Clinical application of laser Doppler flowmetry in neurology

Transcription

1 Perspectives in Medicine (2012) 1, Bartels E, Bartels S, Poppert H (Editors): New Trends in Neurosonology and Cerebral Hemodynamics an Update. Perspectives in Medicine (2012) 1, journal homepage: Clinical application of laser Doppler flowmetry in neurology Zlatka Stoyneva 15 Acad. Ivan Geshov Str., St. Ivan Rilsky University Hospital, 1404 Sofia, Bulgaria KEYWORDS Laser Doppler flowmetry; Clinical application; Neurology Summary Laser Doppler flowmetry is a contemporary method for microcirculatory investigation used in different medical fields including neurology. Aim: To present principles and clinical application of laser-doppler method in neurology and related pathologies. Methods: The diagnostic value was studied by evaluating systematic literature and personal experience. It is based on Doppler principle and uses a laser-generated monochromatic light beam, a fiber-optic probe and sensitive photodetectors. The tissue perfusion of a sample volume is calculated by multiplying the number of moving blood cells and their velocity and is presented in perfusion units. Results: A high diagnostic value was established in studying microcirculation and its autoregulation using a battery of functional tests for evaluation of vasomotor response mediated by sympathetic neural, axon-reflex, receptor or endothelial mechanisms. It has clinical significance in assessment of Raynaud s phenomenon, distal autonomic neuropathy of the small C fibers due to diabetes mellitus, peripheral arterial occlusive disease, systemic autoimmune diseases, chronic venous insufficiency, peripheral neuropathies, for medical expertise of occupational diseases as hand-arm vibration syndrome, toxic neuropathies, etc. By iontophoretic transducer different drugs or substances might be applied locally to test an effect, physiological or pathophysiological mechanisms. Unlike the contemporary ultrasound investigations it studies the blinded sphere for neurosonology microcirculation and its autoregulation. Conclusions: Laser Doppler flowmetry is a valuable and reliable method for diagnostics of microcirculation and perfusion, for assessment of autoregulation and effect of treatment, for experimental studies and research. In combination with ultrasound sonography it gives a thorough information for both macro- and microcirculation Elsevier GmbH. Open access under CC BY-NC-ND license. Corresponding author. Tel.: address: zlatka stoyneva@yahoo.com X 2012 Elsevier GmbH. Open access under CC BY-NC-ND license.

2 90 Z. Stoyneva Introduction Laser Doppler flowmetry (LDF) is a contemporary noninvasive method for microvascular investigation used in different medical fields including neurology. The Doppler shift of the laser beam is the carrier of the information about microcirculatory blood flow. Many studies have proved reliable correlations between LDF and clearance of 133Xe [1], fluorescence flowmetry [2], venous occlusion plethysmography and heat thermal clearance [3] as methods for microcirculatory investigations. Unlike plethysmography and isotope clearance techniques LDF monitors and records sudden microcirculatory changes and reflex responses to sympathetic vasomotor stimuli [4] giving a reproducible parameter of sympathetic vasomotor control [5]. The aim of the study was to present the principles and clinical application of laser-doppler method in neurology and related pathologies. Methods The diagnostic value of LDF was studied by evaluating the systematic literature and our personal experience submitting some data for illustration. Results The working of LDF is based on Doppler principle using a laser-generated monochromatic light beam, a transducer with optic fibers and sensitive photodetectors. The light beam is reflected and scattered by the moving blood cells undergoing a change of the wave length (Doppler shift), dependent on the number and velocities of the cells in the investigated sample volume but not on the direction of their movement [6]. The scattered laser beam is perceived by detectors with the help of optic fibers. The signals are analyzed giving values to the number of the cells and their velocities and perfusion is their product. The depth of penetration of laser beam depends on the tissue characteristics and its vascularisation, on the length of the light wave, the distance between the optic fibers. So the penetration of light source with wave length 633 nm is less than that with 780 nm. By investigation of the skin the depth is from 0.5 to 1.5 mm, and the sample volume is about 1 mm 3. Only the movement in microvessels but not in the bigger blood vessels contributes to the perfusion value because the vessel wall is enough to exclude the greatest part of the laser beam. Calibration of different apparatuses makes their values equal. LDF of the skin is easiest to access noninvasively and thus global skin blood flow including both nutritious (capillaries) and thermoregulatory (arterioles, venules and their shunts) microvessels is investigated. The information about thermoregulatory blood flow prevails because the blood flow from the richly sympathetically innervated arterio-venular anastomoses and subpapillary plexus contribute