Stephen Dashnaw

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.

ObjectivesThe 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 MethodsA 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. ResultsQuantitative 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. ConclusionRegional 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.

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.

Human airway branch variation and chronic obstructive pulmonary disease

Significance The human airway tree is a filter of noxious particulate matter, the primary cause of chronic obstructive pulmonary disease (COPD). We demonstrate that variation in central airway tree branching occurs in over one-quarter of the general population and increases COPD susceptibility, particularly among smokers. We show that these central airway branch variants are biomarkers of altered distal lung structure, the primary site of COPD pathobiology. Finally, we demonstrate the heritability of central airway branch variants within families and identify and replicate an association with FGF10. These findings suggest that central airway branch variants, easily detectable by computed tomography, represent heritable biomarkers of widely altered lung structure and a COPD susceptibility factor. 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) - the mesa copd study

Arterial stiffness had been proposed as the cause of sub-clinical left ventricular dysfunction in patients with COPD. Vascular studies in COPD patients were mainly assessed by carotid-femoral (aortic) pulse wave velocity using micromanometer applanation tonometry. The evaluation of pulmonary artery (PA) elasticity in COPD has not been assessed. This study seeks to evaluate indices of PA stiffness in patients with COPD. We hypothesized that patients with COPD would have increased pulmonary artery stiffness compared to healthy individuals. To test this we determine the pulmonary artery area change (distensibility or pulsatility in %) by cardiac magnetic resonance imaging (MRI) and related PA distensibility to the severity of COPD.

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

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

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.