Comprehensive dosimetric characterization of novel silicon carbide detectors with UHDR electron beams for FLASH radiotherapy.

BACKGROUND: The extremely fast delivery of doses with ultra high dose rate (UHDR) beams necessitates the investigation of novel approaches for real-time dosimetry and beam monitoring. This aspect is fundamental in the perspective of the clinical application of FLASH radiotherapy (FLASH-RT), as conventional dosimeters tend to saturate at such extreme dose rates. PURPOSE: This study aims to experimentally characterize newly developed silicon carbide (SiC) detectors of various active volumes at UHDRs and systematically assesses their response to establish their suitability for dosimetry in FLASH-RT. METHODS: SiC PiN junction detectors, recently realized and provided by STLab company, with different active areas (ranging from 4.5 to 10 mm2) and thicknesses (10-20 µm), were irradiated using 9 MeV UHDR pulsed electron beams accelerated by the ElectronFLASH linac at the Centro Pisano for FLASH Radiotherapy (CPFR). The linearity of the SiC response as a function of the delivered dose per pulse (DPP), which in turn corresponds to a specific instantaneous dose rate, was studied under various experimental conditions by measuring the produced charge within the SiC active layer with an electrometer. Due to the extremely high peak currents, an external customized electronic RC circuit was built and used in conjunction with the electrometer to avoid saturation. RESULTS: The study revealed a linear response for the different SiC detectors employed up to 21 Gy/pulse for SiC detectors with 4.5 mm2/10 µm active area and thickness. These values correspond to a maximum instantaneous dose rate of 5.5 MGy/s and are indicative of the maximum achievable monitored DPP and instantaneous dose rate of the linac used during the measurements. CONCLUSIONS: The results clearly demonstrate that the developed devices exhibit a dose-rate independent response even under extreme instantaneous dose rates and dose per pulse values. A systematic study of the SiC response was also performed as a function of the applied voltage bias, demonstrating the reliability of these dosimeters with UHDR also without any applied voltage. This demonstrates the great potential of SiC detectors for accurate dosimetry in the context of FLASH-RT.

Electron FLASH radiotherapy in vivo studies. A systematic review.

FLASH-radiotherapy delivers a radiation beam a thousand times faster compared to conventional radiotherapy, reducing radiation damage in healthy tissues with an equivalent tumor response. Although not completely understood, this radiobiological phenomenon has been proved in several animal models with a spectrum of all kinds of particles currently used in contemporary radiotherapy, especially electrons. However, all the research teams have performed FLASH preclinical studies using industrial linear accelerator or LINAC commonly employed in conventional radiotherapy and modified for the delivery of ultra-high-dose-rate (UHDRs). Unfortunately, the delivering and measuring of UHDR beams have been proved not to be completely reliable with such devices. Concerns arise regarding the accuracy of beam monitoring and dosimetry systems. Additionally, this LINAC totally lacks an integrated and dedicated Treatment Planning System (TPS) able to evaluate the internal dose distribution in the case of in vivo experiments. Finally, these devices cannot modify dose-time parameters of the beam relevant to the flash effect, such as average dose rate; dose per pulse; and instantaneous dose rate. This aspect also precludes the exploration of the quantitative relationship with biological phenomena. The dependence on these parameters need to be further investigated. A promising advancement is represented by a new generation of electron LINAC that has successfully overcome some of these technological challenges. In this review, we aim to provide a comprehensive summary of the existing literature on in vivo experiments using electron FLASH radiotherapy and explore the promising clinical perspectives associated with this technology.

A bioconvergence study on platinum-free concurrent chemoradiotherapy for the treatment of HPV-negative head and neck carcinoma.

Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is characterized by high rate of recurrence, resulting in a poor survival. Standard treatments are associated with significant toxicities that impact the patient's quality of life, highlighting the urgent need for novel therapies to improve patient outcomes. On this regard, noble metal nanoparticles (NPs) are emerging as promising agents as both drug carriers and radiosensitizers. On the other hand, co-treatments based on NPs are still at the preclinical stage because of the associated metal-persistence.In this bioconvergence study, we introduce a novel strategy to exploit tumour chorioallantoic membrane models (CAMs) in radio-investigations within clinical equipment and evaluate the performance of non-persistent nanoarchitectures (NAs) in combination with radiotherapy with respect to the standard concurrent chemoradiotherapy for the treatment of HPV-negative HNSCCs. A comparable effect has been observed between the tested approaches, suggesting NAs as a potential platinum-free agent in concurrent chemoradiotherapy for HNSCCs. On a broader basis, our bioconvergence approach provides an advance for the translation of Pt-free radiosensitizer to the clinical practice, positively shifting the therapeutic vs. side effects equilibrium for the management of HNSCCs.

New insights on clinical perspectives of FLASH radiotherapy: from low- to very high electron energy.

Radiotherapy (RT) is performed in approximately 75% of patients with cancer, and its efficacy is often hampered by the low tolerance of the surrounding normal tissues. Recent advancements have demonstrated the potential to widen the therapeutic window using "very short" radiation treatment delivery (from a conventional dose rate between 0.5 Gy/min and 2 Gy/min to more than 40 Gy/s) causing a significant increase of normal tissue tolerance without varying the tumor effect. This phenomenon is called "FLASH Effect (FE)" and has been discovered by using electrons. Although several physical, dosimetric, and radiobiological aspects need to be clarified, current preclinical "in vivo" studies have reported a significant protective effect of FLASH RT on neurocognitive function, skin toxicity, lung fibrosis, and bowel injury. Therefore, the current radiobiological premises lay the foundation for groundbreaking potentials in clinical translation, which could be addressed to an initial application of Low Energy Electron FLASH (LEE) for the treatment of superficial tumors to a subsequent Very High Energy Electron FLASH (VHEE) for the treatment of deep tumors. Herein, we report a clinical investigational scenario that, if supported by preclinical studies, could be drawn in the near future.

A diamond detector based dosimetric system for instantaneous dose rate measurements in FLASH electron beams.

Objective.A reliable determination of the instantaneous dose rate (I-DR) delivered in FLASH radiotherapy treatments is believed to be crucial to assess the so-called FLASH effect in preclinical and biological studies. At present, no detectors nor real-time procedures are available to do that in ultra high dose rate (UH-DR) electron beams, typically consisting ofµs pulses characterized by I-DRs of the order of MGy/s. A dosimetric system is proposed possibly overcoming the above reported limitation, based on the recently developed flashDiamond (fD) detector (model 60025, PTW-Freiburg, Germany).Approach.A dosimetric system is proposed, based on a flashDiamond detector prototype, properly modified and adapted for very fast signal transmission. It was used in combination with a fast transimpedance amplifier and a digital oscilloscope to record the temporal traces of the pulses delivered by an ElectronFlash linac (SIT S.p.A., Italy). The proposed dosimetric systems was investigated in terms of the temporal characteristics of its response and the capability to measure the absolute delivered dose and instantaneous dose rate (I-DR). A 'standard' flashDiamond was also investigated and its response compared with the one of the specifically designed prototype.Main results. Temporal traces recorded in several UH-DR irradiation conditions showed very good signal to noise ratios and rise and decay times of the order of a few tens ns, faster than the ones obtained by the current transformer embedded in the linac head. By analyzing such signals, a calibration coefficient was derived for the fD prototype and found to be in agreement within 1% with the one obtained under reference60Co irradiation. I-DRs as high as about 2 MGy s-1were detected without any undesired saturation effect. Absolute dose per pulse values extracted by integrating the I-DR signals were found to be linear up to at least 7.13 Gy and in very good agreement with the ones obtained by connecting the fD to a UNIDOS electrometer (PTW-Freiburg, Germany). A good short term reproducibility of the linac output was observed, characterized by a pulse-to-pulse variation coefficient of 0.9%. Negligible differences were observed when replacing the fD prototype with a standard one, with the only exception of a somewhat slower response time for the latter detector type.Significance.The proposed fD-based system was demonstrated to be a suitable tool for a thorough characterization of UH-DR beams, providing accurate and reliable time resolved I-DR measurements from which absolute dose values can be straightforwardly derived.

