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Up-To-Date View on Technologies for Evidence-Based Medicine in The Diag- nosis of The Cardiovascular System At The Macro-And Microlevels: The Pros and Cons in The Diagnosis of Arteries and Veins, Dysfunction and Arteriove- nous Imbalance In the Whole Vascular System and in Various Regional Vascu- lar Reservoirs

  • Institute of Mathematik of the National Academy of Sciences of Ukraine, Kyiv

Abstract and Figures

This monograph is devoted to a topical issue - applied angiology, the place of different diagnostic methods in the verification and objectification of vascular structural and functional disorders based on deep knowledge of authors - experts in applied hemodynamics, angiology, angiotherapy - Academician of the Ukrainian Academy of Technological Sciences, Professor, Doctor of Medical Science Ulyana Lushchyk and Professor, Doctor of Physical and Mathematical Sciences Viktor Novytsky and the team of scientists headed by them. Methods of objectification of the cardiovascular system, their advantages and limitations for certain segments of the cardiovascular system, their application in the visualization and monitoring of vascular changes at the macro- and microvascular levels are described in detail.
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Advances in Biochemistry & Applications in Medicine
Ulyana B Lushchyk1,3,*; Viktor V Novytskyy1; Ivanna I Legka1; Liudmyla Riabets1; Oleg P Kolomytchuk2;
Igor P Babii3; Nadiya G Lushchyk4
1VeritasResearch Center, Kyiv, Ukraine
2Institute of Mathematics of NAS of Ukraine, Kyiv, Ukraine
3Clinic of Vascular Innovations, Kyiv, Ukraine
4Medical center “Ukrainian medical innovations”, Ternopil, Ukraine
*Correspondence to: Ulyana B Lushchyk, Veritas Research Center, Kyiv, Ukraine
Up-To-Date View on Technologies for
Evidence-Based Medicine in The Diag-
nosis of The Cardiovascular System At
The Macro- And Microlevels: The Pros
and Cons in The Diagnosis of Arteries
and Veins, Dysfunction and Arteriove-
nous Imbalance In the Whole Vascular
System and in Various Regional Vascu-
lar Reservoirs
1. Introduction
It was the 20th year of the 21st century. CVD and oncopathology epidemics consistently
maintained leadership in mortality and disability in the Earth’s population. The emergence
of Covid-19 has become a challenge for all civilization, complicating the course of chronic
pathology, exacerbating the question of survival with additional provoking factors of systemic
microangiothrombopathy in lung tissue and vital organs. Therefore, in vivo visualization of
pathological vascular processes and understanding their role in the formation of blood supply
disorders in the entire cardiovascular system is becoming increasingly relevant and vital for
the survival of world civilization in the 2020 pandemic [1].
Keywords: Hemodynamics; Neoangiogenesis; Vascular Technology; Angiomarkers; Capillaroscopy; Microcirculation;
Evidence Medicine in Angiology; Arteriovenous Vascular Screening; Angiotherapy; Angiocorrection.
Part 1
Advances in Biochemistry & Applications in Medicine
who rst drew attention to the vascular system, many centuries has passed. Technological
progress of the 21st century - the Internet, digital technologies have made incredible - the
information ow per capita has grown tenfold, the natural need for mobility has been replaced
by the deep hypodynamia of the planet’s population - practically constant sitting with a
computer, notebook, I-pad, Smartphone etc. And only realization of the need to ght with
hypodynamia and spend time for motor activity moved conscious people into tness clubs.
In the age-related aspect cardiovascular disease has undergone a certain historical stage:
they rst debuted in older people and in the elderly - in the 60s-70s of the last century, in the
80s the CVD segment spread in 50-year-olds, in the early 90s - isolated cases of stroke in aged
30-40 and children, beginning of the 21st century - strokes in infants, children of preschool
and early school During the Covid-19 pandemic, another formidable factor arose - vascular
coagulopathy with the risk of thrombosis and a high risk of death from thromboembolism in
Covid-19 and in the early post-Covid-19 period.
The CVD statistics more often reects 2 factors:
1) Sudden critical vascular states and lack of current prophylactic diagnostics of cardiovascular
pathology at the preclinical stage of CVD development;
2) Eective treatment before the clinical picture of vascular decompensation - from sudden
death to thromboembolism, heart attack, stroke, thrombosis, haemorrhage.
All these critical conditions are menacing for a person, whose clinical picture develops
suddenly. However, such vascular disorders are formed for a long time, for some years. This is
a golden period when it is necessary to detect CVD at the level of pre-disease and to actively
eliminate pathological hemodynamic blocks and to carry out prophylactic treatment aimed
at correcting altered hemodynamic parameters in arterial,venous and capillary streams in the
integral cardiovascular system.
In this study we try to reveal the essence of cardiovascular and cerebrovascular
disorders based on knowledge of macro-micro-angiology, applied hemodynamics and many
hemodynamic indicators, which doctors usually pay no attention to.
Angiology as a science is relatively young; its age is about 35-40 years. However, thanks
to the advanced visualizing technical potential for blood ow and digital vascular innovative
technologies, the cardiovascular system has become available for research in vivo and non-
invasive. Since the cardiovascular system is a dynamic system with rapidly changing blood
ow parameters, the appearance of non-invasive dynamic diagnostic methods like ultrasound,
capillaroscopy has enabled to in vivo underlying live intimate life processes and vascular
functioning at the macro, peripheral, and at micro levels, to take a new look at the state of
Lushchyk UB
Advances in Biochemistry & Applications in Medicine
CVS, its structure and variants of branching.
Current technical and technological level of the CVS research has allowed the medicine,
biology and blood-related systems of the medical sciences, newly establish laws of blood
circulation, uids in the living organism, pathological or sanogeneous rearrangements in the
arterial and venous channels on the macro- and microvascular levels, mathematically and
experimentally to simulate various situations of angio-transformations in various diseases.
However, angiology as a science about the structure and function of the cardiovascular
system as a complex system of vascular tubes, where ows the non-Newtonian uid, or rather
the suspension of the formed blood elements, in the majority of them puts doctors in a dead end,
because it is another world that is dicult to understand. This requires profound knowledge of
biophysics, rheology, angioarchitectonics, modelling of complex systems, etc.
But for a doctor it’s important to get comprehensive and clear information to make the
right decisions. As CVS is the most dynamic in the human body, static diagnostic methods are
no longer sucient to reect dynamic changes. Therefore, in vivo imaging methods become
the most informative for practical medicine, as they enable to see all segments of CVS live,
observe and analyse dynamic changes in vascular reconstructions, structure transformations
and dysfunction of individual segments of arteries and / or veins, regional reservoirs, assess
the adequacy of drug eects on sanogenic or pathological reorganizations of CVS in the entire
closed tube system - vascular blood supply [3].
Therefore, technology and methodology for obtaining information on the state of the
cardiovascular system plays an extremely important role. In this study we decided to describe
modern diagnostic methodologies in order to cover each method of diagnosis, its advantages
and disadvantages and modern aspects of its application in diagnostic medicine and medical
Ideally, today a medical practitioner requires:
1. In-vivo diagnostics of cardiovascular changes with analytical interpretation as a
variant of applied angiology and clinical interpretation as an option for a correct understanding
of the possible clinical signs of those or other dyshemias.
2.The maximum possible avoidance of subjectivity in the interpretation of the obtained
images and condence in the reliability. Specicity and the informativeness of the clinical
ndings obtained in response to a request for a CVS study.
3.Reliable and clear support during the CVD treatment process as a reliable instrumental
monitoring of changes in CVS, to be sure of the correct treatment approach and the eectiveness
of treatment for adequate sanogenic changes in CVS.
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In process-management such approaches are called as combination of control
instrumental studies of CVS at certain intervals during treatment, depending on the severity of
the disbalance in CVS as a hemodynamically complex system.
Only the use of current control in the treatment process can allow predicting the outcome
of treatment, and mathematical modelling of various possible hemodynamic alterations allows
choosing the optimal route for vascular treatment - individual angiocorrection , angiotherapy
and / or angiosurgery [3].
Over the last 25 years we have been practicing such approach to CVD treatment, gradually
developing applied angiology as a science of the possibility of sanogenic transformation in
vessels’ structure (angio-transformations) in the process of reversal reconstruction of vascular
blood ow from pathology to norm.
The study deals with macro- and micro processes in the vascular system, which are
deeply and inextricably connected with each other and are important for visualization and
objectivation by means of medical technology and methodologies for obtaining images and
information from the human body in static (image) and dynamic (video) modes.
Macro-Angiology studies macro processes in vascular system - a section of knowledge
in applied angiology, which is associated with the structure of the main and peripheral vessels
of the arterial and venous channels, their angio architectonics, arteriovenous interaction in the
integral cardiovascular system as a model of the vascular blood ow, as well as changes in
hemodynamic parameters at dierent CVD at dierent stages - from pre-disease (preclinical
form of the disease signs, which is most often manifested in transformations at the level of the
vascular system and is preceded a disease in 5-7 years) to critical vascular conditions. With
the timely correction of vascular disorders at the stage of pre-disease and the restoration of the
structural and functional status of the vascular system, the development of pathological angio
-transformations can be stopped, thereby avoiding the possibility of the disease development
2. Terminology
2.1. The logic of the approach to terminology in angiology to describe the processes of
angiogenesis and vascularization
For easy perception of various terms in applied angiology, we propose physiological
processes named with simple terms.
Physiological vascular processes, but stimulated by the organism in response to
the problem (skin damage, bone fracture, etc.), angiogenesis and vascularization processes
aimed at temporarily localizing the vascular network in the projection of wounds, ulcers, and
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inammation are presented with a prex neo + term.
All pathological processes of angiogenesis, vascularization and pathological alterations
in the vascular channel are presented with a prex patho + term.
2.2. The most commonly used terms in angiology
Angiology is a science that studies the vascular bed in living organisms, its structure,
functions, and associated changes in the vascular blood ow and in the rheological properties
of the blood as suspensions of formed elements.
Macro-Micro-Angiology is a collection of generalized knowledge from various elds
of science (anatomy and physiology, topographic anatomy of the vascular bed, theoretical
and applied angiology, hemodynamics, uid physics and suspensions, uid mechanics and
suspensions, blood rheology, etc.), structured and analytically synchronized in a model of
vascular blood ow (hemoduct).
The term was proposed by Lushchyk U.B. and Novytskyy V.V. in 2005 [3].
Figure 1: Schematic image of the vascular system as a bloodduct in the human body.
Macro-Micro-Angiology as a scientic concept is created to form doctors and medical
sta, rehabilitation specialists with modern knowledge about features of the structure and
function of the integral cardiovascular system as the basic model of the vascular blood ow for
optimally convenient understanding of those complicated processes that occur in cardiovascular
diseases in general and in regional vascular diseases in particular.
Macro-Micro-Angiology is closely connected with the applied application of the laws of
hydro- and hemodynamics, blood rheology, clinical interpretation of the vascular visualization
results, and the adaptation of life-time dynamic vascular visualization technologies in vivo for
the reliable objectication of available vascular transformations, dierentiation of pathology
and norm in vascular disorders on expert-level, mathematical modeling of possible variants of
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vascular reconstructions both of pathological, and compensatory, sanogenic nature.
Such approach to the application of knowledge on Macro-Micro-Angiology helps
doctors better to understand the processes that occur in the vascular system and with the help
of modern vascular innovative technologies as evidence-based tools, to nd optimal solutions
for diagnosis, mathematical and experimental modeling, monitoring and successful treatment
of cardiovascular pathology.
For easy presentation of the material, we distinguish two sections of applied Macro-
Micro-Angiology, which are fundamentally dierent in nature: Macro-Angiology and Micro-
Micro-Angiology is a section of knowledge in applied angiology, which is associated with
the structure of the microcirculatory channel - arterioles, capillaries, venules and their function
at the microcirculatory level. The microcirculatory level is regarded as the microvascular level
of functioning of the integral cardiovascular system as a model of vascular blood ow.
Macro-Angiology is a section of knowledge in applied angiology, which is related to
the structure of the main and peripheral vessels of the arterial and venous channels, their
angioarchitectonics, arteriovenous interaction in the integral cardiovascular system as a model
of vascular blood ow, as well as changes in hemodynamic parameters with dierent CVDs in
dierent stages - from a predisease to critical vascular conditions.
A theory of vascular blood ow (vascular hemoduct) - a theoretical model of the
cardiovascular system with a prototype of the water pipeline, which allows to understand the
integral nature of the cardiovascular system. Proposed by Lushchyk U.B. and Novytskyy V.V.
in 2005 [3].
