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PROCEEDINGS OF SPIE

SPIEDigitalLibrary.org/conference-proceedings-of-spie

Thermographic and oxygenation

imaging system for non-contact skin

measurements to determine the

effects of regional block anesthesia

Klaessens, John H. G. M., Landman, Mattijs, de Roode,

Rowland, Noordmans, Herke Jan, Verdaasdonk, Rudolf

John H. G. M. Klaessens, Mattijs Landman, Rowland de Roode, Herke Jan

Noordmans, Rudolf M. Verdaasdonk, "Thermographic and oxygenation

imaging system for non-contact skin measurements to determine the effects

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Thermographic and oxygenation imaging system for non-contact skin

measurements to determine the effects of regional block anesthesia

John H.G.M. Klaessens

*

, Mattijs Landman

**

, Rowland de Roode

*

,

Herke Jan Noordmans

*

, Rudolf M. Verdaasdonk

+

*

Department of Medical Technology and Clinical Physics, University Medical Center Utrecht,

**

Department Anesthesiology, University Medical Center Utrecht,

+

Department Physics and Medical Technology, Free University Medical Center, Amsterdam

The Netherlands

ABSTRACT

Regional anesthetic blocks are performed on patients who will undergo surgery of the hand. In this study, thermal and oxygenation imaging techniques were applied to observe the region affected by the peripheral block as a fast objective, non-contact, method compared to the standard pinpricks or cold sensation tests. The temperature images were acquired with an IR thermal camera (FLIR ThermoCam SC640). The data were recorded and analyzed with the ThermaCamTM

Researcher software. Images at selected wavelengths were obtained with a CCD camera combined with a Liquid Crystal Tunable Filter (420–730 nm). The concentration changes of oxygenated and deoxygenated hemoglobin in the dermis of the skin were calculated using the modified Lambert Beer equation. In 10 patients an anesthetic block was placed by administering 20-30 ml Ropivacaine 7,5 mg/ml around the plexus brachialis. The anesthetic block of the axillary, ulnar, median and radial nerve causes dilatation of the blood vessels inducing an increase of blood flow and, consequently, an increase of the skin temperature and skin oxygenation in the lower arm. Both imaging methods showed distinct oxygenation and temperature differences at the surface of the skin of the hand with a good correlation with the areas with the nerve blocks. For oxygenation imaging a CCD camera with LED light source of selected wavelengths might be a relative inexpensive method to observe the effectiveness of regional blocks.

Keywords: Thermography, Near Infrared, 2D, Hemoglobin, Oxygenation.

1. INTRODUCTION

In literature various methods are described to measure the effectiveness of an anesthetic block. Classical techniques to measure the effectiveness of a block are the response of the patient to cold or pain (pinprick) sensations1. A clear

sensation of pinprick or cold after an anesthetic block indicates inadequate pain suppression and either a supplemental block or change to general anaesthesia is necessary. These sensory tests give in daily clinical practice useful information on the efficacy of regional anesthesia. However, the effectiveness of regional analgesia depends on the intensity of the stimulus applied. The stimulation by these sensory tests used in clinical practice is different than the stimulation associated with clinical pain. Therefore these tests have limited predictive value for the effectiveness of regional analgesia and objective and quantitative methods need to be developed.

Blockade of small sympathetic nerves with local anesthetics will cause vasodilatation and will increase the blood flow thereby increasing the local temperature2,3 and the color of the skin. With thermography, the temperature distribution can

be measured over a large skin area in non-contact mode4.

This study will evaluate the usefulness of a thermography imaging system and a multi-spectral imaging system to predict the success or failure of a regional block in an early stage. These methods are compared to the classical method of cold sensation.

