Assessment of pulmonary physiological changes caused by aging, cigarette smoking, and COPD with hyperpolarized 129Xe magnetic resonance.

OBJECTIVE: To comprehensively assess the impact of aging, cigarette smoking, and chronic obstructive pulmonary disease (COPD) on pulmonary physiology using 129Xe MR. METHODS: A total of 90 subjects were categorized into four groups, including healthy young (HY, n = 20), age-matched control (AMC, n = 20), asymptomatic smokers (AS, n = 28), and COPD patients (n = 22). 129Xe MR was utilized to obtain pulmonary physiological parameters, including ventilation defect percent (VDP), alveolar sleeve depth (h), apparent diffusion coefficient (ADC), total septal wall thickness (d), and ratio of xenon signal from red blood cells and interstitial tissue/plasma (RBC/TP). RESULTS: Significant differences were found in the measured VDP (p = 0.035), h (p = 0.003), and RBC/TP (p = 0.003) between the HY and AMC groups. Compared with the AMC group, higher VDP (p = 0.020) and d (p = 0.048) were found in the AS group; higher VDP (p < 0.001), d (p < 0.001) and ADC (p < 0.001), and lower h (p < 0.001) and RBC/TP (p < 0.001) were found in the COPD group. Moreover, significant differences were also found in the measured VDP (p < 0.001), h (p < 0.001), ADC (p < 0.001), d (p = 0.008), and RBC/TP (p = 0.032) between the AS and COPD groups. CONCLUSION: Our findings indicate that pulmonary structure and functional changes caused by aging, cigarette smoking, and COPD are various, and show a progressive deterioration with the accumulation of these risk factors, including cigarette smoking and COPD. CLINICAL RELEVANCE STATEMENT: Pathophysiological changes can be difficult to comprehensively understand due to limitations in common techniques and multifactorial etiologies. 129Xe MRI can demonstrate structural and functional changes caused by several common factors and can be used to better understand patients' underlying pathology. KEY POINTS: Standard techniques for assessing pathophysiological lung function changes, spirometry, and chest CT come with limitations. 129Xe MR demonstrated progressive deterioration with accumulation of the investigated risk factors, without these limitations. 129Xe MR can assess lung changes related to these risk factors to stage and evaluate the etiology of the disease.

Rapid pulmonary 129Xe ventilation MRI of discharged COVID-19 patients with zigzag sampling.

PURPOSE: To demonstrate the feasibility of zigzag sampling for 3D rapid hyperpolarized 129Xe ventilation MRI in human. METHODS: Zigzag sampling in one direction was combined with gradient-recalled echo sequence (GRE-zigzag-Y) to acquire hyperpolarized 129Xe ventilation images. Image quality was compared with a balanced SSFP (bSSFP) sequence with the same spatial resolution for 12 healthy volunteers (HVs). For another 8 HVs and 9 discharged coronavirus disease 2019 subjects, isotropic resolution 129Xe ventilation images were acquired using zigzag sampling in two directions through GRE-zigzag-YZ. 129Xe ventilation defect percent (VDP) was quantified for GRE-zigzag-YZ and bSSFP acquisitions. Relationships and agreement between these VDP measurements were evaluated using Pearson correlation coefficient (r) and Bland-Altman analysis. RESULTS: For 12 HVs, GRE-zigzag-Y and bSSFP required 2.2 s and 10.5 s, respectively, to acquire 129Xe images with a spatial resolution of 3.96 × 3.96 × 10.5 mm3. Structural similarity index, mean absolute error, and Dice similarity coefficient between the two sets of images and ventilated lung regions were 0.85 ± 0.03, 0.0015 ± 0.0001, and 0.91 ± 0.02, respectively. For another 8 HVs and 9 coronavirus disease 2019 subjects, 129Xe images with a nominal spatial resolution of 2.5 × 2.5 × 2.5 mm3 were acquired within 5.5 s per subject using GRE-zigzag-YZ. VDP provided by GRE-zigzag-YZ was strongly correlated (R2 = 0.93, p < 0.0001) with that generated by bSSFP with minimal biases (bias = -0.005%, 95% limit-of-agreement = [-0.414%, 0.424%]). CONCLUSION: Zigzag sampling combined with GRE sequence provides a way for rapid 129Xe ventilation imaging.

