Abstract
The MoistureMeterD is used to noninvasively measure skin and upper subcutis tissue dielectric constant (TDC) at almost any anatomical site to depths from 0.5 mm to 5 mm at a frequency of 300 MHz by touching the skin with a handheld probe for about 10 s. Because TDC at this frequency is largely dependent on free and bound water content of the tissue being measured, TDC measurements are useful to assess localized edema and lymphedema and their changes. In this chapter further aspects of TDC use are elaborated upon, and factors that impact its measurement and value are presented.
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Keywords
- Lymphedema measurement
- Edema measurement
- Dielectric constant
- Permittivity
- Breast cancer
- Tissue dielectric constant
- Lymphedema assessment
- Leg edema
Key Points
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1.
Tissue dielectric constant (TDC) measurements using the MoistureMeterD provide a way to assess an individual’s local skin-to-fat water rapidly and noninvasively.
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2.
Assessments can be done in virtually any anatomical site of clinical interest.
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3.
TDC and thereby relative water can be assessed at different depths, which is a feature that could aid in better characterizing edematous and lymphedematous characteristics.
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4.
Tracking of changes in lymphedematous status over time is easily and rapidly done.
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5.
In cases of potential unilateral lymphedema, inter-side TDC ratios may serve as markers of subclinical lymphedema.
Introduction
The MoistureMeterD (MMD) is a multiprobe device (Fig. 13.1) manufactured by Delfin Technologies (Kuopio Finland) that is used to measure skin and upper subcutis tissue dielectric constant (TDC) at a frequency of 300 MHz by touching the skin’s surface with a handheld probe for about 10 s (Fig. 13.2). Probe outer diameters range from 10 mm for a 0.5 mm effective measurement depth (Fig. 13.3) to 55 mm for a 5 mm measurement depth. Effective measurement depth is defined as the depth at which the electric field decreases to 1/e of its surface field as illustrated in Fig. 13.4 for a 2.5 mm depth measurement probe.
Dielectric constant, also known as relative permittivity, is a dimensionless number equal to the ratio of the permittivity of tissue to the permittivity of vacuum. Because TDC values in part depend on tissue water content, TDC values and their change provide indices of water content and quantitative estimates of water content changes. For reference the dielectric constant of distilled water at 32 °C is about 76. Because the measuring devices operate at a frequency of 300 MHz the measured skin TDC values are sensitive to both free and bound water within the measurement volumes. The vertical dimension for the measurement volume ranges between 0.5 mm and 5.0 mm below the epidermis with the total volume depending on the probe diameter.
Currently available devices come in two flavors. One is the original MMD, the multi-probe version with four separate probes as shown in Fig. 13.1 for effective measurement depths of 0.5, 1.5, 2.5, and 5.0 mm with the largest size probe measuring the deepest. The other device (Fig. 13.5) is a compact version (MMDC) in which the sensor and processing electronics are built into the handheld unit. The MMDC has a bar indicator showing the relative amount of contact pressure being exerted on the skin. The MMD and to a lesser extent the MMDC have been used in basic and clinical research studies in which skin tissue water and its change were of interest. Because either probe system can be used in virtually any anatomical location, data and findings are available for multiple anatomical sites on the upper body including face [1, 2], breast [3], forearm [4–7], biceps, axilla, and thorax [8] and on the leg and foot [1, 9, 10]. One of the most frequent uses to date has been for tracking and possible early detection of subclinical lymphedema in women at-risk for or already having lower extremity lymphedema or upper extremity breast cancer treatment-related lymphedema (BCRL) [11–17]. The method also may have value in differentiating lower extremity lymphedema from lipedema [18], characterizing changes in postsurgical fluid status [19], and assessing skin irradiation effects [3].
Measurement Principles
The control unit (Fig. 13.1) generates and transmits a very low power 300 MHz signal into the probe that is in contact with the skin (Fig. 13.2). The signal is transmitted into the tissue via the probe that acts as an open-ended coaxial transmission line [20]. Part of the signal is absorbed by the tissue, mainly by water, and part is reflected back to the control unit where the complex reflection coefficient is determined [21, 22] from which the dielectric constant is determined [23, 24]. Reflections from the end of this coaxial transmission line depend on the complex permittivity of the tissue which depends on the signal frequency and on the dielectric constant (the real part of the complex permittivity) and the conductivity of the tissue with which the probe is in contact. At 300 MHz the contribution of the conductivity to the overall value of the permittivity is small and the dielectric constant is mainly determined by water molecules (free and bound). Consequently, the device includes and analyzes only the dielectric constant (TDC) that is directly proportional to tissue water content in a manner close to that predicted by Maxwell mixture theory for low water content but a slightly less good prediction for high water content tissues [25]. In all cases TDC is strongly dependent on relative water content with TDC values that decrease with water reductions during hemodialysis [26] and that correlate with whole body water percentages as illustrated in Fig. 13.6 in which forearm TDC values are seen to highly correlate with total body water percentage as determined using bioimpedance measures.
