Mapping Alveolar Oxygen Partial Pressure in COPD Using Hyperpolarized Helium-3: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study.

Chronic obstructive pulmonary disease (COPD) and emphysema are characterized by functional and structural damage which increases the spaces for gaseous diffusion and impairs oxygen exchange. Here we explore the potential for hyperpolarized (HP) 3He MRI to characterize lung structure and function in a large-scale population-based study. Participants (n = 54) from the Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study, a nested case-control study of COPD among participants with 10+ packyears underwent HP 3He MRI measuring pAO2, apparent diffusion coefficient (ADC), and ventilation. HP MRI measures were compared to full-lung CT and pulmonary function testing. High ADC values (>0.4 cm2/s) correlated with emphysema and heterogeneity in pAO2 measurements. Strong correlations were found between the heterogeneity of global pAO2 as summarized by its standard deviation (SD) (p < 0.0002) and non-physiologic pAO2 values (p < 0.0001) with percent emphysema on CT. A regional study revealed a strong association between pAO2 SD and visual emphysema severity (p < 0.003) and an association with the paraseptal emphysema subtype (p < 0.04) after adjustment for demographics and smoking status. HP noble gas pAO2 heterogeneity and the fraction of non-physiological pAO2 results increase in mild to moderate COPD. Measurements of pAO2 are sensitive to regional emphysematous damage detected by CT and may be used to probe pulmonary emphysema subtypes. HP noble gas lung MRI provides non-invasive information about COPD severity and lung function without ionizing radiation.

Quantification of lung ventilation defects on hyperpolarized MRI: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD study.

PURPOSE: To develop an end-to-end deep learning (DL) framework to segment ventilation defects on pulmonary hyperpolarized MRI. MATERIALS AND METHODS: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease (COPD) study is a nested longitudinal case-control study in older smokers. Between February 2016 and July 2017, 56 participants (age, mean ± SD, 74 ± 8 years; 34 men) underwent same breath-hold proton (1H) and helium (3He) MRI, which were annotated for non-ventilated, hypo-ventilated, and normal-ventilated lungs. In this retrospective DL study, 820 1H and 3He slices from 42/56 (75%) participants were randomly selected for training, with the remaining 14/56 (25%) for test. Full lung masks were segmented using a traditional U-Net on 1H MRI and were imported into a cascaded U-Net, which were used to segment ventilation defects on 3He MRI. Models were trained with conventional data augmentation (DA) and generative adversarial networks (GAN)-DA. RESULTS: Conventional-DA improved 1H and 3He MRI segmentation over the non-DA model (P = 0.007 to 0.03) but GAN-DA did not yield further improvement. The cascaded U-Net improved non-ventilated lung segmentation (P < 0.005). Dice similarity coefficients (DSC) between manually and DL-segmented full lung, non-ventilated, hypo-ventilated, and normal-ventilated regions were 0.965 ± 0.010, 0.840 ± 0.057, 0.715 ± 0.175, and 0.883 ± 0.060, respectively. We observed no statistically significant difference in DCSs between participants with and without COPD (P = 0.41, 0.06, and 0.18 for non-ventilated, hypo-ventilated, and normal-ventilated regions, respectively). CONCLUSION: The proposed cascaded U-Net framework generated fully-automated segmentation of ventilation defects on 3He MRI among older smokers with and without COPD that is consistent with our reference method.

Reproducibility and Changes in Vena Caval Blood Flow by Using 4D Flow MRI in Pulmonary Emphysema and Chronic Obstructive Pulmonary Disease (COPD): The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Substudy.

