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Aims: The aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue‐derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischaemic heart failure with reduced ejection fraction (HFrEF). Methods and results: The study was a European multicentre, double‐blind, placebo‐controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were New York Heart Association (NYHA) class II–III, left ventricular ejection fraction (LVEF) <45%, and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) levels >300 pg/ml. CSCC_ASCs or placebo (isotonic saline) were injected directly into viable myocardium. The primary endpoint was change in left ventricular end‐systolic volume (LVESV) at 6‐month follow‐up measured by echocardiography. A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug‐related severe adverse events or difference in cardiac‐related adverse events during a 3‐year follow‐up period. There were no significant differences between groups during follow‐up in LVESV (0.3 ± 5.0 ml, p = 0.945), nor in secondary endpoints of left ventricular end‐diastolic volume (−2.0 ± 6.0 ml, p = 0.736) and LVEF (−1.6 ± 1.0%, p = 0.119). The NYHA class improved slightly within the first year in both groups without any difference between groups. There were no changes in 6‐min walk test, NT‐proBNP, C‐reactive protein or quality of life the first year in any groups. Conclusion: The SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC_ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the pre‐defined endpoints and induce restoration of cardiac function or clinical symptoms. [ABSTRACT FROM AUTHOR]

Aims: Patients suffering from chronic ischaemic heart failure with reduced left ventricular ejection fraction (HFrEF) have reduced quality‐of‐life, repetitive hospital admissions, and reduced life expectancy. Allogeneic cell therapy is currently investigated as a potential treatment option after initially encouraging results from clinical autologous and allogeneic trials in patients with HFrEF. We aimed to investigate the allogeneic Cardiology Stem Cell Centre Adipose tissue derived mesenchymal Stromal Cell product (CSCC_ASC) as an add‐on therapy in patients with chronic HFrEF. Methods and results: This is a Danish multi‐centre double‐blinded placebo‐controlled phase II study with direct intra‐myocardial injections of allogeneic CSCC_ASC. A total of 81 HFrEF patients were included and randomized 2:1 to CSCC_ASC or placebo injections. The inclusion criteria were reduced left ventricular ejection fraction (LVEF ≤ 45%), New York Heart Association (NYHA) class II‐III despite optimal anti‐congestive heart failure medication and no further revascularization options. Injections of 0.3 mL CSCC_ASC (total cell dose 100 × 106 ASCs) (n = 54) or isotonic saline (n = 27) were performed into the viable myocardium in the border zone of infarcted tissue using the NOGA Myostar® catheter (Biological Delivery System, Cordis, Johnson & Johnson, USA). The primary endpoint, left ventricular end systolic volume (LVESV), was evaluated at 6‐month follow‐up. The safety was measured during a 3‐years follow‐up period. Results: Mean age was 67.0 ± 9.0 years and 66.6 ± 8.1 years in the ASC and placebo groups, respectively. LVESV was unchanged from baseline to 6‐month follow‐up in the ASC (125.7 ± 68.8 mL and 126.3 ± 72.5 mL, P = 0.827) and placebo (134.6 ± 45.8 mL and 135.3 ± 49.6 mL, P = 0.855) group without any differences between the groups (0.0 mL (95% CI −9.1 to 9.0 mL, P = 0.992). Neither were there significant changes in left ventricular end diastolic volume or LVEF within the two groups or between groups −5.7 mL (95% CI −16.7 to 5.3 mL, P = 0.306) and −1.7% (95% CI −4.4. to 1.0, P = 0.212), respectively). NYHA classification and 6‐min walk test did not alter significantly in the two groups (P > 0.05). The quality‐of‐life, total symptom, and overall summary score improved significantly only in the ASC group but not between groups. There were 24 serious adverse events (SAEs) in the ASC group and 11 SAEs in the placebo group without any significant differences between the two groups at 1‐year follow‐up. Kaplan–Meier plot using log‐rank test of combined cardiac events showed an overall mean time to event of 30 ± 2 months in the ASC group and 29 ± 2 months in the placebo group without any differences between the groups during the 3 years follow‐up period (P = 0.994). Conclusions: Intramyocardial CSCC_ASC injections in patients with chronic HFrEF were safe but did not improve