The induced electric field within the tissue falls off exponentially and the effective measurement depth, defined as that depth at which the field is 1/e its surface value, depends on the dimensions of the probe [27] with larger dimensions being associated with deeper penetration. If the tissue measurement volume is viewed as being comprised of two layers, one being the skin including stratum corneum, epidermis and dermis with combined skin depth δ, and the other part being the subcutaneous tissue including fat, then it can be shown that measured TDC values depend on dielectric constants of skin (ε skin) and fat (ε fat) and on δ [3, 27]. This relationship can be expressed [2] as \( TDC=\left({\varepsilon}_{\mathrm{skin}}-{\varepsilon}_{\mathrm{fat}}\right)\left(1-{e}^{-q\delta}\right)+{\varepsilon}_{\mathrm{fat}} \) in which q is a device constant that depends on probe dimensions and is about 0.82 for the 1.5 mm depth probe. Changes in TDC values largely reflect changes in skin water content because of the normally large fraction of skin water. However, because TDC values also depend on skin thickness (δ) comparisons of absolute water content between individuals or groups should be done with caution. An equation linking percentage of tissue water content (PWC%) to TDC values has been proposed [26] for high water content tissues and is given by PWC% = 100 (TDC − 1)/77.5. The denominator of this equation (77.5) is based on a TDC value for water of about 78.5 at 25 °C. However, since water’s dielectric constant depends on temperature, the tissue temperature being measured should be taken into account. For example, at a skin temperature of 34 °C, water’s dielectric constant is about 75.2. Table 13.1 lists water dielectric constants for various temperatures. Temperature corrections may result in small TDC changes but under certain circumstances such corrections are useful and easily done. For example if a PWC% reading on the compact device was 36 % at a tissue temperature of 34 °C then the true percent water in this tissue would be closer to (77.5/74.2) × 36 % = 37.6 %, a value that is approximately 4.4 % greater.
Calibration Procedures
Each device is pre-calibrated by the manufacturer. For the multi-probe system each probe is separately calibrated for a given control unit. If two or more systems are being used, probes should not be interchanged between control units. There may be circumstances when independent calibrations or calibration checks are useful. This can be done by exposing the probe tips to various ethanol–water concentrations and comparing values obtained with known solution dielectric constants. The static dielectric constant for ethanol at 25 °C, averaged from multiple sources, is 24.8. The approximate dielectric constant values for various ethanol–water mixtures that are listed in Table 13.2 may be used to compare values obtained with any probe and if needed take appropriate calibration adjustments into account. An example of a full calibration curve is shown in Fig. 13.7, but only a few ethanol–water mixture concentrations would be sufficient.
Measurement Procedure
Touching skin with one of the probes of the multiprobe device or touching it with the compact device activates the measurement that is heralded by short distinctive sound. A single measurement takes about 10 s or less to complete with completion signaled by another distinct audible sound. The TDC value is displayed on the control unit of the multiprobe readout. For the compact device the readout is not directly that of the TDC value, but instead it is a calculated percentage water PCW% determined via the equation previously given. If one is using both multiprobe and compact devices, it is useful to convert compact readings to TDC to achieve uniformity of measures for comparison purposes between results obtained from the two systems. The conversion equation that can be used is TDC = 1 + [(PWC%) (ε water − 1)]/100 in which PWC% is the number displayed on the compact probe (calculated percentage water) and ε water is the dielectric constant of water used by the device for its calculation which is 78.5. For example, a reading of 36 % would correspond to a TDC value of 1 + (36 × 77.5)/100 = 28.9.
Short- and Long-Term Measurement Repeatability
One or Multiple Measurements Averaged
TDC measurements taken in triplicate and averaged are the method most frequently employed. However, it has been shown that for TDC measurements on forearms of healthy women and women with BCRL the average difference in TDC value between the first measurement and the average of three sequential measurements to a depth of 2.5 mm is less than ± 1 TDC unit [6]. This suggests that for many purposes a single measurement may be sufficient; however, similar data on other anatomic sites is not yet available.
