Prospective evaluation of low-dose multiphase hepatic computed tomography for detecting and characterizing hepatocellular carcinoma in patients with chronic liver disease.

BACKGROUND: Knowing the lowest acceptable radiation dose of multiphase hepatic CT may allow us to reduce the radiation dose for detecting HCC. PURPOSE: To prospectively assess the image quality and diagnostic performance of low-dose and ultra-low-dose multiphase hepatic computed tomography using a dual-source CT scanner. METHODS: Three reconstructed different dose scan images (standard-dose, low-dose, and ultra-low-dose) of hepatic multiphase CT were obtained from 67 patients with a dual-source CT scanner. The image quality and the diagnostic performance of the three radiation dose CT scans of the hepatic focal lesion (≥ 0.5 cm) were analyzed by two independent readers using the Liver Imaging Reporting and Data System. RESULTS: Qualitative image quality and signal-to-noise ratio were significantly different among the radiation doses (p < 0.001). In total, 154 lesions comprising 32 hepatocellular carcinomas (HCC) and 122 non-HCC were included. The sensitivities of SDCT, LDCT, and ULDCT were 90.6%(29/32), 81.3%(26/32), and 56.2%(18/32), respectively. The accuracies of SDCT, LDCT, and ULDCT were 98.1%(151/154), 96.1%(148/154), and 89.6%(138/154), respectively. On per-lesion analysis, SDCT and LDCT did not show significantly different sensitivity and accuracy in diagnosing HCC (p = 0.250 and 0.250). CONCLUSIONS: The diagnostic performance of dynamic hepatic LDCT with 33% reduced radiation dose in comparison to SDCT would be acceptable even though its image quality was qualitatively and quantitatively inferior. However, few HCCs could be overlooked. Therefore, with caution, radiation dose reduction by one-third could be implemented for follow-up CT scans for patients suspected of having HCC with caution and further studies are needed in the future.

INR Response to Low-Dose Vitamin K in Warfarin Patients.

BACKGROUND: Literature suggests that 2 mg of vitamin K intravenously (IV) provides a similar effect as 10 mg to reverse warfarin. Doses <5 mg haven't been studied in depth. OBJECTIVE: The objective was to determine the international normalized ratio (INR) reduction effect of ultra low-dose (ULD) IV vitamin K. METHODS: This retrospective, observational cohort study compared IV vitamin K doses of 0.25-0.5 mg (ULD) versus 1-2 mg (standard low dose [SLD]). The primary outcome assessed ΔINR at 36 hours; secondary outcomes assessed ΔINR at 12 hours and 30-day venous thromboembolism (VTE) and mortality rates. RESULTS: Of 88 patients identified (median baseline INR [IQR], 5.1 [3.1, 7.3] vs 4.5 [2.8, 8.2], ULD vs SLD, respectively), 59 had an INR at 12 hours. The ULD had fewer 12-hour INR values <2, with no statistical difference in the ΔINR at 12 hours between the ULD and SLD cohorts (median ΔINR, 2.2 [1.1, 3.4] vs 2.2 [1.1, 6.3]; P = 0.54; median INR, 2.3 vs 1.8). A total of 41 patients had both a 12- and 36-hour INR. No significant difference in the ΔINR between the 12- and 36-hour values occurred (median ΔINR, 0.52 [0.2, 0.91] vs ΔINR, 0.46 [0.18, 0.55]; P = 0.61), suggesting no rebound or excessive reversal and no difference in 30-day rates of VTE (P > 0.99) or death (P = 0.38). CONCLUSION AND RELEVANCE: ULD IV vitamin K reversed INR similarly to doses of 1-2 mg without rebound. A ULD strategy may be considered in patients requiring more cautious reversal.

Direct energy spectrum measurement of X-ray from a clinical linac.

