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Multiple breath washout (MBW) testing is increasingly used as a physiological measurement in the clinic, due in part to the availability of commercial equipment and reference values for MBW indices. Commercial N(2) washout devices are usually based on indirect measurement of N(2) concentration (C(N2)), by directly measuring either molar mass and O(2) and CO(2), or molar mass and CO(2). We aim to elucidate the role of two potential pitfalls associated with N(2)-MBW testing that could override its physiological content: indirect N(2) measurement and blood-solubility of N(2). We performed MBW in 12 healthy adult subjects using a commercial device (MBW(indirect)) with simultaneous direct gas concentration measurements by mass spectrometry (MBW(direct)) and compared C(N2) between MBW(direct) and MBW(indirect). We also measured argon concentration during the same washouts to verify the maximal effect gas solubility can have on N(2)-based functional residual capacity (FRC) and lung clearance index (LCI). Continuous N(2) concentration traces were very similar for MBW(indirect) and MBW(direct), resulting in comparable breath-by-breath washout plots of expired concentration and in no significant differences in FRC(N2), LCI(N2), S(cond), and S(acin) between the two methods. Argon washouts were slightly slower than N(2) washouts, as expected for a less diffusive and more soluble gas. Finally, comparison between LCI(N2) and LCI(Ar) indicates that the maximum impact from blood-tissue represents less than half a LCI unit in normal subjects. In conclusion, we have demonstrated by direct measurement of N(2) and twice as soluble argon, that indirect N(2) measurement can be safely used as a meaningful physiological measurement. NEW & NOTEWORTHY The physiological content of N(2) multibreath washout testing has been questioned due to N(2) indirect measurement accuracy and N(2) blood solubility. With direct measurement of N(2) and twice as soluble argon, we show that these effects are largely outweighed by ease of use.

Obstructive sleep apnea (OSA) is highly prevalent in people living with human immunodeficiency virus (HIV) (PLWH), and it might contribute to frequently reported symptoms and comorbidities. Traditional risk factors for OSA are often absent in PLWH, suggesting that HIV or HIV medications might predispose to OSA. Therefore, we measured the anatomical and nonanatomical traits important for OSA pathogenesis in those with and without HIV. We recruited virally suppressed PLWH who had been previously diagnosed with OSA (PLWH + OSA) adherent to positive airway pressure (PAP) therapy, along with age-, sex-, and body mass index (BMI)-matched OSA controls. All participants underwent a baseline polysomnogram to assess OSA severity and a second overnight research sleep study during which the airway pressure was adjusted slowly or rapidly to measure the OSA traits. Seventeen PLWH + OSA and 17 OSA control participants were studied [median age = 58 (IQR = 54–65) yr, BMI = 30.7 (28.4–31.8) kg/m(2), apnea-hypopnea index = 46 (24–74)/h]. The groups were similar, although PLWH + OSA demonstrated greater sleepiness (despite PAP) and worse sleep efficiency on baseline polysomnography. On physiological testing during sleep, there were no statistically significant differences in OSA traits (including V(eupnea), V(arousal), V(passive), V(active), and loop gain) between PLWH + OSA and OSA controls, using mixed-effects modeling to account for age, sex, and BMI and incorporating each repeated measurement (range = 72–334 measures/trait). Our data suggest that well-treated HIV does not substantially impact the pathogenesis of OSA. Given similar underlying physiology, existing available therapeutic approaches are likely to be adequate to manage OSA in PLWH, which might improve symptoms and comorbidities. NEW & NOTEWORTHY Clinical data suggest an increased risk of obstructive sleep apnea (OSA) in people living with HIV (PLWH), while OSA might account for chronic health issues in this population. We characterized the anatomical and nonanatomical OSA traits in PLWH + OSA compared with OSA controls, using detailed physiological measurements obtained during sleep. Our data suggest against a major impact of HIV on OSA pathogenesis. Available OSA management strategies should be effective to address this potentially important comorbidity in PLWH.

There is substantial evidence of age-related declines in anatomical connectivity during adulthood, with associated alterations in functional connectivity. But the relation of those functional alterations to the structural reductions is unclear. The complexities of both the structural and the functional connectomes make it difficult to determine such relationships. We pursue this question with methods, based on animal research, that specifically target the interhemispheric connections between the visual cortices. We collect t1- and diffusion-weighted imaging data from which we assess the integrity of the white matter interconnecting the bilateral visual cortices. Functional connectivity between the visual cortices is measured with electroencephalography during the presentation of drifting sinusoidal gratings that agree or conflict across hemifields. Our results show age-related reductions in the integrity of the white matter interconnecting the visual cortices, and age-related increases in the difference in functional interhemispheric lagged coherence between agreeing versus disagreeing visual stimuli. We show that integrity of the white matter in the splenium of the corpus callosum predicts the differences in lagged coherence for the agreeing versus disagreeing stimuli; and that this relationship is mediated by age. These results give new insight into the causal relationship between age and functional connectivity.

