Functional Electrical Stimulation Effect on Skeletal Muscle Blood Flow ...

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Functional Electrical Stimulation Effect on Skeletal Muscle Blood Flow Measured With H2150 Positron Emission Tomography Oscar U. Scremin, MD, Phi), Ramon L. Cuevas-Trisan, MD, A. M. Erika Scremin, MD, Charles V. Brown, AID, Mark A. Mandelkern, MD, PhD ABSTRACT. Scremin OU, Cuevas-Trisan RL, Scremin AME, Brown CV, Mandelkern MA. Functional electrical stimulation effect on skeletal muscle blood flow measured with H2150 positron emission tomography. Arch Phys Med Rehabil 1998;79:641-6.

Objective: To test the hypothesis that the limitation in muscle power development with functional electrical stimulation (FES) results from an insufficient increase in muscle blood flow (MBF) in response to activity. Subjects and Methods: Five subjects with neurologically complete spinal cord injury (SCI) were tested to measure the MBF response to FES-induced knee extension. The MBF response to voluntary knee extension was measured in five age-matched, able-bodied controls. MBF was measured with positron emission tomography (PET) using H2150 as a tracer. Three scans were performed with muscle at rest (baseline), immediately after 16rain of FES-induced or voluntary knee extension (activity), and 20rain after the second scan (recovery). Results: In SCI subjects, mean 2 S E MBF (mL/100g/min) values were: baseline = 1.85 -+ .48; post-FES = 31.9 -+ 5.65 (p = .0058 vs baseline); recovery = 6.06 -+ 1.52 (p = .0027 vs baseline). In able-bodied controls, mean _+SE MBF values were: baseline = 8.52 -+ 3.24, post-voluntary exercise = 12.62 _+ 3.03 (p = .023 vs post-FES in SCI subjects); recovery = 10.7 -+ 6.01. Conclusions: MBF does not appear to be the limiting factor in muscle power generation with FES. The greater increase in MBF observed with FES in SCI subjects when compared with able-bodied subjects performing a similar task (unloaded knee extension against gravity) may relate to abnormal metabolism in FES-stimulated muscle.

© 1998 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation UNCTIONAL ELECTRICAL stimulation (FES) has been proposed to provide fitness training to individuals with F spinal cord injury (SCI), and as a possible intervention to prevent or diminish certain complications of SCI, such as From the Departments of Physical Medicine and Rehabilitation (Drs. CuevasTrisan, A.M.E. Scremin), Nuclear Medicine (Drs. Brown, Mandelkern), and Research (Dr. O.U. Scremin), West Los Angeles VA Medical Center; and Departments of Medicine (Dr. A.M.E. Scremin) and Physiology (Dr. O.U. Scremin), UCLA School of Medicine, Los Angeles, CA. Submitted for publication June 1i, 1997. Accepted in revised form November 12, 1997. Supported by the Department of Veterans Affairs Rehabilitation Research and Development, project B 603-RA. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated. Reprint requests to Oscar U. Scremin, MD, Phi), West Los Angeles VA Medical Center, 11301 Wilshire Boulevard, Building 115, R 317, Los Angeles, CA 90073. © 1998 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

