Reduced Dose Levels Research Articles

Comparison of Radiation Dose and Image Quality of Pediatric High-Resolution Chest CT Between Photon-Counting Detector CT and Energy-Integrated Detector CT: A Matched Study.

BACKGROUND. Photon-counting detector (PCD) CT has been shown to reduce radiation dose and improve image quality in adult chest CT examinations; its potential impact in pediatric CT is not well documented. OBJECTIVE. The purpose of our study was to compare radiation dose, objective image quality, and subjective image quality of PCD CT and energy-integrating detector (EID) CT in children undergoing high-resolution CT (HRCT) of the chest. METHODS. This retrospective study included 27 children (median age, 3.9 years; 10 girls, 17 boys) who underwent PCD CT between March 1, 2022, and August 31, 2022, and 27 children (median age, 4.0 years; 13 girls, 14 boys) who underwent EID CT between August 1, 2021, and January 31, 2022; all examinations comprised clinically indicated chest HRCT. The patients in the two groups were matched by age and water-equivalent diameter. Radiation dose parameters were recorded. One observer placed ROIs to measure objective parameters (lung attenuation, image noise, and SNR). Two radiologists independently assessed subjective measures (overall image quality and motion artifacts) using 5-point Likert scales (1 = highest quality). Groups were compared. RESULTS. PCD CT, in comparison with EID CT, showed lower median CTDIvol (0.41 vs 0.71 mGy, p < .001), DLP (10.2 vs 13.7 mGy × cm, p = .008), size-specific dose estimate (0.82 vs 1.34 mGy, p < .001), and tube current-exposure time product (48.0 vs 202.0 mAs, p < .001). PCD CT and EID CT showed no significant difference in right upper lobe (RUL) lung attenuation (mean, -793 vs -750 HU; p = .09), right lower lobe (RLL) lung attenuation (mean, -745 vs -716 HU; p = .23), RUL image noise (mean, 55 vs 51 HU; p = .27), RLL image noise (mean, 59 vs 57 HU; p = .48), RUL SNR (mean, -14.9 vs -15.8; p = .89), or RLL SNR (mean, -13.1 vs -13.6; p = .79). PCD CT and EID CT showed no significant difference in median overall image quality for reader 1 (1.0 vs 1.0, p = .28) or reader 2 (1.0 vs 1.0, p = .17) or median motion artifacts for reader 1 (1.0 vs 1.0, p = .07) or reader 2 (1.0 vs 1.0, p = .22). CONCLUSION. PCD CT showed significantly reduced dose levels without a significant difference in objective or subjective image quality compared with EID CT. CLINICAL IMPACT. These data expand understanding of the capabilities of PCD CT and support its routine use in children.

Unbiased zero-count correction method in low-dose high-resolution photon counting detector CT

Objective. To address the zero-count problem in low-dose, high-spatial-resolution photon counting detector CT (PCD-CT) without introducing statistical biases or degrading spatial resolution. Approach. The classical approach to generate the sinogram projection data for estimating the line integrals of the linear attenuation coefficients of the image object is to take a log transform of detector counts, which requires zero counts to be replaced by positive numbers. Both the log transform and the zero-count replacement introduce biases. After analyzing the statistical properties of the zero-count replaced pre-log and post-log data, a formula for the statistical sinogram bias was derived, based on which a new sinogram estimator was empirically constructed to cancel the statistical biases. Dose- and object-independent free parameters in the proposed estimator were learned from simulated data, and then the estimator was applied to experimental low-dose PCD-CT data of physical phantoms for validation and generalizability testing. Both bias and noise performances of the proposed method were evaluated and compared with those of previous zero-count correction methods, including zero-weighting, zero-replacement, and adaptive filtration-based methods. The impact of these correction methods on spatial resolution was also quantified using line-pair patterns. Main Results. For all objects and reduced-dose levels, the proposed method reduces the statistical CT number biases to be within ± 10 HU, which is significantly lower than the biases given by the classical zero-count correction methods. The Bland-Altman analysis demonstrated that the proposed correction led to negligible sinogram biases at all attenuation levels, whereas the other correction methods did not. Additionally, the proposed method was found to have no discernible impact on image noise and spatial resolution. Significance. The proposed zero-count correction scheme allows the CT numbers of low-dose, high-spatial-resolution PCD-CT images to match those of standard-dose and standard-resolution PCD-CT images.

Pharmacokinetics and Pharmacodynamics of Antibody-Drug Conjugates Administered via Subcutaneous and Intratumoral Routes.