New Findings: What is the central question of this study? How does the interaction between posture and gravity affect the stresses on the lung, particularly in highly inflated gravitationally non-dependent regions, which are potentially vulnerable to increased mechanical stress and injury? What is the main finding and its importance? Changes in stress attributable to gravity are not well characterized between postures. Using a new metric of gravitational stress, we show that regions of the lung near maximal inflation have the greatest gravitational stresses while supine, but not while prone. In simulations of increased lung weight consistent with severe pulmonary oedema, the prone lung has lower gravitational stress in vulnerable, non-dependent regions, potentially protecting them from overinflation and injury. Abstract: Prone posture changes the gravitational vector, and potentially the stress induced by tissue deformation, because a larger lung volume is gravitationally dependent when supine, but non-dependent when prone. To evaluate this, 10 normal subjects (six male and four female; age, means ± SD = 27 ± 6 years; height, 171 ± 9 cm; weight, 69 ± 13 kg; forced expiratory volume in the first second/forced expiratory volume as a percentage of predicted, 93 ± 6%) were imaged at functional residual capacity, supine and prone, using magnetic resonance imaging, to quantify regional lung density. We defined regional gravitational stress as the cumulative weight, per unit area, of the column of lung tissue below each point. Gravitational stress was compared between regions of differing inflation to evaluate differences between highly stretched, and thus potentially vulnerable, regions and less stretched lung. Using reference density values for normal lungs at total lung capacity (0.10 ± 0.03 g/ml), regions were classified as highly inflated (density < 0.13 g/ml, i.e., close to total lung capacity), intermediate (0.13 ≤ density < 0.16 g/ml) or normally inflated (density ≥ 0.16 g/ml). Gravitational stress differed between inflation categories while supine (−1.6 ± 0.3 cmH 2O highly inflated; −1.4 ± 0.3 cmH 2O intermediate; −1.1 ± 0.1 cmH 2O normally inflated; P = 0.05) but not while prone (−1.4 ± 0.2 cmH 2O highly inflated; −1.3 ± 0.2 cmH 2O intermediate; −1.3 ± 0.1 cmH 2O normally inflated; P = 0.39), and increased more with height from dependent lung while supine (−0.24 ± 0.02 cmH 2O/cm supine; −0.18 ± 0.04 cmH 2O/cm prone; P = 0.05). In simulated severe pulmonary oedema, the gradient in gravitational stress increased in both postures (all P 2O/cm supine; −0.34 ± 0.16 cmH 2O/cm prone; P = 0.0004) and was similar to the gradient calculated from supine computed tomography images in a patient with acute respiratory distress syndrome (−0.51 cmH 2O/cm). The non-dependent lung has greater gravitational stress while supine and might be protected while prone, particularly in the presence of oedema.

KEY POINTS The distribution of pulmonary perfusion is affected by gravity, vascular branching structure and active regulatory mechanisms, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. We evaluated pulmonary perfusion in patients who had undergone Fontan procedure, patients with pulmonary arterial hypertension (PAH) and two groups of controls using a proton magnetic resonance imaging technique, arterial spin labelling to measure perfusion. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Gravitational gradients were similar between all groups, but heterogeneity was significantly increased in both patient groups compared to controls and persisted after removing contributions from large blood vessels and gravitational gradients. Patients with Fontan physiology and patients with PAH have increased pulmonary perfusion heterogeneity that is not explainable by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects vascular remodelling in PAH and possibly in Fontan physiology. ABSTRACT Many factors affect the distribution of pulmonary perfusion, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. An example is following the Fontan procedure, where pulmonary perfusion is passive, and heterogeneity may be increased because of the underlying pathophysiology leading to Fontan palliation, remodelling, or increased gravitational gradients from low flow. Another is pulmonary arterial hypertension (PAH), where gravitational gradients may be reduced secondary to high pressures, but remodelling may increase perfusion heterogeneity. We evaluated regional pulmonary perfusion in Fontan patients (n = 5), healthy young controls (Fontan control, n = 5), patients with PAH (n = 6) and healthy older controls (PAH control) using proton magnetic resonance imaging. Regional perfusion was measured using arterial spin labelling. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Mean perfusion was similar (Fontan = 2.50 ± 1.02 ml min-1 ml-1 ; Fontan control = 3.09 ± 0.58, PAH = 3.63 ± 1.95; PAH control = 3.98 ± 0.91, P = 0.26), and the slopes of gravitational gradients were not different (Fontan = -0.23 ± 0.09 ml min-1 ml-1 cm-1 ; Fontan control = -0.29 ± 0.23, PAH = -0.27 ± 0.09, PAH control = -0.25 ± 0.18, P = 0.91) between groups. Perfusion relative dispersion was greater in both Fontan and PAH than controls (Fontan = 1.46 ± 0.18; Fontan control = 0.99 ± 0.21, P = 0.005; PAH = 1.22 ± 0.27, PAH control = 0.91 ± 0.12, P = 0.02) but similar between patient groups (P = 0.13). These findings persisted after removing contributions from large blood vessels and gravitational gradients (all P

The location of lung regions with compromised ventilation (often called ventilation defects) during a bronchoconstriction event may be influenced by posture. We aimed to determine the effect of prone versus supine posture on the spatial pattern of methacholine-induced bronchoconstriction in six healthy adults (ages 21–41, 3 women) using specific ventilation imaging. Three postural conditions were chosen to assign the effect of posture to the drug administration and/or imaging phase of the experiment: supine methacholine administration followed by supine imaging, prone methacholine administration followed by supine imaging, and prone methacholine administration followed by prone imaging. The two conditions in which imaging was performed supine had similar spatial patterns of bronchoconstriction despite a change in posture during methacholine administration; the odds ratio for recurrent constriction was mean (SD) = 7.4 (3.9). Conversely, dissimilar spatial patterns of bronchoconstriction emerged when posture during imaging was changed; the odds ratio for recurrent constriction between the prone methacholine/supine imaging condition and the prone methacholine/prone imaging condition was 1.2 (0.9). Logistic regression showed that height above the dependent lung border was a significant negative predictor of constriction in the two supine imaging conditions ( P < 0.001 for each) but not in the prone imaging condition ( P = 0.20). These results show that the spatial pattern of methacholine bronchoconstriction is recurrent in the supine posture, regardless of whether methacholine is given prone or supine but that prone posture during imaging eliminates that recurrent pattern and reduces its dependence on gravitational height. NEW & NOTEWORTHY The spatial pattern of methacholine bronchoconstriction in the supine posture is recurrent and skewed toward the dependent lung, regardless of whether inhaled methacholine is administered while supine or while prone. However, both the recurrent pattern and the gravitational skew are eliminated if imaging is performed prone. These results suggest that gravitational influence on regional lung inflation and airway topography at the time of measurement play a role in determining regional bronchoconstriction in the healthy lung.