Angio architectonics is a structure of the vascular tree and various types of its branches
that are inherited and aect the change in the hemodynamic parameters of blood ow in the
regional reservoirs and can be as risk factors for the development of vascular pathology at
certain pathological calibers, branching types and branching angles of arteries and veins [4].
Angio-transformation is a change in the structure of the vascular bed at the micro-
and macrolevels as a result of hemodynamic alterations, which leads to the formation of a
pathological type of Angioarchitectonics with the inclusion of structurally modied capillaries
by an “oncocapillary” pattern in the structurally and functionally distorted hemodynamics
of the microcirculatory bed, the formation of intranatal immature capillary networks, and on
macro level - tortuosity, loop formation at the peripheral and major level of arteries, venous
phlebectasy, venular hyperemia and stasis [3].
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Physiological and pathological angiogenesis
Angiogenesis (neoangiogenesis) is a physiological process of development of the
vascular network, which is regarded as a variant of the norm in the process of formation of the
vascular network in the foetus and as a physiological process controlled by the body for the
development of new vessels and timely apoptosis of the old blood vessels in the process of
vital activity [5,6,7,8].
Physiological angiogenesis is a process of formation of new blood vessels in an organ
or tissue. Normally, the processes of angiogenesis occur in the body with moderate intensity
and are activated only in the regeneration of damaged tissues, sewerage of blood clots, the
elimination of foci of inammation, the appearance of scar and similar processes of recovery,
as well as in the growth and development of the organism [9,10,11,12].
Judah Folkman is a pioneer in the study of angiogenesis, who in 1970 published the
theory of onco-angiogenesis [7,8].
Pathoneoangiogenesis is a pathological process of formation of new vessels and
vascular networks uncontrolled by the organism and the impossibility of controlled destruction
(apoptosis) of old vessels [9,13,14].
2.3. Physiological and Pathological Neovascularization
Physiological neovascularization is a physiological, controlled by the organism, process
of development of vessels and the formation of the vascular bed locally at the injured area, or
globally in the development of an embryo, growth of an infant.
Ophthalmology distinguishes corneal neovascularization and choroidal
neovascularization [11,12].
Pathological neovascularization (pathoneovascularization) is a pathological
vasodilatation in places where they should not normally occur, or the emergence of new
vascular networks locally and their uncontrolled progressive growth [10,12,15,16,17].
2.4. Angiooncogenesis and pathoneoangio-oncogenesis
Onconeogenesis is a pathogenetic mechanism that triggers the formation of tumors
with possible malignancy. Today ethiopathogenesis has not been studied enough [7,8,18,19].
Pathoangio-oncogenesis (neoangio-oncogenesis) is a pathological uncontrolled
angio-transformation and neovascularization, which begins at the level of change in the
regular loop-shaped structure of the capillaries into the abnormal oncocapillary [19,20],
forms arteriolar vascular networks that are not characteristic for patients in adolescence and
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adulthood, and promotes the development of a tumor at the micro level [7,8]. Such networks
develop progressively and uncontrollably, grow in volume, do not dierentiate into peripheral
and major vessels, but only arterioles and venules expand in volume, arteriolar-venular shunts
for the formation of a vascular lace of a tumor and its growth with collateral type of blood
supply [18,21,22,23]. The term “pathoneoangio-oncogenesis” is proposed by U. B. Lushchyk
in 2017.
We intentionally use a term pathoneoangio-oncogenesis, but not oncoangiogenesis,
because we are convinced that the vascular channel and the uncontrolled process of
vascularization is a basis for tumor development and the background for the risk of tumor
Pathoneoangio-oncogenesis as a manifestation of pathological uncontrolled angiogenesis
with the formation of the vascular network for tumor growth. In tumor tissues, especially in
tissues of malignant tumors, angiogenesis proceeds constantly and very intensively. This is
probably one of the causes for the rapid growth of malignant tumors, since they are very well
supplied with blood and receive far more nutrients per unit mass of tumor than normal tissue,
thus robbing healthy tissues of the body. In addition, enhanced tumor angiogenesis is one of
the mechanisms of its rapid metastasis, since tumor cells have the ability to create metastasis
along the blood vessels (along the walls) or spread around the body with blood ow [7].
On the other hand, the anaerobic type of the metabolism [7,8,24] in the tumor and
the extremely rapid division of atypical cells receive additional “favourable” conditions
for the progression of the pathology under conditions of hypoxic-ischemic background for
pathoneoangio-oncogenesis in the stage of predisease. Recently there were publications on
the anity of vascular and oncopathology [25], diabetes and oncopathology [26]. Therefore,
in our study, we also tried to make certain correlations between cardiovascular disorders and
In patients with breast cancer, we observed the presence of a modied structure of the
capillaries in the nail bed of ngers homolaterally irrelevant lesion of the mammary gland.
2.5. Vascular innovations and vascular innovative technologies
Vascular innovations are up-to-date innovative approaches to diagnosis, modeling,
process and risk management in the treatment of CVD. Vascular innovations enable the
creation of unique diagnostic and monitoring tools for medical practice assistance, since they
combine technological complexes for obtaining images and information, as well as analytical
IT technologies for image processing, clinical interpretation of received images, with the
formation of an expert-level automated conclusion for minimization time for a clinician
to obtain detailed, reliable information and avoiding subjective inferences with minimal
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knowledge of the eld of applied hydrohemodynamics, Macro-Micro-Angiology, rheology
and clinical angiology [27].
Vascular innovative technologies is a set of modern vascular technologies that are
complex technological sets and combine technical, programmatic, analytical, archival and
methodical blocks for the purpose of obtaining images of the vascular bed at dierent levels of
the vascular blood ow, their calculations, analytical processing and the formation of expert-
level with a clinical interpretation of possible manifestations of vascular dyshemia. Vascular
innovative technologies minimize the work of a physician during the processing of primary
data to obtain an automated conclusion and a clinical interpretation of the existing pathology
in an understandable format [27].
2.6. New terms in the treatment of vascular disorders –angiocorrection and angiotherapy
With the advent of vascular innovative technologies - analytical technologies to assess
the change of many hemodynamic parameters (at least 35-50 parameters of blood ow
evaluation in arterial and venous vascular beds at macro- and microlevels), in contrast to the
estimation of generally accepted parameters of blood ow - volume and linear velocities of
blood ow, vascular diameter, there is a need for correction of these parameters by medicinal
means [3,28,29].
Therefore, new terms like angiosurgery and angiotherapy have been gradually introduced
into the life as a basis for restoring the permeability of the bloodstream and the possibility of
adequate blood supply to the organ [29].
Angiotherapy and angiocorrection are proposed by Lushchyk U.B. in 2004 and 2010
In turn, over time, there was a need to dierentiate the medicinal process of restoring
only hemodynamic parameters of the blood ow in the vascular bed - angiocorrection and
restoring the level of adequate blood supply for optimal organ function - angiotherapy.
Angiocorrection [3,29,31] is a process of correcting hemodynamic parameters at the
level of the main, peripheral and microcirculatory beds to restore adequate, physiological blood
supply for an organ or system that is responsible for the structure and hemodynamic parameters
of the age pattern of the arteriovenous balance and the corresponding structure of the regional
angioarchitectonics in one or another local vascular reservoir by drug or operational means.
Angiotherapy [3,19,29,31] is a process of restoring a decient blood supply for an
organ and / or organism in certain regional vascular reservoirs to the level of the age-old
physiological norm by applying a medicinal sanogenic eect on the logical redistribution of
blood volume in the vascular system in the organism, formation of blood supply adequate
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to the needs of the organism and the elimination of ischemic-hypoxic states at the level of
microcirculation locally in a separate organ and in the organism as a whole, avoiding formation
and use of the eect of the stealing syndrome at the interregional vascular level.
3. Diagnostic methods of the vascular system in applied Macro-Micro-Angiology
3.1. Historical viewpoint of the diagnostic methods of the human vascular system in vitro
and in vivo
For a long time, mankind has been searching for ways for objectivating of structures
and functions of the organism’s vascular system. Claudio Galen [1] established it and he was
actually the rst who assigned the presence of net of tubes for blood ow in the human organism
and started the pathomorphological investigations of the blood circulation system. Further
the pathomorphological diagnostics was supplemented by pathohistological investigations in
order to study structures of small vessels and structure of the vascular walls [32,33].
Despite of the high reliability of pathomorphological investigations the scientic search
is gradually displaced towards the intravital objectivating of vascular problems. Dierent
biophysical diagnostic eects are used in Macro-Micro-Angiology for this purpose such as
electrophysiological, laser, optical, radionuclide, x-ray and ultrasound.
In total, methods of the intravital investigation of the vascular system can be arranged
in the following directions of the Macro-Micro-Angiology:
• Assessment of the structure of the heart and vessels in whole closed cardio-
vascular system as a model of vascular blood ductus (hemoductus);
• Assessment of the functional activity of the heart as a pump for the moving of
blood in whole vascular blood ductus;
• Assessment of vessels’ functions as channels for the blood moving and blood
• Assessment of the perfusion in organs and tissues in the norm and at the pathologies
• Assessment of dierent types of the intravascular pressure in the vascular
• Assessment of the hemorheology of the blood, which are dierent from liquid
Today many instrumental research methods are used for dierentiation of the vascular
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pathology. They are divided into non-invasive (not changing the integrity of a dermal
integument of a patient) and invasive (provides piercing of the skin with further necessary
Modern trend in development of non-invasive diagnosing methods is in the gradual
reducing of application of the Roentgen generating and radiological methods (as a static
images of vascular system) comparing with the increasing of number of methods based on the
ultrasound and biophysical approaches (as a dynamical images of vascular system).
The essential advantage of diagnostic non-invasive methods is in possibility of their
harmless secondary application in order to receive structural and functional changes in dynamics
in the area of injury and adjacent sections. And it becomes possible to apply functional loads
and performance of pharmacological tests that is extremely important for selection of the
treating tactics.
Nowadays there is positive dynamics of reducing the number of invasive methods in
comparison with application of non-invasive one under condition of increasing of their self-
On the other hand, diagnostic methods of the vascular system can be grouped in
the following way concerning the nature of obtaining the information for Macro-Micro-
• Direct methods of visualization – represent the visual information about structural
changes connected with the pathological process;
• Indirect – represent information in the form of digital values of certain coecients
(parameters) known for researcher or in the form of graphs;
• Combined objectivates structural and functional changes, combine static and
dynamical images from the vascular system’s conditions [3,28].
Problems related with adequate assessment of the brain vascular system conditions
are closely indissolubly connected with assessment of the functional condition of the whole
hemodynamic system both in the systemic and in the regional levels.
Global research of the vascular pathology has been going on by means on the application
of the various modern diagnostic methods and analytical processing of the results obtained
from the research for the last time despite of the possibility of the local examination of the
pathology in a certain vessel.
An arsenal of the modern diagnostic equipment is rather manifold and is presented by
such methods of objectivating the vascular pathology, which were tested on the practice, as
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• Rheography (REG);
• Sphygmography;
• EchoCG;
• Optical and smart capillaroscopy;
• Radionuclide diagnostics;
• Angiography;
• Ultrasound diagnosing methods (colored angioscanning and dopplerography);
• Laser dopplerography;
• CT;
• MRI in the vascular mode (MRA);
• Perfusion MRI;
• Color-coding of the grey-scaled scanned MRA and USD- images etc.
Let’s describe in brief dierent methods of diagnostics, paying attention to their
advantages and disadvantages in the applied Macro-Micro-Angiology.
We believe that these information will be useful both for all doctors and medical specialist
for the better understanding of applied Macro-Micro-Angiologie’s technical potential.
3.2. Rheography
(from Greek rheo – ow, grapheo – describe)
Indirect non-invasive dynamic method.
The method is based on the biophysical principle of changes’ registration from the
electric resistance of tissues when the electric current of high frequency (20-40 kHz) and
week force (20 mA) through the examined area with the graphic registration of the pulsate
oscillations of the complex electric resistance.
Living tissue is considered as an electric conductor that has the ionic conductance.
Fluctuations of the electric resistance indirectly reect changes of the velocity and volume
of blood that ows in vessels. Pulsate uctuations of blood ow are registered in the form of
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curves of the synchronous uctuations of the electric resistance [34,35].
The investigating object disorder of the electric conductivity of an organ on the
background of changes in its blood lling.