A new calculation method for the free electron fraction of an ionization chamber in the ultra-high-dose-per-pulse regimen.

The free electron fraction is the fraction of electrons, produced inside the cavity of an ionization chamber after irradiation, which does not bind to gas molecules and thereby reaches the electrode as free electrons. It is a fundamental quantity to describe the recombination processes of an ionization chamber, as it generates a gap of positive charges compared to negative ones, which certainly will not undergo recombination. The free electron fraction depends on the specific chamber geometry, the polarizing applied voltage and the gas thermodynamic properties. Therefore, it is necessary to evaluate such fraction in an accurate and easy way for any measurement condition. In this paper, a simple and direct method for evaluating the free electron fraction of ionization chambers is proposed. We first model the capture process of the electrons produced inside an ionization chamber after the beam pulse; then we present a method to evaluate the free electron fraction based on simple measurements of collected charge, by varying the applied voltage. Finally, the results obtained using an Advanced Markus chamber irradiated with a Flash Radiotherapy dedicated research Linac (ElectronFlash) to estimate the free electron fraction are presented. The proposed method allows the use of a conventional ionization chamber for measurements in ultra-high-dose-per-pulse (UHDP) conditions, up to values of dose-per-pulse at which the perturbation of the electric field due to the generated charge can be considered negligible.

A new solution for UHDP and UHDR (Flash) measurements: Theory and conceptual design of ALLS chamber.

Ultra-High dose-per-pulse regimens (UHDP), necessary to trigger the "FLASH" effect, still pose serious challenges to dosimetry. Dosimetry plays a crucial role, both to significantly improve the accuracy of the radiobiological experiments necessary to fully understand the mechanisms underlying the effect and its dependencies on the beam parameters, and to be able to translate such effect into clinical practice. The standard ionization chamber in UHDP region is significantly affected by the effects of the electric field generated by the enormous density of charges produced by the dose pulse. This work describes the theory and the conceptual design of a gas chamber (the ALLS chamber) which overcomes the above-mentioned problems.

Toward an effective use of laser-driven very high energy electrons for radiotherapy: Feasibility assessment of multi-field and intensity modulation irradiation schemes.

Radiotherapy with very high energy electrons has been investigated for a couple of decades as an effective approach to improve dose distribution compared to conventional photon-based radiotherapy, with the recent intriguing potential of high dose-rate irradiation. Its practical application to treatment has been hindered by the lack of hospital-scale accelerators. High-gradient laser-plasma accelerators (LPA) have been proposed as a possible platform, but no experiments so far have explored the feasibility of a clinical use of this concept. We show the results of an experimental study aimed at assessing dose deposition for deep seated tumours using advanced irradiation schemes with an existing LPA source. Measurements show control of localized dose deposition and modulation, suitable to target a volume at depths in the range from 5 to 10 cm with mm resolution. The dose delivered to the target was up to 1.6 Gy, delivered with few hundreds of shots, limited by secondary components of the LPA accelerator. Measurements suggest that therapeutic doses within localized volumes can already be obtained with existing LPA technology, calling for dedicated pre-clinical studies.

Association between semiquantitative PET parameters and molecular subtypes of breast invasive ductal carcinoma.