0003-9993/98/7906-453753.00/0

spasticity, contractures, neurogenic osteoporosis, deep venous thrombosis, and edema. 1-9 In addition, there is the potential of FES to aid in standing and ambulation. 1°13 These applications rest on the possibility of efficient generation of muscle power at a sustained rate, without imposing muscle injury or undue fatigue. Under the present conditions, these goals appear compromised because of limitations in oxygen delivery to, or substrate use by, muscle activated by FES. 14,15 Understanding the physiologic basis of this limitation is of crucial importance in the design of modalities that could overcome the functional limitations mentioned above and thus allow realization of the full potential of this promising rehabilitation methodology. It is possible that skeletal muscle may retain its ability to adapt to chronic exercise stimuli after SCI but its functional capacity may continue to be limited by local or systemic circulatory impairments. It has been recently shown that when SCI patients perform FES lower extremity cycling, the rates of adjustment of oxygen uptake and carbon dioxide output are markedly slowed both after the onset of, and in recovery from, unloaded cycling. 15 These delayed dynamics are accompanied by exaggerated steady-state responses. The exercise, which would be trivial even for sedentary able-bodied subjects, appeared to represent near-maximal effort for the SCI subjects, as suggested by high end-exertion blood lactate levels and the size of the oxygen deficit and debt. 14 This raises a critical question--that is, to what extent are the reduced exercise tolerance and slowed oxygen and carbon dioxide exchange dynamics caused by a blunted response of local blood flow to exercise in the SCI subjects? This hypothesis was tested by measuring the response of muscle blood flow (MBF) to FES-induced knee extension in SCI subjects. To determine the change in MBF associated with similar work of normal muscle, age-matched able-bodied subjects performed voluntary knee extension for the same period of time and were subjected to MBF measurements with the same methodology. H2150 positron emission tomography (PET) was selected as a method to measure MBF because it is noninvasive, provides quantitative assessment of MBF, and can be repeated sequentially during a short time.

MATERIAL AND METHODS Experimental Subjects Data on volunteer SCI and able-bodied subjects are summarized in table 1. Able-bodied volunteers, age = 27 + 4.2yrs (mean -+ SD), were recruited to approximately match the ages of subjects with SCI (29 + 5.2yrs). Body mass index was calculated as body mass (kg)/height (m) 2. Subjects had no history of vascular, neurologic, or muscular disease, recent ionizing radiation exposure, or significant trauma or surgery to the legs. All subjects gave informed consent on a protocol approved by the Human Subjects Committee of our hospital. Arch Phys Med Rehabil Vol 79, June 1998

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EFFECTS OF FES ON MUSCLE BLOOD FLOW, Scremin Table 1: Characteristics of Research Subjects "time Since Body Mass Height Body Mass (kg) (m) Index

Subject Age (yrs) Lesion Level Injury(yrs)

contraction. The perception of the stimulation trains helped the subjects achieve the correct timing of concentric and eccentric contraction followed by relaxation.

1

33

C5

15

63.5

1.88

17.9

2

24

T5

3

82.5

1.78

26.1

Measurement of MBF

3

34

T4

11

61.2

1.75

19.9

4

31

T8-T9

12

74

1.75

24.4

5 6 7

23 28 33

T7-T8 ---

---

61 74.8 70.3

1.75 1.67 1.67

19.9 26.6 25

8

24

--

--

79.3

1.83

23.7

9

22

--

--

79.4

1.72

26,6

10

28

--

--

68

1.72

22.8

Measurements were obtained using an adaptation of the autoradiographic method 16 in which the arterial input function was derived from the time-activity curve of the superficial femoral artery PET image of the left leg instead of on-line radioactivity measurements from blood obtained by arterial cannulation as described originally. This technique uses water labeled with 150 as a blood flow tracer. Because of the short half-life of 150 (123sec), scans can be repeated at short intervals. Thus, several interventions can typically be performed without removing the subject from the scanner. H2150 was produced in the on-site cyclotron by the bombardment of natural water with protons of 25 to 30 million electron volts (MEV). After purification, approximately 100mCi were transported to the PET suite by pneumatic tube. At the time of injection, approximately 30mCi remaining in the sample was administered as an intravenous bolus in 8 to 10mL of saline. The scanner was started at the moment of injection. Data were stored in 16 frames; the first 12 were 10-sec frames and the last four, 30-sec frames. The positron tomograph at our hospital is a Siemens 953-31 scanner? This instrument consists of 16 rings of bismuth germanate (BGO) crystals, each of 70-cm diameter and containing 384 elements. It produces 31 contiguous transaxial tomographic images at 3.5-ram intervals for an axial field of view of 10.8cm. The center of this field was at the halfpoint of a line between the anterior iliac spine and the anatomic medial landmark for the knee joint. Images were reconstructed using a filter with a cutoff at 0.3 times the Nyquist frequency. MBF was quantified from data of a plane at midthigh using the following equation16:

2

FES Exercise in SCI Subjects Subjects were positioned supine in the PET scanner. The angle of flexion at the hips was kept constant at 150 ° by the use of a standard plastic foam wedge placed between the back of the subject and the scanner bed. The thighs were maintained exactly parallel to the scanner table to avoid distortions and inaccurate readings that would result from diagonal crosssectional slices. The subjects were introduced legs first into the scanner. The knees rested slightly beyond the edge of the scanner bed and the heels rested on an auxilliary adjustableheight table so that the knees were flexed at 30 ° . Standard goniometry was used to measure the angle at the knees (axis at the center of the knee joint line with the stationary arm along the midthigh and the rotating arm along the length of the fibular shaft). A rigid (padded) board was placed between the subject's thighs and the concave scanner table. This helped keep the legs parallel to the table, provided adequate vertical separation from the table to allow knee flexion, and prevented rotation at the hips. Three carbon silastic electrodes were taped on the skin over the quadriceps muscle. A conducting jelly was applied between skin and electrode. Stimulation parameters were as follows: intensity = 10 to 100mA, adjusted to produce full knee extension against gravity; pulse frequency = 30Hz; pulse duration = 300psec; on/off ramp duration = lsec; train duration = 10sec; interval between trains = 20sec. This stimulation schedule was maintained for a period of 15 minutes.

Voluntary Exercise in Able-Bodied Subjects Subjects were positioned on the scanner table as described above and instructed to exercise by periodically fully extending their right leg from a starting angle of 30 °. This activation period consisted of four phases: (1) Isotonic (dynamic) concentric activation of the quadriceps femoris through 30 ° against gravity, proceeding smoothly over lsec in an attempt to reproduce the interval of the on ramp in the electrical stimulation of the SCI subjects. (2) Isometric contraction of the quadriceps to maintain during 8sec the position of full knee extension achieved during phase 1. This attempted to match the tetanic contraction by FES in the subjects with SCI. Subjects were instructed to use the minimal force needed to prevent knee flexion against gravity. (3) Isotonic (dynamic) eccentric contraction of the quadriceps from full knee extension to the initial position (30 ° of knee flexion) proceeding smoothly over a period of 1sec in an attempt to match the off ramp interval in the electrical stimulation of the SCI subjects. (4) Rest period of 20sec preceding the next cycle. The electrical stimulator was connected to the able-bodied subject's right lower extremity with the same lead arrangement as the SCI subjects, but operated at an intensity just sufficient to generate a sensation, thus eliminating any contribution from the stimulator to the Arch Phys Med Rehabil Vol 79, June 1998

Ci(T) = pCa r ® ke -kr = fo r mfCate -k(r-t) dt

mf

(1)

k=--

P where ® signifies the convolution operator, m = extraction fraction, f = muscle blood flow, p = tissue/blood partition coefficient. Assumptions were m = 1, andp = 0.8. Ci (T) was obtained from muscle-tissue region of interest readings at the last frame of a given interval (7) and Cat from the arterial images in the successive frames from 0 to T, corrected for partial volume effect as described below. The equation was used to create a look-up table from whichfvalues for given Ci(T) measurements were obtained. This process was implemented for the last three frames (T = 2.5, 3, and 3.5min) and averaged to obtain MBE Values of Cat were derived from a region of interest placed on the image of the superficial femoral artery of the plane at the center of the field. Since the diameter of the artery was close to the nominal full width at half maximum (FWHM) reported for the scanner, it was necessary to determine a recovery coefficient (RC) correction before applying the Cat values obtained by PET to the MBF calculation. This was accomplished by scanning phantoms of precisely known geometry and dimensions. Two phantoms were used. One consisted of a 21-cm diameter, cylindrical Lucite container, 10cm high, containing six Lucite cylinders with diameters of 6.35, 9.53, 15.9, 22.2, 31.8, and 38.1mm. The body of the main cylinder was filled with water and each of the smaller cylinders, except for the 38.1-mm diameter, was filled with fluid from a common solution