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2. MATERIAL AND METHODS

2.1. Supraclavicular brachial plexus nerve block procedure

Regional anesthetic blocks are a routine practice in anesthesia and pain management of patients. A block provides a reversible loss of sensation in the area where the operation takes place. Supraclavicular block provides anesthesia to the entire arm and hand. The brachial plexus is a collection of nerves trunks that is located in the neck (lower part of the cervical spine, C4, and the upper part of the thorac spine, T1)5,6. The plexus is a braiding of nerves starting at the spine

and splits up in to the axillary, median, ulnar and radial nerves. These nerves control the muscles in and receive sensations from the arm and hand. This study concentrates on changes in de the skin of the hand caused by the induced block. The median nerve gives feeling to the skin of the hand around the palm, the thumb, and the index and middle fingers (fig.1). The ulnar nerve supplies muscles bending the wrist and fingers, and help move the fingers from side to side. It gives feeling to the skin of the half of the back of the hand; ring and little finger and part of the middle finger, the palm of the hand; half of the ring finger and the little finger. The radial nerve muscles that lift and straighten the wrist, thumb, and fingers. The radial nerve gives feeling to the skin on the outside of the thumb and on the back of the hand the index finger and half of the middle finger.

Figure 1 Distribution of cutaneous nerves (radial, Ulnar and median) in the hand for the palmar and dorsal view.

A supraclavicular block is placed around the brachial plexus by injecting 20 to 30 cc Ropivacaine. A prospective, observational study was performed on 10 patients, physical status ASA 1-2, who were scheduled for elective hand and/or wrist surgery under plexus brachialis anaesthesia. The study did not interfere with the normal clinical procedure and informed consent was obtained from each patient before surgery. Exclusion criteria included: contraindication to regional anesthesia, trauma patients, sepsis, and patient refusal. Before insertion of the upraclavicular block, all patients had intravenous (IV) access secured and standard monitoring, electrocardiogram, pulse oximetry and non invasive blood pressure was applied. The patients were placed in a supine position, with their heads turned in the contralateral position of the arm to be anesthesized. Ultrasound was used to have a good perception of the anatomy of the plexus and surrounding vessels and to reduce the complications like a venous or arterial puncture, or intra plexus infiltration of the local anesthetic drug. Using an aseptic technique the 50mm needle (Vygon) was placed in plane with the ultrasound device. A single shot bolus of 20 ml Ropivacaine 0,75% was administered round the plexus. Every 5 minutes cold sensation of the anesthesized arm was tested with a cold pack, the patient was asked if he/she felt cold sensation (score 2), less cold sensation in comparison with the contra- lateral arm (score 1), or no cold sensation (score 0).

2.2. Equipment

2.2.1. Thermographic imaging system

The temperature images were acquired with a calibrated IR thermal camera (FLIR ThermoCam SC640, Seattle, USA), uncooled microbolometer (device for measuring the energy of incident electromagnetic radiation) with a 640x480 pixel array. The sensor has 14 bit dynamic range and the sensitivity is from 7.5 to 13.5 μm. The data were recorded and analyzed with the ThermaCamTM

Researcher 2007 Pro 2.9 (FLIR systems AB, Sweden) software coupled by an

IEEE-1394 FireWire interface with a laptop PC. The thermal camera produces a matrix of temperature values; each pixel in the thermographic image represents one temperature. The data were collected with a temperature resolution of 0.1 degree

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Kelvin (K) and the thermal images were acquired with a 5 second interval. Offline the data were analyzed with software written in MatLab. The LED light used for the multi-spectral imaging did not heat the skin surface. The thermal camera was at a distance of 1 meter from the hand. The emissivity of the skin was set to 0.99.

2.2.2. Multi-spectral camera system

Our basic multi spectral imaging system has been described earlier7-10. A compact temperature compensated

monochrome 12-bit CCD camera (PCO PixelFly QE) is used in combination with a Liquid Crystal Tunable Filter (LCTF) (CRI, Cambridge Research &. Instrumentation, Inc.) . The LCTF is positioned between the lens and the CCD camera and spectrally filters the images between 400 and 720 nm, with a band width of 10 nm. A white LED light source (150 LED’s with a total power of 15 Watt, spectral range 450-700 nm) has been used to illuminate the skin. In front of the light source a linear polarization filter is placed, the polarization filter in front of the camera is positioned 90˚ to the polarization axis of the LCTF, to suppress surface reflection. The acquisition software corrects for the spectrum of the illuminating light source by adapting the integration time for each wavelength. The registration was done at distance of 1 meter. The selected wavelengths where: 440, 470, 530, 560 end 620 nm.