BACKGROUND: Molecular subtypes of breast cancer have been proposed since 2012. The correlation between various baseline [18F]fluorodeoxyglucose ([18F]FDG) uptake parameters, including total lesion glycolysis (TLG), and molecular subtypes of primary breast cancer lesions in patients with invasive ductal cancer will be investigated. METHODS: Staging [18F]FDG PET/CT for breast invasive ductal carcinoma were retrospectively evaluated. Breast lesions were examined for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation index (Ki-67). Breast tumors were classified into five molecular subtypes: Luminal A, Luminal B-HER2(-), Luminal B-HER2(+), HER2(+) and Basal or Triple Negative cancers. The correlations between tumor characteristics and PET semiquantitative data of primary breast lesion (SUVmean, SUVmax, Mean tumor volume (MTV), TLG) were assessed. Specific Breast Uptake Ratio (SBUR) is used as a new quantification method of breast uptake to correct for physiological background activity. RESULTS: Fifty-eight patients were included. TLG was significantly higher in triple negative group when compared with luminal A (P<0.01). Significantly higher uptake was found in triple negative lesions when compared with luminal B-HER2(-) and luminal B-HER2(+) categories using SUVmax, SUVmean and TLG (all P<0.05). Conversely, no statistically significant difference for [18F]FDG uptake was observed between all other molecular subtypes. No value of SBUR in terms of correlation with histopathological parameters was demonstrated. CONCLUSIONS: TLG was superior to SUVmax and SUVmean in differentiating between triple negative breast cancer lesions and all other molecular subtypes. SBUR was not different statistically between various molecular subtypes.

Dosimetric characteristics of electron beams produced by two mobile accelerators, Novac7 and Liac, for intraoperative radiation therapy through Monte Carlo simulation.

The Novac7 and Liac are linear accelerators (linacs) dedicated to intraoperative radiation therapy (IORT), which produce high energy, very high dose-per-pulse electron beams. The characteristics of the accelerators heads of the Novac7 and Liac are different compared to conventional electron accelerators. The aim of this work was to investigate the specific characteristics of the Novac7 and Liac electron beams using the Monte Carlo method. The Monte Carlo code BEAMnrc has been employed to model the head and simulate the electron beams. The Monte Carlo simulation was preliminarily validated by comparing the simulated dose distributions with those measured by means of EBT radiochromic film. Then, the energy spectra, mean energy profiles, fluence profiles, photon contamination, and angular distributions were obtained from the Monte Carlo simulation. The Spencer-Attix water-to-air mass restricted collision stopping power ratios (sw,air) were also calculated. Moreover, the modifications of the percentage depth dose in water (backscatter effect) due to the presence of an attenuator plate composed of a sandwich of a 2 mm aluminum foil and a 4 mm lead foil, commonly used for breast treatments, were evaluated. The calculated sw,air values are in agreement with those tabulated in the IAEA TRS-398 dosimetric code of practice within 0.2% and 0.4% at zref (reference depth in water) for the Novac7 and Liac, respectively. These differences are negligible for practical dosimetry. The attenuator plate is sufficient to completely absorb the electron beam for each energy of the Novac7 and Liac; moreover, the shape of the dose distribution in water strongly changes with the introduction of the attenuator plate. This variation depends on the energy of the beam, and it can give rise to an increase in the maximum dose in the range of 3%-9%.

High diagnostic accuracy of low-dose gated-SPECT with solid-state ultrafast detectors: preliminary clinical results.

PURPOSE: Appropriate use of SPECT imaging is regulated by evidence-based guidelines and appropriateness criteria in an effort to limit the burden of radiation administered to patients. We aimed at establishing whether the use of a low dose for stress-rest single-day nuclear myocardial perfusion imaging on an ultrafast (UF) cardiac gamma camera using cadmium-zinc-telluride solid-state detectors could be used routinely with the same accuracy obtained with standard doses and conventional cameras. METHODS: To this purpose, 137 consecutive patients (mean age 61 ± 8 years) with known or suspected coronary artery disease (CAD) were enrolled. They underwent single-day low-dose stress-rest myocardial perfusion imaging using UF SPECT and invasive coronary angiography. Patients underwent the first scan with a 7-min acquisition time 10 min after the end of the stress protocol (dose range 185 to 222 MBq of (99m)Tc-tetrofosmin). The rest scan (dose range 370 to 444 MBq of (99m)Tc-tetrofosmin) was acquired with a 6-min acquisition time. The mean summed stress scores (SSS) and mean summed rest scores (SRS) were obtained semiquantitatively. RESULTS: Coronary angiograms showed significant epicardial CAD in 83% of patients. Mean SSS and SRS were 10 ± 5 and 3 ± 3, respectively. Overall the area under the ROC curve for the SSS values was 0.904, while the areas under the ROC curves for each vascular territory were 0.982 for the left anterior descending artery, 0.931 for the left circumflex artery and 0.889 for the right coronary artery. CONCLUSION: This pilot study demonstrated the feasibility of a low-dose single-day stress-rest fasting protocol performed using UF SPECT, with good sensitivity and specificity in detecting CAD at low patient exposure, opening new perspectives in the use of myocardial perfusion in ischaemic patients.