predominantly to the laser-doppler signal, especially of the volar site of the hand and plantar site of the feet. About 90 98% of the Figure 1 Finger pulp perfusion during venoarteriolar test in Raynaud s phenomenon patients [16]. PU perfusion units at a finger pulp; PUi initial perfusion; PUb basal perfusion at 32 C; PUh perfusion at heart level; PUd perfusion in the dependent hand; Controls group of healthy controls, Primary RP primary RP group; SSc RP secondary RP group due to sclerodermy; Vibration RP secondary vibration-induced RP group; *p < 0.05; **p < in relation to previous perfusion value according to Wilcoxon matched pairs signed rank test. finger pulp flow passes through arteriovenular anastomoses [7]. Registration of initial skin perfusion in controlled standard laboratory conditions is measured at first with the natural superficial skin temperature of the patient and then the perfusion is recommended to be measured at Celsius superficial skin temperature in order to make skin perfusion at a definite site between different persons comparable. The accuracy and sensitivity of LDF is improved by applying standardized functional tests [8]. Monitoring of microvascular responses to autonomic vasomotor stimuli is a recognized method for functional diagnosis and assessment of peripheral dysautonomy and function of small unmyelinated autonomic fibers [9]. Thus in orthostatic test constriction of skin precapillary and arteriolar sphincters and microvessels due to the increased sympathetic mediation induces a decrease of skin blood flow. Posture changes of the limbs below heart level activate sympathetic venoarteriolar axon-reflex mechanisms and cause increased skin microvascular resistance like in orthostatism with decrease of skin perfusion. Testing of veno-arteriolar reflex at the finger pulp by LDF is an indicator of unmyelinated autonomic C fiber function [8] and pure postganglionic sympathetic nervous activity [10]. It is more sensitive method for assessment of autonomic dysfunction than the sympathetic skin response [11]. Vasoconstrictor response is changed in the limbs of patients with peripheral arterial occlusive disease [12], diabetic [13] or venous hypertensive microangiopathy [14]. In diabetics type 2 and patients with chronic venous insufficiency a primary defect of venoarteriolar axon-reflex is speculated [7]. Dysregulation of feedback mechanisms between venules, identifying the transmural pressure and arterioles, controlling precapillary resistance is found in secondary Raynaud s phenomenon, too [15,16] (Fig. 1). Inspiratory tests of Valsalva, deep breathing, deep inspiration with abdominal arrest induce sympathetic vasoconstriction activity with significant decrease of skin perfusion. Peripheral microvascular resistance is significantly decreased in diabetes mellitus. By cold test a somatic afferent part consisted of pain and temperature nerve fibers in the skin and a sympathetic

3 Clinical application of laser Doppler flowmetry 91 efferent vasoconstrictor part of the reflex arch is evaluated. The effectiveness of the response after cold stress test with temperature below 15 Celsius might be an index of a sympathetic vasoconstrictor activity [17,18]. Tests of isometric muscular constriction and emotional stress also induce sympathetic skin vasoconstriction [19,20]. By heating test an axon-reflex mediated thermoregulatory microvascular vasodilation is studied as a result of activation of heat-induced nociceptors even at a lack of conscious perception of heat-induced pain [21]. The release of vasoactive peptides from primary nociceptor afferents cause an initial local heat-induced vasodilation at temperatures above 40 Celsius followed by a sustained plateau phase induced by nitric oxide. Thermoregulatory vasomotor responses are abnormal in Raynaud s phenomena (Fig. 2) and diabetic foot (Fig. 3). Reactive hyperemia test is mediated by local endothelial dependent vasodilator factors with significant decrease of skin vascular resistance and sudden increase of skin perfusion in healthy persons (Fig. 4). Microcirculatory vasodilator reactivity in response to ischemia reflects functional integrity of terminal vessels and assesses microvascular endothelial dependent dilator capacity in physiological and pathological conditions. Vascular responses to drugs or chemical substances as physiological or pathophysiological mechanisms in different diseases can be studied experimentally by using an iontophoresis system for delivering minute volumes of a substance non-invasively in a controlled fashion together with LDF. Along with other spheres of application LDF is a valuable method in neurology to diagnose small fiber neuropathy Figure 2 Perfusion at finger pulps during heating test in Raynaud s phenomenon patients [22]. PU perfusion units at a finger pulp; PUi initial perfusion; PUb basal perfusion at 32 C; PUh perfusion at 44 C; PUc perfusion back to 32 C; Controls group of healthy controls; Primary RP primary RP group; SSc RP secondary RP group due to sclerodermy; Vibration RP secondary vibration-induced RP group. Figure 3 Heating test applied to tiptoes in a healthy person (A) and diabetic patients (B D) with reduced or absent responses to heating and/or cooling [23].

