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Published online before print March 27, 2008, 10.1148/radiol.2472070828
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(Radiology 2008;247:482-489.)
© RSNA, 2008

Musculoskeletal Imaging

Calf Muscles at Blood Oxygen Level–Dependent MR Imaging: Aging Effects at Postocclusive Reactive Hyperemia1

Anja-Carina Schulte, PhD, Markus Aschwanden, MD, and Deniz Bilecen, MD, PhD

1 From the Biocenter, University of Basel, Basel, Switzerland (A.C.S.); and Departments of Angiology (M.A.) and Radiology (D.B.), University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland. Received May 11, 2007; revision requested July 16; revision received September 25; accepted October 16; final version accepted October 30. D.B. supported by Swiss National Science Foundation Project No. SNF 3100A0-100633. Address correspondence to D.B. (e-mail: dbilecen{at}uhbs.ch).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Purpose: To prospectively investigate age-related changes in muscle reperfusion by using blood oxygen level–dependent (BOLD) magnetic resonance (MR) imaging of the calf in young and elderly healthy volunteers during postocclusive reactive hyperemia.

Materials and Methods: Institutional review board approval and informed consent were obtained. Eleven healthy elderly (mean age, 64.0 years ± 6.4 [standard deviation]; six men, five women) and 17 healthy young volunteers (mean age, 30.3 years ± 6.5; seven men, 10 women) underwent muscle BOLD MR imaging of the calf. A fat-suppressed T2*-weighted single-shot multiecho echo-planar imaging sequence was used. Temporary vascular occlusion was induced with suprasystolic cuff compression of the thigh. T2* time courses of the muscle BOLD MR signal intensity were obtained from four calf muscles and were characterized by the following curve parameters: hyperemia peak value, time to peak, and T2* end value after 360 seconds of hyperemia. Differences in these parameters between the two cohorts were assessed by using a Student t test.

Results: Considerably lower T2* maxima were observed in the elderly group during hyperemia (P < .005), with a mean hyperemia peak value of 13.1% ± 3.0 compared with 18.9% ± 4.8 in young healthy adults. Peaking occurred earlier in the elderly group (P < .05), with a mean time to peak of 32.2 seconds ± 10.6 compared with 43.1 seconds ± 10.7 in young adults. Furthermore, the elderly group had a significantly slower decrease of the muscle BOLD signal after the hyperemia peak (P < .001), which led to a higher end value of 8.6% ± 3.0 compared with 2.6% ± 2.1 in the young group.

Conclusion: BOLD MR imaging results of the calf demonstrated statistically significant age-dependent differences in the rate, intensity, and recovery of the postocclusive muscle BOLD signal.

© RSNA, 2008


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Contrast at blood oxygen level–dependent (BOLD) magnetic resonance (MR) imaging relies on the different magnetic properties of oxyhemoglobin and deoxyhemoglobin. Whereas oxyhemoglobin is slightly diamagnetic, deoxyhemoglobin is a paramagnetic molecule. The presence of deoxyhemoglobin in a blood vessel causes a susceptibility difference between the vessel and its surrounding tissue. Such susceptibility differences cause dephasing of the MR proton signal, which leads to a reduction in T2*. With regard to the brain, during activation the overproportional blood inflow leads to a relative increase in oxyhemoglobin. Because oxyhemoglobin is diamagnetic and does not produce the same dephasing, activation-induced changes in blood oxygenation result in a signal intensity gain on T2*-weighted MR images (1–3).

Some research groups (4–7) have investigated BOLD MR imaging by using paradigms, such as exercise, ischemia, postocclusive reactive hyperemia, or oxygen ventilation. However, while the exact origin of the BOLD effect in skeletal muscle is not yet completely understood, it appears to be multifactorial. It is assumed that the muscle BOLD signal primarily originates from changes in capillary blood and tissue oxygenation. Because the BOLD signal in skeletal muscle has been demonstrated to be associated with muscle perfusion, investigators (8,9) have suggested that muscle BOLD MR imaging may be used as an index of peripheral vascular function.

