MRI Extracellular Volume Fraction in Liver Fibrosis-A Comparison of Different Time Points and Blood Pool Measurements.

BACKGROUND: Extracellular volume (ECV) correlates with the degree of liver fibrosis. PURPOSE: To analyze the performance of liver MRI-based ECV evaluations with different blood pool measurements at different time points. STUDY TYPE: Prospective. SAMPLE: 73 consecutive patients (n = 31 females, mean age 56 years) with histopathology-proven liver fibrosis. FIELD STRENGTH/SEQUENCE: 3T acquisition within 90 days of biopsy, including shortened modified look-locker inversion recovery T1 mapping. ASSESSMENT: Polygonal regions of interest were manually drawn in the liver, aorta, vena cava, and in the main, left and right portal vein on four slices before and after Gd-DOTA administration at 5/10/15 minutes. ECV was calculated 1) on one single slice on portal bifurcation level, and 2) averaged over all four slices. STATISTICAL TESTS: Parameters were compared between patients with fibrosis grades F0-2 and F3-F4 with the Mann-Whitney U and fishers exact test. ROC analysis was used to assess the performance of the parameters to predict F3-4 fibrosis. A P-value <0.05 was considered statistically significant. RESULTS: ECV was significantly higher in F3-4 fibrosis (35.4% [33.1%-37.6%], 36.1% [34.2%-37.5%], and 37.0% [34.8%-39.2%] at 5/10/15 minutes) than in patients with F0-2 fibrosis (33.3% [30.8%-34.8%], 33.7% [31.6%-34.7%] and 34.9% [32.2%-36.0%]; AUC = 0.72-0.75). Blood pool T1 relaxation times in the aorta and vena cava were longer on the upper vs. lower slices at 5 minutes, but not at 10/15 minutes. AUC values were similar when measured on a single slice (AUC = 0.69-0.72) or based on blood pool measurements in the cava or portal vein (AUC = 0.63-0.67 and AUC = 0.65-0.70). DATA CONCLUSION: Liver ECV is significantly higher in F3-4 fibrosis compared to F0-2 fibrosis with blood pool measurements performed in the aorta, inferior vena cava, and portal vein at 5, 10, and 15 minutes. However, a smaller variability was observed for blood pool measurements between slices at 15 minutes. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

"Will I change nodule management recommendations if I change my CAD system?"-impact of volumetric deviation between different CAD systems on lesion management.

OBJECTIVES: To evaluate and compare the measurement accuracy of two different computer-aided diagnosis (CAD) systems regarding artificial pulmonary nodules and assess the clinical impact of volumetric inaccuracies in a phantom study. METHODS: In this phantom study, 59 different phantom arrangements with 326 artificial nodules (178 solid, 148 ground-glass) were scanned at 80 kV, 100 kV, and 120 kV. Four different nodule diameters were used: 5 mm, 8 mm, 10 mm, and 12 mm. Scans were analyzed by a deep-learning (DL)-based CAD and a standard CAD system. Relative volumetric errors (RVE) of each system vs. ground truth and the relative volume difference (RVD) DL-based vs. standard CAD were calculated. The Bland-Altman method was used to define the limits of agreement (LOA). The hypothetical impact on LungRADS classification was assessed for both systems. RESULTS: There was no difference between the three voltage groups regarding nodule volumetry. Regarding the solid nodules, the RVE of the 5-mm-, 8-mm-, 10-mm-, and 12-mm-size groups for the DL CAD/standard CAD were 12.2/2.8%, 1.3/ - 2.8%, - 3.6/1.5%, and - 12.2/ - 0.3%, respectively. The corresponding values for the ground-glass nodules (GGN) were 25.6%/81.0%, 9.0%/28.0%, 7.6/20.6%, and 6.8/21.2%. The mean RVD for solid nodules/GGN was 1.3/ - 15.2%. Regarding the LungRADS classification, 88.5% and 79.8% of all solid nodules were correctly assigned by the DL CAD and the standard CAD, respectively. 14.9% of the nodules were assigned differently between the systems. CONCLUSIONS: Patient management may be affected by the volumetric inaccuracy of the CAD systems and hence demands supervision and/or manual correction by a radiologist. KEY POINTS: • The DL-based CAD system was more accurate in the volumetry of GGN and less accurate regarding solid nodules than the standard CAD system. • Nodule size and attenuation have an effect on the measurement accuracy of both systems; tube voltage has no effect on measurement accuracy. • Measurement inaccuracies of CAD systems can have an impact on patient management, which demands supervision by radiologists.