BackgroundChronic obstructive pulmonary disease (COPD) is associated with hemodynamic changes in the pulmonary vasculature. However, cardiac effects are not fully understood and vary by phenotype of chronic lower respiratory disease.PurposeTo use four-dimensional (4D) flow MRI for comprehensive assessment of the right-sided cardiovascular system, assess its interrater and intraobserver reproducibility, and examine associations with venous return to the right heart in individuals with chronic COPD and emphysema.Materials and MethodsThe Multi-Ethnic Study of Atherosclerosis COPD substudy prospectively recruited participants who smoked and who had COPD and nested control participants from population-based samples. Electrocardiography and respiratory gated 4D flow 1.5-T MRI was performed at three sites with full volumetric coverage of the thoracic vessels in 2014-2017 with postbronchodilator spirometry and inspiratory chest CT to quantify percent emphysema. Net flow, peak velocity, retrograde flow, and retrograde fraction were measured on 14 analysis planes. Interrater reproducibility was assessed by two independent observers, and the principle of conservation of mass was employed to evaluate the internal consistency of flow measures. Partial correlation coefficients were adjusted for age, sex, race/ethnicity, height, weight, and smoking status.ResultsAmong 70 participants (29 participants with COPD [mean age, 73.5 years ± 8.1 {standard deviation}; 20 men] and 41 control participants [mean age, 71.0 years ± 6.1; 22 men]), the interrater reproducibility of the 4D flow MRI measures was good to excellent (intraclass correlation coefficient range, 0.73-0.98), as was the internal consistency. There were no statistically significant differences in venous flow parameters according to COPD severity (P > .05). Greater percent emphysema at CT was associated with greater regurgitant flow in the superior and inferior caval veins and tricuspid valve (adjusted r = 0.28-0.55; all P < .01), particularly in the superior vena cava.ConclusionFour-dimensional flow MRI had good-to-excellent observer variability and flow consistency. Percent emphysema at CT was associated with statistically significant differences in retrograde flow, greatest in the superior vena cava.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Choe in this issue.

Cerebrovascular Disease and Neurodegeneration in Alzheimer's Disease with and without a Strong Family History: A Pilot Magnetic Resonance Imaging Study in Dominican Republic.

The incidence and prevalence of Alzheimer's disease (AD) dementia are higher among Caribbean Hispanics than among non-Hispanic Whites. The causes of this health disparity remain elusive, partially because of the relative limited capacity for biomedical research in the developing countries that comprise Caribbean Latin America. To begin to address this issue, we were awarded a Development Research Award from the US NIH and Fogarty International Center in order to establish the local capacity to integrate magnetic resonance imaging (MRI) into studies of cognitive aging and dementia in Dominican Republic, establish collaborations with Dominican investigators, and conduct a pilot study on the role of cerebrovascular markers in the clinical expression of AD. Ninety older adult participants with and without AD dementia and with and without a strong family history of AD dementia received MRI scans and clinical evaluation. We quantified markers of cerebrovascular disease (white matter hyperintensities [WMH], presence of infarct, and presence of microbleed) and neurodegeneration (entorhinal cortex volume) and compared them across groups. Patients with AD dementia had smaller entorhinal cortex and greater WMH volumes compared with controls, regardless of family history status. This study provides evidence for the capacity to conduct MRI studies of cognitive aging and dementia in Dominican Republic. The results are consistent with the hypothesis that small vessel cerebrovascular disease represents a core feature of AD dementia, as affected participants had elevated WMH volumes irrespective of family history status.

Human airway branch variation and chronic obstructive pulmonary disease.

Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts (n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung. The second most common airway branch variant is associated with COPD among smokers, with narrower airway lumens in all lobes, and with genetic polymorphisms within the FGF10 gene. We conclude that central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.

Pulmonary artery stiffness in chronic obstructive pulmonary disease (COPD) and emphysema: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) and particularly emphysema are characterized by stiffness of the aorta, due in part to accelerated elastin degradation in the lungs and aorta. Stiffness of the pulmonary arteries (PAs) may also be increased in COPD and emphysema, but data are lacking. We assessed PA stiffness using MRI in patients with COPD and related these measurements to COPD severity and percent emphysema. MATERIALS AND METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited 290 participants, age 50-79 years with 10 or more packyears and free of clinical cardiovascular disease. COPD severity were defined on postbronchodilator spirometry by ATS/ERS criteria. Percent emphysema was defined as the percentage of regions of the lung < -950 Hounsfield units on full-lung computed tomography (CT). PA stain was defined by the percent change in cross-sectional PA area between systole and diastole on MRI. Blood flow across the tricuspid and mitral valves was assessed by phase-contrast MRI for determination of the ventricular diastolic dysfunction (E/A ratio). RESULTS: PA strain was reduced in COPD compared with controls (P = 0.002) and was inversely correlated with COPD severity (P = 0.004). PA strain was inversely associated to percent emphysema (P = 0.01). PA strain was also markedly correlated with right ventricular diastolic dysfunction measured by E/A ratios in the fully adjusted mix models (P = 0.02). CONCLUSION: PA strain is reduced in COPD, related in part to percent emphysema on CT scan, which may have implications for pulmonary small vessel flow and right ventricular function. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:262-271.

