Experimental investigation of the determination for the safe operating regime of ultrasound tube-shaped waveguide wire for internal blood vessel debulking

Abstract

BACKGROUND:

Majority of limb amputations are caused by circulatory disturbances such as vascular occlusions and strictures. Discovery of modern and more advanced ultrasonic interventional vascular debulking methodology would likely save limbs of CVD patients and their lives in an economical way. However, there is a lack of researches regarding the ultrasound’s effect on physiological functions of human blood cells. The tube-shaped ultrasound waveguide wire with orifices at its operational end was offered as the alternative to some currently patented interventional thrombosis treatment solutions.

OBJECTIVE:

To establish the safe operating regime of the proposed device.

METHODS:

The temperature rise induced by the cavitation process and friction between the waveguide and surrounding fluids was measured and microscopic pictures of human blood were made.

RESULTS:

Blood insonation lasting 15 seconds, leads to blood clot formation. If insonation continues for 30 seconds some cells are totally destroyed. In addition, the safe operating regime was established. To avoid heating of the environment to the temperature harmful for the medium (blood) and surrounding tissues, is achieved when the system should be on for 40%, and of for 60% of the period of 1 second.

CONCLUSIONS:

The safe operating regime of the proposed device was established.

Keywords

Cavitation ultrasound peripheral artery disease cardiovascular diseases

1. Background

Cardiovascular diseases, often resulting from atherosclerosis, are the leading cause of death in European Union [1]. In total, almost 49 million people live with the CVD in the EU resulting in high cost to the EU economies – nearly €210 billion a year [1]. Of the total cost of CVD in the EU, health care costs account for approx. Fifty-three per cent (€111 billion), productivity losses 26 percent (€54 billion), and informal care of people suffering from CVD 21 percent (€45 billion). Almost half of the individuals who have their extremity amputated due circulatory disturbances (e.g. occlusion), die within 5 years. Nearly 55 percent of people with diabetes who have a lower limb amputation will require amputation of the remaining leg within 2–3 years [2].

Discovery of modern and more advanced ultrasonic interventional vascular clearing methodology would enable saving limbs of CVD patients and their lives in a cost effective way.

Ultrasound refers to a high frequency (0.02 to 200 MHz) acoustic wave that transfers energy in a gas, liquid or solid medium [3]. In gases and liquids, the longitudinal waves of sound mainly propagate, whereas in solid bodies both transverse and longitudinal sound waves can be transmitted. The speed of ultrasound transmission depends on the density and elasticity or stiffness of the medium. The ultrasonic wave occurs due to the rhythmic oscillations of the particles (molecules and atoms) in the medium that cause medium to get denser and to bend (due to particles getting closer and farther from each other, respectively) because of which the pressure tends to increase and decrease, respectively. The vibrations at frequencies higher than 20 kHz are called ultrasonic or the ultrasound. When propagating, the sound pressure oscillations transfer the kinetic energy [4]. The ultrasound energy absorbed by tissues is converted into heat. The ultrasound absorption (conversion into heat) is described by means of the Thermal Index (TI). When TI $=$ 1, the temperature in the medium under consideration rises by 1 degree, when TI $=$ n, by n degrees. TI is mainly dependent on the characteristics of the tissue.

Having sufficient knowledge of the ultrasonic energy etiology and exposimetry, it is possible to plan some bioeffects for therapeutic purposes or to avoid another ones in diagnostic applications [5]. The ultrasound therapeutic effects are induced either by thermal effects or non-thermal mechanisms (gas body activation, ultrasonic cavitation and mechanical stress) [6].