EFFECTS OF FES ON MUSCLE BLOOD FLOW, Scremin

containing a known concentration of H2150. The other phantom was a solid Lucite cylindrical block, 20cm in diameter, with a regular array of holes bored parallel to the cylinder axis with diameters of 2.5, 3, 3.5, 4, 5, and 6.25mm. These phantoms were scanned with the same protocol used in the MBF experiments. RC was calculated by the expression17: RC

= 1

-

(2)

e -rz/2s2

FWHM where s - - and r = radius. 2.355 Equation 2 was fitted by nonlinear regression to the RC vs phantom radii data obtained from maximum activity in phantom measurements (fig 1) to obtain the parameter FWHM. The radius of the superficial femoral artery, at the same plane at which PET measurement of He150 activity was obtained, was measured by ultrasonography with an Advanced Technical Laboratories 7.5-MHz ultrasound system, b Both lateral and anteroposterior dimensions of the vessel were recorded and averaged for every subject. Arterial radius was entered in equation 2 to obtain RC by which the PET-measured arterial H2150 activity was divided to obtain the true Hz150 arterial concentration. Ultrasound imaging of the superficial femoral artery was also used to confirm the assumption of uniform size of the artery at the location used to measure H2150 activity (a 3.5-ram thick plane at midthigh). No significant tapering or branching was detected at this level in any of the subjects. Measurement of activity in the superficial femoral artery was performed on the nonactivated thigh (left) to avoid interference due to H2~50 activity in the surrounding muscle. In addition, this approach also avoids the complication of possible changes of arterial radius in the active side induced by exercise. A circular region of interest approximately the diameter of the vessel was drawn and centered on the vessel's image at each frame. The maximum value of all pixels within this region, divided by RC to obtain the true tracer concentration as described above, was used in calculations of MBE The shape and location of the area of activated muscle following FES-induced or voluntary contractions varied consid1.0

0.8

_

/2(FWHM/2,3512

+ 0 38 mm

>- 0.6 1> 0

0.4

0.2

0.0

0

I

t

I

I

5

10

15

20

Radius

(rn rn)

Fig 1. The recovery coefficient (RC), defined as the ratio of PETmeasured activity at the center of the phantom over the true activity, is plotted against phantom radius. Nonlinear regression yielded a value of 9.31 -+ .38mm (SE of parameter estimate) for full width at half maximum (FWHM).

