•We propose a deep learning approach to generate synthetic CT from low tesla MR images.•Synthetic CT was created for pelvic and abdominal lesions enrolling 120 cases.•The images generated show an ...accuracy sufficient to safely calculate IMRT plans.•This study represents the first experience of CT generation from low tesla MR images.•This is the first experience of CT generation in abdomen independently by B intensity.
Artificial intelligence (AI) can play a significant role in Magnetic Resonance guided Radiotherapy (MRgRT), especially to speed up the online adaptive workflow. The aim of this study is to set up a Deep Learning (DL) approach able to generate synthetic computed tomography (sCT) images from low field MR images in pelvis and abdomen.
A conditional Generative Adversarial Network (cGAN) was used for sCT generation: a total of 120 patients treated on pelvic and abdominal sites were enrolled and divided in training (80) and test sets (40).
Intensity modulated radiotherapy (IMRT) treatment plans were calculated on sCT and original CT and then compared in terms of gamma analysis and differences in Dose Volume Histogram (DVH).
The two one-sided test for paired samples (TOST-P) was used to evaluate the equivalence among different DVH parameters calculated for target and organs at risks (OAR) on CT and sCT images.
Using a CPU architecture, the mean time required by the neural network to generate a synthetic CT was 175 ± 43 seconds (s) for pelvic cases and 110 ± 40 s for abdominal ones.
Mean gamma passing rates for the three tolerance criteria analysed (1%/1 mm, 2%/2 mm and 3%/3 mm) were respectively 90.8 ± 4.5%, 98.7 ± 1.1% and 99.8 ± 0.2% for abdominal cases; 89.3 ± 4.8%, 99.0 ± 0.7% and 99.9 ± 0.2% for pelvic ones, while equivalence within 1% was observed among the DVH indicators.
This study demonstrated that sCT generation using a DL approach is feasible for low field MR images in pelvis and abdomen, allowing a reliable calculation of IMRT plans in MRgRT.
Life has evolved on Earth for about 4 billion years in the presence of the natural background of ionizing radiation. It is extremely likely that it contributed, and still contributes, to shaping ...present form of life. Today the natural background radiation is extremely small (few mSv/y), however it may be significant enough for living organisms to respond to it, perhaps keeping memory of this exposure. A better understanding of this response is relevant not only for improving our knowledge on life evolution, but also for assessing the robustness of the present radiation protection system at low doses, such as those typically encountered in everyday life. Given the large uncertainties in epidemiological data below 100 mSv, quantitative evaluation of these health risk is currently obtained with the aid of radiobiological models. These predict a health detriment, caused by radiation-induced genetic mutations, linearly related to the dose. However a number of studies challenged this paradigm by demonstrating the occurrence of non-linear responses at low doses, and of radioinduced epigenetic effects, i.e., heritable changes in genes expression not related to changes in DNA sequence. This review is focused on the role that epigenetic mechanisms, besides the genetic ones, can have in the responses to low dose and protracted exposures, particularly to natural background radiation. Many lines of evidence show that epigenetic modifications are involved in non-linear responses relevant to low doses, such as non-targeted effects and adaptive response, and that genetic and epigenetic effects share, in part, a common origin: the reactive oxygen species generated by ionizing radiation. Cell response to low doses of ionizing radiation appears more complex than that assumed for radiation protection purposes and that it is not always detrimental. Experiments conducted in underground laboratories with very low background radiation have even suggested positive effects of this background. Studying the changes occurring in various living organisms at reduced radiation background, besides giving information on the life evolution, have opened a new avenue to answer whether low doses are detrimental or beneficial, and to understand the relevance of radiobiological results to radiation protection.
Purpose
Hepatocellular carcinoma (HCC) in early stages benefits from local ablative treatments such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). In this context, ...radiotherapy (RT) has shown promising results but has not been thoroughly evaluated. Magnetic resonance-guided RT (MRgRT) may represent a paradigm shifting improvement in stereotactic body radiotherapy (SBRT) for liver tumors.
Methods
We retrospectively evaluated HCC patients treated on a hybrid low-tesla MRgRT unit. A total biologically effective dose (BED) > 100 Gy was delivered in 5 consecutive fractions, respecting the appropriate organs-at-risk constraints. Hybrid MR scans were used for treatment planning and cine MR was used for delivery gating. Patients were followed up for toxicity and treatment–response assessment.
Results
Ten patients were enrolled, with a total of 12 lesions. All the lesions were irradiated with no interruptions. Six patients had already performed previous local therapies. Median follow-up after SBRT was 6.5 months (1–25). Two cases of acute toxicity were reported (G ≤ 2 according to CTCAE v4.0). At the time of the analysis, 90% of the population presented local control. Child–Pugh before and after treatment remained unchanged in all but one patient.