Level of examination of the vascular system measuring the value of the regional
hemodynamics and peripheric circulation due to the analysis of rheograms by means of
assessment of the pulsate blood lling of various vascular reservoirs, arterial and venous tonus.
With the help of REG method it is possible to:
- assess the level of the regional hemodynamics and examine the peripheric
- dierentiate the complete and partial occlusion of arteries;
- determine the stroke and minute volume of the heart (rheocardiography);
- study the condition of the small circle of the blood circulation with dierent
injuries of the valve apparatus of the heart;
- study circulation in the brain;
- examine the internal hepatic hemodynamics and quantitatively assess the
rheograms of the liver using number of indexes (rheohepatography).
Data processing – quantitative – qualitative (graphical).
Figure 2: Rheograph (
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Rheographic curve reects hemodynamic uctuations that arise in organs and tissues
during the heart contractions and named as a rheovasogram.
The rheovasogram is an integral volumetric curve of all arteries and veins from the
examined area of the body or the whole organ (for example – liver, brain,lungs, heart, limbs).
Advantages of the method.
1. Long and continuous registration even of the slightest changes of circulation without
disturbances of the physiological conditions of the examined area.
2. Non-invasive, long hemodynamic observations.
3. Usage of the functional tests (with hyperventilation, with hypercapnia, with Nitro-glycerine,
with nicotine acid) enables to detect disorders in circulation, dierentiate functional vascular
changes from organic injuries of brain vessels.
4. Wide potential for hemodynamic investigation of vitally important organs and systems,
modern diagnostics of circulation disorders and prescription of the rational therapy.
5. The rheovasography is able to reect condition of whole regional vascular reservoir
(for example cerebral regional reservoir - rheoencephalography, liver regional reservoir–
rheohepathography, heart regional reservoir rheocardiography, lung regional reservoir
6. General conclusions about the arterial and venous links of the vascular system, which
circulation function is reected in one curve.
Disadvantages of the method.
1. Unspecic features for dierent diseases.
Figure 3: Rheovasogram. (ya)
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2. Circulation function is reected in one curve: it’s impossible to dierentiate arterial and
venous problems separately.
3. Thus, rheovasography is unable to observe ethiopathogenesis of vascular disorders, search
domination pathological segment in vascular dyshemia - like arterial or venous.
4. Resolving power of the method is limited by the level of diagnostics of decreasing of blood
lling in the vascular reservoir but not of the segment of a certain vessel.
5. This method might belong to the screening vascular methods and need clinical interpretation
database for medical practice.
Rheovasogram’s hemodynamic parameters:
Dierent amplitude and time characteristics are used for analysis of the rheographic
curves. They pay attention to the curve’s form because rheographic curves are deformed under
the pathology of the vascular system.
In more details we describe peculiar features of the interpretation of the graphic image
because the rheogram is extremely representative for assessment of many hemodynamic
parameters and further realization of processes of the vascular system’s functioning.
On the volumetric rheograms, which characterize changes of blood lling in the
examined organ or site of the tissue, the major, or systolic, curve is allocated (it corresponds
to the anacrotic phase of the pulsating wave) that rhythmically arises after every systole and
reects the inow of the arterial blood to the examined organ or tissue. The point a of the curve
corresponds to the start of the fast blood inow into the examined organ, the point xto the
maximum pick of the dierentiated curve and characterizes the maximum velocity of the fast
lling (Vmax, Ohm/s).
At the absence of the dierentiated rheogram the end of the period of the fast blood
lling and period of the slow blood lling are determined by the graphical method.
The size of the period, which includes the interval from the end point of the fast blood
lling up to the end of the systole, can be determined by the method [7] that enables to state
graphically the end of the systole. It is required to draw a straight line from the lower end. The
place of separation of the inection line by the rheographic curve corresponds to the end of
the systole; the indexes of the time relations are the following: duration of the anacrotic phase
of the rheographic curve that is determined from the beginning of the curve to the moment of
stating of the maximum amplitude; duration of the catacrotic phase of the rheographic curve
that is measured by the time interval from the top of the rheogram up to its end.
Generally, this method of Rheovasography is useful for rapid screening of some regional
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reservoir of the vascular system.
In case of pathological rheovasogram it is strongly recommend more deeply check-
up of whole vascular system at the all levels: heart, main and peripheral arteries and veins,
microcirculation level with the aim of searching all pathological features and pathologically
changed segments.
Only in such way it is possible to understand whole vascular disorders as a cause of vascular
dyshemia and manage it.
3.3. Sphygmography
(from Greek sgmo – pulse, grapheo – describe)
Sphygmography is a mechanocardiographic method of the dynamic recording in the
form of graphs and analysis of the arterial pulse that is caused by the pulsation of the arterial
wall during moving of the volumetric stroke of blood along the arterial link [36].
With every systole the pressure in arteries is increasing and there is an increase of the
transversal section of the vessel, then the vessel returns into the initial position. Whole this
cycle is called as the arterial pulse and its recording in dynamics – sphygmogram.
Figure 4: Sphygmograph(
The method is based on the application of the piezoelectric sensors.
The investigation object graphical representation of characteristics of the arterial pulse in
dynamics, determination of the time and velocity of the pulsating wave, which is spreading
from heart along the main and peripheral limb’s arteries of the elastic and muscular types.
Level of the vascular system investigation – there are distinguished sphygmograms of the
central pulse (major arteries) and peripheric pulse (smaller arterial vessels).
Data processing – quantitative – qualitative (graphical).
Advantages of the method.
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1. Long and continuous registration of the slightest changes in the velocity of the pulsating
wave spreading along arteries.
2. Non-invasiveness, possibility of observations in dynamics.
3. Easy investigating method.
4. Based on comparison between right and left side limbs’ parameters. Asymmetry more than
30% is evidential.
Disadvantages of the method.
1. Less application in practical medicine because requires the profound knowledge about
peculiar features of the pulsating wave spreading..
2. It is more analytic than diagnostic method.
3. This method also might belong to the screening vascular methods and need clinical
interpretation database for medical practice.
Sphygmogram’s hemodynamic parameters:
The synchronous registration with ECG and PCG the sphygmogram enables to analyse phases
of the heart cycle separately for the right and left ventricles. In most cases simultaneously
they put two and more piezosensors or make the synchronous recording from the electro- and
phonocardiograms. Graphics of curves, which are registered from the major and peripheric
vessels, is not similar.
Sphygmogram is similar to rheovasogram and contains ananaсrote, incisure, dicroticrise
and catacrote.
Figure 5: Arterial pulse wave propagation. (
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3.4. Photoplethysmography in assessment of elastic features and reactivity of peripheric
For the last decade the role of endothelium has been paid more attention regarding
increasing of cardiovascular diseases and methods are developing for detecting its dysfunction.
The endothelium secretes substances (vasodilatating and vasopressor), the balance
between them regulates the vascular tonus. In the concept of the cardiovascular continuum the
endothelium dysfunction is an initiating factor of the hypertonic and ischemic heart disease.
Its essence is in the fact that under the long inuence of the number of factors (risk CVD
factors) on the endothelium its reaction to the stimuli, which caused dilatation, appears to be
insucient or even vasopressed. The test with reactive hyperaemia is used as the endothelium-
dependable stimulus. The post-occlusive acceleration of the blood ow causes the increasing
of the strain of the shift on the endothelium of the artery in the brachium and forearm. This
strain of the shift is a stimulus for the endothelium to the production of the vasodilatating
factors that is followed by increasing of the diameter of the examined arteries. Assessment
of the blood ow and diameter of the brachial artery is made with the help of the ultrasound
dopplerography by the method proposed by Celermajer D., with the location of arteries above
or below the area of occlusion. Laser doppler owmetry is another method of determination
of the vasomotor function of the endothelium that enables to assess the degree of increasing of
the microcirculation during the test with the reactive hyperaemia [37].
Figure 6: Sphygmorgam (
Figure 7: Photoplethysmography. (
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Besides the endothelium dysfunction the stiness of large elastic arteries is paid more
attention as the prognostic factor of development of the cardiovascular complications and
independent factor of the mortality from the cardiovascular diseases. The elasticity of arteries
is assessed by the increasing of the velocity of spreading of the pulsating wave.
A planimetric analysis of the peripheric pulsating wave can be another method for
analysis of the transfer function of arteries with the help of the digital photoplethysmography
(PPG) [38,39,40]. The aim of the investigation is to assess potential of PPG for determination
of the vasomotor function of the endothelium and elastic characteristics of arteries. For this
purpose, their changes are studied during the test with the reactive hyperaemia.
For this purpose the initial PPG is registered then the blood pressure cu, where the
pressure is made above the systolic one on 30 mm/Hg, is put on the same extremity, where
the registration of PPG is performed (ipsilateral). The pressure is kept for 5 minutes and then
sharply reduced. The recording of PPG is made continuously during 3 minutes. Parameters are
estimated in the rst 30 seconds on the rst and second seconds after ischemia. The frequency
of the cardiac contractions (FCC), arterial pressure is estimated: systolic (APs), diastolic
(APd), pulsate (AP). Besides the test with the reactive hyperaemia (endothelium-dependable
stimulus), the test with Nitroglycirine is made (NTG). NTG is a donator of the oxide of the
nitrogen and is the endothelium-independent stimulus. Parameters of PPG (FCC, A1, A2, T
etc.) are compared with the background and after application of NTG on the third minute when
its inuence is the maximum.
Figure 8: Principle of Photoplethysmography(
Figure 9: Components of PPG signal waveform. (
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3.5. Echoencephalography (EchoEG)
Indirect non-invasive dynamic method.
The method is based on the application of the one-dimensional ultrasound radiation [41].
The investigating object – ventricular brain system.
Level of the vascular system examination –shift of the median structures of the brain
(B-echo), condition of the ventricular system, presence of the hydrocephalus.
Data processing – quantitative – qualitative (graphical).
Advantages of the method.
1. Screening non-invasive method for the urgent diagnostic of disorders in the liquor dynamic
2. This method can detect the abnormal pulsation in brain arteries. Nowadays this is not actual
due to other methods with better options.
Disadvantages of the method.
1. Less informative on the background of the up-to-date neurovisualizing methods.
Echoencephalography (EchoEG) is an ultrasound method for intracranial structures.
The basis for the existence of the method is the ability of brain tissues to absorb and
reect ultrasound vibrations.
The method may be useful in the diagnosis of brain tumors, craniocerebral traumas,
vascular and inammatory diseases of the brain, as well as hydrocephalus as screening and can
be used in emergency medicine and in the practice of primary care at the pre-hospital stage.
Further we describe in brief some positive moments of application of certain technologies
that were tested by time and remain up-to-date and progressive.
Figure 10: Echoencephalography. (ya.html).
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3.6. Capillaroscopy
Historically, capillaroscopy as a non-invasive visualization of the microcirculation in
the nail bed of ngers was proposed to practical medicine in the 1960’s. However, it was used
in isolated medical institutions that managed to nd certain algorithms for interpreting these
images [3,42,43,44].
With digital technology in the 90s of the 20th century, capillaroscopy as an optical method
of visualizing capillaries is undergoing a renaissance and is transformed into a technically
updated digital capillaroscopy with the ability to group image visualization on the monitor and
its archiving in static (image) and dynamic (video) modes [3,28,44,45,46].
Capillaroscopy has the important place in the continuous chain of investigations of the
pathohemodynamic link in the vascular system: heart- arteries – capillaries – veins- heart. The
incompleteness of the cycle of research of the vascular blood supply for the brain became the
determinative factor both in renascence and modernization of the unmerited forgotten method
and in the development of new approaches to interpretation of images.
Figure 11: Echoencephalography. (
Figure 12: A model of an old capillary scanner (the 60's ofthe 20th century) with the rst attempt to take video, which
became a prototype for digital optical capillaroscopy.
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Direct non-invasive dynamic method.
The method is based on application of the optic visualization method with usage of
modern computer technologies for reection of the obtained image on a monitor’s screen.
The investigating object – stream of erythrocytes in the volume of the tissue.
Level of the vascular system examination –visualization of the blood perfusion on the
microcirculatory level.
Dataprocessing – direct visualization with quantitative – qualitative analysis.
We have constructed a smart capillaroscope on the basis of our own clinic for the
microcirculation investigations. It enables to enlarge the obtained images in 100, 150, 200
times in order to diagnose adequately the condition of the microcirculation in the organism, to
prognosticate the course of a disease, quantitative and qualitative characteristics of eciency
of the vasoactive therapy, possibility of observation of unique microcirculative changes for
predicting the sub- and decompensatory conditions of patients.