Two magnetic resonance specific ventilation imaging (SVI) techniques, namely, oxygen-enhanced proton (OE-1H) and hyperpolarized 3He (HP-3He), were compared in eight healthy supine subjects [age 32 (6) yr]. An in-house radio frequency coil array for 1H configured with the 3He transmit-receive coil in situ enabled acquisition of SVI data from two nuclei from the same slice without repositioning the subjects. After 3 × 3 voxel downsampling to account for spatial registration errors between the two SV images, the voxel-by-voxel correlation coefficient of two SV maps ranged from 0.11 to 0.63 [0.46 mean (0.17 SD); P < 0.05]. Several indexes were analyzed and compared from the tidal volume-matched SV maps: the mean of SV log-normal distribution (SVmean), the standard deviation of the distribution as a measure of SV heterogeneity (SVwidth), and the gravitational gradient (SVslope). There were no significant differences in SVmean [OE-1H: 0.28 (0.08) and HP-3He: 0.32 (0.14)], SVwidths [OE-1H: 0.28 (0.08) and HP-3He: 0.27 (0.10)], and SVslopes [OE-1H: −0.016 (0.006) cm−1 and HP-3He: −0.013 (0.007) cm−1]. Despite the statistical similarities of the population averages, Bland-Altman analysis demonstrated large individual intertechnique variability. SDs of differences in these indexes were 42% (SVmean), 46% (SVwidths), and 62% (SVslopes) of their corresponding overall mean values. The present study showed that two independent, spatially coregistered, SVI techniques presented a moderate positive voxel-by-voxel correlation. Population averages of SVmean, SVwidth, and SVslope were in close agreement. However, the lack of agreement when the data sets were analyzed individually might indicate some fundamental mechanistic differences between the techniques. NEW & NOTEWORTHY To the best of our knowledge, this is the first cross-comparison of two different specific ventilation (SV) MRI techniques in the human lung (i.e., oxygen-enhanced proton and hyperpolarized 3He). The present study showed that two types of spatially coregistered SV images presented a modest positive correlation. The two techniques also yielded similar population averages of SV indexes such as log-normal mean, SV heterogeneity, and the gravitational slope, albeit with some intersubject variability.

Brain enlargement is associated with concomitant growth of interneuronal distance, increased conduction time, and reduced neuronal interconnectivity. Recognition of these functional constraints led to the hypothesis that large-brained mammals should exhibit greater structural and functional brain lateralization. As a taxon with the largest brains in the animal kingdom, Cetacea provides a unique opportunity to examine asymmetries of brain structure and function. In the present study, diffusion tensor imaging and tractography were used to investigate cerebral white matter asymmetry in the bottlenose dolphin (Tursiops truncatus). Widespread white matter asymmetries were observed with the preponderance of tracts exhibiting leftward structural asymmetries. Leftward lateralization may reflect differential processing and execution of behaviorally variant sensory and motor functions by the cerebral hemispheres. The arcuate fasciculus, an association tract linked to human language evolution, was isolated and exhibited rightward asymmetry suggesting a right hemisphere bias for conspecific communication unlike that of most mammals. This study represents the first examination of cetacean white matter asymmetry and constitutes an important step toward understanding potential drivers of structural asymmetry and its role in underpinning functional and behavioral lateralization in cetaceans. Electronic supplementary material The online version of this article (doi:10.1007/s00429-017-1525-9) contains supplementary material, which is available to authorized users.

Objectives Bipolar disorder (BD) is associated with compromised white matter (WM) integrity and deficits in processing speed (PS). Few studies, however, have investigated age relationships with WM structure and cognition to understand possible changes in brain health over the lifespan. This investigation explored whether BD and healthy counterpart (HC) participants exhibited differential age-related associations with WM and cognition, which may be suggestive of accelerated brain and cognitive aging. Design Cross-sectional study. Setting University of California San Diego and the Veterans Administration San Diego Healthcare System. Participants 33 euthymic BD and 38 HC participants. Measurements Diffusion tensor imaging was acquired as a measure of WM integrity, and tract-specific fractional anisotropy (FA) was extracted utilizing the Johns Hopkins University probability atlas. PS was assessed with the Number and Letter Sequencing conditions of the Delis-Kaplan Executive Function System Trail Making Test. Results BD participants demonstrated slower PS compared with the HC group, but no group differences were found in FA across tracts. Multiple linear regressions revealed a significant group-by-age interaction for the right uncinate fasciculus, the left hippocampal portion of the cingulum, and for PS, such that older age was associated with lower FA values and slower PS in the BD group only. The relationship between age and PS did not significantly change after accounting for uncinate FA, suggesting that the observed age associations occur independently. Conclusions Results provide support for future study of the accelerated aging hypothesis by identifying markers of brain health that demonstrate a differential age association in BD.

Pulmonary vascular tone is known to be sensitive to both local alveolar Po2 and Pco2. Although the effects of hypoxia are well studied, the hypercapnic response is relatively less understood. We assessed changes in regional pulmonary blood flow in humans in response to hypercapnia using previously developed MRI techniques. Dynamic measures of blood flow were made in a single slice of the right lung of seven healthy volunteers following a block-stimulus paradigm (baseline, challenge, recovery), with CO2 added to inspired gas during the challenge block to effect a 7-Torr increase in end-tidal CO2. Effects of hypercapnia on blood flow were evaluated based on changes in spatiotemporal variability (fluctuation dispersion, FD) and in regional perfusion patterns in comparison to hypoxic effects previously studied. Hypercapnia increased FD 2.5% from baseline (relative to control), which was not statistically significant ( P = 0.07). Regional perfusion patterns were not significantly changed as a result of increased [Formula: see text] ( P = 0.90). Reanalysis of previously collected data using a similar protocol but with the physiological challenge replaced by decreased [Formula: see text] ([Formula: see text] = 0.125) showed marked flow redistribution ( P = 0.01) with the suggestion of a gravitational pattern, demonstrating hypoxia has the ability to affect regional change with a global stimulus. Taken together, these data indicate that hypercapnia of this magnitude does not lead to appreciable changes in the distribution of pulmonary perfusion, and that this may represent an interesting distinction between the hypoxic and hypercapnic regulatory response. NEW & NOTEWORTHY Although it is well known that the pulmonary circulation responds to local alveolar hypoxia, and that this mechanism may facilitate ventilation-perfusion matching, the relative role of CO2 is not well appreciated. This study demonstrates that an inspiratory hypercapnic stimulus is significantly less effective at inducing changes in pulmonary perfusion patterns than inspiratory hypoxia, suggesting that in these circumstances hypercapnia is not sufficient to induce substantial integrated feedback control of ventilation-perfusion mismatch across the lung.

