Physical and dosimetric characterisation of different Contrast-Enhanced digital mammographic systems: A multicentric study.

PURPOSE: Contrast-enhanced digital mammography (CEDM) is a relatively new imaging technique recombining low- and high-energy mammograms to emphasise iodine contrast. This work aims to perform a multicentric physical and dosimetric characterisation of four state-of-the-art CEDM systems. METHODS: We evaluated tube output, half-value-layer (HVL) for low- and high-energy and average glandular dose (AGD) in a wide range of equivalent breast thicknesses. CIRS phantom 022 was used to estimate the overall performance of a CEDM examination in the subtracted image in terms of the iodine difference signal (S). To calculate dosimetric impact of CEDM examination, we collected 4542 acquisitions on patients. RESULTS: Even if CEDM acquisition strategies differ, all the systems presented a linear behaviour between S and iodine concentration. The curve fit slopes expressed in PV/mg/cm2 were in the range [92-97] for Fujifilm, [31-32] for GE Healthcare, [35-36] for Hologic, and [114-130] for IMS. Dosimetric data from patients were matched with AGD values calculated using equivalent PMMA thicknesses. Fujifilm exhibited the lowest values, while GE Healthcare showed the highest. CONCLUSION: The subtracted image showed the ability of all the systems to give important information about the linearity of the signal with the iodine concentrations. All the patient-collected doses were under the AGD EUREF 2D Acceptable limit, except for patients with thicknesses ≤35 mm belonging to GE Healthcare and Hologic, which were slightly over. This work demonstrates the importance of testing each CEDM system to know how it performs regarding dose and the relationship between PV and iodine concentration.

Safety of Inhomogeneous Dose Distribution IMRT for High-Grade Glioma Reirradiation: A Prospective Phase I/II Trial (GLIORAD TRIAL).

Glioblastoma multiforme (GBM) is the most aggressive astrocytic primary brain tumor, and concurrent temozolomide (TMZ) and radiotherapy (RT) followed by maintenance of adjuvant TMZ is the current standard of care. Despite advances in imaging techniques and multi-modal treatment options, the median overall survival (OS) remains poor. As an alternative to surgery, re-irradiation (re-RT) can be a therapeutic option in recurrent GBM. Re-irradiation for brain tumors is increasingly used today, and several studies have demonstrated its feasibility. Besides differing techniques, the published data include a wide range of doses, emphasizing that no standard approach exists. The current study aimed to investigate the safety of moderate-high-voxel-based dose escalation in recurrent GBM. From 2016 to 2019, 12 patients met the inclusion criteria and were enrolled in this prospective single-center study. Retreatment consisted of re-irradiation with a total dose of 30 Gy (up to 50 Gy) over 5 days using the IMRT (arc VMAT) technique. A dose painting by numbers (DPBN)/dose escalation plan were performed, and a continuous relation between the voxel intensity of the functional image set and the risk of recurrence in that voxel were used to define target and dose distribution. Re-irradiation was well tolerated in all treated patients. No toxicities greater than G3 were recorded; only one patient had severe G3 acute toxicity, characterized by muscle weakness and fatigue. Median overall survival (OS2) and progression-free survival (PFS2) from the time of re-irradiation were 10.4 months and 5.7 months, respectively; 3-, 6-, and 12-month OS2 were 92%, 75%, and 42%, respectively; and 3-, 6-, and 12-month PFS2 were 83%, 42%, and 8%, respectively. Our work demonstrated a tolerable tolerance profile of this approach, and the future prospective phase II study will analyze the efficacy in terms of PFS and OS.

Variations in Head and Neck Treatment Plan Quality Assessment Among Radiation Oncologists and Medical Physicists in a Single Radiotherapy Department.

