Non-Contrast-Enhanced Functional Lung MRI to Evaluate Treatment Response of Allergic Bronchopulmonary Aspergillosis in Patients With Cystic Fibrosis: A Pilot Study.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is associated with severe lung damage and requires specific therapeutic management. Repeated imaging is recommended to both diagnose and follow-up response to treatment of ABPA in CF. However, high risk of cumulative radiation exposure requires evaluation of free-radiation techniques in the follow-up of CF patients with ABPA. PURPOSE: To evaluate whether Fourier decomposition (FD) functional lung MRI can detect response to treatment of ABPA in CF patients. STUDY TYPE: Retrospective longitudinal. POPULATION: Twelve patients (7M, median-age:14 years) with CF and ABPA with pre- and post-treatment MRI. FIELD STRENGTH/SEQUENCE: 2D-balanced-steady-state free-precession (bSSFP) sequence with FD at 1.5T. ASSESSMENT: Ventilation-weighted (V) and perfusion-weighted (Q) maps were obtained after FD processing of 2D-coronal bSSFP time-resolved images acquired before and 3-9 months after treatment. Defects extent was assessed on the functional maps using a qualitative semi-quantitative score (0 = absence/negligible, 1 = <50%, 2 = >50%). Mean and coefficient of variation (CV) of the ventilation signal-intensity (VSI) and the perfusion signal-intensity (QSI) were calculated. Measurements were performed independently by three readers and averaged. Inter-reader reproducibility of the measurements was assessed. Pulmonary function tests (PFTs) were performed within 1 week of both MRI studies as markers of the airflow-limitation severity. STATISTICAL TESTS: Comparisons of medians were performed using the paired Wilcoxon-test. Reproducibility was assessed using intraclass correlation coefficient (ICC). Correlations between MRI and PFT parameters were assessed using the Spearman-test (rho correlation-coefficient). A P-value <0.05 was considered as significant. RESULTS: Defects extent on both V and Q maps showed a significant reduction after ABPA treatment (4.25 vs. 1.92 for V-defect-score and 5 vs. 2.75 for Q-defect-score). VSI_mean was significantly increased after treatment (280 vs. 167). Qualitative analyses reproducibility showed an ICC > 0.90, while the ICCs of the quantitative measurements was almost perfect (>0.99). Changes in VSI_cv and QSI_cv before and after treatment correlated inversely with changes of FEV1%p (rho = -0.68 for both). DATA CONCLUSION: Non-contrast-enhanced FD lung MRI has potential to reproducibly assess response to treatment of ABPA in CF patients and correlates with PFT obstructive parameters. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

Assessment of intravoxel incoherent motion MRI with an artificial capillary network: analysis of biexponential and phase-distribution models.

PURPOSE: To systematically analyze intravoxel incoherent motion (IVIM) MRI in a perfusable capillary phantom closely matching the geometry of capillary beds in vivo and to compare the validity of the biexponential pseudo-diffusion and the recently introduced phase-distribution IVIM model. METHODS: IVIM-MRI was performed at 12 different flow rates ( 0.2⋯2.4mL/min ) in a capillary phantom using 4 different DW-MRI sequences (2 with monopolar and 2 with flow-compensated diffusion-gradient schemes, with up to 16b values between 0 and 800s/mm2 ). Resulting parameters from the assessed IVIM models were compared to results from optical microscopy. RESULTS: The acquired data were best described by a static and a flowing compartment modeled by the phase-distribution approach. The estimated signal fraction f of the flowing compartment stayed approximately constant over the applied flow rates, with an average of f=0.451±0.023 in excellent agreement with optical microscopy ( f=0.454±0.002 ). The estimated average particle flow speeds v=0.25⋯2.7mm/s showed a highly significant linear correlation to the applied flow. The estimated capillary segment length of approximately 189um agreed well with optical microscopy measurements. Using the biexponential model, the signal fraction f was substantially underestimated and displayed a strong dependence on the applied flow rate. CONCLUSION: The constructed phantom facilitated the detailed investigation of IVIM-MRI methods. The results demonstrate that the phase-distribution method is capable of accurately characterizing fluid flow inside a capillary network. Parameters estimated using the biexponential model, specifically the perfusion fraction f , showed a substantial bias because the model assumptions were not met by the underlying flow pattern.

