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Helium-3 Diffusion MR Imaging of the Human Lung Over Multiple Time Scales

Posted May 31, 2008 Updated Apr 7, 2023
By John P. Mugler PhD , Chengbo Wang PhD , G. Wilson Miller PhD , Gordon D. Cates PhD , Jaime F. Mata PhD , James R. Brookeman PhD , Eduard E. de Lange MD , Talissa A. Altes MD
9 min read

Rationale and Objectives

Diffusion magnetic resonance imaging (MRI) with hyperpolarized 3 He gas is a powerful technique for probing the characteristics of the lung microstructure. A key parameter for this technique is the diffusion time, which is the period during which the atoms are allowed to diffuse within the lung for measurement of the signal attenuation. The relationship between diffusion time and the length scales that can be explored is discussed, and representative, preliminary results are presented from ongoing studies of the human lung for diffusion times ranging from milliseconds to several seconds.

Materials and Methods

3 He diffusion MRI of the human lung was performed on a 1.5T Siemens Sonata scanner. Using gradient echo-based and stimulated echo-based techniques for short and medium-to-long diffusion times, respectively, measurements were performed for times ranging from 2 milliseconds to 6.5 seconds in two healthy subjects, a subject with subclinical chronic obstructive pulmonary disease and a subject with bronchopulmonary dysplasia.

Results

In healthy subjects, the apparent diffusion coefficient decreased by about 10-fold, from approximately 0.2 to 0.02 cm 2 /second, as the diffusion time increased from approximately 1 millisecond to 1 second. Results in subjects with disease suggest that measurements made at diffusion times substantially longer than 1 millisecond may provide improved sensitivity for detecting certain pathologic changes in the lung microstructure.

Conclusions

With appropriately designed pulse sequences it is possible to explore the diffusion of hyperpolarized 3 He in the human lung over more than a 1,000-fold variation of the diffusion time. Such measurements provide a new opportunity for exploring and characterizing the microstructure of the healthy and diseased lung.

The lung parenchyma and airspaces are poorly visualized with conventional, proton-based magnetic resonance imaging (MRI) because of the low concentration of water and the inhomogeneous magnetic environment, both of which diminish the strength of the MRI signal compared with that from other organs in the body. In contrast, inhalation of hyperpolarized helium-3 ( 3 He) gas provides a strong signal from the lung airspaces that permits high-spatial-resolution MRI ( ). Before performing an MRI examination with 3 He, the gas is polarized outside of the scanner using a dedicated, laser-based device within which, over minutes to hours (depending on the quantity of gas and details of system design), the nuclear polarization of the 3 He atoms builds up to tens of percent. This polarization is several orders of magnitude larger than that achieved for protons when the human body is placed in an MRI scanner and offsets the low density of the gas so that high-quality MRIs of 3 He in the airspaces of the lung can be obtained.

Several imaging strategies have been used for hyperpolarized 3 He MRI of the lung to investigate diseases such as asthma and emphysema ( ). Of particular interest is the application of diffusion MRI techniques to probe the characteristics of the lung microstructure. These methods provide a measurement that reflects the random Brownian motion of the 3 He gas atoms within the airspaces of the lung (as opposed to the transmembrane diffusion of the gas) and the degree to which this random motion is restricted by the structure of the lung tissue. Diffusion results in attenuation of the MRI signal, from which an apparent diffusion coefficient (ADC) can be calculated. The measured ADC varies inversely with the degree to which the diffusion of the gas is restricted. For example, the ADC for 3 He gas in healthy lung parenchyma is substantially smaller than the corresponding diffusion coefficient in an unrestricted space, and the ADC measured in a lung with severe emphysema is larger than that for a healthy lung, reflecting the enlargement of airspaces caused by the tissue destruction that occurs with emphysema. Thus regional changes of the microstructure that occur in pulmonary diseases such as emphysema can be characterized by measuring the ADC of 3 He gas in the lung ( ). Further, appropriately designed measurement protocols permit representative structural dimensions to be determined ( ), and recent evidence suggests that ADC measurements may permit detection of subtle, subclinical structural changes before they become apparent on high-resolution computed tomography ( ).

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ADC measurement and diffusion time

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Figure 1, (a) Basic framework for making an apparent diffusion coefficient measurement based on a gradient-echo pulse sequence. Spatial encoding gradients, which would be applied following the “un-tag” gradient pulse, are omitted for simplicity. (b) The effect of the tagging gradient pulse on the transverse magnetization. The left side of the diagram shows a series of representative transverse magnetization vectors before application of the tagging pulse. The tips of these magnetization vectors fall along a straight line. The gradient twists the magnetization vectors into a helical pattern as shown on the right side of the diagram.

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Figure 2, Basic framework for making an apparent diffusion coefficient measurement based on a stimulated-echo pulse sequence. Spatial encoding gradients are omitted for simplicity. The “un-tag” gradient pulse is positive (instead of negative) because the second RF pulse phase conjugates the magnetization in the process of storing it.

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Figure 3, Relationship between the diffusion time and the square root of mean squared distance (ie, RMS distance) that 3 He atoms in air diffuse in an unrestricted environment. The approximate dimensions of several structures in the human lung are indicated for comparison.