A realistic X-ray energy spectrum is essential for accurate dose calculation using the Monte Carlo (MC) algorithm. An energy spectrum for dose calculation in the radiation treatment planning system is modeled using the MC algorithm and adjusted to obtain acceptable agreement with the measured percent depth dose (PDD) and off-axis ratio. The simulated energy spectrum may not consistently reproduce a realistic energy spectrum. Therefore, direct measurement of the X-ray energy spectrum from a linac is necessary to obtain a realistic spectrum. Previous studies have measured low photon fluence directly, but the measurement was performed with a nonclinical linac with a thick target and a long target-to-detector distance. In this study, an X-ray energy spectrum from a clinical linac was directly measured using a NaI(Tl) scintillator at an ultralow dose rate achieved by adjusting the gun grid voltage. The measured energy spectrum was unfolded by the Gold algorithm and compared with a simulated spectrum using statistical tests. Furthermore, the PDD was calculated using an unfolded energy spectrum and a simulated energy spectrum was compared with the measured PDD to evaluate the validity of the unfolded energy spectrum. Consequently, there was no significant difference between the unfolded and simulated energy spectra by nonparametric, Wilcoxon's rank-sum, chi-square, and two-sample Kolmogorov-Smirnov tests with a significance level of 0.05. However, the PDD calculated from the unfolded energy spectrum better agreed with the measured compared to the calculated PDD results from the simulated energy spectrum. The adjustment of the incident electron parameters using MC simulation is sensitive and takes time. Therefore, it is desirable to obtain the energy spectrum by direct measurement. Thus, a method to obtain the realistic energy spectrum by direct measurement was proposed in this study.

Diagnosis of foreign body aspiration with ultralow-dose CT using a tin filter: a comparison study.

PURPOSE: Suspected airway foreign body aspiration (FBA) is a common event in paediatric emergency units, especially in children under 3 years of age. It can be a life-threatening event if not diagnosed promptly and accurately. The purpose of this study is to compare the diagnostic performance of an ultralow-dose CT (DLP of around 1 mGycm) with that of conventional radiographic methods (fluoroscopy and chest radiography of the airways) in the diagnosis of FBA children's airways. METHODS: Retrospective cross-sectional study. Data from 136 children were collected: 75 were examined with conventional radiographic methods and 61 with ultralow-dose CT. Effective doses were compared using independent t tests. The results of bronchoscopy, if performed, were used in creating contingency 2 × 2 tables to assess the diagnostic performance between modalities. An extra triple reading of all images was applied for this purpose. RESULTS: The effective doses used in the ultralow-dose CT examinations were lower compared with those in conventional methods (p < 0.001). The median dose for CT was 0.04 mSv compared with 0.1 mSv for conventional methods. Sensitivity and specificity were higher for ultralow-dose CT than those for conventional methods (100% and 98% versus 33% and 96%) as were the positive and negative predicted values (90% and 100% versus 60% and 91%). CONCLUSION: Ultralow-dose CT can be used as the imaging of choice in the diagnosis of airway FBA in emergency settings, thereby avoiding concerns about radiation doses and negative bronchoscopy outcomes.

Pediatric chest CT at chest radiograph doses: when is the ultralow-dose chest CT clinically appropriate?

PURPOSE: Computed tomography (CT) use in emergency departments represents a significant contribution to pediatric patients' exposure to ionizing radiation. Here, we evaluate whether ultralow-dose chest CT can be diagnostically adequate for other diagnoses and whether model-based iterative reconstruction (MBIR) can improve diagnostic adequacy compared to adaptive statistical iterative reconstruction (ASIR) at ultralow doses. METHODS: Twenty children underwent chest CTs: 10 standard-dose reconstructed with ASIR and 10 ultralow-dose reconstructed with ASIR and MBIR. Four radiologists assessed images for their adequacy to exclude five hypothetical diagnoses: foreign body, fracture, lung metastasis, pulmonary infection, and interstitial lung disease. Additionally, pairwise comparison for subjective image quality was used to compare ultralow-dose chest CT with ASIR and MBIR. Radiation dose and objective image noise measures were obtained. RESULTS: For exclusion of an airway foreign body, the adequacy of ultralow-dose CT was comparable to standard-dose (p = 0.6). For the remaining diagnoses, ultralow-dose CT was inferior to standard-dose (p = 0.03-<0.001). MBIR partially recovered the adequacy of ultralow-dose CT to exclude pulmonary infection (p = 0.017), but was suboptimal for the other diagnoses. Image noise was significantly lower with MBIR compared to ASIR in ultralow-dose CT (p < 0.001), although subjective preference showed only a slight advantage of MBIR (58 versus 42%). CONCLUSIONS: Ultralow-dose chest CT may be adequate for airway assessment, but suboptimal for the evaluation parenchymal lung disease. Although MBIR improves objective and subjective image quality, it does not completely restore the diagnostic adequacy of ultralow-dose CT when compared to standard-dose CT.

