Lung CT stabilization with high-frequency non-invasive ventilation (HF-NIV) and breath-hold (BH) in lung nodule assessment by PET/CT.

PURPOSE: To evaluate the effect of lung stabilization using high-frequency non-invasive ventilation (HF-NIV) and breath-hold (BH) techniques on lung nodule detection and texture assessment in PET/CT compared to a free-breathing (FB) standard lung CT acquisition in PET/CT. MATERIALS AND METHODS: Six patients aged 65 ± 7 years, addressed for initial assessment of at least one suspicious lung nodule with 18F-FDG PET/CT, underwent three consecutive lung PET/CT acquisitions with FB, HF-NIV and BH. Lung nodules were assessed on all three CT acquisitions of the PET/CT and characterized for any size, volume and solid/sub-solid nature. RESULTS: BH detected a significantly higher number of nodules (n = 422) compared to HF-NIV (n = 368) and FB (n = 191) (p < 0.001). The mean nodule size (mm) was 2.4 ± 2.1, 2.6 ± 1.9 and 3.2 ± 2.4 in BH, HF-NIV and FB, respectively, for long axis and 1.5 ± 1.3, 1.6 ± 1.2 and 2.1 ± 1.7 in BH, HF-NIV and FB, respectively, for short axis. Long- and short-axis diameters were significantly different between BH and FB (p < 0.001) and between HF-NIV and FB (p < 0.001 and p = 0.008), but not between BH and HF-NIV. A trend for higher volume was shown in FB compared to BH (p = 0.055) and HF-NIV (p = 0.068) without significant difference between BH and HF-NIV (p = 1). We found a significant difference in detectability of sub-solid nodules between the three acquisitions, with BH showing a higher number of sub-solid nodules (n = 128) compared to HF-NIV (n = 72) and FB (n = 44) (p = 0.002). CONCLUSION: We observed a higher detection rate of pulmonary nodules on CT under BH or HF-NIV conditions applied to PET/CT than with FB. BH and HF-NIV demonstrated comparable texture assessment and performed better than FB in assessing size and volume. BH showed a better performance for detecting sub-solid nodules compared to HF-NIV and FB. The addition of BH or HF-NIV to PET/CT can help improve the detection and texture characterization of lung nodules by CT, therefore improving the accuracy of oncological lung disease assessment. The ease of use of BH and its added value should prompt its use in routine practice.

Comparison Between Magnetic Resonance Imaging and Computed Tomography in the Detection and Volumetric Assessment of Lung Nodules: A Prospective Study.

Rationale and Objectives: Computed tomography (CT) lung nodule assessment is routinely performed and appears very promising for lung cancer screening. However, the radiation exposure through time remains a concern. With the overall goal of an optimal management of indeterminate lung nodules, the objective of this prospective study was therefore to evaluate the potential of optimized ultra-short echo time (UTE) MRI for lung nodule detection and volumetric assessment. Materials and Methods: Eight (54.9 ± 13.2 years) patients with at least 1 non-calcified nodule ≥4 mm were included. UTE under high-frequency non-invasive ventilation (UTE-HF-NIV) and in free-breathing at tidal volume (UTE-FB) were investigated along with volumetric interpolated breath-hold examination at full inspiration (VIBE-BH). Three experienced readers assessed the detection rate of nodules ≥4 mm and ≥6 mm, and reported their location, 2D-measurements and solid/subsolid nature. Volumes were measured by two experienced readers. Subsequently, two readers assessed the detection and volume measurements of lung nodules ≥4mm in gold-standard CT images with soft and lung kernel reconstructions. Volumetry was performed with lesion management software (Carestream, Rochester, New York, USA). Results: UTE-HF-NIV provided the highest detection rate for nodules ≥4 mm (n = 66) and ≥6 mm (n = 32) (35 and 50%, respectively). No dependencies were found between nodule detection and their location in the lung with UTE-HF-NIV (p > 0.4), such a dependency was observed for two readers with VIBE-BH (p = 0.002 and 0.03). Dependencies between the nodule's detection and their size were noticed among readers and techniques (p < 0.02). When comparing nodule volume measurements, an excellent concordance was observed between CT and UTE-HF-NIV, with an overestimation of 13.2% by UTE-HF-NIV, <25%-threshold used for nodule's growth, conversely to VIBE-BH that overestimated the nodule volume by 28.8%. Conclusion: UTE-HF-NIV is not ready to replace low-dose CT for lung nodule detection, but could be used for follow-up studies, alternating with CT, based on its volumetric accuracy.

Compressed sensing with signal averaging for improved sensitivity and motion artifact reduction in fluorine-19 MRI.