The effect of aging on the BOLD response in end organs like the brain or myocardial and skeletal muscle is uncertain. Age-dependent alterations in the human brain have been reported to involve changes in the cerebrovascular system. These include vessel wall rigidity and disturbance of vascular coupling, both of which have already been characterized with BOLD measurements (10,11). For the heart muscle, similar results have been published (12,13). However, to our knowledge, no data are available for skeletal muscle. In the supraaortal vessels, arterial resistance increases and maximum vasodilatation decreases with aging, which leads to a reduction in perfusion reserve capacity. It is assumed that similar changes also occur in the peripheral vasculature (11,14–17). Such alterations influence the T2* change of the BOLD signal, which should result in measurable differences of the muscle BOLD signal between elderly and young individuals, in keeping with the hypothesis that there is an aging effect on the BOLD signal of skeletal muscles.

Thus, the purpose of our study was to prospectively investigate age-related changes in muscle reperfusion by using BOLD MR imaging of the calf in young and elderly healthy volunteers during postocclusive reactive hyperemia.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
All subjects gave written informed consent before entering the study. The study protocol was approved by the University Hospital Basel's institutional review board.

Volunteers
Eleven healthy elderly volunteers (mean age, 64.0 years ± 6.4 [standard deviation]; six men, five women) and 17 healthy young volunteers (mean age, 30.3 years ± 6.5; seven men, 10 women) participated in our study. All volunteers were recruited from our Department of Angiology. They were normotensive and had a normal peripheral pulse status, with an ankle-brachial index of more than 1.0. None of the subjects had symptoms of peripheral arterial occlusive disease or clinical signs for venous insufficiency. All were nonsmokers all their life (Table 1).


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  		Table 1. Volunteer Characteristics

 
Exclusion criteria for our study were any chronic disease and cardiovascular risk factors such as hypertension, hyperlipidemia, and so forth. Common contraindications to MR imaging examinations were electrically, magnetically, and mechanically activated pacemakers, ferromagnetic implants, and claustrophobia.

Cuff Compression for Reactive Hyperemia
Reactive hyperemia during rest was provoked by using a cuff-compression paradigm previously proposed in other muscle BOLD MR imaging studies (4,18). For cuff compression, we used a conventional leg sphygmomanometer (Keller, Jungingen, Germany). Because the measuring device contained immobile ferromagnetic parts, the tube was extended to ensure a safe distance from the magnet. The air cuff (15 x 75 cm) was wrapped around the thigh of the investigated leg, which was chosen arbitrarily. The cuff was fixed at mid-thigh level with a Velcro strap to prevent loosening. Ischemia was achieved by using manual inflation of the cuff to an occlusion pressure of 50 mm Hg above the individual brachial systolic blood pressure (19). Initiated by fast opening of the air valve, the cuff compression was released after 360 seconds of ischemia. BOLD MR imaging measurement started contemporaneously with cuff deflation and continued for 360 seconds. Cuff inflation and deflation took approximately 5–10 seconds and 5 seconds, respectively.

MR Imaging
Prior to imaging, subjects were placed supine with feet first on the couch of the MR imager. The air cuff was placed above the knee. To obtain similar venous filling of the calf in all volunteers, each subject had to rest in this horizontal position for 5 minutes before cuff compression. This is necessary because the muscle BOLD signal has been shown to depend on the degree of repletion of leg blood vessels (20).

All muscle BOLD MR imaging measurements were performed with a 1.5-T whole-body imager (Sonata; Siemens Medical Solutions, Erlangen, Germany) equipped with a high-performance gradient system (amplitude, 40 mT/m; slew rate, 200 T/m/sec). A peripheral vascular array coil was used for signal transmission and reception.

A single-shot multiecho gradient-echo echo-planar imaging sequence with fat suppression was used to obtain a consecutive series of 360 measurements with a temporal resolution of one measurement per second. Four transverse sections (section thickness, 5 mm; intersection gap, 2.5 mm) were positioned at the upper calf at maximum diameter. Imaging parameters included repetition time of 1000 msec, flip angle of 90°, field of view of 380 x 238 mm, and 128 x 40 matrix size reconstructed to 2.97 x 2.97-mm in-plane resolution. With each excitation, four images with increasing effective echo times of 16, 38, 61, and 83 msec were acquired. Echo-planar images were supplemented with anatomic reference images of the four acquired sections by using a T1-weighted spin-echo sequence with the following parameters: voxel size, 0.7 x 0.7 x 2.5 mm; repetition time msec/echo time msec, 450/10; and flip angle, 90°.