Feasibility of optimized ultralow-dose pulsed fluoroscopy for upper gastrointestinal tract examinations: a phantom study with clinical correlation.

PURPOSE: To establish an optimized ultralow-dose digital pulsed fluoroscopy (FP) protocol for upper gastrointestinal tract examinations and to investigate the radiation dose and image quality. MATERIALS AND METHODS: An Alderson-Rando-Phantom with 60 thermoluminescent dosimeters was used for dose measurements to systematically evaluate the dose-area product (DAP) and organ doses of the optimized FP protocol with the following acquisition parameters: 86.7 kV; 77 mA; 0.9 mm3, automatic image noise and contrast adaption. Subjective image quality, depiction of contrast agent and image noise (5-point Likert scale; 5 = excellent) were assessed in 41 patients, who underwent contrast-enhanced FP with the aforementioned optimized protocol by two radiologists in consensus. A conventional digital radiograph (DR) acquisition protocol served as the reference standard for radiation dose and image quality analyses. RESULTS: Phantom measurements revealed a general dose reduction of approximately 96% per image for the FP protocol as compared to the DR standard. DAP could be reduced by 97%. Significant dose reductions were also found for organ doses, both in the direct and scattered radiation beam with negligible orbital (FP 5.6 × 10-3 vs. DR 0.11; p = 0.02) and gonadal dose exposure (female FP 2.4 × 10-3 vs. DR 0.05; male FP 8 × 10-4 vs. DR 0.03; p ≤ 0.0004). FP provided diagnostic image quality in all patients, although reading scores were significantly lower for all evaluated parameters as compared to the DR standard (p < 0.05). CONCLUSION: Ultralow-dose FP is feasible for clinical routine allowing a significant reduction of direct and scattered dose exposure while providing sufficient diagnostic image quality for reliable diagnosis.

Performance of ultralow-dose CT with iterative reconstruction in lung cancer screening: limiting radiation exposure to the equivalent of conventional chest X-ray imaging.

OBJECTIVE: To investigate the detection rate of pulmonary nodules in ultralow-dose CT acquisitions. MATERIALS AND METHODS: In this lung phantom study, 232 nodules (115 solid, 117 ground-glass) of different sizes were randomly distributed in a lung phantom in 60 different arrangements. Every arrangement was acquired once with standard radiation dose (100 kVp, 100 references mAs) and once with ultralow radiation dose (80 kVp, 6 mAs). Iterative reconstruction was used with optimized kernels: I30 for ultralow-dose, I70 for standard dose and I50 for CAD. Six radiologists examined the axial 1-mm stack for solid and ground-glass nodules. During a second and third step, three radiologists used maximum intensity projection (MIPs), finally checking with computer-assisted detection (CAD), while the others first used CAD, finally checking with the MIPs. RESULTS: The detection rate was 95.5 % with standard dose (DLP 126 mGy*cm) and 93.3 % with ultralow-dose (DLP: 9 mGy*cm). The additional use of either MIP reconstructions or CAD software could compensate for this difference. A combination of both MIP reconstructions and CAD software resulted in a maximum detection rate of 97.5 % with ultralow-dose. CONCLUSION: Lung cancer screening with ultralow-dose CT using the same radiation dose as a conventional chest X-ray is feasible. KEY POINTS: • 93.3 % of all lung nodules were detected with ultralow-dose CT. • A sensitivity of 97.5 % is possible with additional image post-processing. • The radiation dose is comparable to a standard radiography in two planes. • Lung cancer screening with ultralow-dose CT is feasible.

Comparison of combined hormonal vaginal ring with ultralow-dose combined oral contraceptive pills in the management of heavy menstrual bleeding: A pilot study.

