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6th Internet World Congress for Biomedical Sciences

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Making of virtual skin tumor

Eiichi Yagi(1)
(1)Akita Red Cross Hospital - Akita. Japan

[ABSTRACT] [INTRODUCTION] [MATERIALS & METHODS] [RESULTS] [EXAMINATION OF THE DIMENSION ON HISTOPATHOLOGY OF SKIN DISEASES] [CONCLUSION] [REFERENCE] [Discussion Board]
ABSTRACT Previous: Linear Focal Elastosis: a case report Previous: MCS - MAKING MEDICAL APPOINTMENT SYSTEM AND SERVICES MATERIALS & METHODS
[Dermatology]
Next: PREPARATION OF A 5% FLURBIPROFEN HYDROGEL: 
Pharmaceutical aspects
[Health Informatics]
Next: ACQUISITION AND ANALYSIS OF RR TEMPORAL SERIES FROM HOLTER RECORDINGS

INTRODUCTION Top Page

The virtual epidermal cells on the screen (in the computer memory) were multiplied with changing the various kinds of parameter in these cells, and the morphological change of the total structure after growth was examined.

MATERIALS & METHODS Top Page

Hardware and soft ware: PC-AT compatible computer AMD K2-450 (RAM 256MB)
video RAM 16M, Windows 98,
Visual Basic 5.0 (Microsoft)
( All programs were written by Eiichi Yagi MD)

Virtual cells multiply as a kind of celler automaton algorithm. (Fig. 1)
1- distance of all cells from initial the dividing cell is measured.
2- new cell keeps 1dot from the dividing cell.
3- extract the nearest cell that overlapped with the dividing cell.
4- these cells are supposed to be a ball, then the direction of the move is calculated.
5- the position of cells is corrected not to be overlapped.
6- the cells that overlapped with this cell are computed, and process 4 is done with all cells that are extracted.
7- return to process 2, and the work has been done until all cells are completely divided.
The form of virtual epidermis changes with regulating the selection probability, the mitosis probability, the radius and division direction.

Refer code for execution

Figure 1

Celler automaton
This is an automatic proliferation model devised by Neumann. Unit automaton that is arranged on the plane like a cell changes its internal state only according to the condition of self and its vicinity, so the movement of all units automatically determines the movement of the whole system.

Setting of the parameter and the function of the individual virtual cell
X-coordinate, Y-coordinate, radius, a longer axis, a division tendency, display of division direction, on basal layer or not, Xb of cell (growth factor), Yb of cell (inhibitory growth factor), a history of the successive division which depended on concentration, initial width, initial height, cell number, basal layer - x,y, granular layer - x,y, distance to the horny layer, division frequency, a size difference of a cell in division, division angle after division, division frequency with the same range, division arrest after successive division, elasticity on the horny layer, elimination frequency on the horny layer, elimination frequency on theh horny layer (altitude is not related), How many horny layers is torn off?, only basal cell is divided, probability that high concentration induced the division on the basal layer, ratio of diffusion rate of Xb and Yb, increse of Xb substance synthesis, decrease of Xb substance synthesis, division direction on the basal layer - level, verticality, angle
Random control for each parameter -- another 10-15 parameters are required.
Functions for the internal processing in proliferation -- another 10-15 functions are required.


Application of Turing method 1)
Two substances of P and Q are supposed. P promotes the synthesis of P and Q with the concentration of P. In the location where the concentration of P is high, the synthesis of Q and P is high. Q is supposed to be inhibitor of P synthesis. If concentration of Q is high, the synthesis of P is repressed. P and Q spread through circumference by the diffusion, and the diffusion velocity of Q is assumed to be larger than the diffusion velocity of P. This is Turing method. When the parameter of the reaction and diffusion are selected properly, the condition of system is stabilized in the repetition pattern of wavy shape, even if it begins from any kind of initial condition. Method of Turing is embedding in virtual cell. When substance X and Y spread, the probability of division is set to be influenced by this factor (X, Y). The shift of the cell growth position and the alteration of rete ridge were examined. When the virtual growth factor (virtual inflammation substance) is distributed to individual cells with various kinds of probability in a certain range, the dilatation of multiplied cells, which means the form of exanthema, was examined.

RESULTS Top Page

Simple growth

Figure 2

When the growth rate of surroundings cells selected for growth was increased, the rete ridge like structure of was made (Fig. 2). Rete ridge seemed to be longer when the division probability of the basal layer increased.

Applied case of growth
P (growth factor) and Q (Inhibition factor) were put in cells according to Turing method. Concentration (P) was displayed by the darkness of cell when R (diffusion rate) was regulated appropriately. The cells, which were with high concentration and near to basal layer, were divided with precedence.

Figure 3



By setting of coefficients, P (growth factor) was arranged in layered formation. Virtual epidermis tends to thicken according to the increase of P (Fig 3). P was able to move toward outside by another coefficient setting. Dilatation speed of eruption was controlled with the balance of P, Q and R.


Figure 4 shows virtual eruption looked from upward. Proliferating ability is high in the part of white. An early difference of proliferation power was reinforced with the setting of factor P, Q and R, and a proliferation area (group) was rapidly enlarged.

Figure 4

Cases of proliferation
The switch controlling the proliferation in the lower part of basal layer was set by P, Q factor and the division frequency. Then the structure as a hair root was made (Fig. 5).

Figure 5

A difference of cell size was set large, and a division position was set over the basal layer. It showed like atypicality in situ (in the epidermis)(Fig. 6). Fractal dimension of circumference borderline increases as the probability of difference of cell size rises.