Specific ventilation imaging (SVI) is a functional magnetic resonance imaging technique capable of quantifying specific ventilation ― the ratio of the fresh gas entering a lung region divided by the region’s end-expiratory volume ― in the human lung, using only inhaled oxygen as a contrast agent. Regional quantification of specific ventilation has the potential to help identify areas of pathologic lung function. Oxygen in solution in tissue shortens the tissue’s longitudinal relaxation time (T(1)), and thus a change in tissue oxygenation can be detected as a change in T(1)-weighted signal with an inversion recovery acquired image. Following an abrupt change between two concentrations of inspired oxygen, the rate at which lung tissue within a voxel equilibrates to a new steady-state reflects the rate at which resident gas is being replaced by inhaled gas. This rate is determined by specific ventilation. To elicit this sudden change in oxygenation, subjects alternately breathe 20-breath blocks of air (21% oxygen) and 100% oxygen while in the MRI scanner. A stepwise change in inspired oxygen fraction is achieved through use of a custom three-dimensional (3D)-printed flow bypass system with a manual switch during a short end-expiratory breath hold. To detect the corresponding change in T(1), a global inversion pulse followed by a single shot fast spin echo sequence was used to acquire two-dimensional T(1)-weighted images in a 1.5 T MRI scanner, using an eight-element torso coil. Both single slice and multi-slice imaging are possible, with slightly different imaging parameters. Quantification of specific ventilation is achieved by correlating the time-course of signal intensity for each lung voxel with a library of simulated responses to the air/oxygen stimulus. SVI estimations of specific ventilation heterogeneity have been validated against multiple breath washout and proved to accurately determine the heterogeneity of the specific ventilation distribution.

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.

The LC5 isolate of Little cherry virus (LChV-LC5) is one of at least two distinct viruses contributing to a severe disease of cherry (Little cherry disease [LChD]) in British Columbia. A near-complete nucleotide sequence of LChV-LC5 is available as well as polyclonal antibodies against LChV-LC5 coat protein produced in bacterial cells. A survey for LChV-LC5-infected trees in the Okanagan Valley and Kootenay region of British Columbia was carried out using enzyme-linked immunosorbent assays (ELISA) and LChV-LC5 antibodies. Reverse transcriptase polymerase chain reaction (RT-PCR) and sequence analysis of four different regions of the genomes of 31 of these isolates have been conducted. A high level of sequence variability was found: nucleotide sequence divergence between LChV-LC5 and the other sequenced isolates ranged from 0 to 19.7%, and amino acid sequence divergence ranged from 0 to 9.1%. Further examination of RT-PCR and sequence data identified six discrete groups of isolates, including a group identical to LChV-LC5. The high level of divergence in LChV-LC5 isolates occurring in British Columbia suggests that caution should be used in the selection of methods used for diagnosis during surveys for this virus.

Key points Pulmonary perfusion measurement using magnetic resonance imaging combined with deformable image registration enabled us to quantify the change in the spatial distribution of pulmonary perfusion at different lung volumes. The current study elucidated the effects of tidal volume lung inflation [functional residual capacity (FRC) + 500 ml and FRC + 1 litre] on the change in pulmonary perfusion distribution. Changes in hydrostatic pressure distribution as well as transmural pressure distribution due to the change in lung height with tidal volume inflation are probably bigger contributors to the redistribution of pulmonary perfusion than the changes in pulmonary vasculature resistance caused by lung tissue stretch. Abstract Tidal volume lung inflation results in structural changes in the pulmonary circulation, potentially affecting pulmonary perfusion. We hypothesized that perfusion is recruited to regions receiving the greatest deformation from a tidal breath, thus ensuring ventilation–perfusion matching. Density-normalized perfusion (DNP) magnetic resonance imaging data were obtained in healthy subjects (n = 7) in the right lung at functional residual capacity (FRC), FRC+500 ml, and FRC+1.0 l. Using deformable image registration, the displacement of a sagittal lung slice acquired at FRC to the larger volumes was calculated. Registered DNP images were normalized by the mean to estimate perfusion redistribution (nDNP). Data were evaluated across gravitational regions (dependent, middle, non-dependent) and by lobes (upper, RUL; middle, RML; lower, RLL). Lung inflation did not alter mean DNP within the slice (P = 0.10). The greatest expansion was seen in the dependent region (P