Effect of MRI on breast tissue expanders and recommendations for safe use.

INTRODUCTION: Ferromagnetic port-containing breast tissue expanders are currently labeled MRI-unsafe because of the presumption that magnets should not enter the machine. However, designating these devices as MRI-unsafe can lead to unnecessary procedures or suboptimal imaging choices. This study provides an ex vivo analysis of how breast tissue expanders behave when subjected to strong magnetic fields to determine which variables might affect clinical risk. METHODS: Three different brands of tissue expanders were evaluated in three MRI environments. Translational force was determined using the deflection angle method. Torque on empty, saline-filled, and air-filled expanders was evaluated on a 0-4 scale. Magnetic field was measured using a gaussmeter. The weight required to prevent displacement of the expanders was determined for both air- and saline-filled expanders. Temperature over time was measured using an alcohol thermometer. RESULTS: Magnetic field strength, deflection angle, and torque were the greatest in 3T MRI environments and varied by device manufacturer (Sientra > Mentor > Allergan). Saline-filled expanders required 240 mL and air-filled required 360 mL volume to make the torque undetectable, and the effect of torque could be mitigated with prone positioning. A weight of 120 g was required to prevent displacement of a saline-filled tissue expander and 870 g for an empty expander. There were no appreciable changes in temperature. CONCLUSIONS: Previously described risks may be reduced by using a 1.5T MRI, device selection, filling expanders with saline, and prone positioning. MRI can be considered in patients with breast tissue expanders when appropriate peri-procedural choices have been made so that the benefits of undergoing MRI outweigh the risks.

Quantitative and semiquantitative measures of regional pulmonary microvascular perfusion by magnetic resonance imaging and their relationships to global lung perfusion and lung diffusing capacity: the multiethnic study of atherosclerosis chronic obstructive pulmonary disease study.

OBJECTIVES: The aim of this study was to evaluate the quantitative and semiquantitative measures of regional pulmonary parenchymal perfusion in patients with chronic obstructive pulmonary disease (COPD) in relationship to global lung perfusion (GLP) and lung diffusing capacity (DLCO). MATERIALS AND METHODS: A total of 143 participants in the Multiethnic Study of Atherosclerosis COPD Study were examined by dynamic contrast-enhanced pulmonary perfusion magnetic resonance imaging (MRI) at 1.5 T. Pulmonary microvascular blood flow (PBF) was calculated on a pixel-by-pixel basis by using a dual-bolus technique and the Fermi function model. Semiquantitative parameters for regional pulmonary microvascular perfusion were calculated from signal intensity-time curves in the lung parenchyma. Intraoberserver and interobserver coefficients of variation (CVs) and correlations between quantitative and semiquantitative MRI parameters and with GLP and DLCO were determined. RESULTS: Quantitative and semiquantitative parameters of pulmonary microvascular perfusion were reproducible, with CVs for all parameters of less than 10%. Furthermore, these MRI parameters were correlated with GLP and DLCO, and there was good agreement between PBF and GLP. Quantitative and semiquantitative MRI parameters were closely correlated (eg, r = 0.86 for maximum signal increase with PBF). In participants without COPD, the physiological distribution of pulmonary perfusion could be determined by regional MRI measurements. CONCLUSION: Regional pulmonary microvascular perfusion can reliably be quantified from dynamic contrast-enhanced MRI. Magnetic resonance imaging-derived quantitative and semiquantitative perfusion measures correlate with GLP and DLCO.

A novel adenoviral vector labeled with superparamagnetic iron oxide nanoparticles for real-time tracking of viral delivery.

In vivo tracking of gene therapy vectors challenges the investigation and improvement of biodistribution of these agents in the brain, a key feature for their targeting of infiltrative malignant gliomas. The glioma-targeting Ad5/3-cRGD gene therapy vector was covalently bound to super-paramagnetic iron oxide (Fe(3)O(4)) nanoparticles (SPION) to monitor its distribution by MRI. Transduction of labeled and unlabeled vectors was assessed on the U87 glioma cell line and normal human astrocytes (NHA), and was higher in U87 compared to NHA, but was similar between labeled and unlabeled virus. An in vivo study was performed by intracranial subcortical injection of labeled-Ad5/3-cRGD particles into a pig brain. The labeled vector appeared in vivo as a T2-weighted hyperintensity and a T2-gradient echo signal at the injection site, persisting up to 72 hours post-injection. We describe a glioma-targeting vector that is labeled with SPION, thereby allowing for MRI detection with no change in transduction capability.