Conclusion
MRgRT is a feasible and safe option showing favorable toxicity profile for HCC treatment.
Abstract
Objective
Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality ...and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and < 80%), with or without previous percutaneous coronary intervention (> 6 months) but no HF.
Methods
This was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by (18)F2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by
13
N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT 03313752).
Results
16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 μmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 μmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; p
int
= 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; p
int
= 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054).
Conclusions
SGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction.
Trial registration
EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752
γ-ray spectrometry is a well-known technique in environmental radioactivity measurements where easily handled systems are needed. Scintillators coupled to a photomultiplier tube (PMT), are typically ...favoured over solid-state detectors as mobile spectrometers. Replacing PMT with position sensitive devices represents an innovative solution that provides the evaluation of the interaction point of the incident radiation. The knowledge of spectrometry as a function of the depth of interaction (DoI) assures a better understanding of the spectrum and a more reliable identification of the source. In this paper, the efficiency of a simple DoI estimator has been studied using a CRY018 monolithic crystal coupled to a multi-anode photomultiplier tube. The DoI estimator has been evaluated studying charge distributions and the dependency of spectrometric properties on the DoI has been qualitatively analyzed. The estimator has shown to be highly sensitive to the DoI, enabling a better understanding of the internal interaction processes of light and an efficient rejection of the background component on the spectra. The novelty of this work lies in the application of the DoI selection in spectrometry made available by the use of MAPMT. The proposed method is practical since it does not require complicated hardware solutions or complex computational procedures.
Purpose
Stereotactic body radiotherapy is increasingly used for the treatment of oligometastatic disease. Magnetic resonance-guided stereotactic radiotherapy (MRgSBRT) offers the opportunity to ...perform dose escalation protocols while reducing the unnecessary irradiation of the surrounding organs at risk. The aim of this retrospective, monoinstitutional study is to evaluate the feasibility and clinical benefit (CB) of MRgSBRT in the setting of oligometastatic patients.
Materials and methods
Data from oligometastatic patients treated with MRgSBRT were collected. The primary objectives were to define the 12-month progression-free survival (PFS) and local progression-free survival (LPFS) and 24-month overall survival (OS) rate. The objective response rate (ORR) included complete response (CR) and partial response (PR). CB was defined as the achievement of ORR and stable disease (SD). Toxicities were also assessed according to the CTCAE version 5.0 scale.
Results
From February 2017 to March 2021, 59 consecutive patients with a total of 80 lesions were treated by MRgSBRT on a 0.35 T hybrid unit. CR and PR as well as SD were observed in 30 (37.5%), 7 (8.75%), and 17 (21.25%) lesions, respectively. Furthermore, CB was evaluated at a rate of 67.5% with an ORR of 46.25%.
Median follow-up time was 14 months (range: 3–46 months). The 12-month LPFS and PFS rates were 70% and 23%, while 24-month OS rate was 93%. No acute toxicity was reported, whereas late pulmonary fibrosis
G
1 was observed in 9 patients (15.25%).
Conclusion
MRgSBRT was well tolerated by patients with reported low toxicity levels and a satisfying CB.
Molecular Radiation Therapy (MRT) is a valid therapeutic option for a wide range of malignancies, such as neuroendocrine tumors and liver cancers. In its practice, it is generally acknowledged that ...there is a need to evaluate the influence of different factors affecting the accuracy of dose estimates and to define the actions necessary to maintain treatment uncertainties at acceptable levels. The present study addresses the problem of uncertainty propagation in 90Y-PET quantification. We assessed the quantitative accuracy in reference conditions of three PET scanners (namely, Siemens Biograph mCT, Siemens Biograph mCT flow, and GE Discovery DST) available at three different Italian Nuclear Medicine centers. Specific aspects of uncertainty within the quantification chain have been addressed, including the uncertainty in the calibration procedure. A framework based on the Guide to the Expression of Uncertainty in Measurement (GUM) approach is proposed for modeling the uncertainty in the quantification processes, and ultimately, an estimation of the uncertainty achievable in clinical conditions is reported.
Abstract
Background
The THUNDER-2 phase II single institutional trial investigates the benefits of MRI-guided radiotherapy (MRIgRT) in treating locally advanced rectal cancer (LARC). This study ...focuses on evaluating the impact of escalating radiation therapy dose in non-responder patients using the Early Tumour Regression Index (ERI) for predicting complete response (CR). The trial’s primary endpoint is to increase the CR rate in non-responders by 10% and assess the feasibility of the delta radiomics-based MRIgRT predictive model. This interim analysis assesses the feasibility and safety of the proposed MRIgRT dose escalation strategy in terms of acute toxicity (gastrointestinal, genitourinary and haematological) and treatment adherence.
