Pulmonary functional imaging may be defined as the regional quantification of lung function by using primarily CT, MRI, and nuclear medicine techniques. The distribution of pulmonary physiologic parameters, including ventilation, perfusion, gas exchange, and biomechanics, can be noninvasively mapped and measured throughout the lungs. This information is not accessible by using conventional pulmonary function tests, which measure total lung function without viewing the regional distribution. The latter is important because of the heterogeneous distribution of virtually all lung disorders. Moreover, techniques such as hyperpolarized xenon 129 and helium 3 MRI can probe lung physiologic structure and microstructure at the level of the alveolar-air and alveolar-red blood cell interface, which is well beyond the spatial resolution of other clinical methods. The opportunities, challenges, and current stage of clinical deployment of pulmonary functional imaging are reviewed, including applications to chronic obstructive pulmonary disease, asthma, interstitial lung disease, pulmonary embolism, and pulmonary hypertension. Among the challenges to the deployment of pulmonary functional imaging in routine clinical practice are the need for further validation, establishment of normal values, standardization of imaging acquisition and analysis, and evidence of patient outcomes benefit. When these challenges are addressed, it is anticipated that pulmonary functional imaging will have an expanding role in the evaluation and management of patients with lung disease.

Functional Imaging

10.1148/radiol.2021204033

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Citations (37)

Quantitative 1H and hyperpolarized 3He magnetic resonance imaging: Comparison in chronic obstructive pulmonary disease and healthy never-smokers

European Journal of Radiology (2012)

Amir Owrangi Jian X. Wang Andrew Wheatley David G. McCormack Grace Párraga

10.1016/j.ejrad.2012.02.018

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Carotid ultrasound phenotypes in vulnerable populations

Cardiovascular Ultrasound (2006)

Silvia A. Riccio Andrew A. House J. David Spence Aaron Fenster Grace Párraga

Biomarkers of carotid atherosclerosis range from those that are widely available and relatively simple to measure such as serum cholesterol levels, and B-mode Ultrasound measurement of intima media thickness (IMT) to those that are more complex and technologically demanding but perhaps potentially more sensitive and specific to disease such as total plaque volume and total plaque area measured from 3-dimensional ultrasound images. In this study we measured and compared intima media thickness (IMT), total plaque volume (TPV) and total plaque area (TPA) in two separate populations, both vulnerable to carotid atherosclerosis.In total, 88 subjects (mean age 72.8) with carotid stenosis of at least 60%, based on a peak Doppler flow, and 82 subjects (mean age 60.9) with diabetic nephropathy were assessed in a cross-sectional study. Conventional atherosclerotic risk factors were examined and the associations and correlations between these and carotid ultrasound phenotypes measured from B-mode and 3-dimensional ultrasound images were assessed.IMT and TPV were only modestly correlated in the two separate populations (r = .6, p < .01). ANOVA analyses indicated that both IMT and TPV were significantly associated with age (p < .001) and Framingham score (p < .05), but only TPV was associated with diabetes (p < .001) and presence of plaque ulcerations (p < .01)IMT and TPV were modestly correlated in a diabetic patient population and only TPV was associated with diabetes and the presence of plaque ulcerations in a diabetic population and carotid stenosis group. The 3-dimensional information provided by TPV can be critically important in unmasking association with risk factors not observed with less complex single-dimension assessments of carotid atherosclerosis such as those provided by IMT.

Intima-media thickness

Angiology

Tunica media

10.1186/1476-7120-4-44

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Free-breathing Pulmonary MR Imaging to Quantify Regional Ventilation

Radiology (2018)

