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Non-contact tissue perfusion and oxygenation imaging using a LED based multispectral and a thermal imaging system, first results of clinical intervention studies

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PROCEEDINGS OF SPIE

SPIEDigitalLibrary.org/conference-proceedings-of-spie

Non-contact tissue perfusion and

oxygenation imaging using a LED

based multispectral and a thermal

imaging system, first results of

clinical intervention studies

John H. G. M. Klaessens, Martin Nelisse, Rudolf M.

Verdaasdonk, Herke Jan Noordmans

John H. G. M. Klaessens, Martin Nelisse, Rudolf M. Verdaasdonk, Herke Jan

Noordmans, "Non-contact tissue perfusion and oxygenation imaging using a

LED based multispectral and a thermal imaging system, first results of clinical

intervention studies," Proc. SPIE 8572, Advanced Biomedical and Clinical

Diagnostic Systems XI, 857207 (22 March 2013); doi: 10.1117/12.2003807

Event: SPIE BiOS, 2013, San Francisco, California, United States

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Non-contact tissue perfusion and oxygenation imaging using a LED

based multispectral and a thermal imaging system, first results of

clinical intervention studies

John H.G.M. Klaessens

*

, Martin Nelisse

*

, Rudolf M. Verdaasdonk

+

, Herke Jan Noordmans

*

*

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

Utrecht, The Netherlands.

+

Department Physics and Medical Technology, Free University Medical Center,

Amsterdam, The Netherlands

ABSTRACT

During clinical interventions objective and quantitative information of the tissue perfusion, oxygenation or temperature can be useful for the surgical strategy. Local (point) measurements give limited information and affected areas can easily be missed, therefore imaging large areas is required. In this study a LED based multispectral imaging system (MSI, 17 different wavelengths 370nm-880nm) and a thermo camera were applied during clinical interventions: tissue flap transplantations (ENT), local anesthetic block and during open brain surgery (epileptic seizure). The images covered an area of 20x20 cm, when doing measurements in an (operating) room, they turned out to be more complicated than laboratory experiments due to light fluctuations, movement of the patient and limited angle of view. By constantly measuring the background light and the use of a white reference, light fluctuations and movement were corrected. Oxygenation concentration images could be calculated and combined with the thermal images. The effectively of local anesthesia of a hand could be predicted in an early stage using the thermal camera and the reperfusion of transplanted skin flap could be imaged. During brain surgery, a temporary hyper-perfused area was witnessed which was probably related to an epileptic attack.

A LED based multispectral imaging system combined with thermal imaging provide complementary information on perfusion and oxygenation changes and are promising techniques for real-time diagnostics during clinical interventions.

Keywords: Multi-spectral, Near Infrared, Image processing, Hemoglobin, Oxygen, Thermography

1. INTRODUCTION

Reflectance spectroscopy and thermography are used as non- invasive, non-contact imaging method to study the physiology of superficial tissue processes. For more then 3 decades near infrared (NIR) light has been used to study regional blood and tissue oxygenation changes in animal studies, clinical intervention studies and in oxygen supply and

consumption in the brain and muscles 1-5. In these studies contact measurements were done using fibers to acquire

regional tissue oxygenation from deeper tissue layers (depending on the distance between the transmitter and the receiver), this in contrary to the imaging methods described in this proceeding. The theory to calculate tissue oxygenation changes is adapted for these applications. Multi-spectral imaging using a CMOS camera is applied for monitoring hemodynamic and metabolic changes in superficial tissue layers like skin, muscle or brain (open skull) over

large areas6. A tunable LED multispectral imaging system has been developed, algorithms are still being developed7 to

calculate oxygenation changes.

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CCD camera

Lens

IIII

iii

mil

LED

Light

LED controller

2. MATERIAL AND METHODS

2.1 Multi-spectral imaging system

A multispectral imaging sytem has been built and validated in our department. It can homogeneous illuminate from large distance (in practice ~ 1 meter), and be used as a continuous or flashing light source. The LEDs range from UV to the near infrared (370nm – 880 nm). The lamp is built up as a 2D flat panel with a total of 600 LEDs, consisting of 17 different wavelengths. The characteristics of all the LEDs have been measured for different power settings and frequencies (full illumination intensity, wavelength temperature dependency, etc.). The back scattered light from the tissue is collected by a CMOS camera which is mounted in the middle of the panel (figure 1). The multispectral imaging system is optimized for non-lab environments by real-time background subtraction to eliminate the fluctuations of the ambient light. Afterwards corrections for the movements in the images was done using home written Match software.

8 bit

CMOS

camera

Figure 1, The multispectral imaging system, on the right the LED multispectral tunable lamp. During clinical use extra

plastic sheets cover the wires to prevent dust from entering the surgical scene.