Ultrasound-induced heating results from the absorption of ultrasonic energy by biological tissue. Using ultrasound for diagnostic purposes, the temperature elevations and the potential for bioeffects are kept relatively low or negligible [7] by carefully following the described indications for use, applying the ALARA (As Low As Reasonably Achievable) principal, limited temporal average intensities, and generally short exposure times. On the other hand, therapeutic applications of ultrasonic heating therefore either involve longer durations of heating with unfocused beams or use higher-intensity (than for diagnostic purposes) focused ultrasound. The use of unfocused heating, for example, in physical therapy to treat highly absorbing tissues such as bone or tendon, can be moderated to produce enhanced healing without injury [8]. Alternatively, the heat can be concentrated by focused beams until tissue is coagulated for the purpose of tissue ablation. Ultrasonic heating, which can lead to irreversible tissue changes, follows an inverse time-temperature relationship. Depending on the temperature gradients, the effects from ultrasound exposure can include mild heating, coagulative or liquefactive necrosis, tissue vaporization, or all three [9, 11].

Endothelial dysfunction in blood vessels, leading to impaired vascular relaxation, is an independent risk factor in patients with the suspected coronary insufficiency [10, 11, 12, 13]. Thus, tools to restore endothelial function are to be sought for. Ultrasonic vasomodulation may remedy this problem.

1.1 Objective

To investigate experimentally the newly designed waveguide of an innovative structure by describing the effect it has on human tissues and determining the operational characteristics.

2. Methods

The tube-shaped ultrasound waveguide wire with orifices at its operational end may be used for atherectomy (Figs 1 and 2).

Figure 1.

Ultrasonic vascular cleaning device (cross-section).

Figure 2.

Ultrasonic blood vessels cleaning system, where: 1) Tube-shaped waveguide; 2) Waveguide hole; 3) Fixing screw; 4) Lug; 5) Intake; 6) Concentrator; 7) Transducer.

The waveguide wire of 260 mm in length and 1.5 mm in diameter is considered to be an interventional medical device.

The waveguide wire of such a structure allows impacting the occlusion not only mechanically but also by the flow of physiological fluid infused through the intake (denoted 5 in Fig. 2) [12].

The dimensions of the waveguide were selected based on the standard diameter of arteries in lower human limbs. To ensure the device is capable of operating even at the level of popliteal arteries, the diameter of 1.5 mm was specifically chosen for the waveguide.

The vascular clearing device showed in Fig. 2 involves a tube-shaped waveguide [1] with the holes drilled at its tip [1], trough and open aperture [3] for infusion of drugs and physiological saline solution to the required site of the blood vessel treated, and a metal screw used to attach the waveguide to the concentrator [4] through a specific lug [4]. The system is excited by the high-frequency vibration generator.

During operation of the vascular clearing device the mechanical work accomplished by its operational part [1] not only destroys harmful formulations present in its vicinity inside the blood vessel by means of induced cavitation process but also effectively distributes drugs being fed to the site of lesion. The tube-shaped part [1] of the waveguide while vibrating in its radial and frontal directions causes cavitation process in blood.

Process of cavitation causes microbubbles to form in the fluid (i.e. in blood), and microenergy released during rupture of these bubbles disrupts sediments built-up on the interior walls of the blood vessels thus destroying (removing) blockage from the blood vessel.

Table 1

Technical characteristics of the ultrasound generator VT-400

Supply voltage, V	200–240
Output power, W	Up to 400
Number of channels	1
Output frequency, kHz	15–60
Dimensions, mm	300 $\times$ 425 $\times$ 135
Capacity, W	500

Figure 3.

Ultrasound generator VT-400.

Figure 4.

The Construction of ultrasonic blood vessel cleaning system, where: 1) Conical concentrator, 2) Piezo ceramics ring, 3) Copper ring, 4) Pressing element.

In order to increase efficiency of interior vascular clearing while simultaneously expanding functional capabilities of the ultrasonic device for internal vascular clearing, a steel tube [1] was used as one of the parts comprising the waveguide with the holes drilled at its tip [1]. The open orifice [2] at the tip of tube-shaped part of the waveguide enables feeding an unlimited amount of drugs through the trough to the damaged site of the blood vessel treated, and at the same time allows sucking away scurf of broken harmful formulations generated during operation of the clearing system.