Nonuniform Fourier-decomposition MRI for ventilation- and perfusion-weighted imaging of the lung.

PURPOSE: To improve the robustness of pulmonary ventilation- and perfusion-weighted imaging with Fourier decomposition (FD) MRI in the presence of respiratory and cardiac frequency variations by replacing the standard fast Fourier transform with the more general nonuniform Fourier transform. THEORY AND METHODS: Dynamic coronal single-slice MRI of the thorax was performed in 11 patients and 5 healthy volunteers on a 1.5T whole-body scanner using a 2D ultra-fast balanced steady-state free-precession sequence with temporal resolutions of 4-9 images/s. For the proposed nonuniform Fourier-decomposition (NUFD) approach, the original signal with variable physiological frequencies that was acquired with constant sampling rate was retrospectively transformed into a signal with (ventilation or perfusion) frequency-adapted sampling rate. For that purpose, frequency tracking was performed with the synchro-squeezed wavelet transform. Ventilation- and perfusion-weighted NUFD amplitude and signal delay maps were generated and quantitatively compared with regularly sampled FD maps based on their signal-to-noise ratio (SNR). RESULTS: Volunteers and patients showed statistically significant increases of SNR in frequency-adapted NUFD results compared to regularly sampled FD results. For ventilation data, the mean SNR increased by 43.4%±25.3% and 24.4%±31.9% in volunteers and patients, respectively; for perfusion data, SNR increased by 93.0%±36.1% and 75.6%±62.8% . Two patients showed perfusion signal in pulmonary areas with NUFD that could not be imaged with FD. CONCLUSION: This study demonstrates that using nonuniform Fourier transform in combination with frequency tracking can significantly increase SNR and reduce frequency overlaps by collecting the signal intensity onto single frequency bins.

Ventilation and perfusion MRI at a 0.35 T MR-Linac: feasibility and reproducibility study.

BACKGROUND: Hybrid devices that combine radiation therapy and MR-imaging have been introduced in the clinical routine for the treatment of lung cancer. This opened up not only possibilities in terms of accurate tumor tracking, dose delivery and adapted treatment planning, but also functional lung imaging. The aim of this study was to show the feasibility of Non-uniform Fourier Decomposition (NuFD) MRI at a 0.35 T MR-Linac as a potential treatment response assessment tool, and propose two signal normalization strategies for enhancing the reproducibility of the results. METHODS: Ten healthy volunteers (median age 28 ± 8 years, five female, five male) were repeatedly scanned at a 0.35 T MR-Linac using an optimized 2D+t balanced steady-state free precession (bSSFP) sequence for two coronal slice positions. Image series were acquired in normal free breathing with breaks inside and outside the scanner as well as deep and shallow breathing. Ventilation- and perfusion-weighted maps were generated for each image series using NuFD. For intra-volunteer ventilation map reproducibility, a normalization factor was defined based on the linear correlation of the ventilation signal and diaphragm position of each scan as well as the diaphragm motion amplitude of a reference scan. This allowed for the correction of signal dependency on the diaphragm motion amplitude, which varies with breathing patterns. The second strategy, which can be used for ventilation and perfusion, eliminates the dependency on the signal amplitude by normalizing the ventilation/perfusion maps with the average ventilation/perfusion signal within a selected region-of-interest (ROI). The position and size dependency of this ROI was analyzed. To evaluate the performance of both approaches, the normalized ventilation/perfusion-weighted maps were compared and the deviation of the mean ventilation/perfusion signal from the reference was calculated for each scan. Wilcoxon signed-rank tests were performed to test whether the normalization methods can significantly improve the reproducibility of the ventilation/perfusion maps. RESULTS: The ventilation- and perfusion-weighted maps generated with the NuFD algorithm demonstrated a mostly homogenous distribution of signal intensity as expected for healthy volunteers regardless of the breathing maneuver and slice position. Evaluation of the ROI's size and position dependency showed small differences in the performance. Applying both normalization strategies improved the reproducibility of the ventilation by reducing the median deviation of all scans to 9.1%, 5.7% and 8.6% for the diaphragm-based, the best and worst performing ROI-based normalization, respectively, compared to 29.5% for the non-normalized scans. The significance of this improvement was confirmed by the Wilcoxon signed rank test with [Formula: see text] at [Formula: see text]. A comparison of the techniques against each other revealed a significant difference in the performance between best ROI-based normalization and worst ROI ([Formula: see text]) and between best ROI-based normalization and scaling factor ([Formula: see text]), but not between scaling factor and worst ROI ([Formula: see text]). Using the ROI-based approach for the perfusion-maps, the uncorrected deviation of 10.2% was reduced to 5.3%, which was shown to be significant ([Formula: see text]). CONCLUSIONS: Using NuFD for non-contrast enhanced functional lung MRI at a 0.35 T MR-Linac is feasible and produces plausible ventilation- and perfusion-weighted maps for volunteers without history of chronic pulmonary diseases utilizing different breathing patterns. The reproducibility of the results in repeated scans significantly benefits from the introduction of the two normalization strategies, making NuFD a potential candidate for fast and robust early treatment response assessment of lung cancer patients during MR-guided radiotherapy.