Distinct but overlapping neural networks subserve depression and insecure attachment.

Insecure attachment has been linked to depression and to outcome in psychotherapy. The neural mechanisms subserving the relationship between attachment security and depression are not well understood. We have developed a method to examine attachment-related brain activity in depression. Twenty-eight women, half depressed, viewed images of their mother, a female friend, and female strangers during fMRI scanning. The effects of depression and insecure attachment were determined with whole-brain multiple linear regression of blood-oxygen-level-dependent response against subjects' Beck Depression Inventory and Adult Attachment Interview (AAI) coherence of mind scores. Interaction effects were analyzed with ANOVA. Activity associated with depression and with insecure attachment was found in the cortico-striato-thalamic circuits of affect regulation. For early attachment (mother-friend contrast), depression scores correlated with activation of cortical and sub-cortical components of these circuits, while attachment insecurity correlated with sub-cortical activity in the same circuitry. Depression and attachment insecurity correlated with both cortical and sub-cortical activities for mother-stranger, and areas of overlap and of enhancing interactions between depression and insecure attachment were found. For late attachment (friend-stranger contrast), only cortical effects were found. Depression and attachment insecurity may be subserved by similar but distinct components of affect regulating circuits. Their interactions may explain the greater difficulty of treating depression in insecurely attached patients and suggest a contributing role for insecure attachment in depression. Further, differential sub-cortical vs cortical encoding of early vs late attachment suggests a top-down model of late attachment, potentially relevant to psychotherapeutic outcome.

Thigh muscle volume measured by magnetic resonance imaging is stable over a 6-month interval in spinal muscular atrophy.

Changes in thigh muscle volume over 6 months were assessed using magnetic resonance imaging in 11 subjects aged 6 to 47 years with spinal muscular atrophy (4 type 2 and 7 type 3; 4 ambulatory and 3 nonambulatory). Muscle volume with normal and abnormal signal was measured using blinded, semiautomated analysis of reconstructed data. Volumes at baseline and 6 months were correlated with clinical function at each epoch. There was minimal increase in normal (0.3 ± 1.4 mL/cm) and total (0.1 ± 1.3 mL/cm) muscle. Muscle volume correlated closely with clinical function. Minimal interval change in muscle volume is consistent with the established clinical history of minimal disease progression over intervals shorter than 1 year. Relative constancy of muscle volume estimation and correlation with established functional measures suggest a role for segmental magnetic resonance imaging as a biomarker of treatment effect in future therapeutic trials.

Functional imaging with reinforcement, eyetracking, and physiological monitoring.

We use functional brain imaging (fMRI) to study neural circuits that underlie decision-making. To understand how outcomes affect decision processes, simple perceptual tasks are combined with appetitive and aversive reinforcement. However, the use of reinforcers such as juice and airpuffs can create challenges for fMRI. Reinforcer delivery can cause head movement, which creates artifacts in the fMRI signal. Reinforcement can also lead to changes in heart rate and respiration that are mediated by autonomic pathways. Changes in heart rate and respiration can directly affect the fMRI (BOLD) signal in the brain and can be confounded with signal changes that are due to neural activity. In this presentation, we demonstrate methods for administering reinforcers in a controlled manner, for stabilizing the head, and for measuring pulse and respiration.

Reproducibility of single- and multi-voxel 1H MRS measurements of intramyocellular lipid in overweight and lean subjects under conditions of controlled dietary calorie and fat intake.

The reproducibility of repeated single-voxel 1H MRS (SV-MRS) and spectroscopic imaging (MRSI) measurements of intramyocellular lipid (IMCL) in the tibialis anterior muscle of five lean and five overweight female Caucasians, during 7 days of controlled dietary fat and calorie intake, was assessed at 1.5 T. Duplicate measures of IMCL relative to total muscle creatine (IMCL/tCr) obtained 3 days apart by both SV-MRS and MRSI correlated well (r = 0.65 and r = 0.95, respectively, P < 0.05). The coefficients of variation for repeated measures of IMCL/tCr by SV-MRS and MRSI were 24.4% and 10.7%, respectively. IMCL/tCr measured by MRSI was higher in overweight subjects than in lean subjects (8.3 +/- 3.8 vs 4.3 +/- 2.4, P < 0.05). Although both methods achieved good reproducibility in measuring IMCL in vivo, MRSI was found to offer greater flexibility and reliability, and higher sensitivity to IMCL differences, whereas SV-MRS was advantageous with respect to shorter scan time and ease of implementation.