Dante P. I. Capaldi Rachel L. Eddy Sarah Svenningsen Fumin Guo John S. H. Baxter

Purpose To measure regional specific ventilation with free-breathing hydrogen 1 (1H) magnetic resonance (MR) imaging without exogenous contrast material and to investigate correlations with hyperpolarized helium 3 (3He) MR imaging and pulmonary function test measurements in healthy volunteers and patients with asthma. Materials and Methods Subjects underwent free-breathing 1H and static breath-hold hyperpolarized 3He MR imaging as well as spirometry and plethysmography; participants were consecutively recruited between January and June 2017. Free-breathing 1H MR imaging was performed with an optimized balanced steady-state free-precession sequence; images were retrospectively grouped into tidal inspiration or tidal expiration volumes with exponentially weighted phase interpolation. MR imaging volumes were coregistered by using optical flow deformable registration to generate 1H MR imaging–derived specific ventilation maps. Hyperpolarized 3He MR imaging– and 1H MR imaging–derived specific ventilation maps were coregistered to quantify regional specific ventilation within hyperpolarized 3He MR imaging ventilation masks. Differences between groups were determined with the Mann-Whitney test and relationships were determined with Spearman (ρ) correlation coefficients. Statistical analyses were performed with software. Results Thirty subjects (median age: 50 years; interquartile range [IQR]: 30 years), including 23 with asthma and seven healthy volunteers, were evaluated. Both 1H MR imaging–derived specific ventilation and hyperpolarized 3He MR imaging–derived ventilation percentage were significantly greater in healthy volunteers than in patients with asthma (specific ventilation: 0.14 [IQR: 0.05] vs 0.08 [IQR: 0.06], respectively, P < .0001; ventilation percentage: 99% [IQR: 1%] vs 94% [IQR: 5%], P < .0001). For all subjects, 1H MR imaging–derived specific ventilation correlated with plethysmography-derived specific ventilation (ρ = 0.54, P = .002) and hyperpolarized 3He MR imaging–derived ventilation percentage (ρ = 0.67, P < .0001) as well as with forced expiratory volume in 1 second (FEV1) (ρ = 0.65, P = .0001), ratio of FEV1 to forced vital capacity (ρ = 0.75, P < .0001), ratio of residual volume to total lung capacity (ρ = −0.68, P < .0001), and airway resistance (ρ = −0.51, P = .004). 1H MR imaging–derived specific ventilation was significantly greater in the gravitational-dependent versus nondependent lung in healthy subjects (P = .02) but not in patients with asthma (P = .1). In patients with asthma, coregistered 1H MR imaging specific ventilation and hyperpolarized 3He MR imaging maps showed that specific ventilation was diminished in corresponding 3He MR imaging ventilation defects (0.05 ± 0.04) compared with well-ventilated regions (0.09 ± 0.05) (P < .0001). Conclusion 1H MR imaging–derived specific ventilation correlated with plethysmography–derived specific ventilation and ventilation defects seen by using hyperpolarized 3He MR imaging. © RSNA, 2018 Online supplemental material is available for this article.

Interquartile range

10.1148/radiol.2018171993

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Citations (36)

What are ventilation defects in asthma?

Thorax (2013)

Sarah Svenningsen Miranda Kirby Danielle Starr Harvey O. Coxson Nigel A. M. Paterson

Background

Hyperpolarised ³He MRI provides a way to visualise regional pulmonary functional abnormalities that in asthma are thought to be related to airway morphological abnormalities. However, the exact aetiology of ventilation defects in asthma is not well understood.

Objective

To better understand the determinants of ventilation defects in asthma, we evaluated well-established clinical as well as ³He MRI and X-ray CT airway measurements in healthy subjects and subjects with asthma.

Methods

Thirty-four subjects (n=26 subjects with asthma, n=8 healthy volunteers) underwent MRI, spirometry, plethysmography, fraction of exhaled nitric oxide analysis, methacholine challenge and CT for a region-of-interest proximal to ventilation defects. For subjects who consented to CT (n=18 subjects with asthma, n=5 healthy volunteers), we evaluated 3^rd to 5th generation airway wall area and wall thickness per cent and lumen area.

Results

Seventeen subjects with asthma (17/26=65%) had visually obvious evidence of ³He ventilation defects prior to bronchoprovocation and nine subjects with asthma had no ventilation defects prior to bronchoprovocation (9/26=35%). Subjects with asthma with defects were older (p=0.01) with worse forced expiratory volume in 1 s (FEV₁)/forced vital capacity (p=0.0003), airways resistance (p=0.004), fraction of exhaled nitric oxide (p=0.03), greater bronchoprovocation concentration of methacholine that reduced FEV₁ by 20% (p=0.008) and wall thickness per cent (p=0.02) compared with subjects with asthma without defects. There was a moderate correlation for wall area per cent with ventilation defect per cent (r=0.43, p=0.04).

Conclusions

Subjects with asthma with ³He ventilation defects were older with significantly worse airway hyper-responsiveness, inflammation and airway remodelling but similar FEV₁ as subjects with asthma without defects; hyperpolarised ³He ventilation abnormalities were spatially and quantitatively related to abnormally remodelled airways.

10.1136/thoraxjnl-2013-203711

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Validation of 3D Ultrasound Vessel Wall Volume: An Imaging Phenotype of Carotid Atherosclerosis

Ultrasound in Medicine & Biology (2007)

Micaela Egger J. David Spence Aaron Fenster Grace Párraga

10.1016/j.ultrasmedbio.2007.01.013

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Citations (118)

Anatomical distribution of ³He apparent diffusion coefficients in severe chronic obstructive pulmonary disease

Journal of Magnetic Resonance Imaging (2007)