Two magnetic resonance specific ventilation imaging (SVI) techniques, namely, oxygen-enhanced proton (OE-(1)H) and hyperpolarized (3)He (HP-(3)He), were compared in eight healthy supine subjects [age 32 (6) yr]. An in-house radio frequency coil array for (1)H configured with the (3)He transmit-receive coil in situ enabled acquisition of SVI data from two nuclei from the same slice without repositioning the subjects. After 3 × 3 voxel downsampling to account for spatial registration errors between the two SV images, the voxel-by-voxel correlation coefficient of two SV maps ranged from 0.11 to 0.63 [0.46 mean (0.17 SD); P < 0.05]. Several indexes were analyzed and compared from the tidal volume-matched SV maps: the mean of SV log-normal distribution (SVmean), the standard deviation of the distribution as a measure of SV heterogeneity (SVwidth), and the gravitational gradient (SVslope). There were no significant differences in SVmean [OE-(1)H: 0.28 (0.08) and HP-(3)He: 0.32 (0.14)], SVwidths [OE-(1)H: 0.28 (0.08) and HP-(3)He: 0.27 (0.10)], and SVslopes [OE-(1)H: −0.016 (0.006) cm(−1) and HP-(3)He: −0.013 (0.007) cm(−1)]. Despite the statistical similarities of the population averages, Bland-Altman analysis demonstrated large individual intertechnique variability. SDs of differences in these indexes were 42% (SVmean), 46% (SVwidths), and 62% (SVslopes) of their corresponding overall mean values. The present study showed that two independent, spatially coregistered, SVI techniques presented a moderate positive voxel-by-voxel correlation. Population averages of SVmean, SVwidth, and SVslope were in close agreement. However, the lack of agreement when the data sets were analyzed individually might indicate some fundamental mechanistic differences between the techniques. NEW & NOTEWORTHY To the best of our knowledge, this is the first cross-comparison of two different specific ventilation (SV) MRI techniques in the human lung (i.e., oxygen-enhanced proton and hyperpolarized (3)He). The present study showed that two types of spatially coregistered SV images presented a modest positive correlation. The two techniques also yielded similar population averages of SV indexes such as log-normal mean, SV heterogeneity, and the gravitational slope, albeit with some intersubject variability.

We used magnetic resonance imaging (MRI) to quantify change in upper airway dimension during tidal breathing in subjects with obstructive sleep apnea (OSA, N=7) and BMI-matched healthy controls (N=7) during both wakefulness and natural sleep. Dynamic MR images of the upper airway were obtained on a 1.5T MR scanner in contiguous 7.5mm-thick axial slices from the hard palate to the epiglottis along with synchronous MRI-compatible electroencephalogram and nasal/oral flow measurements. The physiologic data were retrospectively scored to identify sleep state, and synchronized with dynamic MR images. For each image, the upper airway was characterized by its area, and linear dimensions (lateral and anterior-posterior). The dynamic behavior of the upper airway was assessed by the maximum change in these parameters over the tidal breath. Mean upper airway caliber was obtained by averaging data over the tidal breath. There was no major difference in the upper airway structure between OSA and controls except for a narrower airway at the low-retropalatal/high-retroglossal level in OSA than in controls. Changes in upper airway size over the tidal breath ((maximum-minimum)/mean) were significantly larger in the OSA than in the control group in the low retropalatal/high retroglossal region during both wakefulness and sleep. In the four OSA subjects who experienced obstructive apneas during MR imaging, the site of airway collapse during sleep corresponded to the region of the upper airway where changes in caliber during awake tidal breathing were the greatest. These observations suggest a potential role for dynamic OSA imaging during wakefulness.

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.

Evidence for abnormal brain function as measured with diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) and cognitive dysfunction have been observed in inter-episode bipolar disorder (BD) patients. We aimed to create a joint statistical model of white matter integrity and functional response measures in explaining differences in working memory and processing speed among BD patients. Medicated inter-episode BD (n=26; age=45.2±10.1 years) and healthy comparison (HC; n=36; age=46.3±11.5 years) participants completed 51-direction DTI and fMRI while performing a working memory task. Participants also completed a processing speed test. Tract-based spatial statistics identified common white matter tracts where fractional anisotropy was calculated from atlas-defined regions of interest. Brain responses within regions of interest activation clusters were also calculated. Least angle regression was used to fuse fMRI and DTI data to select the best joint neuroimaging predictors of cognitive performance for each group. While there was overlap between groups in which regions were most related to cognitive performance, some relationships differed between groups. For working memory accuracy, BD-specific predictors included bilateral dorsolateral prefrontal cortex from fMRI, splenium of the corpus callosum, left uncinate fasciculus, and bilateral superior longitudinal fasciculi from DTI. For processing speed, the genu and splenium of the corpus callosum and right superior longitudinal fasciculus from DTI were significant predictors of cognitive performance selectively for BD patients. BD patients demonstrated unique brain-cognition relationships compared to HC. These findings are a first step in discovering how interactions of structural and functional brain abnormalities contribute to cognitive impairments in BD. (JINS, 2015, 21, 330–341)

Hypoxic pulmonary vasoconstriction (HPV) is thought to actively regulate ventilation-perfusion (V̇a/Q̇) matching, reducing perfusion in regions of alveolar hypoxia. We assessed the extent of HPV in the healthy human lung using inhaled nitric oxide (iNO) under inspired oxygen fractions (FiO2) of 0.125, 0.21, and 0.30 (a hyperoxic stimulus designed to abolish HPV without the development of atelectasis). Dynamic measures of blood flow were made in a single sagittal slice of the right lung of five healthy male subjects using an arterial spin labeling (ASL) MRI sequence, following a block stimulus pattern (3 × 60 breaths) with 40 ppm iNO administered in the central block. The overall spatial heterogeneity, spatiotemporal variability, and regional pattern of pulmonary blood flow was quantified as a function of condition (FiO2× iNO state). While spatial heterogeneity did not change significantly with iNO administration or FiO2, there were statistically significant increases in Global Fluctuation Dispersion,(a marker of spatiotemporal flow variability) when iNO was administered during hypoxia (5.4 percentage point increase, P = 0.003). iNO had an effect on regional blood flow that was FiO2dependent ( P = 0.02), with regional changes in the pattern of blood flow occurring in hypoxia ( P = 0.007) and normoxia ( P = 0.008) tending to increase flow to dependent lung at the expense of nondependent lung. These findings indicate that inhaled nitric oxide significantly alters the distribution of blood flow in both hypoxic and normoxic healthy subjects, and suggests that some baseline HPV may indeed be present in the normoxic lung.

