OBJECTIVE: Clinical radiographic imaging is seated upon the principle of differential keV photon transmission through an object. At clinical x-ray energies the scattering of photons causes signal noise and is utilized solely for transmission measurements. However, scatter - particularly Compton scatter, is characterizable. In this work we hypothesized that modern radiation sources and detectors paired with deep learning techniques can use scattered photon information constructively to resolve superimposed attenuators in planar x-ray imaging.
METHODS: We simulated a monoenergetic x-ray imaging system consisting of a pencil beam x-ray source directed at an imaging target positioned in front of a high spatial- and energy-resolution detector array. The setup maximizes information capture of transmitted photons by measuring off-axis scatter location and energy. The signal was analyzed by a convolutional neural network, and a description of scattering material along the axis of the beam was derived. The system was virtually designed/tested using Monte Carlo processing of simple phantoms consisting of 10 pseudo-randomly stacked air/bone/water materials, and the network was trained by solving a classification problem.
RESULTS: From our simulations we were able to resolve traversed material depth information to a high degree, within our simple imaging task. The average accuracy of the material identification along the beam was 0.91±0.01, with slightly higher accuracy towards the entrance/exit peripheral surfaces of the object. The average sensitivity and specificity was 0.91 and 0.95, respectively.
CONCLUSIONS: Our work provides proof of principle that deep learning techniques can be used to analyze scattered photon patterns which can constructively contribute to the information content in radiography, here used to infer depth information in a traditional 2D planar setup. This principle, and our results, demonstrate that the information in Compton scattered photons may provide a basis for further development. The work was limited by simple testing scenarios and without yet integrating complexities or optimizations. The ability to scale performance to the clinic remains unexplored and requires further study.

The latest X-ray photon-counting computed tomography (PCCT) for extremity allows multi-energy high-resolution (HR) imaging for tissue characterization and material decomposition. However, both radiation dose and imaging speed need improvement for contrast-enhanced and other studies. Despite the success of deep learning methods for 2D few-view reconstruction, applying them to HR volumetric reconstruction of extremity scans for clinical diagnosis has been limited due to GPU memory constraints, training data scarcity, and domain gap issues. In this paper, we propose a deep learning-based approach for PCCT image reconstruction at halved dose and doubled speed in a New Zealand clinical trial. Particularly, we present a patch-based volumetric refinement network to alleviate the GPU memory limitation, train network with synthetic data, and use model-based iterative refinement to bridge the gap between synthetic and real-world data. The simulation and phantom experiments demonstrate consistently improved results under different acquisition conditions on both in- and off-domain structures using a fixed network. The image quality of 8 patients from the clinical trial are evaluated by three radiologists in comparison with the standard image reconstruction with a full-view dataset. It is shown that our proposed approach is essentially identical to or better than the clinical benchmark in terms of diagnostic image quality scores. Our approach has a great potential to improve the safety and efficiency of PCCT without compromising image quality.

This study aims to investigate the maximum achievable dose reduction for applying a new deep learning-based reconstruction algorithm, namely the artificial intelligence iterative reconstruction (AIIR), in computed tomography (CT) for hepatic lesion detection. A total of 40 patients with 98 clinically confirmed hepatic lesions were retrospectively included. The mean volume CT dose index was 13.66 ± 1.73 mGy in routine-dose portal venous CT examinations, where the images were originally obtained with hybrid iterative reconstruction (HIR). Low-dose simulations were performed in projection domain for 40%-, 20%-, and 10%-dose levels, followed by reconstruction using both HIR and AIIR. Two radiologists were asked to detect hepatic lesion on each set of low-dose image in separate sessions. Qualitative metrics including lesion conspicuity, diagnostic confidence, and overall image quality were evaluated using a 5-point scale. The contrast-to-noise ratio (CNR) for lesion was also calculated for quantitative assessment. The lesion CNR on AIIR at reduced doses were significantly higher than that on routine-dose HIR (all p < 0.05). Lower qualitative image quality was observed as the radiation dose reduced, while there were no significant differences between 40%-dose AIIR and routine-dose HIR images. The lesion detection rate was 100%, 98% (96/98), and 73.5% (72/98) on 40%-, 20%-, and 10%-dose AIIR, respectively, whereas it was 98% (96/98), 73.5% (72/98), and 40% (39/98) on the corresponding low-dose HIR, respectively. AIIR outperformed HIR in simulated low-dose CT examinations of the liver. The use of AIIR allows up to 60% dose reduction for lesion detection while maintaining comparable image quality to routine-dose HIR.