The aim of this study was to compare combined hormonal vaginal ring with ultralow-dose combined oral contraceptive (COC) pills in management of heavy menstrual bleeding (HMB). Fifty patients were randomised into Group I: vaginal ring (n = 25) and group II: COC pills (n = 25). Menstrual blood loss (MBL) was assessed at baseline, 1, 3 and 6 months (while on treatment) and at 9 months (3 months after stopping therapy). There was significant reduction in baseline pictorial blood loss assessment chart (PBAC) score from 440 ± 188 (Mean ± SD) to 178 ± 95, 139 ± 117, 112 ± 84 and 120 ± 108 in group I and from 452 ± 206 to 204 ± 152, 179 ± 125, 176 ± 164 and 202 ± 167 in group II at 1, 3, 6 and 9 months, respectively (p = 0.001). Reduction in MBL was 72% and 62% at 6 months and up to 71% and 55% at 9 months in group I and group II, respectively (p = 0.001). Reduction in MBL with ring was greater at higher baseline PBAC score but lesser in patients with fibroid > 2 cm. Combined vaginal hormonal treatment for HMB is as effective as oral hormonal therapy, with minor and transient side effects and persistence of response after cessation of therapy.

Ultralow-dose CT of the craniofacial bone for navigated surgery using adaptive statistical iterative reconstruction and model-based iterative reconstruction: 2D and 3D image quality.

OBJECTIVE. The purpose of this article is to evaluate 2D and 3D image quality of high-resolution ultralow-dose CT images of the craniofacial bone for navigated surgery using adaptive statistical iterative reconstruction (ASIR) and model-based iterative reconstruction (MBIR) in comparison with standard filtered backprojection (FBP). MATERIALS AND METHODS. A formalin-fixed human cadaver head was scanned using a clinical reference protocol at a CT dose index volume of 30.48 mGy and a series of five ultralow-dose protocols at 3.48, 2.19, 0.82, 0.44, and 0.22 mGy using FBP and ASIR at 50% (ASIR-50), ASIR at 100% (ASIR-100), and MBIR. Blinded 2D axial and 3D volume-rendered images were compared with each other by three readers using top-down scoring. Scores were analyzed per protocol or dose and reconstruction. All images were compared with the FBP reference at 30.48 mGy. A nonparametric Mann-Whitney U test was used. Statistical significance was set at p < 0.05. RESULTS. For 2D images, the FBP reference at 30.48 mGy did not statistically significantly differ from ASIR-100 at 3.48 mGy, ASIR-100 at 2.19 mGy, and MBIR at 0.82 mGy. MBIR at 2.19 and 3.48 mGy scored statistically significantly better than the FBP reference (p = 0.032 and 0.001, respectively). For 3D images, the FBP reference at 30.48 mGy did not statistically significantly differ from all reconstructions at 3.48 mGy; FBP and ASIR-100 at 2.19 mGy; FBP, ASIR-100, and MBIR at 0.82 mGy; MBIR at 0.44 mGy; and MBIR at 0.22 mGy. CONCLUSION. MBIR (2D and 3D) and ASIR-100 (2D) may significantly improve subjective image quality of ultralow-dose images and may allow more than 90% dose reductions.

A CTL-Inspired Killing System Using Ultralow-Dose Chemical-Drugs to Induce a Pyroptosis-Mediated Antitumor Immune Function.

A Cytotoxic T lymphocyte-inspired system capable of using ultralow-dose chemical drugs to manipulate cell death is needed to investigate the antitumor immunotherapy. Recent studies reveal pyroptosis promotes antitumor immune function. However, high-dose chemotherapy leads to cytokine release syndrome by pyroptosis. Therefore, pyroptosis-inducing ultralow-dose chemotherapy is potential in preclinical and clinical research, but its efficacy, safety, and the antitumor immune responses are not clear. Here, a near-infrared light controllable killing system (BIK system) is established by which ultralow-dose doxorubicin can be spatiotemporally transported to tumor cells and mediate efficient pyroptosis. This BIK system reduces total drug consumption to less than one-thirtieth the common dose in vitro. Moreover, this BIK system exhibited good tumor targeting and tumor penetration. This system is applied for pyroptosis-induced antitumor therapies, which shows less than ≈25 µg kg-1 doxorubicin is sufficient for tumor regression with negligible injuries to major organs. The antitumor immune function are proven to correlate with the impressive efficacy of pyroptosis-inducing ultralow-dose chemotherapy. This study provides new insights into the design of nanoassisted systems for activating the antitumor immunity by microstimulation; the application of the BIK system suggests that ultralow-dose chemotherapy is sufficient for inducing a robust pyroptosis-mediated antitumor immunity.

