Free-breathing Pulmonary MR Imaging to Quantify Regional Ventilation.

In subjects with chronic obstructive pulmonary disease (COPD), hyperpolarized xenon-129 ((129)Xe) magnetic resonance imaging (MRI) reveals significantly greater ventilation defects than hyperpolarized helium-3 ((3)He) MRI. The physiological and/or morphological determinants of ventilation defects and the differences observed between hyperpolarized (3)He and (129)Xe MRI are not yet understood. Here we aimed to determine the structural basis for the differences in ventilation observed between (3)He and (129)Xe MRI in subjects with COPD using apparent diffusion coefficients (ADC) and computed tomography (CT). Ten COPD ex-smokers provided written, informed consent and underwent MRI, CT, spirometry, and plethysmography. (3)He and (129)Xe MRI ventilation volume was generated using semiautomated segmentation, and ADC maps were registered to generate ADC values for lung regions of interest ventilated by both gases (ADCHX) and by (3)He gas only (ADCHO). CT wall area percentage and the lowest 15th percentile point of the CT lung density histogram (HU15%) were also evaluated. For lung regions accessed by (3)He gas only, mean (3)He ADCHO was significantly greater than for regions accessed by both gases (ADCHO = 0.503 ± 0.119 cm(2)/s, ADCHX = 0.470 ± 0.125 cm(2)/s, P < 0.0001). The difference between (3)He and (129)Xe ventilation volume was significantly correlated with CT HU15% (r = -65, P = 0.04) and (3)He ADCHO (r = 0.70, P = 0.02), but not CT wall area percentage (r = -0.34, P = 0.33). In conclusion, in this small study in COPD subjects, we observed significantly decreased (129)Xe MRI ventilation compared with (3)He MRI, and these regions of decreased (129)Xe ventilation were spatially and significantly correlated with regions of increased pulmonary emphysema, but not airway wall thickness.

To evaluate the safety of hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging. Local institutional review board approval and informed consent were obtained. Physiologic monitoring data were obtained before, during, and after hyperpolarized (3)He MR imaging in 100 consecutive subjects (57 men, 43 women; mean age, 52 years +/- 14 [standard deviation]). The subjects inhaled 1-3 L of a gas mixture containing 300-500 mL (3)He and 0-2700 mL N(2) and held their breath for up to 15 seconds during MR imaging. Heart rate and rhythm and oxygen saturation of hemoglobin as measured by pulse oximetry (Spo(2)) were monitored continuously throughout each study. The effects of (3)He MR imaging on vital signs and Spo(2) and the relationship between pulmonary function, number of doses, and clinical classification (healthy volunteers, patients with asthma, heavy smokers, patients undergoing lung volume reduction surgery for severe emphysema, and patients with lung cancer) and the lowest observed Spo(2) were assessed. Any subjective symptoms were noted. Except for a small postimaging decrease in mean heart rate (from 78 beats per minute +/- 13 to 73 beats per minute +/- 11, P < .001), there was no effect on vital signs. A mean transient decrease in Spo(2) of 4% +/- 3 was observed during the first minute after gas inhalation (P < .001) in 77 subjects who inhaled a dose of 1 L for 10 seconds or less, reaching a nadir of less than 90% at least once in 20 subjects and of less than 85% in four subjects. There was no correlation between the lowest Spo(2) and pulmonary function parameters other than baseline Spo(2) (r = 0.36, P = .001). The lowest mean Spo(2) varied by 1% between the first and second and second and third doses (P < .001) and was unrelated to clinical classification (P = .40). Minor subjective symptoms were noted by 10 subjects. No serious adverse events occurred. Hyperpolarized (3)He MR imaging can be safely performed in healthy subjects, heavy smokers, and those with severe obstructive airflow limitation, although unpredictable transient desaturation suggests that potential subjects should be carefully screened for comorbidities.

3He MR Imaging of Porcine Paranasal Sinuses

BackgroundTemperatures below the freezing point of water and the ensuing ice crystal formation pose serious challenges to cell structure and function. Consequently, species living in seasonally cold environments have evolved a multitude of strategies to reorganize their cellular architecture and metabolism, and the underlying mechanisms are crucial to our understanding of life. In multicellular organisms, and poikilotherm animals in particular, our knowledge about these processes is almost exclusively due to invasive studies, thereby limiting the range of conclusions that can be drawn about intact living systems.MethodologyGiven that non-destructive techniques like 1H Magnetic Resonance (MR) imaging and spectroscopy have proven useful for in vivo investigations of a wide range of biological systems, we aimed at evaluating their potential to observe cold adaptations in living insect larvae. Specifically, we chose two cold-hardy insect species that frequently serve as cryobiological model systems–the freeze-avoiding gall moth Epiblema scudderiana and the freeze-tolerant gall fly Eurosta solidaginis.ResultsIn vivo MR images were acquired from autumn-collected larvae at temperatures between 0°C and about −70°C and at spatial resolutions down to 27 µm. These images revealed three-dimensional (3D) larval anatomy at a level of detail currently not in reach of other in vivo techniques. Furthermore, they allowed visualization of the 3D distribution of the remaining liquid water and of the endogenous cryoprotectants at subzero temperatures, and temperature-weighted images of these distributions could be derived. Finally, individual fat body cells and their nuclei could be identified in intact frozen Eurosta larvae.ConclusionsThese findings suggest that high resolution MR techniques provide for interesting methodological options in comparative cryobiological investigations, especially in vivo.