2.2.3. Experimental setup

The hand was resting on a pillow of foam (Tempur) and the camera systems were positioned above the hand. The camera’s were positioned as perpendicular as possible above the hand at a distance of 1 meter (see figure 2). The whole procedure from the start of injection of Ropivacaine, till 30 minutes after was recorded by both imaging systems.

Figure 2: The experimental setup of the thermal camera and multi-spectral imaging. Both cameras’ make images of the surface of a hand in non-contact mode. On the right is a photo of the mobile measuring system.

3. THEORY

3.1. Skin oxygenation calculation

The attenuation of light in tissue is caused by absorption and scattering. The absorption mechanism can be separated in two parts: one due to chromophores with (in time) a constant tissue concentration and one due to chromophores with a variable concentration. In skin tissue, the main varying components are the concentrations of oxy- and deoxyhemoglobin (O2Hb and HHb). These concentrations depend on the oxygen saturation and the total blood volume in the tissue. The

absorbance A in optical densities (OD) is defined as:

10 10 0 log( ) log n n n I A T c d I ε = − = − = Σ (3-1)

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I0 is the intensity of the incident light, I the intensity of the received light, T is the transmission I/I0, d is the optical pathlength in the tissue, ε is the molar extinction coefficient [M-1 cm-1] describing the absorption per molar concentration of the substance per centimeter of optical path, c the concentration of the substance [M] summed over all the particle types (n). Scattering causes light propagation in all directions, which increases the light path through the tissue and thus influences the received light intensity. All together these effects can be comprised in the modified Lambert-Beer law11 (MLBL): ( ) ( ) ( ) ( ) ( ) ( ) Aλ ε λ= c t DPF λ d G+ λ +H t (3.2)

( )

A

λ

Measured absorbence [-]

( )

ε λ

Molar extinction coefficients [mM-1cm-1]

c

(t) Concentration of molecules [mM]

( )

G

λ

Oxygen independent, wavelength dependent losses [-]

( )

H t

Oxygen independent, time dependent losses [-]

d

Source detector distance (optode distance) [cm]

( )

DPF

λ

Differential path length factor [-]

DPF(λ) is the differential pathlength factor, which corrects the geometrical source-detector distance to the mean optical path in the tissue. G(λ) and H(t) are the oxygen independent loss caused by scattering, absorption, geometry and other boundary losses12,13.

Equation 3-2 can be written out for multiple wavelengths to calculate the concentration of chromophores in the skin. During the anesthetic block it is expected that only the blood concentration will change. Equation 3-2 can for example be written out for two chromophores O2Hb and HHb and 3 wavelengths:

( )

2 2 2 2 1 1 1 1 1 1 2 2 2 2 2 2 3 3 3 3 3 3 ( ) ( ) ( ) ( ) ( , ) ( ) ( ) ( ) ( ) ( ) ( ) ( , ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( , ) ( ) O Hb HHb O Hb O Hb HHb HHb O Hb HHb DPF DPF G A t H t c t DPF DPF A t d G H t c t H t DPF DPF A t G ε λ λ ε λ λ λ λ ε λ λ ε λ λ λ λ ε λ λ ε λ λ λ λ ⎡ ⎤ ⎡ ⎤ ⎡ ⎤ ⎢ ⎥ ⎢ ⎥ ⎢ ⎥ ⎡ ⎤ = + ⎢ ⎥ + ⎢ ⎥ ⎢ ⎥ ⎢ ⎥ ⎢ ⎥ ⎣ ⎦ ⎢ ⎥ ⎢ ⎥ ⎢ ⎥ ⎣ ⎦ ⎣ ⎦ ⎤ ⎥ ⎥ ⎢ ⎥⎦ (3.3)