Feline immunodeficiency virus vector as a tool for preventative strategies against human breast cancer.

Breast cancer is the most common type of neoplasia in women. Currently 90% cases are sporadic whereas up to 10% are hereditary and likely due to germ-line mutations in specific genes. Eighty percent hereditary breast cancers are associated with inactivation of breast cancer-associated genes (BRCA) type 1 and 2 by sequential mutations. Loss of functionality of one or both genes greatly increases the risk to develop breast cancer and set the basis for the design of strategies to restore BRCA functions or replace the inactive gene(s) before the emergence of the neoplasia. We have produced a lentiviral vector from the feline immunodeficiency virus (FIV) to transduce wild type BRCA1 into primary mammary cells with a non-functional gene. The system was set up and optimized in tumor cells expressing a truncated gene. Transduced BRCA1 was expressed efficiently and fully functional as demonstrated by the restored ability to repair DNA damages upon exposure of transduced cells to ionizing radiations. This work sets the basis for innovative gene therapy strategies against human breast cancer.

Evaluation of a method for activity estimation in Sm-153 EDTMP imaging.

Absolute activity evaluation is fundamental for internal radionuclide dosimetry when patient-specific therapy optimization is wanted. Often, quantification is attempted with 3D SPECT image based (IB) methods, but the true concentration values can be underestimated due to the partial volume effect (PVE). This is especially true when small diffuse lesions are present. In this paper, we describe a 3D region of interest (ROI) based quantification method (LS-ROI), which estimates the ROI concentration values directly from the projection data acquired in the tomographic scan once ROIs have been segmented on a CT and/or a SPECT image. The method, which has inherent PVE correction capabilities, was applied both on simulated and on real phantom data. Simulations reflected the case of a patient with bone metastases treated with 153Sm-EDTMP: Both the activity in the metastases and the total retention in the skeleton were evaluated. Thirty noisy data sets were produced in order to evaluate the accuracy and precision of the method. The effect of region segmentation errors on estimated concentrations was thoroughly investigated. Real data were acquired on a NEMA phantom, where a cylindrical central region (283 cm3) simulated the bone and two spheres (10.3 and 25.5 cm3) simulated the metastases. The results obtained with the LS-ROI method were compared with those of a conventional 3D IB method and those of a quantitative conjugate view approach derived from LS-ROI and applied to the anterior and posterior views acquired in the tomographic scan (LS-ROI anterior-posterior: LS-ROI-AP). Simulations showed that when the geometry of regions is known, the LS-ROI method recovered the simulated concentration values within 20%, while the IB method underestimated the concentration in high activity small lesions by as much as 49%. Segmentation errors, up to 44% of the true region volume, produced a higher variation in LS-ROI estimates than in IB ones; however, the overall bias of the LS-ROI estimates (< or = 25%) remained lower than that of IB estimates. In the case of the evaluation of the total retention in the skeleton, the LS-ROI method recovered the simulated value within 2%, while IB underestimated it up to 13%. In all the cases, the LS-ROI-AP method showed an accuracy comparable with that of the LS-ROI one, and a worse precision just because of the lower number of counts used in the analysis. However, a worsening of LS-ROI-AP performances was demonstrated in the case of strong overlap of regions: In this case, a bias of up to 40% was observed. The results obtained on real phantom data confirmed the simulation results: The IB method underestimated activity up to 47% in the smallest sphere, while the bias was reduced to 13% with LS-ROI and LS-ROI-AP estimates. The good quantification capabilities of the LS-ROI method can be useful for absolute activity quantification in the case of small active diffused lesions and constitute the basis for the development of an accurate patient-specific planning strategy in internal radionuclide treatments, provided there is a reliable segmentation of lesions.

