Magnetization tagging decay to measure long‐range ³He diffusion in healthy and emphysematous canine lungs

Abstract

Spatial modulation (tagging) of the longitudinal magnetization allows diffusive displacements to be measured over times approximately as long as T 1 and over correspondingly long distances. Magnetization tagging is used here with hyperpolarized 3 He gas in canine lungs with unilateral elastase-induced emphysema. A new scheme for analyzing images subsequent to tagging determines the spatially-resolved fractional modulation and its decay rate, using a sliding window. The free diffusivity D o of 3 He, dilute in air or N 2 , is exceptionally large at 0.88 cm 2 /s. Thus, the root mean square (RMS) free displacement of a typical 3 He atom during several milliseconds is larger than the diameter of the acinar airways, with the result that the apparent diffusivity measured over such times is restricted by collisions with airway walls and is near 0.2 cm 2 /s in healthy lung (1-4). Airway expansion and destruction of airway and alveolar walls in emphysema (5) result in reduced restriction of diffusion (D Ϸ 0.55 cm 2 /s in a group of severely diseased subjects) (3). Nearly all of the work to date has measured D msec , taken from the decay of transverse magnetization measured at two b-values (that is, with and without a pulsed, diffusion-sensitizing field gradient) (3,4,6 -8). The experiment is sensitive to displacements during the gradient waveform that is typically several milliseconds in duration, corresponding to displacements of a few hundred microns. This time is limited by the short T* 2 of 3 He in lung (about 20 ms in 1.5 T) (9,10). The small length scale associated with this method limits the motion to individual acinar airways where 95% of the gas resides; the time is not sufficient for many of the atoms to move from one airway to the next. Multi-b-value measurements of the decay of transverse magnetization over times of milliseconds have been understood in terms of anisotropic diffusion, with different values longitudinal and transverse to the airways (D L and D T ) (1). Diffusion values so measured are sensitive indicators of the changes in localized lung morphology that accompany emphysema.However, by probing gas diffusion over longer times, one can examine the structure of the airway network over longer length scales. In the canonical description of lung (11), there are 24 levels of branching airways, where the trachea is Z ϭ 0 and the alveolar sacs are Z ϭ 23. The acinar units are the primary regions of gas exchange and comprise the highest-numbered eight airway levels. The mean linear size of an acinar unit is about 7 mm, with individual acinar airways having lengths of approximately 1 mm (11). Because the average acinar-airway length is small, and the acini contain the vast majority of gas in the lung, diffusion between arbitrary points that are centimeter(s) apart requires that atoms must travel from one acinus to another, connecting via a common conducting airway node. From the alveolar sacs, for example, this is a path through eight or more airway levels. The diffusion coefficient measured over such long ...

The Role of Collateral Paths in Long-range Diffusion of 3He in Lungs

“…The LRDC in healthy human volunteers (24,25) and healthy canines (22) has been measured to be about 0.02 cm 2 /s using λ = 2 cm, approximately 10 times smaller than the 2 ms measurements of ADC. Similar values have been obtained (23) in explanted normal donor lungs (Figure 1).…”

“…Longer diffusion times (seconds) are required for the 3 He to explore longer distances, to reveal the connectivity of the airways and acini. Measurements of the long-range diffusion coefficient (LRDC) have appeared, using sinusoidal spatial modulation (20) of the 3 He spin magnetization, with modulation wavelengths λ of typically 2-3 cm (21)(22)(23). Diffusion occurring after the initial modulation (or tagging, or striping) reduces the amplitude of the modulation; small-angle (FLASH) imaging can follow the decaying amplitude and allow a LRDC value to be determined.…”

“…By using the longitudinal spin magnetization, the decay due to diffusion can be followed to times of order T 1 , the longest relaxation time in the spin system. Specifically, the modulated magnetization amplitude S will decay exponentially as (22) [1] [2] and k = 2π/λ. The relevant diffusion distance is of order λ/2.…”

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

“…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).…”

“…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 associated with lung disease, using stimulated echo (7,15,16) and magnetization tagging methods (17). 3 He ADC mapping in humans typically uses two images with changing diffusion-weighted gradient strength to compute a single mean ADC for each voxel.…”