Figure 13: Capillaroscope. (
Figure 14: Capillaroscopic image in a healthy human. Classical loop.
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Advantages of the method.
1. Easy in work, non-invasive, high quality of visualization both of capillaries and the velocity
of the circulating blood, possibility of archiving both of separate static images and video les
for processing images in order to increasing the contrasts and receiving of the maximally
useful information.
2. Enables to increase signicantly the resolution of the capillaroscopic picture.
3. The image on the monitor enables to perform the consultation of some doctors with dierent
professions avoiding subjectivization in interpretation of the obtained images.
4. Enables to perform the archiving images, compare them in the dynamics of treatment and
the disease’s course.
5. Microcirculation visualization on a screen appears to be the factor of the increased trust to
a doctor by a patient, realizing necessity of treatment for elimination of the detected disorders.
6. Unlike digital parameters of assessment of the level of microcirculation in the volume unit,
the qualitative picture of visualization of disorders in blood circulation is the most informative
and reliable.
7. Development of the method of the computed analysis of the obtained capillaroscopic
images enables to formulate the algorithm for the quantitative qualitative analysis of the
microcirculation level that further will improve quality of objectivation of the detected
8. The information about the capillary structure (structure, caliber, form and tortuosity of a
certain capillary, presence of the capillary net, angioarchitectonics of the microcirculatory
bed) and functions of the microcirculatory link of the blood supply (circulation rate, character
of circulation, presence of the sludge – phenomenon).
9. Theoretical possibility of obtaining the digital processing of the volumetric perfusion. The
formula is used where the velocity of the blood ow in a capillary is multiplied on the volume
Figure 15: Capillaroscopic image. Atypical form of the capillaries.
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of the capillary and on the density of the capillaries in the unit area. This enables to receive
much more all-round information than usage of the indirect method of the laser doppleric
10 .Possibility of performance of functional loads, comparison in dynamics.
Disadvantages of the method, which promotes creation of a new technology for vascular
Without computer monitoring the optic capillaroscopy used to be signicantly limited in
possibility of the clinical interpretation (only one researcher can see one and the same picture
in the real time in the radiographic cone of the capillaroscope and interpret subjectively it).
Therefore, capillaroscopy was not widely recognized in the 20th century, and only a few
physicians understood its essence and in dependentlyfoundalgorithmsforitsapplication [41].
Renaissance of capillaroscopy: from smart optic capillaroscopy into vascular screening
technology (VST) for 1997-2017 period
The greatest breakthrough in the development of digital optical capillaroscopy was
made by Ukrainian scientists U.B. Lushchyk and V.V.Novytskyy [3,44,46,47], which since
1997 became interested in this method and began to study it clinically and technically improve
For 20 years, this technical device has undergone a number of modications and
modernization with the use of modern lenses and the creation of fundamentally new lighting
schemes and optical image focusing, enhancement of optical and digital enhancement, image
resolution enhancement [44, 45, 46, 47].
The technology ideologist An Academician of the Academy of Technological Sciences
of Ukraine, UlyanaLushchyk, Prof., MD [45, 46, 47].
The main idea of the renaissance project of capillary method was to develop the method
from visualization of the capillary to a technology for assessment of a vascular pathology and
the risk prevention.
Each new version provides improved resolution and image quality, methodology
improvement for application in diagnostic and treatment process.
1st version of the device and the example of capillary images, 1999.
Disadvantages: old optics, poor visualization, low increase, a lot of artifacts.
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Figure 16: 1st version of the device and the example of capillary images, 1999.
2nd version of the capillaroscope, 2003.
Improved contrast, the quality of visualization, the ability to increase up to 100 times, the ability to observe
the speed of blood ow.
Disadvantages: unclear and unstable images do not allow counting capillary parameters.
Figure 17: 2nd version of the capillaroscope, 2003.
3rd versionofthedevice, 2006.
Improved clarity of visualization of capillaroscopic images, the ability to increase has risen to 300. The ob-
tained images enabled to calculate large number of microcirculation parameters in the semi-automatic mode
and managed to gain experience to create a vascular screening technology.
Disadvantages: currently this version is obsolete.
Figure 18: 3rd version of the device, 2006.
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4th version (2013) of smart optic capillaroscopy enabled to:
signicantly improve the quality and clarity at dierent magnications;
increase the dynamic range of the optical zoom from 50 to 400 times;
apply the automatic processing of static images;
create a series of instruments and subtechnologies for dierent specialists
angio- and cardiosurgeons, oncologists, psychoneurologists, cardiologists, neonatologists and
pediatricians, intensive care and rehabilitation specialists, endocrinologists;
apply this technology due to non-contact technique in dentistry (periodontics),
neurosurgery and gynecology;
predict vascular risk in insurance medicine, health resorts, pharmaceutical
5-th version (2015) of smart toptic capillaroscopy has received modern new design.
Figure 19: 4th version (2013).
Figure 20: Screening of capillaries with vascular screening technology (
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Also, the optical system and the system of a uniform illumination have been improved.
Improved image quality and the ability to smoothly change the optical zoom from 50 to 300
with out displacement of the studied area.
Figure 21: Capillary image enlargement.
Figure 22: Data processing
Archiving capillaroscopic images and video, and ability to image processing resulted
for software developing for database and the ability to assess the necessary parameters for
clinical interpretation.
Examples of program decoding
Process-management in vascular screening: 4 steps for 10 minutes
1. Obtaining pictures and saving in database.
2. Initial data processing
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Figure 23: Data processing
Figure 24: Data processing
The interface of the Vascular screening technology shows the easy use of the technology
for the understanding for a doctor or a patient during examination and image results. This
technology can work in English, Ukrainian, Russian and Arabic languages
3. Program decoding: analytical processing with automatic clinical interpretation
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Figure 26: The program is able to generate clinical output in 4 languages: Ukrainian, Russian, English, German
Figure 25: Program decoding.
4. Clinical conclusion
The program is able to generate clinical output in 4 languages: Ukrainian, Russian,
English, German
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Therefore, after 60 years of its creation due to the digital technology in the 90’s of the
20th century, optical capillaroscopy has undergone a renaissance and has grown up into the
vascular screening technology with IT-software.
The daily 20 years of clinical application for the diagnosis and treatment of vascular
disorders has been accumulated and integrated into the technology of clinical interpretation
and digital measurement of the hemodynamic parameters of the microcirculation, and nally
lled the vascular screening technology for microcirculatory changes with the intellectual
component of in-depth knowledge of Macro-Micro-Angiology.
This approach of the long-term and expensive project of clinical research of the
capillaroscopy method allowed redening the possibility of a method in the framework
of vascular screening technology as an evidence base for microcirculatory changes in the
vascular bed and monitoring its sanogenic or pathological changes during angiocorrection and
Figure 27: Technology for vascular screening
Today the vascular screening technology makes reliable diagnosis, which doctors and
patients can understand.
For a patient rapid and available information about the cardiovascular system’s
For a doctor – quick objectication of processes for decision-making, enhanced
For health care – independent tool of evidence-based medicine, means for legal
support and protection against medical mistakes.
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IT component of VST enables to:
visualize problems at various stages of CVD,
make computer analysis of detected disorders and possible risks,
create subtechnologies for making tactic decisions in neonatology, pediatrics,
angiology, cardiology, angioneurology, oncology, rehabilitation, balneology, insurance
The vascular screening technology is a unique technology created on the basis
of combination of technical components, scientic knowledge of microcirculation and
hemodynamics, angioarchitechtonics combined in a single complex.
Variety of technical models
Stationary device for vascular screening in a unit for functional or vascular diagnostics.
Mobile version (for elding advice, diagnosis at a patient’s bedside in intensive care
and operating room).
Figure 28: Vascular screening.
high visualization of information for understanding by a patient;
patients’ condence and visualization of real images allow a doctor and a patient
immediately to discuss ways of the problem solving;
easy to use: diagnosis lasts 5 minutes;
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high accuracy;
bloodless, painless, safe;
absence of contra indications;
high quality of imaging both of capillaries and circulation rate.
VST’s hemodynamic parameters:
Visualization of microangioarchitectonics and capillary blood lling is a determinative
factor in evaluation of suciency of functioning of the whole hemodynamic system so much
as capillaries form microcirculatory channel that it is an end link of blood supply system.
Capillaries lled with blood evenly are a proof of correct functioning of the system heart –
arteries – capillaries – veins – heart.
Microcirculation research by digital optical capillaroscopy gives an opportunity to get
an enlarged capillary image on the monitor (1 of native microcirculation segment is
displayed on the 15’-monitor and lls in the entire monitor eld). Therefore, the operator of
measurements manually generates a number of macro-mistakes, since movements of the hand
with a digital pointer and digital increase of micro-processes and cause signicant errors in the
measurement of diameter in dierent segments of the capillary. Therefore, it is necessary to
search for digital technologies for stabilization and digital image processing.
This was the aim of creation and development of the technology for vascular screening
[30, 44, 45, 46, 47], which allowed not only to improve the technological complex, but also to
transfer the software into a fundamentally new level of initial measurement and analytical data
processing and the automatic formation of the expert-level conclusion in the form of a clinical
interpretation of possible signs of pre-disease, predictions and risks of further development of
CVD with a possible clinical picture of the dyshemia.
Figure 29: The norm of capillary picture during vascular screening.
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For about 20 years Veritas Research Center (
tehnolohiya-sudynnoho-skryninhu/?lang=en) has been working under development of the
vascular innovative technology for visualization, objectivation and analysis of changes in the
microcirculatory channel.
Thanks to the clinical interpretation and smart analytical IT-software, the vascular
screening technology has a wide range of application for dierent levels of medical institutions
and the prole of medical practice - from neonatology to psychoneurology, endocrinology,
oncology and stomatology.
Vascular screening subtechnology as an improvement software for specic basic medical
Biomarkers of neoangiogenesis as “onco-capillaries”
Application: family doctors, oncologist, urologist, gynecologist.
Benets: the subtechnology oers an innovative approach to the cancer diagnosis and,
importantly, it is an eective tool in the onco-screening, future monitoring of disease conditions
of the onco-patients and the disease’s progress at the dierent stages of cancer pathology.
Congenital malformations of vessels
Application: obstetric, neonatal, pediatric and genetic departments.
Benets:diagnosis of congenital forms of vascular anomalies.
Normal formation of vessels - the guarantee of health of the nation and the state.
Cardiology and cardiac surgery
Application: cardiology, cardiosurgery, angiosurgery, anesthesiology.
For cardiac surgery to quickly assess the eectiveness of the operation into the operating
Figure 30: The pathology of capillary picture duringvascular screening.
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Benets:to provide immediately examination of the eciency of heart pump function for
whole body with personally approach.
Application: family doctors, child and adult neurologists, angiologist
Benets:nd vascular pathology at the pre-clinical stage and prescribe personalized appropriate
treatment, a neurologist may withdraw completely from strokes statistics among their patients.
Pathology of vessels may develop 2-3 years before having a stroke. Vascular screening is an
indicator of troubles in human vascular system and the brain in particular.
Application: for cases like depression, epilepsy, dementia, sleep disorders, phobias and so
Benets: early detection of abnormal conditions of brain vessels would allow identifying
congenital or acquired vascular disorders and partially correcting them, thereby improving the
quality of life of these patients.
Application: intensive care unit, cardiovascular, neurovascular and angiologic centers.
Benets: xation of necessary parameters at all stages of therapy that enables specialists
dynamically react to obtained results and adjust treatment plans in accordance with patients’
Rehabilitology and balneology
Application: SPA-centres, rehabilitation department
Benets:This may be like an evidence for protection of the sanatorium, spa and rehabilitation
center from critical situation with patients.
Endocrinology and dermatology
Application: diabetes mellitus, thyroid and mammary gland pathology, hypophyseal pathology,
obesity, alopecia, hormonal and structural disturbances in the sexual sphere: endometriosis,
bromioma, prostate adenoma, adrenal pathology.
Benets: it’s possible to correct some pathological endocrine disorders due to specic
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Application: for dentist’s therapy of periodontitis and periodontosis, temporal arteritis with
the aim to save native teeth.
Benets:adequate treatment and preservation of natural teeth due to detection of vascular
disease in the blood supply for the teeth and gum.