4 92 Z. Stoyneva Figure 4 Reactive hyperemia test applied to tiptoes in healthy persons (A, B) and diabetic patients (C, D)[23]. and distal acral vasomotor dysautonomia as an idiopathic or secondary manifestation of polyneuropathies, radiculopathies, mononeuropathies, reflex sympathetic dystrophy, neurovascular syndromes caused by diabetes mellitus, thyroid dysfunction, rheumatic diseases, amyloidosis, lepra, AIDS, venous limb insufficiency, neuropathic pain or occupationally induced by overstrain, vibration, micrortrauma, toxic exposure, etc. The method is valuable to follow up the effect of applied therapy. It is reliable and with very good reproducibility. A laser Doppler blood perfusion imager is created scanning tissue with a low-power laser beam and colour-coded images of the blood perfusion in the microvasculature. Conclusions Unlike the contemporary ultrasound investigations laser Doppler flowmetry studies the blinded sphere for neurosonology, i.e. microcirculation and its autoregulation. Laser Doppler flowmetry is a valuable, easy to use, nonexpensive microcirculatory method of investigation which in combination with ultrasound sonography gives thorough information for both macro- and microcirculation. Laser-generated monochromatic light beam is directed towards the surface of the investigated tissue by a probe with optic fibers. The tissue perfusion of the investigated sample volume monitored by the flowmeter is calculated automatically by multiplying the number of the moving blood cells and their velocity and is presented in perfusion units (PU). Laser beam penetrates tissues, so monitoring of perfusion is noninvasive. for assessment of the integrity of constrictor microcirculatory mechanisms. Afterwards with increased skin flux, decreased venoarteriolar response and increased skin filtration inducing edema Using functional reflex vasomotor tests contribute for differentiation of primary from secondary Raynaud s phenomenon. diabetic distal sympathetic neuropathy and microangiopathy; small fiber neuropathy; polyneuropathies or radiculopathies with autonomic dysfunction., distal sympathetic neuropathy, neurovascular syndromes, toxic neuropathies and microvascular reflex vasomotor reactivity and evaluation of microcirculatory vasomotor response mediated by sympathetic neural, axon-reflex, receptor or endothelial mechanisms; It is reliable to follow up the effect of applied therapy. Measurements are less dynamic than with the probe-based single-point laser Doppler monitor but the microcirculation can be studied over a larger area. Laser Doppler flowmetry not only measures and monitors microvascular blood flow but also evaluates microcirculation and its autoregulation. References [1] Tur E, Tur M, Maibach HI, Guy RH. Basal perfusion of the cutaneous microcirculation: measurements as a function of anatomic position. Journal of Investigative Dermatology 1983;81: [2] Proano E, Svensson L, Perbeck L. Correlation between the uptake of sodium fluorescein in the tissue and xenon-133 clearance and laser Doppler fluxmetry in measuring changes in skin circulation. International Journal of Microcirculation: Clinical and Experimental 1997;17:22 8. [3] Saumet JL, Dittmar A, Leftheriotis G. Non-invasive measurement of skin blood flow: comparison between plethysmography, laser-doppler flowmeter and heat thermal clearance