Quantitative CT analysis of lung parenchyma to improve malignancy risk estimation in incidental pulmonary nodules.

OBJECTIVES: To assess the value of quantitative computed tomography (QCT) of the whole lung and nodule-bearing lobe regarding pulmonary nodule malignancy risk estimation. METHODS: A total of 251 subjects (median [IQR] age, 65 (57-73) years; 37% females) with pulmonary nodules on non-enhanced thin-section CT were retrospectively included. Twenty percent of the nodules were malignant, the remainder benign either histologically or at least 1-year follow-up. CT scans were subjected to in-house software, computing parameters such as mean lung density (MLD) or peripheral emphysema index (pEI). QCT variable selection was performed using logistic regression; selected variables were integrated into the Mayo Clinic and the parsimonious Brock Model. RESULTS: Whole-lung analysis revealed differences between benign vs. malignant nodule groups in several parameters, e.g. the MLD (-766 vs. -790 HU) or the pEI (40.1 vs. 44.7 %). The proposed QCT model had an area-under-the-curve (AUC) of 0.69 (95%-CI, 0.62-0.76) based on all available data. After integrating MLD and pEI into the Mayo Clinic and Brock Model, the AUC of both clinical models improved (AUC, 0.91 to 0.93 and 0.88 to 0.91, respectively). The lobe-specific analysis revealed that the nodule-bearing lobes had less emphysema than the rest of the lung regarding benign (EI, 0.5 vs. 0.7 %; p < 0.001) and malignant nodules (EI, 1.2 vs. 1.7 %; p = 0.001). CONCLUSIONS: Nodules in subjects with higher whole-lung metrics of emphysema and less fibrosis are more likely to be malignant; hereby the nodule-bearing lobes have less emphysema. QCT variables could improve the risk assessment of incidental pulmonary nodules. KEY POINTS: • Nodules in subjects with higher whole-lung metrics of emphysema and less fibrosis are more likely to be malignant. • The nodule-bearing lobes have less emphysema compared to the rest of the lung. • QCT variables could improve the risk assessment of incidental pulmonary nodules.

Influence of CT dose reduction on AI-driven malignancy estimation of incidental pulmonary nodules.

OBJECTIVES: The purpose of this study was to determine the influence of dose reduction on a commercially available lung cancer prediction convolutional neuronal network (LCP-CNN). METHODS: CT scans from a cohort provided by the local lung cancer center (n = 218) with confirmed pulmonary malignancies and their corresponding reduced dose simulations (25% and 5% dose) were subjected to the LCP-CNN. The resulting LCP scores (scale 1-10, increasing malignancy risk) and the proportion of correctly classified nodules were compared. The cohort was divided into a low-, medium-, and high-risk group based on the respective LCP scores; shifts between the groups were studied to evaluate the potential impact on nodule management. Two different malignancy risk score thresholds were analyzed: a higher threshold of ≥ 9 ("rule-in" approach) and a lower threshold of > 4 ("rule-out" approach). RESULTS: In total, 169 patients with 196 nodules could be included (mean age ± SD, 64.5 ± 9.2 year; 49% females). Mean LCP scores for original, 25% and 5% dose levels were 8.5 ± 1.7, 8.4 ± 1.7 (p > 0.05 vs. original dose) and 8.2 ± 1.9 (p < 0.05 vs. original dose), respectively. The proportion of correctly classified nodules with the "rule-in" approach decreased with simulated dose reduction from 58.2 to 56.1% (p = 0.34) and to 52.0% for the respective dose levels (p = 0.01). For the "rule-out" approach the respective values were 95.9%, 96.4%, and 94.4% (p = 0.12). When reducing the original dose to 25%/5%, eight/twenty-two nodules shifted to a lower, five/seven nodules to a higher malignancy risk group. CONCLUSION: CT dose reduction may affect the analyzed LCP-CNN regarding the classification of pulmonary malignancies and potentially alter pulmonary nodule management. CLINICAL RELEVANCE STATEMENT: Utilization of a "rule-out" approach with a lower malignancy risk threshold prevents underestimation of the nodule malignancy risk for the analyzed software, especially in high-risk cohorts. KEY POINTS: • LCP-CNN may be affected by CT image parameters such as noise resulting from low-dose CT acquisitions. • CT dose reduction can alter pulmonary nodule management recommendations by affecting the outcome of the LCP-CNN. • Utilization of a lower malignancy risk threshold prevents underestimation of pulmonary malignancies in high-risk cohorts.