Short-Term Intrarater and Interrater Repeatability
Because some applications use pre- and post-TDC measurements to assess single treatment therapeutic modalities [11, 15] the measurement repeatability over intervals of the order of 60 min are of interest. Intrarater reliability has been assessed based on bilateral forearm TDC measurements to 2.5 mm depth on five subjects at 0, 30, and 60 min by a person with familiarity with TDC measurements. Intrarater repeatability has been assessed using intraclass correlation coefficients (ICC) that broadly express the percentage of variability attributable to true subject variance as opposed to measurement related variability (between-subject variation/total variation). Results revealed a single measure ICC value (ICC2,1) of 0.996 with a 95 % confidence interval of 0.96–1.000. Additional tests based on measurements of a minimally trained rater under the same circumstances yielded ICC2,1 values 0.999 with 95 % confidence intervals of 0.994–1.000. Interrater reliability (ICC2,2) has also been assessed via triplicate measurements made on four subjects at 30 min intervals by two medical students who were minimally trained in TDC measurements. ICC2,2 values obtained were quite good at 0.997 with a 95 % confidence interval of 0.988–0.999. Assessments of interrater reliability of TDC measurements made 1 week apart by two other minimally trained medical students yielded reasonable ICC values for both the 2.5 mm and the 1.5 mm depth probes as summarized in Table 13.3 for forearm, leg, and foot. Interobsever agreement of absolute TDC measurements in lower extremities has also been assessed based on measurements of three minimally trained measurers who each measured TDC at calf, ankle, and foot to a depth of 2.5 mm in 34 healthy women [10]. Results showed average ICC2,3 values for ankle and calf at excellent levels of 0.94 at both ankle and calf but a lesser value of 0.77 for the foot.
Long-Term Reliability
Longer term intrarater repeatability has been assessed by measurements of normal control arms in 32 women on six separate occasions by the same therapist over a 24 month period. These women had been diagnosed with unilateral breast cancer and their contralateral arms measured prior to surgery and then at 3, 6, 12, 18, and 24 months post-surgery. Intraclass correlation coefficients (ICC2,1) determined for forearm TDC measurements to a depth of 2.5 mm was 0.900 with a 95 % confidence interval of 0.835–0.946.
Factors Effecting Measured TDC Values
Effective Measurement Depth
Depending on the anatomical site, measured TDC values will vary with generally higher values at lesser depths and lesser values at greater depths. This dependence is not necessarily linear as illustrated by measurements made on the anterior forearm of a large group of women (Fig. 13.8). For this data set the TDC averaged between both arms decreased according to a nonlinear power regression equation given by TDC = 32.44 δ −0.185 in which δ is measurement depth. This observed pattern is at least in part due to the inclusion of increasing amounts of low water content fat in the measurement volume with increasing depth [8]. Although this pattern is commonly observed in tissues such as forearm and biceps it may be different in other anatomical sites. For example no significant difference in TDC values was detected among depths of 0.5, 1.5, and 2.5 mm on the cheek or the dorsum of hand or foot [1]. Contrastingly, significant differences in TDC values as a function effective measurement depth were observed for forehead; forearm; and medial, lateral, and anterior gaiter areas of the leg [1].
Anatomical Site Variations
Not unexpectedly TDC values depend on the anatomical site being measured. There appears to be no specific guiding principle that will predict which anatomical site for a given effective measurement site will have a particular value range. Table 13.4 summarizes some absolute TDC values previously measured [1] at various sites and effective depths for a group of 32 healthy women. Local TDC values may also vary slightly depending on the exact location of the measurement. The range of such potential variations has been assessed on the forearm of 30 healthy females [5] with triplicate measurements along and on either side of the forearm midline at various distances (Z, cm) from the antecubital crease for a total of nine separate sites. Mean TDC differences between adjacent longitudinal sites along the midline separated by 4 cm ranged from 0.7 to 4.2 % for 2.5 mm depth and 0.4 to 3.1 % for 1.5 mm depth. Variations among adjacent sites 1.2 cm distant from the midline in the medial direction ranged from 0.0 to 1.8 % for 2.5 mm depth and from 0.8 to 2.4 % for 1.5 mm depth. Table 13.5 summarizes absolute TDC values measured along the forearm midline [5]. For the 2.5 depth probe the regression equation was TDC = 0.26Z + 25.2 (r 2 = 0.999) and for 1.5 mm depth TDC = 0.20Z + 27.7 (r 2 = 0.994).