Dynamic evaluation of acute lung injury using hyperpolarized 129 Xe magnetic resonance.

Prognosticating acute lung injury (ALI) is challenging, in part because of a lack of sensitive biomarkers. Hyperpolarized gas magnetic resonance (MR) has unique advantages in pulmonary function measurement and can provide promising biomarkers for the assessment of lung injuries. Herein, we employ hyperpolarized 129 Xe MRI and generate a number of imaging biomarkers to detect the pulmonary physiological and morphological changes during the progression of ALI in an animal model. We find the measured ratio of 129 Xe in red blood cells to interstitial tissue/plasma (RBC/TP) is significantly lower in the ALI group on the second (0.32 ± 0.03, p = 0.004), seventh (0.23 ± 0.03, p < 0.001), and 14th (0.29 ± 0.04, p = 0.001) day after lipopolysaccharide treatment compared with that in the control group (0.41 ± 0.04). In addition, significant differences are also observed for RBC/TP measurements between the second and seventh day (p = 0.001) and between the seventh and 14th day (p = 0.018) in the ALI group after treatment. Besides RBC/TP, significant differences are also observed in the measured exchange time constant (T) on the second (p = 0.038) and seventh day (p = 0.009) and in the measured apparent diffusion coefficient (ADC) and alveolar surface-to-volume ratio (SVR) on the 14th day (ADC: p = 0.009 and SVR: p = 0.019) after treatment in the ALI group compared with that in the control group. These findings indicate that the parameters measured with 129 Xe MR can detect the dynamic changes in pulmonary structure and function in an ALI animal model.

Assessment of pulmonary morphometry using hyperpolarized 129 Xe diffusion-weighted MRI with variable-sampling-ratio compressed sensing patterns.

BACKGROUND: Hyperpolarized (HP) 129 Xe multiple b-values diffusion-weighted magnetic resonance imaging (DW-MRI) has been widely used for quantifying pulmonary microstructural morphometry. However, the technique requires long acquisition times, making it hard to apply in patients with severe pulmonary diseases, who cannot sustain long breath holds. PURPOSE: To develop and evaluate the technique of variable-sampling-ratio compressed sensing (VCS) patterns for accelerating HP 129 Xe multiple b-values DW-MRI in humans. METHODS: Optimal variable sampling ratios and corresponding k-space undersampling patterns for each b-value were obtained by retrospective simulations based on the fully sampled (FS) DW-MRI dataset acquired from six young healthy volunteers. Then, the FS datasets were retrospectively undersampled using both VCS patterns and conventional compressed sensing (CS) pattern with a similar average acceleration factor. The quality of reconstructed images with retrospective VCS (rVCS) and CS (rCS) datasets were quantified using mean absolute error (MAE) and structural similarity (SSIM). Pulmonary morphometric parameters were also evaluated between rVCS and FS datasets. In addition, prospective VCS multiple b-values 129 Xe DW-MRI datasets were acquired from 14 cigarette smokers and 13 age-matched healthy volunteers. The differences of lung morphological parameters obtained with the proposed method were compared between the groups using independent samples t-test. Pearson correlation coefficient was also utilized for evaluating the correlation of the pulmonary physiological parameters obtained with VCS DW-MRI and pulmonary function tests. RESULTS: Lower MAE and higher SSIM values were found in the reconstructed images with rVCS measurement when compared to those using conventional rCS measurement. The details and quality of the images obtained with rVCS and FS measurements were found to be comparable. The mean values of the morphological parameters derived from rVCS and FS datasets showed no significant differences (p > 0.05), and the mean differences of measured acinar duct radius, mean linear intercept, surface-to-volume ratio, and apparent diffusion coefficient with cylinder model were -0.87%, -2.42%, 2.04%, and -0.50%, respectively. By using the VCS technique, significant differences were delineated between the pulmonary morphometric parameters of healthy volunteers and cigarette smokers (p < 0.001), while the acquisition time was reduced by four times. CONCLUSION: A fourfold reduction in acquisition time was achieved using the proposed VCS method while preserving good image quality. Our preliminary results demonstrated that the proposed method can be used for evaluating pulmonary injuries caused by cigarette smoking and may prove to be helpful in diagnosing lung diseases in clinical practice.