Methods
Stage cT2-3, N0-2, or cT4 patients with anal sphincter involvement, N0-2a, M0, but without high-risk features were enrolled. MRIgRT treatment consisted of a standard dose of 55 Gy to the Gross Tumor Volume (GTV) and mesorectum, and 45 Gy to the mesorectum and drainage nodes in 25 fractions with concomitant chemotherapy. 0.35 T MRI was used for simulation imaging and daily alignment. ERI was calculated at the 10th fraction. Non-responders with an ERI above 13.1 received intensified dose escalation from the 11th fraction, resulting in a total dose of 60.1 Gy. Acute toxicity was assessed using the CTCAE v.5 scale.
Results
From March 2021 to November 2022, 33 out of the total number of 63 patients to be enrolled (52.4%) were included, with one withdrawal unrelated to treatment. Sixteen patients (50%) underwent dose escalation. Treatment was well tolerated, with only one patient (3.1%) in the standard treatment group experiencing acute Grade 3 diarrhea, proctitis, and cystitis. No significant differences in toxicity were observed between the two groups (p = 0.5463).
Conclusions
MRIgRT treatment with dose escalation up to 60.1 Gy is well tolerated in LARC patients predicted as non-responders by ERI, confirming the feasibility and safety of this approach. The THUNDER-2 trial’s primary and secondary endpoints will be fully analyzed when all planned patients will be enrolled.
To evaluate the performance of eleven Knowledge-Based (KB) models for planning optimization (RapidPlantm (RP), Varian) of Volumetric Modulated Arc Therapy (VMAT) applied to whole breast comprehensive ...of nodal stations, internal mammary and/or supraclavicular regions.
Six RP models have been generated and trained based on 120 VMAT plans data set with different criteria. Two extra-structures were delineated: a PTV for the optimization and a ring structure. Five more models, twins of the previous models, have been created without the need of these structures.
All models were successfully validated on an independent cohort of 40 patients, 30 from the same institute that provided the training patients and 10 from an additional institute, with the resulting plans being of equal or better quality compared with the clinical plans. The internal validation shows that the models reduce the heart maximum dose of about 2 Gy, the mean dose of about 1 Gy and the V20Gy of 1.5 Gy on average. Model R and L together with model B without optimization structures ensured the best outcomes in the 20% of the values compared to other models. The external validation observed an average improvement of at least 16% for the V5Gy of lungs in RP plans. The mean heart dose and for the V20Gy for lung IPSI were almost halved. The models reduce the maximum dose for the spinal canal of more than 2 Gy on average.
All KB models allow a homogeneous plan quality and some dosimetric gains, as we saw in both internal and external validation. Sub-KB models, developed by splitting right and left breast cases or including only whole breast with locoregional lymph nodes, have shown good performances, comparable but slightly worse than the general model. Finally, models generated without the optimization structures, performed better than the original ones.
This study aims to assess the quality of a new diffusion-weighted imaging (DWI) sequence implemented on an MR-Linac MRIdian system, evaluating and optimizing the acquisition parameters to explore the ...possibility of clinically implementing a DWI acquisition protocol in a 0.35-T MR-Linac.
All the performed analyses have been carried out on two types of phantoms: a homogeneous 24-cm diameter polymethylmethacrylate (PMMA) sphere (SP) and a homemade phantom (HMP) constating in a PMMA cylinder filled with distilled water with empty sockets into which five cylindrical vials filled with five different concentrations of methylcellulose water solutions have been inserted. SP was used to evaluate the dependence of diffusion gradient inhomogeneity artifacts on gantry position. Four diffusion sequences with
-values of 500 s/mm
and 3 averages have been acquired: three with diffusion gradients in the three main directions (phase direction, read direction, slice direction) and one with the diffusion gradients switched off. The dependence of diffusion image uniformity and SNR on the number of averages in the MR sequences was also investigated to determine the optimal number of averages. Finally, the ADC values of HMP have been computed and then compared between images acquired in the scanners at 0.35 and 1.5 T.
In order to acquire high-quality artifact-free DWI images, the "slice" gradient direction has been identified to be the optimal one and 0° to be the best gradient angle. Both the SNR ratio and the uniformity increase with the number of averages. A threshold value of 80 for SNR and 85% for uniformity was adopted to choose the best number of averages. By making a compromise between time and quality and limiting the number of
-values, it is possible to reduce the acquisition time to 78 s. The Passing-Bablok test showed that the two methods, with 0.35 and 1.5 T scanners, led to similar results.
The quality of the DWI has been accurately evaluated in relation to different sequence parameters, and optimal parameters have been identified to select a clinical protocol for the acquisition of ADC maps sustainable in the workflow of a hybrid radiotherapy system with a 0.35-T MRI scanner.
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