RU2555397C1 - Method of estimating microvasculature condition - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: non-invasive examination of vessels is performed by means of a probe, installed on the skin surface in the projection of a vessel, by a method of optic coherent (OC) tomography, tomograms, obtained without compression test and OC tomograms under conditions of the compression test by the displacement of tissues by the probe by 1 mm towards the visualised vessel, are analysed. Compressibility of the vessel, tissues and formations and uniformity of the vessel configuration change under compression are estimated on the images. If a non-uniform and/or incomplete compressibility and a non-uniformity of the vessel configuration change are detected, microangiopathy is identified.

EFFECT: method ensures the high accuracy and objectivity of non-invasive diagnostics of the condition of microvasculature, in particular, the presence of intra-vascular formations, including differential diagnostics of vasculopathy due to the identification of particular criteria for the determination of pathological changes.

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Description

The invention relates to medicine, namely to methods and devices for medical examination of tubular organs, and can be used in cardiology, rheumatology, endocrinology, dermatovenerology and cardiovascular surgery to assess the state of blood vessels of the microvasculature in the diagnosis of microangiopathies.

The pathogenesis of many widespread, including socially significant diseases, accompanied by a high percentage of patients with disabilities and high mortality, is the pathology of distal blood vessels and impaired microcirculation [Smith M.M., Chen P.C., Li C.S., Ramanujam S., Cheung A.T., "Whole blood viscosity and microvascular abnormalities in Alzheimer′s Disease," Clin. Hemorheol. Microcirc. 2009. 41 (4), 229-239].

Microangiopathy is a generic term for lesions of small blood vessels (usually arterioles, capillaries, venules). Often has a systemic nature, for example, with arteriosclerosis, diabetes mellitus or systemic lupus erythematosus, and leads to damage to the kidneys, peripheral nervous system. Damage to cerebral arterioles with prolonged arterial hypertension (hypertensive cerebral microangiopathy) is the cause of hypertensive discirculatory encephalopathy and others. Thrombotic microangiopathy with thrombosis of arterioles and capillaries is observed with thrombocytopenic purpura.

It is proven that microcirculation changes reflect metabolic shifts, and monitoring these changes can help identify early signs of the disease [Weidlich K., Kroth J., Nussbaum C, Hiedl S., Bauer A., Christ F., Genzel-Boroviczeny O., " Changes in microcirculation as early markers for infection in preterm infants-an observational prospective study, "Pediatr. Res. 2009.66 (4), 461-465). Therefore, the visualization of the microvasculature is of key importance for the diagnosis of the initial, including preclinical, stages of the disease.

Biopsy followed by histological examination (The histological assessment of cutaneous vasculitis. Carlson JA. // Histopathology. 2010; Jan; 56 (l): 3-23) is considered the “gold standard” for diagnosing the condition of superficially located vessels. The main disadvantage of this method is its invasiveness. Conducted histological studies disrupt skin integrity, are associated with tissue ischemia and biopsy structure distortion, and increase the risk of hemorrhagic and infectious complications (Wahie S, Lawrence CM. Wound complications following diagnostic skin biopsies in dermatology inpatients // Arch Dermatol. 2007; 143 (10): 1267-71).

In experimental and clinical studies using methods of intravital imaging of superficially located vessels, in particular the vascular component of the skin.

A known method for assessing the state of blood vessels using magnetic resonance imaging (MPT) (Serup J. Origin and patterns of ultrasound reflections from the dermis // Zentrabl. Haut. Geschlechtskrankheiten. 1990; 157: 319).

However, the known method allows you to visualize blood vessels whose dimensions are 100 μm or more. An MRI scan is not possible in patients with implanted metallized or all-metal structures and claustrophobia.

For the prototype of the invention, a well-known method for assessing the state of blood vessels of the microvasculature is selected, including non-invasive examination of blood vessels using a sensor installed on the surface of the skin in the projection of the vessel, image acquisition and analysis (E. Pryadkina, Ultrasound scanning as a non-invasive method for diagnosing basal cell skin cancer / E.V. Pryadkina, O.R. Katunina // Bulletin of Dermatology and Venereology. 2009; 5: 63-67).

The known method is as follows.