Analysis of the composition of culturable airborne microorganisms in the archaeological excavation protection site of the Nanhai No. 1 Ancient Shipwreck.

After the recovery of the ship from the sea on 2007, the Nanhai No. 1 Ancient Shipwreck is currently exposed to the air. Air microorganisms settle on wooden shipwrecks, and they can use wood matrix to grow and multiply, causing biocorrosion and biodegradation. In this study, a systematical survey of the composition of culturable airborne microorganisms was performed at the conservation site of the Nanhai No. 1 Ancient Shipwreck. Airborne microorganisms were collected from seven sites in the preservation Nanhai No. 1 area over five periods. Molecular identification of the culturable microorganisms isolated from the air was done by sequencing both 16S rRNA (bacteria) and ITS (fungi) gene regions. The biodegradability of these strains was evaluated by degradation experiments with cellulose and lignin as substrate. The results showed that the composition of the isolated microbial communities was different in each period, and microbial spatial distribution was dissimilar in the same period. In the recent 2020, the dominant bacterial genus was Acinetobacter, and the dominant fungal genera were Penicillium, Aspergillus, and Cerrena. Acinetobacter spp. can degrade cellulose and lignin. Penicillium spp., Aspergillus spp., and Cerrena spp. degraded cellulose but only Cerrena spp. could utilize lignin. These dominant strains may have a harmful effect on the Nanhai No. 1 Ancient Shipwreck. This study provides data on the airborne microbial community found inside the protective chamber where Nanhai No. 1 Shipereck is placed, which can be used as a reference basis for the future conservation of the ship.

Antifungal Substances Produced by Xenorhabdus bovienii and Its Inhibition Mechanism against Fusarium solani.

Fungal colonization can severely damage artifacts. Nematode endosymbiotic bacteria exhibit good prospects in protecting artifacts from fungal damage. We previously found that supernatant from the fermentation of nematode endosymbiotic bacterium, Xenorhabdus bovienii, is effective in inhibiting the growth of Fusarium solani NK-NH1, the major disease fungus in the Nanhai No.1 Shipwreck. Further experiments proved that X. bovienii produces volatile organic compounds (VOCs) that inhibit NK-NH1. Here, using metabolomic analysis, GC-MS, and transcriptomic analysis, we explored the antifungal substances and VOCs produced by X. bovienii and investigated the mechanism underlying its inhibitory effect against NK-NH1. We show that X. bovienii produces several metabolites, mainly lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds. The VOCs produced by X. bovienii showed two specific absorption peaks, and based on the library ratio results, these were predicted to be of 2-pentanone, 3-(phenylmethylene) and 1-hexen-3-one, 5-methyl-1-phenyl. The inhibition of F. solani by VOCs resulted in upregulation of genes related to ribosome, ribosome biogenesis, and the oxidative phosphorylation and downregulation of many genes associated with cell cycle, meiosis, DNA replication, and autophagy. These results are significant for understanding the inhibitory mechanisms employed by nematode endosymbiotic bacteria and should serve as reference in the protection of artifacts.

Analysis of Microbial Community in the Archaeological Ruins of Liangzhu City and Study on Protective Materials.

This study aims to provide a reference for the protection of the Archaeological Ruins of Liangzhu City. As a basis for the further preservation of these cultural relics, it is essential to analyze the microflora colonizing these soil objects. To do that, samples with microbial characteristics were obtained and analyzed by SEM and metagenomic sequencing to reveal the constitute of the microflora. We investigated the biodegradation of the protective material-epoxy resin by microorganisms in the Archaeological Ruins of Liangzhu City, and found that they would interact with each other, which would affect the performance of the epoxy resin. The specific mechanism of action requires further investigations. We evaluated the effect of ethyl orthosilicate on soil properties. Interestingly, we found that excess ethyl orthosilicate added to the soil of the Archaeological Ruins of Liangzhu City will cause a change in particle size and allowed the soil to condense in the laboratory. This indicates that the large use of orthosilicate may lead to intensified soil weathering, which in turn will cause soil erosion.

Fungal Community and Biodeterioration Analysis of Hull Wood and Its Storage Environment of the Nanhai No. 1 Shipwreck.