Gender and Age as Factors
Comparisons of TDC values measured to a depth of 1.5 mm in young adult males and females [2, 28] indicates that TDC values measured at the forehead, cheek, and forearm are all significantly greater in males than in females (p < 0.001). On average male TDC values were found to be about 13 % greater than females on the forearm [28] and about 5.6 % and 9.5 % greater on the forehead and cheek respectively [2]. These TDC differences may be related to male–female differences in skin thickness or to actual differences in water content. In either case male–female differences should be considered in any protocol that includes both genders.
The role of age has been investigated by comparing forearm TDC values at multiple depths in two groups of women divided by age above and below 55 years [12]. The results showed that to depths of 0.5 mm and 1.5 mm the older group TDC values were significantly greater than for the younger group but for the deeper depths of 2.5 mm and 5.0 mm there was no detectible difference. Table 13.6 summarizes the comparative TDC values.
Body Fat Percentage as a Factor
TDC values tend to decrease with increasing body fat percentage and also to decrease with the percentage of arm fat. This feature is illustrated in Fig. 13.9 that is based on whole body and segmental body composition measurements via bioimpedance in 130 subjects. The fat dependence is greater when the effective measurement depth is greatest since for this condition the contribution of the low water content fat to the overall measurement is also greatest.
Vascular Factors
The potential impact of skin blood flow and vascular volume on TDC values has been investigated by measuring arm TDC values under various test conditions [4]. Arm vascular volume and skin blood flow was changed using an upper arm cuff inflated to 50 mmHg as illustrated in Fig. 13.10 with TDC measurements before and after inflation. Changes in skin blood flow were also produced via changes in arm position ranging from horizontal positioning to arm elevated above the head. Illustrative results of such perturbations on skin blood flow measured via laser Doppler methods are shown in Fig. 13.11. As anticipated the various maneuvers caused significant vascular volume and blood flow changes but only minor effects on measured TDC values in the range of ±3 %. This suggests that vascular changes in most conditions are of minor importance vis-à-vis measured TDC values. However, from a technical viewpoint one should avoid placing the measuring probes directly over visible blood vessels.
Hormonal Factors
Because at least one anticipated application of the TDC method is the evaluation of edema and lymphedema in female patients the potential impact of hormonal influences associated with the menstrual cycle are of interest. This issue has been addressed via TDC measurements in premenopausal and postmenopausal women with premenstrual measurements made at three time points in the monthly cycle [7]. Results as summarized in Table 13.7 showed that forearm TDC values were not significantly different over the menstrual cycle at any measurement depth.
Diabetes Mellitus (DM)
Given the incidence of diabetes and its possible impact on skin physiology, awareness of possible impacts on skin tissue water is useful. This aspect has been investigated by comparing TDC values at multiple depths in forearm and foot dorsum in persons with and without diabetes mellitus [9]. Forearm TDC values tended to be slightly greater at all depths for the DM group but did not reach statistical significance. Contrastingly TDC values measured on foot dorsum were on average about 15 % greater in persons with DM. Absolute TDC values for persons with and without DM are summarized in Table 13.8. Although average foot TDC values were significantly (p < 0.05) greater for the DM group, inter-foot TDC ratios were similar at all depths with no significant differences between groups.
Breast Cancer
Earlier published work evaluated TDC values at four strategic anatomical sites in women diagnosed with unilateral breast cancer [8]. These sites, forearm, biceps, axilla, and lateral thorax, were measured, and values obtained were compared to those obtained from a control group of women. Subsequently forearm TDC values were compared among three groups of women with groups classed as (1) healthy controls, (2) with breast cancer but prior to surgery, and (3) those patients who had developed BCRL [13]. The most current data available for these comparisons is for TDC measurements made in 80 women who were diagnosed with unilateral breast cancer and who were evaluated prior to their surgery. A summary of TDC values for the at-risk (cancer) side and for the contralateral (healthy) side as well as at-risk/contralateral side ratios are shown in Fig. 13.12. Side-to-side TDC values did not significantly differ for any site, but differences among sites were significant (p < 0.001) with each site being significantly different from any other site. Contrastingly, side-to-side TDC ratios did not differ among measured sites.