Andrea Evans David G. McCormack Alexei Ouriadov Roya Etemad‐Rezai Giles Santyr

Abstract Purpose To evaluate the anatomical distribution of apparent diffusion coefficients (ADC) using hyperpolarized helium‐3 ( 3 He) MRI in chronic obstructive pulmonary disease (COPD). Materials and Methods Hyperpolarized 3 He MRI was performed in eight healthy and seven COPD subjects under breathhold conditions in the supine position to determine ADC values from diffusion‐weighted images and evaluate anterior–posterior (AP) and superior–inferior (SI) differences. Results ADC differences between anterior and posterior slices, ΔAP, was 0.06 ±0.01 cm 2 /second for healthy volunteers and 0.04 ±0.02 cm 2 /second for COPD subjects and was significant for each subject (P < 0.01). The AP ADC gradient was –3.98 × 10 –3 ±0.59 cm 2 /second/cm for healthy volunteers and –2.04 × 10 –3 ±0.89 cm 2 /second/cm for COPD subjects. The difference in ADC between superior and inferior regions of interest (ROIs), ΔSI, was 0.02 ±0.02 cm 2 /second for healthy volunteers and 0.10 ±0.09 cm 2 /second for COPD subjects, which was significant for each subject (P < 0.05). The SI ADC gradient was –0.63 × 10 –3 ±2.23 cm 2 /second/cm for healthy volunteers and –6.61 × 10 –3 ±6.68 cm 2 /second/cm for COPD subjects. ΔAP, AP‐gradient, and SI‐gradient were significantly different between healthy volunteers and COPD subjects (P < 0.05). Conclusion In all subjects, ADC anatomical differences were significant and mean ADC was dependent on anatomic location and disease status. J. Magn. Reson. Imaging. © 2007 Wiley‐Liss, Inc.

Supine position

10.1002/jmri.21205

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Citations (57)

Normalisation of MRI ventilation heterogeneity in severe asthma by dupilumab

Thorax (2019)

Sarah Svenningsen Ehsan Haider Rachel L. Eddy Grace Párraga Parameswaran Nair

Ventilation heterogeneity in asthma could be due to many reasons. Luminal obstruction due to inflammatory cells or mucus, smooth muscle constriction and airway wall thickness could all contribute individually or collectively to ventilation heterogeneity. Interleukin-4 and interleukin-13, acting through the common interleukin-4 receptor, have the potential to modulate all of these features of asthma.1 Inhaled hyperpolarised gas MRI provides a way to regionally visualise and quantify the functional consequence of these features.2 Dupilumab is a fully human monoclonal antibody directed against the alpha-subunit of the interleukin-4 receptor.3 Here, we report a severe asthmatic who showed significant improvement and normalisation of MRI ventilation heterogeneity and associated clinical and physiological variables with dupilumab treatment, suggesting that dupilumab modulated various aspects of luminal airway obstruction. A 39-year-old atopic woman (total serum immunoglobulin E 1009 kU/L and peripheral blood eosinophils 1200 cells/µL) was seen for asthma in January 2015. She had mixed obstructive and non-obstructive spirometry (forced expiratory volume in one second (FEV1) 1.42 L (44%pred), forced vital capacity (FVC) 1.72 L (44%pred) and total lung capacity (TLC) 3.78 L (71%pred)), with 13% reversibility to salbutamol. Her asthma …

Dupilumab

Vital capacity

Benralizumab

Airway obstruction

10.1136/thoraxjnl-2019-213415

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Citations (19)

Early stage radiation‐induced lung injury detected using hyperpolarized ¹²⁹Xe Morphometry: Proof‐of‐concept demonstration in a rat model

Magnetic Resonance in Medicine (2015)

Alexei Ouriadov Matthew S. Fox Elaine Hegarty Grace Párraga Eugene Wong

Purpose Radiation‐induced lung injury (RILI) is still the major dose‐limiting toxicity related to lung cancer radiation therapy, and it is difficult to predict and detect patients who are at early risk of severe pneumonitis and fibrosis. The goal of this proof‐of‐concept preclinical demonstration was to investigate the potential of hyperpolarized 129 Xe diffusion‐weighted MRI to detect the lung morphological changes associated with early stage RILI. Methods Hyperpolarized 129 Xe MRI was performed using eight different diffusion sensitizations (0.0–115 s/cm 2 ) in a small group of control rats (n = 4) and rats 2 wk after radiation exposure (n = 5). The diffusion‐weighted images were used to obtain morphological estimates of the pulmonary parenchyma including external radius ( R ), internal radius ( r ), alveolar sleeve depth ( h ), and mean airspace chord length ( L m ). The histological mean linear intercept ( MLI ) were obtained for five control and five irradiated animals. Results Mean R , r , and L m were both significantly different ( P < 0.02) in the irradiated rats (74 ± 17 µm, 43 ± 12 µm, and 54 ± 17 µm, respectively) compared with the control rats (100 ± 12 µm, 67 ± 10 µm, and 79 ± 12 µm, respectively). Changes in measured L m values were consistent with changes in MLI values observed by histology. Conclusions Hyperpolarized 129 Xe MRI provides a way to detect and measure regional microanatomical changes in lung parenchyma in a preclinical model of RILI. Magn Reson Med 75:2421–2431, 2016. © 2015 Wiley Periodicals, Inc.

Radiation injury

10.1002/mrm.25825

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Citations (29)