Pulmonary Recovery 12 Months after Non-Severe and Severe COVID-19: The Prospective Swiss COVID-19 Lung Study.

BACKGROUND: Lung function impairment persists in some patients for months after acute coronavirus disease 2019 (COVID-19). Long-term lung function, radiological features, and their association remain to be clarified. OBJECTIVES: We aimed to prospectively investigate lung function and radiological abnormalities over 12 months after severe and non-severe COVID-19. METHODS: 584 patients were included in the Swiss COVID-19 lung study. We assessed lung function at 3, 6, and 12 months after acute COVID-19 and compared chest computed tomography (CT) imaging to lung functional abnormalities. RESULTS: At 12 months, diffusion capacity for carbon monoxide (DLCOcorr) was lower after severe COVID-19 compared to non-severe COVID-19 (74.9% vs. 85.2% predicted, p < 0.001). Similarly, minimal oxygen saturation on 6-min walk test and total lung capacity were lower after severe COVID-19 (89.6% vs. 92.2%, p = 0.004, respectively, 88.2% vs. 95.1% predicted, p = 0.011). The difference for forced vital capacity (91.6% vs. 96.3% predicted, p = 0.082) was not statistically significant. Between 3 and 12 months, lung function improved in both groups and differences in DLCO between non-severe and severe COVID-19 patients decreased. In patients with chest CT scans at 12 months, we observed a correlation between radiological abnormalities and reduced lung function. While the overall extent of radiological abnormalities diminished over time, the frequency of mosaic attenuation and curvilinear patterns increased. CONCLUSIONS: In this prospective cohort study, patients who had severe COVID-19 had diminished lung function over the first year compared to those after non-severe COVID-19, albeit with a greater extent of recovery in the severe disease group.

MRI Shows Lung Perfusion Changes after Vaping and Smoking.

Background Evidence regarding short-term effects of electronic nicotine delivery systems (ENDS) and tobacco smoke on lung ventilation and perfusion is limited. Purpose To examine the immediate effect of ENDS exposure and tobacco smoke on lung ventilation and perfusion by functional MRI and lung function tests. Materials and Methods This prospective observational pilot study was conducted from November 2019 to September 2021 (substudy of randomized controlled trial NCT03589989). Included were 44 healthy adult participants (10 control participants, nine former tobacco smokers, 13 ENDS users, and 12 active tobacco smokers; mean age, 41 years ± 12 [SD]; 28 men) who underwent noncontrast-enhanced matrix pencil MRI and lung function tests before and immediately after the exposure to ENDS products or tobacco smoke. Baseline measurements were acquired after 2 hours of substance abstinence. Postexposure measurements were performed immediately after the exposure. MRI showed semiquantitative measured impairment of lung perfusion (RQ) and fractional ventilation (RFV) impairment as percentages of affected lung volume. Lung clearance index (LCI) was assessed by nitrogen multiple-breath washout to capture ventilation inhomogeneity and spirometry to assess airflow limitation. Absolute differences were calculated with paired Wilcoxon signed-rank test and differences between groups with unpaired Mann-Whitney test. Healthy control participants underwent two consecutive MRI measurements to assess MRI reproducibility. Results MRI was performed and lung function measurement was acquired in tobacco smokers and ENDS users before and after exposure. MRI showed a decrease of perfusion after exposure (RQ, 8.6% [IQR, 7.2%-10.0%] to 9.1% [IQR, 7.8%-10.7%]; P = .03) and no systematic change in RFV (P = .31) among tobacco smokers. Perfusion increased in participants who used ENDS after exposure (RQ, 9.7% [IQR, 7.1%-10.9%] to 9.0% [IQR, 6.9%-10.0%]; P = .01). RFV did not change (P = .38). Only in tobacco smokers was LCI elevated after smoking (P = .02). Spirometry indexes did not change in any participants. Conclusion MRI showed a decrease of lung perfusion after exposure to tobacco smoke and an increase of lung perfusion after use of electronic nicotine delivery systems. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kligerman in this issue.