We hypothesize that different routes of administration may lead to altered pharmacokinetics/pharmacodynamics (PK/PD) behavior of antibody-drug conjugates (ADCs) and may help to improve their therapeutic index. To evaluate this hypothesis, here we performed PK/PD evaluation for an ADC administered via subcutaneous (SC) and intratumoral (IT) routes. Trastuzumab-vc-MMAE was used as the model ADC, and NCI-N87 tumor-bearing xenografts were used as the animal model. The PK of multiple ADC analytes in plasma and tumors, and the in vivo efficacy of ADC, after IV, SC, and IT administration were evaluated. A semi-mechanistic PK/PD model was developed to characterize all the PK/PD data simultaneously. In addition, local toxicity of SC-administered ADC was investigated in immunocompetent and immunodeficient mice. Intratumoral administration was found to significantly increase tumor exposure and anti-tumor activity of ADC. The PK/PD model suggested that the IT route may provide the same efficacy as the IV route at an increased dosing interval and reduced dose level. SC administration of ADC led to local toxicity and reduced efficacy, suggesting difficulty in switching from IV to SC route for some ADCs. As such, this manuscript provides unprecedented insight into the PK/PD behavior of ADCs after IT and SC administration and paves the way for clinical evaluation of these routes.

Quantitative Analysis of Image Quality in Low-Dose Computed Tomography Imaging for COVID-19 Patients.

Computed tomography (CT) scan is one of the main tools to diagnose and grade COVID-19 progression. To avoid the side effects of CT imaging, low-dose CT imaging is of crucial importance to reduce population absorbed dose. However, this approach introduces considerable noise levels in CT images. In this light, we set out to simulate four reduced dose levels (60% dose, 40% dose, 20% dose, and 10% dose) of standard CT imaging using Beer-Lambert's law across 49 patients infected with COVID-19. Then, three denoising filters, namely Gaussian, bilateral, and median, were applied to the different low-dose CT images, the quality of which was assessed prior to and after the application of the various filters via calculation of peak signal-to-noise ratio, root mean square error (RMSE), structural similarity index measure, and relative CT-value bias, separately for the lung tissue and whole body. The quantitative evaluation indicated that 10%-dose CT images have inferior quality (with RMSE = 322.1 ± 104.0 HU and bias = 11.44% ± 4.49% in the lung) even after the application of the denoising filters. The bilateral filter exhibited superior performance to suppress the noise and recover the underlying signals in low-dose CT images compared to the other denoising techniques. The bilateral filter led to RMSE and bias of 100.21 ± 16.47 HU and - 0.21% ± 1.20%, respectively, in the lung regions for 20%-dose CT images compared to the Gaussian filter with RMSE = 103.46 ± 15.70 HU and bias = 1.02% ± 1.68% and median filter with RMSE = 129.60 ± 18.09 HU and bias = -6.15% ± 2.24%. The 20%-dose CT imaging followed by the bilateral filtering introduced a reasonable compromise between image quality and patient dose reduction.

Glabridin Plays Dual Action to Augment the Efficacy and Attenuate the Hepatotoxicity of Methotrexate in Arthritic Rats.

Glabridin is chemically an isoflavane class of natural phenols and is found mainly in the roots of Glycyrrhiza glabra. It has several beneficial pharmacological actions for the management of inflammatory disorders as well as can counteract drug-induced toxic effects. On the other hand, methotrexate (MTX) is the first-line disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis. However, its treatment is associated with major side effects like hepatotoxicity. In the quest to explore a suitable combination therapy that can improve the efficacy and reduce the hepatotoxicity of MTX, we hypothesized that glabridin might serve the purpose for which there is no literature precedent to date. We explored the antiarthritic efficacy of MTX in the presence or the absence of glabridin using Mycobacterium-induced arthritic model in rats. The results of reduction in paw swelling, inhibition of serum cytokines (TNF-α, IL-6, and IL-1β), and improvement in the bone joints from radiological and histopathological findings suggest that glabridin can substantially augment the antiarthritic efficacy of MTX. Further, results of concomitant glabridin treatment with MTX in the experimental time frame demonstrate that glabridin could considerably prevent the MTX-induced hepatic alteration in serum biochemical markers (SGPT and SGOT) and oxidative stress markers (malondialdehyde (MDA) and glutathione reduced (GSH)). Moreover, glabridin showed a marked effect in impeding the regulation of NF-κB/IκBα and Nrf2/Keap1 pathways in the hepatic tissues. The results of simultaneous administration of glabridin with MTX in the rat model indicate that glabridin had no pronounced effect of causing severe alteration in the pharmacokinetic behavior of MTX. In summary, glabridin can significantly potentiate the antiarthritic efficacy of MTX and can also minimize its hepatotoxicity via the inhibition of inflammation and oxidative stress. Further research should be performed to develop glabridin as a phytotherapeutics for the improved efficacy and better tolerability of MTX at the reduced dose level of MTX.

