Regional airflow obstruction after bronchoconstriction and subsequent bronchodilation in subjects without pulmonary disease.

Some subjects with asthma have ventilation defects that are resistant to bronchodilator therapy, and it is thought that these resistant defects may be due to ongoing inflammation or chronic airway remodeling. However, it is unclear whether regional obstruction due to bronchospasm alone persists after bronchodilator therapy. To investigate this, six young, healthy subjects, in whom inflammation and remodeling were assumed to be absent, were bronchoconstricted with a PC20 [the concentration of methacholine that elicits a 20% drop in forced expiratory volume in 1 s (FEV1)] dose of methacholine and subsequently bronchodilated with a standard dose of albuterol on three separate occasions. Specific ventilation imaging, a proton MRI technique, was used to spatially map specific ventilation across 80% of each subject's right lung in each condition. The ratio between regional specific ventilation at baseline and after intervention was used to classify areas that had constricted. After albuterol rescue from methacholine bronchoconstriction, 12% (SD 9) of the lung was classified as constricted. Of the 12% of lung units that were classified as constricted after albuterol, approximately half [7% (SD 7)] had constricted after methacholine and failed to recover, whereas half [6% (SD 4)] had remained open after methacholine but became constricted after albuterol. The incomplete regional recovery was not reflected in the subjects' FEV1 measurements, which did not decrease from baseline (P = 0.97), nor was it detectable as an increase in specific ventilation heterogeneity (P = 0.78).NEW & NOTEWORTHY In normal subjects bronchoconstricted with methacholine and subsequently treated with albuterol, not all regions of the healthy lung returned to their prebronchoconstricted specific ventilation after albuterol, despite full recovery of integrative lung indexes (forced expiratory volume in 1 s and specific ventilation heterogeneity). The regions that remained bronchoconstricted following albuterol were those with the highest specific ventilation at baseline, which suggests that they may have received the highest methacholine dose.

Spatial persistence of reduced specific ventilation following methacholine challenge in the healthy human lung.

Specific ventilation imaging was used to identify regions of the healthy lung (6 supine subjects, ages 21-41 yr, 3 men) that experienced a fall in specific ventilation following inhalation of methacholine. This test was repeated 1 wk later and 3 mo later to test for spatial recurrence. Our data showed that 53% confidence interval (CI; 46%, 59%) of volume elements that constricted during one methacholine challenge did so again in another and that this quantity did not vary with time; 46% CI (28%, 64%) recurred 1 wk later, and 56% CI (51%, 61%) recurred 3 mo later. Previous constriction was a strong predictor for future constriction. Volume elements that constricted during one challenge were 7.7 CI (5.2, 10.2) times more likely than nonconstricted elements to constrict in a second challenge, regardless of whether the second episode was 1 wk [7.7 CI (2.9, 12.4)] or 3 mo [7.7 CI (4.6, 10.8)] later. Furthermore, posterior lung elements were more likely to constrict following methacholine than anterior lung elements (volume fraction 0.43 ± 0.22 posterior vs. 0.10 ± 0.03 anterior; P = 0.005), and basal elements that constricted were more likely than their apical counterparts to do so persistently through all three trials (volume fraction 0.14 ± 0.04 basal vs. 0.04 ± 0.04 apical; P = 0.003). Taken together, this evidence suggests a physiological predisposition toward constriction in some lung elements, especially those located in the posterior and basal lung when the subject is supine. NEW & NOTEWORTHY The spatial pattern of bronchoconstriction following methacholine is persistent over time in healthy individuals, in whom chronic inflammation and airway remodeling are assumed to be absent. This suggests that regional lung inflation and airway structure may play dominant roles in determining the spatial pattern of methacholine bronchoconstriction.

The effect of supine exercise on the distribution of regional pulmonary blood flow measured using proton MRI.