We have developed a novel functional proton magnetic resonance imaging (MRI) technique to measure regional ventilation-perfusion (V̇A/Q̇) ratio in the lung. We conducted a comparison study of this technique in healthy subjects ( n = 7, age = 42 ± 16 yr, Forced expiratory volume in 1 s = 94% predicted), by comparing data measured using MRI to that obtained from the multiple inert gas elimination technique (MIGET). Regional ventilation measured in a sagittal lung slice using Specific Ventilation Imaging was combined with proton density measured using a fast gradient-echo sequence to calculate regional alveolar ventilation, registered with perfusion images acquired using arterial spin labeling, and divided on a voxel-by-voxel basis to obtain regional V̇A/Q̇ ratio. LogSDV̇ and LogSDQ̇, measures of heterogeneity derived from the standard deviation (log scale) of the ventilation and perfusion vs. V̇A/Q̇ ratio histograms respectively, were calculated. On a separate day, subjects underwent study with MIGET and LogSDV̇ and LogSDQ̇ were calculated from MIGET data using the 50-compartment model. MIGET LogSDV̇ and LogSDQ̇ were normal in all subjects. LogSDQ̇ was highly correlated between MRI and MIGET (R = 0.89, P = 0.007); the intercept was not significantly different from zero (−0.062, P = 0.65) and the slope did not significantly differ from identity (1.29, P = 0.34). MIGET and MRI measures of LogSDV̇ were well correlated (R = 0.83, P = 0.02); the intercept differed from zero (0.20, P = 0.04) and the slope deviated from the line of identity (0.52, P = 0.01). We conclude that in normal subjects, there is a reasonable agreement between MIGET measures of heterogeneity and those from proton MRI measured in a single slice of lung. NEW & NOTEWORTHY We report a comparison of a new proton MRI technique to measure regional V̇A/Q̇ ratio against the multiple inert gas elimination technique (MIGET). The study reports good relationships between measures of heterogeneity derived from MIGET and those derived from MRI. Although currently limited to a single slice acquisition, these data suggest that single sagittal slice measures of V̇A/Q̇ ratio provide an adequate means to assess heterogeneity in the normal lung.

Specific ventilation imaging (SVI) uses proton MRI to quantitatively map the distribution of specific ventilation (SV) in the human lung, using inhaled oxygen as a contrast agent. To validate this recent technique, we compared the quantitative measures of heterogeneity of the SV distribution in a 15-mm sagittal slice of lung obtained in 10 healthy supine subjects, (age 37 ± 10 yr, forced expiratory volume in 1 s 97 ± 7% predicted) using SVI to those obtained in the whole lung from multiple-breath nitrogen washout (MBW). Using the analysis of Lewis et al. (Lewis SM, Evans JW, Jalowayski AA. J App Physiol 44: 416–423, 1978), the most likely distribution of SV from the MBW data was computed and compared with the distribution of SV obtained from SVI, after normalizing for the difference in tidal volume. The average SV was 0.30 ± 0.10 MBW, compared with 0.36 ± 0.10 SVI ( P = 0.01). The width of the distribution, a measure of the heterogeneity, obtained using both methods was comparable: 0.51 ± 0.06 and 0.47 ± 0.08 in MBW and SVI, respectively ( P = 0.15). The MBW estimated width of the SV distribution was 0.05 (10.7%) higher than that estimated using SVI, and smaller than the intertest variability of the MBW estimation [inter-MBW (SD) for the width of the SV distribution was 0.08 (15.8)%]. To assess reliability, SVI was performed twice on 13 subjects showing small differences between measurements of SV heterogeneity (typical error 0.05, 12%). In conclusion, quantitative estimations of SV heterogeneity from SVI are reliable and similar to those obtained using MBW, with SVI providing spatial information that is absent in MBW.

Despite modern antiretroviral therapy, HIVassociated sensory neuropathy affects over 50% of HIV patients. The clinical expression of HIV neuropathy is highly variable: many individuals report few symptoms, but about half report distal neuropathic pain (DNP), making it one of the most prevalent, disabling, and treatment-resistant complications of HIV disease. The presence and intensity of pain is not fully explained by the degree of peripheral nerve damage, making it unclear why some patients do, and others do not, report pain. To better understand central nervous system contributions to HIV DNP, we performed a cross-sectional analysis of structural magnetic resonance imaging volumes in 241 HIV-infected participants from an observational multi-site cohort study at five US sites (CNS HIV Anti-Retroviral Treatment Effects Research Study, CHAR TER). The association between DNP and the structural imaging outcomes was investigated using both linear and nonlinear (Gaussian Kernel support vector) multivariable regression, controlling for key demographic and clinical variables. Severity of DNP symptoms was correlated with smaller total cerebral cortical gray matter volume (r = -0.24; p =0.004). Understanding the mechanisms for this association between smaller total cortical volumes and DNP may provide insight into HIV DNP chronicity and treatment-resistance. © Journal of NeuroVirology, Inc. 2014.