Non-contrast-enhanced MRI of the pulmonary blood volume using two-compartment-modeled T1 -relaxation.

PURPOSE: To introduce a novel technique, based on a two-compartment model and nonselective inversion recovery (TCIR) for the non-contrast-enhanced evaluation of the fractional pulmonary blood volume (fPBV). MATERIALS AND METHODS: Ten healthy volunteers and one patient with focal lung destruction underwent examination with conventional magnetic resonance imaging (MRI) and TCIR. The reproducibility of TCIR was evaluated statistically, analyzing three consecutive measurement series. In order to evaluate the sensitivity of TCIR, the influence of gravitation on fPBV values along the anterior-posterior direction was assessed. Therefore, two transverse parameter maps of each volunteer in supine and prone position were acquired and analyzed. A comparison of patient images from TCIR-MRI, dynamic contrast-enhanced (DCE) MRI, and contrast-enhanced computed tomography (CT) was performed visually. RESULTS: The statistical evaluation showed significant similarity within the volunteer group, proving reproducibility. The detected slope of the fPBV values in anterior-posterior direction for both supine and prone position demonstrated the sensitivity of TCIR to the gravitational effect on the pulmonary blood distribution. The comparison between CT, DCE-, and TCIR-MRI patient datasets showed high similarity in dimension and location of the pathological part of the lung parenchyma. CONCLUSION: The introduced TCIR-technique is able to provide reproducible maps of the fPBV without the application of intravenous contrast media.

Pulmonary functional imaging: qualitative comparison of Fourier decomposition MR imaging with SPECT/CT in porcine lung.

PURPOSE: To compare unenhanced lung ventilation-weighted (VW) and perfusion-weighted (QW) imaging based on Fourier decomposition (FD) magnetic resonance (MR) imaging with the clinical reference standard single photon emission computed tomography (SPECT)/computed tomography (CT) in an animal experiment. MATERIALS AND METHODS: The study was approved by the local animal care committee. Lung ventilation and perfusion was assessed in seven anesthetized pigs by using a 1.5-T MR imager and SPECT/CT. For time-resolved FD MR imaging, sets of lung images were acquired by using an untriggered two-dimensional balanced steady-state free precession sequence (repetition time, 1.9 msec; echo time, 0.8 msec; acquisition time per image, 118 msec; acquisition rate, 3.33 images per second; flip angle, 75°; section thickness, 12 mm; matrix, 128 × 128). Breathing displacement was corrected with nonrigid image registration. Parenchymal signal intensity was analyzed pixelwise with FD to separate periodic changes of proton density induced by respiration and periodic changes of blood flow. Spectral lines representing respiratory and cardiac frequencies were integrated to calculate VW and QW images. Ventilation and perfusion SPECT was performed after inhalation of dispersed technetium 99m ((99m)Tc) and injection of (99m)Tc-labeled macroaggregated albumin. FD MR imaging and SPECT data were independently analyzed by two physicians in consensus. A regional statistical analysis of homogeneity and pathologic signal changes was performed. RESULTS: Images acquired in healthy animals by using FD MR imaging and SPECT showed a homogeneous distribution of VW and QW imaging and pulmonary ventilation and perfusion, respectively. The gravitation-dependent signal distribution of ventilation and perfusion in all animals was similarly observed at FD MR imaging and SPECT. Incidental ventilation and perfusion defects were identically visualized by using both modalities. CONCLUSION: This animal experiment demonstrated qualitative agreement in the assessment of regional lung ventilation and perfusion between contrast media-free and radiation-free FD MR imaging and conventional SPECT/CT.