Can clinicians identify community-acquired pneumonia on ultralow-dose CT? A diagnostic accuracy study.

BACKGROUND: Without increasing radiation exposure, ultralow-dose computed tomography (CT) of the chest provides improved diagnostic accuracy of radiological pneumonia diagnosis compared to a chest radiograph. Yet, radiologist resources to rapidly report the chest CTs are limited. This study aimed to assess the diagnostic accuracy of emergency clinicians' assessments of chest ultralow-dose CTs for community-acquired pneumonia using a radiologist's assessments as reference standard. METHODS: This was a cross-sectional diagnostic accuracy study. Ten emergency department clinicians (five junior clinicians, five consultants) assessed chest ultralow-dose CTs from acutely hospitalised patients suspected of having community-acquired pneumonia. Before assessments, the clinicians attended a focused training course on assessing ultralow-dose CTs for pneumonia. The reference standard was the assessment by an experienced emergency department radiologist. Primary outcome was the presence or absence of pulmonary opacities consistent with community-acquired pneumonia. Sensitivity, specificity, and predictive values were calculated using generalised estimating equations. RESULTS: All clinicians assessed 128 ultralow-dose CTs. The prevalence of findings consistent with community-acquired pneumonia was 56%. Seventy-eight percent of the clinicians' CT assessments matched the reference assessment. Diagnostic accuracy estimates were: sensitivity = 83% (95%CI: 77-88), specificity = 70% (95%CI: 59-81), positive predictive value = 80% (95%CI: 74-84), negative predictive value = 78% (95%CI: 73-82). CONCLUSION: This study found that clinicians could assess chest ultralow-dose CTs for community-acquired pneumonia with high diagnostic accuracy. A higher level of clinical experience was not associated with better diagnostic accuracy.

Eliminating Non-Corner-Sharing Octahedral for Efficient and Stable Perovskite Solar Cells.

The metal halide (BX6)4- octahedron, where B represents a metal cation and X represents a halide anion, is regarded as the fundamental structural and functional unit of metal halide perovskites. However, the influence of the way the (BX6)4- octahedra connect to each other has on the structural stability and optoelectronic properties of metal halide perovskite is still unclear. Here, the octahedral connectivity, including corner-, edge-, and face-sharing, of various CsxFA1-xPbI3 (0 ≤ x ≤ 0.3) perovskite films is tuned and reliably characterized through compositional and additive engineering, and with ultralow-dose transmission electron microscopy. It is found that the overall solar cell device performance, the charge carrier lifetime, the open-circuit voltage, and the current density-voltage hysteresis are all improved when the films consist of corner-sharing octahedra, and non-corner sharing phases are suppressed, even in films with the same chemical composition. Additionally, it is found that the structural, optoelectronic, and device performance stabilities are similarly enhanced when non-corner-sharing connectivities are suppressed. This approach, combining macroscopic device tests and microscopic material characterization, provides a powerful tool enabling a thorough understanding of the impact of octahedral connectivity on device performance, and opens a new parameter space for designing high-performance photovoltaic metal halide perovskite devices.

Lung-Optimized Deep-Learning-Based Reconstruction for Ultralow-Dose CT.

RATIONALE AND OBJECTIVES: To evaluate the image properties of lung-specialized deep-learning-based reconstruction (DLR) and its applicability in ultralow-dose CT (ULDCT) relative to hybrid- (HIR) and model-based iterative-reconstructions (MBIR). MATERIALS AND METHODS: An anthropomorphic chest phantom was scanned on a 320-row scanner at 50-mA (low-dose-CT 1 [LDCT-1]), 25-mA (LDCT-2), and 10-mA (ULDCT). LDCT were reconstructed with HIR; ULDCT images were reconstructed with HIR (ULDCT-HIR), MBIR (ULDCT-MBIR), and DLR (ULDCT-DLR). Image noise and contrast-to-noise ratio (CNR) were quantified. With the LDCT images as reference standards, ULDCT image qualities were subjectively scored on a 5-point scale (1 = substantially inferior to LDCT-2, 3 = comparable to LDCT-2, 5 = comparable to LDCT-1). For task-based image quality analyses, a physical evaluation phantom was scanned at seven doses to achieve the noise levels equivalent to chest phantom; noise power spectrum (NPS) and task-based transfer function (TTF) were evaluated. Clinical ULDCT (10-mA) images obtained in 14 nonobese patients were reconstructed with HIR, MBIR, and DLR; the subjective acceptability was ranked. RESULTS: Image noise was lower and CNR was higher in ULDCT-DLR and ULDCT-MBIR than in LDCT-1, LDCT-2, and ULDCT-HIR (p < 0.01). The overall quality of ULDCT-DLR was higher than of ULDCT-HIR and ULDCT-MBIR (p < 0.01), and almost comparable with that of LDCT-2 (mean score: 3.4 ± 0.5). DLR yielded the highest NPS peak frequency and TTF50% for high-contrast object. In clinical ULDCT images, the subjective acceptability of DLR was higher than of HIR and MBIR (p < 0.01). CONCLUSION: DLR optimized for lung CT improves image quality and provides possible greater dose optimization opportunity than HIR and MBIR.