Application: vascular treatment department, intensive care department
Benets:the visualized assessment of the patient’s state before vascular treatment and after
its completion, which conrm the eectiveness of medicines. Evidence based software for
treatment managements helps to create adequate treatment scheme and receive predicative
successful treatment process with 100 % guaranty due to treatment monitoring management.
Application: to determine the risk of critical conditions
Today life insurance is one of the hardest segments in the insurance industry, which is caused
by high-risk because of lack of an objective assessment of the insured.
Benets:This subtechnology in the screening mode makes it possible to assess risks of vascular
events and predict possible insurance claims.
Thus, the method of optical visualization of capillaries over the past 20 years has undergone
a global renaissance and has developed into a smart technological complex - a technology for
vascular screening with high parameters of 100% visualization and objectication available to
physicians and patients to understand.
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At present, the informational capacity of VST is 96%, the specicity is 87%, the sensitivity
is 92%, which is achieved owing to analytical data processing and IT technologies of clinical
expert-level interpretation [3, 43, 44, 46, 47].
3.7. Radionuclide diagnostics (SCINTIGRAPHY)
Direct non-invasive method.
The method is based on registration of radiation from the articial radioactive substances
injected into the organism with the tropism to one or another organ. The isotopic mark of the
radiopharmpreparation allows tracing the character and way of accumulation and excretion of
the preparation from the examined organs and tissues [48].
Figure 31: Applied technology for vascular screening in the monitoring of personalised angiotherapy.
Figure 32: Scintigraphy of a shoulder tumor at the right humerus (white arrow). (
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Figure 33: The scintigraphy. (
The investigating object – permeability of the vascular system of a certain organ or tissue.
Level of the vascular system examination determination of parameters of the regional
blood ow in assessment of the organ’s functioning (radiohepatography, radiocardiography,
radiopulmonography, radiorenography, radioencephalography).
Dataprocessing quantitatively- visual by means of assessment of the period of the half-
Advantages of the method.
1. Applied method for dynamic investigations of the organ’s functioning.
2. It reects functioning of the vascular system in the organ as the whole without explanation
of causes of absence of the contrast accumulation.
Disadvantages of the method.
1. Results of application of the method have the statical image and doesn’t specify the
pathogenetic mechanisms of origin of one or another pathology.
This method is gradually superseded by modern spectrographic programs (SPECT) as a part
of CT-MRI studies of organ and system perfusion.
3.8. Radiopaque angiography
Digital subtraction angiography (DSA) is a uoroscopy technique used in interventional
radiology to clearly visualize blood vessels in a bony or dense soft tissue environment. Images
are produced using contrast medium by subtracting a “pre-contrast image” or mask from
subsequent images, once the contrast medium has been introduced into a structure. Subtraction
angiography was rst described in 1935 and in English sources in 1962 as a manual technique.
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Digital technology made DSA practical from the 1970s [49].
Direct invasive statistic method.
The method is based on the puncture or catheterization of various peripheric arteries, injection
of the radiopaque liquid with the further performance of the x-ray lms [49,50].
The investigating object – stream of erythrocytes in the volume of the tissue.
Level of the vascular system examination visualization of the regional arterial
(arteriography) and/or venous vascular system (venography, phlebography), lymphatic system
Data processing the obtained– visual, quantitative.
Shortly about angiography methods and methodics:
In traditional angiography, images are acquired by exposing an area of interest with time-
controlled x-rays while injecting contrast medium into the blood vessels. The image obtained
includes the blood vessels and all overlying and underlying structures.The images are useful
for determining anatomical position and variations, but unhelpful for visualizing blood vessels
accurately [49].
In order to remove these distracting structures to see the vessels better, rst a mask
image is acquired. The mask image is simply an image of the same area before the contrast
is administered. The radiological equipment used to capture this is usually an X-ray image
intensier, which then keeps producing images of the same area at a set rate (1 to 7.5 frames
per second). Each subsequent image gets the original “mask” image subtracted out [49].
The radiologist controls how much contrast media is injected and for how long. Smaller
structures require less contrast to ll the vessel than others. Images produced appear with a
very pale grey background, which produces a high contrast to the blood vessels, which appear
a very dark grey [49].
The images are all produced in real time by the computer, while the contrast is injected
into the blood vessels.
Intravenous digital subtraction angiography (IV-DSA) is a form of angiography which
was rst developed in the late 1970s [49].
IV-DSA is a computer technique which compares an X-ray image of a region of the
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body before and after radiopaque iodine based dye has been injected intravenously into the
body. Tissues and blood vessels on the rst image are digitally subtracted from the second
image, leaving a clear picture of the artery which can then be studied independently and in
isolation from the rest of the body [49, 50].
Some limited studies have indicated that IV-DSA is not suitable for patients
with diabetes or renal insuciency because the dye load is signicantly higher than that used
in arteriography [48].However, IV-DSA has been used successfully to study the vessels of
the brain and heart and has helped to detect carotid artery obstruction and to map patterns
of cerebral blood ow. It also helps to detect and diagnose lesions in the carotid arteries, a
potential cause of strokes [49, 50].
IV-DSA has also been useful in assessing patients prior to surgery and after coronary
artery bypass surgery and some transplant operations [49].
Figure 34: Radiopaque angiography of carotid arteries. (
Advantages of the method.
1. Visibility on the large length of the region of the vascular system with the consecutive
representation of the passing of the radiopaque substance from the place of injection along the
arterial system with the transition through the capillary phase into the venous system.
2. Detects injuries and defects of vessels’ development, disorder of their permeability.
3. Makes possible not only to trace the arterial, capillary and venous phases of the cerebral
circulation, detect their length in dierent sections of the vascular system in the organ, but also
to examine hemodynamics of separate vascular reservoirs, vascular net of the pathological
focal formations (tumours, arteriovenous malformations) by means of the selective injection
of the contrast.
4. High diagnostic information in case of tumours with well-developed vascular net, traumatic
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and spontaneous hemorrhages, occlusive – stenotic injuries of the major arteries, arterial
aneurisms, arteriovenous and arteriosinus pathological shunts.
5. During diagnostic research the catheterizing angiography can transform into the treating
method of the endovascular surgery: aneurisms and/or arteriovenous pathological anastomosis
are “ungeared” (blocked) with the help of various balloon-catheters, the angioplastics is made
under the arterial stenosis, and the regional infusion of medical agents is made.
6. Recently new method of the angiography performance has appeared digital subtraction
angiography – it is the contrast study of vessels with the further computer processing. Change
for digital technologies in the angiography has number of advantagessuch as:
- high quality of allocation of a certain vessel from the general picture and high
informative images;
- minimum dose of the contrast substance during the examination;
- convenient archiving and data retrieval;
- absence of an x-ray lm and chemicals, low cost per one observation;
- allows reducing traumas during observation due to the possibility of refusal from
catheterization and/or decreasing of the number of the injected radiopaque substance. This
substance can be injected less traumatic for a patient – intravenous, without using the artery’s
Figure 35: Digital subtraction angiography. (
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Disadvantages of the method.
1. Invasive.
2. High risk of complications from the injection of the contrast (allergic reaction to the contrast,
hematoma, thromboembolism), large list of contraindications under the acute inammatory
and infectious diseases, serious patient’s condition, mental diseases, allergic reactions to iodine
preparations, obvious cardiac, hepatic and renal insuciency.
3. Delimitation in time of the visualization of the arterial and venous phases of blood ow,
impossibility of the simultaneous examination of arteries and veins in the real time.
4. Obtaining images only in one projection of the vessel signicantly limits the method’s
potential in case of the vessel’s tortuosity, stenosing injuries, soft arteriosclerotic plaques.
5. Limited time for examination is caused by the fast passing of the portion of the contrast
substance through the vascular system, with this connection they assign the arterial, capillary
and venous phases of this substance spreading.
6. The obtained angiographic image is static that is the one-moment section. Consequently, it
is impossible to perform functional tests and observation in dynamics.
Venography is prescribed according special indications such as chronic thrombophlebitis,
thromboembolism, anomaly in development of venous trunks, dierent disturbances of the
venous circulation. The venography is made by the direct and indirect ways. With the direct
venography the contrast substance is injected directly to the vein by means of puncture,
sometimes catheterization. The indirect venography is made by three ways:
- injection of the contrast substance into the arteries then it comes into veins through the
capillary system;
- injection of the contrast substance into the organ’s tissues, with this veins are made on lms
that brings blood from the organ;
- injection of the contrast substance in the medullar space.
Radiopaque angiography in the 90s of the 20th century was considered the gold standard for
angiosurgery and cardiosurgery [49, 50].
However, with the advent of CT-MRI technology visualization of the vascular bed in the
angio-mode, gradually loses its positions:
DSA is done less and less routinely in imaging departments. It is being replaced
by computed tomography angiography(CTA), which can produce 3D images through a test
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which is less invasive and stressful for the patient, and magnetic resonance angiography (MRA),
which avoids X-rays and nephrotoxic contrast agents [49].
3.9. Ultrasound diagnostics of vessels
Ultrasound vascular diagnostics as a new, non-invasive method of rendering vascular
segments alive began its lifecycle in the 90s of the 20th century, due to the emergence of
colorcoding programs for blood ow.
Ultrasound diagnostics of vessels includes two complementary methods: ultrasound
coloured angioscanning (USAS) and ultrasound dopplerography (USDG). USAS visualizes
the vessels’ structure and functions of the vessels’ wall. And USDG graphically records
circulation rate in vessel and characteristics of functioning the vascular wall, interconnection
of all links of blood circulation at the local level [3, 23, 28].
Figure 36: Ultrasound diagnostic system with the eect of coloured cartography of blood ow and ultrasound
Generally, ultrasound angiology has the next vascular approach for objectivisation vascular
1. US angioscanning
1.1. Black and white mode
1.2. Color-coded mode
1.3. Energetic Doppler-coded mode
1.4. Small-vascular perfusion mode
2. Ultrasound dopplerography
2.1. USDG as separate medical equipment (appeared in the 80’s of the 20th century)
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2.2. USD as an option for US systems
2.3. Laser Doppler owmetry (velocimetry)
Non-invasive dynamic method (USAS – direct visual, USDG – indirect graphical).
The method is based on application of the ultrasound radiation with usage of the Doppler
eect: the ultrasound wave changes its frequency while it is reected from the moving elements
of blood, in particular erythrocytes.
The investigation object – segment of the major artery or vein.
Level of the vascular system investigation – major vessels.
Data processing– quantitative-qualitative (digital and/or graphical).
US-angioscanning (USAS) can be used in several modes of functioning of the
ultrasound system depending on its type and kind such as: in modes of black-and-white image,
eect of the colored cartography of blood ow (colored angioscanning) and energetic color-
coding of blood volume, color-coding of the tissue perfusion:
• using modern US-system with color-coding and dopplerography one can obtain
more information about the condition of circulation in major arteries and veins. In the mode of
the colored doppleric picturing it is made the qualitative assessment of the size of the lumen,
elastic-tonic and pulsation characteristics of the examined segment of the artery, width of
the vascular wall, organization of blood ow with diagnostics of areas of disorganization in
the form of turbulence, prognostication of the risk of the possible embolisation of cerebral
• modern USD-system with color-coding of the eect of the energetic doppler
enables to obtain monochrome pattern of the circulation in organs but doesn’t give the possibility
to analyze the tissue’s type in organs, especially of areas with the intensive circulation, that
is typical for an individual pathogenetic approach to the treatment tactics. The mode of
the energetic doppleric picturing enables to visualize cerebral arteries with the transcranial
scanning, assess the character of the arterial angioarchitectonics, tortuosity of the proximal
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The energetic Doppler reects the blood volume in vessels in one color, depending on
the direction of blood ow.
Red and blue colors reect dierent directions of blood ow and not always coincide
with the common image of arteries and veins in atlases (arteries red-colored, veins – blue-
colored). Red or blue color on the US-angioscannograms shows only the direction of blood
ow – towards the sensor or from the sensor.
Figure 38: Eects of color-coding of blood ow with visualization of the angio architectonics of organs.
Figure 37: Ultrasound colored angioscanning.
US-angioscanning enables to visualize structural changes lengthening of an artery
(tortuosity, exure, loop), aneurysmal extension, stenosing- occlusive injury of arteries with a
defect of blood lling of the vascular lumen, presence of the heterogenous formations – from
enlargement of complex intima-media up to atherosclerotic plaques, thromboemboli.