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erably among individuals. To provide consistency, regions of interest were defined with the isodensity contour feature in the scanner analysis software. The value of 40% of maximum activity for these isodensity contours was arrived at empirically to provide an estimate that would eliminate reconstruction artifacts from entering the measurements. The mean activity and cross-sectional area of the regions of interest thus defined were recorded in plane 10 at midthigh. Three injections of H2150 followed by scans were performed in every subject. The first (baseline), before any stimulation or exercise; the second, immediately after the end of a 16-min period of FES-induced or voluntary exercise (activity); and the third (recovery), 20min after the second. RESULTS Calculation of MBF requires knowledge of the kinetics of arterial tracer concentration. This was obtained from the PET image time-activity curve of the superficial femoral artery. This image was easily identifiable within 20 to 40sec after injection in both thighs. However, as activity in the surrounding muscle tissue increased with time, the arterial image of the stimulated side was lost. For this reason, arterial tracer concentration was always measured on the left (nonstimulated) side. A correction for partial volume effect was applied to the superficial femoral artery activity, described in Methods. Immediately after FES-induced exercise, a significant increase in MBF was found in the stimulated thigh of SCI subjects (p = .0058) when compared with baseline within the same group and also when compared to the equivalent condition (voluntary knee extension against gravity) of able-bodied subjects (p = .023). The measurements of MBF obtained 20min after the end of FES-induced exercise in SCI subjects were significantly higher than baseline for the same group (p = .027), indicating persistence of the conditions that were responsible for the active hyperemia generated by muscle activation (fig 2). Muscle activation was strictly confined to the stimulated side in four SCI subjects. One of the SCI subjects, however, demonstrated a bilateral, symmetrical increase of MBF. This patient was known to have frequent spontaneous spasms. It is interesting to note that the area activated in the contralateral (nonstimulated) lower limb was confined to the anterior compartment with approximately the same spatial distribution as the area activated by direct electrical stimulation. The magnitude of the MBF response was 19.5 mL/100g/min on the directly stimulated side and 14. lmL/100g/min on the contralateral side. In this case, and since the arterial time-activity curve of the left (nonstimulated) side was contaminated by muscle activity, arterial tracer concentration data from the previous (baseline) scan were used. The assumption of similar arterial tracer kinetics was reasonable because the amount of H2150 injected was the same and the two scans were separated by a few minutes. In able-bodied volunteers performing voluntary exercise, which was similar to the FES-induced exercise of SCI subjects, a small, statistically nonsignificant increase in MBF was observed (fig 2). MBF at baseline did not differ between able-bodied and SCI subjects (fig 2). The total area of muscle activated in both groups of subjects, as estimated from regions of interest enclosing areas 40% of the maximum activity or higher, was similar: able-bodied controls = 5,137 + 1,009rmn 2 (mean +- SE); SCI = 5,284 _+ 357mm 2. However, since SCI subjects had a smaller thigh circumference (50.2 -+ 2.3cm) than able-bodied subjects (56.3 _+ 3.3cm), the area of activated muscle was relatively greater in the former. There was greater variability of activated area in able-bodied Arch Phys Med Rehabil Vol 79, June 1998

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40

I_= E 30 o

20

'kA 0

Baseline

Activity

Recovery

Condition Fig 2. Means (bars) and SE (brackets) of MBF (mL/lOOg/min) obtained from SCI (11) and able-bodied ([]) subjects, The activity MBF mean of SCI subjects was significantly higher (p = .0058) than the baseline mean MBF of the same group and also higher than the mean MBF of the equivalent condition (voluntary knee extension against gravity) of able-bodied subjects (p = .010}, The mean MBF for recovery (20min after the end of FES-induced exercise) in SCI subjects was significantly higher than baseline for the same group (p = ,027). No significant differences were found among the three conditions in able-bodied subjects.

controls than in SCI subjects and the shape of these areas was essentially different in both groups. In SCI subjects there was a single, large area enclosed by the isodensity line, whereas in able-bodied controls there were generally several small irregular areas, stacked at different depths within the muscle (fig 3). The radius of the superficial femoral artery measured with ultrasonography, used in the calculation of RC with equation 2, did not differ significantly between left and right sides within a group nor between the two groups of subjects (SCI: left = 2.7 _+ .26mm, right = 2.6 + .25mm; able-bodied: left = 3.1 ___ .29mm, right = 3.3 + .35mm). DISCUSSION To avoid catheterization of an artery to obtain the input function required for calculation of MBF, we used the timeactivity curve of the superficial femoral artery PET image instead. Because of the small dimensions of the imaged superficial femoral artery, a correction was required for which we used the approach described by Germano and associates. 17 These authors have described the underlying assumptions of