BACKGROUND: Agreement between planners and treating radiation oncologists (ROs) on plan quality criteria is essential for consistent planning. Differences between ROs and planning medical physicists (MPs) in perceived quality of head and neck cancer plans were assessed. MATERIALS AND METHODS: Five ROs and four MPs scored 65 plans for in total 15 patients. For each patient, the clinical (CLIN) plan and two or four alternative plans, generated with automated multi-criteria optimization (MCO), were included. There was always one MCO plan aiming at maximally adhering to clinical plan requirements, while the other MCO plans had a lower aimed quality. Scores were given as follows: 1-7 and 1-2, not acceptable; 3-5, acceptable if further planning would not resolve perceived weaknesses; and 6-7, straightway acceptable. One MP and one RO repeated plan scoring for intra-observer variation assessment. RESULTS: For the 36 unique observer pairs, the median percentage of plans for which the two observers agreed on a plan score (100% = 65 plans) was 27.7% [6.2, 40.0]. In the repeat scoring, agreements between first and second scoring were 52.3% and 40.0%, respectively. With a binary division between unacceptable (scores 1 and 2) and acceptable (3-7) plans, the median inter-observer agreement percentage was 78.5% [63.1, 86.2], while intra-observer agreements were 96.9% and 86.2%. There were no differences in observed agreements between RO-RO, MP-MP, and RO-MP pairs. Agreements for the highest-quality, automatically generated MCO plans were higher than for the CLIN plans. CONCLUSIONS: Inter-observer differences in plan quality scores were substantial and could result in inconsistencies in generated treatment plans. Agreements among ROs were not better than between ROs and MPs, despite large differences in training and clinical role. High-quality automatically generated plans showed the best score agreements.

A Multicentre Evaluation of Dosiomics Features Reproducibility, Stability and Sensitivity.

Dosiomics is a texture analysis method to produce dose features that encode the spatial 3D distribution of radiotherapy dose. Dosiomic studies, in a multicentre setting, require assessing the features' stability to dose calculation settings and the features' capability in distinguishing different dose distributions. Dose distributions were generated by eight Italian centres on a shared image dataset acquired on a dedicated phantom. Treatment planning protocols, in terms of planning target volume coverage and dose-volume constraints to the organs at risk, were shared among the centres to produce comparable dose distributions for measuring reproducibility/stability and sensitivity of dosiomic features. In addition, coefficient of variation (CV) was employed to evaluate the dosiomic features' variation. We extracted 38,160 features from 30 different dose distributions from six regions of interest, grouped by four features' families. A selected group of features (CV < 3 for the reproducibility/stability studies, CV > 1 for the sensitivity studies) were identified to support future multicentre studies, assuring both stable features when dose distributions variation is minimal and sensitive features when dose distribution variations need to be clearly identified. Dosiomic is a promising tool that could support multicentre studies, especially for predictive models, and encode the spatial and statistical characteristics of the 3D dose distribution.

Artificial intelligence applications in medical imaging: A review of the medical physics research in Italy.

PURPOSE: To perform a systematic review on the research on the application of artificial intelligence (AI) to imaging published in Italy and identify its fields of application, methods and results. MATERIALS AND METHODS: A Pubmed search was conducted using terms Artificial Intelligence, Machine Learning, Deep learning, imaging, and Italy as affiliation, excluding reviews and papers outside time interval 2015-2020. In a second phase, participants of the working group AI4MP on Artificial Intelligence of the Italian Association of Physics in Medicine (AIFM) searched for papers on AI in imaging. RESULTS: The Pubmed search produced 794 results. 168 studies were selected, of which 122 were from Pubmed search and 46 from the working group. The most used imaging modality was MRI (44%) followed by CT(12%) ad radiography/mammography (11%). The most common clinical indication were neurological diseases (29%) and diagnosis of cancer (25%). Classification was the most common task for AI (57%) followed by segmentation (16%). 65% of studies used machine learning and 35% used deep learning. We observed a rapid increase of research in Italy on artificial intelligence in the last 5 years, peaking at 155% from 2018 to 2019. CONCLUSIONS: We are witnessing an unprecedented interest in AI applied to imaging in Italy, in a diversity of fields and imaging techniques. Further initiatives are needed to build common frameworks and databases, collaborations among different types of institutions, and guidelines for research on AI.

EPID-based 3D dosimetry for pre-treatment FFF VMAT stereotactic body radiotherapy plan verification using dosimetry CheckTM.