OBJECTIVE: To investigate safety and effectiveness of disease activity-guided dose optimisation of TNF-inhibitors in rheumatoid arthritis over 10 years.
METHODS: Observational long-term extension of a randomised study of participants who completed the 3-year extension of the DRESS-study. After the randomised phase (month 0-18), disease activity-guided dose optimisation was allowed for all. Main outcomes were mean time-weighted DAS28-CRP; biological and targeted synthetic anti-rheumatic drug (b/tsDMARD) use per year as proportion of daily defined dose; proportion of patients reaching discontinuation; durability, effectiveness of subsequent dose reduction attempts; and radiographic progression between 3 and 10 years using the Sharp-van der Heijde score.
RESULTS: 170 patients were included of whom 127 completed 10-year follow-up. The mean disease activity remained low (DAS28-CRP 2.13, 95% confidence interval 2.10-2.16), whilst the b/tsDMARD dose reduced from 97% at baseline (95%CI 96% to 99%, n = 170)% to56% at year 10 (49% to 63%, n = 127). 119 of 161 participants (74%) with an optimisation attempt reached discontinuation, with a median duration of 7 months (interquartile range 3-33 months), and 25 participants never had to restart their b/tsDMARD (21%, 14% to 29%). The mean dose reduction after dose optimisation was 48% (n = 159) for the first optimisation attempt and 33% for subsequent attempt (n = 86). 48% (41/86) of participants had radiographic progression exceeding the smallest detectable change (5.7 units), and progression was associated with disease activity, not b/tsDMARD use.
CONCLUSIONS: Long-term disease activity-guided dose optimisation of TNF-inhibitors in rheumatoid arthritis, including discontinuation and multiple tapering attempts, remains safe and effective.

BACKGROUND: Low-dose emicizumab can potentially offer a cost-effective treatment option in persons with hemophilia A, especially in developing countries.
OBJECTIVE: To compare the efficacy and safety of low-dose emicizumab with those on low-dose factor (F)VIII prophylaxis via chart review.
METHODS: After ethics approval, chart data of 2 groups of patients were reviewed: group 1 (low-dose emicizumab, n = 10; 3 mg/kg monthly without a loading dose) and group 2 (low-dose FVIII prophylaxis, n = 10; 10-20 IU/kg of FVIII concentrates twice a week). Outcomes were target joints, annual bleeding rate, annual joint bleeding rate, Hemophilia Joint Health Score, nonactivated thromboelastometry-rotational thromboelastometry clotting time, plasma emicizumab levels, and direct costs of treatment.
RESULTS: All outcome measures were significantly better in the low-dose emicizumab group than in the low-dose FVIII prophylaxis group. For nonactivated thromboelastometry-rotational thromboelastometry, median values after 6 months in the low-dose emicizumab group were comparable with values seen in patients with mild hemophilia, while the values in the low-dose FVIII prophylaxis group were similar to those of patients with moderate hemophilia. The direct cost of low-dose emicizumab was found to be approximately US $6000 and that for low-dose recombinant FVIII prophylaxis used in our study was US $6282 (the cost may range from US $3432 to $7920 depending on the type of factor) when compared to approximately US $15 000 for standard-dose emicizumab.
CONCLUSIONS: Low-dose emicizumab offers a cost-effective treatment option and can improve access in developing countries. These findings need to be confirmed in a larger and better-controlled study.

To explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis.
A retrospective cohort study.
Tertiary-care academic medical center.
A total of 3173 infertile women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020.
A total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed.
The primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate.
We created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; P < 0.01). The duration of Gn, the number of follicles with diameter more than 16 mm on trigger day, the estradiol (E2) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; P < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups.
The combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol.

BACKGROUND: Imaging of the cervical spine in general radiography is most frequently performed using an anti-scatter grid. The purpose of this study was to investigate the effects of a gridless setting on image quality and radiation dose during digital radiography of the anteroposterior (AP) and lateral (LAT) cervical spine.
METHODS: A phantom study was performed with a variety of tube voltages (63-75 kV) with and without an anti-scatter grid. The tube current time product (mAs) and dose area product (DAP) were recorded and used to calculate effective dose (ED) and individual organ dose using PCXMC 2.0 software, as well as entrance surface dose (ESD) and objective image quality: signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective visual image quality grading characteristics (VGC) was performed by five qualified radiographers.
RESULTS: In a gridless setting, the AP and LAT positions showed significantly lower DAP (1.6 μGym2; 61.3 % and 1.6 μGym2; 51.2%), ESD (27.6 μGy; 57.3% and 77.2 μGy; 47.2%) and ED (4.2 μSv; 61.3% and 2.3 μSv; 48.9%). In a gridless setting in the AP position, there is a slight significant deterioration in image quality. In the lateral projection, on the other hand, the image quality without the use of grid was only significantly reduced in three of six criteria and there was no difference in the objective image quality between the two settings examined.
CONCLUSIONS: The results of this study show that gridless setting significantly decreases radiation dose and image quality, but the quality in the lateral projection is still acceptable for diagnostic purpose.
CONCLUSIONS: The protocol without the use of the anti-scatter grid in cervical spine radiography leads to a reduction in the radiation dose in both projections, but the image quality in the AP is significantly reduced for all criteria examined, with a slight deterioration in image quality in the lateral projection.