Lymphedema
The presence of clinical lymphedema is associated with a significant increase in TDC values [13, 17] with affected arm values having average TDC values between 44 % to 65 % greater than contralateral arm values depending on the effective measurement depth [17]. Further, TDC values have been observed to decrease with various forms of therapy in lymphedematous legs [14, 15] and in arms and legs [11] by amounts ranging between 10 % and 16.8 % for legs and 8.2 % for arms. Table 13.9 summarizes the most recent data for TDC values measured at 2.5 mm depth in arms of 80 women with BCRL, in 80 women with breast cancer (BC) but no lymphedema and in 80 women without breast cancer (NOBC). TDC values of the lymphedematous arm greatly exceed TDC values obtained from contralateral arms. In patients with BCRL, contralateral arm TDC values are not significantly different from those measured in patients with breast cancer without lymphedema or in healthy women free of breast cancer.
Multiprobe Versus Compact Probe as a Factor in TDC Values
All reported TDC measurements so far are based on use of the multiprobe system (Fig. 13.1). Because of construction and design feature differences of the compact TDC probe (Fig. 13.5) an assessment of comparative TDC values produced by the different devices is useful. For that purpose TDC values obtained with the compact probe were compared with the multiprobe system for probes to depths of 1.5 mm and 2.5 mm in forearms and biceps of 32 males and 32 females. Results of this comparison are summarized in Table 13.10. The compact device measurements were found to be between the 1.5 mm and 2.5 mm measurements. Including both male and female values, compact device values are 5.6 % to 5.8 % higher than the 2.5 mm probe.
Potential Use of TDC for Early Lymphedema Detection
Based on the normal variance in TDC values among persons it is possible to develop criteria potentially useful to aid in the detection of early incipient lymphedema in persons at risk of developing unilateral arm lymphedema. To this end TDC bilateral forearm and biceps measurements were made to a depth of 2.5 mm in 103 women (60.6 ± 13.2 years) who had been diagnosed with breast cancer. Measurements were made prior to their scheduled surgery to eliminate surgery as a variable. Because of the relative site independence of inter-arm TDC ratios, inter-arm TDC ratios were chosen as the potential detection parameter and determined as the ratio of TDC values measured on the at-risk arm to the TDC value measured on the contralateral arm. This ratio is designated by the symbol γ and is for the forearm γ forearm and for the biceps as γ biceps. A summary of these measurements is shown in Table 13.11. Theoretical lymphedema detection thresholds might be based on γ + 2.5 SD (includes 99.4 % of cases) or on γ + 3.0 SD (includes 99.9 % of cases). A determination of the number of patients that exceed the γ + 3.0 SD threshold was investigated in the course of tracking 104 different patients evaluated on average 26.3 ± 17.5 months post-surgery. Ten patients (9.6 %) exceeded the forearm threshold and six (5.8 %) exceeded the biceps threshold. Further, patients reporting at least one lymphedema-related symptom (N = 34, 32.7 %) also had a significantly greater value for γ biceps than patients with no symptoms (1.113 ± 0.335 vs. 1.001 ± 0.119, p = 0.014) and also had a greater value for γ forearm (1.100 ± 0.231 vs. 1.026 ± 0.129, p = 0.038). Although these findings are encouraging vis-à-vis threshold detection, the concept remains theoretical at this time while awaiting outcomes of ongoing prospective sequential studies.
Conclusion
Measurements of the tissue dielectric constant (TDC) of the skin are a noninvasive, rapid, and reliable way to assess skin-to-fat relative water content and its change at almost any anatomical site. As described, the method has a well-documented physical basis and has a fairly extensive background of use in a variety skin sites and has been investigated for use in several conditions including lymphedema evaluation. The ability to measure water rapidly and locally provides the advantage of tracking changes in anatomical sites of particular interest either for pretreatment and posttreatment reasons or for longer-term follow-up assessments. In addition, the method allows for easy tracking of those anatomical sites deemed to be particularly at risk of developing lymphedema or those sites that on clinical examination already appear slightly edematous. Investigations into the use of TDC measures for early detection of incipient lymphedema have indicated significant potential, but studies are as yet incomplete and thresholds not yet validated.
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Mayrovitz, H.N. (2015). Assessing Free and Bound Water in Skin at 300 MHz Using Tissue Dielectric Constant Measurements with the MoistureMeterD. In: Greene, A., Slavin, S., Brorson, H. (eds) Lymphedema. Springer, Cham. https://doi.org/10.1007/978-3-319-14493-1_13
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