PURPOSE: The software Dosimetry Check (DC) reconstructs the 3D dose distribution on CT images data set by using EPID measured signal. This study aimed to evaluate DC for stereotactic body radiotherapy (SBRT) with unflattened photon beams (FFF) for dosimetric independent plan verification in pre-treatment modality. METHODS: DC v.4.1 was configured for Varian TrueBeam STx FFF beams equipped with EPID aS-1200. The DC FFF models were tested using arc open fields (from 1×1 cm2 to 15×15 cm2) and VMAT (Volumetric Modulated Arc Therapy) SBRT plans on phantom and patient CTs. DC dose distributions (DDC) were compared with that calculated by Eclipse with Acuros XB algorithm (DAXB) and one measured by Octavius 1000 SRS detector (DOCT). All differences were quantified in terms of the local 3D gamma passing rate (%GP), DVH and point dose differences. RESULTS: DC was configured for FFF VMAT using an appropriate correction procedure. %GP2%2mm (mean±standard deviation) of DOCT-DDC was 96.3±2.7% for open fields whereas it was 90.1±5.9% for plans on homogeneous phantom CT. However, average %GP3%3mm of DAXB-DDC was 95.0±4.1 for treatments on patient CT. The fraction of plans passing the %GP3%3mm DQA tolerance level [10% (50%) of maximum dose threshold] were 20/20 (14/20) and 18/20 (16/20) for OCT on phantom CT and DC on patient CT, respectively. CONCLUSIONS: DC characterization for FFF beams was performed. For stereotactic VMAT plan verifications DC showed good agreement with TPS whereas underlined discrepancies with Octavius in the high dose regions. A customized tolerance level is required for EPID-based VMAT FFF pre-treatment verification when DC system is applied.

Diagnostic performances of [18F]fluorocholine positron emission tomography in brain tumors.

BACKGROUND: Brain tumors characterization by molecular imaging that allows the depiction of brain lesions metabolic pattern is crucial. Our study aimed to: 1) to evaluate the diagnostic performances of [18F]fluoroethylcholine positron emission tomography/computed tomography ([18F]FECH PET/CT), and 2) correlate PET imaging derived parameters of [18F]FECH to survival in brain tumors. METHODS: From 2009 to 2012, we enrolled 30 patients who underwent [18F]FECH PET/CT. Final diagnosis was established by clinical and radiological follow-up. RESULTS: Final diagnosis was consistent with tumor disease in 27/30 cases. In 3/30 cases tumor disease was ruled out. [18F]FECH PET/CT resulted true positive and negative in 21/30 and 9/30 patients, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of [18F]FECH PET/CT were 78%, 100%, 100%, 33%, and 80%, respectively. Mean and maximum standardized uptake value (SUVmean and SUVmax) resulted statistically correlated to histology (P=0.0255 and P=0.0222, respectively). Using a SUVmax cut-off of 2.0 or 3.2, we distinguished between low- and high-grade gliomas with a good specificity (70% and 80%, respectively). SUVmax and histology resulted correlated to overall survival and disease related survival at multivariate analysis. CONCLUSIONS: Our results, worthy of further investigations, show high diagnostic performances of [18F]FECH PET/CT, and a correlation between PET imaging derived parameters and survival.

Contrast-enhanced spectral mammography in neoadjuvant chemotherapy monitoring: a comparison with breast magnetic resonance imaging.