A study of the possibility of curing Graves' disease based on the desired reduction of thyroid mass (volume) as a consequence of 131I therapy: a speculative paper.

PURPOSE: The possibility of predicting the final volume of Graves' disease thyroids submitted to 131I therapy could allow the physician to decide what activity to administer based on the desired volume reduction instead of on a fixed value of the thyroid radiation absorbed dose. In this paper the relationship between maximum uptake of 131I, fractional reduction of thyroid volume and outcome of Graves' disease is discussed. METHODS: The results are based on ultrasonography thyroid volume measurements before administration of therapy and at the moment of recovery from Graves' disease (thyroid stimulating hormone >0.3 microIU x ml(-1) in the absence of anti-thyroid drug therapy) and on measurements of 131I uptake in 40 patients. It is shown that the possibility of curing Graves' disease may be individually related to the final volume of the patient's thyroid. An equation is presented to calculate the 'optimal' final thyroid volume. RESULTS: A comparison between the traditional method, based on absorbed dose, and the final method, based on volume, has been carried out retrospectively. In the first case a median activity of 529 MBq has been administered; in the second, a median activity of 394 MBq (non-parametric Wilcoxon test, P<0.05) should be administered. The corresponding thyroid median absorbed doses are, respectively, 353 Gy and 320 Gy (non-parametric Wilcoxon test, P<0.02). CONCLUSION: A method to evaluate individually the 'optimal' final thyroid mass is presented and discussed. The method based on 'volume reduction' could probably reduce the activity and the thyroid absorbed dose compared to the method based on 'empirical' calculations, thus allowing the administration of 131I therapy to be optimized.

Comparison of different thyroid committed doses in radioiodine therapy for Graves' hyperthyroidism.

Despite vast worldwide experience in the use of 131I for treating Graves' disease (GD), no consensus of opinion exists concerning the optimal method of dose calculation. In one of the most popular equations, the administered (131)I dose is directly proportional to the estimated thyroid gland volume and inversely proportional to the measured 24-hour radioiodine uptake. In this study, we compared the efficiency of different tissue-absorbed doses to induce euthyroidism or hypothyroidism within 1 year after radioiodine therapy in GD patients. The study was carried out in 134 GD patients (age, 53 +/- 14 year; range, 16-82 year; thyroid volume, 28 +/- 18 mL; range, 6-95 mL; average 24-hour thyroid uptake, 72%) treated with (131)I therapy. The average radioiodine activity administered to patients was 518 +/- 226 MBq (range, 111-1110). The corresponding average thyroid absorbed dose, calculated by a modified Medical Internal Radiation Dose (MIRD) equation was 376 +/- 258 Gy (range, 99-1683). One year after treatment, 58 patients (43%) were hypothyroid, 57 patients (43%) were euthyroid, and 19 patients (14%) remained hyperthyroid. The patients were divided into 3 groups: 150 Gy (n = 32), 300 Gy (n = 58) and >300 Gy (n = 44). No significant difference in the rate of recurrent hyperthyroidism was found among the 3 groups (150 Gy: 15%; 300 Gy: 14%; and > or =300 Gy: 14%; chi-square test, p = 0.72). Whereas, the rate of hypothyroidism in the 3 groups was significantly correlated with the dose (150 Gy: 30%; 300 Gy: 46%; >300 Gy: 71%; chi-square test, p = 0.0003). The results obtained in this study show no correlation between dose and outcome of radioiodine therapy (in terms of persistent hyperthyroidism) for thyroid absorbed doses > or =150 Gy, while confirming the relation between the thyroid absorbed dose and the incidence of hypothyroidism in GD patients.