Ultralow-Dose Intraoperative Computed Tomography During Endoscopic Stone Surgery: A Quality Improvement Project.

Objectives: To improve care in patients with large kidney stones using advanced intraoperative imaging techniques to reduce perioperative radiation exposure, improve stone-free rates (SFRs), and reduce the number of surgical interventions in a quality improvement project. Patients and Methods: Patients with kidney stones appropriate for percutaneous nephrolithotomy (PCNL) treatment were scheduled into a hybrid operating room for endoscopic surgery (PCNL and/or ureteroscopy) with intent to perform intraoperative CT (ICT). Imaging was performed using an Artis Zeego Care+Clear™ (Siemens) robotic-armed multiplanar fluoroscopy system with collimation to the level of the affected kidney(s). After the initial case, the proprietary CARE™ (combined applications to reduce exposure) protocol was used. When the hybrid room was unavailable, a mobile CT scanner (O-Arm; Medtronics) was used in the traditional room (n = 2). Results: Thirty-one ICTs were performed in 23 consecutive patients during endoscopic stone procedures with a median effective radiation dose of 1.39 mSv per scan, significantly less than the preoperative noncontrast CT (12.02 mSv) in the same patients (p < 0.001). Longitudinal radiation exposure associated with stone treatment significantly decreased by 83% (15.80 to 2.68 mSv, p < 0.001) compared with a similar historical PCNL cohort. Clinically significant residual stones (≥3 mm) were identified at initial ICT in eight patients (35%) and further treated in six patients. One patient had missed residual stone diagnosed 34 days after surgery, which was apparent on re-review of the ICT. Thus, final verified SFR was 87% for all stages. Mean number of procedures improved from 1.77 to 1.30 (p = 0.05) and rate of postoperative CT scans improved from 82% to 26% (p < 0.001). Conclusion: Ultralow-dose ICT was demonstrated to simultaneously improve SFR and number of staged treatments, and greatly reduce the perioperative radiation dose for our patients. The findings support the continued use of this modality to benefit all patients with large stones.

Preclinical Evaluation of a Protein-Based Nanoscale Contrast Agent for MR Angiography at an Ultralow Dose.

Purpose: BSA-biomineralized Gd nanoparticles (Gd@BSA NPs) have been recognized as promising nanoscale MR contrast agents. The aim of this study was to carry out a preclinical evaluation of these NPs in a middle-sized animal model (rabbits). Methods: New Zealand white rabbits were treated intravenously with Gd@BSA NPs (0.02 mmol Gd/kg) via a clinically-used high-pressure injector, with commercial Gd-diethylene triamine pentaacetate (Gd-DTPA)-injected group as control. Then MR angiography was performed according to the standard clinical protocol with a 3.0-T MR scanner. The SNR and CNR of the main arteries and branches were monitored. Pharmacokinetics and bioclearance were continuously evaluated in blood, urine, and feces. Gd deposition in vital organs was measured by ICP‒MS. Weight monitoring, HE staining, and blood biochemical analysis were also performed to comprehensively estimate systemic toxicity. Results: The ultrasmall Gd@BSA NPs (<6 nm) exhibited high stability and T1 relaxivity. Compared to Gd-DTPA, Gd@BSA NPs demonstrated superior vascular system imaging performance at ultralow doses, especially of the cardiac artery and other main branches, and exhibited a significantly higher SNR and CNR. Notably, the Gd@BSA NPs showed a shorter half-life in blood, less retention in organs, and improved biocompatibility. Conclusion: The preclinical evaluations here demonstrated that Gd@BSA NPs are promising and advantageous MR CA candidates that can be used at a low dose with excellent MR imaging performance, thus suggesting its further clinical trials and applications.