Diagnostic validation of a deep learning nodule detection algorithm in low-dose chest CT: determination of optimized dose thresholds in a virtual screening scenario.

OBJECTIVES: This study was conducted to evaluate the effect of dose reduction on the performance of a deep learning (DL)-based computer-aided diagnosis (CAD) system regarding pulmonary nodule detection in a virtual screening scenario. METHODS: Sixty-eight anthropomorphic chest phantoms were equipped with 329 nodules (150 ground glass, 179 solid) with four sizes (5 mm, 8 mm, 10 mm, 12 mm) and scanned with nine tube voltage/current combinations. The examinations were analyzed by a commercially available DL-based CAD system. The results were compared by a comparison of proportions. Logistic regression was performed to evaluate the impact of tube voltage, tube current, nodule size, nodule density, and nodule location. RESULTS: The combination with the lowest effective dose (E) and unimpaired detection rate was 80 kV/50 mAs (sensitivity: 97.9%, mean false-positive rate (FPR): 1.9, mean CTDIvol: 1.2 ± 0.4 mGy, mean E: 0.66 mSv). Logistic regression revealed that tube voltage and current had the greatest impact on the detection rate, while nodule size and density had no significant influence. CONCLUSIONS: The optimal tube voltage/current combination proposed in this study (80 kV/50 mAs) is comparable to the proposed combinations in similar studies, which mostly dealt with conventional CAD software. Modification of tube voltage and tube current has a significant impact on the performance of DL-based CAD software in pulmonary nodule detection regardless of their size and composition. KEY POINTS: • Modification of tube voltage and tube current has a significant impact on the performance of deep learning-based CAD software. • Nodule size and composition have no significant impact on the software's performance. • The optimal tube voltage/current combination for the examined software is 80 kV/50 mAs.

Avoiding the Intercostal Arteries in Percutaneous Thoracic Interventions.

The purpose of this study was to define relevant intercostal artery (ICA) anatomy potentially impacting the safety of thoracic percutaneous interventional procedures. An ICA abutting the upper rib and running in the subcostal groove was defined as the lowest risk zone for interventions requiring a supracostal needle puncture. A theoretical high-risk zone was defined by the ICA coursing in the lower half of the intercostal space (ICS), and a theoretical moderate-risk zone was defined by the ICA coursing below the subcostal groove but in the upper half of the ICS. Arterial phase computed tomography data from 250 patients were analyzed, revealing demographic variability, with high-risk zones extending more laterally with advancing age and with more cranial ribs. Overall, within the 97.5th percentile, an ICS puncture >7-cm lateral to the spinous process incurs moderate risk and >10-cm lateral incurs the lowest risk.

Knee Diameter and Cross-Sectional Area as Biomarkers for Cartilage Knee Degeneration on Magnetic Resonance Images.

Background and Objectives: Osteoarthritis (OA) of the knee is a degenerative disorder characterized by damage to the joint cartilage, pain, swelling, and walking disability. The purpose of this study was to assess whether demographic and radiologic parameters (knee diameters and knee cross-sectional area from magnetic resonance (MR) images) could be used as surrogate biomarkers for the prediction of OA. Materials and Methods: The knee diameters and cross-sectional areas of 481 patients were measured on knee MR images, and the corresponding demographic parameters were extracted from the patients' clinical records. The images were graded based on the modified Outerbridge arthroscopic classification that was used as ground truth. Receiver-operating characteristic (ROC) analysis was performed on the collected data. Results: ROC analysis established that age was the most accurate predictor of severe knee cartilage degeneration (corresponding to Outerbridge grades 3 and 4) with an area under the curve (AUC) of the specificity-sensitivity plot of 0.865 ± 0.02. An age over 41 years was associated with a sensitivity and specificity for severe degeneration of 82.8% (CI: 77.5-87.3%), and 76.4% (CI: 70.4-81.6%), respectively. The second-best degeneration predictor was the normalized knee cross-sectional area, with an AUC of 0.767 ± 0.04), followed by BMI (AUC = 0.739 ± 0.02), and normalized knee maximal diameter (AUC = 0.724 ± 0.05), meaning that knee degeneration increases with increasing knee diameter. Conclusions: Age is the best predictor of knee damage progression in OA and can be used as surrogate marker for knee degeneration. Knee diameters and cross-sectional area also correlate with the extent of cartilage lesions. Though less-accurate predictors of damage progression than age, they have predictive value and are therefore easily available surrogate markers of OA that can be used also by general practitioners and orthopedic surgeons.