2.1 Equipment used for the research

The ultrasonic system under consideration has been designed to operate jointly with Ultrasound Generator VT-400 and non-standard transducer constructed in situ. The descriptions of the ultrasound generator capable of operating under the pulsed regime and of the piezo-transducer are offered below. Unless specified otherwise, all the experiments under consideration here, involved these two non-standard parts of the system.

2.2 Ultrasound generator VT-400

The main technical characteristics of the ultrasound generator (Fig. 3) are described in Table 1.

Figure 5.

Dimensions of the piezo ring used in the transducer of the ultrasonic system.

Figure 6.

Experimental setup, where 1) Waveguide in a tube filled with water; 2) Thermovisor FLIR SC7000; 3) Generator; 4) PC.

Figure 7.

Schematic view of the experiment.

Figure 8.

Fluid temperature per time, ${}^{\circ}$ C.

Figure 9.

Microscopic photo of erythrocytes exposed to the ultrasound, the control group.

Figure 10.

Microscopic photo of erythrocytes exposed to the ultrasound after 15 s of influence of the cavitation.

Figure 11.

Microscopic photo of erythrocytes exposed to the ultrasound after 30 s of influence of the cavitation.

Figure 12.

The temperature inside a tube when operating under pulsed regime with 60% on, 40% off.

Figure 13.

The temperature inside a tube when operating under pulsed regime with 40% on, 60% off.

2.3 The ultrasound transducer

The ultrasound transduce (Fig. 4) is comprised of the conical concentrator [1] and four piezo ceramic rings (Fig. 5) [1] with the diameter of 25 mm and thickness of 5 mm that are fitted on the conical concentrator and spaced by copper rings with the diameter of 0.5 mm and paper insulation. The entire system is reinforced by the fastening component made of stainless steel with thickness of 16 mm and being smaller by 1 mm in diameter [2].

3. Results

3.1 Mechanical and thermal influence to blood

The device induces cavitation and friction between the waveguide and surrounding fluids leading to drastic temperature rise. Human body temperature above 42 ${}^{\circ}$ C may damage tissues, as red blood cells undergo in vivo haemolysis [13]. To investigate thermal effects, Thermovisor FLIR SC7000, generic generator, PC and the tube-shaped waveguide system was used (Figs 6 and 7).

The first experiment was carried using the operating system inside the tube with the diameter of 3 mm, which in its structure was very similar to a human artery. Data gathered in a course of the experiment revealed that it takes as little as 4 seconds to reach the lethal temperature of 42 ${}^{\circ}$ C (when the starting point was 36 ${}^{\circ}$ C) [12] (Fig. 8).

Next, series of figures presented below indicates what happens to the red blood cells (erythrocytes) after exposing blood to an ultrasound for 30 s. The same experiment setup, as described in Figs 6 and 7 was used.

After blood was affected with ultrasound, blood samples were gathered and thin 1-cell layer was spread on transparent glass plate and checked with electronic microscope. Pictures obtained with microscope can be seen in Figs 9–11.

The microscopic pictures of human blood made after exposing blood to the ultrasound generated by the ultrasonic system with a tube-shaped waveguide revealed that after 15 seconds of treatment, the blood clots are formed, and after 30 seconds of treatment, some cells are totally destroyed. Consequently, it is vital to find and establish the safe operating regime for the ultrasonic vascular clearing system of the innovative design offered here. Bearing all the above in mind, experiments described below were undertaken.

3.2 Determination of the safe operating regime for the ultrasound system

The second experiment was carried out with the aim to determine the safe operating regime of the ultrasonic system under research. Figures 12 and 13 show the results of the experiment.

It was experimentally found that the safe operating regime, i.e. which enables to avoid heating of the environment to the temperature harmful for the medium (blood) and surrounding tissues, is achieved when the system is 40% on, and 60% off over the period of 1 second.