5 Clinical application of laser Doppler flowmetry 93 method. International Journal of Microcirculation: Clinical and Experimental 1986;5: [4] Oberg PA. Laser-Doppler flowmetry. Biomedical Engineering 1990;18: [5] Hilz MJ, Hecht MJ, Berghoff M, Singer W, Neundoerfer B. Abnormal vasoreaction to arousal stimuli-an early sign of diabetic sympathetic neuropathy demonstrated by laser Doppler flowmetry. Journal of Clinical Neurophysiology 2000;17: [6] Oberg PA. Blood flow measurements. Linkoping University: CRC Press; [7] Nuzzaci G, Evangelisti A, Righi D, Giannico G, Nuzzaci I. Is there any relationship between cold-induced vasodilatation and vasomotion? Microvascular Research 1999;57:1 7. [8] Wahlberg E, Olofsson P, Swedenborg J, Fagrell B. Level of arterial obstruction in patients with peripheral arterial occlusive disease (PAOD) determined by laser Doppler fluxmetry. European Journal of Vascular Surgery 1993;7: [9] Abbot NC, Beck JS, Mostofi S, Weiss F. Sympathetic vasomotor dysfunction in leprosy patients: comparison with electrophysiological measurement and qualitative sensation testing. Neuroscience Letters 1996;206: [10] Birklein F, Riedl B, Neundorfer B, Handwerker HO. Sympathetic vasoconstrictor reflex pattern in patients with complex regional pain syndrome. Pain 1998;75: [11] Wilder-Smith A, Wilder-Smith E. Electrophysiological evaluation of peripheral autonomic function in leprosy patients, leprosy contacts and controls. International Journal of Leprosy and Other Mycobacterial Diseases 1996;64: [12] Creutzig A, Caspary L, Alexander K. Disturbances of skin microcirculation in patients with chronic arterial occlusive disease and venous incompetence. VASA 1988;17: [13] Rayman G, Hassan A, Tooke JE. Blood flow in the skin of the foot related to posture in diabetes mellitus. British Medical Journal 1986;292: [14] Belcaro G, Laurora G, Cesarone MR, De Sanctis MT, Incandela L. Microcirculation in high perfusion microangiopathy. Journal of Cardiovascular Surgery 1995;36: [15] Edwards CM, Marshall JM, Pugh M. Cardiovascular responses evoked by mild cool stimuli in primary Raynaud s disease: the role of endothelin. Clinical Science (London) 1999;96: [16] Stoyneva Z. Laser Doppler-recorded venoarteriolar reflex in Raynaud s phenomenon. Autonomic Neuroscience 2004;116:62 8. [17] Kurvers HA, Tangelder GJ, De-Mey JG, Slaaf DW, Beuk RJ, vanden-wildenberg FA, et al. Skin blood flow abnormalities in a rat model of neuropathic pain: result of decreased sympathetic vasoconstrictor outflow? Journal of the Autonomic Nervous System 1997;63: [18] Hodges GJ, Traeger 3rd JA, Tang T, Kosiba WA, Zhao K, Johnson JM. Role of sensory nerves in the cutaneous vasoconstrictor response to local cooling in humans. American Journal of Physiology Heart and Circulatory Physiology 2007;293:H [19] Tuck RR, McLeod JG. Vasomotor function and dysfunction. In: Asbury AK, McHaun GM, McDonald WI, editors. Diseases of the Nervous System. Clinical Neurobiology, I II, 2nd ed. London, Toronto, Montreal, Sydney, Tokyo, Philadelphia: WB Saunders Co.; p [20] Stanton AW, Levick JR, Mortimer PS. Assessment of noninvasive tests of cutaneous vascular control in the forearm using a laser Doppler meter and a Finapres blood pressure monitor. Clinical Autonomic Research 1995;5: [21] Tew GA, Klonizakis M, Moss J, Ruddock AD, Saxton JM, Hodges GJ. Role of sensory nerves in the rapid cutaneous vasodilator response to local heating in young and older endurance-trained and untrained men. Experimental Physiology 2011;96: [22] Stoyneva Z. Raynaud s Phenomenon. Sofia: AEM AMS Infopress; p. 252 (in Bulgarian). [23] Stoyneva Z. Diabetic Peripheral Neuropathy. Sofia: AEM AMS Infopress; p. 260 (in Bulgarian).