BACKGROUND: Neoadjuvant-chemotherapy (NAC) is considered the standard treatment for locally advanced breast carcinomas. Accurate assessment of disease response is fundamental to increase the chances of successful breast-conserving surgery and to avoid local recurrence. The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) and contrast-enhanced-MRI (MRI) in the evaluation of tumor response to NAC. METHODS: This prospective study was approved by the institutional review board and written informed consent was obtained. Fifty-four consenting women with breast cancer and indication of NAC were consecutively enrolled between October 2012 and December 2014. Patients underwent both CESM and MRI before, during and after NAC. MRI was performed first, followed by CESM within 3 days. Response to therapy was evaluated for each patient, comparing the size of the residual lesion measured on CESM and MRI performed after NAC to the pathological response on surgical specimens (gold standard), independently of and blinded to the results of the other test. The agreement between measurements was evaluated using Lin's coefficient. The agreement between measurements using CESM and MRI was tested at each step of the study, before, during and after NAC. And last of all, the variation in the largest dimension of the tumor on CESM and MRI was assessed according to the parameters set in RECIST 1.1 criteria, focusing on pathological complete response (pCR). RESULTS: A total of 46 patients (85%) completed the study. CESM predicted pCR better than MRI (Lin's coefficient 0.81 and 0.59, respectively). Both methods tend to underestimate the real extent of residual tumor (mean 4.1mm in CESM, 7.5mm in MRI). The agreement between measurements using CESM and MRI was 0.96, 0.94 and 0.76 before, during and after NAC respectively. The distinction between responders and non-responders with CESM and MRI was identical for 45/46 patients. In the assessment of CR, sensitivity and specificity were 100% and 84%, respectively, for CESM, and 87% and 60% for MRI. CONCLUSION: CESM and MRI lesion size measurements were highly correlated. CESM seems at least as reliable as MRI in assessing the response to NAC, and may be an alternative if MRI is contraindicated or its availability is limited.

Knowledge-based treatment planning: An inter-technique and inter-system feasibility study for prostate cancer.

PURPOSE: Helical Tomotherapy (HT) plans were used to create two RapidPlan knowledge-based (KB) models to generate plans with different techniques and to guide the optimization in a different treatment planning system for prostate plans. Feasibility and performance of these models were evaluated. MATERIAL AND METHODS: two sets of 35 low risk (LR) and 30 intermediate risk (IR) prostate cancer cases who underwent HT treatments were selected to train RapidPlan models. The KB predicted constraints were used to perform new 20KB plans using RapidArc technique (KB-RA) (inter-technique validation), and to optimise 20 new HT (KB-HT) plans in the Tomoplan (inter-system validation). For each validation modality, KB plans were benchmarked with the manual plans created by an expert planner (EP). RESULTS: RapidPlan was successfully configured using HT plans. The KB-RA plans fulfilled the clinical dose-volume requirements in 100% and 92% of cases for planning target volumes (PTVs) and organs at risk (OARs), respectively. For KB-HT plans these percentages were found to be a bit lower: 90% for PTVs and 86% for OARs. In comparison to EP plans, the KB-RA plans produced higher bladder doses for both LR and IR, and higher rectum doses for LR. KB-HT and EP plans produced similar results. CONCLUSION: RapidPlan can be trained to create models by using plans of a different treatment modality. These models were suitable for generating clinically acceptable plans for inter-technique and inter-system applications. The use of KB models based on plans of consolidated technique could be useful with a new treatment modality.

Radiation protection procedures in 131I treatments for thyroid cancer in patients requiring hemodialysis.

BACKGROUND: Hemodialysis is essential for patients with renal failure, and iodine-131 ((131)I) administration is the standard of care in thyroid carcinoma treatment. Although the need for hemodialysis during (131)I treatment is very rare, it raises some concerns due to the involvement of personnel not exposed to radiation and to the contamination of devices used for other patients. In this paper, a radioprotection protocol to perform hemodialysis safely on patients during (131)I treatment has been presented. PATIENTS AND METHODS: The exposure of personnel who assisted 13 patients over the course of 10 years was monitored: external exposure was measured through electronic dosimeters, and internal contamination was checked by thyroid uptake and urine sample gamma spectrometry. Over this period, room layout was optimized to allow an improvement of radioprotection procedures.Two nurses were involved in patient assistance. RESULTS: After hemodialysis, measurements of internal contamination were below the minimum detectable activity and external exposure was in the range of 1-82 µSv in terms of H(p)(10). A reduction in personnel exposure was observed after hospitalization room renovation: H(p)(10) normalized to the activity administered to the patient was about halved. CONCLUSION: The data show that hemodialysis can be performed safely during I treatments when appropriate radioprotection actions are implemented.

Personnel exposure in labelling and administration of (177)Lu-DOTA-D-Phe1-Tyr3-octreotide.