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Materials and methods

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Results and discussion

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Figure 4, Global apparent diffusion coefficient (ADC) values from the lung of a healthy human volunteer for diffusion times ranging from 20 milliseconds to 6.5 seconds. ADC values for diffusion times from 20 milliseconds to 1.5 seconds were measured during a breath-hold using a tag wavelength of 5 mm. ADC values for diffusion times from 200 milliseconds to 6.5 seconds were measured during a second breath-hold using a tag wavelength of 10 mm. For a given tag wavelength, the ADC decreased monotonically with increasing diffusion time. Each of the two measurements was performed using a single application of a stimulated echo–based pulse sequence with the following parameters: repetition time, 62 milliseconds; echo time for stimulated echoes, 6.0 milliseconds; echo time for calibration data, 0.5 milliseconds; flip angle, 5°; number of ADC values per measurement, 24 (5-mm tag wavelength) or 102 (10-mm tag wavelength).

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Figure 5, Coronal projection apparent diffusion coefficient (ADC) maps from the lung of a healthy human volunteer for diffusion times ranging from 2 milliseconds to 1.5 seconds. Each ADC map was acquired during a separate breath-hold period. The short time scale ADC map (diffusion time: 2 milliseconds) was acquired using a gradient echo–based pulse sequence, and the medium and long time scale ADC maps (diffusion times: 50, 200, and 1,500 milliseconds) were acquired using a stimulated echo–based pulse sequence. The ADC values decreased monotonically with increasing diffusion time, consistent with the behavior for global ADC values illustrated in Fig 4 . The artifactual dark regions near the base of the lung were caused by the large susceptibility interface at the diaphragmatic surface. Parameters for the gradient-echo acquisition included: repetition time (TR), 6.3 milliseconds; echo time (TE), 4.5 milliseconds; flip angle, 10°; b values, 0 and 1.6 seconds/cm 2 ; diffusion-sensitization direction, anteroposterior. Parameters for the stimulated-echo acquisition included: TR, 8.0 milliseconds; TE for stimulated echo, 7.0 milliseconds; TE for diffusion-weighted image, 2.3 milliseconds; TE for calibration data, 3.6 milliseconds; flip angle, 5°; tag wavelength, 5 mm (diffusion time 50 or 200 milliseconds) or 10 mm (diffusion time 1,500 milliseconds); diffusion-sensitization direction, anteroposterior. Parameters common to both acquisitions included: in-plane resolution, 5.9 × 5.9 mm 2 ; slice thickness, projection. Adapted from Fig 2 in reference ( 20 ).

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Figure 6, Coronal short time scale (a) and long time scale (b) apparent diffusion coefficient (ADC) maps from a subject with subclinical chronic obstructive pulmonary disease. The diffusion times were 2 milliseconds and 1.5 seconds for the short time scale and long time scale measurements, respectively. The long time scale ADC map exhibits markedly elevated ADC values in the lung apices; the values in the mid-section and base of the lung are also elevated compared to those for a healthy subject (eg, Fig 5 , right-most ADC map). In contrast, the short time scale ADC values in the lung apices are only mildly elevated compared with those in the rest of the lung. Parameters for the short time scale, gradient-echo acquisition included: repetition time (TR), 6.3 milliseconds; echo time (TE), 4.5 milliseconds; flip angle, 10°; in-plane resolution, 5.0 × 10.0 mm 2 ; slice thickness, projection; b values, 0 and 1.6 s/cm 2 ; diffusion-sensitization direction, anteroposterior. Parameters for the long time scale, stimulated-echo acquisition included: TR, 6.4 milliseconds; TE for stimulated echoes, 7.0 milliseconds; TE for calibration data, 1.3 milliseconds; flip angle, 5°; in-plane resolution, 6.3 × 7.3 mm 2 ; slice thickness, projection; tag wavelength, 10 mm; diffusion-sensitization direction, anteroposterior. Adapted from Fig 9 in reference ( 10 ).

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Figure 7, Axial short time scale (a) and long time scale (b) apparent diffusion coefficient (ADC) maps from a subject with bronchopulmonary dysplasia. The diffusion times were 2 milliseconds and 1.0 seconds for the short time scale and long time scale measurements, respectively. The ADC values are quite uniform within the lung parenchyma in the short time scale ADC map (the elevated values are gas within large airways), whereas local elevations of the ADC are seen in both lungs in the long time scale ADC map. Parameters for the short time scale, gradient-echo acquisition included: repetition time (TR), 11.0 milliseconds; echo time (TE), 6.7 milliseconds; flip angle, 3°; b values, 0 and 1.6 seconds/cm 2 ; diffusion-sensitization direction, head-foot. Parameters for the long time scale, stimulated-echo acquisition included: TR, 6.4 milliseconds; TE for stimulated echoes, 7.0 milliseconds; TE for calibration data, 1.3 milliseconds; flip angle, 5°; tag wavelength, 10 mm; diffusion-sensitization direction, head-foot. Parameters common to both acquisitions included: in-plane resolution, 5.9 × 5.9 mm 2 ; slice thickness, 40 mm.

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Conclusions

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Acknowledgments

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Academic Radiology, Volume 15, Issue 6
Journals General Radiology
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