3D <sup>3</sup>He diffusion MRI as a local in vivo morphometric tool to evaluate emphysematous rat lungs

Jacob, Richard E.; Minard, Kevin R.; Laicher, Gernot; Timchalk, Charles

doi:10.1152/japplphysiol.90375.2008

Cited by 26 publications

(26 citation statements)

References 39 publications

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“…It also suggests that R may not be as sensitive to early changes in lung morphology but may become very sensitive once the disease exceeds a critical point. A DC BC and l og(L x ), as previously described (18,28), are strongly correlated (product moment correlation coefficient: 0.85, P ϭ 0.002), and A DC BC monotonically increases as l og(L x ) increases, so we anticipate that the ADC, like l og(L x ), will be sensitive to early changes in airway structure and, thus, suitable for early disease detection.…”

Section: Discussionsupporting

confidence: 57%

Regional function-structure relationships in lungs of an elastase murine model of emphysema

Ishii

Emami

Xin

et al. 2012

Journal of Applied Physiology

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PL, Rizi RR. Regional function-structure relationships in lungs of an elastase murine model of emphysema. J Appl Physiol 112: 135-148, 2012. First published September 22, 2011 doi:10.1152/japplphysiol.01181.2010.-Changes in lung function and structure were studied using hyperpolarized 3 He MRI in an elastaseinduced murine model of emphysema. The combined analysis of the apparent diffusion coefficient (ADC) and fractional ventilation (R) were used to distinguish emphysematous changes and also to develop a model for classifying sections of the lung into diseased and normal. Twelve healthy male BALB/c mice (26 Ϯ 2 g) were randomized into healthy and elastase-induced mice and studied ϳ8 -11 wk after model induction. ADC and R were measured at a submillimeter planar resolution. Chord length (Lx) data were analyzed from histology samples from the corresponding imaged slices. Logistic regression was applied to estimate the probability that an imaged pixel came from a diseased animal, and bootstrap methods (1,000 samples) were used to compare the regression results for the morphological and imaging results. Multivariate ANOVA (MANOVA) was used to analyze transformed ADC (ADCBC), and R (RBC) data and also to control for the experiment-wide error rate. MANOVA and ANOVA showed that elastase induced a statistically measureable change in the average transformed Lx and ADCBC but not in the average RBC. Marginal mean analysis demonstrated that ADCBC was on average 0.19 [95% confidence interval (CI): 0.16, 0.22] higher in the emphysema group, whereas RBC was on average 0.05 (95% CI: 0.04, 0.06) lower. Logistic regression supported the hypothesis that ADCBC and R BC, together, were better at differentiating normal from diseased tissue than either measurement alone. The odds ratios for ADCBC and R BC were 7.73 (95% CI: 5.23, 11.42) and 9.14 ϫ 10 Ϫ5 (95% CI: 3.33 ϫ 10 Ϫ5 , 25.06 ϫ 10 Ϫ5 ), respectively. Using a 50% probability cutoff, this model classified 70.6% of pixels correctly. The sensitivity and specificity of this model at the 50% cutoff were 74.9% and 65.2%, respectively. The area under the receiver operating characteristic curve was 0.76 (95% CI: 0.74, 0.78). The regression model presented can be used to map MRI data to disease probability maps. These probability maps present a future possibility of using both measurements in a more clinically feasible method of diagnosing this disease. lung physiology; relationship of lung function and structure; regional fractional ventilation; apparent diffusion coefficient; hyperpolarized gas magnetic resonance imaging

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Section: Discussionsupporting

confidence: 57%

Regional function-structure relationships in lungs of an elastase murine model of emphysema

Ishii

Emami

Xin

et al. 2012

Journal of Applied Physiology

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“…D L measured at a diffusion time of 1.8 ms has been previously shown to be sensitive to emphysema in humans (6,19). Diffusion studies using the cylinder model have also been done using dogs and showed strong correlation to quantitative computed tomography (CT) lung density and volume measurements (13), and histology measurements in rats (9,20) and mice (21).…”

mentioning

confidence: 98%

“…This enables the tracking of disease progression, such as human chronic obstructive pulmonary disease (1,2) and asthma in mouse models (3). 3 He ADC has been shown to be sensitive to changes in terminal airway anatomy, specifically alveolar damage due to emphysema in both humans (1,(4)(5)(6) and animal models (3,(7)(8)(9).…”

mentioning

confidence: 99%

Mapping of ³He apparent diffusion coefficient anisotropy at sub‐millisecond diffusion times in an elastase‐instilled rat model of emphysema