OBJECTIVE: The introduction of peptide receptor radionuclide therapy, mainly performed with (90)Y and (177)Lu-labelled somatostatin analogues, has widened the therapeutic horizon of nuclear medicine.The handling of (177)Lu-labelled pharmaceuticals implies an increase of the personnel exposure and this aspect is evaluated in this paper, in comparison with personal exposure in (90)Y manipulation. MATERIALS AND METHODS: Personal dose measurements were performed during 26 (177)Lu-DOTATOC preparations by using a series of thin active layer LiF: Mg,Cu,P thermoluminescence dosimeters fixed at the operator's fingertips to evaluate the skin equivalent dose and by means of direct reading dosimeters positioned at the chest to evaluate the personal effective dose. Individual protection devices, such as shielded aprons and anti-X gloves, were also used. RESULTS: The 95th percentile of the skin equivalent dose distribution for (177)Lu operations by using 0.20-mm anti-X gloves was 0.080 mSv/GBq for the chemist and 0.011 mSv/GBq for the physician, whereas the 75th percentile was 0.058 mSv/GBq for the chemist and 0.006 mSv/GBq for the physician. The use of the 0.25 mm Pb-equivalent anti-X apron halved the personal equivalent dose measured over the apron by a direct reading dosimeter. Skin doses were compared with (90)Y-DOTATOC procedures: no relevant exposure reduction is observed for chemists, whereas doses are considerably lower during administration procedures performed by physicians. CONCLUSION: In this study, an evaluation of the skin equivalent doses during (177)Lu-DOTATOC labelling and administration is presented. These data can be useful to assess the risk for workers in centres that are starting to implement PRRT using (177)Lu. The use of appropriate protection devices and procedures allows the observance of International Commission for Radiological Protection dose limits for exposed workers.

Contrast detail phantom comparison on a commercially available unit. Digital breast tomosynthesis (DBT) versus full-field digital mammography (FFDM).

The performance of a commercial digital mammographic system working in 2D planar versus tomosynthesis mode was evaluated in terms of the image signal difference to noise ratio (SDNR). A contrast detail phantom was obtained embedding 1 cm Plexiglas, including 49 holes of different diameter and depth, between two layers containing a breast-simulating material. The phantom was exposed with the details plane perpendicular to the X-ray beam using the manufacturer's standard clinical breast acquisition parameters. SDNR in the digital breast tomosynthesis (DBT) images was higher than that of the full-field digital mammography (FFDM) for 38 out of 49 details in complex background conditions. These differences (p < 0.05) are statistically significant for 19 details out of 38. The relative SDNR results for DBT and FFDM images showed a dependence on the diameter of the details considered. This paper proposes an initial framework for a global image quality evaluation for commercial systems that can operate with different image acquisition modality using the same detector.

Semiautomatic technique for defining the internal gross tumor volume of lung tumors close to liver/spleen cupola by 4D-CT.

PURPOSE: It has been shown that in cases of lung tumors close to the liver cupola, the four dimensional (4D)-CT postprocessing maximum intensity projection (MIP) algorithm does not fully recover the radiotherapy internal gross tumor volume (IGTV). In this work, a semiautomatic technique was evaluated by which the residual IGTV that was not included into the IGTV by MIP algorithm was actually added. METHODS: A moving phantom and five selected patients were considered. The various IGTVs produced by the semiautomatic approach were compared to those generated by 4D-CT manual contouring. RESULTS: In all cases, the radiation oncologist qualitatively concurred with the semiautomatic IGTV. A quantitative difference in volume of 2.6% was found in the phantom study, whereas a mean difference of 0.1 +/- 4.6% was obtained in the patient studies. CONCLUSIONS: A semiautomatic technique to include the residual part of IGTV covered by liver/spleen cupola when using MIP algorithm was validated on phantom and on selected patients, revealing the possibility of defining the IGTV for patients with lesions located near liver/spleen cupola by performing only the contours on the MIP series.

4D-PET data sorting into different number of phases: a NEMA IQ phantom study.

