Citations

Abstract Background Accurate low‐dose CT simulation is required to efficiently assess reconstruction and dose reduction techniques. Projection domain noise insertion requires proprietary information from manufacturers. Analytic image domain noise insertion methods are successful for linear reconstruction algorithms, however extending them to non‐linear algorithms remains challenging. Emerging, deep‐learning‐based image domain noise insertion methods have potential, but few approaches have explicitly incorporated physics information and a texture‐synthesis model to guide the generation of locally and globally correlated noise texture. Purpose We proposed a p hysics‐informed model‐based gener a tive neura l network for simulating scann e r‐ and algori t hm‐specific low‐dose C T e xams (PALETTE). It is expected to provide an alternative to projection domain noise insertion methods in the absence of manufacturers’ proprietary information and tools. Methods PALETTE integrated a physics‐based noise prior generation process, a Noise2Noisier sub‐network, and a noise texture synthesis sub‐network. The Noise2Noisier sub‐network provided a bias prior, which, combined with the noise prior, served as the inputs to noise texture synthesis sub‐network. Explicit regularizations in spatial and frequency domains were developed to account for noise spatial correlation and frequency characteristics. For proof‐of‐concept, PALETTE was trained and validated for a commercial iterative reconstruction algorithm (SAFIRE, Siemens Healthineers), using the paired routine and 25% dose images from CT phantoms (lateral size 30–40 cm; three training and four testing phantoms) and open‐access patient cases (10 training and 20 testing cases). In phantom validation, noise power spectra (NPS) were compared in water background and tissue‐mimicking inserts, using peak frequency and mean‐absolute‐error (MAE). In patient case evaluation, visual inspection and quantitative assessment were conducted on axial, coronal, and sagittal planes. Local and global noise texture were visually inspected in low‐dose CT images and the difference images between routine and low dose. Noise levels in liver and fat were measured. Local and global 2D Fourier magnitude spectra of the difference images and the corresponding radial mean profiles were used to assess similarity in noise frequency components within tissues and entire field‐of‐view, using spectral correlation mapper (SCM) and spectral angle mapper (SAM). Several baseline neural network models (e.g., GAN) were included in the evaluation. Statistical significance was tested using a t ‐test for related samples. Results PALETTE‐derived NPS showed accurate noise peak frequency (PALETTE/reference: water 1.40/1.40 lp/cm; inserts 1.7/1.7lp/cm) and small MAE (≤0.65 HU 2 cm 2 ). PALETTE created anatomy‐dependent noise texture, showing realistic local and global granularity and streaks. No statistically significant difference was observed in noise levels ( p > 0.05). Noise range was comparable across 3D image volume (PALETTE / reference):liver – [18.0, 53.4] / [19.3, 50.0] HU; fat – [11.7, 42.4] / [12.1, 41.3] HU. Percent absolute difference of local noise was small (mean ± standard deviation): liver 4.1%±3.1%, fat 4.6%±3.1%. Noise frequency distribution was close to the reference (mean per case): SCM ≥ 0.92, SAM ≤ 0.22. Additionally, PALETTE outperformed all baseline models in visual inspection and quantitative comparison. Conclusion PALETTE can provide high‐quality image domain noise insertion for simulating accurate low‐dose CT images created with a commercial non‐linear reconstruction algorithm.

Abstract The common practice in meta‐analysis and clinical practice guidelines is to derive the absolute treatment effect (also called risk difference, RD) from a combination of a pooled relative risk (RR) that resulted from a meta‐analysis, and a user‐provided baseline risk (BR). However, this method does not address the uncertainty in BR. We developed a web‐based R Shiny tool to perform simple microsimulation and incorporate uncertainty in BR into the precision of RD. We empirically evaluated this approach by estimating the impact of incorporating this uncertainty when BR is derived from the control group rates in 3,128 meta‐analyses curated from the Cochrane Library (26,964 individual studies). When BR was derived from the largest study in each meta‐analysis, the median width of the CI of BR was 11.6% (interquartile range (IQR), 6.30%–18.5%). Incorporating this uncertainty in BR led to expansion of the RD CI by a median of 8 per 1,000 persons (IQR 2–24). This expansion increased in a linear fashion with BR imprecision and was more prominent in meta‐analyses with low BR. This study provides a web‐based tool to perform simple microsimulation and incorporate uncertainty in BR into the CI of RD.