Post-traumatic stress disorder (PTSD) is a leading cause of sustained impairment, distress, and poor quality of life in military personnel, veterans, and civilians. Indirect functional neuroimaging studies using PET or fMRI with fear-related stimuli support a PTSD neurocircuitry model that includes amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC). However, it is not clear if this model can fully account for PTSD abnormalities detected directly by electromagnetic-based source imaging techniques in resting-state. The present study examined resting-state magnetoencephalography (MEG) signals in 25 active-duty service members and veterans with PTSD and 30 healthy volunteers. In contrast to the healthy volunteers, individuals with PTSD showed: 1) hyperactivity from amygdala, hippocampus, posterolateral orbitofrontal cortex (OFC), dorsomedial prefrontal cortex (dmPFC), and insular cortex in high-frequency (i.e., beta, gamma, and high-gamma) bands; 2) hypoactivity from vmPFC, Frontal Pole (FP), and dorsolateral prefrontal cortex (dlPFC) in high-frequency bands; 3) extensive hypoactivity from dlPFC, FP, anterior temporal lobes, precuneous cortex, and sensorimotor cortex in alpha and low-frequency bands; and 4) in individuals with PTSD, MEG activity in the left amygdala and posterolateral OFC correlated positively with PTSD symptom scores, whereas MEG activity in vmPFC and precuneous correlated negatively with symptom score. The present study showed that MEG source imaging technique revealed new abnormalities in the resting-state electromagnetic signals from the PTSD neurocircuitry. Particularly, posterolateral OFC and precuneous may play important roles in the PTSD neurocircuitry model., Highlights • Resting-state MEG detects abnormal electromagnetic activity in PTSD neurocircuitry • PTSD showed hyperactivity in amygdala, hippocampus, and orbitofrontal cortex • PTSD showed hypoactivity in vmPFC, frontal pole, and dlPFC • PTSD symptom score correlated with MEG activity

Objective: A recent study of ill individuals with anorexia nervosa (AN) reported microstructural alterations in white matter integrity including lower fractional anisotropy and higher mean diffusivity. This study was designed to determine whether such alterations exist in longterm recovered AN individuals and to examine potential associations with underlying AN traits. Method: Twelve adult women recovered from restricting-type AN and 10 control women were studied using diffusion tensor imaging. Results: Overall, there was no significant fractional anisotropy alteration in recovered AN, in contrast to a prior study reporting lower fractional anisotropy in ill AN. Further, recovered AN showed lower mean diffusivity in frontal, parietal and cingulum white matter relative to control women, contrary to elevated mean diffusivity previously reported in ill AN. Lower longitudinal diffusivity in recovered AN was associated with higher harm avoidance. However, more severe illness history was associated with worse white matter integrity after recovery in the same direction as reported in prior work. Discussion: Our findings suggest that fractional anisotropy in recovered AN is not different from controls, however, a novel pattern of lower mean diffusivity was evidenced in recovered AN, and this alteration was associated with harm avoidance. Notably, severity of illness history may have long-term consequences, emphasizing the importance of aggressive treatment.

Heavy exercise increases ventilation-perfusion mismatch and decreases pulmonary gas exchange efficiency. Previous work using magnetic resonance imaging (MRI) arterial spin labeling in athletes has shown that, after 45 min of heavy exercise, the spatial heterogeneity of pulmonary blood flow was increased in recovery. We hypothesized that the heterogeneity of regional specific ventilation (SV, the local tidal volume over functional residual capacity ratio) would also be increased following sustained exercise, consistent with the previously documented changes in blood flow heterogeneity. Trained subjects ( n = 6, maximal O2consumption = 61 ± 7 ml·kg−1·min−1) cycled 45 min at their individually determined ventilatory threshold. Oxygen-enhanced MRI was used to quantify SV in a sagittal slice of the right lung in supine posture pre- (preexercise) and 15- and 60-min postexercise. Arterial spin labeling was used to measure pulmonary blood flow in the same slice bracketing the SV measures. Heterogeneity of SV and blood flow were quantified by relative dispersion (RD = SD/mean). The alveolar-arterial oxygen difference was increased during exercise, 23.3 ± 5.3 Torr, compared with rest, 6.3 ± 3.7 Torr, indicating a gas exchange impairment during exercise. No significant change in RD of SV was seen after exercise: preexercise 0.78 ± 0.15, 15 min postexercise 0.81 ± 0.13, 60 min postexercise 0.78 ± 0.08 ( P = 0.5). The RD of blood flow increased significantly postexercise: preexercise 1.00 ± 0.12, 15 min postexercise 1.15 ± 0.10, 45 min postexercise 1.10 ± 0.10, 60 min postexercise 1.19 ± 0.11, 90 min postexercise 1.11 ± 0.12 ( P < 0.005). The lack of a significant change in RD of SV postexercise, despite an increase in the RD of blood flow, suggests that airways may be less susceptible to the effects of exercise than blood vessels.

The temporal dynamics of blood flow in the human lung have been largely unexplored due to the lack of appropriate technology. Using the magnetic resonance imaging method of arterial spin labeling (ASL) with subject-gated breathing, we produced a dynamic series of flow-weighted images in a single sagittal slice of the right lung with a spatial resolution of ∼1 cm3and a temporal resolution of ∼10 s. The mean flow pattern determined from a set of reference images was removed to produce a time series of blood flow fluctuations. The fluctuation dispersion (FD), defined as the spatial standard deviation of each flow fluctuation map, was used to quantify the changes in distribution of flow in six healthy subjects in response to 100 breaths of hypoxia (FiO2= 0.125) or hyperoxia (FiO2= 1.0). Two reference frames were used in calculation, one determined from the initial set of images (FDglobal), and one determined from the mean of each corresponding baseline or challenge period (FDlocal). FDlocalthus represented changes in temporal variability as a result of intervention, whereas FDglobalencompasses both FDlocaland any generalized redistribution of flow associated with switching between two steady-state patterns. Hypoxic challenge resulted in a significant increase (96%, P < 0.001) in FDglobalfrom the normoxic control period and in FDlocal(46%, P = 0.0048), but there was no corresponding increase in spatial relative dispersion (spatial standard deviation of the images divided by the mean; 8%, not significant). There was a smaller increase in FDglobalin response to hyperoxia (47%, P = 0.0015) for the single slice, suggestive of a more general response of the pulmonary circulation to a change from normoxia to hyperoxia. These results clearly demonstrate a temporal change in the sampled distribution of pulmonary blood flow in response to hypoxia, which is not observed when considering only the relative dispersion of the spatial distribution.