Dose Reduction and Image Quality in Photon-counting Detector High-resolution Computed Tomography of the Chest: Routine Clinical Data.

Photon-counting detector computed tomography (PCD-CT) has the potential to significantly improve CT imaging in many ways including, but not limited to, low-dose high-resolution CT (HRCT) of the lung. The aim of this study was to perform an intrapatient comparison of the radiation dose and image quality of PCD-CT compared with conventional energy-integrating detector CT (EID-CT). A total of 32 consecutive patients with available PCD-CT and EID-CT HRCT scans were included in the final analysis. The CT dose index (CTDI vol ) was extracted from patient dose reports. Qualitative image analysis comprised the lung parenchyma and mediastinal structures and was assessed by 3 readers using a 5-point Likert scale. Quantitative image analysis included assessment of noise and signal-to-noise ratio in the lung parenchyma, trachea, aorta, muscle, and background. The mean CTDI vol was 2.0 times higher in the conventional EID-CT scans (1.8±0.5mGy) compared with PCD-CT (0.9±0.5mGy, P <0.001). The overall image quality was rated significantly better by all 3 raters ( P <0.001) in the PCD-CT relative to the EID-CT. Quantitative analysis showed no significant differences in noise and signal-to-noise ratio in the lung parenchyma between PCD-CT and EID-CT. Compared with conventional EID-CT scans, PCD-CT demonstrated similar or better objective and subjective image quality at significantly reduced dose levels in an intrapatient comparison. These results and their effect on clinical decision-making should be further investigated in prospective studies.

Epicatechin exerts dual action to shield sickling and hydroxyurea-induced myelosuppression: Implication in sickle cell anemia management

Hydroxyurea (HU) is the key drug to treat Sickle cell anemia (SCA). However, its treatment is associated with the liability of myelosuppression. The present study aimed to investigate the potential of epicatechin as a supplementation therapy for the symptomatic management of SCA under HU therapy. A panel of experiments were performed at first to observe epicatechin's effect on sickling and hemolytic behaviour using SCA patient's blood (ex vivo). Thereafter, the effect of HU in the presence or absence of epicatechin was investigated on cytokine inhibition in rat splenocytes (ex vivo) as well as alterations in hematological parameters and kidney function tests in rats (in vivo). Then, any effect of epicatechin on pharmacokinetic modulation of HU in rats was elucidated along with the underlying mechanism using a battery of in vitro and in vivo models. Epicatechin exhibited potent action on anti-sickling, polymerization inhibition, and erythrocyte membrane stability. It did not show any inherent hemolytic activity and reduced TNF-α level during concomitant administration with HU. Based on hematological changes in rats, epicatechin treatment aided to the beneficial effect of HU and prevented the treatment-linked disadvantageous effects of HU like neutropenia. The plasma exposure of HU was significantly augmented in rats upon simultaneous oral administration of epicatechin with HU. Down-regulation of Oatp1b2 and catalase possibly contributed to the pharmacokinetic interaction of HU. Epicatechin is found to be a promising candidate and should be explored at a reduced dose level of HU towards offsetting the dose-dependent myelosuppressive effect of HU under the frame of supplementation therapy in SCA.

Deep learning\u2013based denoising of low-dose SPECT myocardial perfusion images: quantitative assessment and clinical performance