Two different methods can be applied to calculate the concentration changes; the classical Δt-method and the ΔtΔλ-method14. In the classical Δt-method the assumption is made that the H term is zero, or constant in time, and the

wavelength dependent G terms are constant during the period of measurement. Calculating the difference in concentrations over a time period (Δt) relative to a stable starting point the absolute concentration changes can be calculated using known DPF values of the interrogated tissue from literature. This leads to the formula for the concentrations: 1 t t DPF A c d ε −Δ Δ = (3.4)

The ΔtΔλ-method is derived from equation 3.3 under the assumptions; the optical path-length is wavelength dependent but constant in time during the experiments, the geometry factor G is wavelength dependent and the geometry factor H is time dependent. The equation 3.3 can then be rewritten as:

2 2 2 1 1 3 3 12 1 2 1 1 2 2 13 1 3 1 1 3 3 1 1 2 2 1 ( ( ) ( ) ( ) ( ))[ ( ) ( ( ) ( ))] ( ( ) ( ) ( ) ( ))[ ( ) ( ( ) ( ))] ( ) [( ( ) ( ) ( ) ( )) ( ( ) ( ) ( ) ( )) ( ( HHb HHb HHb HHb O Hb HHb HHb O Hb O Hb DPF DPF A t G G DPF DPF A t G G c t d DPF DPF DPF DPF λ λ ε λ λ ε λ λ λ λ ε λ λ ε λ λ λ λ ε λ λ ε λ λ ε λ λ ε λ λ ε λ − Δ − − − − Δ − − = − − − 2 2 1 2 2 1 1 3 3 )HHbDPF( )λ −ε λ( )HHbDPF( ))( ( )λ ε λ O HbDPF( )λ − ε λ( )O HbDPF( )) ]λ

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2 2 2 2 2 2 2 1 1 3 3 12 1 2 1 1 2 2 13 1 3 1 1 3 3 1 1 2 2 1 ( ( ) ( ) ( ) ( ))[ ( ) ( ( ) ( ))] ( ( ) ( ) ( ) ( ))[ ( ) ( )] ( ) [( ( ) ( ) ( ) ( )) ( ( ) ( ) ( ) ( )) ( ( ) O Hb O Hb O Hb O Hb HHb O Hb O Hb HHb HHb O DPF DPF A t G G DPF DPF A t G G c t d DPF DPF DPF DPF λ λ ε λ λ ε λ λ λ λ ε λ λ ε λ λ ε λ λ ε λ λ ε λ λ ε λ λ ε λ − Δ − − − − Δ − − = − − − 2 1 2 2 1 1 3 3 ( ) ( ) ( ))( ( ) ( ) ( ) ( ))] HbDPF λ − ε λ O HbDPF λ ε λ HHbDPF λ −ε λ HHbDPF λ (3-5)

Under the assumption that the G’s are wavelength independent, these factors eliminate each other, resulting in an absolute concentration expression for cO2Hb(t) and cHHb(t). If the G terms cannot be neglected they have to be eliminated from the formula by applying the delta time method to equation 3-5. This results in concentration changes according to the delta wavelength method (Δλ-method).

2 2 2 0 0 ( ) ( ) ( ) ( ) ( ) ( ) O Hb O Hb O Hb t t HHb HHb HHb c t c t c t c t c t c t Δ = − Δ = − (3-6)

The collected multi spectral images of the skin surface can be converted to the reflectance spectrum by correcting them for spatially non uniform light distribution and the camera dark current:

Ref ( , ) ( ) ( , ) ( , ) ( ) S t D R t W t D λ λ λ λ λ − = − (3-7)

S(λ) measured light CCD camera D(λ) Dark current signal

Wref(λ) Reference of 100% reflectance of a white standard

By replacing the A by the R oxygen changes during interventions can be calculated in the backscatter mode.

3.2. Analyzing method

3.2.1. Analyzing Thermography Images

The thermographic images were analyzed by positioning Regions of Interest (ROI’s) on the fingers and on the back of the hand. From the time of injection of Ropivacaine till 30 minutes after, every 5 seconds a temperature image was acquired. As the hand moved during acquisition the ROIs were re-positioned manually to the original position on the hand. With Matlab the average temperature was calculated inside the ROIs. The typical temperature curve after Ropivacaine injection is shown on the right of figure 3 and described by the time till the temperature start rising (T1), the

time till the temperature reaches its maximum (T3) and the time till the temperature reaches half maximum (T2) and the

total temperature rising (ΔTemptot).