Diagnostic accuracy of magnetic resonance imaging for the detection of pulmonary nodules simulated in a dedicated porcine chest phantom.

OBJECTIVE: CT serves as gold standard for the evaluation of pulmonary nodules. However, CT exposes patients to ionizing radiation, a concern especially in screening scenarios with repeated examinations. Due to recent technological advances, MRI emerges as a potential alternative for lung imaging using 3D steady state free precession and ultra-short echo-time sequences. Therefore, in this study we assessed the performance of three state-of-the-art MRI sequences for the evaluation of pulmonary nodules. METHODS: Lesions of variable sizes were simulated in porcine lungs placed in a dedicated chest phantom mimicking a human thorax, followed by CT and MRI examinations. Two blinded readers evaluated the acquired MR-images locating and measuring every suspect lesion. Using the CT-images as reference, logistic regression was performed to investigate the sensitivity of the tested MRI-sequences for the detection of pulmonary nodules. RESULTS: For nodules with a diameter of 6 mm, all three sequences achieved high sensitivity values above 0.91. However, the sensitivity dropped for smaller nodules, yielding an average of 0.83 for lesions with 4 mm in diameter and less than 0.69 for lesions with 2 mm in diameter. The positive predictive values ranged between 0.91 and 0.96, indicating a low amount of false positive findings. Furthermore, the size measurements done on the MR-images were subject to a bias ranging from 0.83 mm to -1.77 mm with standard deviations ranging from 1.40 mm to 2.11 mm. There was no statistically significant difference between the three tested sequences. CONCLUSION: While showing promising sensitivity values for lesions larger than 4 mm, MRI appears to be not yet suited for lung cancer screening. Nonetheless, the three tested MRI sequences yielded high positive predictive values and accurate size measurements; therefore, MRI could potentially figure as imaging method of the chest in selected follow-up scenarios, e.g. of incidental findings subject to the Fleischner Criteria.

Detection of artificial pulmonary lung nodules in ultralow-dose CT using an ex vivo lung phantom.

OBJECTIVES: To assess the image quality of 3 different ultralow-dose CT protocols on pulmonary nodule depiction in a ventilated ex vivo-system. MATERIALS AND METHODS: Four porcine lungs were inflated inside a dedicated chest phantom and prepared with n = 195 artificial nodules (0.5-1 mL). The artificial chest wall was filled with water to simulate the absorption of a human chest. Images were acquired with a 2x192-row detector CT using low-dose (reference protocol with a tube voltage of 120 kV) and 3 different ULD protocols (respective effective doses: 1mSv and 0.1mSv). A different tube voltage was used for each ULD protocol: 70kV, 100kV with tin filter (100kV_Sn) and 150kV with tin filter (150kV_Sn). Nodule delineation was assessed by two observers (scores 1-5, 1 = unsure, 5 = high confidence). RESULTS: The diameter of the 195 detected artificial nodules ranged from 0.9-21.5 mm (mean 7.84 mm ± 5.31). The best ULD scores were achieved using 100kV_Sn and 70 kV ULD protocols (4.14 and 4.06 respectively). Both protocols were not significantly different (p = 0.244). The mean score of 3.78 in ULD 150kV_Sn was significantly lower compared to the 100kV_Sn ULD protocol (p = 0.008). CONCLUSION: The results of this experiment, conducted in a realistic setting show the feasibility of ultralow-dose CT for the detection of pulmonary nodules.