Fluorine-19 (19 F) MRI of injected perfluorocarbon emulsions (PFCs) allows for the non-invasive quantification of inflammation and cell tracking, but suffers from a low signal-to-noise ratio and extended scan time. To address this limitation, we tested the hypotheses that a 19 F MRI pulse sequence that combines a specific undersampling regime with signal averaging has both increased sensitivity and robustness against motion artifacts compared with a non-averaged fully sampled pulse sequence, when both datasets are reconstructed with compressed sensing. As a proof of principle, numerical simulations and phantom experiments were performed on selected variable ranges to characterize the point spread function of undersampling patterns, as well as the vulnerability to noise of undersampling and reconstruction parameters with paired numbers of x signal averages and acceleration factor x (NAx-AFx). The numerical simulations demonstrated that a probability density function that uses 25% of the samples to fully sample the k-space central area allowed for an optimal balance between limited blurring and artifact incoherence. At all investigated noise levels, the Dice similarity coefficient (DSC) strongly depended on the regularization parameters and acceleration factor. In phantoms, the motion robustness of an NA8-AF8 undersampling pattern versus NA1-AF1 was evaluated with simulated and real motion patterns. Differences were assessed with the DSC, which was consistently higher for the NA8-AF8 compared with the NA1-AF1 strategy, for both simulated and real cyclic motion patterns (P < 0.001). Both strategies were validated in vivo in mice (n = 2) injected with perfluoropolyether. Here, the images displayed a sharper delineation of the liver with the NA8-AF8 strategy than with the NA1-AF1 strategy. In conclusion, we validated the hypotheses that in 19 F MRI the combination of undersampling and averaging improves both the sensitivity and the robustness against motion artifacts.

Lung MRI assessment with high-frequency noninvasive ventilation at 3 T.

PURPOSE: To investigate three MR pulse sequences under high-frequency noninvasive ventilation (HF-NIV) at 3 T and determine which one is better-suited to visualize the lung parenchyma. METHODS: A 3D ultra-short echo time stack-of spirals Volumetric Interpolated Breath-hold Examination (UTE Spiral VIBE), without and with prospective gating, and a 3D double-echo UTE sequence with spiral phyllotaxis trajectory (3D radial UTE) were performed at 3 T in ten healthy volunteers under HF-NIV. Three experienced radiologists evaluated visibility and sharpness of normal anatomical structures, artifacts assessment, and signal and contrast ratio computation. The median of the three readers'scores was used for comparison, p < .05 was considered statistically significant. Incidental findings were recorded and reported. RESULTS: The 3D radial UTE resulted in less artifacts than the non-gated and gated UTE Spiral VIBE in inferior (score 3D radial UTE = 3, slight artifact without blurring vs. score UTE Spiral VIBE non-gated and gated = 2, moderate artifact with blurring of anatomical structure, p = .018 and p = .047, respectively) and superior lung regions (score 3D radial UTE = 3, vs. score UTE Spiral VIBE non-gated = 2.5, p = .48 and score UTE Spiral VIBE gated = 1, severe artifact with no normal structure recognizable, p = .014), and higher signal and contrast ratios (p = .002, p = .093). UTE Spiral VIBE sequences provided higher peripheral vasculature visibility than the 3D radial UTE (94.4% vs 80.6%, respectively, p < .001). The HF-NIV was well tolerated by healthy volunteers who reported on average minor discomfort. In three volunteers, 12 of 18 nodules confirmed with low-dose CT were identified with MRI (average size 2.6 ±â€¯1.2 mm). CONCLUSION: The 3D radial UTE provided higher image quality than the UTE Spiral VIBE. Nevertheless, a better nodule assessment was noticed with the UTE Spiral VIBE that might be due to better peripheral vasculature visibility, and requires confirmation in a larger cohort.

A characterization of ABL-101 as a potential tracer for clinical fluorine-19 MRI.

The two main challenges that prevent the translation of fluorine-19 (19 F) MRI for inflammation monitoring or cell tracking into clinical practice are (i) the relatively low signal-to-noise ratio generated by the injected perfluorocarbon (PFC), which necessitates long scan times, and (ii) the need for regulatory approval and a high biocompatibility of PFCs that are also suitable for MRI. ABL-101, an emulsion of perfluoro(t-butylcyclohexane), is a third-generation PFC that is already used in clinical trials, but has not yet been used for 19 F MRI. The objective of this study was therefore to assess the performance of ABL-101 as a 19 F MRI tracer. At magnetic field strengths of 3, 9.4 and 14.1 T, the CF3 groups of ABL-101 generated a large well-separated singlet with T2 /T1 ratios of >0.27, >0.14 and > 0.05, respectively. All relaxation times decreased with the increase in magnetic field strength. The detection limit of ABL-101 in a 0.25 mm3 voxel at 3 T, 37°C and with a 3-minute acquisition time was 7.21mM. After intravenous injection, the clearance half-lives of the ABL-101 19 F MR signal in mouse (n = 3) spleen and liver were 6.85 ± 0.45 and 3.20 ± 0.35 days, respectively. These results demonstrate that ABL-101 has 19 F MR characteristics that are similar to those of PFCs developed specifically for MRI, while it has clearance half-lives similar to PFCs that have previously been used in large doses in non-MRI clinical trials. Overall, ABL-101 is thus a very promising candidate tracer for future clinical trials that use 19 F MRI for cell tracking or the monitoring of inflammation.