4. Conclusions

Testing the ultrasonic system in human blood, the critical temperature of 42 degrees at the tip of the waveguide was achieved in less than 3 s with the waveguide being vibrated in a continuous mode. For this reason, it is absolutely necessary to ensure the pulsed operating regime, to avoid harmful heating of the environment (blood) and surrounding tissues. The safe operating regime is achieved when the system is 40% on, and 60% off over the period of 1 second.

Investigation of the ultrasonic system in several different positions (for instance, with the clamped tip in air, in the tube filled with water, etc.) allowed finding changes in impedance resistance depending on the position of the tube. This provides exploratory evidence to describe what could happen to the device and surrounding tissue, if the waveguide is reclined against the occlusive malformation or if it is bent-over while in the human artery.

Footnotes

Acknowledgments

This research was funded by the Research Council of Lithuania (project grant no. MIP-097/15). This research was also supported by the Research, Development and Innovation Fund of Kaunas University of Technology (project grant no. PP22/186) and the Research Fund of Lithuanian University of Health Sciences.

Conflict of interest

None to report.

References

Nichols

Townsend

Scarborough

Rayner

. Cardiovascular disease in Europe 2014: epidemiological update. Eur Heart J2014; 35: 2950–9. doi: 10.1093/eurheartj/ehu299.

Robbins

Strauss

Aron

Long

Kuba

Kaplan

. Mortality Rates and Diabetic Foot Ulcers. J Am Podiatr Med Assoc2008; 98: 489–93. doi: 10.7547/0980489.

Hallow

. Measurement and Correlation of Acoustic Cavitation with Cellular and Tissue Bioeffects 2006.

Brujan

Williams

. Bubble dynamics and cavitation in non-newtonian liquids. Rheol Rev 2005: 147–72.

Zeqiri

. Exposure criteria for medical diagnostic ultrasound: II. Criteria based on all known mechanisms. Ultrasound Med Biol2003; 29: 1809. doi: 10.1016/j.ultrasmedbio.2003.09.002.

Fowlkes

, Bioeffects Committee of the American Institute of Ultrasound in Medicine. American Institute of Ultrasound in Medicine consensus report on potential bioeffects of diagnostic ultrasound: executive summary. J Ultrasound Med2008; 27: 503–15.

Alves

Angrisani

Santiago

. The use of extracorporeal shock waves in the treatment of osteonecrosis of the femoral head: a systematic review. Clin Rheumatol2009; 28: 1247–51. doi: 10.1007/s10067-009-1231-y.

Hundt

Yuh

Bednarski

Guccione

. Gene Expression Profiles, Histologic Analysis, and Imaging of Squamous Cell Carcinoma Model Treated with Focused Ultrasound Beams. Am J Roentgenol2007; 189: 726–36. doi: 10.2214/AJR.07.2371.

Silberstein

Lakin

Kellogg Parsons

. Shock wave lithotripsy and renal hemorrhage. Rev Urol2008; 10: 236–41.

10.

Monnink

SHJ

Tio

van Boven

van Gilst

van Veldhuisen

. The role of coronary endothelial function testing in patients suspected for angina pectoris. Int J Cardiol2004; 96: 123–9. doi: 10.1016/j.ijcard.2003.05.030.

11.

Landmesser

Hornig

Drexler

. Endothelial Function: A Critical Determinant in Atherosclerosis? Circulation2004; 109: II-27-II-33. doi: 10.1161/01.CIR.0000129501.88485.1f.

12.

Kargaudas

Bubulis

Navickas

Vitkus

Venslauskas

. Theoretical and experimental investigation of the tube-shaped waveguide wire. J Meas Eng2017; 5: 257–65. doi: 10.21595/jme.2017.19481.

13.

Choi

Pai

. Changes in hematologic parameters induced by thermal treatment of human blood. Ann Clin Lab Sci2002; 32: 393–8.