A predictive mathematical model for the calculation of the final mass of Graves' disease thyroids treated with 131I.

Substantial reductions in thyroid volume (up to 70-80%) after radioiodine therapy of Graves' hyperthyroidism are common and have been reported in the literature. A relationship between thyroid volume reduction and outcome of 131I therapy of Graves' disease has been reported by some authors. This important result could be used to decide individually the optimal radioiodine activity A0 (MBq) to administer to the patient, but a predictive model relating the change in gland volume to A0 is required. Recently, a mathematical model of thyroid mass reduction during the clearance phase (30-35 days) after 131I administration to patients with Graves' disease has been published and used as the basis for prescribing the therapeutic thyroid absorbed dose. It is well known that the thyroid volume reduction goes on until 1 year after therapy. In this paper, a mathematical model to predict the final mass of Graves' diseased thyroids submitted to 131I therapy is presented. This model represents a tentative explanation of what occurs macroscopically after the end of the clearance phase of radioiodine in the gland (the so-called second-order effects). It is shown that the final thyroid mass depends on its basal mass, on the radiation dose absorbed by the gland and on a constant value alpha typical of thyroid tissue. Alpha has been evaluated based on a set of measurements made in 15 reference patients affected by Graves' disease and submitted to 131I therapy. A predictive equation for the calculation of the final mass of thyroid is presented. It is based on macroscopic parameters measurable after a diagnostic 131I capsule administration (0.37-1.85 MBq), before giving the therapy. The final mass calculated using this equation is compared to the final mass of thyroid measured 1 year after therapy administration in 22 Graves' diseased patients. The final masses calculated and measured 1 year after therapy are in fairly good agreement (R = 0.81). The possibility, for the physician, to decide a therapeutic activity based on the desired decrease of thyroid mass instead of on a fixed thyroid absorbed dose could be a new opportunity to cure Graves' disease.

A dosimetric approach to patient-specific radioiodine treatment of Graves' disease with incorporation of treatment-induced changes in thyroid mass.

The traditional algorithms (Marinelli-Quimby and MIRD) used for the absorbed dose calculation in radionuclide therapy generally assume that the mass of the target organs does not change with time. In radioiodine therapy for Graves' disease this approximation may not be valid. In this paper a mathematical model of thyroid mass reduction during the clearance phase (30-35 days) after 131I administration to patients with Graves' disease is presented. A new algorithm for the absorbed dose calculation is derived, taking into account the reduction of the mass of the gland resulting from the 131I therapy. It is demonstrated that thyroid mass reduction has a considerable effect on the calculated radiation dose. Either the model of the thyroid mass reduction or the new equation for the absorbed dose calculation depend on a parameter k for each patient. This parameter can be calculated after the administration of a diagnostic amount of radioiodine activity (0.37-1.85 MBq). Thus, thyroid absorbed dose and thyroid mass reduction during the first month after therapy can be predicted before therapy administration. The absorbed dose values calculated by the new algorithm are compared to those calculated by the traditional Marinelli-Quimby and MIRD algorithms.

An automatic method for the recognition and classification of the A-phases of the cyclic alternating pattern.

OBJECTIVES: The aim of this research has been to introduce an automatic method, simple from the mathematical and computational points of view, for the recognition and classification of the A-phases of the cyclic alternating pattern. METHODS: The automatic method was based on the computation of 5 descriptors, which were derived from the EEG signal and were able to provide a meaningful data reduction. Each of them corresponded to a different frequency band. RESULTS: The computation of these descriptors, followed by the introduction of two suitable thresholds and of simple criteria for logical discrimination, provided results which were in good agreement with those obtained with visual analysis. The method was versatile and could be applied to the study of other important microstructure phenomena by means of very small adaptations. CONCLUSIONS: The simplicity of the method leads to a better understanding and a more precise definition of the visual criteria for the recognition and classification of the microstructure phenomena.