SCI 1

co. 1

SCI 2

co. 2

Arch Phys Med Rehabil Vol 79, June 1998

SCI 3

co. a

this approach, which, as they apply to our study, may be summarized in the following five points. (1) Equation 2 can be used directly only if the radius of the vessel is known by other procedures. We have used ultrasonography for this purpose. (2) The vessel's axis must be perpendicular to the transaxial image plane. In our case, the thigh was parallel to the table surface and the trajectory of the superficial femoral artery at the plane used for measurement of H2150 activity was very closely parallel to the thigh axis and thus perpendicular to the image plane. (3) It is assumed that there was no spillover from adjacent structures. This was true in the absence of significant activation of MBF in the adjacent muscle, a condition met in the initial frames for both lower limbs but certainly not in the later frames of the stimulated side. This is the reason why the arterial PET images of the nonstimulated side were used for derivation of the time activity curves. (4) Accuracy in calculation of arterial activity requires a small region of interest (less than one fifth of the artery diameter). In our case we determined the maximum value of H2150 activity within a small region of interest centered on the vessel. The same procedure was used for RC determination from phantom measurements. (5) The vessel must not move to assure reproducibility of measurements. In our case we saved the region of interest of the most clearly visible arterial image (usually frame number 2 or 3, at 20 and 30 sec after initiation of the scan, respectively) and used it to read the rest of the frames, adjusting the position when necessary to compensate for displacements, which were for the most part absent. The experiments were designed to avoid exercise-associated movement by commencement of the scans either with no stimulation (baseline and recovery) or immediately after electrical stimulation. The values of MBF obtained at rest in both groups of subjects were within the range reported for this variable by use of plethysmography and washout of radioactive inert gases I8 as well as H2150-PET. 19-22 The fact that able-bodied controls showed a minimal activation of MBF with voluntary exercise may relate to two factors. First, the level of MBF at baseline in this group was somewhat larger (although it did not reach statistical significance) than that of SCI subjects. There may have been then a certain effect of anticipation of exercise on MBF. Second, the exercise intensity (unloaded knee extension over 30 ° ) was very light for able-bodied subjects and far removed from their maximum exercise capacity. SCI subjects, on the other hand, were closer to their maximum exercise capacity. These considerations raise the issue of the rationale for the experimental design used in this study. There are at least two possible approaches: to ask the able-bodied subjects to perform the same task (unloaded knee extension against gravity), or to ask them to exercise at the same equivalent load

SCI 4

CON 4

SCI 5

CON 5

Fig 3. Images from PET scans of the last frame in plane 10 (midthigh) obtained from a scan immediately after the end of activation (FES-induced or voluntary knee extension) in SCl and able-bodied (Con) subjects, The thin black lines enclosed areas with activity ->40% of maximum,


(ie, 30% of maximum) as the SCI subjects. The two types of exercise address two different questions. The first one, used in this study, deals with the task of moving a limb segment through a prescribed length and compares the performance of the natural system (voluntary contraction) with FES. The second one tries to reproduce the same workload relative to the maximal force development that the muscle is capable of and compares the performance of both systems. Unfortunately, the two designs were mutually exclusive for reasons of cost and radiation exposure. We decided to use the task-oriented approach first, and if differences could be demonstrated between the two modes of obtaining knee flexion, the second approach would be implemented to answer the question of whether the differences resulted from the variation in relative workload (if the responses turned out to be the same under the same relative workload) or to some other factor if that was not the case. The first approach is more general, because the relative workload may not be that different (in theory) between the two groups of subjects. It is true that disuse atrophy decreases the cross-sectional area (and hence the maximal force) of the SCI subjects' lower extremity muscles, but by the same token it decreases (probably by a proportionate amount) the weight of the limb to be moved that represents the load. Furthermore, it could have happened that the muscle of SCI subjects would have responded to exercise with the same (or lower) magnitude of MBF as in able-bodied subjects, in which case the second (relative workload) approach would have been uninformative. The results of this study open the question of whether the greater response of MBF to exercise in SCI subjects as compared with able-bodied controls is due to the difference in relative workload, or to other factors associated with disuse atrophy (eg, change in fiber type composition, metabolic changes) or abnormal motor unit recruitment. Experiments in progress in our laboratory are currently addressing these issues. It is likely that measuring MBF immediately after rather than during exercise (in order to avoid movement artifacts as discussed above) may have underestimated the MBF response to exercise, especially in able-bodied subjects. It is well known that after a contraction, blood flow in the exercising muscle increases to a maximum and then decreases exponentially over time. TM If the rate at which MBF decreases after exercise is fast enough with regard to the scan duration (3.5min), an underestimation of the true MBF response to exercise would occur. It could be hypothesized that this decrease in MBF after exercise proceeds at a slower rate in SCI subjects, since they did not recover their baseline MBF 20min after activity, whereas able-bodied controls did. This phenomenon may have contributed to the difference observed in MBF response to exercise between both groups. These experiments have demonstrated the feasibility of noninvasive, quantitative determination of MBF in humans by means of H2150 PET. In the past, MBF in humans has been measured by a number of methods, such as plethysmography, 23,24 a technique that has been used extensively but has the main disadvantage of estimating blood flow changes in large masses of tissue, such as an entire limb. This technique inevitably averages blood flow in muscle, connective tissue, and skin to a variable extent. The same criticism can be raised about measurements of volume flow in large arteries by means of electromagnetic or Doppler ultrasound probes. 25 A significantly better localization can be achieved by the use of thermo probe needles 26 or local radioactive Xe clearance. 27,28 The first method provides only a relative index of flow, whereas the latter, although it yields information in terms of absolute flow, cannot avoid including nonmuscular tissue in the blood flow

