A novel method to obtain proximal plethysmographic information from distal measurements using the impedance plethysmogram

The increasing prevalence of cardiovascular diseases over the last decades is forcing healthcare systems to shift its focus to early detection and preventive therapies, in order to reduce the overall spending on treatments and to decrease their impact on patients’ lives [1]. However, traditional technologies for screening and diagnosing are not well suited to this new scenario since these often rely on the availability of limited resources such as expensive devices and highly trained staff. Consequently, a heavy effort is currently being devoted to the conception of novel reliable and cost-effective technologies suitable for performing fast screenings and regular self-administrated health status checks at home or in secondary health facilities, which better suit the present needs of healthcare systems.

Arterial stiffness has been identified as a key factor for assessing cardiovascular disease risk [2,3] since it can be obtained noninvasively in ambulatory environments from the Pulse Wave Velocity (PWV), i.e. the propagation speed of the pressure pulse generated by the cardiac ejection of blood from the heart to the arterial tree on each heartbeat. The timing delay in the arrival of the pressure pulse between a proximal and a distal site, the so-called Pulse Transit Time (PTT), is generally accepted as the most simple, robust, and reproducible method to obtain the PWV [4], which can be calculated from the PTT according to

where D is the distance between the two recording sites measured on the body surface. Photoplethysmography (PPG) [5], impedance plethysmography (IPG) [6], mechanical transducers [7], and arterial tonography [8] are the most common technologies for PTT measurements [9] because they are simple, non-invasive, and cost-effective.

Nevertheless, PTT measurements using these common technologies require time to expose and clean a proximal and a distal site, and to place the sensors and wires, which is a nuisance for fast screenings or regular self-administrated health status checks. This preparation time can be reduced by placing the sensors in areas that are habitually uncovered or easily accessible, such as the distal parts of the limbs [6]. However, short distances D between sensors yield low-accuracy PTT measurements hence the placement of the proximal sensor onto an area proximal to the torso is often required, and that area is less accessible than the hands or feet. Further, PTT measurements in central arteries such as the aorta, which show the highest predictive value for cardiovascular risk assessment [10], include large portions of other arteries when performed with common pressure-pulse recording devices placed at the limbs and this reduces the measurement performance [11] hence measurements in areas proximal to the torso are more advisable.

In addition to common measurements along a single artery, the IPG can also be measured from hands to feet, the so-called whole-body impedance plethysmogram [12]. Even though the specific contribution of the different body segments in the current path is unknown, whole-body IPG waveforms precede the IPG obtained on the foot, which indicates that the IPG upstroke forcefully reflects plethysmographic changes in proximal sites with respect to the recording sites hence the PTT can be derived from these two signals. However, the method proposed in [12] requires the exposure of four recording sites and the placement of six electrodes, which is still unpractical for fast screenings or regular self-administrated health status checks.

Alternatively, the IPG can be measured from hand to hand [13] and from foot to foot [14], which only requires the exposure of two measurement sites. Since the current injected in limb-to-limb measurements travels through proximal and distal arteries, it is reasonable to assume that certain features of the recorded waveform will reflect volume changes in arteries more proximal to the torso than the recording site, analogously to whole-body impedance measurements. This fact was first observed in the signals obtained from a four-electrode system intended for measuring the Pulse Arrival Time (PAT) [15], which is defined as the time delay between the electrical activation of the heart and the arrival of the pressure pulse to a specific body site.

In this paper, we compare the timing of the hand-to-hand IPG (IPG_hh) and the foot-to-foot IPG (IPG_ff) with several local IPG waveforms simultaneously obtained with two close electrodes placed on the target area, in order to investigate the suitability of limb-to-limb IPG measurements to obtain proximal plethysmographic information by using four electrodes placed only on distal sites.

Fig. 5 shows the traces of the IPG_hh and the local IPG obtained at the shoulder, elbow, wrist, and the index finger.

Fig.5

Compared to the local IPG waveforms, which have similar foot and upstroke shapes and only differ in the arrival time, the IPG_hh waveform is smoother, especially in the area of the foot. The minimum of the signal precedes any of the other local IPGs but the leading edge comes after that of the elbow IPG and the peak coincides with that of the wrist IPG. T he P AT to the I PG_hh using the tangent intersection method is 178 ms, whereas the PAT to the shoulder, elbow, wrist, and the finger using the same method are 148 ms, 164 ms, 201 ms, and 210 ms, respectively.

Fig. 6 shows the traces of the IPG_ff and the local IPG obtained at the femoral artery, knee, and the ankle.

Fig.6

Similar to the IPG_hh, the foot of the IPG_ff is smoother than that of local IPG waveforms and the upstroke arrives later, but less than in the IPG_hh. The minimum of the IPG_ff signal and its maximal slope are located close to those of the knee IPG, and the peak of the IPG_ff comes later than that of the ankle IPG. The PAT to the IPG_ff is 2 36 ms, whereas the PAT to the femoral artery, knee, and the ankle are 198 ms, 220 ms, and 250 ms, respectively.

The measured PAT to the IPG_hh and the I PG_ff were significantly lower than the PAT to the local IPG obtained at the different measurement sites in the arm and leg. The values reported with respect to other local pulse-pressure waveforms suggest that the PAT to the IPG_hh could be used as a surrogate of the PAT to the elbow whereas the PAT to the IPG_ff could be used as a surrogate for the PAT to the knee. Combined with a local pressure-pulse waveform, it is possible to measure a PTT of 32 ms at the hands and a PTT of 14 ms at the feet, which are longer PTT values than those in other IPG measurements [6] in spite of being measured in a smaller area.

Further, the longer delay between the minimum of the signal and the maximal slope of the upstroke in limb-to-limb IPG waveforms as compared to the local IPG waveforms suggests that common algorithms to detect the foot of the limb-to-limb IPG signal that rely on features of the upstroke, such as the tangent intersection, could be unsuitable. This could explain the discrepancy between PAT values here measured with the IPG_hh and PAT values measured with a finger PPG as reported in [15], where the pressure-pulse arrival is determined by the mid-raise of the upstroke. Since the finger PPG arrives later than the foot of the IPG_hh determined by the intersecting tangents method, it is reasonable to assume that it will yield longer timings in limb-to-limb waveforms due to the slower slope of the upstroke.

We have studied the suitability of limb-to-limb measurements performed with two distal electrode pairs for assessing proximal plethysmographic information with respect to the recording sites. Our results show that the foot of the wave detected by the intersecting tangents method is close to the pressure-pulse arrival at the elbow for the IPG_hh and to the pressure-pulse arrival at the knee for the IPG_ff, which allows us to obtain PTT values of 32 ms at the hands and 14 ms at the feet when combined with a distal pressure-pulse waveform. These PTT values are longer than those obtained by current methods. This is remarkable as the limb-to-limb IPG only requires the exposure of two easily accessible recording sites at the distal parts of the limbs. Further, our results suggest that limb-to-limb signals should yield better aortic PTT measurements than other methods that use signals obtained at the limbs because these include a larger contribution of distal arteries.

A limitation of this study is that the performance of limb-to-limb IPG waveforms under hemodynamic variations has not been explored. Future work should focus on determining the accuracy of the pressure pulse timing under diverse maneuvers intended to induce hemodynamic changes and in a wider group of test subjects to test the intra-subject variability. Another area of future work could be the development of methods to detect the foot of limb-to-limb IPG signals as their leading edge is different from that of local IPG signals.

This notwithstanding, limb-to-limb IPG systems can open new opportunities to design reliable and cost-effective methods to enable fast PTT measurements in clinic and ambulatory environments.