All muscle BOLD MR imaging measurements were obtained successfully. Suprasystolic cuff compression of the thigh was well tolerated in both groups. Substantial calf motion or muscle contraction during measurement did not occur.

Image Analysis
T2* (oxygenation) and initial signal intensity effects were separated by a pixel-by-pixel least-square fit of a monoexponential decay to the signal intensities of the four images at four different echo times: Si(TEi), where S is signal intensity, TE is echo time, and i is one of the four echo times. Parameter maps of T2* were computed from multiecho echo-planar imaging data according to the following equation: S(I0, T2*) = I0 · exp(–TE1–4/T2*), where TE1–4 is one of the four echo times and I0 refers to the initial signal intensity, which is modulated by perfusion, T1, and proton density. This parameter fit for multiecho data with subsequent motion correction is routinely implemented on the image reconstruction system of our MR imager. The two-dimensional motion correction uses a rigid transformation (translation and rotation) in combination with a least-squares fitting procedure.

Data analysis was performed in a blinded fashion. For analysis of T2* maps, a region-of-interest (ROI) analysis was performed by using statistical parametric mapping software (BrainVoyager; Brain Innovation, Maastricht, the Netherlands). Rectangular ROIs were manually placed in four calf muscles: soleus, gastrocnemius, peroneus, and tibial anterior. The ROIs were chosen to exclude pixels of bones and large vessels. The tibial posterior muscle was not investigated because it contains a relatively large number of vessels. The mean size of the ROIs was 106 pixels ± 20 (corresponding to 9.4 cm2 ± 1.8) in the soleus, 88 pixels ± 20 (corresponding to 7.8 cm2 ± 1.8) in the gastrocnemius, 53 pixels ± 11 (corresponding to 4.7 cm2 ± 1.0) in the peroneus, and 69 pixels ± 13 (corresponding to 6.1 cm2 ± 1.2) in the tibial anterior muscle. All ROIs were defined by the same author (D.B., 9 years of experience in musculoskeletal MR imaging) who was blinded to the subject's identity and group assignment.

Further image analysis was performed by one author (A.C.S., 8 years of experience in analyzing data) who was blinded to identity and group assignment of the subjects. Data analysis was performed for each muscle separately by using self-developed Matlab (Mathworks, Natick, Mass) routines. Mean T2* time courses of each subject were calculated by averaging the T2* time courses of each ROI within the four acquired sections. Each subject's mean T2* time course in the specific muscle tissue was then normalized by taking the mean T2* value during the first 2 seconds of the measurement (ie, immediately after cuff deflation, as baseline set to 100%). The mean time course in each of the four muscles and the mean time course for all muscles were calculated by averaging the time courses of all subjects belonging to the same age group.

Three key parameters were determined to characterize the normalized T2* time course during postocclusive muscle reperfusion: the hyperemia peak value, which refers to the height of the T2* maximum during hyperemia relative to the baseline; the time to peak, which is the time interval between cuff deflation and T2* maximum; and the T2* end value, which is the mean T2* of the last 2 seconds of the entire measurement lasting 360 seconds relative to the baseline. For each muscle, mean values of these key parameters were computed by averaging each parameter over all subjects belonging to the same group. In addition, means for hyperemia peak value, time to peak, and end value were calculated by averaging the curve parameters of all four studied muscles.

Statistical Analysis
Statistical analysis by using Matlab and Excel (Microsoft, Redmond, Wash) was performed to determine the effect of age on the muscle BOLD time course. Differences in the key parameters (hyperemia peak value, time to peak, and end value) between elderly and young healthy volunteers were calculated for each parameter separately. An unpaired two-sided Student t test was applied to assess statistical differences in hyperemia peak value, time to peak, and end value between the two groups. A statistically significant difference was considered to be indicated by a P value of less than .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
T2* Time Courses
In both groups, a rapid increase of T2* was observed after cuff deflation (Figs 1, 2). The T2* maximum was reached after approximately 35–40 seconds. In the young healthy volunteers, the hyperemia peak was followed by a rapid decline and a subsequent slower decrease. Thereafter, a steady-state condition was observed with nearly baseline value. This pattern contrasts with that seen in elderly patients, where T2* hardly decreased after the maximum and remained almost constant until the end of the measurement. This curve behavior was observed in all four calf muscles (Fig 2).