The Nanhai No. 1 shipwreck is a Chinese merchant ship in the Southern Song Dynasty, and now it is stored in a huge enclosed glass warehouse in Maritime Silk Road Museum in Guangdong Province. At present, the hull of the Nanhai No. 1 shipwreck is still being excavated, and a small part of the hull wood is soaked in a specific solution to desalt. Through long-term exploration, we found that the above two states of hull wood had undergone biodeterioration, so the purpose of this study is to analyze the fungal community of exposed and soaked wood from the Nanhai No. 1 shipwreck. We sampled 10 exposed hull wood and sea mud samples, two wood storage water samples, and air samples in the glass warehouse. We used scanning electron microscope and optical microscope to find that there were obvious fungal structures in exposed wood and wood storing water samples. High-throughput sequencing of fungi revealed that the most abundant genera in exposed and soaked wood were Fusarium sp., and Scedosporium sp., respectively. In addition, Fusarium solani and Scedosporium apiospermum were successfully isolated from the hull wood surface and wood storing water samples, and the degradation tests of lignin and cellulose, the sensitivity tests of biocides and growth curve assay were carried out. We also found that Penicillium sp. and Cladosporium sp. are the most abundant in the glass warehouse air. Our research results show that F. solani and S. apiospermum should be regarded as a major threat to the preservation of the Nanhai No. 1 shipwreck. These results provide a reference for our protection of shipwrecks and other similar artifacts.

Quantitative evaluation of lung injury caused by PM2.5 using hyperpolarized gas magnetic resonance.

PURPOSE: To demonstrate the feasibility of 129 Xe MR in evaluating the pulmonary physiological changes caused by PM2.5 in animal models. METHODS: Six rats were treated with PM2.5 solution (16.2 mg/kg) by intratracheal instillation twice a week for 4 weeks, and another six rats treated with normal saline served as the control cohort. Pulmonary function tests, hyperpolarized 129 Xe multi-b diffusion-weighted imaging, and chemical shift saturation recovery MR spectroscopy were performed on all rats, and the pulmonary structure and functional parameters were obtained from hyperpolarized 129 Xe MR data. Additionally, histological analysis was performed on all rats to evaluate alveolar septal thickness. Statistical analysis of all the obtained parameters was performed using unpaired 2-tailed t tests. RESULTS: Compared with the control group, the measured exchange time constant increased from 11.74 ± 2.39 to 14.00 ± 2.84 ms (P < .05), and the septal wall thickness increased from 6.17 ± 0.48 to 6.74 ± 0.52 µm (P < .05) in the PM2.5 cohort by 129 Xe MR spectroscopy, which correlated well with that obtained using quantitative histology (increased from 5.52 ± 0.32 to 6.20 ± 0.36 µm). Additionally, the mean TP/GAS ratio increased from 0.828 ± 0.115 to 1.019 ± 0.140 in the PM2.5 cohort (P = .021). CONCLUSIONS: Hyperpolarized 129 Xe MR could quantify the changes in gas exchange physiology caused by PM2.5 , indicating that the technique has the potential to be a useful tool for evaluation of pulmonary injury caused by air pollution in the future.

Quantitative evaluation of pulmonary gas-exchange function using hyperpolarized 129 Xe CEST MRS and MRI.

Hyperpolarized 129 Xe gas MR has been a powerful tool for evaluating pulmonary structure and function due to the extremely high enhancement in spin polarization, the good solubility in the pulmonary parenchyma, and the excellent chemical sensitivity to its surrounding environment. Generally, the quantitative structural and functional information of the lung are evaluated using hyperpolarized 129 Xe by employing the techniques of chemical shift saturation recovery (CSSR) and xenon polarization transfer contrast (XTC). Hyperpolarized 129 Xe chemical exchange saturation transfer (Hyper-CEST) is another method for quantifying the exchange information of hyperpolarized 129 Xe by using the exchange of xenon signals according to its different chemical shifts, and it has been widely used in biosensor studies in vitro. However, the feasibility of using hyperpolarized 129 Xe CEST to quantify the pulmonary gas exchange function in vivo is still unclear. In this study, the technique of CEST was used to quantitatively evaluate the gas exchange in the lung globally and regionally via hyperpolarized 129 Xe MRS and MRI, respectively. A new parameter, the pulmonary apparent gas exchange time constant (Tapp ), was defined, and it increased from 0.63 s to 0.95 s in chronic obstructive pulmonary disease (COPD) rats (induced by cigarette smoke and lipopolysaccharide exposure) versus the controls with a significant difference (P = 0.001). Additionally, the spatial distribution maps of Tapp in COPD rats' pulmonary parenchyma showed a regionally obvious increase compared with healthy rats. These results indicated that hyperpolarized 129 Xe CEST MR was an effective method for globally and regionally quantifying the pulmonary gas exchange function, which would be helpful in diagnosing lung diseases that are related to gas exchange, such as COPD.