PurposeThis work was set out to investigate the feasibility of dose reduction in SPECT myocardial perfusion imaging (MPI) without sacrificing diagnostic accuracy. A deep learning approach was proposed to synthesize full-dose images from the corresponding low-dose images at different dose reduction levels in the projection space.MethodsClinical SPECT-MPI images of 345 patients acquired on a dedicated cardiac SPECT camera in list-mode format were retrospectively employed to predict standard-dose from low-dose images at half-, quarter-, and one-eighth-dose levels. To simulate realistic low-dose projections, 50%, 25%, and 12.5% of the events were randomly selected from the list-mode data through applying binomial subsampling. A generative adversarial network was implemented to predict non-gated standard-dose SPECT images in the projection space at the different dose reduction levels. Well-established metrics, including peak signal-to-noise ratio (PSNR), root mean square error (RMSE), and structural similarity index metrics (SSIM) in addition to Pearson correlation coefficient analysis and clinical parameters derived from Cedars-Sinai software were used to quantitatively assess the predicted standard-dose images. For clinical evaluation, the quality of the predicted standard-dose images was evaluated by a nuclear medicine specialist using a seven-point (− 3 to + 3) grading scheme.ResultsThe highest PSNR (42.49 ± 2.37) and SSIM (0.99 ± 0.01) and the lowest RMSE (1.99 ± 0.63) were achieved at a half-dose level. Pearson correlation coefficients were 0.997 ± 0.001, 0.994 ± 0.003, and 0.987 ± 0.004 for the predicted standard-dose images at half-, quarter-, and one-eighth-dose levels, respectively. Using the standard-dose images as reference, the Bland–Altman plots sketched for the Cedars-Sinai selected parameters exhibited remarkably less bias and variance in the predicted standard-dose images compared with the low-dose images at all reduced dose levels. Overall, considering the clinical assessment performed by a nuclear medicine specialist, 100%, 80%, and 11% of the predicted standard-dose images were clinically acceptable at half-, quarter-, and one-eighth-dose levels, respectively.ConclusionThe noise was effectively suppressed by the proposed network, and the predicted standard-dose images were comparable to reference standard-dose images at half- and quarter-dose levels. However, recovery of the underlying signals/information in low-dose images beyond a quarter of the standard dose would not be feasible (due to very poor signal-to-noise ratio) which will adversely affect the clinical interpretation of the resulting images.

Increased potency of recombinant VWF D′D3 albumin fusion proteins engineered for enhanced affinity for coagulation factor VIII

BackgroundWe have recently reported on a recombinant von Willebrand factor (VWF) D′D3 albumin fusion protein (rD′D3‐FP) developed to extend the half‐life of coagulation factor VIII (FVIII) for the treatment of hemophilia A. Based on predictive modelling presented in this study, we hypothesized that modifying rD′D3‐FP to improve FVIII interaction would reduce exchange with endogenous VWF and provide additional FVIII half‐life benefit. ObjectivesThe aim of this study was to identify novel rD′D3‐FP variants with enhanced therapeutic efficacy in extending FVIII half‐life. MethodsThrough both directed mutagenesis and random mutagenesis using a novel mammalian display platform, we identified novel rD′D3‐FP variants with increased affinity for FVIII (rVIII‐SingleChain) under both neutral and acidic conditions and assessed their ability to extend FVIII half‐life in vitro and in vivo. ResultsIn rat preclinical studies, rD′D3‐FP variants with increased affinity for FVIII displayed enhanced potency, with reduced dose levels required to achieve equivalent rVIII‐SingleChain half‐life extension. In cell‐based imaging studies in vitro, we also demonstrated reduced dissociation of rVIII‐SingleChain from the rD′D3‐FP variants within acidic endosomes and more efficient co‐recycling of the rD′D3‐FP/rVIII‐SingleChain complex via the FcRn recycling system. ConclusionsIn summary, at potential clinical doses, the rD′D3‐FP variants provide marked benefits with respect to dose levels and half‐life extension of co‐administered FVIII, supporting their development for use in the treatment of hemophilia A.

Preserving image texture while reducing radiation dose with a deep learning image reconstruction algorithm in chest CT: A phantom study.

To assess whether a deep learning image reconstruction algorithm (TrueFidelity) can preserve the image texture of conventional filtered back projection (FBP) at reduced dose levels attained by ASIR-V in chest CT. Phantom images were acquired using a clinical chest protocol (7.6mGy) and two levels of dose reduction (60% and 80%). Images were reconstructed with FBP, ASIR-V (50% and 100% blending) and TrueFidelity (low (DL-L), medium (DL-M) and high (DL-H) strength). Noise (SD), noise power spectrum (NPS) and task-based transfer function (TTF) were calculated. Noise texture was quantitatively compared by computing root-mean-square deviations (RMSD) of NPS with respect to FBP. Four experienced readers performed a contrast-detail evaluation. The dose reducing potential of TrueFidelity compared to ASIR-V was assessed by fitting SD and contrast-detail as a function of dose. DL-M and DL-H reduced noise and NPS area compared to FBP and 50% ASIR-V, at all dose levels. At 7.6mGy, NPS of ASIR-V 50/100% was shifted towards lower frequencies (fpeak=0.22/0.13mm-1, RMSD=0.14/0.38), with respect to FBP (fpeak=0.30mm-1). Marginal difference was observed for TrueFidelity: fpeak=0.33/0.30/0.30mm-1 and RMSD=0.03/0.04/0.07 for L/M/H strength. Values of TTF50% were independent of DL strength and higher compared to FBP and ASIR-V, at all dose and contrast levels. Contrast-detail was highest for DL-H at all doses. Compared to 50% ASIR-V, DL-H had an estimated dose reducing potential of 50% on average, without impairing noise, texture and detectability. TrueFidelity preserves the image texture of FBP, while outperforming ASIR-V in terms of noise, spatial resolution and detectability at lower doses.