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. Injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1–4 Hz) that can be measured and localized by magnetoencephalography (MEG). We developed a new automated MEG low-frequency source imaging method and applied this method in 45 mild TBI (23 from combat-related blasts, and 22 from non-blast causes) and 10 moderate TBI patients (non-blast causes). Seventeen of the patients with mild TBI from blasts had tertiary injuries resulting from the blast. The results show our method detected abnormalities at the rates of 87% for the mild TBI group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities were 96% and 77% for the blast and non-blast TBI groups, respectively. The spatial characteristics of abnormal slow-wave generation measured by Z scores in the mild blast TBI group significantly correlated with those in non-blast mild TBI group. Among 96 cortical regions, the likelihood of abnormal slow-wave generation was less in the mild TBI patients with blast than in the mild non-blast TBI patients, suggesting possible protective effects due to the military helmet and armor. Finally, the number of cortical regions that generated abnormal slow-waves correlated significantly with the total post-concussive symptom scores in TBI patients. This study provides a foundation for using MEG low-frequency source imaging to support the clinical diagnosis of TBI.

Typical adults show an inverse relation between callosal fiber length and degree of interhemispheric connectivity. This has been hypothesized to be a consequence of the influence of conduction delays and cellular costs during development on axonal pruning, both of which increase with fiber length. Autism spectrum disorder (ASD) provides a test of this hypothesis: Children with ASD are known to have enlarged brains; thus, adults with ASD should show reductions in interhemispheric connectivity proportional to their degree of brain overgrowth during development. This prediction was tested by assessing the relation between both the size and structure of the corpus callosum and callosal fiber length, adjusting for intracranial volume, which is thought to reflect maximum brain size achieved during development. Using tractography to estimate the length of callosal fibers emanating from all areas of cortex, and through which region of the corpus callosum they pass, we show that adults with ASD show an inverse relation between callosal fiber length, adjusted for intracranial volume, and callosum size, and a positive relation between adjusted callosal fiber length and radial diffusivity. The results provide support for the hypothesized impact of fiber length during development. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.

Purpose: To validate a fast gradient echo sequence for rapid (9 s) quantitative imaging of lung water. Materials and Methods: Eleven excised pig lungs were imaged with a fast GRE sequence in triplicate, in the sagittal plane at 2 levels of inflation pressure (5 and 15 cm H2O), an intervention that alters T2*, but not total lung water. Images were acquired alternating between two closely-spaced echoes and data were fit (voxel-by-voxel) to a single exponential to determine T2* and water content, and compared with gravimetric measurements of total water. Results: T2* averaged 1.08 ± 0.02 ms at 5 cm H2O and 1.02 ± 0.02 ms at 15 cm H2O (P < 0.05). The measure was reliable (R2 = 0.99), with an average mean error of 1.8%. There was a significant linear relationship between the two measures of water content: The regression equations for the relationship were y = 0.92x + 19 (R2 = 0.94), and y = 1.04x + 4 (R2 = 0.96), for 5 and 15 cm H2O inflation pressure respectively. Y-intercepts were not statistically different from zero (P = 0.86). Conclusion: The multi-echo GRE sequence is a reliable and valid technique to assess water content in the lung. This technique enables rapid assessment of lung water, which is advantageous for in vivo studies. J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc.

Beamformer spatial filters are commonly used to explore the active neuronal sources underlying magnetoencephalography (MEG) recordings at low signal-to-noise ratio (SNR). Conventional beamformer techniques are successful in localizing uncorrelated neuronal sources under poor SNR conditions. However, the spatial and temporal features from conventional beamformer reconstructions suffer when sources are correlated, which is a common and important property of real neuronal networks. Dual-beamformer techniques, originally developed by Brookes et al. to deal with this limitation, successfully localize highly-correlated sources and determine their orientations and weightings, but their performance degrades at low correlations. They also lack the capability to produce individual time courses and therefore cannot quantify source correlation. In this paper, we present an enhanced formulation of our earlier dual-core beamformer (DCBF) approach that reconstructs individual source time courses and their correlations. Through computer simulations, we show that the enhanced DCBF (eDCBF) consistently and accurately models dual-source activity regardless of the correlation strength. Simulations also show that a multi-core extension of eDCBF effectively handles the presence of additional correlated sources. In a human auditory task, we further demonstrate that eDCBF accurately reconstructs left and right auditory temporal responses and their correlations. Spatial resolution and source localization strategies corresponding to different measures within the eDCBF framework are also discussed. In summary, eDCBF accurately reconstructs source spatio-temporal behavior, providing a means for characterizing complex neuronal networks and their communication.

Specific ventilation (SV) is the ratio of fresh gas entering a lung region divided by its end-expiratory volume. To quantify the vertical (gravitationally dependent) gradient of SV in eight healthy supine subjects, we implemented a novel proton magnetic resonance imaging (MRI) method. Oxygen is used as a contrast agent, which in solution changes the longitudinal relaxation time (T1) in lung tissue. Thus alterations in the MR signal resulting from the regional rise in O2concentration following a sudden change in inspired O2reflect SV—lung units with higher SV reach a new equilibrium faster than those with lower SV. We acquired T1-weighted inversion recovery images of a sagittal slice of the supine right lung with a 1.5-T MRI system. Images were voluntarily respiratory gated at functional residual capacity; 20 images were acquired with the subject breathing air and 20 breathing 100% O2, and this cycle was repeated five times. Expired tidal volume was measured simultaneously. The SV maps presented an average spatial fractal dimension of 1.13 ± 0.03. There was a vertical gradient in SV of 0.029 ± 0.012 cm−1, with SV being highest in the dependent lung. Dividing the lung vertically into thirds showed a statistically significant difference in SV, with SV of 0.42 ± 0.14 (mean ± SD), 0.29 ± 0.10, and 0.24 ± 0.08 in the dependent, intermediate, and nondependent regions, respectively (all differences, P < 0.05). This vertical gradient in SV is consistent with the known gravitationally induced deformation of the lung resulting in greater lung expansion in the dependent lung with inspiration. This SV imaging technique can be used to quantify regional SV in the lung with proton MRI.