2.2 Thermal camera system

For thermography a standard calibrated FLIR camera was used (FLIR ThermoCam SC640, Seattle, USA). It can measure absolute temperatures using an uncooled microbolometer with a 640x480 pixel array with a 14 bit dynamic

range sensor operating in the range from 7.5 to 13.5 μm. The data were recorded and analyzed with the ThermaCamTM

Researcher 2007 Pro 2.9 software (FLIR systems AB, Sweden). The data were collected with a temperature resolution of 0.1 degree Kelvin (K) and acquired with a 1 second interval.

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2.3 Clinical measurements

To apply multispectral imaging in the operation room precautions have to be taken. First we have to take account of the fact that the illumination spectrum and the camera sensitivity spectra are not flat. Also, the used system can be unstable over time. To correct for this, a white/grey reference must be used and be visible in all the images.

In the operation room there are always fluctuations in the ambient light: moving persons, shadows, and headlights are disturbing the multispectral measurements. The first step is to reduce the environment light to what is necessary for the clinical procedure, turn-off fluorescent lightning; low intense halogen bulbs are acceptable. Real-time corrections for the background are preformed to correct for slow changes in ambient light and integration times and individual LED intensities are adapted to avoid saturation of the 8 bit CMOS camera.

All the measurements must be done with 100% safety for personnel and patient, extensive risk analyses were done and approval from Medical Ethical Committee of the hospital was acquired.

3. THEORY

3.1 Oxygen calculation

From the backscattered reflectance images concentration changes of oxy- and deoxy-hemoglobin were calculated using

three different methods. The theory has been described before8, and is based on the modified Lambert-Beer law9

(MLBL). Delta time method (∆t) solves the Lambert Beer equation by taking differences in time relative to a steady

base level to remove the unknown constant in the equation. Delta wavelength method (∆λ) uses differences between the

wavelengths to remove the unknown constant in the Lambert Beer equation, this is done instantaneously. The Fit method (FIT) is based on the pseudo inverse method (Moore-Penrose) to match the found spectra with the literature reflection spectra.

4. RESULTS

The hyper-spectral and thermal imaging systems are applied in several clinical trials and we will report the first results of three studies: ENT flap transplantation, anesthetic block and epilepsy surgery. Measuring in pre-operation or operation room is more complicated then under laboratory conditions.

4.1 ENT flap transplantation

Radial free arm flap transplantation is a frequently used method to restore oral cavity defects caused by surgery when removing cancer. The flap is an area of skin and fat layer that is removed together with an artery and venous blood

Figure 2, Thermal and Multispectral imaging during

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In our study all patients had a tumor in the tongue which was removed, hereafter the tongue is reconstructed with the forearm flap. After the flap is transplanted to the tongue and the vessels are reconnected, they are opened and the flap will be reperfused and filled with oxygenated blood.

Both the moments of re-perfusion of the tissue flap are imaged with the multi-spectral and thermal imaging systems.

Figure 3, Schematic overview of flap on arm, on the right harvested flap on arm.

In our study five flap transplantations have been imaged with approval of the Medical Ethecal Commission. The flaps are analyzed by calculating oxy and deoxy images. In ROIs over the flap and underarm oxy and deoxy changes over time were calculated (figure 4). A clear increase in oxy and a decrease n deoxyhemoglobin is seen over the whole flap.

Figure 4, results of analyzes of flap on arm, 5 regions of interest are chosen. In these points the oxy and deoxy changes

are calculated over the time of the measurement. The three images on the down are oxy-hemoglobin images before,

during and after opening of the blood pressure cuff; blue represents low and red high O2Hb changes relative to the blood

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29.5 o e ms ììN 27.5 25 5 Flap 04),r,rit"w^'1",,,,e+r,,,A,+"fr

/Pi

0 1 2 3 Time [minutes] 4 5 t= 0 minutes t-- 2.5 minutes t= 4 minutes -035 c 32e - 80 28e 26e time [minutes]

-

002HB

_

AHEB

Figure 5, Temperature imaging of reperfusion of flap on arm. In two ROIs the temperature is measured over the whole

registration: on the flap and on the lower arm.

Simultaneous temperature images were recorded. Analyzes of temperature in ROIs show a clear increase of temperature after reperfusion.(figure 5).

The same is done after transplantation of the flap to the mouth. Here also a clear inflow of blood is seen after reconnection of the blood vessels (figure 6), increase of oxy- and decrease of deoxy-hemoglobin. The temperature registration did not show the expected increase because the flap was already heated up in the mouth before the blood flow was restored and the flap was wet which influences the temperature registered with an IR thermal camera.

Figure 6, Flap transplanted to tongue. The oxygenation changes in one ROI on the flap show clearly oxy- increase and

deoxy-hemoglobin decrease (in the figure the flow is opened 2 times).

