (-1.2%), AM (-3.0%) and RSM (4.5%), whereas showed an oscillating trend with LED.The major concern for 3D-dosimetry on clinical SPECT images is more strongly represented by image blurring than by differences among the VSVs calculation methods. For volume sizes about 2-fold the spatial resolution, D95% and D50% underestimations up to about 60 and 50% could result, so the usefulness of 3D-dosimetry is highly questionable for small tumors, unless adequate corrections for partial volume effects are adopted.

Plastic materials as a radiation shield for β− sources: a comparative study through Monte Carlo calculation

We have developed a Monte Carlo simulation in Geant4 to compare the attenuation properties and the bremsstrahlung radiation yield of different types of plastic materials employed as shields for beta- radioactive sources. Code validation results against Sandia and NIST data are presented. For polypropylene (C3H6), polystyrene (C2H3), polyamide nylon-6 (C6H11ON), poly-methyl methacrylate (C5H8O2), polycarbonate (C16H6O3), polyethylene terephthalate (C10H8O4), polyvinyl chloride (C2H3Cl) and polytetrafluoroethylene (C2F4) we evaluated the mean and maximum ranges for electrons originating from 90Sr and 90Y, as well as the number and spectrum of the bremsstrahlung x-rays produced. Significant differences appear between the various materials, and the choice of the best one also depends on the physical properties requested for each specific application.

The Italian multicentre dosimetric study for lesion dosimetry in (223)Ra therapy of bone metastases: Calibration protocol of gamma cameras and patient eligibility criteria.

PURPOSE The aims of this work were to explore patient eligibility criteria for dosimetric studies in 223Ra therapy and evaluate the effects of differences in gamma camera calibration procedures into activity quantification. METHODS Calibrations with 223Ra were performed with four gamma cameras (3/8-inch crystal) acquiring planar static images with double-peak (82 and 154keV, 20% wide) and MEGP collimator. The sensitivity was measured in air by varying activity, source-detector distance, and source diameter. Transmission curves were measured for attenuation/scatter correction with the pseudo-extrapolation number method, varying the experimental setup. 223Ra images of twenty-five patients (69 lesions) were acquired to study the lesions visibility. Univariate ROC analysis was performed considering visible/non visible lesions on 223Ra images as true positive/true negative group, and using as score value the lesion/soft tissue contrast ratio (CR) derived from 99mTc-MDP WB scan. RESULTS Sensitivity was nearly constant varying activity and distance (maximum s.d.=2%). Partial volume effects were negligible for object area ⩾960mm2. Transmission curve measurements are affected by experimental setup and source size, leading to activity quantification errors up to 20%. The ROC analysis yielded an AUC of 0.972 and an optimal threshold of CR of 10, corresponding to an accuracy of 92%. CONCLUSION The minimum calibration protocol requires sensitivity and transmission curve measurements varying the object size, performing a careful procedure standardisation. Lesions with 99mTc-MDP CR higher than 10, not overlapping the GI tract, are generally visible on 223Ra images acquired at 24h after the administration, and possibly eligible for dosimetric studies.

Thyroid remnant ablation in differentiated thyroid cancer: searching for the most effective radioiodine activity and stimulation strategy in a real-life scenario.

ObjectiveDifferentiated thyroid cancer is rare, but the incidence has been increasing in the last few decades. Early treatment is based on surgery and thyroid remnant ablation (TRA) by means of radioiodine therapy. Despite radioiodine being widely used for decades, the choice of ablative activity is generally empirical and no consensus has been reached to date. The aim of our study was to compare the efficacy and safety of different radioiodine activities. In addition, we compared the ablation rate in patients treated in the hypothyroid state or after recombinant human thyroid-stimulating hormone (rhTSH) administration, retrospectively reviewing the records of 471 patients affected by differentiated thyroid cancer. Patients and methodsPatients were subdivided into three groups on the basis of the different activities of radioiodine administered and taking into account the different approaches used to perform the therapy: thyroid hormonal withdrawal or rhTSH stimulation. ResultsThe success of TRA was evaluated 12 months later. TRA was obtained in 62/79 (78.5%) in group A (1110 MBq in the hypothyroid state), 183/190 (96.3%) in group B [2220 MBq in the hypothyroid state or after rhTSH administration: 87/90 (97%) and 96/100 (96%) patients, respectively], 199/202 (98.5%) in group C [3700 MBq in hypothyroid state or after rhTSH administration: 98/100 (98%) and 101/102 (99%) patients, respectively]. ConclusionOur data demonstrate that 2220 and 3700 MBq radioiodine are more effective compared with 1110 MBq in TRA, without significant differences between 2220 and 3700 MBq or between hypothyroidism and euthyroidism. We suggest rhTSH-aided TRA with 2220 MBq iodine-131, as this approach permits efficacious treatment, thereby reducing side effects, absorbed dose to body and hospital stay.