Towards Quantification of Inflammation in Atherosclerotic Plaque in the Clinic - Characterization and Optimization of Fluorine-19 MRI in Mice at 3 T.

Fluorine-19 (19F) magnetic resonance imaging (MRI) of injected perfluorocarbons (PFCs) can be used for the quantification and monitoring of inflammation in diseases such as atherosclerosis. To advance the translation of this technique to the clinical setting, we aimed to 1) demonstrate the feasibility of quantitative 19F MRI in small inflammation foci on a clinical scanner, and 2) to characterize the PFC-incorporating leukocyte populations and plaques. To this end, thirteen atherosclerotic apolipoprotein-E-knockout mice received 2 × 200 µL PFC, and were scanned on a 3 T clinical MR system. 19F MR signal was detected in the aortic arch and its branches in all mice, with a signal-to-noise ratio of 11.1 (interquartile range IQR = 9.5-13.1) and a PFC concentration of 1.15 mM (IQR = 0.79-1.28). Imaging flow cytometry was used on another ten animals and indicated that PFC-labeled leukocytes in the aortic arch and it branches were mainly dendritic cells, macrophages and neutrophils (ratio 9:1:1). Finally, immunohistochemistry analysis confirmed the presence of those cells in the plaques. We thus successfully used 19F MRI for the noninvasive quantification of PFC in atherosclerotic plaque in mice on a clinical scanner, demonstrating the feasibility of detecting very small inflammation foci at 3 T, and advancing the translation of 19F MRI to the human setting.

Accelerated and high-resolution cardiac T2 mapping through peripheral k-space sharing.

PURPOSE: To develop high-spatial-resolution cardiac T2 mapping that allows for a reduced acquisition time while maintaining its precision. We implemented and optimized a new golden-angle radial T2 mapping technique named SKRATCH (Shared k-space Radial T2 Characterization of the Heart) that shares k-space peripheries of T2 -weighted images while preserving their contrasts. METHODS: Six SKRATCH variants (gradient-recalled echo and balanced SSFP, free-breathing and breath-held, with and without a saturation preparation) were implemented, and their precision was compared with a navigator-gated reference technique in phantoms and 22 healthy volunteers at 3 T. The optimal breath-held SKRATCH technique was applied in a small cohort of patients with subacute myocardial infarction. RESULTS: The faster free-breathing SKRATCH technique reduced the acquisition time by 52.4%, while maintaining the precision and spatial resolution of the reference technique. Similarly, the most precise and robust breath-held SKRATCH technique demonstrated homogenous T2 values that did not significantly differ from the navigator-gated reference (T2 = 39.9 ± 3.4 ms versus 39.5 ± 3.4 ms, P > .20, respectively). All infarct patients demonstrated a large T2 elevation in the ischemic regions of the myocardium. CONCLUSION: The optimized SKRATCH technique enabled the accelerated acquisition of high-spatial-resolution T2 maps, was validated in healthy adult volunteers, and was successfully applied to a small initial group of patients.

Chemical shift encoding (CSE) for sensitive fluorine-19 MRI of perfluorocarbons with complex spectra.

PURPOSE: To implement a fluorine-19 (19 F) chemical shift encoding (CSE) approach for the sensitive imaging of molecules with multi-resonance spectra to remove their chemical shift displacement (CSD) artifacts, and to characterize its sensitivity versus established pulse sequences. METHODS: The feasibility of CSE spoiled gradient echo (GRE) and balanced steady-state free precession (bSSFP) was first demonstrated in a phantom study. The dependence of the sensitivity of CSE-bSSFP on several pulse sequence parameters was then established, after which the occurrence of out-of-plane excitation was assessed for 2D and 3D techniques. Next, the sensitivity (in mm-3 s-0.5 ) of both CSE techniques was compared to bSSFP ultrashort echo time (bSSFP-UTE) imaging and multi-chemical-shift-selective turbo spin echo (MCSS-TSE) in a second phantom study. Finally, the sensitivity of the CSE-bSSFP, bSSFP-UTE, and MCSS-TSE pulse sequences was compared in a preliminary in vivo mouse study. RESULTS: Both CSE approaches were successfully implemented and resulted in negligible residual CSD artifacts, while large-volume 3D acquisitions should be considered to reduce problems related to out-of-plane excitation. CSE-bSSFP was shown to have a higher sensitivity than the bSSFP-UTE and MCSS-TSE pulse sequences (15.8 ± 1.3 vs. 11.7 ± 1.0 vs. 13.3 ± 0.9 mm-3 s-0.5 , respectively, P < 0.001), whereas CSE-GRE technique had a lower sensitivity (4.8 ± 1.1 mm-3 s-0.5 ). CONCLUSION: CSE 19 F MR imaging enables the unambiguous visualization of compounds with complex spectra, and provides high sensitivity both in vitro and in vivo. Magn Reson Med 79:2724-2730, 2018. © 2017 International Society for Magnetic Resonance in Medicine.