Simultaneous assessment of both lung morphometry and gas exchange function within a single breath-hold by hyperpolarized 129 Xe MRI.

During the measurement of hyperpolarized 129 Xe magnetic resonance imaging (MRI), the diffusion-weighted imaging (DWI) technique provides valuable information for the assessment of lung morphometry at the alveolar level, whereas the chemical shift saturation recovery (CSSR) technique can evaluate the gas exchange function of the lungs. To date, the two techniques have only been performed during separate breaths. However, the request for multiple breaths increases the cost and scanning time, limiting clinical application. Moreover, acquisition during separate breath-holds will increase the measurement error, because of the inconsistent physiological status of the lungs. Here, we present a new method, referred to as diffusion-weighted chemical shift saturation recovery (DWCSSR), in order to perform both DWI and CSSR within a single breath-hold. Compared with sequential single-breath schemes (namely the 'CSSR + DWI' scheme and the 'DWI + CSSR' scheme), the DWCSSR scheme is able to significantly shorten the breath-hold time, as well as to obtain high signal-to-noise ratio (SNR) signals in both DWI and CSSR data. This scheme enables comprehensive information on lung morphometry and function to be obtained within a single breath-hold. In vivo experimental results demonstrate that DWCSSR has great potential for the evaluation and diagnosis of pulmonary diseases.

Detection of smoke-induced pulmonary lesions by hyperpolarized 129 Xe diffusion kurtosis imaging in rat models.

PURPOSE: To demonstrate that hyperpolarized (HP) xenon diffusion kurtosis imaging (DKI) is able to detect smoke-induced pulmonary lesions in rat models. METHODS: Multi-b DKI with hyperpolarized xenon was used for the first time in five smoke-exposed rats and five healthy rats. Additionally, DKI with b values of up to 80 s/cm2 were used in two healthy rats to probe the critical b value (a limit beyond which the DKI cannot describe the non-Gaussian diffusion). RESULTS: The mean apparent diffusion coefficient (Dapp ) and diffusion kurtosis (Kapp ) extracted by the DKI model revealed significant changes in the smoke-exposed rats compared with those in the control group (P = 0.027 and 0.039, respectively), exhibiting strong correlations with mean linear intercept (Lm ) from the histology. Although the maximum b value was increased to 80 s/cm2 , the DKI could still describe the non-Gaussian diffusion (R2 > 0.97). CONCLUSION: DKI with hyperpolarized xenon exhibited sensitivity in the detection of pulmonary lesions induced by smoke, including moderate emphysema and small airway diseases. The critical b value was rarely exceeded in DKI of the lungs due to the limited gradient strength of the MRI scanner used in our study. Magn Reson Med 78:1891-1899, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Detection of the mild emphysema by quantification of lung respiratory airways with hyperpolarized xenon diffusion MRI.

PURPOSE: To demonstrate the feasibility to quantify the lung respiratory airway in vivo with hyperpolarized xenon diffusion magnetic resonance imaging (MRI), which is able to detect mild emphysema in the rat model. MATERIALS AND METHODS: The lung respiratory airways were quantified in vivo using hyperpolarized xenon diffusion MRI (7T) with eight b values (5, 10, 15, 20, 25, 30, 35, 40 s/cm2 ) in five control rats and five mild emphysematous rats, which were induced by elastase. The morphological results from histology were acquired and used for comparison. RESULTS: The parameters DL (longitudinal diffusion coefficient), r (internal radius), h (alveolar sleeve depth), Lm (mean linear intercept), and S/V (surface area to lung volume ratio) derived from the hyperpolarized xenon diffusion MRI in the emphysematous group showed significant differences from those in the control group (P < 0.05). Additionally, these parameters correlated well with the Lm obtained by the traditional histological sections (Pearson's correlation coefficients >0.8). CONCLUSION: The lung respiratory airways can be quantified by hyperpolarized xenon diffusion MRI, showing the potential for mild emphysema diagnosis. Also, the study suggested that the hyperpolarized xenon DL is more sensitive than DT (transverse diffusion coefficient) to detect mild emphysema. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:879-888.