1 3 4 10 9 2 5 7 6 8

Figure 3: Ten regions of interest (ROI’s) are positioned on the hand. The typical temperature curve after anesthetic injection is shown on the right. The curve is characterized by the times after the anesthetic injection till the temperature starts rising (T1), time till maximum temperature level is reached (T3),

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3.2.2. Analyzing Multispectral Images

The multi-spectral imaging system acquires a series of images at one wavelength each; with these wavelength-images concentrations of oxygenated and deoxygenated blood in the tissue were calculated. The wavelengths of the acquired images with the extinction coefficients of oxy- and deoxy-hemoglobin are given in table 1 15,16.

Classical delta time method (Δt method formula 3-4) analyses were done with 4 wavelengths: 530, 560, 610 and 650 nm. The inverse matrix is calculated using the speudo-inverse method for non-square matrixes. Formula 3-4 becomes:

2 1 2 3 4 ( , ) ( , ) ( ) 0.0533368 -0.0333579 -0.0259484 -0.01139885 -0.0306518 0.0364707 0.0212027 0.00922596 ( , ) ( ) ( , ) O Hb HHb A t A t c t A t c t A t λ λ λ λ Δ ⎡ ⎤ ⎢ ⎥ Δ Δ ⎡ ⎤= ⎡ ⎤ ⎢ ⎥ ⎢Δ ⎥ ⎢ ⎥ ⎢ Δ ⎥ ⎣ ⎦ Δ ⎥ ⎣ ⎦

The delta Wavelength method (Δλ method formula 3-5) is applied using 560, 610 and 650nm wavelengths, this results in: 2 0 12 13 12 13 0.3951 ( ) 0.3501 ( ) 0.25459 ( ) 0.2456 ( ) Hb HHb c A t A t c A t A t λ λ λ λ = Δ − Δ = − Δ + Δ 4. RESULTS 4.1. Multi-spectral imaging

Figure 4: Example of the results with the delta wavelength method, on the left images of O2Hb and on the right an image of HHb. In the ROI the changes of O2Hb and HHb during

the whole registration are shown in figure 5. Table 1 Used extinction coefficients

Wavelength [nm] HHb [cm-1mM-1] O 2Hb [cm-1mM-1] 530 39.036 39.957 560 53.788 32.6132 585 33.592 30.620 610 9.444 1.506 650 3.7501 0.368

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The Multi-spectral images were analyzed with the formula from 3-3 and 3-5 with the extinction matrixes from chapter 3.2.2. The concentration changes of O2Hb and HHb were calculated with the two methods: delta time and delta

wavelengths. The delta time method compares all the images with the first reference image. Since the patients are moving the hand during the 30 minutes of measurement, the motion blur corrupts the data. Only when a selection is made of image with minimal movement the calculations give consistent results (fig. 5). The Δt method proves to be not practical for this application. The delta wavelength method calculates differences between wavelengths (recorded within 1 second), this method has only small movement artefacts. Positioning ROI’s on the fingers the mean value of changes in O2Hb and HHb during the time of the measurement were calculated. The time between injections of Ropivacaine till the

time of rising or falling of the concentration change were calculated (T1) and the time till maximum change was reached

(T3). In figure 4 an example of the oxy and deoxy images of the hand are shown based on the Δλ method.

Figure 5: In the ROI both concentration calculation methods were applied resulting in changes of O2Hb and

HHb concentration during the block procedure.

Time response oxygenation change

0,00 1,00 2,00 3,00 4,00 5,00 6,00 7,00 8,00 9,00 10,00

Thumb fore finger middle finger ring finger little finger

Del

ta T

ime

ΔT1 ΔT3

Figure 6: The times till first start of changes in concentrations of O2Hb and HHb (T1) and the

time till maximum effect is reached (T3). This is measured for all the fingers average of 5

patients using the delta wavelength method. 4.2. Thermo imaging

The thermo image of a normal hand and a hand with a block are shown in figure 6, the left hand has normal skin temperatures (~ 300 Kelvin) and the anesthesized hand has higher temperatures (310 Kelvin) and the veins are clearly visible.