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determination, and its spatial resolution is poor due to the use of external, relatively large detectors. The H2 clearance method has also been used for the measurement of skeletal MBF in humans and animals. 29-31 Based like the Xe clearance in the Fick principle, this procedure uses an internal detector, a platinum electrode, that in some applications in experimental animals has been made small enough to detect blood flow changes over a distance of 0.2mm. 32,33 Thus, the degree of localization provided by this blood flow measuring technique is far superior to any other. A drawback of this methodology, however, is the limited number of sites that can be sampled. A technique using S2Rb, with measurements by an external [3 detector, has been recently shown to provide good correlation with the well-established microsphere technique. 34 However, this isotope has a large positron energy (max 3.35MEV) that compromises image resolution, and it cannot provide an accurate blood flow measurement because of variable and unknown extraction. 81Rb has been applied to PET measurements of tumor perfusion in humans, 35 but its long half-life (4.58h) prevents serial measurements with activation and creates unfavorable dosimetry conditions. H2150 has been successfully used to measure blood flow in a number of organs, including skeletal muscle and bone as well as brain and heart, 19-22,36-38and due to the extremely short half-life of 150 (123sec) it allows repeated measurements of the same subject in a single session. This characteristic seems ideally suited to experiments that intend to characterize the vascular response of muscle of paralyzed subjects to FES, and it could also be effectively applied to estimation of the functional reserve of the muscle vasculature of able-bodied subjects with peripheral vascular disease. The last application could be of help in the accurate determination of the level of amputation, a decision that qualifies the type of prosthesis to be used and the subsequent ability of the patient to walk. 39 CONCLUSION SCI subjects demonstrated a large response of MBF to FES-induced unloaded knee extension exercise, far greater than that observed in able-bodied controls performing voluntary unloaded knee extension exercise. This fact is contrary to the hypothesis that a limitation in MBF response is the basis for the limited power developed by muscle in FES-induced exercise. The fact that the response of MBF to activity was much greater and lasted longer in SCI subjects than in able-bodied controls argues for a greater metabolic change in response to FES than to voluntary exercise, probably related to less efficient energy conversion in deconditioned muscle. It is also possible that the nonphysiologic pattern of muscle recruitment characteristic of FES may have contributed to the differences observed. Acknowledgments: The aathors are indebted to Dr. William Blahd and Dr. Edward Grant, departments of Nuclear Medicine and Radiology, West LAVA Medical Center, and to Dr. Edward Hoffman, Department of Medical and Molecular Pharmacology, UCLA School of Medicine, for helpful advice and for making available the equipment used in the study. References

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