Pulmonary function and radiological features 4 months after COVID-19: first results from the national prospective observational Swiss COVID-19 lung study.

BACKGROUND: The infectious coronavirus disease 2019 (COVID-19) pandemic is an ongoing global healthcare challenge. Up to one-third of hospitalised patients develop severe pulmonary complications and acute respiratory distress syndrome. Pulmonary outcomes following COVID-19 are unknown. METHODS: The Swiss COVID-19 lung study is a multicentre prospective cohort investigating pulmonary sequelae of COVID-19. We report on initial follow-up 4 months after mild/moderate or severe/critical COVID-19 according to the World Health Organization severity classification. RESULTS: 113 COVID-19 survivors were included (mild/moderate n=47, severe/critical n=66). We confirmed several comorbidities as risk factors for severe/critical disease. Severe/critical disease was associated with impaired pulmonary function, i.e. diffusing capacity of the lung for carbon monoxide (D LCO) % predicted, reduced 6-min walk distance (6MWD) and exercise-induced oxygen desaturation. After adjustment for potential confounding by age, sex and body mass index (BMI), patients after severe/critical COVID-19 had a D LCO 20.9% pred (95% CI 12.4-29.4% pred, p=0.01) lower at follow-up. D LCO % pred was the strongest independent factor associated with previous severe/critical disease when age, sex, BMI, 6MWD and minimal peripheral oxygen saturation at exercise were included in the multivariable model (adjusted odds ratio per 10% predicted 0.59, 95% CI 0. 37-0.87; p=0.01). Mosaic hypoattenuation on chest computed tomography at follow-up was significantly associated with previous severe/critical COVID-19 including adjustment for age and sex (adjusted OR 11.7, 95% CI 1.7-239; p=0.03). CONCLUSIONS: 4 months after severe acute respiratory syndrome coronavirus 2 infection, severe/critical COVID-19 was associated with significant functional and radiological abnormalities, potentially due to small-airway and lung parenchymal disease. A systematic follow-up for survivors needs to be evaluated to optimise care for patients recovering from COVID-19.

Performance of a diagnostic algorithm for fibrotic hypersensitivity pneumonitis. A case-control study.

BACKGROUND: The differential diagnosis fibrotic hypersensitivity pneumonitis (HP) versus idiopathic pulmonary fibrosis (IPF) is important but challenging. Recent diagnostic guidelines for HP emphasize including multidisciplinary discussion (MDD) in the diagnostic process, however MDD is not comprehensively available. We aimed to establish the diagnostic accuracy and prognostic validity of a previously proposed HP diagnostic algorithm that foregoes MDD. METHODS: We tested the algorithm in patients with an MDD diagnosis of fibrotic HP or IPF (case control study) and determined diagnostic test performances for diagnostic confidences of ≥ 90% and ≥ 70%. Prognostic validity was established using Cox proportional hazards models. RESULTS: Thirty-one patients with fibrotic HP and 50 IPF patients were included. The algorithm-derived ≥ 90% confidence level for HP had high specificity (0.94, 95% confidence interval [CI] 0.83-0.99), but low sensitivity (0.35 [95%CI 0.19-0.55], J-index 0.29). Test performance was improved for the ≥ 70% confidence level (J-index 0.64) with a specificity of 0.90 (95%CI 0.78-0.97), and a sensitivity of 0.74 (95%CI 0.55-0.88). MDD fibrotic HP diagnosis was strongly associated with lower risk of death (adjusted hazard ratio [HR] 0.10 [0.01-0.92], p = 0.04), whereas the algorithm-derived ≥ 70% and ≥ 90% confidence diagnoses were not significantly associated with survival (adjusted HR 0.37 [0.07-1.80], p = 0.22, and adjusted HR 0.41 [0.05-3.25], p = 0.39, respectively). CONCLUSION: The algorithm-derived ≥ 70% diagnostic confidence had satisfactory test performance for MDD-HP diagnosis, with insufficient sensitivity for ≥ 90% confidence. The lowest risk of death in the MDD-derived HP diagnosis validates the reference standard and suggests that a diagnostic algorithm not including MDD, might not replace the latter.