Method of color-coding of the blood ow with angioscanning enables to study its
character, presence of the turbulence of the ow and its cause. However, during one heart
cycle (on the average 1 heart cycle per 1 second) rate of changing of dierent hemodynamic
parameters signicantly exceeds the potential of perception of the visual analyzer of the human
and therefore it requires more detailed graphical layout. Very in this aspect the USDG method
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is more sensitive in that time.
With the help of the pencil-gauge ultrasound dopplerography (USDG) makes possible
to receive a graphical signal from the separately taken point in the projection of one or another
vessel. Graphical prole of changes of the linear circulation rate during the heart cycle reects
the character of the ow laminar or turbulent, continuous or expressed intermittent blood
ow, elastic-tonic characteristics of a certain vessel, level of the intravascular resistance distally
from the place of location and dependence of blood ow on signs of the hydrodynamic conict
Figure 39: Ultrasound doppler.
Peculiar features and main advantages of the dopplerography method is in the generalization of all local data from
the examined segments of arteries and veins, and the information from separate points is analyzed according to the
assessment of hemodynamics of the whole regional system.
However, every above-mentioned method has its own advantages and disadvantages. The
dopplerographic method is a graphical representation of changes of the velocities’ prole
during the heart cycle, therefore perfect knowledge of hemodynamic laws, mutual inuence
of the elasticity of the vascular wall and its tonus on the character of passing of the pulsating
wave signicantly expands informative and specic features of the method.
It is possible that application of the specic graphical methods will increase the
informative feature of the US-angioscanning method.
On the other hand, these investigating methods for the vessels’ condition are closely
interconnected and must include both examination of major arteries and veins starting from the
aortic arch and intraorgan’s scanning and dopplerography of the regional arteries and veins.
Only this sequence of performance of US-investigation of the vascular system can give the
overall picture of etiopathogenesis of the vascular-organ insuciency.
Advantages of the method
1. Non-invasive.
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2. Harmless and possibility of the numerous applications in dynamics.
3. USAS is sensitive to slightest changes in diameter of vessels, localizes areas of
stenosis, atherosclerotic plaques, burbles of blood ow in the place of segmental stenosis of
4. Transcranial angioscanning enables to visualize arteries from the Willis’s circle,
detect tracts of the collateral change of blood ow with the stenosis and occlusions of major
5. Obtaining the dynamic image unlike static image with the radiopaque angiography
(AG) and MRA.
6. Simultaneous investigation of the arterial and venous beds.
7. Experimental modeling of various pathological states and application of various
provoking factors for objectivation of causes of the vascular-cerebral insuciency:
• tests with stretching of the arm for diagnostics of the expressiveness of the
syndrome of the thoracic output;
• respiratory tests;
• tests with the head turning;
• compression Matas’s test
• ortho- and antiorthostatic tests;
• tests with dosed physical load;
• acute pharmacological tests.
8. The USDG method proved to be promising in the development of a methodology for
analyzing not only the linear velocity of blood ow in systole and diastole and independent of
the location angle of the indexes of pulsation, resistance, turbulence, etc. [23].
Disadvantages of the method
1. Impossibility of the review visualization of all vessels: unlike methods MRA and AG
US-method enables only investigate a vessel by segments. Nowadays lack of the eect of the
review/survey is partially compensated by new technologies – panoramic scanning.
2. Method of USDG is limitedly sensitive for stenosing injuries of arteries up to 50% of
the reduction of the lumen.
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3. At the same time, the USDG method proved to be more informative about the
functioning of the vessel due to a qualitative analysis of the entire dopplerographic curve
with the evaluation of elastic-tonic properties, blood pressure, intravascular pressure, and the
inuence of intracranial pressure. However, for most physicians, such an analysis requires in-
depth knowledge of dierent areas of Macro-Micro-Angiology to formulate proper conclusions
and clinical interpretations.
4. As for the ultrasound scanning, the stage of vascular visualization and measurement
of their diameter, the intima-media complex, the diagnosis of tortuosity and loops, and
atherosclerotic plaques has actually exhausted itself. Therefore, the passion for visualization
and ease of perception of these images in 20 years of the 21stcentury has gradually ceased
and today the technique of angioscanning requires more profound knowledge of physicians
for clinical interpretation and application in the Macro-Micro-Angiology for personalized
angiocorrection and angiotherapy.
The combination of in-depth knowledge of Macro-Micro-Angiology and the possibilities
of using ultrasound examination of angioscanning and USDG to form a new ideology for
screening vascular disorders at the macro- and peripheral regional levels, with a clinical
understanding of the revealed changes [4, 23, 51] and the possibilities of personalized treatment
on the principles of evidence-based medicine [4, 29].
During 2010-2017, the methodology of USDG of major arteries and veins gradually
developed into Angiomarker technology with the possibility of analysis of about 50
hemodynamic parameters that proved to be signicant pathohemodynamic indicators of
vascular blood ow disorders, in contrast to structural changes at the macro level [52, 53, 54,
55, 56, 57, 58].
For a successful application of the USDG methodology doctor should have deep
knowledge of the anatomy and physiology of the human vascular system, basic knowledge of
hydrodynamics and hemodynamics, physics of the ultrasound, characteristics of blood ow as
a non-Newtonian liquid.
The methodology essence is in the comprehensive consideration of the blood system as
the integral system of the closed arteriovenous-capillary tubing - with its resistance, elasticity
of the vascular wall, vascular tone, hydrophilicity of the surrounding tissues.
Up-to-date high-sensitive equipment enables to work both with arterial and venous
segments simultaneously, and specially designed software can calculate how signicant
deviations in a patient from the condition of the arteriovenous balance in the direction to
unjustied arterial hyperemia or venous stasis of any degree.
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Today, this technique is urgently necessary not only for functional and ultrasound
diagnostics, it is relevant to many areas of medicine, such as paediatrics, neonatology, neurology,
psychiatry, urology, gynaecology and obstetrics, oncology, cardiology, surgery.
Only inexperienced physician allows himself to ignore the results of the doppler studies
of the major and peripheral vessels.
Figure 40: Angiomarkers. The norm.
Figure 41: Angiomarkers. The pathology.
Normally histogram should be in green and yellow stripes.
If your hemodynamic parameters are depicted in the orange-red range, you should
undertake treatment aimed at preventing vascular crises, stroke and heart attack and other life-
threatening critical vascular conditions.
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Non-invasive indirect graphical method
The method is based on the application of the laser radiation with usage of the Doppler’s
eect [37].
The investigation object – tissue microcirculation in the external layers of the skin, mucous
membrane. The control volume: 1mm3 contains nearly 200 microvessels.
Figure 42: Angiomarker technology for a personalized angiocorrection monitoring: from pathology to recovery.
Figure 43: Dynamics of laser doppler owmetry development from prototype to mini-device.
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Level of the vascular system investigation – radiation of the magnitude of the blood
perfusion in tissue on the microcirculatory level.
Data processing– quantitative- qualitative (digital and/or graphical).
There are low-frequency, high-frequency and pulsate uctuations of the tissue circulation
that is the physiologically important.
Low-frequency uctuations (LF) from 4 to 12 uctuations per minute are caused by the
activity of smooth-cell myocytes in the wall of microvessels and precapillary sphincters. LF-
uctuations are the representation of the mechanism of an active change in the microcirculation
– vasomotion.
High-frequency uctuations of circulation (HF) from 13 to 30 uctuations per minute
are caused by the periodical changes of the pressure in the venous section of the vascular
bed due to the respiratory uctuations. This compensatory mechanism is observed with the
ischemic disorders of the dermal circulation.
Pulsate uctuations of the circulation (CF) is considered as the basic but passive
mechanism of circulation in the microcirculatory bed, it is forming far outside the bed.
Modern laser analyzers are equipped with the mathematical wavelet-converters of amplitudes
and frequencies of uctuations of circulation connected with endothelial, neurogenic
and biogenic activity. The inuence of the respiratory and cardiac rhythms on the level of
microcirculation is taken into account.
Figure 44: Laser Doppler owmetry (LDF). (
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Advantages of the method
1. Unlike the ultrasound dopplerography methods, application of the sounding wavelet laser
radiation enables to obtain the mapped signal of the greatest amplitude from the thin surface
layer (nearly 1mm), that contain structures of the microcirculatory bed such as arterioles,
capillaries, venules and arteriolar-venular anastomoses.
2. Possibility of performance of functional tests for investigation of the vasoconstriction and
vasodilatation, endothelial activity and neurogenic regulation.
Disadvantages of the method
1. General character of the obtained information: absence of the information dierentiation
about the certain microvessels – arterioles and venules.
2. LDF method is a relative way of the microcirculation control because the calibration of the
device before measurements sharply depends on the heterogeneity of erythrocytes distribution
in the tissue, pigmentation and width of the epidermis, which are not controlled under non-
invasive investigations.
3. Unlike the optic capillaroscopy the method is indirect with the absence of the visualization
of the form and caliber of the capillary, density of capillaries per unit area that essentially
inuence the nal interpretation of the obtained data.
3.11. Computed Tomography
Figure 45: Computed tomography. (
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Direct non-invasive visualizing method
The method is based on application of the x-ray radiation [59].
The investigation object – layer-by-layer investigation of the axial plane.
Level of investigation – state of the liquorodynamic in the brain, with contrast study – state of
the regional angioarchitectonics.
Data processing – quantitative- qualitative visualizing method.
Advantages of the method
1. Distinguishes more than hundred stages of changes of the density of the examined
tissues – from 0 (for water, liquor) to 100 and more (for bones and calcicates) that enables to
dierentiate the densitometric dierences of normal and pathological parts of the tissue within
the limits 0.5-1% that is in 20-30 times more than on common roentgenograms.
2. Minimum width of sections is 2-5mm and enables to dierentiate reactive changes in
the surrounding tissues (areas of the perifocal brain edema-swelling, ischemic foci, degree of
hydrocephalus, tracts of liquor circulation).
3. Resolution – foci of the diameter to 0.5 sm.
4. Sometimes cardio synchronizers are used in the cardiology with CT, which enables to
obtain pictures in the certain phase of the heart cycle. This make possible to assess size of the
auricles and ventricles and also the heart functioning according many functional parameters.
5. The spiral tomography is a new method of obtaining CT-images due to the movements
of emitter by the spiral around the patient’s body. Owing to this one can receive information
about the full structure of the certain part of the body in some seconds. The computed
angiography, which enables to detect eciently the vascular pathology, 3D-reontgenorgaphy
and even virtual endoscopy have appeared on the basis of the method.
Disadvantages of the method
1. Necessity of the intravenous infusion of radiopaque substances for visualization of
2. Inferior in criteria of informativeness and sharp image to the MRI method.
3. 12. Magnetic Resonance Imaging in Angiomode (MRA)
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Magneto-resonance tomography (MRT)– nuclear-magnetic resonance (NMR) is
relatively new kind of obtaining images of organs that is based on the eect of nuclear-magnetic
resonance [60, 61].
Zavoyskyy J.K. discovered the phenomenon of NMR in 1944 as the paramagnetic
resonance and independently of him Bloch F. and Purcell E.M. discovered it in 1946 as
resonance phenomenon of the magnetic moments of the nuclear kerns and for that the received
Nobel Prize in 1952. Clinical samples of MR-tomographers appeared in they beginning of 80s
for investigation of the internal organs and the head. Latter potential of MRT was expanded
for examination of vessels and the heart because it was succeeded to receive images in the real
time with application of the sections’ synchronization.
Direct non-invasive visualizing method of the introscopy.
The method is based on application of radiation of the radiowave diapason with the
wavelength from 1 to 300 m, with application of the phenomenon of the short-term resonating
of protons in the electromagnetic eld for visualization of tissues depending on the dierent
water containment in them.
The investigation object –visualization of the vascular system on the virtual section of
the organ.
Level of investigation –regional angioarchitectonics.
Data processing visualization of the vascular system, made on the principle of automate
scanning controlled by a computer, processing and receiving of the layer-by-layer image of the
internal structure of organs.
Figure 46: Magnetic resonance imaging. (
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MRA method (magneto-resonance angiography) visualizes the circulating blood and
creates additional potential for detection of vascular injuries.
Magneto-resonance angiography enables to obtain the selective image of vessels (like
an image obtained on the common angiograms) safely for patients to assess the degree of
tortuosity of major arteries and veins in the head, and also to detect the presence of stenosis
and occlusions.
Thus, owing to the advanced method of the observe diagnostics MRT in the angiomode
it is possible to visualize injuries of major arteries of the head and cerebral arteries due
to receiving of their static (xed) image on the background of MRT-structural injury of the
cerebral substance.