Micro-imaging of Brain Cancer Radiation Therapy Using Phase-contrast Computed Tomography.

PURPOSE: Experimental neuroimaging provides a wide range of methods for the visualization of brain anatomic morphology down to subcellular detail. Still, each technique-specific detection mechanism presents compromises among the achievable field-of-view size, spatial resolution, and nervous tissue sensitivity, leading to partial sample coverage, unresolved morphologic structures, or sparse labeling of neuronal populations and often also to obligatory sample dissection or other sample invasive manipulations. X-ray phase-contrast imaging computed tomography (PCI-CT) is an experimental imaging method that simultaneously provides micrometric spatial resolution, high soft-tissue sensitivity, and ex vivo full organ rodent brain coverage without any need for sample dissection, staining or labeling, or contrast agent injection. In the present study, we explored the benefits and limitations of PCI-CT use for in vitro imaging of normal and cancerous brain neuromorphology after in vivo treatment with synchrotron-generated x-ray microbeam radiation therapy (MRT), a spatially fractionated experimental high-dose radiosurgery. The goals were visualization of the MRT effects on nervous tissue and a qualitative comparison of the results to the histologic and high-field magnetic resonance imaging findings. METHODS AND MATERIALS: MRT was administered in vivo to the brain of both healthy and cancer-bearing rats. At 45 days after treatment, the brain was dissected out and imaged ex vivo using propagation-based PCI-CT. RESULTS: PCI-CT visualizes the brain anatomy and microvasculature in 3 dimensions and distinguishes cancerous tissue morphology, necrosis, and intratumor accumulation of iron and calcium deposits. Moreover, PCI-CT detects the effects of MRT throughout the treatment target areas (eg, the formation of micrometer-thick radiation-induced tissue ablation). The observed neurostructures were confirmed by histologic and immunohistochemistry examination and related to the micro-magnetic resonance imaging data. CONCLUSIONS: PCI-CT enabled a unique 3D neuroimaging approach for ex vivo studies on small animal models in that it concurrently delivers high-resolution insight of local brain tissue morphology in both normal and cancerous micro-milieu, localizes radiosurgical damage, and highlights the deep microvasculature. This method could assist experimental small animal neurology studies in the postmortem evaluation of neuropathology or treatment effects.

T1 relaxation time constants, influence of oxygen, and the oxygen transfer function of the human lung at 1.5T-A meta-analysis.

PURPOSE: To pool and summarize published data from magnetic resonance longitudinal relaxation measurements of the human lung at 1.5T to provide a reliable basis of T1 relaxation time constants of healthy lung tissue both under respiration of room air and of pure oxygen. In particular, the oxygen-induced shortening of T1 was evaluated. MATERIALS AND METHODS: The PubMed database was comprehensively searched up to June 2016 for original publications in English containing quantitative T1 data (at least mean values and standard deviations) of the lung parenchyma of healthy subjects (minimum subject number: 3) at 1.5T. From all included publications, T1 values of the lung of healthy subjects were extracted (inhaling room air and, if available, inhaling pure oxygen). Weighted mean values and standard deviations of all extracted data and the oxygen transfer function (OTF) were calculated. RESULTS: 22 publications were included with a total number of 188 examined healthy subjects. 103 of these subjects (from 13 studies) were examined while breathing pure oxygen and room air; 85 subjects were examined only under room-air conditions. The weighted mean value (weighted sample standard deviation) of the room-air T1 values over all 22 studies was 1196ms (152ms). Based on studies with room-air and oxygen results, the mean T1 value at room-air conditions was 1172ms (161ms); breathing pure oxygen, the mean T1 value was reduced to 1054ms (138 ms). This corresponds to a mean T1 reduction by 118ms (35ms) or 10.0 % (2.3 %) and to a mean OTF value of 1.22 (0.32)×10-3s-1/(%O2). CONCLUSION: This meta-analysis with data from 188 subjects indicates that the average T1 relaxation time constant of healthy lung tissue at 1.5T is distributed around 1200ms with a standard deviation of about 150 ms; breathing pure oxygen reduces this value significantly by 10 % to about 1050 ms.