Finite Element Analysis-Based Vertebral Bone Strength Prediction Using MDCT Data: How Low Can We Go?

Objective: To study the impact of dose reduction in MDCT images through tube current reduction or sparse sampling on the vertebral bone strength prediction using finite element (FE) analysis for fracture risk assessment.Methods: Routine MDCT data covering lumbar vertebrae of 12 subjects (six male; six female; 74.70 ± 9.13 years old) were included in this study. Sparsely sampled and virtually reduced tube current–based MDCT images were computed using statistical iterative reconstruction (SIR) with reduced dose levels at 50, 25, and 10% of the tube current and original projections, respectively. Subject-specific static non-linear FE analyses were performed on vertebra models (L1, L2, and L3) 3-D-reconstructed from those dose-reduced MDCT images to predict bone strength. Coefficient of correlation (R2), Bland-Altman plots, and root mean square coefficient of variation (RMSCV) were calculated to find the variation in the FE-predicted strength at different dose levels, using high-intensity dose-based strength as the reference.Results: FE-predicted failure loads were not significantly affected by up to 90% dose reduction through sparse sampling (R2 = 0.93, RMSCV = 8.6% for 50%; R2 = 0.89, RMSCV = 11.90% for 75%; R2 = 0.86, RMSCV = 11.30% for 90%) and up to 50% dose reduction through tube current reduction method (R2 = 0.96, RMSCV = 12.06%). However, further reduction in dose with the tube current reduction method affected the ability to predict the failure load accurately (R2 = 0.88, RMSCV = 22.04% for 75%; R2 = 0.43, RMSCV = 54.18% for 90%).Conclusion: Results from this study suggest that a 50% radiation dose reduction through reduced tube current and a 90% radiation dose reduction through sparse sampling can be used to predict vertebral bone strength. Our findings suggest that the sparse sampling–based method performs better than the tube current–reduction method in generating images required for FE-based bone strength prediction models.

Evaluation of the effect of reducing administered activity on assessment of function in cardiac gated SPECT

BackgroundWe previously optimized several reconstruction strategies in SPECT myocardial perfusion imaging (MPI) with low dose for perfusion-defect detection. Here we investigate whether reducing the administered activity can also maintain the diagnostic accuracy in evaluating cardiac function. MethodsWe quantified the myocardial motion in cardiac-gated stress 99m-Tc-sestamibi SPECT studies from 163 subjects acquired with full dose (29.8 ± 3.6 mCi), and evaluated the agreement of the obtained motion/thickening and ejection fraction (EF) measures at various reduced dose levels (uniform reduction or personalized dose) with that at full dose. We also quantified the detectability of abnormal motion via a receiver-operating characteristics (ROC) study. For reconstruction we considered both filtered backprojection (FBP) without correction for degradations, and iterative ordered-subsets expectation-maximization (OS-EM) with resolution, attenuation and scatter corrections. ResultsWith dose level lowered to 25% of full dose, the obtained results on motion/thickening, EF and abnormal motion detection were statistically comparable to full dose in both reconstruction strategies, with Pearson’s r > 0.9 for global motion measures between low dose and full dose. ConclusionsThe administered activity could be reduced to 25% of full dose without degrading the function assessment performance. Low dose reconstruction optimized for perfusion-defect detection can be reasonable for function assessment in gated SPECT.

Improving Diagnostic Accuracy in Low-Dose SPECT Myocardial Perfusion Imaging With Convolutional Denoising Networks.

