Application of Hilbert-Huang Transform to the data of blood glucose profile

Ing. Stanislava Burskov

Abstrakt: Hilbert Huangova transformace (HHT) je doplnnm Hilbertovy transformace o metodu EMD (Empirical Mode Decomposition), kter rozkld vchoz data na sadu funkc - vnitn modln funkce (Intrisic Mode Function - IMF) a vznamn tak roziuje monosti pouit na analzu irokho spektra nelinernch a nestacionrnch signl. Tento lnek se zamuje na monosti analzy dat glykemickch profil pomoc HHT. Mechanismus ovlivovn glykemie v lidskm tle je stejn jako vtina biologickch proces natolik komplexn, e jej nelze povaovat za linern ani stacionrn. Proto byla zvolena pro analzu prv metoda HHT. Abstract: Hilbert-Huang Transform (HHT) complements Hilbert Transform by EMD method (Empirical Mode Decomposition). EMD decomposes original data to function series IMF (Intrinsic Mode Function) and this significantly extends possibilities of use on wide spectra of nonlinear and nonstationary signals analysis. This paper targets the analyse of blood glucose profiles possibilities by HHT. Mechanism of blood glucose interaction in human body is very compound event like most of biological processes. So it cant be thought to be neither linear nor stationary. Thats why HHT method was selected for this analyse.

1. Shortly about HHT

In signal analysis branch we usually use some integral transforms or more precisely their discreet forms. Fourier Transform, Laplace Transform, Hilbert Transform, wavelet transform and other belong to the most important integral transforms. The Fourier spectral analysis is based on transforming the function (or signal) from time domain to frequency domain. So we obtain frequency spectra. We think over the supposal that every signal can be implied as superposition of infinite number of sine signals its Fourier progression. Fourier Transform is simple and it is successfully used for a long time with success for linear and stationary signals. There are also techniques how to extend possibilities on non-stationary data i.e. window technique but there is still the requirement on stationarity inside the window which we usually cannot guarantee. HHT is a new method for data analysis and it is applicable for nonlinear and non-stationary signals. It is Hilbert Transform extension with EMD method, which decomposes original data into series of functions called IMF (Intrinsic Mode Functions). After that Hilbert Transform is applicable for these components. These components fulfill two basic conditions (which are required but are not always sufficient): 1) In the whole data set the number of local extrema and the number of zero crossing must either equal or differ at most by one. 2) The mean value of the envelope defined by the local maxima and the envelope defined by the local minima is zero (or enough small).

Hilbert Transform theory H { f (t )} = 1

f ( ) d t

(1.1)

The equation (1.1) defines Hilbert transform. P is Cauchy principal value. Thanks to this it is possible to compute integral with points of singularity. Definition 1.1 [5]: Let [ , ] be a real interval and let f be a complex-valued function defined on [ , ] . If f is unbounded near an interior point of [ , ] , the integral of f over [ , ] does not always exist. However, the two limits (1.2) and (1.3)

lim
0

f ( x)dx

(1.2) (1.3)

lim
0

f ( x)dx

still may exist, and if they do their sum is called the improper integral of f over [ , ] and is denoted by the ordinary integration symbol (1.4).

f ( x)dx

(1.4)

Even if these two limits (1.2) and (1.3) do not exist, it may happen that the symmetric limit (1.5) exists.
lim+ f ( x)dx + f ( x)dx 0 +

(1.5)

If it does, it is called the principal value integral of f from to and is denoted by the symbol (1.6)
P f ( x)dx
a b

(1.6)

2. Blood glucose profile

Blood glucose profile is an examination which monitors blood glucose level. It is instrumental in following diabetes mellitus affection. Diabetics can monitor blood glucose level every day by personal blood glucose meters. It is measured every morning and then randomly during the day when diabetic feels tired, when has suspect to hypoglycaemia (too low blood glucose level) or has suspect to hyperglycaemia (too high blood glucose level) or before activities with heightened physical effort. Furthermore it is recommended to measure approximately

one day in a week in periodical intervals to make so-called big blood glucose profile. Treatment for diabetes mellitus is based on holding blood glucose level in normal range or on prevention of its big variation [2]. Blood glucose level depends on many factors: on food intake, on physical activity (it implicates decrease of blood glucose level), on brain-fag (with increased epinephrinaemia blood glucose level goes up) etc. After eating blood glucose level increases. Healthy human body responds by increased production of insulin. Diabetics control blood glucose variation by diet, by medicines or syringe application of insulin [2]. This paper targets the blood glucose profile of type 1 diabetics. Type 1 diabetes (dependent on insulin) originates by Beta-cells damage (cells of pancreas, where insulin is created) by auto-immune process [3].

2.1 Blood glucose profile analysis

It is necessary to have enough long data set for math analysis of these profiles. Unfortunately data from diabetics personal blood glucose meters doesnt satisfy this condition. In the Czech Republic diabetics can measure glucose level at most forth a day. It is caused by insufficient number of sensor strips defrayable by health insurance companies. Continuous glucose monitoring system is indeed used today, but very rarely (thanks to price of sensors 1500 K/3-5 days). Nevertheless data from these monitoring systems are at disposal. They store blood glucose level every 5 minutes. Continuous glucose monitoring systems sensor consists of thin electrode with thin layer of glucose oxidase under biocompatible membrane. It continually transmits imperceptible glucose quantity contained in intercellular humour (liquid) in patients hypodermis to electric signal whose size is equal to present glucose quantity. Monitor receives every 10 seconds electric signal from sensor and every 5 minutes it saves to the memory an averaged value of glucose concentration, so it is 288 values a day [4].