myocardial function or structure, nor clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: There is increased interest in in vivo dosimetry for 192Ir brachytherapy (BT) treatments using high atomic number (Z) inorganic scintillators. Their high light output enables construction of small detectors with negligible stem effect and simple readout electronics. Experimental determination of absorbed‐dose energy dependence of detectors relative to water is prevalent, but it can be prone to high detector positioning uncertainties and does not allow for decoupling of absorbed‐dose energy dependence from other factors affecting detector response. Purpose: To investigate which measurement conditions and detector properties could affect their absorbed‐dose energy dependence in BT in vivo dosimetry. Methods: We used a general‐purpose Monte Carlo (MC) code PENELOPE for the characterization of high‐Z inorganic scintillators with the focus on ZnSe (Z¯=32$\bar{Z}=32$) Z. Two other promising media CsI (Z¯=54$\bar{Z}=54$) and Al2O3 (Z¯=11$\bar{Z}=11$) were included for comparison in selected scenarios. We determined absorbed‐dose energy dependence of crystals relative to water under different scatter conditions (calibration phantom 12 × 12 × 30 cm3, characterization phantoms 20 × 20 × 20 cm3, 30 × 30 × 30 cm3, 40 × 40 × 40 cm3, and patient‐like elliptic phantom 40 × 30 × 25 cm3). To mimic irradiation conditions during prostate treatments, we evaluated whether the presence of pelvic bones and calcifications affect ZnSe response. ZnSe detector design influence was also investigated. Results: In contrast to low‐Z organic and medium‐Z inorganic scintillators, ZnSe and CsI media have substantially greater absorbed‐dose energy dependence relative to water. The response was phantom‐size dependent and changed by 11% between limited‐ and full‐scatter conditions for ZnSe, but not for Al2O3. For a given phantom size, a part of the absorbed‐dose energy dependence of ZnSe is caused not due to in‐phantom scatter but due to source anisotropy. Thus, the absorbed‐dose energy dependence of high‐Z scintillators is a function of not only the radial distance but also the polar angle. Pelvic bones did not affect ZnSe response, whereas large and intermediate size calcifications reduced it by 9% and 5%, respectively, when placed midway between the source and the detector. Conclusions: Unlike currently prevalent low‐ and medium‐Z scintillators, high‐Z crystals are sensitive to characterization and in vivo measurement conditions. However, good agreement between MC data for ZnSe in the present study and experimental data for ZnSe:O by Jørgensen et al. (2021) suggests that detector signal is proportional to the average absorbed dose to the detector cavity. This enables an easy correction for non‐TG43‐like scenarios (e.g., patient sizes and calcifications) through MC simulations. Such information should be provided to the clinic by the detector vendors. [ABSTRACT FROM AUTHOR]

• 3D dose reconstruction based on in vivo dosimetry was performed for high-dose-rate prostate BT. • Maximum relative deviation in the clinical target volume D 90% was 5%. • In one fraction a 18% increase in bladder D 2cm 3 was observed and a maximum deviation of 15% in urethra dose. • 3D dose reconstruction can aid in determining the dosimetric impact of geometric variations in BT. In vivo dosimetry (IVD) can be used for source tracking (ST), i.e., estimating source positions, during brachytherapy. The aim of this study was to exploit IVD-based ST to perform 3D dose reconstruction for high-dose-rate prostate brachytherapy and to evaluate the robustness of the treatments against observed geometric variations. Twenty-three fractions of high-dose-rate prostate brachytherapy were analysed. The treatment planning was based on MRI. Time-resolved IVD was performed using a fibre-coupled scintillator. ST was retrospectively performed using the IVD measurements. The ST identified 2D positional shifts of each treatment catheter and thereby inferred updated source positions. For each fraction, the dose was recalculated based on the source-tracked catheter positions and compared with the original plan dose using differences in dose volume histogram indices. Of 352 treatment catheters, 344 had shifts of less than 5 mm. Shifts between 5 and 10 mm were observed for 3 catheters, and shifts greater than 10 mm for 2 catheters. The ST failed for 3 catheters. The maximum relative difference in clinical target volume (prostate + 3 mm isotropic margin) D 90% was 5%. In one fraction, the bladder D 2cm 3 dose increased by 18% (1.4 Gy) due to a single source position being inside the bladder rather than nearby as planned. The max increase in urethra dose was 1.5 Gy (15%). IVD-based 3D dose reconstruction for high-dose-rate prostate brachytherapy is feasible. The dosimetric impact of the observed catheter shifts was limited. Dose reconstruction can therefore aid in determining the dosimetric impact of geometric variations and errors in brachytherapy. [ABSTRACT FROM AUTHOR]

