Spatial-temporal dynamics of pulmonary blood flow in the healthy human lung in response to altered Fi_O2

Abstract

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 cm(3) and 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 (FI(O(2)) = 0.125) or hyperoxia (FI(O(2)) = 1.0). Two reference frames were used in calculation, one determined from the initial set of images (FD(global)), and one determined from the mean of each corresponding baseline or challenge period (FD(local)). FD(local) thus represented changes in temporal variability as a result of intervention, whereas FD(global) encompasses both FD(local) and 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 FD(global) from the normoxic control period and in FD(local) (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 FD(global) in 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.

Advances in functional and structural imaging of the human lung using proton MRI

“…As temporal ASL in the lung is a new technique, only limited studies have been performed to date. The lone published study examines the effects of altered inspired O 2 levels on the spatial–temporal heterogeneity of pulmonary blood flow . The rationale behind this study lies in the knowledge that alveolar hypoxia results in vasoconstriction of the blood vessels flowing into the hypoxic region of the lung .…”

“…To do so we developed the fluctuation dispersion (FD) metric, which focuses on comparing multiple identically acquired images to a reference condition and examining the fluctuations that result. The technique is fully described in and only outlined here. Briefly, a “stack” of ASL difference images (blood‐bright minus blood‐dark) are evaluated by first normalizing the mean of each to 1.0, to eliminate any artifacts from changes in cardiac stroke volume, changes in T 1 or T 2 , or scanner drift.…”

“…Each of the remaining images is then subtracted from the reference, and the standard deviation of the differences is taken as the FD. Depending on what reference subset was chosen, the calculated value of FD reflects either a combination of the temporal variability in the images and any change in the underlying static distribution of blood flow (when the reference period is during the initial baseline condition, termed FD Global ) or just the temporal variability in the images (when the reference period is from within a particular physiological condition, termed FD Local ) .…”

Hypoxic Pulmonary Vasoconstriction and Chronic Lung Disease

“…23,24 At a regional level within the lung vasculature the magnitude of HPV may not be equivalent in all areas or static over time. [25][26][27][28] As a consequence of this unevenness of regional HPV, some areas of the vasculature may be more perfused than others if they have a lower HPV response. This appears to be the case in those with a stronger global HPV response and susceptibility to high altitude pulmonary edema (HAPE).…”

A statistical clustering approach to discriminating perfusion from conduit vessel signal contributions in a pulmonary ASL MR image

“…In arterial spin labeling (ASL) magnetic resonance imaging, magnetically tagged blood water is used as a non-invasive endogenous tracer to produce a spatial flow map. Predominantly used to measure blood flow in the brain (1), ASL has recently been adapted for the investigation of pulmonary perfusion under various conditions (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Throughout this article, the term perfusion is used to signify blood destined for capillary vessels within a voxel.…”