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In view of the spreading of the Covid-19 virus, Real-Time Background Oriented Schlieren (RT-BOS) and backlight scatter imaging were used to visualize the air motion and droplets during talking, coughing, sneezing, singing, playing wind instruments. The effectiveness of personal protection like face masks and shields were studied. The distance of air (aerosols) spreading depends on the diameter/shape of the opening and air volume blown out per unit of time. Remarkably, the aerosol and droplet spreading of singing is similar or less than talking and even less for wind instruments. Any mouth mask although leaking air is effective in preventing droplets to spread.

To follow the development of pigment disorders like vitiligo over time, a newly developed full spectral modified ‘UV camera’ was introduced to enhance the image quality of vitiligo lesions in comparison to conventional images and surface area drawings. The quality of 31 images of lesions was assessed as good for 100% for the UV camera and 26% for the conventional camera by experts. The intraclass correlation coefficients (ICCs) of the lesion size between the imaging techniques were > 0.98. The UV camera provides high contrast images and enables the assessment of vitiligo lesions and accurate quantification of the surface area.

Smart phones have come out with advanced features that can be useful for medical diagnosis. The Iphone X has a face recognition function to unlock the phone which could actually be used as a full functional 3D scanner. Unfortunately, only a few app developers have seen the potential of the Iphone X. The Bellus3D IOS app is dedicated for face scanning with the option to export data in slt/obj format for analysis on other software platforms. The face scans can be performed in 30 seconds including processing. A hardware adaption was developed to perform 3D scans also in the direction of backside of the Iphone X. To test the resolution and color representation of the Iphone X, scans were obtained of face phantoms and compared with high-end 3D scanners (Artec Spider/EVA and Vectra) using deviation maps. The Iphone X/Bellus3D performed best for the front view of the face. Presence of hair resulted in distortion of the side view. The mesh density was around 0.6-0.8 mm which is less compared to the Artec scanners (

Currently, allergy testing is performed by exposing the skin to small quantities of potential allergens on the inner forearm thereby scratching the protective epidermis to increase exposure. After 15 minutes the dermatologist performs a visual check of the 'bump' induced by swelling and erythema. In this study, two high resolution 3D scanners (Artec Spider and EVA) were used to quantify the dimensions (circumference, surface area, thickness) of the bump and to assess which parameters correlate with the diagnosis of the dermatologist. For comparison and validation of the scanners and the analysis-software (Artec Studio and GOM Inspect), phantom 'bumps' were developed. In a small clinical feasibility study, data of 3 patients with 17 positive allergic reactions were obtained and analyzed with the optimum settings based on the phantom study. Although both scanners could differentiate between the reaction grade 1, 2 or 3 assigned by the dermatologist, the results were not significant due to the small number of reactions at this time of the study. Both in the phantom and clinical study, the Artec Spider 3D scanner showed the allergic reactions clearly but an practical method of analysis needs to be developed to grade them similar to dermatologists. The resolution of the Artec EVA 3D scanner is lower but this scanner is more practical for use in the clinic (fast and easy to use). 3D scanners have a great potential for quantitative imaging in dermatology and aesthetic surgery.

Recently, low cost smart phone based thermal cameras are being considered to be used in a clinical setting for monitoring physiological temperature responses such as: body temperature change, local inflammations, perfusion changes or (burn) wound healing. These thermal cameras contain uncooled micro-bolometers with an internal calibration check and have a temperature resolution of 0.1 degree. For clinical applications a fast quality measurement before use is required (absolute temperature check) and quality control (stability, repeatability, absolute temperature, absolute temperature differences) should be performed regularly. Therefore, a calibrated temperature phantom has been developed based on thermistor heating on both ends of a black coated metal strip to create a controllable temperature gradient from room temperature 26 °C up to 100 °C. The absolute temperatures on the strip are determined with software controlled 5 PT-1000 sensors using lookup tables. In this study 3 FLIR-ONE cameras and one high end camera were checked with this temperature phantom. The results show a relative good agreement between both low-cost and high-end camera's and the phantom temperature gradient, with temperature differences of 1 degree up to 6 degrees between the camera's and the phantom. The measurements were repeated as to absolute temperature and temperature stability over the sensor area. Both low-cost and high-end thermal cameras measured relative temperature changes with high accuracy and absolute temperatures with constant deviations. Low-cost smart phone based thermal cameras can be a good alternative to high-end thermal cameras for routine clinical measurements, appropriate to the research question, providing regular calibration checks for quality control.

In the development of new near-infrared (NIR) fluorescence dyes for image guided surgery, there is a need for new NIR sensitive camera systems that can easily be adjusted to specific wavelength ranges in contrast the present clinical systems that are only optimized for ICG. To test alternative camera systems, a setup was developed to mimic the fluorescence light in a tissue phantom to measure the sensitivity and resolution. Selected narrow band NIR LED's were used to illuminate a 6mm diameter circular diffuse plate to create uniform intensity controllable light spot (μW-mW) as target/source for NIR camera's. Layers of (artificial) tissue with controlled thickness could be placed on the spot to mimic a fluorescent 'cancer' embedded in tissue. This setup was used to compare a range of NIR sensitive consumer's cameras for potential use in image guided surgery. The image of the spot obtained with the cameras was captured and analyzed using ImageJ software. Enhanced CCD night vision cameras were the most sensitive capable of showing intensities < 1 μW through 5 mm of tissue. However, there was no control over the automatic gain and hence noise level. NIR sensitive DSLR cameras proved relative less sensitive but could be fully manually controlled as to gain (ISO 25600) and exposure time and are therefore preferred for a clinical setting in combination with Wi-Fi remote control. The NIR fluorescence testing setup proved to be useful for camera testing and can be used for development and quality control of new NIR fluorescence guided surgery equipment.