The Zone model of pulmonary perfusion predicts that exercise reduces perfusion heterogeneity because increased vascular pressure redistributes flow to gravitationally nondependent lung, and causes dilation and recruitment of blood vessels. However, during exercise in animals, perfusion heterogeneity as measured by the relative dispersion (RD, SD/mean) is not significantly decreased. We evaluated the effect of exercise on pulmonary perfusion in six healthy supine humans using magnetic resonance imaging (MRI). Data were acquired at rest, while exercising (∼27% of maximal oxygen consumption) using a MRI-compatible ergometer, and in recovery. Images were acquired in most of the right lung in the sagittal plane at functional residual capacity, using a 1.5-T MR scanner equipped with a torso coil. Perfusion was measured using arterial spin labeling (ASL-FAIRER) and regional proton density using a fast multiecho gradient-echo sequence. Perfusion images were corrected for coil-based signal heterogeneity, large conduit vessels removed and quantified (in ml·min(-1)·ml(-1)) (perfusion), and also normalized for density and quantified (in ml·min(-1)·g(-1)) (density-normalized perfusion, DNP) accounting for tissue redistribution. DNP increased during exercise (11.1 ± 3.5 rest, 18.8 ± 2.3 exercise, 13.2 ± 2.2 recovery, ml·min(-1)·g(-1), P < 0.0001), and the increase was largest in nondependent lung (110 ± 61% increase in nondependent, 63 ± 35% in mid, 70 ± 33% in dependent, P < 0.005). The RD of perfusion decreased with exercise (0.93 ± 0.21 rest, 0.73 ± 0.13 exercise, 0.94 ± 0.18 recovery, P < 0.005). The RD of DNP showed a similar trend (0.82 ± 0.14 rest, 0.75 ± 0.09 exercise, 0.81 ± 0.10 recovery, P = 0.13). In conclusion, in contrast to animal studies, in supine humans, mild exercise decreased perfusion heterogeneity, consistent with Zone model predictions.

Reduced frontal white matter volume in long-term childhood leukemia survivors: a voxel-based morphometry study.

BACKGROUND AND PURPOSE: To our knowledge, no published studies have examined whole-brain regional differences to identify more discrete volumetric changes in the brains of childhood leukemia survivors. We used voxel-based morphometry (VBM) to examine regional gray and white matter differences in a group of long-term survivors of acute lymphoblastic leukemia (ALL) compared with a group of healthy controls. Differences in regional white matter volume were expected, given previous reports of white matter changes during treatment for ALL and reduced brain white matter volumes in long-term survivors. Follow-up analyses examined the relationship of regional brain volumes to cognitive function. MATERIALS AND METHODS: We compared 9 long-term survivors of ALL with 14 healthy controls. Survivors of ALL were treated with systemic and intrathecal chemotherapy only. T1-weighted axial 3D spoiled gradient high-resolution images collected on a 1.5T MR imaging scanner were used for the VBM analysis. Neuropsychological evaluations were conducted within 2 months of the MR imaging to assess cognitive function. RESULTS: VBM analysis revealed 2 specific regions of reduced white matter in the right frontal lobes of survivors of ALL compared with healthy controls. Survivors of ALL had lower performances on tests of attention, visual-constructional skills, mental flexibility, and math achievement compared with healthy individuals. Decreased performance on neuropsychological measures was associated with decreased regional white matter volumes. No differences were found between the groups with respect to gray matter regions. CONCLUSION: These findings are consistent with previous literature describing the long-term cognitive, academic, and imaging findings of survivors of ALL and suggest that right frontal white matter is particularly vulnerable to disruption following intensive chemotherapy for ALL. Future studies should focus on further clarifying the white matter changes observed.

Chemical-shift imaging utilizing the positional shifts along the readout gradient direction.

In this work, we describe a method that uses the linear phase acquired during the readout period due to chemical shift to generate individual magnetic resonance (MR) images of chemically shifted species. The method utilizes sets of Fourier (or k-space) data acquired with different directions of the readout gradient and a postprocessing algorithm to generate chemical shift images. The methodology is developed for both Cartesian data acquisition and for radial data acquisition. The method is presented here for two chemically shifted species but it can be extended to more species. In this work, we present the theory, show the results in phantoms and in human images, and discuss the artifacts and signal-to-noise ratio of the images obtained with the technique.

High-resolution diffusion imaging with DIFRAD-FSE (diffusion-weighted radial acquisition of data with fast spin-echo) MRI.

A novel MRI method, DIFRAD-FSE (diffusion-weighted radial acquisition of data with fast spin-echo), is demonstrated that enables rapid, high-resolution multi-shot diffusion-weighted MRI without significant artifacts due to motion. Following a diffusion-weighting spin-echo preparation period, multiple radial lines of Fourier data are acquired using spin-echo refocusing. Images can be reconstructed from the radial data set using a magnitude-only filtered back-projection reconstruction algorithm that removes phase errors due to motion. Results from human brain imaging demonstrate the ability of DIFRAD-FSE to acquire multiple radial lines of Fourier data each TR period without significant artifacts due to relaxation and to produce high-resolution diffusion-weighted MRI images without significant artifacts from motion.