The aim of this phantom study was to assess the detectability and volumetric accuracy of pulmonary nodules on photon-counting detector CT (PCD-CT) at different low-dose levels compared to conventional energy-integrating detector CT (EID-CT). In-house fabricated artificial nodules of different shapes (spherical, lobulated, spiculated), sizes (2.5-10 mm and 5-1222 mm3), and densities (-330 HU and 100 HU) were randomly inserted into an anthropomorphic thorax phantom. The phantom was scanned with a low-dose chest protocol with PCD-CT and EID-CT, in which the dose with PCD-CT was lowered from 100% to 10% with respect to the EID-CT reference dose. Two blinded observers independently assessed the CT examinations of the nodules. A third observer measured the nodule volumes using commercial software. The influence of the scanner type, dose, observer, physical nodule volume, shape, and density on the detectability and volumetric accuracy was assessed by a multivariable regression analysis. In 120 CT examinations, 642 nodules were present. Observer 1 and 2 detected 367 (57%) and 289 nodules (45%), respectively. With PCD-CT and EID-CT, the nodule detectability was similar. The physical nodule volumes were underestimated by 20% (range 8-52%) with PCD-CT and 24% (range 9-52%) with EID-CT. With PCD-CT, no significant decrease in the detectability and volumetric accuracy was found at dose reductions down to 10% of the reference dose (p > 0.05). The detectability and volumetric accuracy were significantly influenced by the observer, nodule volume, and a spiculated nodule shape (p < 0.05), but not by dose, CT scanner type, and nodule density (p > 0.05). Low-dose PCD-CT demonstrates potential to detect and assess the volumes of pulmonary nodules, even with a radiation dose reduction of up to 90%.

Measuring left ventricular ejection fraction (LVEF) is important for detecting heart failure, e.g., in treatment with potentially cardiotoxic chemotherapy. MRI is considered the reference standard for LVEF, but availability may be limited and claustrophobia or metal implants still present challenges. CT has been shown to be accurate and would be advantageous, as LVEF could be measured in conjunction with routine chest-abdomen-pelvis oncology CT. However, the use of CT is not recommended due to the excessive radiation dose. This study aimed to explore the potential for dose reduction using simulation. Using an anthropomorphic heart phantom scanned at 13 dose levels, a noise simulation algorithm was developed to introduce controlled Poisson noise. Filtered backprojection parameters were iteratively tested to minimise differences in myocardium-to-ventricle contrast/noise ratio, as well as structural similarity index (SSIM) differences between real and simulated images at all dose levels. Fifty-one clinical CT coronary angiographies, scanned with full dose through end-systolic and -diastolic phases, were located retrospectively. Using the developed algorithm, noise was introduced corresponding to 25, 10, 5 and 2% of the original dose level. LVEF was measured using clinical software (Syngo.via VB50) with papillary muscles in and excluded from the LV volume. At each dose level, LVEF was compared to the 100% dose level, using Bland-Altman analysis. The effective dose was calculated from DLP using a conversion factor of 0.026 mSv/mGycm.
In the clinical images, mean CTDIvol and DLP were 47.1 mGy and 771.9 mGycm, respectively (effective dose 20.0 mSv). Measurements with papillary muscles excluded did not exhibit statistically significant LVEF bias to full-dose images at 25, 10 and 5% simulated dose. At 2% dose, a significant bias of 4.4% was found. With papillary muscles included, small but significant biases were found at all simulated dose levels.
Provided that measurements are performed with papillary muscles excluded from the LV volume, the dose can be reduced by a factor of 20 without significantly affecting LVEF measurements. This corresponds to an effective dose of 1 mSv. CT can potentially be used for LVEF measurement with minimal excessive radiation.

Histogram indices (HIs) and texture features (TFs) are considered to play an important role in future oncologic PET-imaging and it is unknown how these indices are affected by changes of tracer doses. A randomized undersampling of PET list mode data enables a simulation of tracer dose reduction. We performed a phantom study to compare HIs/TFs of simulated and measured tracer dose reductions and evaluated changes of HIs/TFs in the liver of patients with PETs from simulated reduced tracer doses. Overall, 42 HIs/TFs were evaluated in a NEMA phantom at measured and simulated doses (stepwise reduction of [18 F] from 100% to 25% of the measured dose). [18 F]-FDG-PET datasets of 15 patients were simulated from 3.0 down to 0.5 MBq/kgBW in intervals of 0.25 MBq/kgBW. HIs/TFs were calculated from two VOIs placed in physiological tissue of the right and left liver lobe and linear correlations and coefficients of variation analysis were performed.
All 42 TFs did not differ significantly in measured and simulated doses (p > 0.05). Also, 40 TFs showed the same behaviour over dose reduction regarding differences in the same group (measured or simulated), and for 26 TFs a linear behaviour over dose reduction for measured and simulated doses could be validated. Out of these, 13 TFs could be identified, which showed a linear change in TF value in both the NEMA phantom and patient data and therefore should maintain the same informative value when transferred in a dose reduction setting. Out of this Homogeneity 2, Entropy and Zone size non-uniformity are of special interest because they have been described as preferentially considerable for tumour heterogeneity characterization.
We could show that there was no significant difference of measured and simulated HIs/TFs in the phantom study and most TFs reveal a linear behaviour over dose reduction, when tested in homogeneous tissue. This indicates that texture analysis in PET might be robust to dose modulations.