The vessels of the microvasculature are examined using ultrasound scanning at a frequency of transmission of an echo signal of 10-20 MHz, which allows you to scan skin areas to a depth of 8-10 mm and provide images with a resolution of 20-70 microns and visualize objects located at different depths from ultrasound sensor.

The disadvantages of this method is the inability to verify blood vessels, sebaceous and sweat glands of the skin, which are displayed on the screen in the form of hypoechoic foci. Also, it is not possible to visualize the skin arterial branches of the 3rd order, with a diameter of 15 microns or less, and to verify the vascular branches of the 4th order, which are smaller (Yu.N. Koshevenko. Human skin. Volume 1. Structure, physiology and purpose of the functional elements of the skin organ person. - M.: “Medicine.” 2006, p. 116-125). Images obtained by ultrasound of the skin have a lower contrast, which complicates the visualization of the wall layers available for verification of vessels of small diameter, which reduces the accuracy of diagnosis.

The task of the invention is to increase the accuracy and objectivity of the evaluation method by providing verification of the lumen and structure of the vessel wall of the microvasculature with a diameter of about 100 microns.

The problem is solved in that in the known method for assessing the state of blood vessels of the microvasculature, including non-invasive examination of blood vessels using a sensor mounted on the surface of the skin in the projection of the vessel, obtaining and subsequent image analysis, the study is carried out using optical coherence tomography, analyze tomograms obtained without compression test and in the conditions of a compression test carried out by displacing the tissues with a probe by 1 mm in the direction of the imaged vessel, evaluate the compressibility of the vessel, tissues and formations and the uniformity of the change in the configuration of the vessel during compression and when uneven and / or incomplete compressibility and uneven changes in the configuration of the vessel are determined determine microangiopathy.

The present invention meets the criterion of "novelty", since the conducted patent information research did not reveal the sources of scientific, technical and patent information discrediting the novelty of the proposed method.

The present invention meets the criterion of "inventive step", because not identified technical solutions with significant features of the proposed method.

The prior art currently knows a method for assessing the condition of peripheral vessels (Kolsanov A.V. et al. Diagnostic capabilities of ultrasound when choosing a surgical correction method for chronic venous insufficiency of the lower extremities. Cardiology and cardiovascular surgery. 2011, v. 4, No. 6. S. 57-59). The known method includes conducting an ultrasound with a compression sample, which allows you to evaluate the biomechanical properties of the vascular wall. In the stage of decompensation and in a complicated form, tortuosity, uneven expansion, thickening, and an increase in the echogenicity of the walls of the main saphenous veins and their tributaries were noted. The main signs of post-thrombotic lesions of the veins were thickening, increased echogenicity of the walls of the veins, rigidity of the lumen of the veins (partial compressibility with compression by the sensor, etc.)

However, the known method is applicable only to vessels with a diameter of more than 1 mm.

Optical coherence tomography is known in the art as a high-resolution, non-invasive method for visualizing the structure of biological tissues, which allows obtaining information about the morphological structure of healthy and pathologically altered biological tissue in real time (RF patent No. 2148378, IPC АВВ 6/08, publ. From 10.05.2000) .

The basis for obtaining an OCT tomogram (OCT image) is based on a principle similar to ultrasound, using low-intensity light of the near infrared range as a probe radiation with a power that does not damage tissue. The OCT image is a two-dimensional cross-sectional image of a biological tissue to a depth of 1.5 mm, presented in a pseudo-color brown palette. The magnitude of the received signal in each image element (pixel) is characterized by brightness and color. Brighter (lighter) sections of the OCT image correspond to a higher intensity of the back-reflected radiation. The OCT image has the same orientation as the transverse histological section.

To date, the following criteria for evaluating an optical image (tomogram) are known.

1. The brightness of the tomographic palette in the image is determined by the level of backscattering of the signal. Direct communication - the higher the level of the tomographic signal, the higher the brightness of a given point in the image. Brightness can be high, moderate and low trust - a change (difference) in brightness at the interface of tissues (media). The greater the difference in brightness at the boundary of these areas, the greater the contrast.

2. Characteristics of the image border - sharp (unsharp), smooth (uneven, crimped), continuous (intermittent).

3. Inhomogeneity (optical heterogeneity) - an area (of any shape) with a signal brightness that differs from the background.