Figure 1A
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  		Figure 1a: Muscle BOLD MR data obtained with single-shot multiecho gradient-echo echo-planar imaging (1000/16, 38, 61, 83; flip angle, 90°) of right calf in a 70-year-old woman (top row) and in a 28-year-old man (bottom row) during postocclusive reactive hyperemia. (a) Graphs of mean T2* time course obtained from ROI in soleus muscle. (b) Transverse T2* maps calculated from decay of the four images with different echo times. Box = ROI. (c) Transverse multiecho gradient-echo echo-planar images acquired with first echo time (1000/16). (d) Transverse T1-weighted anatomic images of the same section obtained with spin-echo sequence (450/10; flip angle, 90°). Note the difference in the T2* time courses between the two subjects after the maximum. Whereas a rather fast and linear return to the baseline was observed in the 28-year-old subject (a, bottom), the 70-year-old subject had only a minor decline in T2* until the end of measurement (a, top). t[s] = time in seconds.

 

Figure 1B
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  		Figure 1b: Muscle BOLD MR data obtained with single-shot multiecho gradient-echo echo-planar imaging (1000/16, 38, 61, 83; flip angle, 90°) of right calf in a 70-year-old woman (top row) and in a 28-year-old man (bottom row) during postocclusive reactive hyperemia. (a) Graphs of mean T2* time course obtained from ROI in soleus muscle. (b) Transverse T2* maps calculated from decay of the four images with different echo times. Box = ROI. (c) Transverse multiecho gradient-echo echo-planar images acquired with first echo time (1000/16). (d) Transverse T1-weighted anatomic images of the same section obtained with spin-echo sequence (450/10; flip angle, 90°). Note the difference in the T2* time courses between the two subjects after the maximum. Whereas a rather fast and linear return to the baseline was observed in the 28-year-old subject (a, bottom), the 70-year-old subject had only a minor decline in T2* until the end of measurement (a, top). t[s] = time in seconds.

 

Figure 1C
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  		Figure 1c: Muscle BOLD MR data obtained with single-shot multiecho gradient-echo echo-planar imaging (1000/16, 38, 61, 83; flip angle, 90°) of right calf in a 70-year-old woman (top row) and in a 28-year-old man (bottom row) during postocclusive reactive hyperemia. (a) Graphs of mean T2* time course obtained from ROI in soleus muscle. (b) Transverse T2* maps calculated from decay of the four images with different echo times. Box = ROI. (c) Transverse multiecho gradient-echo echo-planar images acquired with first echo time (1000/16). (d) Transverse T1-weighted anatomic images of the same section obtained with spin-echo sequence (450/10; flip angle, 90°). Note the difference in the T2* time courses between the two subjects after the maximum. Whereas a rather fast and linear return to the baseline was observed in the 28-year-old subject (a, bottom), the 70-year-old subject had only a minor decline in T2* until the end of measurement (a, top). t[s] = time in seconds.

 

Figure 1D
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  		Figure 1d: Muscle BOLD MR data obtained with single-shot multiecho gradient-echo echo-planar imaging (1000/16, 38, 61, 83; flip angle, 90°) of right calf in a 70-year-old woman (top row) and in a 28-year-old man (bottom row) during postocclusive reactive hyperemia. (a) Graphs of mean T2* time course obtained from ROI in soleus muscle. (b) Transverse T2* maps calculated from decay of the four images with different echo times. Box = ROI. (c) Transverse multiecho gradient-echo echo-planar images acquired with first echo time (1000/16). (d) Transverse T1-weighted anatomic images of the same section obtained with spin-echo sequence (450/10; flip angle, 90°). Note the difference in the T2* time courses between the two subjects after the maximum. Whereas a rather fast and linear return to the baseline was observed in the 28-year-old subject (a, bottom), the 70-year-old subject had only a minor decline in T2* until the end of measurement (a, top). t[s] = time in seconds.

 

Figure 2
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  		Figure 2: Graphs of mean normalized T2* time courses (BOLD responses) of all four investigated calf muscles during 360 seconds of reactive hyperemia in elderly healthy subjects (gray lines) and young healthy subjects (black lines). Note significantly lower T2* hyperemia peak value (P < .005) and significantly elevated T2* end value (P < .001) in elderly group compared with those in the young group. t[s] = time in seconds.