A comprehensive review of imaging findings in COVID-19 - status in early 2021.

Medical imaging methods are assuming a greater role in the workup of patients with COVID-19, mainly in relation to the primary manifestation of pulmonary disease and the tissue distribution of the angiotensin-converting-enzyme 2 (ACE 2) receptor. However, the field is so new that no consensus view has emerged guiding clinical decisions to employ imaging procedures such as radiography, computer tomography (CT), positron emission tomography (PET), and magnetic resonance imaging, and in what measure the risk of exposure of staff to possible infection could be justified by the knowledge gained. The insensitivity of current RT-PCR methods for positive diagnosis is part of the rationale for resorting to imaging procedures. While CT is more sensitive than genetic testing in hospitalized patients, positive findings of ground glass opacities depend on the disease stage. There is sparse reporting on PET/CT with [18F]-FDG in COVID-19, but available results are congruent with the earlier literature on viral pneumonias. There is a high incidence of cerebral findings in COVID-19, and likewise evidence of gastrointestinal involvement. Artificial intelligence, notably machine learning is emerging as an effective method for diagnostic image analysis, with performance in the discriminative diagnosis of diagnosis of COVID-19 pneumonia comparable to that of human practitioners.

T1 mapping of the liver and the spleen in patients with liver fibrosis-does normalization to the blood pool increase the predictive value?

PURPOSE: To analyze whether the T1 relaxation time of the liver is a good predictor of significant liver fibrosis and whether normalization to the blood pool improves the predictive value. METHODS: This prospective study was conducted between 03/2016 and 02/2018. One hundred seventy-three patients underwent multiparametric liver MRI at 3 T. The T1 relaxation time was measured in the liver and the spleen, in the aorta, the portal vein, and the inferior vena cava (IVC). T1 relaxation times with and without normalization to the blood pool were compared between patients with (n = 26) and without (n = 141) significant liver fibrosis, based on a cutoff value of 3.5 kPa in MRE as the noninvasive reference standard. For statistics, Student's t test, receiver operating characteristic (ROC) curve analysis, and Pearson's correlation were used. RESULTS: The T1 relaxation time of the liver was significantly longer in patients with liver fibrosis, both with and without blood pool normalization (p < 0.001). T1 relaxation time of the liver allowed prediction of significant liver fibrosis (AUC = 0.88), while normalization to the IVC resulted in a slightly lower performance (AUC = 0.82). The lowest performance was achieved when the T1 relaxation times of the liver were normalized to the aorta (AUC = 0.66) and to the portal vein (AUC = 0.62). The T1 relaxation time of the spleen detected significant liver fibrosis with an AUC of 0.68, and 0.51-0.64 with normalization to the blood pool. CONCLUSION: The T1 relaxation time of the liver is a good predictor of significant liver fibrosis. However, normalization of the blood pool did not improve the predictive value. KEY POINTS: • The T1 relaxation time of the liver is a good predictor of significant liver fibrosis. • Normalization to the blood pool did not improve the predictive value of T1 mapping. • If the blood pool normalization was weighted 30% to the aorta and 70% to the portal vein, the performance was better than normalization to the aorta alone but still lower than normalization to the IVC.

Minimum perceivable size difference: how well can radiologists visually detect a change in lung nodule size from CT images?