A Monte Carlo approach to small-scale dosimetry of solid tumour microvasculature for nuclear medicine therapies with 223Ra-, 131I-, 177Lu- and 111In-labelled radiopharmaceuticals

The small-scale dosimetry of radionuclides in solid-tumours is directly related to the intra-tumoral distribution of the administered radiopharmaceutical, which is affected by its egress from the vasculature and dispersion within the tumour. The aim of the present study was to evaluate the combined dosimetric effects of radiopharmaceutical distribution and range of the emitted radiation in a model of tumour microvasculature. We developed a computational model of solid-tumour microenvironment around a blood capillary vessel, and we simulated the transport of radiation emitted by (223)Ra, (111)In, (131)I and (177)Lu using the GEANT4 Monte Carlo. For each nuclide, several models of radiopharmaceutical dispersion throughout the capillary vessel were considered. Radial dose profiles around the capillary vessel, the Initial Radioactivity (IR) necessary to deposit 100 Gy of dose at the edge of the viable tumour-cell region, the Endothelial Cell Mean Dose (ECMD) and the Tumour Edge Mean Dose (TEMD), i.e. the mean dose imparted at the 250-μm layer of tissue, were computed. The results for beta and Auger emitters demonstrate that the photon dose is about three to four orders of magnitude lower than that deposited by electrons. For (223)Ra, the beta emissions of its progeny deliver a dose about three orders of magnitude lower than that delivered by the alpha emissions. Such results may help to characterize the dose inhomogeneities in solid tumour therapies with radiopharmaceuticals, taking into account the interplay between drug distribution from vasculature and range of ionizing radiations.

Influence of the X-ray beam quality on the dose increment in CT with iodinated contrast medium

BACKGROUND In computed tomography (CT), the image contrast is given by the difference in X-ray attenuation in the various tissues of the patient and contrast media are used to enhance image contrast in anatomic regions characterized by similar attenuation coefficients. OBJECTIVE Aim of the present work is to enlarge the range of applicability of the method previously introduced for organ dosimetry in contrast-enhanced CT, by studying the effects of X-ray beam quality on the parameters of the model. Furthermore, an experimental method for the evaluation of the attenuation properties of iodinated solutions is proposed. METHODS Monte Carlo simulations of anthropomorphic phantoms were carried out to determine a bi-parametrical (a and b) analytical relationship between iodine concentration and dose increase in organs of interest as a function of the tube kilo-voltage peak potential (kVp) and filtration. Experimental measurements of increments in Hounsfield Units (HU) were conducted in several CT scanners, at all the kVp available, in order to determine the parameter γ which relates the HU increment with the iodine mass fraction. A cylindrical phantom that can be filled with iodine solutions provided with an axial housing for a pencil ionization chamber was designed and assembled in order to measure the attenuation properties of iodine solutions under irradiation of a CT scanner and to obtain a further validation of Monte Carlo simulations. RESULTS The simulation-derived parameters of the model, a and b, are only slightly dependent upon the tube kilo-voltage peak potential and filtration, while such scanner-dependent features influence mainly the experimentally-derived γ parameter. Relative dose variations registered by the ionization chamber inside the iodine-filled cylindrical phantom decrease when the X-ray mean energy increases, and reaches about 50% for 10 mg/ml of iodine. CONCLUSIONS The dosimetric method for contrast-enhanced CT can be applied to all CT scanners by adopting average simulative parameters and by carrying out a simple measurement with a series of iodine contrast solutions. The novel experimental methodology introduced can provide a direct measurement of iodine attenuation properties.