Abstract The phosphorylation of histone H2A.X into γH2A.X is a crucial early event in the DNA damage response, marking DNA damage sites and initiating repair processes. While ATM kinase is traditionally recognized as the primary mediator of H2A.X phosphorylation, our study identifies serine/threonine kinase 39 (STK39) as a novel enhancer of this critical signaling pathway. We demonstrate that after DNA damage, STK39 undergoes phosphorylation by the ATM kinase, facilitating its interaction with the Mre11-Rad50-Nbs1 complex and subsequent recruitment to chromatin. This recruitment enables STK39 to further phosphorylate H2A.X, thus amplifying γH2A.X production and promoting homologous recombination repair. Notably, we observe a significant upregulation of STK39 in pancreatic adenocarcinoma (PAAD) tissues, correlating with heightened resistance to PARPi therapy. Furthermore, we demonstrate the synergistic efficacy of combining STK39 inhibition with PARP inhibitors in suppressing and reversing PAAD growth. This study not only provides new insights into the molecular dynamics of H2A.X phosphorylation but also highlights the therapeutic potential of targeting STK39 to enhance PARPi sensitivity in PAAD (created with BioRender).

Background SynthesiZed Improved Resolution and Concurrent nOise reductioN (ZIRCON) is a multi-kernel synthesis method that creates a single series of thin-slice computed tomography (CT) images displaying low noise and high spatial resolution, increasing reader efficiency and minimizing partial volume averaging. Purpose To compare the diagnostic performance of a single set of ZIRCON images to two routine clinical image series using conventional CT head and bone reconstruction kernels for diagnosing intracranial findings and fractures in patients with trauma or suspected acute neurologic deficit. Material and Methods In total, 50 patients underwent clinically indicated head CT in the ER (15 normal, 35 abnormal cases). A non-reader neuroradiologist established the reference standard. Three neuroradiologists reviewed two routine clinical series (head and bone kernels) and a single ZIRCON series, detecting intracranial findings or fractures and rating confidence (0–100). Sensitivity, specificity, and jackknife free-response receiver operating characteristic (JAFROC) figure of merit (FOM) were compared (limit of non-inferiority: −0.10). Results ZIRCON and conventional images demonstrated comparable performance for fractures (sensitivity: 51.5% vs. 54.5%; specificity: 40.2% vs. 34.2%) and intracranial findings (sensitivity: 88.2% vs. 91.4%; specificity: 77.2% vs. 73.7%).The estimated difference of JAFROC FOM demonstrated ZIRCON non-inferiority for acute pathologies overall (0.003 [95% CI=−0.051–0.057]) and fractures (0.048 [95% CI=−0.050–0.145]) but not for intracranial findings alone (−0.024 [95% CI=−0.100–0.052]). Conclusion Thin-slice, low noise, and high spatial resolution images can be created to display intracranial findings and fractures replacing multiple images series in head CT with similar performance. Future studies in more patients and further algorithmic development are warranted.

