Comparison of Laser Speckle Contrast Imaging and Laser Doppler Imaging
Condition: Microcirculation
Study type: Interventional

Summary: 
      The microcirculation plays a fundamental role in metabolic reactions and has been shown as an
      essential determinant in many clinical scenarios such as shock states, chronic and
      cardio-metabolic diseases. Microcirculation can be assessed directly using laser-based
      techniques and intravital microscopes. When combined with provocation tests, microvascular
      monitorization can be used to assess microvascular function.

      Laser-based techniques are consist of two different methods named laser doppler imaging
      (LDI), laser speckle contrast imaging (LSCI). LSCI is a technique based on speckle contrast
      analysis that provides an index of blood flux. No need for skin contact, continuous and
      real-time assessment of the microcirculation led the LSCI to be broadly used in clinical
      practice. LDI is also a non-invasive diagnostic method used to measure the blood flux of
      tissue. The technique is based on measuring the doppler shift induced by moving red blood
      cells to the illuminating coherent light. Iontophoresis is one of the most commonly used
      provocation tests to study the endothelium in terms of endothelium-dependent and
      endothelium-independent vasodilation. Simultaneously with LDI and LSCI are used to follow and
      assess the skin blood flux during iontophoresis. Therefore, it provides a state to make a
      comparison between two different laser-based techniques in terms of flux characteristics.

      The accurate assessment of burn depth is a critical step in the management of the
      burn-injured patient. Currently, LDI is the most widely used non-invasive measurement tool
      for assessing burn wounds and the only technique approved by the U.S. Food and Drug
      Administration. However, the LDI device is rather costly, cumbersome, and has a poor spatial
      resolution. LSCI measures perfusion in a similar way, but it provides high-quality images
      with a much higher spatial resolution. In addition, LSCI is much quicker, maneuverable, and
      able to assess larger skin areas. In order to use the LSCI technique in the clinical practice
      of burn-injured patients, as a first step, the linearity of LDI and LSCI should be shown. In
      this study, we aimed to compare LSCI and LDI with iontophoresis and stepwise occlusion
      technique. So, we will test the linearity of devices over a large range of blood flux values.
    

Detailed description: 
      Measurements of microcirculation were initiated upon the ethical consent was approved. 15
      healthy volunteer were included in the study. All volunteers were asked for the existence of
      any symptoms for the on-going disease like flu, infectious disease, and chronic disease
      (Diabetes, hypertension, rheumatologic disorders, epileptic disorders, etc.). Once the
      volunteer met inclusion criteria, he/she became eligible for study. Volunteers were advised
      to beware from food and drink for at least two hours before measurement. Also, they were
      advised to come at least two hours after big meals like lunch or dinner. All the volunteers
      were evaluated at the same position (sitting and hand at heart level), room and temperature
      to provide equal standards. The volunteer had rest for at least 30 minutes in a
      semi-recumbent and extending leg position. The room temperature was 24-26C and checked with a
      thermometer intermittently. The door was closed to prevent air movement. Lights were switched
      off, and the curtains were closed to prevent the effect of light on devices. Once all the
      environmental conditions met, two investigators evaluated the volunteer. One investigator
      checked the volunteer's blood pressure, temperature, and heart rate.

      A vacuum pillow was used to hold the arm stable during the procedure. Two different devices
      (laser speckle contrast imaging (LSCI) and laser doppler imaging (LDI)) were ready next to
      the volunteer. An appropriate intact skin area, inner side of the forearm were used for the
      investigation and both electrodes were attached. The skin surface was cleaned with alcohol or
      deionized water to remove remnants of cosmetics and creams with low conductivity. This helped
      to prevent spots with high current density that may result in local burns and non-specific
      vascular reactions. After peeling off the protective tape layer on the bottom of the Drug
      Delivery Electrode, the electrode was firmly attached to the skin. The Dispersive Electrode
      was placed approximately 10-15 cm from the Drug Delivery Electrode. Power supply was
      connected by attaching the electrodes to the leads. After lifting the lid of the Drug
      Delivery Electrode using the pointed tab, tip of the syringe was slided under the lid of the
      Drug Delivery Electrode and the Drug Delivery Chamber was filled with approximately 0.5 mL of
      a 10 mg/ml SNP solution. The drug was then delivered using cathodal iontophoresis for 1
      minute with a current strength of 200 µA. The LDI and LSCI instruments are positioned so they
      can alternately measure the delivery site. Basal perfusion was measured with both instruments
      before starting iontophoresis. Subsequently, iontophoresis was started and measurements are
      made alternating between the two instruments. Therefore, we would be able to compare both
      devices in terms of supra-baseline flux values. When all measurements were finished, the
      electrodes removed from the patient and the Drug Delivery Electrode and the Dispersive
      Electrode was removed.

      The second part of the study was performed as step-wise occlusion. The arm which was not used
      for iontophoresis test was used for step-wise occlusion. The baseline blood flux was followed
      for 2 minutes by LDI and LSCI. After 2 minutes, the upper arm was occluded for 30 seconds
      with a pneumatic cuff up to 50 mmHg, 80 mmHg, 110 mmHg, 140 mmHg, and 170 mmHg. Between each
      part, the volunteer had rest for 5 minutes to let the blood flux to turn the baseline. Once
      reaching to the planned pressure, LSCI and LDI devices were alternately be used to record
      blood flux. Therefore, we were able to compare both devices in terms of sub-baseline flux
      values.

      All data were recorded in 2 external electronic storage, and the names of the volunteers were
      coded with numbers. Only main investigator was aware of who corresponds to which number.
      Results of Perimed and Moore Devices were analyzed with the software PIMsoft 1.5 (Perimed AB,
      Järfälla, Sweden), MoorLDI2-BI Burn's Software Version 4.0, respectively. Two investigators
      performed the analysis. If one investigator made the analysis, the other checked the results,
      as well.
    

Intervention name(s): Iontophoresis; Stepwise occlusion
Intervention type(s): Device; Other
Intervention description(s): By using the PeriIont (Perimed, Jarfalla, Sweden) device, 0.5 mL of a 10 mg/ml Sodium nitroprusside solution was used transdermally and ionised with a current strength of 200 µA for 1 minute.; The upper arm was occluded for 30 seconds with a pneumatic cuff up to 50 mmHg, 80 mmHg, 110 mmHg, 140 mmHg, and 170 mmHg. The volunteer had rest for 5 minutes between each occlusion procedure.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Screening
Keywords: microcirculation; laser speckle contrast imaging; laser doppler perfusion imaging; iontophoresis; comparison; flux