Lowering the administered dose in SPECT myocardial perfusion imaging (MPI) has become an important clinical problem. In this study we investigate the potential benefit of applying a deep learning (DL) approach for suppressing the elevated imaging noise in low-dose SPECT-MPI studies. We adopt a supervised learning approach to train a neural network by using image pairs obtained from full-dose (target) and low-dose (input) acquisitions of the same patients. In the experiments, we made use of acquisitions from 1,052 subjects and demonstrated the approach for two commonly used reconstruction methods in clinical SPECT-MPI: 1) filtered backprojection (FBP), and 2) ordered-subsets expectation-maximization (OSEM) with corrections for attenuation, scatter and resolution. We evaluated the DL output for the clinical task of perfusion-defect detection at a number of successively reduced dose levels (1/2, 1/4, 1/8, 1/16 of full dose). The results indicate that the proposed DL approach can achieve substantial noise reduction and lead to improvement in the diagnostic accuracy of low-dose data. In particular, at 1/2 dose, DL yielded an area-under-the-ROC-curve (AUC) of 0.799, which is nearly identical to the AUC = 0.801 obtained by OSEM at full-dose ( p -value = 0.73); similar results were also obtained for FBP reconstruction. Moreover, even at 1/8 dose, DL achieved AUC = 0.770 for OSEM, which is above the AUC = 0.755 obtained at full-dose by FBP. These results indicate that, compared to conventional reconstruction filtering, DL denoising can allow for additional dose reduction without sacrificing the diagnostic accuracy in SPECT-MPI.

Advancing Safety: Role of Equipment Design and Configuration Change in Pediatric Fluoroscopy.

Diagnostic x-ray exams irradiate the patient to produce an x-ray pattern in space, which is captured and processed into a visible image, followed by clinical interpretation. Diagnostic-quality images at a well-managed radiation dose are required. Improvements to image receptors and image processing algorithms have resulted in improved images at reduced dose levels. However, careful management of x-ray production via design or configuration changes of the imaging device also affect patient dose. This initial dose management step is the focus of this discussion. Imaging equipment vendors, in general, have produced quality images of adults at reasonably managed patient doses. This achievement required teamwork between leading adult hospital staff members and representatives of the imaging equipment vendor within the adult hospital. Most manufacturers have had less opportunity to develop similar optimized configurations for pediatric imaging, the imaging of patients ranging from 2-200 kg between 0-21 y of age. Challenges: The wider dynamic range of patient thicknesses in the pediatric size range compared to the adult range of only 45-140 kg challenges automatic control features. In recent years reduction of patient dose as opposed to proper management has been stressed. The principal objectives of end users and vendors, respectively, are patient care and the bottom line. This too often hampers (if not prevents) a productive working relationship between the vendor and the end user. Too many end users rely too heavily on their equipment vendor to solve imaging/dose concerns. The vendors have an important role to play in this challenge but should not be the sole solution. Qualified medical physicists need an understanding of the design of the imaging device, an understanding that many vendors do not support out of proprietary concerns. The performance of the equipment should be judged based on data acquired with better tools. Solutions: Multiple equipment configurations are needed-each designed to excel at a reduced size of patients. Dose reductions that significantly impact image quality must be rejected. Radiologists and their qualified medical physicists should develop target patient doses (size based) for their unique imaging equipment and preferred level of quantum mottle. Once target doses are established as a function of patient size, vendor application specialists and design engineers should leverage the equipment's strengths and weaknesses to best achieve desired results. The qualified medical physicist should function as an interpreter between the end user and the vendor's design engineers. Are the radiologists' and technologists' expectations of the vendor reasonable and vice versa? While better tools are being developed, vendors may hesitate to make them available or charge excessive dollars for these new features to further slow their adoption. Conclusion: The challenges and solutions require the radiologist, technologist, qualified medical physicist, and vendor representatives to work as a team to manage patient dose and maintain image quality. The installed imaging device will be only as successful as the working relationship between the parties. These challenges and conflicts must continually be overcome to provide the best patient care.

Emphysema quantification using chest CT: influence of radiation dose reduction and reconstruction technique

BackgroundComputed tomography (CT) emphysema quantification is affected by both radiation dose (i.e. image noise) and reconstruction technique. At reduced dose, filtered back projection (FBP) results in an overestimation of the amount of emphysema due to higher noise levels, while the use of iterative reconstruction (IR) can result in an underestimation due to reduced noise. The objective of this study was to determine the influence of dose reduction and hybrid IR (HIR) or model-based IR (MIR) on CT emphysema quantification.MethodsTwenty-two patients underwent inspiratory chest CT scan at routine radiation dose and at 45%, 60% and 75% reduced radiation dose. Acquisitions were reconstructed with FBP, HIR and MIR. Emphysema was quantified using the 15th percentile of the attenuation curve and the percentage of voxels below -950 HU. To determine whether the use of a different percentile or HU threshold is more accurate at reduced dose levels and with IR, additional measurements were performed using different percentiles and HU thresholds to determine the optimal combination.ResultsDose reduction resulted in a significant overestimation of emphysema, while HIR and MIR resulted in an underestimation. Lower HU thresholds with FBP at reduced dose and higher HU thresholds with HIR and MIR resulted in emphysema percentages comparable to the reference. The 15th percentile quantification method showed similar results as the HU threshold method.ConclusionsThis within-patients study showed that CT emphysema quantification is significantly affected by dose reduction and IR. This can potentially be solved by adapting commonly used thresholds.