AbstractBackgroundThe first commercially available photon‐counting‐detector CT (PCD‐CT) has been introduced for clinical use. However, its spectral performance on single‐ and dual‐contrast imaging tasks has not been comprehensively assessed.PurposeTo evaluate the spectral imaging performance of a clinical PCD‐CT system for single‐contrast material [iodine (I) or gadolinium (Gd)] and dual‐contrast materials (I and Gd) in comparison with a dual‐source dual‐energy CT (DS‐DECT).MethodsIodine (5, 10, and 15 mg/mL) and gadolinium (3.3, 6.6, and 9.9 mg/mL) samples, and their mixtures (I/Gd: 5/3.3 and 10/6.6 mg/mL) were prepared and placed in two torso‐shaped water phantoms (lateral dimensions: 30 and 40 cm). These phantoms were scanned on a PCD‐CT (NAEOTOM Alpha, Siemens) at 90, 120, and 140 kV. The same phantoms were scanned on a DS‐DECT (SOMATOM Force, Siemens) with 70/Sn150, 80/Sn150, 90/Sn150, and 100/Sn150 kV. The radiation dose levels were matched [volume CT dose index (CTDIvol): 10 mGy for the 30 cm phantom and 20 mGy for the 40 cm phantom] across all tube voltage settings and between scanners. Two‐material decomposition (I/water or Gd/water) was performed on iodine or gadolinium samples, and three‐material decomposition (I/Gd/water) on both individual samples and mixtures. On each decomposed image, mean mass concentration (± standard deviation) was measured in circular region‐of‐interests placed on the contrast samples. Root‐mean‐square‐error (RMSE) values of iodine and gadolinium concentrations were reported based on the measurements across all contrast samples and repeated on 10 consecutive slices.ResultsFor all material decomposition tasks on the DS‐DECT, the kV pairs with greater spectral separation (70/Sn150 kV and 80/Sn150 kV) yielded lower RMSE values than other DS‐DECT and PCD‐CT alternatives. Specifically, for the optimal 70/Sn150 kV, RMSE values were 1.2 ± 0.1 mg/mL (I) for I/water material decomposition, 1.0 ± 0.1 mg/mL (Gd) for Gd/water material decomposition, and 4.5 ± 0.2 mg/mL (I) and 3.7 ± 0.2 mg/mL (Gd), respectively, for I/Gd/water material decomposition. On the PCD‐CT, the optimal tube voltages were 120 or 140 kV for I/water decomposition with RMSE values of 2.0 ± 0.1 mg/mL (I). For Gd/water decomposition on PCD‐CT, the optimal tube voltage was 140 kV with gadolinium RMSE values of 1.5 ± 0.1 mg/mL (Gd), with the 90 kV setting on PCD‐CT generating higher RMSE values for gadolinium concentration compared to all DS‐DECT and PCD‐CT alternatives. For three material decomposition, both imaging modalities demonstrated substantially higher RMSE values for iodine and gadolinium, with 90 kV being the optimal tube potential for Gd/I quantitation on PCD‐CT [5.4 ± 0.3 mg/mL (I) and 3.9 ± 0.2 mg/mL (Gd)], and DS‐DECT at 100/Sn150 kV having larger RMSE values for both materials compared to the alternatives for either modality.ConclusionOptimal tube voltage for material decomposition on the clinical PCD‐CT is task‐dependent but inferior to DS‐DECT using 70/Sn150 kV or 80/Sn150 kV in two‐material decomposition for single‐contrast imaging (iodine/water or gadolinium/water). Three material decomposition (iodine/gadolinium/water) in dual‐contrast imaging yields substantially higher RMSE for both imaging platforms.

AbstractPurposeA dual‐source CT system can be operated in a high‐pitch helical mode to provide a temporal resolution of 66 ms, which reduces motion artifacts in CT pulmonary angiography (CTPA). It can also be operated in a multi‐energy (ME) mode to provide iodine maps, beneficial in the evaluation of pulmonary embolism (PE). No energy‐integrating detector (EID) CT can perform simultaneous ME and high‐pitch acquisition. This phantom study aimed to evaluate the ability of a photon‐counting‐detector (PCD) CT to perform simultaneous high‐pitch and ME imaging for CTPA.MethodsA motion phantom was used to mimic the respiratory motion. Two tubes filled with iodine with intravascular thrombus mimicked by injecting glue within the tubes were placed along with 5, 10, and 15 mg/mL iodine samples, on a motion phantom at 20 and 30 revolutions per minute. Separate high‐pitch and ME EID‐CT scans and a single high‐pitch ME PCD scan were acquired and virtual monoenergetic images and iodine maps reconstructed. Percent thrombus occlusion was measured and compared between static and moving images.ResultsWhen there was motion, EID‐CT ME suffered from significant motion artifacts. The measured iodine concentrations with PCD‐CT in high‐pitch ME were more stable when there was a motion, with a lower standard deviation than EID‐CT in ME mode. The estimated percent thrombus occlusion dropped significantly with applied motion on EID‐CT, while PCD‐CT high‐pitch ME mode showed good agreement between measurements on static or moving images.ConclusionPCD‐CT with combined ME and high‐pitch mode facilitates simultaneous accurate iodine quantification and assessment of intravascular occlusion.