Fast Determination of Flip Angle and T1 in Hyperpolarized Gas MRI During a Single Breath-Hold.

MRI of hyperpolarized media, such as (129)Xe and (3)He, shows great potential for clinical applications. The optimal use of the available spin polarization requires accurate flip angle calibrations and T1 measurements. Traditional flip angle calibration methods are time-consuming and suffer from polarization losses during T1 relaxation. In this paper, we propose a method to simultaneously calibrate flip angles and measure T1 in vivo during a breath-hold time of less than 4 seconds. We demonstrate the accuracy, robustness and repeatability of this method and contrast it with traditional methods. By measuring the T1 of hyperpolarized gas, the oxygen pressure in vivo can be calibrated during the same breath hold. The results of the calibration have been applied in variable flip angle (VFA) scheme to obtain a stable steady-state transverse magnetization. Coupled with this method, the ultra-short TE (UTE) and constant VFA (CVFA) schemes are expected to give rise to new applications of hyperpolarized media.

Oxygen-dependent hyperpolarized (129) Xe brain MR.

Hyperpolarized (HP) (129) Xe MR offers unique advantages for brain functional imaging (fMRI) because of its extremely high sensitivity to different chemical environments and the total absence of background noise in biological tissues. However, its advancement and applications are currently plagued by issues of signal strength. Generally, xenon atoms found in the brain after inhalation are transferred from the lung via the bloodstream. The longitudinal relaxation time (T1 ) of HP (129) Xe is inversely proportional to the pulmonary oxygen concentration in the lung because oxygen molecules are paramagnetic. However, the T1 of (129) Xe is proportional to the pulmonary oxygen concentration in the blood, because the higher pulmonary oxygen concentration will result in a higher concentration of diamagnetic oxyhemoglobin. Accordingly, there should be an optimal pulmonary oxygen concentration for a given quantity of HP (129) Xe in the brain. In this study, the relationship between pulmonary oxygen concentration and HP (129) Xe signal in the brain was analyzed using a theoretical model and measured through in vivo experiments. The results from the theoretical model and experiments in rats are found to be in good agreement with each other. The optimal pulmonary oxygen concentration predicted by the theoretical model was 21%, and the in vivo experiments confirmed the presence of such an optimal ratio by reporting measurements between 25% and 35%. These findings are helpful for improving the (129) Xe signal in the brain and make the most of the limited spin polarization available for brain experiments. Copyright © 2016 John Wiley & Sons, Ltd.

Experimental performance evaluation of multi-echo ICNE pulse sequence in magnetic resonance electrical impedance tomography.

Latest experimental results in magnetic resonance electrical impedance tomography (MREIT) demonstrated high-resolution in vivo conductivity imaging of animal and human subjects using imaging currents of 5 to 9 mA. Externally injected imaging currents induce magnetic flux density distributions, which are affected by a conductivity distribution. Since we extract the induced magnetic flux density images from MR phase images, it is essential to reduce noise in the phase images. In vivo human and disease model animal experiments require reduction of imaging current amplitudes and scan times. In this article, we investigate a multi-echo based MREIT pulse sequence where we utilize a remaining time after the first echo within one TR to obtain more echo signals. It also allows us to prolong the total current injection time. From phantom and animal imaging experiments, we found that this method significantly reduces the noise level in measured magnetic flux density images. We describe experimental validation of the multi-echo sequence by comparing its performance with a single-echo method using 3 mA imaging currents. The proposed method will be advantageous for an imaging region with long T2 values such as the brain and knee. Depending on T2 values, we suggest using two or three echoes in future experimental studies.