4. Structurality - the presence of areas (of any shape) with contrasting borders.

5. Layering is a specific variant of structurality, assuming the presence on the tomogram of several (usually two) contrasting horizontally oriented zones, which, according to the results of clinical-morphological comparison, are interpreted as different tissue layers.

6. The signal fading rate is the rate of brightness decrease with depth in a given area. The fading of the tomographic signal can be fast or slow.

In the proposed method, for the first time during the OCT study, a compression test is used, which contributed to the emergence of new OCT criteria:

1. The compressibility of tissues and formations - the ability of formations to change configuration when compressed by a sensor.

2. Compressibility uniformity - uniformity of vessel configuration changes during compression.

The proposed method is illustrated by the following graphic material.

In FIG. 1a shows a histological preparation; FIG. 1b presents a native optical coherent tomogram of a rabbit ear artery, indicated: 1 - adventitia; 2 - the lumen of the vessel; 3 - sex and media; 4 - "bed" of the vessel.

In FIG. Figure 2 shows an optical coherent tomogram of a rabbit ear artery during compression by a sensor: complete uniform compressibility of the vessel.

In FIG. 3a shows a histological preparation; FIG. 3b shows a compression optical coherence tomogram of a rabbit ear artery with subintimal cholesterol deposits, indicated: 5 - vessel wall; 6 - subintimal deposits of cholesterol, corresponding 7 - zone of the obstacle to uniform compression of the vessel.

In FIG. 4a shows the OCT of the vessels of the skin and adjacent tissues in normal: native optical coherence tomogram. In FIG. 4b shows a compression optical coherent tomogram.

In FIG. 5a shows OCT of blood vessels of the skin and adjacent tissues in case of atherosclerotic lesion of arteries and critical ischemia: native optical coherent tomogram. In FIG. 5b shows a compression optical coherent tomogram.

To carry out the study, the present invention uses a visualizer-topograph optically coherent computerized for non-invasive studies of the internal structure of human surface tissues "VOK". Registration certificate No. ФС 022а2005 / 2035-05 dated August 05, 2005. The company is a manufacturer of the Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod.

Specifications: radiation wavelength 1300 nm; radiation source power - 2 mW; power at the facility - 0.75 mW; spatial resolution - 15-20 microns, scanning depth - 1.5 mm; transverse scanning range - 1.8 mm; the time to obtain a two-dimensional image of 200 × 200 pixels in size is 1.5-2 seconds.

The device is equipped with a removable flexible probe with a microscanner, the outer diameter of which is 2.7 mm, to be processed between studies according to the protocol of endoscopic equipment. The dimensions of the device are 15 × 40 × 40 cm, weight 10 kg.

The technical result of the proposed method for assessing the state of blood vessels of the microvasculature is to increase the accuracy and objectivity of the diagnosis of microangiopathies, including developing on the background of the existing pathology of the great vessels. The method provides the possibility of non-invasive assessment of the presence and characteristics of the pathological condition of peripheral vessels (inflammation, thrombosis, sclerosis, calcification), as it allows you to verify vessels with a diameter of about 100 microns and conduct a functional compression test, which is crucial for the differential diagnosis of vasculopathies and the elimination of errors when choosing a method treatment of the patient, which is most relevant for multiple concomitant vascular pathology of various calibers.

The technical effect of the proposed method is confirmed by experimental, clinical, laboratory and instrumental studies.

The proposed method is as follows.

To obtain an image, a visualization-topograph optical-coherent computerized for non-invasive study of the internal structure of human superficial tissues “VOK” is used, registration certificate No. FS 022a2005 / 2035-05 dated August 05, 2005 (the manufacturer is the Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod). In the study, the end section of the probe under visual control is brought into direct contact with the skin area with the existing vessels of the microvasculature. The probe is fixed in a stable position perpendicular to the skin surface. From each plot, 2-3 repeating images are obtained, which are two-dimensional images of a transverse cut of the skin to a depth of 1.5 mm, displayed in a pseudocolor brown palette and having the same orientation as the transverse histological cut, with brighter (lighter) portions of images correspond to a greater intensity of backward reflected radiation. Next, each image is encoded and entered into the computer's memory; frames with technical artifacts are not taken into account in further analysis. When recording images, comments are recorded that include information about the time, method and plot of scanning and features of the clinical picture.