4.2 Anesthetic Block

In the pre-operation room a supraclavicular block was placed under ultrasound guidance around the brachial plexus. This resulted in the relaxation of the muscles around the blood vessels and arterioles causing an increase of perfusion and temperature in the skin. The multispectral and thermal imaging was started a few minutes before the block was placed till 20 minutes after. A response in temperature increase in the fingertips war seen minutes after the block was placed and large increase of temperature was seen (8-10 degrees).

An example of these physiologic effects is shown in figure 7, we observed a small oxygenation change in the skin but a large temperature response.

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eo2HB _el-EHB time [minutes 38 36 34 32

i

30 28 26 2.00 4.00 6.00 8.00 10.00 12.00 0.00 time [minutes] t=12min

Figure 7, Monitoring of the hand during an anesthetic block, the response in oxygenation and temperature are shown. In

the lower row thermal images over time are shown (temperature range 22-38 degrees Celsius).

4.3 Epileptic center localization

During brain surgery the cortex of an epilepsy patient with recurring seizures was imaged with the multi-spectral camera. The thermal camera is not used because of the fluid layer on top of the cortex, the cortex temperature will be influenced by the vaporization of that fluid layer. Intracranial EEG examination located the epileptic center in the sensory cortex. During seizures an increase in oxygenated and total blood volume in the same area of the sensory cortex could be observed in the calculated hemoglobin images (results not shown). After multiple subpial transections in this motor area, clinical seizures abated. Multispectral oxygenation imaging opens prospects of intra operative function localization.

5. DISCUSSION AND CONCLUSIONS

The LED multispectral imaging system was successful in measuring perfusion and oxygenation changes during clinical interventions studies. Compared to lab experiments, clinical experiments with multi-spectral imaging are complicated by fluctuations in ambient light and movements of patients. It is important to reduce the ambient light intensity as low as possible and turn of the fluorescent lightning. Additional to this we applied successfully background correction to correct for slow variations in the ambient light. Stability and motions were corrected by measuring a white reference and image matching respectively.

The ENT flap reperfusion measurements on the arm and in the mouth gave good results for the oxygenation images. In the mouth it is difficult to see the whole flap but the reperfusion was successful monitored with the multispectral imaging system. In the mouth the flap had adapted to the body temperature before the vessels were connected, the reperfusion of the flap was difficult to see in the thermal images. For this application multispectral imaging gives the best results. The

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anesthetic block measurements showed nearly no oxygenation changes on the hand, this could be caused by the fact that the peripheral perfusion of the hand was open and the block effected only the large vessels. This would explain the good results for the thermal imaging and the subtle changes in the oxygenation images.

The imaging of the cortex during epilepsy surgery was only done with our multispectral imaging system. The focus of epilepsy was clearly seen in the increase of O2Hb in that area.

Physiological changes in tissues in clinical practice, like oxygenation and temperature, can be observed using the LED based multi-spectral imaging system and IR thermography. These techniques can be useful tools for real-time diagnostics for physiological processes in different fields in medicine.

REFERENCES

[1] Delpy, D. T. and Cope, M., "Quantification in tissue near-infrared spectroscopy", Philosophical

Transactions of the Royal Society B-Biological Sciences352, 649-659 (1997).

[2] Ferrari, M., Mottola, L., and Quaresima, V., "Principles, techniques, and limitations of near

infrared spectroscopy", Can.J.Appl.Physiol29, 463-487 (2004).

[3] Jobsis, F. F., "Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency

and circulatory parameters", Science198, 1264-1267 (1977).

[4] Klaessens, J. H., Hopman, J. C., Liem, K. D., van Os, S. H., and Thijssen, J. M., "Effects of

skin on bias and reproducibility of near-infrared spectroscopy measurement of cerebral

oxygenation changes in porcine brain", J.Biomed.Opt.10, 44003 (2005).

[5] Madsen, P. L. and Secher, N. H., "Near-infrared oximetry of the brain", Prog.Neurobiol.58,

541-560 (1999).

[6] Kawauchi, S., Nishidate, I., Uozumi, Y., Nawashiro, H., Ashida, H., and Sato, S., "Diffuse

light reflectance signals as potential indicators of loss of viability in brain tissue due to

hypoxia: charge-coupled-device-based imaging and fiber-based measurement",

J.Biomed.Opt.18, 15003 (2013).

[7] 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: 7174 (2009).

[8] Klaessens, J. H. G. M., Landman, M., de Roode, R., Noordmans, H. J., and Verdaasdonk, R.

M., "Thermographic and oxygenation imaging system for non-contact skin measurements to

determine the effects of regional block anesthesia", SPIE7548G-157, Session 3 (2010).

[9] 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).

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