 
Differences Observed
When we compared the mean key values for all muscles of the two groups, three relevant differences were observed: First, hyperemia peak value was significantly lower in the elderly volunteers compared with that in young volunteers (P < .005), with a mean hyperemia peak value of 13.1% ± 3.0 compared with 18.9% ± 4.8. Second, the hyperemia peak occurred earlier in the elderly group (P < .05) than in the young group, with a shorter mean time to peak of 32.2 seconds ± 10.6 versus 43.1 seconds ± 10.7. Third, because of the diminished decline of T2* after the maximum in the elderly group, the end value was significantly higher (P < .001) than that in the young group, with 8.6% ± 3.0 versus 2.6% ± 2.1.

A difference in the distribution of hyperemia peak value and end value between groups was observed, which underlined the lack of correlation in curve parameters between young and elderly subjects (Fig 3).


Figure 3
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  		Figure 3: Plot of hyperemia peak value (HPV) versus end value (EV) for each individual elderly (gray circles) and young (black circles) subject. Distribution of the two key parameters is clearly different in the two groups, which indicates an age-related change in these parameters.

 
Specific Muscle Analysis
Muscle-by-muscle analysis yielded quantitative differences in the T2* time courses. For both groups, the largest hyperemia peak value was found in the soleus muscle (elderly group: 19.0% ± 5.2, young group: 28.6% ± 8.6). A rather low hyperemia peak value was observed in the tibial anterior muscle (elderly group: 8.8% ± 2.4, young group: 12.8% ± 5.7). Comparable results were also found for the end value, where high end values were assessed in the soleus muscle (elderly group: 12.6% ± 5.4, young group: 5.1% ± 3.0) and low end values were assessed in the tibial anterior muscle (elderly group: 5.4% ± 2.4, young group: 0.0% ± 2.8) (Table 2).


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  		Table 2. Hyperemia Peak Value, Time to Peak, and T2* End Value in Elderly and Young Healthy Volunteers for Four Calf Muscles

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
The BOLD signal change at conventional single-shot echo-planar imaging is related to changes in T2* and initial signal intensity. However, the initial signal intensity is influenced by several parameters such as inflow, changes in T1, and baseline drifts (21). In our study, we used a multiecho echo-planar imaging sequence to separate oxygenation-related changes (T2*) from other effects (21,22).

The relevant finding of our muscle BOLD MR study was the observation of different T2* time courses for young and old healthy volunteers during postocclusive reperfusion. These differences are expressed with the key parameters of hyperemia peak value, time to peak, and end value. The observed changes seem to be systemic because all investigated calf muscles—soleus, gastrocnemius, peroneus, and tibial anterior muscle—had similar changes. We assume that these age-related findings refer to changes of the vascular control of the skeletal muscle, including vessel number, size, and stiffness; to deterioration of endothelium-dependent vasodilatation; to augmented sympathetic vasoconstriction; and to alterations in the metabolic control of muscle tissue (23–27). However, it cannot presently be excluded that there may be other effects that also contribute to the observed changes.

A significant reduction in hyperemia peak value was observed in the elderly group compared with that in the young group. The physiologic substrate for the decline of the full BOLD amplitude might be an increase in vessel wall rigidity, predilation of the vasculature, and/or reduction in the number of vessels during aging. All of these factors would lead to a reduction in the total vasodilator capacity that restrains the total oxyhemoglobin overshoot during postocclusive hyperemia (14). This finding is in agreement with results of BOLD imaging studies (28–30) of the cerebral cortex, where a decrease in the relative BOLD signal amplitude with aging was observed.

The considerable shortening of time to peak in the elderly group is of interest. Time to peak reflects the time from cuff deflation to maximum T2* value. At least two age-related changes of the arterial vasculature might contribute to this accelerated peaking. First, reduction of time to peak might indicate an accelerated blood inflow into the muscle parenchyma, which might be due to an increased stiffness of the arterial wall. Second, vasoconstriction might occur as a protective mechanism to counteract the rapid increase in blood pressure. A slight impairment of the vasomotor function may lead to a delay of vasoconstriction and therefore enable earlier BOLD peaking in comparison to that in younger volunteers. This phenomenon can be referred to as endothelial dysfunction during aging (31). For one of the four calf muscles, the tibial anterior, no statistically significant difference in time to peak between the elderly and young cohorts was observed. Currently, we do not have an explanation for this result. Further measurements will be necessary to elucidate this observation.

