Implementation of digital optical capillaroscopy for quantifying and

estimating the microvascular abnormalities in diabetes mellitus

Yu.I. Gurfinkel, O.V. Suchkova, M.L. Sasonko Research Clinical Center of JSC “Russian Railways”, Moscow, Russia

A.V. Priezzhev Lomonosov Moscow State University, Moscow, Russia

V.M.Volkov, N.B.Margaryants

ITMO University, St. Petersburg, Russia

Saratov, Russia 2015

1

Diabetes mellitus (DM) affects approximately 387 million

persons worldwide and is expected to dramatically rise in

both industrially developed and developing countries in the

next decades (www.idf.org/diabetesatlas, 2014).

Diabetic patients have higher susceptibility than nondiabetic

individuals to develop major cardiovascular events, such as

myocardial infarction, stroke, and cardiovascular death,

because of an inability of the vascular systems to adequately

perfuse tissues and organs relative to their metabolic demand

(Levitan, et al. 2004).

Diabetes mellitus, whether insulin dependent or

not, is associated with increased prevalence of

macro- and microangiopathy (Bolinger and Fagrel, 1991).

2

3

This study was aimed to define the extent of digital capillaroscopy possibilities for the quantification and estimation of the level of

microvascular abnormalities in diabetes mellitus

4

Participants and method

A total of 196 adult persons were examined in the study.

The first group consisted of 52 patients with compensated DM, the level of glycated hemoglobin (HbA1c) was 6.3 ± 0.5 %.

The second group included 68 patients without compensation of DM (HbA1c 9.4 ± 1.7 %).

The group of volunteers (n = 76) included healthy adults with normal blood glucose and without signs of cardiovascular pathology.

5

Microcirculation study

The capillary circulation in all participants of the study group was examined with the nail-bed using the digital optical capillaroscope developed by the company "AET", Russia. This instrument is equipped with a sophisticated image-processing program allowing for quantifying the diameters of the arterial and venous segments of the capillaries and their ratio (coefficient of remodeling), perivascular zone size, capillary blood velocity, the degree of arterial loops narrowing and the density of the capillary network. Also we estimated the relative amount of coil-shaped capillaries.

6

Clinical characteristic of participants (n=196)

Parameters

Healthy volunteers

(n = 76)

Compensated diabetes

(n = 52)

Decompensated diabetes

(n = 68)

Age, years 52.2 ± 8.7 52.8 ± 8.7 52.8 ± 8.1

Duration, years ---- 4.9 ± 4.2 5.7 ± 5.7

HBA1C, % 5.3 ± 0.5 6.3 ± 0.5* 9.4 ± 1.7*

Male/Female 31/45 21/31 26/42

BMI, kg/m2 25.8 ± 2.7 32.4 ± 6.4* 33.5 ± 6.2*

Systolic BP, mm Hg 115,1±10,9 124,5±15,4* 132,4±18,6*/**

Diastolic BP, mm Hg 70,0±8,1 75,9±11,0* 79,4±11,6*

Pulse, beats/ min 67,4±8,1 73,7±10,7* 76,6±11,2*

7

Note: HBA1C, %- glycated hemoglobin; BMI- Body mass index; Male/Female - Gender, number;

Duration- duration of diabetes, years. Comparison was conducted between pairs: healthy volunteers group and 1-st group, healthy volunteers group

and 2-nd group.

Microscope + CMOS

camera up to 200 frame/sec

Computer + original

software

9

10

Details of data processing

1) Image sequence stabilization -compensation of frame shifts (dx,dy,da)

- high precision stabilization with multiple base frames

2) Capillaries detection -edges detection

-blood flow velocity estimation

-capillary lines detection

-capillary radius detection

3) Local parameters of blood flow recovery -local blood flow detection at points of capillary lines

11

Image sequence stabilization (initial stabilization with dx,dy correction)

Frame shifts )1,1()2,2( dxdydxdy nn of frame n from the base frame n0, are calculated

by:

1

0

1

0

1

0

1

0

2

1,1,,,0

))1,..,0)1(()1,..,0)1(((,0

)1,..,0)1(()1,..,0)1((,1

))1,..,0)1(()1,..,0)1(((,0

)1,..,0)1(()1,..,0)1((,)(

:)1,1(Y

y

X

x

Y

y

X

x

dxxdyynxyn

XdxxYdyy

XdxxYdyy

XdxxYdyy

XdxxYdyyAA

dxdy

1

0

1

0

1

0

1

0

2

,,,,0

,..,,..,

))1,..,0)(()1,..,0)(((,0

)1,..,0)(()1,..,0)((,1

))1,..,0)(()1,..,0)1(((,0

)1,..,0)(()1,..,0)((,)(

minY

y

X

x

Y

y

X

x

dxxdyynxyn

mdmddxmdmddy

XdxxYdyy

XdxxYdyy

XdxxYdyy

XdxxYdyyAA

,

where 1,..,0 Nn , md is the maximum of frame sequence xynA ,, shift.

12

Image sequence stabilization (advanced stabilization with dx,dy,da correction, 10 base frames)

13

Before stabilization Data preprocessing compensated

low-frequency (background) and

high frequency (noise matrix

camera) components and improve

the contrast of the capillaries.

Final stage of stabilization

Capillary blood velocity estimation

Averaged

capillary blood

velocity (pix/frame)

(fram

es)

Local capillary blood velocity (pix/frame)

Capillary radius (pix)

Capillary area (pix^2)/30

Capillary line

points (num)

Capillary line points (num)

Capillary line and markers

14

m1,m2 – borders of

arterial segment m3,m4 – borders of

venous segment

m1 m2 m3 m4

Local capillary blood velocity estimation (contrasted capillaries, capillary lines, markers, capillary blood velocity)

15

Comparative microcirculation parameters of participants (n=196)

Parameters

Healthy volunteers

(n = 76)

Compensated diabetes

(n = 52)

Decompensated diabetes

(n = 68)

PZ size, µm 101.3 ± 15.2 105.2 ± 12.6 110.1 ± 16.5*

Arterial diameter, µm 8.5 ± 2.0 8.4 ± 2.0 7.5 ± 1.5 */**

Apex diameter, µm 14.7 ± 3.4 14.9 ± 3.4 14.6 ± 3.9

Venous diameter, µm 11.3 ± 2.3 12.2 ± 2.9* 12.4 ± 2.7*

Remodeling coefficient 1.36 ± 0.14 1.47 ± 0.22* 1.63 ± 0.19*/**

Coiling, аrbitrary units 1.49 ± 1.39 1.96 ± 0.74* 2.08 ± 0.65*

Density, аrbitrary units 2.19 ± 0.62 1.84 ± 0.76* 1.96 ± 0.68*/**

Polymorphism, аrbitrary units 1.59 ± 0.69 2.02 ± 0.76* 2.03 ± 0.6*

16

Note: *- statistical significance of the estimated parameter was obtained while comparison of the diabetes group with the group of volunteers,

with adjustment for multiple comparisons; **- statistical significance of the estimated parameter was obtained while comparison between both

diabetes group, with adjustment for multiple comparisons;

PZ size - perivascular zone size, Arterial diameter - diameter of arterial segment; Apex diameter - diameter of apex segment; Venous

diameter - diameter of venous segment; Remodeling coefficient - ratio of capillary venous segment diameters to arterial segment

diameters, Coiling - degree of capillaries coiling; Density - density of the capillary network; Polymorphism - capillary polymorphism;

17

Comparison remodeling factor and capillary

blood velocity (CBV) in studied groups

Results The study revealed significant difference in the capillary density but not in the capillary density between the patients with compensated and decompensated DM.

The number of coil-shaped capillaries differed greatly in patients healthy subjects as compared to the DM patients, capillary network of diabetic patients had signs of polymorphism significantly more than in healthy subjects.

In DM patients the significant narrowing of the arterial segments and dilatation of the venous segments of capillaries have led to increase the coefficient of remodeling in comparison with non-diabetic individuals.

The study revealed a reduction in capillary blood velocity in patients with diabetes compared to healthy volunteers.

18

Conclusions

Thus, the digital optical capillaroscopy equipped with the state-of-the-art image-processing algorithm opens up new possibilities for obtaining clinically important information on microvascular abnormalities in patients suffering from diabetes mellitus.

Acknowledgment. The investigation was partially supported by the Russian Scientific Foundation grant № 14-15-00602.

19