MDCT-based Finite Element Analysis of Vertebral Fracture Risk: What Dose is Needed?

The aim of this study was to compare vertebral failure loads, predicted from finite element (FE) analysis of patients with and without osteoporotic vertebral fractures (OVF) at virtually reduced dose levels, compared to standard-dose exposure from multidetector computed tomography (MDCT) imaging and evaluate whether ultra-low dose derived FE analysis can still differentiate patient groups. An institutional review board (IRB) approval was obtained for this retrospective study. A total of 16patients were evaluated at standard-dose MDCT; eight with and eight without OVF. Images were reconstructed at virtually reduced dose levels (i. e. half, quarter and tenth of the standard dose). Failure load was determined at L1-3 from FE analysis and compared between standard, half, quarter, and tenth doses and used to differentiate between fracture and control groups. Failure load derived at standard dose (3254 ± 909 N and 3794 ± 984 N) did not significantly differ from half (3390 ± 890 N and 3860 ± 1063 N) and quarter dose (3375 ± 915 N and 3925 ± 990 N) but was significantly higher for one tenth dose (4513 ± 1762 N and 4766 ± 1628 N) for fracture and control groups, respectively. Failure load differed significantly between the two groups at standard, half and quarter doses, but not at tenth dose. Receiver operating characteristic (ROC) curve analysis also demonstrated that standard, half, and quarter doses can significantly differentiate the fracture from the control group. The use of MDCT enables adose reduction of at least 75% compared to standard-dose for an adequate prediction of vertebral failure load based on non-invasive FE analysis.

Low-dose cone-beam CT via raw counts domain low-signal correction schemes: Performance assessment and task-based parameter optimization (Part I: Assessment of spatial resolution and noise performance).

Low-signal correction (LSC) in the raw counts domain has been shown to effectively reduce noise streaks in CT because the data inconsistency associated with photon-starved regions may be mitigated prior to the log transformation step. However, a systematic study of the performance of these raw data correction methods is still missing in literature. The purpose of this work was to provide such a systematic study for two well-known low-signal correction schemes using either the adaptive trimmed mean (ATM) filter or the anisotropic diffusion (AD) filter in the raw counts domain. Image data were acquired experimentally using an anthropomorphic chest phantom and a benchtop cone-beam CT (CBCT) imaging system. Phantom scans were repeated 50 times at a reduced dose level of 0.5 mGy and a reference level of 1.9 mGy. The measured raw counts at 0.5 mGy underwent LSC using the ATM and AD filters. Two relevant parameters were identified for each filter and approximately one hundred operating points in each parameter space were analyzed. Following LSC and log transformation, FDK reconstruction was performed for each case. Noise and spatial resolution properties were assessed across the parameter spaces that define each LSC filter; the results were summarized through 2D contour maps to better understand the trade-offs between these competing image quality features. 2D noise power spectrum (NPS) and modulation transfer function (MTF) were measured locally at two spatial locations in the field-of-view (FOV): a posterior region contaminated by noise streaks and an anterior region away from noise streaks. An isotropy score metric was introduced to characterize the directional dependence of the NPS and MTF (viz., ϵNPS and ϵMTF , respectively), with a range from 0 for highly anisotropic to 1 for perfectly isotropic. The noise magnitude and coarseness were also measured. (a) Both the ATM and AD LSC methods were successful in reducing noise streaks, but their noise and spatial resolution properties were found to be highly anisotropic and shift-variant. (b) NPS isotropy scores in the posterior region were generally improved from ϵNPS = 0.09 for the images without LSC to the range ϵNPS = (0.11, 0.67) for ATM and ϵNPS = (0.06, 0.67) for AD, depending on the filter parameters used. (c) The noise magnitude was reduced across the parameter space of either LSC filter whenever a change along the axis of the controlling parameter led to stronger raw data filtration. Changes in noise magnitude were inversely related to changes in spatial resolution along the direction perpendicular to the streaks. No correlation was found, however, between the contour maps of noise magnitude and the NPS isotropy. (d) Both filters influenced the noise coarseness anisotropically, with coarser noise occurring along directions perpendicular to the noise streaks. The anisotropic noise coarseness was intrinsically and directly related to resolution losses in a given direction: coarseness plots mimic the topography of the 2D MTF, i.e., the coarser the noise, the lower the resolution. Both AD and ATM LSC schemes enable low-dose CBCT imaging. However, it was found that noise magnitude and overall spatial resolution vary considerably across the parameter space for each filter, and more importantly these image quality features are highly anisotropic and shift-variant.