OBJECTIVE: The purpose of this study was to determine how well radiologists could visually detect a change in lung nodule size on the basis of visual image perception alone. SUBJECTS AND METHODS: Under IRB approval, 109 standard chest CT image series were anonymized and exported from PACS. Nine hundred forty virtual lung nodule pairs (six baseline diameters, six relative volume differences, two nodule types-solid and ground glass-and 14 repeats) were digitally inserted into the chest CT image series (same location, different sizes between the pair). These digitally altered CT image pairs were shown to nine radiologists who were tasked to visually determine which image contained the larger nodule using a two-alternative forced-choice perception experimental design. These data were statistically analyzed using a generalized linear mixed effects model to determine how accurately the radiologists were able to correctly identify the larger nodule. RESULTS: Nominal baseline nodule diameter, relative volume difference, and nodule type were found to be statistically significant factors (p < 0.001) in influencing the radiologists' accuracy. For solid (ground-glass) nodules, the baseline diameter needed to be at least 6.3 mm (13.2 mm) to be able to visually detect a 25% change in volume with 95 ± 1.4% accuracy. Accuracy was lowest for the nodules with the smallest baseline diameters and smallest relative volume differences. Additionally, accuracy was lower for ground-glass nodules compared to solid nodules. CONCLUSIONS: Factors that impacted visual size assessment were baseline nodule diameter, relative volume difference, and solid versus non-solid nodule type, with larger and more solid lesions offering a more precise assessment of change. KEY POINTS: • For solid nodules, radiologists could visually detect a 25% change in volume with 95% accuracy for nodules having greater than 6.3-mm baseline diameter. • For ground-glass nodules, radiologists could visually detect a 25% change in volume with 95% accuracy for nodules having greater than 13.2-mm baseline diameter. • Accuracy in detecting a change in nodule size began to stabilize around 90-100% for nodules with larger baseline diameters (> 8 mm for solid nodules, > 12 mm for ground-glass nodules) and larger relative volume differences (>15% for solid nodules, > 25% for ground-glass nodules).

Preparation and Tracking of Oblate Core-Shell Polymethyl-Methacrylate Ellipsoids.

Although single-particle level studies on prolate ellipsoidal colloids are relatively abundant, similar studies on oblate ellipsoids are rare because suitable model systems are scarcely available. Here, we present the preparation of monodisperse hard core-shell oblate ellipsoids that can be imaged and tracked in 3D with confocal laser scanning microscopy. Using a thermomechanical squeezing method, we transform spherical core-shell polymethyl-methacrylate (PMMA) particles into oblate ellipsoids. We show how the shape polydispersity as well as the aspect ratio of the obtained oblate ellipsoids can be controlled. In addition, we discuss how the core-shell geometry limits the range of aspect ratios because of the different viscoelastic properties of the cross-linked PMMA core and linear PMMA shell. We further demonstrate imaging of the core-shell oblate dispersions on a single-particle level in real space and time and the tracking of position and orientation using our recently developed tracking algorithm for anisotropic core-shell colloids. Our results thus provide the tools for the future investigation of the behavior of oblate ellipsoids, especially in dense suspensions.

Double modulation SRS and SREF microscopy: signal contributions under pre-resonance conditions.

Pre-electronic resonance enhancement can increase the sensitivity of non-linear Raman microscopy to the single molecule detection limit. A major problem, however, is the generation of background signal due to unwanted linear and non-linear photophysical processes. In this work, we report the setup of a novel detection scheme for stimulated Raman scattering microspectroscopy based on the simultaneous modulation of pump and Stokes beam. Apart from allowing the parallel detection of stimulated Raman loss and gain (SRL and SRG), the setup gives access to the quantitative analysis of different sources of background signal. We report spectrally and temporally resolved measurements on three exemplary rhodamine dyes and derive the contributions of two-photon absorption and stimulated emission to their SRL, SRG, and stimulated Raman excited fluorescence signals. These results give guidelines for the further improvement of the sensitivity of non-linear Raman micospectroscopy under electronic pre-resonance conditions.

Yb fiber based laser source for tunable, narrow bandwidth picosecond pulses in the visible.

We present a simple Yb fiber pumped source for narrow bandwidth picosecond pulses which are tunable in the visible spectral region. This emission is obtained by frequency doubling of a soliton generated in a photonic crystal fiber. The system is attractive for different types of nonlinear optical microscopy and can easily be adapted to meet different experimental prerequisites. As an example, we demonstrate coherent anti-Stokes Raman scattering microscopy using the laser source described.