AbstractBackgroundInserting noise into existing patient projection data to simulate lower‐radiation‐dose exams has been frequently used in traditional energy‐integrating‐detector (EID)‐CT to optimize radiation dose in clinical protocols and to generate paired images for training deep‐learning‐based reconstruction and noise reduction methods. Recent introduction of photon counting detector CT (PCD‐CT) also requires such a method to accomplish these tasks. However, clinical PCD‐CT scanners often restrict the users access to the raw count data, exporting only the preprocessed, log‐normalized sinogram. Therefore, it remains a challenge to employ projection domain noise insertion algorithms on PCD‐CT.PurposeTo develop and validate a projection domain noise insertion algorithm for PCD‐CT that does not require access to the raw count data.Materials and MethodsA projection‐domain noise model developed originally for EID‐CT was adapted for PCD‐CT. This model requires, as input, a map of the incident number of photons at each detector pixel when no object is in the beam. To obtain the map of incident number of photons, air scans were acquired on a PCD‐CT scanner, then the noise equivalent photon number (NEPN) was calculated from the variance in the log normalized projection data of each scan. Additional air scans were acquired at various mA settings to investigate the impact of pulse pileup on the linearity of NEPN measurement. To validate the noise insertion algorithm, Noise Power Spectra (NPS) were generated from a 30 cm water tank scan and used to compare the noise texture and noise level of measured and simulated half dose and quarter dose images. An anthropomorphic thorax phantom was scanned with automatic exposure control, and noise levels at different slice locations were compared between simulated and measured half dose and quarter dose images. Spectral correlation between energy thresholds T1 and T2, and energy bins, B1 and B2, was compared between simulated and measured data across a wide range of tube current. Additionally, noise insertion was performed on a clinical patient case for qualitative assessment.ResultsThe NPS generated from simulated low dose water tank images showed similar shape and amplitude to that generated from the measured low dose images, differing by a maximum of 5.0% for half dose (HD) T1 images, 6.3% for HD T2 images, 4.1% for quarter dose (QD) T1 images, and 6.1% for QD T2 images. Noise versus slice measurements of the lung phantom showed comparable results between measured and simulated low dose images, with root mean square percent errors of 5.9%, 5.4%, 5.0%, and 4.6% for QD T1, HD T1, QD T2, and HD T2, respectively. NEPN measurements in air were linear up until 112 mA, after which pulse pileup effects significantly distort the air scan NEPN profile. Spectral correlation between T1 and T2 in simulation agreed well with that in the measured data in typical dose ranges.ConclusionsA projection‐domain noise insertion algorithm was developed and validated for PCD‐CT to synthesize low‐dose images from existing scans. It can be used for optimizing scanning protocols and generating paired images for training deep‐learning‐based methods.

Simultaneous dual-contrast imaging of iodine and bismuth has shown promise in prior phantom and animal studies utilizing spectral CT. However, it is noted that in previous studies, Pepto-Bismol has frequently been employed as the source of bismuth, exceeding the recommended levels for human subjects. This investigation sought to assess the feasibility of visually differentiating and precisely quantifying low-concentration bismuth using clinical dual-source photon-counting CT (PCCT) in a scenario involving both iodinated and bismuth-based contrast materials. Four bismuth samples (0.6, 1.3, 2.5, and 5.1 mg/mL) were prepared using Pepto-Bismol, alongside three iodine rods (1, 2, and 5 mg/mL), inserted into multi-energy CT phantoms with three different sizes, and scanned on a PCCT system at three tube potentials (120, 140, and Sn140 kV). A generic image-based three-material decomposition method generated iodine and bismuth maps, with mean mass concentrations and noise levels measured. The root-mean-square errors for iodine and bismuth determined the optimal tube potential. The tube potential of 140 kV demonstrated optimal quantification performance when both iodine and bismuth were considered. Distinct differentiation of iodine rods with all three concentrations and bismuth samples with mass concentrations ≥ 1.3 mg/mL was observed across all phantom sizes at the optimal kV setting.