This study aims at evaluating the dependence of 4D-PET data sorting on the number of phases in which the respiratory cycle can be divided. The issue is to find the best compromise to reduce the conflicting effects induced by increasing the number of phases: lesion motion on each set of images decreases, but on the other hand image noise increases. The IQ NEMA 2001 IEC body phantom was used to simulate the movement of neoplastic lesions in the thorax and abdomen, investigating the effect of target size (10-37 mm), lesion to background activity concentrations ratio (4-to-1 and 8-to-1), total acquisition time (3, 6, 12, 20 min) and number of phase partition (1, 2, 4, 6, 8, 10, 13). The phantom was moved in a cranial-caudal direction with an excursion of 25 mm and with a period of 4.0 s. Five parameters associated to lesion volume and activity concentration were considered to assess the capability of the 4D-PET technique to "freeze" the phantom motion. The results for all the parameters showed the capability of the 4D-PET acquisition technique to "freeze" the lesion motion. The division into 6 phases was found to be the best compromise between temporal resolution and image noise for the phase where the "lesions" move faster, whereas the partition into 4 phases could be used if a stable breathing phase is considered.

Radiation protection in 90Y-labelled DOTA-D-Phe1-Tyr3-octreotide preparations.

OBJECTIVE: Beta-emitting radionuclides are being increasingly used in targeted radionuclide therapy in nuclear medicine. In particular, the pure high-energy beta-emitter 90Y (Emax=2.27 MeV) has a physical half-life compatible with the pharmacokinetics of peptides. The use of this isotope implies an increase in the radiation dose received by the nuclear medicine staff. The aim of this study is thus the evaluation of the personal beta-dosimetry data related to therapeutic 90Y-labelled DOTA-D-Phe1-Tyr3-octreotide preparation and administration in a nuclear medicine department. METHODS: Personal dose measurements were carried out with a series of thin active layer ultrasensitive MCP-Ns (LiF: Mg, Cu, P) dosimeters fixed at the operator's fingertips and by means of some direct reading dosimeters; other individual protection devices, such as shielded aprons and anti-X gloves, were also used. RESULTS: The 95th percentile of the chemist's skin equivalent dose distribution was 1.759 mSv/GBq by using 0.10-mm anti-X gloves and 0.265 mSv/GBq by using 0.20-mm anti-X gloves. The 95th percentile of the physician's skin equivalent dose distribution was 1.198 mSv/GBq by using 0.10-mm anti-X gloves. The use of an anti-X apron during administration permits saving absorbed doses by a factor over 97% for both Hp(10) and Hp(0.07). CONCLUSION: Because of the physical properties of beta-emitters, an increased number of therapeutic sessions is to be expected. The dose values measured till now, resulting from a high radioprotection level modus operandi, have always respected the threshold limits reported by the European Directive EURATOM 96/29 05/13/1996 for exposed workers, even in addition to other clinical practices in the department.

Validation of (68)Ge/(68)Ga generator processing by chemical purification for routine clinical application of (68)Ga-DOTATOC.

INTRODUCTION: Imaging of somatostatin receptor expressing tumours has been greatly enhanced by the use of (68)Ga-DOTATOC and PET/CT. METHODS: In this work, a purification method for the (68)Ge/(68)Ga generator eluate and a method to produce (68)Ga-DOTATOC suitable for clinical use were evaluated. The generator eluate was purified and concentrated on a cation-exchange cartridge in HCl/acetone media. The efficacy of this procedure in eliminating metal impurities from the (68)Ga solution was investigated by ICP-MS. The radiotracer quality was evaluated by radio-TLC, GC and gamma-ray spectrometry. RESULTS: (68)Ga-DOTATOC preparations (n=33) were carried out with a mean synthesis yield of 59.3+/-2.8% (not corrected for decay) and a batch activity ranging from 555 to 296 MBq. The radiochemical and radionuclidic purity were >98% and 99.9999%, respectively. With this purification process, >95% of the Fe(III), Zn(II) and Mn(II) were eliminated from the solution. CONCLUSIONS: (68)Ga-DOTATOC produced with this method can be efficiently used in nuclear medicine departments for PET evaluations.