Semi-automated volumetry of pulmonary nodules: Intra-individual comparison of standard dose and chest X-ray equivalent ultralow dose chest CT scans.

PURPOSE: To assess the performance of semi-automated volumetry of solid pulmonary nodules on single-energy tin-filtered ultralow dose (ULD) chest CT scans at a radiation dose equivalent to chest X-ray relative to standard dose (SD) chest CT scans and assess the impact of kernel and iterative reconstruction selection. METHODS: Ninety-four consecutive patients from a prospective single-center study were included and underwent clinically indicated SD chest CT (1.9 ± 0.8 mSv) and additional ULD chest CT (0.13 ± 0.01 mSv) in the same session. All scans were reconstructed with a soft tissue (Br40) and lung (Bl64) kernel as well as with Filtered Back Projection (FBP) and Iterative Reconstruction (ADMIRE-3 and ADMIRE-5). One hundred and forty-eight solid pulmonary nodules were identified and analysed by semi-automated volumetry on all reconstructions. Nodule volumes were compared amongst all reconstructions thereby focusing on the agreement between SD and ULD scans. RESULTS: Nodule volumes ranged from 58.5 (28.8-126) mm3 for ADMIRE-5 Br40 ULD reconstructions to 72.5 (39-134) mm3 for FBP Bl64 SD reconstructions with significant differences between reconstructions (p < 0.001). Interscan agreement of volumes between two given reconstructions ranged from ICC = 0.605 to ICC = 0.999. Between SD and ULD scans, agreement of nodule volumes was highest for FBP Br40 (ICC = 0.995), FBP Bl64 (ICC = 0.939) and ADMIRE-5 Bl64 (ICC = 0.994) reconstructions. ADMIRE-3 reconstructions exhibited reduced interscan agreement of nodule volumes (ICCs from 0.788 - 0.882). CONCLUSIONS: The interscan agreement of node volumes between SD and ULD is high depending on the choice of kernel and reconstruction algorithm. However, caution should be exercised when comparing two image series that were not identically reconstructed.

Short-term infusion of ultralow-dose dopamine in an adult horse with acute kidney injury: A case report.

Much is known regarding a good prognosis of acute kidney injury (AKI) is achieved with adequate, intensive, and early treatment, which leads to acceleration of the renal blood flow rate and associated urination. Low-dose dopamine (1 to 5 µg/kg bwt per min) is a treatment option for AKI in humans but remains controversial for use in horses because of the lack of extensive clinical trial data. A 19-year-old Westfalen horse gelding was referred to the Animal Medical Center with a 1-hour history of mild abdominal pain and anorexia after dressage exercise for 1 hour. Since elevated serum levels of blood urea nitrogen (BUN) and creatinine were found on days 4 and 5, the horse was diagnosed with AKI. In addition to basic hydration therapy with lactated Ringer's solution, we decided to use ultralow-dose dopamine because of the possibilities of the upregulation of dopamine receptors in the affected kidney and general large animal specificity of drug doses. Infusions with 0.04 and 0.02 µg/kg bwt per min for 1 hour on days 6 and 7, respectively, were effective in decreasing serum levels of BUN and creatinine accompanied with a diuretic effect. Thus, short-term infusion of ultralow-dose dopamine may be useful in controlling the renal blood flow rate and clinical conditions in horses with AKI.

Simulated Annealing-Based Image Reconstruction for Patients With COVID-19 as a Model for Ultralow-Dose Computed Tomography.

