multi-modal-pulmonary-imaging-using-complementary-information-from-ct

Multi-modal Pulmonary Imaging: Using Complementary Information from CT and Hyperpolarized <sup>129</sup>Xe MRI to Evaluate Lung Structure-Function

Hyperpolarized 129Xe gas MRI is an emerging technique to evaluate and measure regional lung function including pulmonary gas distribution and gas ...

University of Kansas Medical Center

Structural remodeling in lung disease is progressive and heterogeneous, making temporally and spatially explicit information necessary to understand disease initiation and progression. While mouse models are essential to elucidate mechanistic pathways underlying disease, the experimental tools commonly available to quantify lung disease burden are typically invasive (, histology). This necessitates large cross-sectional studies with terminal endpoints, which increases experimental complexity and expense. Alternatively, magnetic resonance imaging (MRI) provides information noninvasively, thus permitting robust, repeated-measures statistics. Although lung MRI is challenging due to low tissue density and rapid apparent transverse relaxation (T* <1 ms), various imaging methods have been proposed to quantify disease burden. However, there are no widely accepted strategies for preclinical lung MRI. As such, it can be difficult for researchers who lack lung imaging expertise to design experimental protocols-particularly for novel mouse models. Here, we build upon prior work from several research groups to describe a widely applicable acquisition and analysis pipeline that can be implemented without prior preclinical pulmonary MRI experience. Our approach utilizes 3D radial ultrashort echo time (UTE) MRI with retrospective gating and lung segmentation is facilitated with a deep-learning algorithm. This pipeline was deployed to assess disease dynamics over 255 days in novel, transgenic mouse models of lung fibrosis based on disease-associated, loss-of-function mutations in Surfactant Protein-C. Previously identified imaging biomarkers (tidal volume, signal coefficient of variation, etc.) were calculated semi-automatically from these data, with an objectively-defined high signal volume identified as the most robust metric. Beyond quantifying disease dynamics, we discuss common pitfalls encountered in preclinical lung MRI and present systematic approaches to identify and mitigate these challenges. While the experimental results and specific pedagogical examples are confined to lung fibrosis, the tools and approaches presented should be broadly useful to quantify structural lung disease in a wide range of mouse models.

Preclinical MRI to Quantify Pulmonary Disease Severity and Trajectories in Poorly Characterized Mouse Models: A Pedagogical Example Using Data from Novel Transgenic Models of Lung Fibrosis.

Hyperpolarized (HP)  Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP  Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP  Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies. To promote uniformity and adoption of HP  Xe MRI more widely in translational research, multi-site trials, and ultimately clinical practice, this position paper from the  Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP  Xe MRI. Recommendations are described for the most common HP gas MRI techniques-calibration, ventilation, alveolar-airspace size, and gas exchange-across MRI scanner manufacturers most used for this application. Moreover, recommendations are described for  Xe dose volumes and breath-hold standardization to further foster consistency of imaging studies. The intention is that sites with HP  Xe MRI capabilities can readily implement these methods to obtain consistent high-quality images that provide regional insight into lung structure and function. While this document represents consensus at a snapshot in time, a roadmap for technical developments is provided that will further increase image quality and efficiency. These standardized dosing and imaging protocols will facilitate the wider adoption of HP  Xe MRI for multi-site pulmonary research.

Protocols for multi-site trials using hyperpolarized  Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: A position paper from the  Xe MRI clinical trials consortium.

To reduce scan duration in hyperpolarized  Xe 1-point Dixon gas exchange imaging by utilizing flip angle (FA)/TR equivalence.

Utilizing flip angle/TR equivalence to reduce breath hold duration in hyperpolarized  Xe 1-point Dixon gas exchange imaging.

Asthma is a heterogeneous disease characterized by chronic airway inflammation that affects more than 300 million people worldwide. Clinically, asthma has a widely variable presentation and is defined based on a history of respiratory symptoms alongside airflow limitation. Imaging is not needed to confirm a diagnosis of asthma, and thus the use of imaging in asthma has historically been limited to excluding alternative diagnoses. However, significant advances continue to be made in novel imaging methodologies, which have been increasingly used to better understand respiratory impairment in asthma. As a disease primarily impacting the airways, asthma is best understood by imaging methods with the ability to elucidate airway impairment. Techniques such as computed tomography, magnetic resonance imaging with gaseous contrast agents, and positron emission tomography enable assessment of the small airways. Others, such as optical coherence tomography and endobronchial ultrasound enable high-resolution imaging of the large airways accessible to bronchoscopy. These imaging techniques are providing new insights in the pathophysiology and treatments of asthma and are poised to impact the clinical management of asthma.

Article	Year
Preclinical MRI to Quantify Pulmonary Disease Severity and Trajectories in Poorly Characterized Mouse Models: A Pedagogical Example Using Data from Novel Transgenic Models of Lung Fibrosis. Journal of magnetic resonance open\| PubMed ID: 34414381	2021
Protocols for multi-site trials using hyperpolarized Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: A position paper from the Xe MRI clinical trials consortiu... Magnetic resonance in medicine\| PubMed ID: 34478584	2021
Utilizing flip angle/TR equivalence to reduce breath hold duration in hyperpolarized Xe 1-point Dixon gas exchange imaging. Magnetic resonance in medicine\| PubMed ID: 34644815	2022
Imaging in Asthma Management. Seminars in respiratory and critical care medicine\| PubMed ID: 35211923	2022

Chase S Hall

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