Purpose: High‐dose rate (HDR) and pulsed‐dose rate (PDR) brachytherapy would benefit from an independent treatment verification system to monitor treatment delivery and to detect errors in real time. This paper characterizes and provides an uncertainty budget for a detector based on a fiber‐coupled high‐Z inorganic scintillator capable of performing time‐resolved in vivo dosimetry during HDR and PDR brachytherapy. Method: The detector was composed of a detector probe and an optical reader. The detector probe consisted of either a 0.5 × 0.4 × 0.4 mm3 (HDR) or a 1.0 × 0.4 × 0.4 mm3 (PDR) cuboid ZnSe:O crystal glued onto an optical‐fiber cable. The outer diameter of the detector probes was 1 mm, and fit inside standard brachytherapy catheters. The signal from the detector probe was read out at 20 Hz by a photodiode and a data acquisition device inside the optical reader. In order to construct an uncertainty budget for the detector, six characteristics were determined: (1) temperature dependence of the detector probe, (2) energy dependence as a function of the probe‐to‐source position in 2D (determined with 2 mm resolution using a robotic arm), (3) the signal‐to‐noise ratio (SNR), (4) short‐term stability over 8 h, and (5) long‐term stability of three optical readers and four probes used for in vivo monitoring in HDR and PDR treatments over 21 months (196 treatments and 189 detector calibrations, and (6) dose‐rate dependence. Results: The total uncertainty of the detector at a 20 mm probe‐to‐source distance was < 5.1% and < 5.8% for the HDR and PDR versions, respectively. Regarding the above characteristics, (1) the sensitivity of the detector decreased by an average of 1.4%/°C for detector probe temperatures varying from 22 to 37°C; (2) the energy dependence of the detector was nonlinear and depended on both probe‐to‐source distance and the angle between the probe and the brachytherapy source; (3) the median SNRs were 187 and 34 at a 20 mm probe‐to‐source distance for the HDR and PDR versions, respectively (corresponding median source activities of 4.8 and 0.56 Ci, respectively); (4) the detector response varied by 0.6% in 11 identical irradiations over 8 h; (5) the sensitivity of the four detector probes decreased systematically by 0–1.2%/100 Gy of dose delivered to the probes, and random fluctuations of 4.8% in the sensitivity were observed for the three probes used in PDR and 1.9% for the probe used in HDR; and (6) the detector response was linear with dose rate. Conclusion: ZnSe:O detectors can be used effectively for in vivo dosimetry and with high accuracy for HDR and PDR brachytherapy applications. [ABSTRACT FROM AUTHOR]

The potential of using computer vision to estimate the weight of pigs has been demonstrated in several studies. In this paper, we propose a Vision Analysis and Prediction (VAP) system, which consisted of two main parts: (1) computer vision – a vision algorithm was developed to segment the pigs and identify which pig area could be used to estimate the corresponding weight; (2) statistical analysis – a statistical method for predicting pig weight using the area was presented, including BLUP model and linear regression as well as a prediction function. The results showed that our approach has successfully estimated the weight of growing pigs (approximate ranges from 20 to 105 kg) with an accuracy of weight estimation of 97.76% on average for the predicted mean weight at pen level. The proposed system does not require modifications to the building and shows a strong potential to be utilized in pig weight estimation in slaughter pens. • A VAP system has great potential for pig weight estimation in slaughter pens. • The VAP includes two parts: a computer vision algorithm and a predicting model. • The VAP can accurately predict pig weights from 20 to 105 kg in a slaughter pen. • The VAP can help for optimal decision making to improve animal productivity. [ABSTRACT FROM AUTHOR]