The proposed algorithm of inverse problem of computed tomography (CT), using limited views, is based on stochastic techniques, namely simulated annealing (SA). The selection of an optimal cost function for SA-based image reconstruction is of prime importance. It can reduce annealing time, and also X-ray dose rate accompanying better image quality. In this paper, effectiveness of various cost functions, namely universal image quality index (UIQI), root-mean-squared error (RMSE), structural similarity index measure (SSIM), mean absolute error (MAE), relative squared error (RSE), relative absolute error (RAE), and root-mean-squared logarithmic error (RMSLE), has been critically analyzed and evaluated for ultralow-dose X-ray CT of patients with COVID-19. For sensitivity analysis of this ill-posed problem, the stochastically estimated images of lung phantom have been reconstructed. The cost function analysis in terms of computational and spatial complexity has been performed using image quality measures, namely peak signal-to-noise ratio (PSNR), Euclidean error (EuE), and weighted peak signal-to-noise ratio (WPSNR). It has been generalized for cost functions that RMSLE exhibits WPSNR of 64.33 ± 3.98 dB and 63.41 ± 2.88 dB for 8 × 8 and 16 × 16 lung phantoms, respectively, and it has been applied for actual CT-based image reconstruction of patients with COVID-19. We successfully reconstructed chest CT images of patients with COVID-19 using RMSLE with eighteen projections, a 10-fold reduction in radiation dose exposure. This approach will be suitable for accurate diagnosis of patients with COVID-19 having less immunity and sensitive to radiation dose.

Improving the sensitivity of T1 contrast-enhanced MRI and sensitive diagnosing tumors with ultralow doses of MnO octahedrons.

Rationale: Sensitive and accurate imaging of cancer is essential for early diagnosis and appropriate treatment. For generally employed magnetic resonance imaging (MRI) in clinic, comprehending how to enhance the contrast effect of T1 imaging is crucial for improving the sensitivity of cancer diagnosis. However, there is no study ever to reveal the clear mechanism of how to enhance the effect of T1 imaging and accurate relationships of influencing factors. Herein, this study aims to figure out key factors that affect the sensitivity of T1 contrast-enhanced MRI (CE-MRI), thereby to realize sensitive detection of tumors with low dose of CAs. Methods: Manganese oxide (MnO) nanoparticles (NPs) with various sizes and shapes were prepared by thermal decomposition. Factors impacting T1 CE-MRI were investigated from geometric volume, surface area, crystal face to r2/r1 ratio. T1 CE-MR imaging of liver, hepatic and subcutaneous tumors were conducted with MnO NPs of different shapes. Results: The surface area and occupancy rate of manganese ions have positive impacts on the sensitivity of T1 CE-MRI, while volume and r2/r1 ratio have negative effects. MnO octahedrons have a high r1 value of 20.07 mM-1s-1 and exhibit an excellent enhanced effect in liver T1 imaging. ZDS coating facilitates tumor accumulation and cellular uptake, hepatic and subcutaneous tumors could be detected with MnO octahedrons at an ultralow dose of 0.4 mg [Mn]/kg, about 1/10 of clinical dose. Conclusions: This work is the first quantitative study of key factors affecting the sensitivity of T1 CE-MRI of MnO nanoparticles, which can serve as a guidance for rational design of high-performance positive MRI contrast agents. Moreover, these MnO octahedrons can detect hepatic and subcutaneous tumors with an ultralow dose, hold great potential for sensitive and accurate diagnosis of cancer with lower cost, less dosages and side effects in clinic.

Indirect monitoring of ultralow dose API content in continuous wet granulation and tableting by machine vision.

This paper presents new machine vision-based methods for indirect real-time quantification of ultralow drug content during continuous twin-screw wet granulation and tableting. Granulation was performed with a solution containing carvedilol (CAR) as API in the ultralow dose range (0.05w/w% in the granule) and the addition of riboflavin (RI) as a coloured tracer. An in-line calibration in the range of 0.047-0.058 w/w% was prepared for the measurement of CAR concentration using colour analysis (CA) and particle size analysis (PSA), and the validation with HPLC resulted in respective relative errors of 2.62% and 2.30% showing great accuracy. To improve the technique, a second in-line calibration was conducted in a broader CAR concentration range of 0.039-0.063 w/w% utilizing only half the amount of RI (0.045 w/w%), while doubling the output of the granulation line to 2 kg/h, producing a relative error of 4.51% and 4.29%, respectively. Finally, it was shown that the CA technique can also be carried on to monitor the CAR content of tablets in the 42-62 µg dose range with a relative error of 5.20%. Machine vision was proven to be a potent indirect method for the in-line, determination and monitoring of ultralow API content during continuous manufacturing.