Hyperpolarized helium MRI assessment of the spatial heterogeneity in lung function with potential relationship to radiation response

Noncystic Fibrosis Bronchiectasis: Regional Abnormalities and Response to Airway Clearance Therapy Using Pulmonary Functional Magnetic Resonance Imaging

Four patients with cystic fibrosis (CF) were examined with combined hyperpolarized helium 3-enhanced and conventional proton magnetic resonance (MR) imaging. After inhalation of the polarized 3He gas, single breath-hold, gradient-echo images (resonant frequency of 3He) were obtained to depict lung ventilation. Conventional T2-weighted fast spin-echo (hydrogen) images were also obtained to depict morphologic abnormalities. 3He images were successfully and reproducibly generated that showed both morphologic abnormalities and, often more extensive, ventilation abnormalities. 3He MR imaging may provide a method for evaluating progression of pulmonary disease in patients with CF.

Background: Image-guided bronchoscopy using hyperpolarized 3 He magnetic resonance imaging (HP-MRI) to prospectively identify poorly- and well-ventilated lung regions has revealed differences in inflammatory cells and mediators between regions in mild-moderate asthma following a virus-induced exacerbation. Thus, we hypothesize that image-guided bronchoscopy targeting HP-MRI ventilation defects that emerge following an exacerbation in severe asthma can characterize inflammatory cell and gene expression profiles active in airway remodeling. Methods: Severe asthma patients enrolled in the Severe Asthma Research Program (SARPIII) who experienced a subsequent exacerbation underwent HP-MRI after symptom recovery. Emergent ventilation defects (defect) and persistently well-ventilated (control) regions were identified and brushings and bronchial biopsies were obtained. Biopsy tissues were fixed, paraffin-embedded, sectioned, and labeled for immune-specific antigens. Cell counts were made above the lamina reticulum in the airway epithelium (epi) and deep to the epithelium (deep) (Figure 1A); airway wall area (WA%) for 20 bronchopulmonary segments were quantified from baseline and 3-year CT using VIDAvision. Differences between regions were evaluated using Wilcoxon signed rank tests. Spearman correlations were used to evaluate relationships for baseline to 3-year change in CT measures and post-exacerbation bronchoscopy measures. RNA-sequencing and differential expression analysis was performed on bronchial brushings from paired control and defect airways. Results: Twelve participants (6M/6F, age=49±9years, post-bronchodilator FEV1=80±21%predicted) were recruited; eleven were treated with oral corticosteroids for their exacerbation. In defect versus control, CD117 was significantly increased (p=0.04), while CD20 (p=0.1) and EPX-deep (p=0.1) trended towards an increase. Correlations were significant for the change in WA% with CD4-deep, CD8-deep, CD68, CD68-deep, CD117, CD117-epi, CD138-deep and Ki67. We found 111 up- and 137 down-regulated genes in defect versus control regions (p&amp;lt;0.05, log2 fold change&amp;gt;0.25 or &amp;lt;-0.25). Pathway and cell type enrichment analyses of upregulated genes revealed strong enrichments for innate immune system and T cell activation pathways and for markers for NK, dendritic, mast, and CD4/CD8 T cells. Additionally, upregulated genes were strongly enriched for markers of mucus secretory cells, indicating mucus metaplasia in defect regions (AGR2, MUC5AC, SPDEF, TFF3, CXCL17, BPIFB1, CEACAM6). Conclusion: Image-guided bronchoscopic assessment using HP-MRI targeting specific regions of obstruction after recovery from exacerbation identified enrichment of mast cells and gene expression consistent with T-cell activation and mucus metaplasia compared to well-ventilated control regions in the same asthma patient. Subsequent comparisons on follow-up CT &amp;gt;1 year after exacerbation found airway specific remodeling in the corresponding airway segments correlated to post-exacerbation segmental immune cell counts.