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Figure 7: Normal hand before anesthesia (left) and the hand 30 minutes after Ropivacaine injection that resulted in a successful nerve block.

Thermo images were analyzed by calculating the average temperatures in the ROI on the hand, an example of the thermo images before and after the block are presented in figure 7. The typical curves of the mean temperature in the ROIs are presented in figure 8, in these curves the T1, T2, T3 and temperature increase are determined. The averages of 5 patients

with successful blocks were analyzed and the result are presented in figure 9.

Figure 8: Typical examples of the mean temperature curves in the ROI (diameter 10 mm), the Ropivacaine is injected 1 minute after the start of the registration.

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Figure 9: First results from 5 successful patients with heating starting in the thumb.

After analyzing the data the patient can be divided in 3 groups; group 1 has first temperature rising in the thumb, the second group starts with temperature rising in the little finger and the third group has a high (305Kelvin) skin

temperature in the normal condition. Most patients behave like group 1, the first temperature rising starts in the thumb (Figure 9). The temperature rises maximal 8 to 9 degrees Kelvin (Figure 9).

Figure 10: The maximum temperature rise at T3 in the ROI on the hand,

The group with starting temperature rising in the little finger is smaller and the maximal temperature rising is also 8-9 degrees. The last group with high skin temperature (305 K, this is 7 degrees higher then normal skin temperature) gives nearly no rising of temperature (1-2 degrees K).

The cold response is measured by touching the ventral (front) or dorsal (back) of the under arm with a cold compress, the response of the patient is categorized in three groups: normal cold feeling, less temperature sensing or no cold sensing. The results are presented in table 3.

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Ventral Dorsal Time [min] Pat1 Pat 2 Pat3 Pat4 Pat5 Pat6 Pat1 Pat 2 Pat3 Pat4 Pat5 Pat6

5

10

15

20

25

Cold sensation compared to other arm Score 2 Normal cold feeling

Score 1 Less temperature sensing Score 0 No cold sensing

Table 3: Results of cold sensation test in 6 patients with a successful block.

5. DISCUSSION

Both methods measuring temperature and oxygenation changes provide early indications of a successful anesthetic block. Thermography has consistent results while multi-spectral imaging; the T1 and T3 are in both techniques early

predictors of changes caused by the block. The time response T1 and T3 are faster in Multi-spectral spectroscopic

measurements then in the thermography recordings. But we have to little patients to tell if this is structural. To calculate oxygenation changes on a moving hand only the Δλ-method can be used. The Δt-method can not be used due to the movement of the patient’s hand. This could be improved by better fixation however this is not practical and comfortable for the patient. The oxygenation changes induced by the anesthetics (blood flow increase) using the Δλ-method are relatively small. However the data provide sufficient information to give a prediction. Due to the limited number of patients, it is difficult to identify the predictors in the multispectral data for a successful block. The software needs to be improved. We found a maximum temperature rise in the fingers of 8 -9 degrees up to 37 Celsius. This indicates that the vessels are fully dilated. Cold response is not objective; patients feel the touching and the cold sensation, they need to separate these feelings and only respond to cold sensation. This requires a clear understanding and patients need to give expression to their feelings, this is not an objective measurement. In table 3, patient 6 feels no cold sensation till 25 minutes after Ropivacaine, or patients keep feeling cold sensation till 25 minutes after anesthesized, this while all blocks were successful. This can cause delay in operation scheduling or the patient is given extra unnecessary aesthetics. The multi-spectral imaging system used in this study is based on a LCT filter; this could be replaced by a less expensive LED light source which can flash in high speed. It is to be expected that this faster system will give less movement artefacts in the concentration calculation algorithms. The IR camera used could also be replaced by a less sophisticated camera or point measurement system. This system could observe only the ROIs that give an early indication of the effectiveness of the block.