Sequential acquisition and processing of perfusion and diffusion MRI data for a porcine stroke model.

An automated data processing pipeline, designed for handling a large throughput of sequentially acquired MRI brain data, is described. The system takes as input multiple diffusion weighted (DWI) and perfusion weighted imaging (PWI) volumes acquired at different temporal points, automatically segments and registers them, and ultimately outputs a database used to track various perfusion and diffusion parameters through time at individual brain voxels. This pipeline has been utilized to successfully process two pig brains from an induced stroke experiment.

Feasibility of stent placement in carotid arteries with real-time MR imaging guidance in pigs.

All examinations were performed with approval from the institutional animal care and use committee of Columbia University. To assess the feasibility of real-time magnetic resonance (MR) imaging-guided neurovascular intervention in a swine model, the authors placed stents in the carotid arteries of five domestic pigs. Seven-French vascular sheaths were placed in the target carotid arteries via femoral access by using active MR tracking. Ten nitinol stents (8-10 x 20-40 mm) were successfully deployed in the target segments of carotid arteries bilaterally. MR imaging and necropsy findings confirmed stent position. Necropsy revealed no gross vascular injury. Study results demonstrated the feasibility of performing real-time MR imaging-guided neurovascular intervention by using an active-tracking technique in an animal model.

Transfemoral catheterization of carotid arteries with real-time MR imaging guidance in pigs.

All procedures and protocols were approved by the institutional animal care and use committee of Columbia University. To determine whether transfemoral catheterization of the carotid arteries can be performed entirely with real-time magnetic resonance (MR) imaging guidance, the authors catheterized the carotid arteries in six domestic pigs by using active-tracking catheters and guidewires and MR tracking software created for neurovascular procedures. The carotid arteries were successfully catheterized 24 times, on average within 5 minutes after insertion of the catheter into the femoral artery. Results demonstrated the feasibility of performing transfemoral catheterization of the carotid arteries with active MR tracking devices in a conventional MR imaging unit.

Breast lesions detected on MR imaging: features and positive predictive value.

OBJECTIVE: The purpose of this study was to analyze features of breast lesions detected on MR imaging that had subsequent biopsy and to determine the positive predictive value (PPV) of these features. MATERIALS AND METHODS: Retrospective review was performed of 100 consecutive solitary MR imaging-detected breast lesions that had MR imaging-guided needle localization and surgical excision. We described lesions, using terms found in a proposed breast MR imaging lexicon. Histologic findings were reviewed. RESULTS: Carcinoma was identified in 25 lesions (25%), including ductal carcinoma in situ (DCIS) in 13 (52%) and infiltrating carcinoma in 12 (48%). Carcinoma was found in 15 (25%) of 60 masses versus 10 (25%) of 40 nonmass lesions; most malignant masses (73%) were infiltrating carcinoma, whereas most malignant nonmass lesions (90%) were DCIS. The features with the highest PPV were spiculated margin (80% carcinoma), rim enhancement (40% carcinoma), and irregular shape (32% carcinoma) for mass lesions and segmental (67% carcinoma) or clumped linear and ductal enhancement (31% carcinoma) for nonmass lesions. Visually assessed kinetic patterns were not significant predictors of carcinoma, but washout was present in 70% of infiltrating carcinomas versus 9% of DCIS lesions (p < 0.01). Carcinoma was present in 17 (19%) of 88 lesions classified as suspicious versus eight (67%) of 12 lesions classified as highly suggestive of malignancy (p = 0.001). CONCLUSION: Among MR imaging-detected breast lesions referred for biopsy, carcinoma was found in 25%, of which half were DCIS. Features with the highest PPV were spiculated margin, rim enhancement, and irregular shape for mass lesions and segmental or clumped linear and ductal enhancement for nonmass lesions. Final assessment categories were significant predictors of carcinoma.