Hyperpolarized gas magnetic resonance imaging (MRI) generates highly detailed maps of lung ventilation and physiological function while CT provides corresponding anatomical and structural information. Fusion of such complementary images enables quantitative analysis of pulmonary structure-function. However, direct image registration of hyperpolarized gas MRI to CT is problematic, particularly in lungs whose boundaries are difficult to delineate due to ventilation heterogeneity. This study presents a novel indirect method of registering hyperpolarized gas MRI to CT utilizing 1H-structural MR images that are acquired in the same breath-hold as the gas MRI. The feasibility of using this technique for regional quantification of ventilation of specific pulmonary structures is demonstrated for the lobes.The direct and indirect methods of hyperpolarized gas MRI to CT image registration were compared using lung images from 15 asthma patients. Both affine and diffeomorphic image transformations were implemented. Registration accuracy was evaluated using the target registration error (TRE) of anatomical landmarks identified on 1H MRI and CT. The Wilcoxon signed-rank test was used to test statistical significance.For the affine transformation, the indirect method of image registration was significantly more accurate than the direct method (TRE = 14.7 ± 3.2 versus 19.6 ± 12.7 mm, p = 0.036). Using a deformable transformation, the indirect method was also more accurate than the direct method (TRE = 13.5 ± 3.3 versus 20.4 ± 12.8 mm, p = 0.006).Accurate image registration is critical for quantification of regional lung ventilation with hyperpolarized gas MRI within the anatomy delineated by CT. Automatic deformable image registration of hyperpolarized gas MRI to CT via same breath-hold 1H MRI is more accurate than direct registration. Potential applications include improved multi-modality image fusion, functionally weighted radiotherapy planning, and quantification of lobar ventilation in obstructive airways disease.

In the last few years there has been rapid progress in the application of nuclear magnetic resonance clinical imaging as a diagnostic aid (Partain et al, 1983; Steiner, 1983; Worthington, 1983). Records kept by the operators of NMR imaging equipment indicate that about 1800 individuals have now been examined without incident within the United Kingdom. In view of this progress, an advisory group (Appendix) appointed by the National Radiological Protection Board recommends some modifications to the original advice given in 1981 (NRPB, 1981). The principal modifications are that: (1) It is no longer considered necessary to exclude volunteers with a history of epilepsy or cardiac disease. (2) It is not obligatory that a registered medical practitioner trained in resuscitation techniques be present during an exposure. (3) Higher limits are recommended for rates of change of magnetic flux density when the period of change is less than 10 ms. (4) The radiofrequency limit of 15 MHz has been removed. Theoretical considerations indicate that the interaction of an applied magnetic field with the intrinsic magnetic moments of protons and electrons within a molecule could alter its rate of chemical reaction (McLauchlan, 1981). Chemical reactions involving radical pair intermediates are expected to be sensitive to magnetic fields for this reason and a number of enzyme reactions that might be expected to be affected have been identified (A. Cass, personal communication). However, there is no experimental confirmation of these theoretical possibilities at present.

Rationale: In patients with asthma, X-ray computed tomography (CT) has provided evidence of thickened airway walls and airway occlusions, but the total number of CT-visible airways and its relationship with disease severity is unknown.Objectives: To measure CT total airway count (TAC) in asthma and evaluate relationships with asthma severity, airway morphology, pulmonary function, and magnetic resonance imaging (MRI) ventilation.Methods: Participants underwent post-bronchodilator inspiratory CT, and prebronchodilator and post-bronchodilator spirometry and hyperpolarized 3He MRI. CT TAC was quantified as the sum of airways in the segmented airway tree, and airway wall area percent (WA%) and lumen area were measured. MRI ventilation abnormalities were quantified as the ventilation defect percent.Measurements and Main Results: We evaluated 70 participants, including 15 Global Initiative for Asthma (GINA) steps 1 to 3, 19 GINA 4, and 36 GINA 5 participants with asthma. As compared with GINA 1 to 3, TAC was significantly diminished in GINA 4 (P = 0.03) and GINA 5 (P = 0.045). Terminal airway intraluminal occlusion was present in 5 (2 GINA 4 and 3 GINA 5) of 70 participants. Sub-subsegmental airways were CT-invisible or missing in 69 out of 70 participants; the most common number of missing sub-subsegments was 10. Participants with ≥10 missing subsegments had worse WA% (P < 0.0001), lumen area (P < 0.0001), and ventilation defect percent (P = 0.03) than those with <10 missing subsegments. In a multivariable model, TAC (standardized regression coefficient = 0.50; P = 0.001) independently predicted FEV1 (R2 = 0.27; P = 0.003) and, in a separate model, TAC (standardized regression coefficient = -0.53; P < 0.0001) independently predicted airway WA% (R2 = 0.32; P = 0.0001).Conclusions: TAC was significantly diminished in participants with greater asthma severity and was related to airway wall thickness and ventilation defects. Fewer airways in severe than in mild asthma challenges our understanding of airway disease in asthma.Clinical trial registered with www.clinicaltrials.gov (NCT02351141).