Then, compression OCT is performed on the same skin sites, for which they press the probe onto the skin with a surface shift of 1 mm in depth and evaluate the compressibility of the vessel, tissues and formations and the uniformity of the compressibility of the vessel during compression, that is, a change in the configuration and ratio of the layers of the vessel wall. Evaluation and interpretation of images is carried out using the following OCT criteria:

- Image brightness.

- Contrast image.

- Image layering.

- Delineation of layers and formations.

- Optical uniformity of layers and formations.

- Structurality of layers and formations.

- The rate of fading of the signal.

- Compressibility of the vessel, tissues and formations

- Compressibility uniformity - changes in vessel configuration during compression.

In the OCT image, the vessel is differentiated as the formation of an ellipsoidal shape in which zones of high and low signal intensity alternate: in the center of the formation there is a linear dark zone with a low signal intensity (clearance with shaped blood elements), surrounded by a lighter zone with a higher signal intensity ( intima and media), limited to a linear zone of low signal intensity (adventitia); the formation is surrounded by a bright zone of high signal intensity ("bed"). For the most complete diagnosis, an assessment is made of the condition of the tissues surrounding the vessel, the stratum corneum and the cellular layers of the epidermis, papillary and reticular dermis, skin appendages. Measure the height of the layers of the OCT image, as well as the thickness of the structures corresponding to the OCT layers of the vessel wall.

When the vessel wall is compressed in the direction perpendicular to the axis, the formation of an ellipsoidal shape, significantly elongated and symmetrical along the longitudinal axis, is represented on the OCT image, represented by a central zone with a high signal intensity (intima and media), surrounded by a linear zone of low signal intensity (adventitia). Incomplete compressibility or incompressibility (invariance of configuration) of the vascular wall is interpreted as a significant decrease in its elasticity (arteriosclerosis), incomplete compressibility or incompressibility (invariance of area or configuration) of the lumen - as the presence of intraluminal formation. In this case, uniform incomplete compressibility is considered a sign of a common process in the vessel wall (arteritis, fibrosis) or its lumen (occlusive thrombosis). Uneven compressibility i.e. the absence of the correct geometry of the OCT layers and the lack of their symmetry with respect to the longitudinal axis of the tomogram are regarded as a local lesion (atherosclerotic plaque, calcine, parietal thrombosis). With full compression and a uniform change in the configuration of the vessel during compression, the norm is diagnosed.

Specific examples of the method are given in the form of research protocols

Example 1

Object of study - rabbit ear artery. We performed OCT visualization of rabbit ear arteries and compression OCT.

To identify the components of the image, light microscopy of histological sections of the rabbit's ear was performed with an increase comparable to the size of the scanned area, since the resolution of the OCT is comparable to the lower boundary of the size of the cellular elements of the tissues (Fig. 1a).

With native OCT, the artery was visualized as an ellipsoid formation surrounded by a light zone of high signal intensity, in the center of which there was a linear dark zone with a low signal intensity, surrounded by a lighter zone with a high signal intensity, limited by a linear zone of low signal intensity; education (Fig. 1b).

When performing compression OCT, a change in the shape of the vessel was noted while maintaining the layer structure and symmetry against the background of significant elongation along the longitudinal axis (Fig. 2) —uniform compressibility of the vessel. Diagnosed with the norm.

Example 2

To simulate vascular pathology, the rabbit was fed food with a high cholesterol content, which led to the development of hypercholesterolemia and the formation of its deposits in the vessel walls.

Next, native and compression OCT visualization of rabbit ear arteries was performed.

To identify the components of the image, light microscopy of histological sections of the rabbit's ear was performed with an increase comparable to the size of the scanned area, since the resolution of the OCT is comparable to the lower boundary of the size of the cellular elements of the tissues (Fig. 3a).

When performing compression OCT, a change in the shape of the vessel, the absence of the correct geometry of the OCT layers and their symmetry with respect to the longitudinal axis of the tomogram were noted — uneven compressibility of the vessel (Fig. 3b). The pathology was diagnosed - the presence of an intravascular formation associated with the vessel wall - subintimal cholesterol deposits.

