Assessment of Global and Regional Lung Compliance in Pulmonary Fibrosis With Hyperpolarized Gas MRI.

BACKGROUND: Lung compliance, a biomarker of pulmonary fibrosis, is generally measured globally. Hyperpolarized 129Xe gas MRI offers the potential to evaluate lung compliance regionally, allowing for visualization of changes in lung compliance associated with fibrosis. PURPOSE: To assess global and regional lung compliance in a rat model of pulmonary fibrosis using hyperpolarized 129Xe gas MRI. STUDY TYPE: Prospective. ANIMAL MODEL: Twenty Sprague-Dawley male rats with bleomycin-induced fibrosis model (N = 10) and saline-treated controls (N = 10). FIELD STRENGTH/SEQUENCE: 7-T, fast low-angle shot (FLASH) sequence. ASSESSMENT: Lung compliance was determined by fitting lung volumes derived from segmented 129Xe MRI with an iterative selection method, to corresponding airway pressures. Similarly, lung compliance was obtained with computed tomography for cross-validation. Direction-dependencies of lung compliance were characterized by regional lung compliance ratios (R) in different directions. Pulmonary function tests (PFTs) and histological analysis were used to validate the pulmonary fibrosis model and assess its correlation with 129Xe lung compliance. STATISTICAL TESTS: Shapiro-Wilk tests, unpaired and paired t-tests, Mann-Whitney U and Wilcoxon signed-rank tests, and Pearson correlation coefficients. P < 0.05 was considered statistically significant. RESULTS: For the entire lung, the global and regional lung compliance measured with 129Xe gas MRI showed significant differences between the groups, and correlated with the global lung compliance measured using PFTs (global: r = 0.891; regional: r = 0.873). Additionally, for the control group, significant difference was found in mean regional compliance between areas, eg, 0.37 (0.32, 0.39) × 10-4 mL/cm H2O and 0.47 (0.41, 0.56) × 10-4 mL/cm H2O for apical and basal lung, respectively. The apical-basal direction R was 1.12 ± 0.09 and 1.35 ± 0.13 for fibrosis and control groups, respectively, indicating a significant difference. DATA CONCLUSION: Our findings demonstrate the feasibility of using hyperpolarized gas MRI to assess regional lung compliance. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

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.

Activatable Graphene Quantum-Dot-Based Nanotransformers for Long-Period Tumor Imaging and Repeated Photodynamic Therapy.

Photodynamic therapy (PDT) is considered as an emerging therapeutic modality against cancer with high spatiotemporal selectivity because the utilized photosensitizers (PSs) are only active and toxic upon light irradiation. To maximize its effectiveness, PDT is usually applied repetitively for ablating various tumors. However, the total overdose of PSs from repeated administrations causes severe side effects. Herein, acidity-activated graphene quantum dots-based nanotransformers (GQD NT) are developed as PS vehicles for long-period tumor imaging and repeated PDT. Under the guidance of Arg-Gly-Asp peptide, GQD NT targets to tumor tissues actively, and then loosens and enlarges in tumor acidity, thus promising long tumor retention. Afterwards, GQD NT transforms into small pieces for better penetration in tumor. Upon laser irradiation, GQD NT generates mild hyperthermia that enhances cell membrane permeability and further promotes the PSs uptake. Most intriguingly, the as-prepared GQD NT not only "turns-on" fluorescence/magnetic resonance signals, but also achieves efficient repeated PDT. Notably, the total PSs dose is reduced to 3.5 µmol kg-1 , which is 10-30 times lower than that of other reported works. Overall, this study exploits a smart vehicle to enhance accumulation, retention, and release of PSs in tumors through programmed deformation, thus overcoming the overdose obstacle in repeated PDT.

A local-saturation-and-delay MRI method for evaluation of red blood cells aggregation in vivo for tumor-bearing or drug-used rats.

Hyperviscosity syndrome (HVS) is a combination of clinical signs and symptoms related to increased blood viscosity. HVS can increase the thrombotic risk by causing a major disturbance to the blood flow, which is usually found in the advanced stages of the tumor. Moreover, some of the drugs used in chemotherapy, such as 5-fluorouracil and erythropoietin, are also capable of causing HVS through their respective pathways. Clinically, the viscosity of a patient's blood sample is measured by a rotary rheometer to estimate the risk of hyperviscosity syndrome. However, the measurement of blood viscosity in vitro is easily affected by storage time, storage environment, and anticoagulants. In addition, the fluid conditions in the rheometer are quite different from those in natural blood vessels, making this method inappropriate for evaluating blood viscosity and its effects in vivo under physiological condition. Herein, we presented a novel magnetic resonance imaging method called local-saturation-and-delay imaging (LSDI). The radial distributions of flow velocity measured by LSDI are consistent with the Ultrasonic (US) method (Spearman correlation coefficient r = 0.990). But the result of LSDI is more stable than US (p < 0.0001). With the LSDI method, we can directly measure the radial distribution of diastolic flow velocity, and further use these data to calculate the whole blood relative viscosity (WBRV) and erythrocyte aggregation trend. It was a strong correlation between the results measured by LSDI and rotary rheometer in the group of rats given erythropoietin. Furthermore, experimental results in glioma rats indicate that LSDI is equivalent to a rheometer as a method for predicting the risk of hyperviscosity syndrome. Therefore, LSDI, as a non-invasive method, can effectively follow the changes in WBRV in rats and avoid the effect of blood sampling during the experiment on the results. In conclusion, LSDI is expected to become a novel method for real-time in vivo recognition of the cancer progression and the influence of drugs on blood viscosity and RBC aggregation.

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.

A congenital CMV infection model for follow-up studies of neurodevelopmental disorders, neuroimaging abnormalities, and treatment.

Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neurodevelopmental disorders. However, the neuropathogenesis remains largely elusive due to a lack of informative animal models. In this study, we developed a congenital murine CMV (cMCMV) infection mouse model with high survival rate and long survival period that allowed long-term follow-up study of neurodevelopmental disorders. This model involves in utero intracranial injection and mimics many reported clinical manifestations of cCMV infection in infants, including growth restriction, hearing loss, and impaired cognitive and learning-memory abilities. We observed that abnormalities in MRI/CT neuroimaging were consistent with brain hemorrhage and loss of brain parenchyma, which was confirmed by pathological analysis. Neuropathological findings included ventriculomegaly and cortical atrophy associated with impaired proliferation and migration of neural progenitor cells in the developing brain at both embryonic and postnatal stages. Robust inflammatory responses during infection were shown by elevated inflammatory cytokine levels, leukocyte infiltration, and activation of microglia and astrocytes in the brain. Pathological analyses and CT neuroimaging revealed brain calcifications induced by cMCMV infection and cell death via pyroptosis. Furthermore, antiviral treatment with ganciclovir significantly improved neurological functions and mitigated brain damage as shown by CT neuroimaging. These results demonstrate that this model is suitable for investigation of mechanisms of infection-induced brain damage and long-term studies of neurodevelopmental disorders, including the development of interventions to limit CNS damage associated with cCMV infection.

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.