To prospectively determine if a combined magnetic resonance (MR) protocol that includes T1-weighted dynamic contrast agent-enhanced (DCE) MR imaging, hydrogen 1 (1H) MR spectroscopy, and T2*-weighted perfusion MR imaging improves specificity in the diagnosis of breast cancer. The combined MR imaging-MR spectroscopy protocol was performed in 50 patients after positive findings at mammography but prior to biopsy. Single-voxel proton MR spectroscopy and perfusion MR imaging were conducted only if DCE MR images showed rapid contrast enhancement in the lesion. Biopsy results were used as the reference for comparison with MR results and for calculation of sensitivity and specificity in the detection of breast malignancy. DCE MR imaging alone showed 100% sensitivity and 62.5% specificity. The specificity improved to 87.5% with the addition of 1H MR spectroscopy and to 100% with the further addition of perfusion MR imaging. Twenty-eight patients underwent both MR spectroscopy and perfusion MR imaging. Two patients underwent MR spectroscopy but declined to undergo perfusion MR imaging. The remaining 20 patients had negative results at DCE MR imaging and therefore did not undergo the additional examinations. The combined MR protocol of DCE MR imaging, 1H MR spectroscopy, and perfusion MR imaging has high sensitivity and specificity in the diagnosis of breast cancer.

2-Deoxy-D-glucose (2DG) is a known surrogate molecule that is useful for inferring glucose uptake and metabolism. Although (13)C-labeled 2DG can be detected by nuclear magnetic resonance (NMR), its low sensitivity for detection prohibits imaging to be performed. Using chemical exchange saturation transfer (CEST) as a signal-amplification mechanism, 2DG and the phosphorylated 2DG-6-phosphate (2DG6P) can be indirectly detected in (1)H magnetic resonance imaging (MRI). We showed that the CEST signal changed with 2DG concentration, and was reduced by suppressing cerebral metabolism with increased general anesthetic. The signal changes were not affected by cerebral or plasma pH, and were not correlated with altered cerebral blood flow as demonstrated by hypercapnia; neither were they related to the extracellular glucose amounts as compared with injection of D- and L-glucose. In vivo (31)P NMR revealed similar changes in 2DG6P concentration, suggesting that the CEST signal reflected the rate of glucose assimilation. This method provides a new way to use widely available MRI techniques to image deoxyglucose/glucose uptake and metabolism in vivo without the need for isotopic labeling of the molecules.

Magnetic Resonance (MR) imaging using hyperpolarized noble gases (HNG's), 3He and 129Xe, provide non‐invasive approaches for probing lung function and structure. In particular, measurement of HNG ventilated lung volumes (e.g., ventilation defects) and apparent diffusion coefficients (ADC) are useful for characterizing chronic obstructive pulmonary disease (COPD) and emphysema. Of particular interest, hyperpolarized 129Xe also dissolves in the lung parenchyma and blood compartments, offering an interesting palette of potential biomarkers of pulmonary disease, including quantifying xenon diffusing capacity in inflammatory disease and may be useful for assessing pulmonary perfusion. 129Xe dissolved in tissue and blood experience large chemical shifts and can be selectively saturated and allowed to recover as a function of delay time as in the chemically selective saturation recovery (CSSR) technique. CSSR has previously been used to study surface‐to‐volume ratio (S/V) and diffusing capacity of xenon (DXe) in the lung which is analogous to diffusing capacity of carbon monoxide. In this work, the 129Xe CSSR technique is used to measure S/V ratios and Dxelp in whole healthy rat lungs as a function of ventilated lung volume assessed with 3He MR imaging. The data follow theoretically predicted trends for Ttr, S/V and DXeLP. In parallel to this study, 3D 129Xe imaging was also investigated and compared to 3He for lung volume assessment in an effort to remove the reliance on 3He which is costly and scarce. Absolute ventilated volumes (|VLV|) derived from preliminary results for 3He and 129Xe were 9.74 mL and 9.14 mL respectively for a pressure of 9.1cmH2O.

Introduction. Magnetic Resonance Imaging (MRI) has modified the practice of radiology. MRI is base on safe interaction between radiowaves at a particular frequency and hydrogen nuclei in the body. Metabolic encephalophaties are by definition those disorder of the central nervous system that are not due primarily to structural abnormalities. Aim. Here we present the 1H MRI and functional MRI (fMRI) method applied to diagnosis of disorders of the central nervous system. Material and methods. Analysis of literature and self-research. Results.We have discussed the major MRI applications in the characteristic of the central nervous system. The relationship beteen the motion of flowing blood and the representation of the blood on images is complex. This work is an introduction to the basic ideas and techniques of fMRI. Therefore, both, 1H MRI and functional MRI, methods are ued in neuroscience. Conclusion. Nonivasive MRI and functional MRI are daily diagnostics methods in neurology.