Example 3

Patient K., 53 years old. Routine inspection. No complaints. Anamnestic data on skin diseases, diabetes mellitus, other diseases of the endocrine, nervous and vascular systems are absent. On examination, the skin and visible mucous membranes of normal physiological color, free of rashes, normal skin turgor, pink dermographism. Sebaceous and sweat glands are not changed, appendages of the skin without signs of pathology.

The lower limbs are warm to the touch, sensitivity is preserved. Active and passive movements in all joints are performed in full. The veins of the feet are full, pulsation in the arteries is distinct in all segments of both lower extremities. The distance of painless walking is more than 1000 meters.

When conducting a general study of a blood test, a general urinalysis, or a biochemical blood test, no abnormalities were found.

Ultrasonic duplex angioscanning: the iliac, femoral, popliteal, tibial arteries are visualized, their course is smooth, the walls are not changed, the lumen is clear, the bloodstream is of the main type; iliac, femoral, popliteal, sural, large and small saphenous veins are visualized, are not dilated, compressible, blood flow is synchronized with breathing, reflux is absent.

When conducting a native OCT of the skin and underlying structures of the anterior surface of the lower leg without compression, an image of 1.71 mm deep was obtained (the depth of the useful signal is 0.9 mm), in which 5 optical layers are differentiated:

1 layer - a light thin homogeneous horizontally oriented zone, characterized by a high-intensity signal;

2 layer - a dark thin homogeneous horizontally oriented zone, characterized by a signal of lower intensity;

3 layer - light higher homogeneous horizontally oriented zone, characterized by a signal of high intensity;

4 layer - less light high heterogeneous horizontally oriented zone, characterized by a signal of medium intensity;

5 layer - a high dark inhomogeneous horizontally oriented zone located in the lower part of the image and characterized by a low-intensity signal, includes zones of minimal signal scattering, presented in the form of dark regions of round, oval and slit-like outlines.

The boundaries between the optical layers are clear, the horny (0.05 mm) cell (0.13 mm) layers of the epidermis are differentiated, the area of the dermoepidermal junction (0.09 mm). At the boundary of optical layers 4 and 5, there is an ellipsoidal formation, differentiated as an artery, in which zones of high and low signal intensity alternate: in the center of the formation there is a slit-like dark zone of low signal intensity, surrounded by a lighter zone of higher signal intensity, limited by a linear zone of low signal intensity; the formation is surrounded by a bright zone of high signal intensity. The distance from the upper boundary of the image to the center of the described formation is 0.29 mm, the outer vertical diameter of the formation is 0.44 mm, and the inner is 0.25 mm.

When conducting compression OCT, an image of 1.71 mm deep was obtained.

At the boundary of the 4th and 5th optical layers, a formation is visible, differentiated as an artery, but slit-like: in the center of the formation there is a light linear zone with a low signal intensity, limited by a dark linear zone of a higher signal intensity, the lumen of the vessel is not visualized. The distance from the upper border of the image to the center of the artery is 0.31 mm, the outer vertical diameter of the vessel is 0.11 mm, the inner is not measured due to compression of the vessel.

In FIG. Figure 4 shows the native (a) and compression (b) optical coherence tomograms of the arteries of the skin of the anterior surface of the middle third of the leg: the contours of the vessel are clear, the layers are visualized, the structure is not broken, the compressibility is complete and uniform against the background of a distinct compressibility of the surrounding tissues (a clear decrease in the size of the optical layers : stratum corneum - 0.05 mm, cell layers of the epidermis - 0.1 mm, zone of dermoepidermal junction - 0.08 mm, useful signal depth 0.84 mm), the surrounding tissue is structural, no pathology is revealed.

Example 4

Patient T., 89 years old. Complaints of numbness, cooling of the lower extremities, pain in them, more in the left foot and lower leg, when walking less than 100 m, at rest with the position of the limbs elevated relative to the level of the heart. Anamnestic data on diseases of the skin, endocrine and nervous systems are absent. On examination, the skin of the lower extremities is pale, on the feet it is stagnantly hyperemic and moderately cyanotic, free of rashes, there is slight peeling, skin turgor is reduced, pink dermographism. Sebaceous and sweat glands are not changed, appendages of the skin without signs of pathology.