Fig. 2.1: Continuous glucose monitoring system

There is shown an example of continuous glucose monitoring system in figure 2.1: 1) Measuring electrode patient has it placed in hypodermis for 3-5 days. Measuring electrode (sensor) periodically sends the information about generated amperage and voltage to the monitor. 2) Transmitter it is connected by short wire with measuring electrode and it is attached to skin by a special plaster. Transmitter broadcasts by radio waves every 5 minutes information about glucose concentration to the monitor. 3) Monitor it records measured values and shows its 5 minutes averages on the display. This number of data already enables applying of HHT analysis. Using of this method is justified by clear and explicit complicated mechanism of blood glucose interaction and regulation in human body. So this data profile surely doesnt fall into the stationary neither linear processes class.

3. Application of HHT to the data of blood glucose profile

Before it is possible to apply HHT method on the data it is necessary to modify original data. There are vacancies in original data. Small vacancies (in order 3 points are missing) we can replace by interpolated points. Unfortunately it isnt possible to replace bigger vacancies because it isnt possible to establish how the blood glucose will change in about two hours interval. In figure 3.1 you can see one of these vacancies. This vacancy endures about 2,5 hours. These vacancies are usually caused by changing sensor or batteries in monitor.

Fig. 3. 1: Seven days blood glucose profile of type 1 diabetic. Curve disconnection is caused by sensor changing.

HHT method was applied on the first part of this data (see figure 3.2):
18

16

Blood glucose [mml/l]

14

12

10

100

200

300

400

500

600

700

800

900

1000

t [5 min]

Fig. 3.2: First part of glucose data HHT Method will be applied on this data
There are IMF components of original data in figure 3.3. Certain patterns can be seen in this figure. Periodically repeated oscillations are already evident in the first IMF component. This oscillations are changed to alone waves in the following components. This phenomenon would be interpreted as an application of insulin in these intervals together with food intake. But if we look in figure again and more detailed we can uncover that this oscillations are repeated in about 17 hours intervals. It isnt periodical application of insulin flow from this. So this phenomenon is caused by some else mechanism. Unfortunately I obtained this data without any more information about patients life and thats why it is very difficult to deduce what could cause these oscillations.

Fig. 3.3: IMF components

Now it is possible to apply Hilbert Transform on these IMF components. The result can be seen in figure 3.4. There is a frequency spectrum of IMF 2 and IMF 3 components from the previous figure. There are negative frequencies, which have no physical meaning and are caused by very quick changes of amplitude. This problem can be well treated by using of data normalization. It is a signal transform to the modality with constant amplitude of 1. Process is as following: 1) Make absolute value of signal. 2) Count up an envelope defined by local maxima. 3) Divide absolute signal by this envelope. If the information about amplitude is important for us, we have to include properties of envelope to the result.
4

IMF 2
f(t)

2 0 -2 -4 2

100

200

300

400

500

600

700

800

900

1000

IMF 3
1

f(t)

0 -1

-2

100

200

300

400

t [5 min]

500

600

700

800

900

1000

Fig. 3.4: Frequency spektra of IMF 2 and IMF 3

1 0 -1 4 2 0 -2 2 0 -2 0 2 0 -2 0 2 0 -2 0 2 0 -2 0 2 0 -2 0 100 200 300 400 500 600 700 800 900 1000 100 200 300 400 500 600 700 800 900 1000 100 200 300 400 500 600 700 800 900 1000 100 200 300 400 500 600 700 800 900 1000 100 200 300 400 500 600 700 800 900 1000 0 100 200 300 400 500 t [5 min] 600 700 800 900 1000 0 100 200 300 400 500 600 700 800 900 1000

Blood glucose [mmol/l]

t [5 min]

Fig. 3.5: Normalised IMF components

IMF 2

f(t)
0 -1 -2 0 2 100 200 300 400 500 600 700 800 900 1000

IMF 3
1.5

f(t)

0.5

100

200

300

400

500

600

700

800

900

1000

t [5 min]

Fig. 3.6: Frequency spektra of normalised IMF 2 and IMF 3

There are normalized IMF components in figure 3.5 and there are frequency spectra of some of these components in figure 3.6. Negative frequencies were eliminated. Especially in IMF 3 spectrum there are higher frequencies seen in periodical intervals. These peaks correspond to oscillations as discussed above.

4. Conclusion:
Experiments with data of blood glucose profile data decomposed by EMD and further analyzed by Hilbert Transform show a chance for usage of this method for better understanding of this complicated process. Range of made experiments isnt enough for deducing clinical conclusions so far but from the technical point of view HHT is applicable for glucose profile analysis . For following research would be eligible to cooperate with diabetics, which use continuous blood glucose monitoring system to enable better data interpretation.

5. References:
[1] N.E. Huang, Z. Shen, S.R. Long, M.L. Wu, H.H. Shih, Q. Zheng, N.C. Yen, C.C. Tung and H.H. Liu: The empirical mode decomposition and Hilbert spectrum for nonlinear and nonstationary time series analysis, Proc. Roy. Soc. London A, Vol. 454, pp. 903995, 1998.
https://www.zdravcentra.cz/index.php?act=bq-31&aid=1&oid=123&OFF=30&DIR=&ORD=, 15.1.2007

[2]

[3] [4] [5]

http://prodia.milackove.net/clanek/co-je-vlastne-cukrovka, 15.1.2007 http://www.minimed.cz/senzory.php, 15.1.2007 M. Johansson: The Hilbert Transform, Master thesis, Vxjo University, Schweden