Multireader Determination of Clinically Significant Obstruction Using Hyperpolarized 129Xe-Ventilation MRI.

OBJECTIVE: The objective of our study was to identify the magnitude and distribution of ventilation defect scores (VDSs) derived from hyperpolarized (HP) 129Xe-MRI associated with clinically relevant airway obstruction. MATERIALS AND METHODS: From 2012 to 2015, 76 subjects underwent HP 129Xe-MRI (48 healthy volunteers [mean age ± SD, 54 ± 17 years]; 20 patients with asthma [mean age, 44 ± 20 years]; eight patients with chronic obstructive pulmonary disease [mean age, 67 ± 5 years]). All subjects underwent spirometry 1 day before MRI to establish the presence of airway obstruction (forced expiratory volume in 1 second-to-forced vital capacity ratio [FEV1/FVC] < 70%). Five blinded readers assessed the degree of ventilation impairment and assigned a VDS (range, 0-100%). Interreader agreement was assessed using the Fleiss kappa statistic. Using FEV1/FVC as the reference standard, the optimum VDS threshold for the detection of airway obstruction was estimated using ROC curve analysis with 10-fold cross-validation. RESULTS: Compared with the VDSs in healthy subjects, VDSs in patients with airway obstruction were significantly higher (p < 0.0001) and significantly correlated with disease severity (r = 0.66, p < 0.0001). Ventilation defects in subjects with airway obstruction did not show a location-specific pattern (p = 0.158); however, defects in healthy control subjects were more prevalent in the upper lungs (p = 0.014). ROC curve analysis yielded an optimal threshold of 12.4% ± 6.1% (mean ± SD) for clinically significant VDS. Interreader agreement for 129Xe-MRI was substantial (κ = 0.71). CONCLUSION: This multireader study of a diverse cohort of patients and control subjects suggests a 129Xe-ventilation MRI VDS of 12.4% or greater represents clinically significant obstruction.

Using hyperpolarized 129Xe MRI to quantify regional gas transfer in idiopathic pulmonary fibrosis.

BACKGROUND: Assessing functional impairment, therapeutic response and disease progression in patients with idiopathic pulmonary fibrosis (IPF) continues to be challenging. Hyperpolarized 129Xe MRI can address this gap through its unique capability to image gas transfer three-dimensionally from airspaces to interstitial barrier tissues to red blood cells (RBCs). This must be validated by testing the degree to which it correlates with pulmonary function tests (PFTs) and CT scores, and its spatial distribution reflects known physiology and patterns of disease. METHODS: 13 healthy individuals (33.6±15.7 years) and 12 patients with IPF (66.0±6.4 years) underwent 129Xe MRI to generate three-dimensional quantitative maps depicting the 129Xe ventilation distribution, its uptake in interstitial barrier tissues and its transfer to RBCs. For each map, mean values were correlated with PFTs and CT fibrosis scores, and their patterns were tested for the ability to depict functional gravitational gradients in healthy lung and to detect the known basal and peripheral predominance of disease in IPF. RESULTS: 129Xe MRI depicted functional impairment in patients with IPF, whose mean barrier uptake increased by 188% compared with the healthy reference population. 129Xe MRI metrics correlated poorly and insignificantly with CT fibrosis scores but strongly with PFTs. Barrier uptake and RBC transfer both correlated significantly with diffusing capacity of the lungs for carbon monoxide (r=-0.75, p<0.01 and r=0.72, p<0.01), while their ratio (RBC/barrier) correlated most strongly (r=0.94, p<0.01). RBC transfer exhibited significant anterior-posterior gravitational gradients in healthy volunteers, but not in IPF, where it was significantly impaired in the basal (p=0.02) and subpleural (p<0.01) lung. CONCLUSIONS: Hyperpolarized129Xe MRI is a rapid and well-tolerated exam that provides region-specific quantification of interstitial barrier thickness and RBC transfer efficiency. With further development, it could become a robust tool for measuring disease progression and therapeutic response in patients with IPF, sensitively and non-invasively.