Quantitative analysis of the postcontractile blood-oxygenation-level-dependent (BOLD) effect in skeletal muscle

Abstract

Previous studies show that transient increases in both blood flow and magnetic resonance image signal intensity (SI) occur in human muscle after brief, single contractions, and that the SI increases are threefold larger in physically active compared with sedentary subjects. This study examined the relationship between these transient changes by measuring anterior tibial artery flow (Doppler ultrasound), anterior muscle SI (3T, one-shot echo-planar images, TR/TE = 1,000/35), and muscle blood volume and hemoglobin saturation [near-infrared spectroscopy (NIRS)] in the same subjects after 1-s-duration maximum isometric ankle dorsiflexion contractions. Arterial flow increased to a peak 5.9 ± 0.7-fold above rest (SE, n = 11, range 2.6-10.2) within 7 s and muscle SI increased to a peak 2.7 ± 0.6% (range 0.0-6.0%) above rest within 12 s after the contractions. The peak postcontractile SI change was significantly correlated with both peak postcontractile flow (r = 0.61, n = 11) and with subject activity level (r = 0.63, n = 10) estimated from 7-day accelerometer recordings. In a subset of 7 subjects in which NIRS data acquisition was successful, the peak magnitude of the postcontractile SI change agreed well with SI calculated from the NIRS blood volume and saturation changes (r = 0.80, slope = 1.02, intercept = 0.16), confirming the blood-oxygenation-level-dependent (BOLD) mechanism underlying the SI change. The magnitudes of postcontractile changes in blood saturation and SI were reproduced by a simple one-compartment muscle vascular model that incorporated the observed pattern of postcontractile flow, and which assumed muscle O(2) consumption peaks within 2 s after a brief contraction. The results show that muscle postcontractile BOLD SI changes depend critically on the balance between O(2) delivery and O(2) consumption, both of which can be altered by chronic physical activity.

Figures

Fig. 1.

Doppler ultrasound recording of blood velocity (cm/s) in the proximal anterior tibial artery over 10 cardiac cycles. A single 1-s-duration maximal voluntary contraction (MVC) ankle dorsiflexion was performed at the time marked by the yellow arrow. The blue line is the mean velocity, and the vertical dashed lines illustrate a region over one cardiac cycle used to calculate the time-averaged mean velocity (TAMEAN) and blood flow. The first cardiac cycle coincident with or immediately after the contraction (as in this example) was distorted by probe motion and was not included in the analysis.

Fig. 2.

Time course of anterior tibial artery flow (mean ± SD) before and after 1-s-duration MVC (from −1 to 0 s). Vertical lines indicate when data collection stopped for an individual due to movement of the ultrasound probe. Thus, from −10 to 12 s, n = 11; from 12 to 23 s, n = 10, etc.

Fig. 3.

Relationship between peak postcontractile anterior tibial artery flow vs. subject activity level as measured by 7-day activity monitoring. The regression line (y = 0.07x +1.96, r = 0.97) excludes the two subjects (open circles) with low activity and large postcontractile flow (see text).

Fig. 4.

Representative anatomic T2-weighted (A) and echo-planar (B) images acquired from a subject during the MRI protocol. The green marks in the echo-planar image enclose the region-of-interest in anterior tibial muscle from which the time course of signal intensity (SI) (panel C) was extracted. The spikes in SI at 1-min intervals are T1-related motion artifacts caused by movement of unsaturated muscle into and out of the imaging plane during and immediately after the contraction (40).

Fig. 5.

Relationship between peak anterior tibial artery flow vs. peak MRI-measured muscle SI increase after 1-s MVC of the ankle dorsiflexors. The line is a linear regression (r =0.61, n = 11, P = 0.048). Note: the two outliers in Fig. 3 (low activity, but peak flow 8- to 9-fold above rest) are included in this relationship.

Fig. 6.

Illustrative NIRS data (arbitrary units) acquired at 3 Hz from anterior muscle of a relatively active subject during a sequence of three 1-s-duration MVCs separated by 80 s of rest. The peak in blood volume (dotted gray line) occurs before the peak in oxyhemoglobin (dashed) and the nadir of deoxyhemoglobin (solid).

Fig. 7.

Intravascular (top) and extravascular (bottom) BOLD effects for gradient-echo images at echo time (TE) of 35 ms over a range of blood volumes and saturations, calculated as described in methods. SI is normalized relative to the value at baseline conditions of 50% hemoglobin saturation and a 3% blood volume (black dot locations on the surfaces). For the extravascular calculation, blood volume was increased by adding more vessels. Increasing blood volume by increasing vessel size had even smaller extravascular effects on calculated SI.

Fig. 8.

Blood volume and hemoglobin saturation (top), and calculated and measured muscle SI response (bottom) to a 1-s MVC of the ankle dorsiflexors. These data are from the most active individual in the study, who also exhibited the largest postcontractile increases in blood flow (10.2-fold above rest).

Fig. 9.

Comparison of calculated (●) vs. measured (○) muscle BOLD response from three different individuals (see text).

Fig. 10.

Linear regression (solid line, y = 1.02x + 0.16, r = 0.80, P = 0.03) between peak postcontractile SI increase calculated from NIRS blood volume and saturation data vs. SI increase observed by MRI in the same subjects. The dashed line is the line of identity.

Fig. 11.

Mean blood flow (top panel, data linearly interpolated to 1 Hz); blood volume (●) and %saturation (○) (middle); and model-calculated (●) and measured (○) muscle BOLD (bottom) for 7 subjects for whom ultrasound, NIRS, and MRI are all available.

Fig. 12.

Dynamic model of muscle blood flow (top panel), oxygen consumption (second panel), blood volume and oxygenation (third panel), and MRI SI change (bottom panel), as described in appendix. The modeled postcontractile increase in blood flow is idealized from the mean flows reported in Figs. 2 and 11. The modeled postcontractile increase in muscle oxygen consumption is based the extent of depletion and the rate of recovery of phosphocreatine in human muscle after short contractions (59).

Fig. 13.

Effect of variation in the peak of the first phase of the postcontractile increase in blood flow on the simulated SI change in muscle. The time course of muscle O2 consumption and other model parameters were the same as in the base model shown in Fig. 11. These simulated flow variations (between 3- and 9-fold) result in simulated peak postcontractile muscle SI over the entire range observed in subjects (from 100 to 106%).