Evaluation of a method for measuring the radioprotective metabolite WR-1065 in plasma using chemical derivatization combined with UHPLC-MS/MS

Hypotension is the dose-limiting side effect of the radio-protective drug Amifostine and results from relaxation of the vascular smooth muscle, which is directly mediated by the active metabolite, WR-1065, of Amifostine. The route of administration (currently FDA-approved only for intravenous administration) and the rapid metabolic conversion of Amifostine combine to yield high systemic levels of WR-1065 and facilitate the onset of hypotension. Research efforts aiming to optimize the delivery of WR-1065 to maintain efficacy while reducing its peak, systemic concentration below levels that induce hypotension are underway. To fully characterize the effect of reduced dose levels and alternative routes of administration of Amifostine on systemic WR-1065 concentrations, improved analytical techniques are needed. We have developed and evaluated a highly sensitive method for measuring WR-1065 in rat plasma that employs chemical derivatization, protein precipitation and UPLC-MS/MS analysis. The method exhibits a limit of quantification (LOQ) of 7.4 nM in plasma, which is a significant improvement over conventional approaches that utilize LC-electrochemical detection (ECD) (LOQ 150 nM or higher). The method was assessed in a pharmacokinetics study in rats administered Amifostine intravenously and via direct jejunal injection (10 mg/kg each route). The bioavailability of WR-1065 was 61.5% after direct jejunal injection indicating rapid conversion and absorption of the metabolite in the intestinal tract. This demonstrates that an oral formulation of Amifostine designed for site-specific release of the drug in the upper GI tract can deliver systemic absorption/conversion to WR-1065, provided that the formulation protects the therapeutic from gastric decomposition in the stomach.

MR-Guided Kernel EM Reconstruction for Reduced Dose PET Imaging.

PET image reconstruction is highly susceptible to the impact of Poisson noise, and if shorter acquisition times or reduced injected doses are used, the noisy PET data become even more limiting. The recent development of kernel expectation maximisation (KEM) is a simple way to reduce noise in PET images, and we show in this work that impressive dose reduction can be achieved when the kernel method is used with MR-derived kernels. The kernel method is shown to surpass maximum likelihood expectation maximisation (MLEM) for the reconstruction of low-count datasets (corresponding to those obtained at reduced injected doses) producing visibly clearer reconstructions for unsmoothed and smoothed images, at all count levels. The kernel EM reconstruction of 10% of the data had comparable whole brain voxel-level error measures to the MLEM reconstruction of 100% of the data (for simulated data, at 100 iterations). For regional metrics, the kernel method at reduced dose levels attained a reduced coefficient of variation and more accurate mean values compared to MLEM. However, the advances provided by the kernel method are at the expense of possible over-smoothing of features unique to the PET data. Further assessment on clinical data is required to determine the level of dose reduction that can be routinely achieved using the kernel method, whilst maintaining the diagnostic utility of the scan.

Chitosan-Gellan Gum Bipolymeric Nanohydrogels—a Potential Nanocarrier for the Delivery of Epigallocatechin Gallate

Encapsulation of a hydrophilic drug into a polymeric matrix always remains a challenging process due to poor loading and retention capacity. A novel nanoscale drug delivery system, i.e., nanohydrogels, has been developed by virtue of combination of ionotropic gelation and polyelectrolyte complexation technique for the delivery of a popular hydrophilic drug, (−)-epigallocatechin gallate (EGCG). EGCG is one of the popular bioactive compounds present in green tea. Chitosan and gellan gum were used as cationic and anionic polysaccharides, and magnesium chloride was used as cross-linking agent for the synthesis of nanohydrogels in the present study. Effects of polymers and cross-linker were optimized using a three-level two-factor central composite Design-Expert Software. The final optimized EGCG-loaded nanohydrogels were evaluated for particle size, encapsulation efficiency, stability, and morphological and drug release studies. Comparative antioxidant and antibacterial potentials of EGCG-loaded nanohydrogels and EGCG were examined. EGCG-loaded nanohydrogels show more antioxidant and antibacterial potential at the same dose level as compared to the pure EGCG. Therefore, advanced nanoscale drug delivery systems with a reduced dose level and significant effectiveness over the conventional systems may increase their use in the near future for the betterment of healthcare applications.