Feet, lower legs are cool to the touch, sensitivity on the feet is reduced, more proximal - saved. Active and passive movements in all joints are performed in full. The veins of the feet are full, pulsation in the arteries of the feet is not determined. The pain-free distance is less than 100 meters.

Ultrasonic duplex angioscanning: occlusion of the left femoral artery, left posterior tibial artery and occlusion of the right popliteal artery, stenosis of the right femoral, left popliteal and left anterior tibial arteries. The femoral, popliteal, sural, large and small saphenous veins are not dilated, compressible, blood flow is synchronized with respiration, and there is no reflux.

Computed tomography with angiography of the arteries of the lower extremities: occlusion of the left femoral artery, left posterior tibial artery and occlusion of the right popliteal artery, pronounced diffuse atherocalcinosis of the main vessels, developed collateral network.

Diagnosed with atherosclerosis obliterans of lower limb arteries, occlusion of the left femoral artery, left posterior tibial artery and right popliteal artery. KHAN 3 tbsp. Critical lower limb ischemia.

When conducting a native OCT of the skin and the underlying structures of the anterior surface of the lower leg without compression, an image of 1.86 mm deep was obtained (the depth of the useful signal is 0.92 mm), in which 5 optical layers are differentiated:

1 layer - a light thin homogeneous horizontally oriented zone, characterized by a high-intensity signal;

2 layer - a dark thin homogeneous horizontally oriented zone, characterized by a signal of lower intensity;

3 layer - light higher heterogeneous horizontally oriented zone, characterized by a signal of greater intensity; 4 layer - less light high heterogeneous horizontally oriented zone, characterized by a signal of medium intensity;

5 layer - a high dark inhomogeneous horizontally oriented zone located in the lower part of the image and characterized by a low-intensity signal, includes zones of minimal signal scattering, presented in the form of dark regions of round, oval and slit-like outlines.

The boundaries between the optical layers are fuzzy, the horny (0.06 mm) and cellular (0.13 mm) layers of the epidermis are differentiated, the dermoepidermal connection zone (0.15 mm). In the lower part 5 of the optical layer there is an oval-shaped formation, differentiated as an artery, in which zones of high and low signal intensity alternate: in the center of the formation there is a linear dark zone of low signal intensity, surrounded by a lighter zone of higher signal intensity, the boundary between the layers of the artery wall fuzzy. The distance from the upper border of the image to the center of the artery is 0.66 mm, the outer vertical diameter of the vessel is 0.29 mm, and the inner is 0.09 mm.

During the compression OCT, an image of 1.92 mm deep was obtained (the depth of the useful signal is 0.92 mm).

In the lower part 5 of the optical layer there is an oval-shaped formation, differentiated as an artery, in which zones of high and low signal intensity alternate: in the center of the formation there is a linear dark zone of low signal intensity, surrounded by a lighter zone of higher signal intensity, the boundary between the layers of the artery wall fuzzy. The distance from the upper border of the image to the center of the artery is 0.49 mm, the outer vertical diameter of the vessel is 0.29 mm, the inner is 0.07 mm.

The study revealed uniform incompressibility of the vessel against the background of compressibility of the tissues. Arteriosclerosis is diagnosed.

In FIG. Figure 5 shows a native OCT image of the skin artery of the anterior surface of the middle third of the leg (a) and with skin compression by the sensor (b): the contours of the vessel are fuzzy, the layers are visualized, the structure is broken, the compressibility is complete and uniform, the surrounding tissues are weakly structural, when comparing the native and compression OK-tomograms showed a decrease in the size of horizontal optical layers while maintaining the vertical diameters of the artery: the stratum corneum 0.05 mm, the cell layers of the epidermis 0.11 mm, the area of the dermoepidermal joint 0.12 mm

Claims (1)

A method for assessing the state of blood vessels of the microvasculature, including non-invasive examination of blood vessels using a probe installed on the skin surface in the projection of the vessel, obtaining and analyzing the image, characterized in that the study is carried out by optical coherence (OK) tomography, analyze tomograms obtained without compression samples, and OK tomograms in a compression sample by displacing tissues with a probe 1 mm in the direction of the imaged vessel, evaluate the compressibility of the vessel, tissues and formations and uniformity of changes in vessel configuration during compression and when uneven and / or incomplete compressibility and uneven changes in vessel configuration are detected, microangiopathy is determined.

Images