Figure 6

When the division directionality and the adherence to circumference of virtual cell are regulated, a cyst-like structure is constructed (Fig. 7). Keratinization can be done from upward of the tumor. When the direction or speed of the initial keratinization is in a certain range, the structure may be destructed and absorbed immediately.

Figure 7

Cases of proliferation -- addition of horny and granular layer
Virtual granular layer (differentiation stage) is added (Fig. 8), and keratinization is occurred in random position. Virtual granule cells are shown as oval cells, and horny cells are shown as light blued oval cells.

Figure 8

Increase of keratinization tendency and difference of size are added (Fig. 9).

Figure 9

Addition of the randomized differentiation phase and the difference of size (Fig. 10)

Figure 10

Addition of virtual infiltrate cell (Fig. 11)
Similar structure as subcorneal abscess can be made by this option. Implantation of acceleration / inhibiting factor of proliferation in this cell is possible.

Figure 11

By using this growth model the relationship between the arrangement of cellular level and the mass/fractal dimension of structure and the configuration dimension of macro-construction can be examined. If z-axis is added to the functions, the extension to three-dimensional structure is possible. However, the computation time may become enormous.

EXAMINATION OF THE DIMENSION ON HISTOPATHOLOGY OF SKIN DISEASES Top Page

Image processing of histopathological data
Figure 12

These images were automatically made, and the dimensions were
simultaneously calculated by the system ( View1 1.1 made by E Yagi)

Making of time series data (making of 700-2000 vectors )
1)Distance between cells
a. Cell interval is sought when the marker is arranged in concentric circular from the center of the image.
b. All combinations of distance between all 2 cells are sought, and the cell number that two cells enter in the limited interval divided with equal length is counted.
c. Cells are plotted with a certain width lengthwise, and arranged in order from near side. Distance of all pairs is measured.
2)Size of nucleus, A length / area of circumference, Concentration difference of nucleus
Value is put away in order of coordinate, and nucleus is extracted by order of 1).

Specimens to examine histopathologically
normal skin, seborrheic keratosis 6 cases, actinic keratosis 8 cases, Bowen´s disease 6 cases, basal cell carcinoma 5 cases, squamous cell carcinoma 4 cases, Paget´s disease 4 cases, dermatofibroma 3 cases, hemangioma 4 cases, pigmented nevus 6 cases

The time series data made from distance between cells ( left oblong figure).
The attractor made from time series data (right figure)
Figure 13

k=8, m=6, 6 dimension

Lyapunov exponent
normal skin: 0.21 (0.16-0.27), seborrheic keratosis: 0.18(0.07-0.28), actinic keratosis: 0.16(0.13-0.24) Bowen disease: 0.17(0.14-0.195) basal cell cancer: 0.2(0.15-0.26) squamous cell carcinoma: 0.22 (0.2-0.22) Paget disease: dermatofibroma: 0.15(0.06-0.25) hemangioma: 0.25(0.23-0.27) pigmented nevus: 0.22(0.17-0.27)

Mean of correlation dimension
Distance between cells Size of nucleus A length / area of circumference Concentration difference of nucleus
normal skin 6.1 3.31 6.0 5.92
seborrheic keratosis 5.1 4.3 5.82 5.34
actinic keratosis 5.0 2.61 6.4 4.2
Bowen disease 5.0 1.42 6.75 4.02
squamous cell carcinoma 4.9 0.85 7.87 6.15
basal cell cancer 5.2 1.35 6.67 1.74
Paget disease 4.6 2.65 7.4 3.1
dermatofibroma 4.84 2.6 7.68 6.88
hemangioma 3.6 2.22 6.8 7.9
pigmented nevus 6.05 3.0 6.16 6.2


Analysis of simple fractal dimension of the circumference in virtual tumor
Simple fractal
dimension of
the circumference
in virtual tumor
Probability of the cell size change at one division of cell (0 to 0.9)

(This result was already presented Inabis98.)

In order to bring the character of virtual tumor close to the real tumor the coincidence of these dimensions is necessary. Coincidence within a small range may be possible, although a lot of computation process is necessary even in such accordance. If various kinds of algorithms (Genetic Algorithms, serious inquiry method etc.) are used and applied appropriately to choose the functions and coefficients, the examination of character with spreading of cells may be possible.

CONCLUSION Top Page

The unique characteristics of the total structure were given by changing the parameters and the functions of virtual cell, and the virtual eruption derived from dilatation tendency and the various kinds of form were made by the delicate and ideal balance control of parameters. This system of making virtual skin tumors may be useful as the apparatus, which investigates characteristic and relationship between macro and microstructure.

REFERENCE Top Page

  1. The molecular basis of morphogenesis, Turing A.M., Rhil. Trans. R. Soc. B237, 37-72


Discussion Board
Discussion Board

Any Comment to this presentation?

[ABSTRACT] [INTRODUCTION] [MATERIALS & METHODS] [RESULTS] [EXAMINATION OF THE DIMENSION ON HISTOPATHOLOGY OF SKIN DISEASES] [CONCLUSION] [REFERENCE] [Discussion Board]

ABSTRACT Previous: Linear Focal Elastosis: a case report Previous: MCS - MAKING MEDICAL APPOINTMENT SYSTEM AND SERVICES MATERIALS & METHODS
[Dermatology]
Next: PREPARATION OF A 5% FLURBIPROFEN HYDROGEL: 
Pharmaceutical aspects
[Health Informatics]
Next: ACQUISITION AND ANALYSIS OF RR TEMPORAL SERIES FROM HOLTER RECORDINGS
Eiichi Yagi
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Last update: 30/1/2000