Quantitative Mapping of Lung Ventilation Using Hyperpolarized Gas Magnetic Resonance Imaging

The main objective of this project was to develop and implement techniques for high-resolution quantitative imaging of ventilation in lungs using hyperpolarized gas magnetic resonance imaging (MRI). Pulmonary ventilation is an important aspect of lung function and is frequently compromised through several different mechanisms and at varying degrees in presence of certain lung conditions, such as chronic obstructive pulmonary diseases. The primary focus of this development is on large mammalian species as a steppingstone towards translation to human subjects. The key deliverables of this project are a device for real-time mixing and delivery of hyperpolarized gases such as 3He and 129Xe in combination with O2, an MRI acquisition scheme for practical imaging of ventilation signal build-up in the lungs, and a robust mathematical model for estimation of regional fractional ventilation values at a high resolution. A theoretical framework for fractional gas replacement in the lungs is presented to describe MRI signal dynamics during continuous breathing of a mixture of hyperpolarized gases in presence of several depolarization mechanisms. A hybrid ventilation and imaging acquisition scheme is proposed to acquire a series of images during short end-inspiratory breath-holds over several breaths. The sensitivity of the estimation algorithm is assessed with respect to noise, model uncertainty and acquisition parameters, and subsequently an optimal set of acquisition parameters is proposed to minimize the fractional ventilation estimation error. This framework is then augmented by an undersampled parallel MRI scheme to accelerate image acquisition to enable fractional ventilation imaging over the entire lung volume in a single pass. The image undersampling was also leveraged to minimize the coupling associated with signal buildup in the airways and the irreversible effect of RF pulses. The proposed technique was successfully implemented in pigs under mechanical ventilation, and preliminary measurements were performed in an adult human subject under voluntary breathing

Attitude toward Plagiarism among Iranian Medical Faculty Members

The goal of this study was to assess attitude towards plagiarism in faculty members of Medical School at Tehran University of Medical Sciences. One hundred and twenty medical faculty members ofTehran University of Medical Sciences were enrolled in this cross-sectional study. They were asked to answer to valid and reliable Persian version of attitude towards plagiarism questionnaire. Attitude toward plagiarism, positive attitude toward self-plagiarism and plagiarism acceptance were assessed. Eighty seven filled-up questionnaires were collected. Mean total number of correct answers was 11.6 ± 3.1. Mean number of correct answers to questions evaluating self-plagiarism was 1.7 ± 0.4 and mean number of correct answers to questions evaluating plagiarism acceptance was 1.4 ± 0.2. There was no significant correlation between plagiarism acceptance and self-plagiarism (r=0.17, P=0.1). It is essential to provide materials (such as workshops, leaflets and mandatory courses) to make Iranian medical faculty members familiar with medicalresearch ethics issues such as plagiarism

Regional correlation of emphysematous changes in lung function and structure: a comparison between pulmonary function testing and hyperpolarized MRI metrics

Regional and global relationships of lung function and structure were studied using hyperpolarized 3He MRI in a rat elastase-induced model of emphysema (n = 4) and healthy controls (n = 5). Fractional ventilation (r) and apparent diffusion coefficient (ADC) of 3He were measured at a submillimeter planar resolution in ventral, middle, and dorsal slices 6 mo after model induction. Pulmonary function testing (PFT) was performed before MRI to yield forced expiratory volume in 50 ms (FEV50), airway resistance (RI), and dynamic compliance (Cdyn). Cutoff threshold values of ventilation and diffusion, r* and ADC*, were computed corresponding to 80% population of pixels falling above or below each threshold value, respectively. For correlation analysis, r* was compared with FEV50/functional residual capacity (FRC), RI and Cdyn, whereas ADC* was compared with FEV50/FRC, total lung capacity (TLC), and Cdyn. Regional correlation of r and ADC was evaluated by dividing each of the three lung slices into four quadrants. Cdyn was significantly larger in elastase rats (0.92 ± 0.16 vs. 0.61 ± 0.12 ml/cmH2O). The difference of RI and FEV50 was insignificant between the two groups. The r* of healthy rats was significantly larger than the elastase group (0.42 ± 0.03 vs. 0.28 ± 0.06), whereas ADC* was significantly smaller in healthy animals (0.27 ± 0.04 vs. 0.36 ± 0.01 cm2/s). No systematic difference in these quantities was observed between the three lung slices. A significant 33% increase in ADC* and a significant 31% decline in r* for elastase rats was observed compared with a significant 51% increase in Cdyn and a nonsignificant 26% decline in FEV50/FRC. Correlation of imaging and PFT metrics revealed that r and ADC divide the rats into two separate clusters in the sample space

Quantitative imaging of alveolar recruitment with hyperpolarized gas MRI during mechanical ventilation

The aim of this study was to assess the utility of 3He MRI to noninvasively probe the effects of positive end-expiratory pressure (PEEP) maneuvers on alveolar recruitment and atelectasis buildup in mechanically ventilated animals. Sprague-Dawley rats (n = 13) were anesthetized, intubated, and ventilated in the supine position (4He-to-O2 ratio: 4:1; tidal volume: 10 ml/kg, 60 breaths/min, and inspiration-to-expiration ratio: 1:2). Recruitment maneuvers consisted of either a stepwise increase of PEEP to 9 cmH2O and back to zero end-expiratory pressure or alternating between these two PEEP levels. Diffusion MRI was performed to image 3He apparent diffusion coefficient (ADC) maps in the middle coronal slices of lungs (n = 10). ADC was measured immediately before and after two recruitment maneuvers, which were separated from each other with a wait period (8–44 min). We detected a statistically significant decrease in mean ADC after each recruitment maneuver. The relative ADC change was −21.2 ± 4.1 % after the first maneuver and −9.7 ± 5.8 % after the second maneuver. A significant relative increase in mean ADC was observed over the wait period between the two recruitment maneuvers. The extent of this ADC buildup was time dependent, as it was significantly related to the duration of the wait period. The two postrecruitment ADC measurements were similar, suggesting that the lungs returned to the same state after the recruitment maneuvers were applied. No significant intrasubject differences in ADC were observed between the corresponding PEEP levels in two rats that underwent three repeat maneuvers. Airway pressure tracings were recorded in separate rats undergoing one PEEP maneuver (n = 3) and showed a significant relative difference in peak inspiratory pressure between pre- and poststates. These observations support the hypothesis of redistribution of alveolar gas due to recruitment of collapsed alveoli in presence of atelectasis, which was also supported by the decrease in peak inspiratory pressure after recruitment maneuvers

A bioengineering method for modeling alveolar Rhabdomyosarcoma and assessing chemotherapy responses

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue malignant tumor. Treatment of RMS usually includes primary tumor resection along with systemic chemotherapy. Two-dimensional (2D) cell culture systems and animal models have been extensively used for investigating the potential efficacy of new RMS treatments. However, RMS cells behave differently in 2D culture than in vivo, which has recently inspired the adoption of three-dimensional (3D) culture environments. In the current paper, we will describe the detailed methodology we have developed for fabricating a 3D engineered model to study alveolar RMS (ARMS) in vitro. This model consists of a thermally cross-linked collagen disk laden with RMS cells that mimics the structural and bio-chemical aspects of the tumor extracellular matrix (ECM). This process is highly reproducible and produces a 3D engineered model that can be used to analyze the cytotoxicity and autophagy induction of drugs on ARMS cells. The most improtant bullet points are as following: • We fabricated 3D model of ARMS. • The current ARMS 3D model can be used for screening of chemotherapy drugs. • We developed methods to detect apoptosis and autophagy in ARMS 3D model to detect the mechansims of chemotherapy agents