Background: In vivo dosimetry (IVD) is rarely performed in brachytherapy (BT), allowing potential dose misadministration to go unnoticed. This study presents a clinical routine-calibration method of detectors for IVD in high (HDR) and pulsed dose rate (PDR) Ir-192 BT., Purpose: To evaluate the dosimetric precision and feasibility of an in-clinic calibration routine of detectors for IVD in afterloading BT., Methods: Calibrations were performed in a PMMA phantom with two needles inserted 20 mm apart. The source was loaded in one of the needles at 15 dwells for 10 s. The detector was placed in the other needle, and its signal was recorded. The mean signal at each dwell position was fitted to the expected dose rate with the calibration factor and the detector's longitudinal position being free parameters. The method was tested with an inorganic scintillation detector using one Ir-192 FlexiSource HDR and two Ir-192 GammaMedPlus PDR sources and followed by validation measurements in water., Results: The standard measurement uncertainty (k = 1) of the calibration factor in absolute terms (Gy/s) was 3.2/3.4% for the HDR/PDR source. The uncertainty was dominated by source strength uncertainty, and the precision of the method was <1%. The mean ± 1SD of the difference in measured and expected dose rate during validation was 1.5 ± 4.7% (HDR) and 0.0 ± 4.1% (PDR) with a positional uncertainty in the setup of 0.33/0.23 mm (HDR/PDR) (k = 1)., Conclusion: A precise and feasible in-clinic calibration method for IVD and source strength consistency tests in BT was presented., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: There is increased interest in in vivo dosimetry for 192 Ir brachytherapy (BT) treatments using high atomic number (Z) inorganic scintillators. Their high light output enables construction of small detectors with negligible stem effect and simple readout electronics. Experimental determination of absorbed-dose energy dependence of detectors relative to water is prevalent, but it can be prone to high detector positioning uncertainties and does not allow for decoupling of absorbed-dose energy dependence from other factors affecting detector response ., Purpose: To investigate which measurement conditions and detector properties could affect their absorbed-dose energy dependence in BT in vivo dosimetry., Methods: We used a general-purpose Monte Carlo (MC) code PENELOPE for the characterization of high-Z inorganic scintillators with the focus on ZnSe ( Z ¯ = 32 $\bar{Z}=32$ ) Z. Two other promising media CsI ( Z ¯ = 54 $\bar{Z}=54$ ) and Al 2 O 3 ( Z ¯ = 11 $\bar{Z}=11$ ) were included for comparison in selected scenarios. We determined absorbed-dose energy dependence of crystals relative to water under different scatter conditions (calibration phantom 12 × 12 × 30 cm 3 , characterization phantoms 20 × 20 × 20 cm 3 , 30 × 30 × 30 cm 3 , 40 × 40 × 40 cm 3 , and patient-like elliptic phantom 40 × 30 × 25 cm 3 ). To mimic irradiation conditions during prostate treatments, we evaluated whether the presence of pelvic bones and calcifications affect ZnSe response. ZnSe detector design influence was also investigated., Results: In contrast to low-Z organic and medium-Z inorganic scintillators, ZnSe and CsI media have substantially greater absorbed-dose energy dependence relative to water. The response was phantom-size dependent and changed by 11% between limited- and full-scatter conditions for ZnSe, but not for Al 2 O 3 . For a given phantom size, a part of the absorbed-dose energy dependence of ZnSe is caused not due to in-phantom scatter but due to source anisotropy. Thus, the absorbed-dose energy dependence of high-Z scintillators is a function of not only the radial distance but also the polar angle. Pelvic bones did not affect ZnSe response, whereas large and intermediate size calcifications reduced it by 9% and 5%, respectively, when placed midway between the source and the detector., Conclusions: Unlike currently prevalent low- and medium-Z scintillators, high-Z crystals are sensitive to characterization and in vivo measurement conditions. However, good agreement between MC data for ZnSe in the present study and experimental data for ZnSe:O by Jørgensen et al. (2021) suggests that detector signal is proportional to the average absorbed dose to the detector cavity. This enables an easy correction for non-TG43-like scenarios (e.g., patient sizes and calcifications) through MC simulations. Such information should be provided to the clinic by the detector vendors., (© 2022 American Association of Physicists in Medicine.)