Technical Note: Quantitative dynamic contrast-enhanced MRI of a 3-dimensional artificial capillary network.

PURPOSE: Variability across devices, patients, and time still hinders widespread recognition of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as quantitative biomarker. The purpose of this work was to introduce and characterize a dedicated microchannel phantom as a model for quantitative DCE-MRI measurements. METHODS: A perfusable, MR-compatible microchannel network was constructed on the basis of sacrificial melt-spun sugar fibers embedded in a block of epoxy resin. Structural analysis was performed on the basis of light microscopy images before DCE-MRI experiments. During dynamic acquisition the capillary network was perfused with a standard contrast agent injection system. Flow-dependency, as well as inter- and intrascanner reproducibility of the computed DCE parameters were evaluated using a 3.0 T whole-body MRI. RESULTS: Semi-quantitative and quantitative flow-related parameters exhibited the expected proportionality to the set flow rate (mean Pearson correlation coefficient: 0.991, P < 2.5e-5). The volume fraction was approximately independent from changes of the applied flow rate through the phantom. Repeatability and reproducibility experiments yielded maximum intrascanner coefficients of variation (CV) of 4.6% for quantitative parameters. All evaluated parameters were well in the range of known in vivo results for the applied flow rates. CONCLUSION: The constructed phantom enables reproducible, flow-dependent, contrast-enhanced MR measurements with the potential to facilitate standardization and comparability of DCE-MRI examinations.

Pulmonary perfusion imaging: Qualitative comparison of TCIR MRI and SPECT/CT in porcine lung.

OBJECTIVES: To validate the anatomical accuracy, homogeneity and sensitivity of two-compartment modeled inversion recovery (TCIR) magnetic resonance imaging (MRI) in a multimodal animal experiment as a non-invasive alternative to standard functional imaging techniques. METHODS: Seven pigs were studied on a 1.5 T whole-body MR scanner and SPECT/CT. The specimens were intubated and maintained in general anesthesia throughout the experiment. TCIR maps of the fractional pulmonary blood volume were compared to dynamic contrast enhanced MRI and SPECT/CT via a region of interest (ROI) based reader study. A comprehensive statistical analysis was performed on the coefficient of variation to evaluate homogeneity properties. Sensitivity was assessed by detecting gravitation dependent perfusion variation and delineation of pathological areas. RESULTS: The fPBV-maps of all examined specimens indicate a superior homogeneity in the computed values (p<1.3×10(-4)). The sensitivity of the TCIR maps to a gravitation effect on the blood distribution was verified and a similar anteroposterior signal and count dependency was observed in DCE MRI and SPECT. Bland-Altman analysis showed no significant intra- or inter-observer difference within the ROI reader study (p>0.06). CONCLUSION: Superior information content, significantly higher homogeneity and similar sensitivity of TCIR when compared to DCE and SPECT/CT demonstrated the feasibility of TCIR MRI as an alternative contrast agent-free, non-invasive functional lung imaging approach.

Rapid dynamic radial MRI via reference image enforced histogram constrained reconstruction.

Exploiting spatio-temporal redundancies in sub-Nyquist sampled dynamic MRI for the suppression of undersampling artifacts was shown to be of great success. However, temporally averaged and blurred structures in image space composite data poses the risk of false information in the reconstruction. Within this work we assess the possibility of employing the composite image histogram as a measure of undersampling artifacts and as basis of their suppression. The proposed algorithm utilizes a histogram, computed from a composite image within a dynamically acquired interleaved radial MRI measurement as reference to compensate for the impact of undersampling in temporally resolved data without the incorporation of temporal averaging. In addition an image space regularization utilizing a single frame low-resolution reconstruction is implemented to enforce overall contrast fidelity. The performance of the approach was evaluated on a simulated radial dynamic MRI acquisition and on two functional in vivo radial cardiac acquisitions. Results demonstrate that the algorithm maintained contrast properties, details and temporal resolution in the images, while effectively suppressing undersampling artifacts.