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6. CONCLUSION

The classical test of the effectiveness of a regional block is the response of the patient to a cold sensation. This method depends on many subjective factors related to the patient and is unreliable. The IR thermography method proves to be an objective method and can be used as an early predictor for the success of the regional block. The multispectral imaging shows only small changes and needs to be improved to become a reliable method with the potential to develop a low cost detection system. Further study will be necessary to obtain the sensitivity and specificity of both the methods of detecting the success or failure of the regional block.

7. ACKNOWLEDGEMENT

The authors acknowledge the contribution of Jay Sardjoe and Stefan Janssen for performing the measurements as a BSc project.

8. LITERATURE

[1] Curatolo, M., Petersen-Felix, S., and rendt-Nielsen, L., "Sensory assessment of regional analgesia in humans: a review of methods and applications", Anesthesiology93, 1517-1530 (2000).

[2] Iwase, S., Cui, J., Wallin, B. G., Kamiya, A., and Mano, T., "Effects of increased ambient temperature on skin sympathetic nerve activity and core temperature in humans", Neurosci.Lett.327, 37-40 (2002).

[3] Davis, S. L., Fadel, P. J., Cui, J., Thomas, G. D., and Crandall, C. G., "Skin blood flow influences near-infrared spectroscopy-derived measurements of tissue oxygenation during heat stress", J.Appl.Physiol100, 221-224 (2006).

[4] Niehof, S. P., Huygen, F. J., van der Weerd, R. W., Westra, M., and Zijlstra, F. J., "Thermography imaging during static and controlled thermoregulation in complex regional pain syndrome type 1: diagnostic value and involvement of the central sympathetic system", Biomed.Eng Online.5, 30 (2006).

[5] Partridge, B. L., Katz, J., and Benirschke, K., "Functional anatomy of the brachial plexus sheath: implications for anesthesia", Anesthesiology66, 743-747 (1987).

[6] Thompson, G. E. and Rorie, D. K., "Functional anatomy of the brachial plexus sheaths", Anesthesiology59, 117-122 (1983).

[7] de Roode, R., Noordmans, H. J., Verdaasdonk, R. M., and Sigurdsson, V., "Multispectral system evaluates treatments in dermatology", Laser Focus World, 102-104 (2006).

[8] de Roode, R., Noordmans, H. J., and Verdaasdonk, R. M., "Feasibility of multi-spectral imaging system to provide enhanced demarcation for skin tumor resection", SPIE (2007).

[9] Noordmans, H. J., de Roode, R., and Verdaasdonk, R. M., "Compact multi-spectral imaging system for dermatology and neurosurgery", SPIE6510 (2007).

[10] Noordmans, H. J., de Roode, R., and Verdaasdonk, R. M., "Multi-spectral image enhancement in dermatology and neurosurgery", S128-S130 (2007).

[11] Delpy, D. T., Cope, M., van der Zee, P., Arridge, S., Wray, S., and Wyatt, J., "Estimation of optical pathlength through tissue from direct time of flight measurement", .Phys.Med.Biol.33, 1433-1442 (1988).

[12] Delpy, D. T. and Cope, M., "Quantification in tissue near-infrared spectroscopy", Philosophical Transactions of the Royal Society B-Biological Sciences352, 649-659 (1997).

[13] Edwards, A. D., Richardson, C., van der, Z. P., Elwell, C., Wyatt, J. S., Cope, M., Delpy, D. T., and Reynolds, E. O., "Measurement of hemoglobin flow and blood flow by near-infrared spectroscopy

2", J.Appl.Physiol75, 1884-1889 (1993).

[14] Klaessens, J. H. G. M., Noordmans, H. J., de Roode, R., and Verdaasdonk, R. M., "Non-invasive skin oxygenation imaging using a multi-spectral camera system: effectiveness of various concentration algorithms applied on human skin", SPIE Vol: 7174Optical Tomography and Spectroscopy of Tissue VIII, 717408 (2009). [15] Wray, S., Cope, M., Delpy, D. T., Wyatt, J. S., and Reynolds, E. O., "Characterization of the near infrared

absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation", Biochim.Biophys.Acta933, 184-192 (1988).

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