One of the most striking findings of muscle BOLD MR imaging is the reduced decrease of T2* in the elderly group, which leads to an elevated end value at the conclusion of the measurement. This finding suggests maintenance of the oxyhemoglobin overshoot in the skeletal muscle. Presently, it is unclear if this effect can be explained by the impairment of vasomotor function, by changes in blood volume content, and/or by alterations in the composition of muscle tissue.

Although T2* time courses during postocclusive hyperemia are qualitatively similar for all four calf muscles in their respective group, there are quantitative differences between the individual muscles. In both age groups, the largest values of hyperemia peak value and end value were observed in the soleus muscle. This finding regarding the hyperemia peak value has been described previously by Lebon and coauthors (18). The soleus belongs to the slow-twitch oxidative tissue, whereas the gastrocnemius is a fast-twitch glycolytic (white) muscle (6). Slow-twitch muscles have higher capillary density and thus higher blood volume content than fast-twitch muscles, which might explain the different values of hyperemia peak value and end value. Besides the capillary density, the orientation of the muscle's capillaries relative to the magnetic field might influence the absolute value of the key parameters in the individual muscle (32).

The ankle-brachial index is a measure providing objective data for the diagnosis of lower extremity peripheral arterial occlusive disease. The ankle-brachial index can be used as a screening tool or to monitor the efficacy of therapeutic interventions (33). However, in contrast to the key parameters of the muscle BOLD signal, only negligible differences in the ankle-brachial index values between young and old subjects were observed. All ankle-brachial index values were more than 1.0, excluding peripheral arterial occlusive disease of the macrovasculature, with a high sensitivity and specificity. The ankle-brachial index reflects neither changes of the microvascularization of the musculature nor cellular or biochemical changes. These might include changes in enzyme activity, protein content, and/or mitochondrial content of the different muscle fiber types (34,35).

A limitation of our study was the lack of a reference standard against which the T2* time courses could be compared. However, in a recent study (36) the muscle BOLD signal intensity in the calf was compared with laser Doppler flowmetry (LDF) and transcutaneous oxygen pressure (TcPo2) measurements. These two techniques are routinely used in the lower extremities to assess tissue perfusion (at LDF) and tissue oxygenation (at TcPo2). Although LDF and TcPo2 measurements are restricted to the skin's microvasculature and do not measure changes in the muscle itself, the muscle BOLD signal intensity in the calf muscle was found to correlate well with LDF and TcPo2 during ischemia (correlation coefficient: 0.86 and 0.96, respectively) and reactive hyperemia (correlation coefficient: 0.81 and 0.78, respectively) in healthy volunteers (36).

Presently, the results of our muscle BOLD study remain descriptive. Although we suspect that aging of the arterial wall might be responsible for the observed differences in the key parameters during postocclusive reactive hyperemia, a detailed and conclusive interpretation of the presented data is theorized at this time. Further investigations of the muscle BOLD effect, as well as comparison to established techniques like near-infrared MR spectroscopy, arterial spin labeling, or others, might help to elucidate the physiologic substrate of the muscle BOLD signal and its underlying mechanisms.

In conclusion, our study results demonstrate statistically significant differences in the muscle BOLD key parameters between young and old healthy volunteers during postocclusive reactive hyperemia at calf level. Aging has a measurable effect on the BOLD signal intensity in the calf muscle. The reduction of the total change in T2* and the delay in signal recovery were the most striking findings in the elderly group.


   ADVANCES IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
IMPLICATION FOR PATIENT CARE
 References
 


   IMPLICATION FOR PATIENT CARE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
References
 


   FOOTNOTES
 

Abbreviations: BOLD = blood oxygen level dependent • ROI = region of interest

Author contributions: Guarantors of integrity of entire study, all authors; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, all authors; clinical studies, M.A.; statistical analysis, A.C.S.; and manuscript editing, all authors

Authors stated no financial relationship to disclose.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 

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