Boudreau

Ouriadov

et al. 2011

Magnetic Resonance in Med

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Hyperpolarized 3 He gas can provide detailed anatomical maps of the macroscopic airways in the lungs (i.e., ventilation) as well as insight into the lung microstructure through the apparent diffusion coefficient. In particular, the apparent diffusion coefficient of 3 He in the lung exhibits anisotropic effects that depend on diffusion time (d), and it has been shown to be extraordinarily sensitive to enlargement in terminal airways and alveoli associated with emphysema. In this study, the anisotropic nature of the 3 He apparent diffusion coefficient is studied in a rat model of emphysema, based on elastase instillation, specifically for d values less than one millisecond. Hyperpolarized helium 3 ( 3 He) MR imaging can provide both anatomical and functional information that may be important for diagnosing lung diseases. One of the most interesting implementations of 3 He imaging is diffusionweighted MR imaging, taking advantage of the much larger apparent diffusion coefficient (ADC) of 3 He compared to 1.1 Â 10 À5 cm 2 /s for hydrogen ( 1 H). 3 He diffusion in the lungs is restricted by airway and alveolar walls and therefore is highly dependent on lung microstructure. Diffusion measurements are sensitive to lung morphological information such as airway sizes and surface to volume ratio, by measuring the ADC that is largely dependent on lung geometry (1). This enables the tracking of disease progression, such as human chronic obstructive pulmonary disease (1,2) and asthma in mouse models (3). 3 He ADC has been shown to be sensitive to changes in terminal airway anatomy, specifically alveolar damage due to emphysema in both humans (1,4-6) and animal models (3,7-9).The lungs branch off from the trachea to bronchi, bronchioles, and eventually terminate at the alveolar sacs after approximately 25 divisions. The radii of alveoli range from approximately 0.12 to 0.18 mm (10,11) in humans to approximately 0.05 mm alveolar radius in rats (12). The duct size in humans range from 0.22 to 0.60 mm, depending on the generation (10), up to three times the size of an alveoli radius. In this geometry, diffusion is highly restricted for 3 He nuclei as the diffusion lengthis about 0.6 mm given a diffusion time (d) of 1.8 ms, which is typical of diffusion-weighted MR imaging. D 0 in Eq. 1 is the free diffusion coefficient and is equal to 1.91 Â 10 À4 m 2 /s (11) for pure 3 He at room temperature and 0.88 cm 2 /s when diluted in air. It has been shown that 3 He ADC obtained at millisecond diffusion times can distinguish normal from emphysematous tissue and correlates with mean linear intercept histology, an accepted measure of alveolar damage (12,13). 3 He ADC values obtained at sub-millisecond diffusion times (14) are expected to be even more sensitive to emphysema, especially in small animals. At longer diffusion times on the order of seconds, 3 He ADC is expected to reflect changes in lung anatomy over much larger length scales on the order of centimetres. Recent work has demonstrated ADC sensitivity to collateral pathway changes...

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“…Single lobe dosing was monitored using magnetic resonance imaging to verify the dose location. Dose levels were based on previous work in which 3 He diffusion MRI showed a significant disease response [32].…”

Section: Methodsmentioning

confidence: 99%

Dynamic Multiscale Boundary Conditions for 4D CT of Healthy and Emphysematous Rats

et al. 2013

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Changes in the shape of the lung during breathing determine the movement of airways and alveoli, and thus impact airflow dynamics. Modeling airflow dynamics in health and disease is a key goal for predictive multiscale models of respiration. Past efforts to model changes in lung shape during breathing have measured shape at multiple breath-holds. However, breath-holds do not capture hysteretic differences between inspiration and expiration resulting from the additional energy required for inspiration. Alternatively, imaging dynamically – without breath-holds – allows measurement of hysteretic differences. In this study, we acquire multiple micro-CT images per breath (4DCT) in live rats, and from these images we develop, for the first time, dynamic volume maps. These maps show changes in local volume across the entire lung throughout the breathing cycle and accurately predict the global pressure-volume (PV) hysteresis. Male Sprague-Dawley rats were given either a full- or partial-lung dose of elastase or saline as a control. After three weeks, 4DCT images of the mechanically ventilated rats under anesthesia were acquired dynamically over the breathing cycle (11 time points, ≤100 ms temporal resolution, 8 cmH2O peak pressure). Non-rigid image registration was applied to determine the deformation gradient – a numerical description of changes to lung shape – at each time point. The registration accuracy was evaluated by landmark identification. Of 67 landmarks, one was determined misregistered by all three observers, and 11 were determined misregistered by two observers. Volume change maps were calculated on a voxel-by-voxel basis at all time points using both the Jacobian of the deformation gradient and the inhaled air fraction. The calculated lung PV hysteresis agrees with pressure-volume curves measured by the ventilator. Volume maps in diseased rats show increased compliance and ventilation heterogeneity. Future predictive multiscale models of rodent respiration may leverage such volume maps as boundary conditions.

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3D ³He diffusion MRI as a local in vivo morphometric tool to evaluate emphysematous rat lungs

Cited by 26 publications

References 39 publications

Regional function-structure relationships in lungs of an elastase murine model of emphysema

Regional function-structure relationships in lungs of an elastase murine model of emphysema

Mapping of ³He apparent diffusion coefficient anisotropy at sub‐millisecond diffusion times in an elastase‐instilled rat model of emphysema

Dynamic Multiscale Boundary Conditions for 4D CT of Healthy and Emphysematous Rats

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3D 3He diffusion MRI as a local in vivo morphometric tool to evaluate emphysematous rat lungs

Cited by 26 publications

References 39 publications

Regional function-structure relationships in lungs of an elastase murine model of emphysema

Regional function-structure relationships in lungs of an elastase murine model of emphysema

Mapping of 3He apparent diffusion coefficient anisotropy at sub‐millisecond diffusion times in an elastase‐instilled rat model of emphysema

Dynamic Multiscale Boundary Conditions for 4D CT of Healthy and Emphysematous Rats

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3D ³He diffusion MRI as a local in vivo morphometric tool to evaluate emphysematous rat lungs

Mapping of ³He apparent diffusion coefficient anisotropy at sub‐millisecond diffusion times in an elastase‐instilled rat model of emphysema