Advantages of the method
1. Almost harmless for patient’s health because removes the problem of gamma-
radial load on the patient and a doctor (unlike CT).
2. High sensitive to separate vitally important isotopes and hydrogen that provides
high contrast range of received images.
3. Possibility of receiving images of the vascular bed without injection of the contrast
substance and with determination of parameters of blood ow.
4. High resolution – one can observe objects sized by portions of a millimetre.
5. It is possible to obtain not only the transversal but also longitudinal sections,
images of structures of vessels in dierent planes, to form three-dimensional constructions of
organs and tissues with high resolution and large contrast range (comparing to CT).
6. High resolution by tonality of black-and-white image with possibility of
dierentiation gradation of tones from white (fatty tissue) to black (air, bones, calcicates).
7. Precise visualization of vascular walls, atherosclerotic plagues, intracranial
aneurysms, arteriovenous malformations, arteriosinus pathological connections.
8. For investigation of extremely small biological objects the resolution is reached
10 mkm on special applications, i.e. it is possible to obtain images of the cell and its internal
structures. Therefore, a term MR-microscopy is established.
Disadvantages of the method
1. Necessity of the magnetic eld creation with high voltage requires huge energy
consumption, application of expensive technologies for providing the super conductance.
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2. Impossibility of examination of patients with cardio stimulators, metallic implants,
3. Impossibility of detection of foci of the ossication and calcication.
4. Intravenous injection of the magneto intensifying contrasts (such as magnevist,
omniscan etc.) are required for increasing of the diagnostic information.
3.13. Perfusion MRT
Method of the positron- emission tomography (PET) enables to obtain simultaneously
tomographic sections, perform investigations of the regional circulation and metabolism
with the help of the registration of short-living radioindicators that beforehand were injected
intravenously. Visualization is provided by the colored scale of the quantitative level of
perfusion [62].
Perfusion MRT enables to reect parts of intensication of circulation during performance
of functional mental loads that requires increasing of perfusion in the corresponding area of
blood supply.
Taking into account specic features of the functioning of the visual human analyzer
and potential of the brain to percept decoded colored images the specic gravity is increasing
of the multi-colored images under diagnostics of manipulations.
3.14. Color-coding of gray-scaled scanned MRA- and USD-images
Despite of the sucient level of visualization with MRA and USD-investigations today
new methodological approach is formed to increasing the resolution of received scanned gray-
scaled images of the brain and vessels due to the application of the eect of the color-coding
On the rst view a mode of 4-64 colored scale seems to be a random set of multiple
Figure 47: Image of perfusion with application of MRT method (perfusion MRT) gives the possibility to reect in color
dierent levels of blood supply in tissues of the examined organ. (http://
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colors but it is quite informative for investigation of the circulatory capacity. Only this mode
enables to visualize section of the size of 0.5-milimeter of walls in arterioles and venules,
character of microcirculation and to color-code blood ows with the help of eect of the optic
Figure 48: The color-coding of the gray-scaled MRT-images enables to see dierent densities that signicantly expands
the potential for interpretation of the received images.
The color-coding of the MRA- images enables to visualize more accurately tracts of
the cerebral arteries, their angioarchitectonics, and types of divisions of distal segments. The
dirty-brown color visualized the mistiness of the small vessels that was not visible on the gray-
scale image.
The mistiness, which was dierentiated in color in the aneurysmous formation, is
visualized most of all in this projection.
Approaching of small-caliber arterioles (red spots) conrms the presence of the vascular
malformation (brown color).
Main advantages of the method
1. In fact,an image, which is got due to color-coding, is like pseudohystological image
(approximate to the histological, but not based on the optical visualization of the microstructure,
but on the gradation of radiological density and tissue permeability) of organs and tissues that
allows to examine dierent physiological and pathological processes in them;
2. Using the eect of the adequate color-coding owing to the peculiarities of the program
we can change dierent ranges of colors connected with dierent tissue densities;
3. Color-coding of scanned images help to characterize parts with intensive or weak
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microcirculation (ischemia, arterial and venous hyperemia) to dierentiate the smallest layers
of tissues in organs with dierent acoustic density (tumors, cysts).
-investigation of the circulation and condition of the vessels’ walls in distal segments
of the limbs in the normal condition;
-assessment of hemodynamic parameters of the microcirculation as a result of formation
of collateral tracts with the presence of stenosis (thrombosis or atherosclerotic vascular
-dening the structure of the deeply situated venous valves and thrombus in the deep
veins of the low limbs and peripheric circulation for dierentiation of the acute, subacute
thromboses and postthrombophlebitous syndrome.
Using color-coding of US-image we receive the possibility to characterize dierent
types of tissues, parts with intensive or weak microcirculation (ischemia, arterial and venous
hyperemia) unambiguously to objectivate and qualitatively to interpret presence of tissues in
organs with dierent density (tumors, cirrhosis, postmyocardial infarction cicatrices, edema of
tissues, calcications) that can be subjectively and not always distinguished on the black-and-
white image and also level of their microcirculation.
This ideology has only partial development in the technology of elastography in some
ultrasound systems, but did not fully reveal its potential.
Technology formation requires time, labor and nancial resources to create a high-
quality, intelligent product that would allow ultrasound and MRI specialists to receive reliable
expert-level analytical information.
Perhaps this will happen in the near future, when the society will denitely depart from
medical instrument development, and will move on to the development and sale of medical
technological sets [27].
3.15. Comparative characteristics of informative features of some investigating methods
in Macro-Micro-Angiology
We were trying to describe in brief the methodology of the intravital examination of the
vascular system. It is typical that such number of investigating methods causes the sensation of
bewilderment concerning the choice of the required equipment and the wish to have all above-
mentioned one simultaneously.
However gradually the life arranges everything: resources are usually not enough,
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equipment becomes morally and physically outdated and only profound knowledge of basics
of hemodynamics can compensate the insucient number of the equipment supply with the
formulation of correct diagnosis.
Therefore, we decided to share our experience and to formulate some algorithms of
selection of the necessary diagnostic equipment or consequence of performing the study from
screening to nal diagnosis pathohemodynamically substantiated.
1. Let’ start with the initial diagnostics stage of screening of the distal links of
blood supply on the microlevel. According to the logic the assessment of a link in the vascular
bed that is the most distant from the heart – the periphery of blood supply. This can be realized
by two means: 1 – assessment of the microcirculation level (optic or computed capillaroscopy);
2 assessment of impairments of passing of the pulsate wave (sphygmography, computed
pletismography). That is the usage of the methods that can answer for the question concerning
global disorders in blood supply in the vascular conglomerate the heart – vascular bed.
2. Next stage – search for causes of disorders in blood supply – stage of the
pathohemodynamic factors on the macrolevel: examination of the pumping function of the
myocardium and condition of the major vessels in the human organism. Here naturally we can
assign screening and specic levels.
At the screening level the method of the ultrasound dopplerography is the most
informative, which enables to detect with high accuracy disorders of blood supply in a segment
of the blood carrying bed, suspect stenosing-occlusive injuries or aneurysmal formation in a
certain segment of the artery.
Next specic level specifying the character of the injury of the vascular wall
with the help of its ultrasound scanning and investigation of the vessel’s permeability. On
this stage it is succeeded to detect with 80-90% reliability atherosclerotic plaques, thrombotic
masses in the lumen of the vascular wall that hinder an adequate blood supply for an organ,
and apart (distal places of location of a certain segment of the artery or vein).
3. Stage of the precise diagnostics – the stage of proving demonstration. High-technological
methods for investigation: radiopaque angiography, magneto-resonance tomography in the
angiomode, USD-equipment of the experimental class. Only these methods can unambiguously
conrm the pathology detected on the second stage and helps to make a decision concerning
the choice of the certain tactics for the operating treatment.
The methods of capillaroscopy and USDG are quite sensitive and informative regarding
assessment of lack of the blood supply in the projection of the major arteries of the head and
in the microcirculatory bed. As according to the ontogenesis laws capillaries of the nail bed
Advances in Biochemistry & Applications in Medicine
and capillaries of the cerebral cortex are formed in one gestation period so their likeness has
been proved. Thus we indirectly can judge about the condition of blood supply for the cerebral
Our experience of treatment patient of the psychoneurological prole has shown
the validity of the approach. We have formed the following postulate in our practice: if the
pumping function of the myocardium, condition of the major blood supply and condition of
the microcirculation correspond to the norm so functioning of the hemodynamic system is
stable. Therefore, it can “resist” and adequately react to pathological factors of inuencing
of the environment. We can send this patient home under the clinical observation without
prescription of vasoactive agents. Besides, we can be absolutely sure in relative safety of
functioning of its hemodynamic system. Even in patients with epilepsy the hemodynamic
system, which was led to stability of all parameters, didn’t miss the rhythm and didn’t provoke
convulsive paroxysms after having the procedure and acute respiratory disease.
Table 1. Comparative characteristics of the informative characteristics of investigation of the vascular system (in
Criteria of the informative
characteristics MRA AG USAS USDG
Resolution (segment of an artery/
Visible within
the reservoir Segmental Local-regional
Sensitivity to deciency of the
cerebral circulation 83 87 60 89
Specicity 60 56 93 91
Hydrodynamic signs of ICH - - - 100
Hemodynamic importance for
CVD 53 50 65 100
Stenosis lesion of major arteries 34 95 93 74
Collateralization 95 98 36 94
Changes of elasticity of the
vascular wall - - 48 100
Changes of tonus of the vascular
wall - - 26 99
Steal-syndrome 54 95 38 75
Condition of the arteriovenous
balance 33 30 24 100
Venous dyshemia 57 Venography 57 47 98
Advances in Biochemistry & Applications in Medicine
Data from the table 1 show that every method for investigation of the vascular system has its
advantages. Therefore, it is necessary to unite them in the complex.
USDG can be considered as a screening method of diagnostics of the hemodynamically
indicated pathology, it is highly sensitive under various dyshemias in the proximal segments
of major arteries and veins in the head and the neck.
4. Conclusion
If we investigate profoundly every method of examination of the condition of the
vascular system, then unambiguously we can say that all they are necessary for the completed
diagnostics of the vascular bed injury. The dierence is in assessment way – survey or local,
a caliber of the vessel or circulation, pressure or volumetric blood ow, perivascular edema
or extravasal compression of the artery, one-moment assessment of function of the artery and
vein that follows it can be dened.
As we can see all above-mentioned methods have both advantages and disadvantages
and certain limitations in adoption. The choice of one or another algorithm of observation
depends only on level of intellect of a doctor and necessity in the depth of diagnostics. Of
course, if one doesn’t have lack of knowledge for assessment of the seen image the best he will
assess the potential to examine dierent aspects of blood supply.
Therefore, today in the age of digital technology it is required not only medical devices for
visualizing vascular pathology, but also powerful software products for in vivo visualization of
vascular pathology and monitoring the dynamics of all necessary processes that are important
for a practitioner and clinician during treatment of a particular patient.
Thus, the modern level of medical technology allows visualization virtually the whole
cardiovascular system, not arterial or venous channel, with non-invasive or X-ray diraction
However, it should be emphasized that CT-MRT technology in the angio-mode allows
visualizing the vascular regional channel for the subject of gross structural changes in
angioarchitectonics, stenotic-occlusive processes, which often require surgical intervention by
an angiosurgeons or a vascular neurosurgeon.
At the same time, the disadvantage of these technologies is static images that do not
always fully reect problems in the hemodynamics of CVS, since it is a dynamic system of
vascular blood ow.
Therefore, from the standpoint of dynamism, visualization methods that are capable
for analytically processing information and providing counselling assistance to a practitioner
Advances in Biochemistry & Applications in Medicine
in the process of personalized angiotherapy and angiocorrection are more prioritized in the
evidence base of the therapeutic Macro-Micro-Angiology. The rst such smart technologies
are the capillaroscopy in the model of vascular screening technology and the transformation of
USDG in angiomarker technoogy due to the extensive knowledge base of expert-level, which
is the basis of automated software to formulate conclusions of the clinical interpretation of
detected vascular changes in a particular patient.
Such vascular dynamical methods require further development in technological
complexes with the possibility of obtaining a completed and reliable conclusion with clinical
interpretation, which is understood by a practical physician and algorithms for using vascular
innovative technologies in personalized angiocorrection and angiotherapy.
