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Purpose: To examine the utility of a (3)He spectroscopic q-space technique for detecting changes in lung morphometry in vivo., Materials and Methods: A diffusion-weighted spectroscopy sequence was used to collect global diffusion data from healthy adults (N = 11), healthy children (N = 5), and chronic obstructive pulmonary disease (COPD) patients (N = 2) using 40 cc of hyperpolarized (3)He gas within a two second breathhold. Displacement probability profiles (DPP) were obtained by Fourier transformation of diffusion data with respect to q. A bi-Gaussian model was used to decompose the DPPs into narrow and broad components, characterized by root-mean-square displacements X(rms1) and X(rms2), respectively., Results: In healthy adults, the narrow component (X(rms,1)) of the DPP had a mean displacement of 188 +/- 10 microm, slightly less than the reported average size of the alveoli. The broad component (X(rms,2)) had a mean value of 474 +/- 44 microm, comparable to the diameter of the respiratory bronchioles in the acinus. In children, both X(rms1) (167 +/- 4 microm) and X(rms2) (382 +/- 22 microm) compared to healthy adults (P < 0.01). In COPD patients, the mean displacements were elevated (X(rms1): 265 +/- 71 microm; X(rms2): 530 +/- 109 microm) compared to healthy adults. Excellent correlation was found between rms displacements and age (age vs. X(rms,1): r = 0.78, P < 0.001; age vs. X(rms,2): r = 0.90, P < 0.001)., Conclusion: The q-space parameters agreed remarkably well with published alveolar morphometry data. The results suggest that the technique may be sensitive to disease, as evident from the elevated mean displacements in COPD patients compared to healthy volunteers. Detailed lung microstructural information can be obtained using a very low volume of inhaled (3)He., ((c) 2006 Wiley-Liss, Inc.)