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Photoplethysmographic signals are useful for heart rate variability analysis in practical ambulatory applications. While reducing the sampling rate of signals is an important consideration for modern wearable devices that enable 24/7 continuous monitoring, there have not been many studies that have investigated how to compensate the low timing resolution of low-sampling-rate signals for accurate heart rate variability analysis. In this study, we utilized the parabola approximation method and measured it against the conventional cubic spline interpolation method for the time, frequency, and nonlinear domain variables of heart rate variability. For each parameter, the intra-class correlation, standard error of measurement, Bland-Altman 95% limits of agreement and root mean squared relative error were presented. Also, elapsed time taken to compute each interpolation algorithm was investigated. The results indicated that parabola approximation is a simple, fast, and accurate algorithm-based method for compensating the low timing resolution of pulse beat intervals. In addition, the method showed comparable performance with the conventional cubic spline interpolation method. Even though the absolute value of the heart rate variability variables calculated using a signal sampled at 20 Hz were not exactly matched with those calculated using a reference signal sampled at 250 Hz, the parabola approximation method remains a good interpolation method for assessing trends in HRV measurements for low-power wearable applications.
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Background Light at night creates a conflicting signal to the biological clock and disrupts circadian physiology. In rodents, light at night increases the risk to develop mood disorders, overweight, disrupted energy metabolism, immune dysfunction and cancer. We hypothesized that constant light (LL) in rats may facilitate tumor growth via disrupted metabolism and increased inflammatory response in the host, inducing a propitious microenvironment for tumor cells. Methods Male Wistar rats were exposed to LL or a regular light-dark cycle (LD) for 5 weeks. Body weight gain, food consumption, triglycerides and glucose blood levels were evaluated; a glucose tolerance test was also performed. Inflammation and sickness behavior were evaluated after the administration of intravenous lipopolysaccharide. Tumors were induced by subcutaneous inoculation of glioma cells (C6). In tumor-bearing rats, the metabolic state and immune cells infiltration to the tumor was investigated by using immunohistochemistry and flow cytometry. The mRNA expression of genes involved metabolic, growth, angiogenes and inflammatory pathways was measured in the tumor microenvironment by qPCR. Tumor growth was also evaluated in animals fed with a high sugar diet. Results We found that LL induced overweight, high plasma triglycerides and glucose levels as well as reduced glucose clearance. In response to an LPS challenge, LL rats responded with higher pro-inflammatory cytokines and exacerbated sickness behavior. Tumor cell inoculation resulted in increased tumor volume in LL as compared with LD rats, associated with high blood glucose levels and decreased triglycerides levels in the host. More macrophages were recruited in the LL tumor and the microenvironment was characterized by upregulation of genes involved in lipogenesis (Acaca, Fasn, and Pparγ), glucose uptake (Glut-1), and tumor growth (Vegfα, Myc, Ir) suggesting that LL tumors rely on these processes in order to support their enhanced growth. Genes related with the inflammatory state in the tumor microenvironment were not different between LL and LD conditions. In rats fed a high caloric diet tumor growth was similar to LL conditions. Conclusions Data indicates that circadian disruption by LL provides a favorable condition for tumor growth by promoting an anabolic metabolism in the host. Electronic supplementary material The online version of this article (10.1186/s12885-017-3636-3) contains supplementary material, which is available to authorized users.
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Electrochemotherapy of colorectal liver metastases has been proven to be feasible, safe and effective in a phase I/II study. In that study, a specific group of patients underwent two-stage operation, and the detailed histopathological evaluation of the resected tumors is presented here. Regressive changes in electrochemotherapy-treated liver metastases were evaluated after the second operation (in 8–10 weeks) in 7 patients and 13 metastases when the treated metastases were resected. Macroscopic and microscopic changes were analyzed. Electrochemotherapy induced coagulation necrosis in the treated area encompassing both tumor and a narrow band of normal tissue. The area became necrotic, encapsulated in a fibrous envelope while preserving the functionality of most of the vessels larger than 5 mm in diameter and a large proportion of biliary structures, but the smaller blood vessels displayed various levels of damage. At the time of observation, 8–10 weeks after electrochemotherapy, regenerative changes were already seen in the peripheral parts of the treated area. This study demonstrates regressive changes in the whole electrochemotherapy-treated area of the liver. Further evidence of disruption of vessels less than 5 mm in diameter and preservation of the larger vessels by electrochemotherapy is provided. These findings are important because electrochemotherapy has been indicated for the therapy of metastases near major blood vessels in the liver to provide a safe approach with good antitumor efficacy. © 2017 Gasljevic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Aims/hypothesis: Diabetes promotes cerebral neovascularisation via increased vascular endothelial growth factor (VEGF) angiogenic signalling. Roundabout-4 (ROBO4) protein is an endogenous inhibitor of VEGF signalling that stabilises the vasculature. Yet, how diabetes affects ROBO4 function remains unknown. We hypothesised that increased VEGF signalling in diabetes decreases ROBO4 expression and function via binding of ROBO4 with VEGF-activated β3 integrin and that restoration of ROBO4 expression prevents/repairs cerebral neovascularisation in diabetes. Methods: ROBO4 protein expression in a rat model of type 2 diabetes (Goto-Kakizaki [GK] rats) was examined by western blotting and immunohistochemistry. ROBO4 was locally overexpressed in the brain and in primary brain microvascular endothelial cells (BMVECs). GK rats were treated with SKLB1002, a selective VEGF receptor-2 (VEGFR-2) antagonist. Cerebrovascular neovascularisation indices were determined using a FITC vascular space-filling model. Immunoprecipitation was used to determine ROBO4-β3 integrin interaction. Results: ROBO4 expression was significantly decreased in the cerebral vasculature as well as in BMVECs in diabetes (p < 0.05). Silencing Robo4 increased the angiogenic properties of control BMVECs (p < 0.05). In vivo and in vitro overexpression of ROBO4 inhibited VEGF-induced angiogenic signalling and increased vessel maturation. Inhibition of VEGF signalling using SKLB1002 increased ROBO4 expression (p < 0.05) and reduced neovascularisation indices (p < 0.05). Furthermore, SKLB1002 significantly decreased ROBO4-β3 integrin interaction in diabetes (p < 0.05). Conclusions/interpretation: Our study identifies the restoration of ROBO4 and inhibition of VEGF signalling as treatment strategies for diabetes-induced cerebral neovascularisation.
We report an angle-selective optical filter (ASOF) for highly sensitive reflection photoplethysmography (PPG) sensors. The ASOF features slanted aluminum (Al) micromirror arrays embedded in transparent polymer resin, which effectively block scattered light under human tissue. The device microfabrication was done by using geometry-guided resist reflow of polymer micropatterns, polydimethylsiloxane replica molding, and oblique angle deposition of thin Al film. The angular transmittance through the ASOF is precisely controlled by the angle of micromirrors. For the mirror angle of 30 degrees, the ASOF accepts an incident light between - 90 to + 50 degrees and the maximum transmittance at - 55 degrees. The ASOF exhibits the substantial reduction of both the in-band noise of PPG signals over a factor of two and the low-frequency noise by three times. Consequently, this filter allows distinguishing the diastolic peak that allows miscellaneous parameters with diverse vascular information. This optical filter provides a new opportunity for highly sensitive PPG monitoring or miscellaneous optical tomography.
Purpose To evaluate the reproducibility and interuser agreement of measurements of choroidal neovascularisation in optical coherence tomography angiography (OCTA). Design Prospective non-interventional study. Methods Consecutive patients, presenting with neovascular age-related macular degeneration (AMD), underwent two sequential OCTA examinations (AngioVue, Optovue, Fremont, California, USA), performed by the same trained examiner. Neovascular lesion area was then measured on both examinations in the choriocapillaris automatic segmentation by two masked readers, using the semiautomated measuring software embedded in the instrument. Two measuring features were used: the first corresponding to the total manually contoured lesion area with the flow draw tool (select area) and the second to the total area of solely vessels with high flow within the lesion (vessel area). These measurements were then compared in order to assess both the reproducibility of OCTA examination and the interuser agreement with the embedded software. Results Forty-eight eyes of 46 patients (77.4 mean age,+/-8.2 SD, range from 62 to 95 years old, eight men, 38 women) were included in our study. Mean choroidal neovascularisation area was of 0.72+/-0.7 mm² for the first measurement and 0.75+/-0.76 mm² for the second measurement; difference between the first and the second measurement was 0.03 mm². Intrauser agreement was of 0.98 (CI 0.98 to 0.99) for both ‘vessel area’ and ‘select area’ features. Interuser agreement was of 0.98 (CI 0.97 to 0.99) for ‘select area’ and ‘vessel area’ features. Conclusion Our data suggest that OCTA provide reproducible imaging for evaluation of the neovascular size in the setting of AMD.
Ocular toxicity as a consequence of chronic pesticide exposure is one of the health hazards caused due to extended exposure to pesticides. The cornea, due to its position as the outer ocular layer and its role in protecting the internal layers of the eye; is gravely affected by this xenobiotic insult to the eye, leading to ocular irritation and damage to normal vision. The deleterious effects of chronic pesticide exposure on the various corneal layers and the ocular risks involved therein, were explored by mimicking the on-field scenario. Cytological, histological and flowcytometric parameters were taken into consideration to determine the enhanced risk of corneal neovascularisation and keratectasia, specifically, keratoconus. Chronic exposure to pesticides leads to heightened ocular morbidity wherein there were visible pathophysiological changes to the ocular surface. The cornea was found to be adversely affected with visible protuberance in a cone-like shape, characteristic of keratoconus in a majority of the experimental animals. Further analyses revealed a detrimental impact on all the corneal layers and an amplified expression of inflammation markers such as TNF-α, VCAM-1 and ICAM-1. Additionally, it was found that post pesticide exposure, the corneal surface developed hypoxia, leading to a significant increase of angiogenesis promoting factors and consequential neovascularisation. Apart from ocular toxicity, chronic exposure to pesticides significantly increases the risks of keratectasia and corneal neovascularisation; disorders which lead to diminished vision and if untreated, blindness.
Aims To characterise the vasculature of the retina in patients with Best vitelliform dystrophy, including those with choroidal neovascularisation (CNV), using optical coherence tomography angiography (OCTA) and correlate with fluorescein angiography (FA). Methods This prospective observational study included 19 eyes of 10 patients with Best disease. Using OCTA, all layers of retina were qualitatively characterised for each eye. Patients with CNV also underwent FA, and areas of CNV were measured by OCTA and FA and correlated. Results Retinal characteristics revealed 14 (74%) eyes with abnormal foveal avascular zone (FAZ) in the superficial layer, 19 eyes (100%) had an abnormal FAZ in deep layers, 11 (58%) eyes had a hyper-reflective centre in the superficial layer, 18 (95%) had patchy vascularity loss in the deep layer, 17 (89%) eyes had hyporeflective centre in the choriocapillary (CC) layer and 12 (63%) of those eyes had hyper-reflective material within the hyporeflective centre. Also, notably 6 (86%) CNV eyes had a "halo" or a hypolucent area surrounded in the CNV complex in the outer retinal layer. CNV patterns resembled dense net, loose net, mixed and a new found pattern of a ring shape. CNV measurements revealed an average area of 1.66±1.18mm² using OCTA and an average area of 0.88±0.76mm²⇓ using FA (p=0.15). Conclusion OCTA reveals that eyes with Best disease have abnormal FAZ, patchy vascularity loss in the superficial and deep layers of the retina and capillary dropout with a hyporeflective centre in CC layer. Further, OCTA is superior to FA in measuring CNV.
Background: The impact of old scar tissue on the venous anatomy of a flap's pedicle is an important question in reconstructive surgery. This study tried to investigate the venous component in scar penetrating neovascularisation. Methods: Fifty Sprague-Dawley rats were used in this experimental study. Two experimental groups were designed. In the first group, incisions were performed over the epigastric flap pedicles. In the second group, 1 cm wide segments were excised over the pedicles. Ten weeks after the initial operations, angiographies and histological examinations were performed. A control group was used to demonstrate the normal arterial and venous anatomy of the pedicle. Results: Arterial angiographies revealed that axial pattern arteries were visible in the incision group as opposed to the excision group. Although venous angiographies showed that there were more venous capillary formations in the incision group, none of the experimental groups had regenerated a vein with an axial pattern. Histological examinations revealed that venous vessel formations were significantly less in the distal samples of the experimental groups when compared to the control group (p < 0.05). Conclusions: In this study, it has been observed that arterial pedicles do regenerate over old incision scars as opposed to veins. In the excision scars neither arterial or venous restoration of the axial pedicle was possible. In these cases, only a random type of limited circulation was restored.