It is difficult to obtain quantitative measurements as to surface areas and volumes from standard photos of the body parts of patients which is highly desirable for objective follow up of treatments in e.g. dermatology. plastic, aesthetic and reconstructive surgery. Recently, 3-D scanners have become available to provide quantification. Phantoms (3-D printed hand, nose and ear, colored bread sculpture) were developed to compare a range from low-cost (Sense), medium (HP Sprout) to high end (Artec Spider, Vectra M3) scanners using different 3D imaging technologies, as to resolution, working range, surface color representation, user friendliness. The 3D scans files (STL, OBJ) were processed with Artec studio and GOM software as to deviation compared to the high resolution Artec Spider scanner taken as †golden' standard. The HP Spout, which uses a fringe projection, proved to be nearly as good as the Artec, however, needs to be converted for clinical use. Photogrammetry as used by the Vectra M3 scanner is limited to provide sufficient data points for accurate surface mapping however provides good color/structure representation. The low performance of the Sense is not recommended for clinical use. The Artec scanner was successfully used to measure the structure/volume changes in the face after hormone treatment in transgender patients. 3D scanners can greatly improve quantitative measurements of surfaces and volumes as objective follow up in clinical studies performed by various clinical specialisms (dermatology, aesthetic and reconstructive surgery). New scanning technologies, like fringe projection, are promising for development of low-cost, high precision scanners.

In burn wounds early discrimination between the different depths plays an important role in the treatment strategy. The remaining vasculature in the wound determines its healing potential. Non-invasive measurement tools that can identify the vascularization are therefore considered to be of high diagnostic importance. Thermography is a non-invasive technique that can accurately measure the temperature distribution over a large skin or tissue area, the temperature is a measure of the perfusion of that area. The aim of this study was to investigate the clinimetric properties (i.e. reliability and validity) of thermography for measuring burn wound depth. In a cross-sectional study with 50 burn wounds of 35 patients, the inter-observer reliability and the validity between thermography and Laser Doppler Imaging were studied. With ROC curve analyses the ΔT cut-off point for different burn wound depths were determined. The inter-observer reliability, expressed by an intra-class correlation coefficient of 0.99, was found to be excellent. In terms of validity, a ΔT cut-off point of 0.96°C (sensitivity 71%; specificity 79%) differentiates between a superficial partial-thickness and deep partial-thickness burn. A ΔT cut-off point of -0.80°C (sensitivity 70%; specificity 74%) could differentiate between a deep partial-thickness and a full-thickness burn wound. This study demonstrates that thermography is a reliable method in the assessment of burn wound depths. In addition, thermography was reasonably able to discriminate among different burn wound depths, indicating its potential use as a diagnostic tool in clinical burn practice.

Allergy testing is usually performed by exposing the skin to small quantities of potential allergens on the inner forearm and scratching the protective epidermis to increase exposure. After 15 minutes the dermatologist performs a visual check for swelling and erythema which is subjective and difficult for e.g. dark skin types. A small smart phone based thermo camera (FLIR One) was used to obtain quantitative images in a feasibility study of 17 patients Directly after allergen exposure on the forearm, thermal images were captured at 30 seconds interval and processed to a time lapse movie over 15 minutes. Considering the 'subjective' reading of the dermatologist as golden standard, in 11/17 pts (65%) the evaluation of dermatologist was confirmed by the thermo camera including 5 of 6 patients without allergic response. In 7 patients thermo showed additional spots. Of the 342 sites tested, the dermatologist detected 47 allergies of which 28 (60%) were confirmed by thermo imaging while thermo imaging showed 12 additional spots. The method can be improved with user dedicated acquisition software and better registration between normal and thermal images. The lymphatic reaction seems to shift from the original puncture site. The interpretation of the thermal images is still subjective since collecting quantitative data is difficult due to motion patient during 15 minutes. Although not yet conclusive, thermal imaging shows to be promising to improve the sensitivity and selectivity of allergy testing using a smart phone based camera.

During laparoscopic surgery, devices are require to either cut, ablate or coagulate tissue and veins with high precision and controlled lateral damage preferably in an one-for-all modality. The tissue interactions of 3 new treatment modalities were studied using special imaging techniques to obtain a better understanding the working mechanism in view of effective and safe application. The Plasmajet produces a high temperature ionized gas 'flame' directed to the tissue surface at the tip of a 4 mm diameter rigid hand piece. The Lumenis DUO CO2 laser enables endoscopic laser energy delivery through a 1 mm outer diameter flexible hollow waveguide. The 2 µm 'Thulium' laser is delivered by (standard) 400 µm diameter optical fiber. Thermal imaging and Schlieren techniques were used to assess the superficial ablative and coagulation effects these surgical instruments scanning at preset velocities and distances from the surface of biological tissues and phantoms . The CO2 was very effective in tissue ablation even at a distance up to 10 mm due to a very small diverging beam from the hollow waveguide. In contrast, the Thulium laser showed less ablation and increasing coagulation at larger distance to the tissue. The gas 'flame' of the Plasmajet spread the thermal energy over the surface for effective superficial ablation and coagulation. However, the pressure of the gas flow is substantial on the tissue surface creating turbulence and even indirect cooling. The specific ablation and coagulation effects of the three treatment modalities have to be appreciate and the effective and safe application will depend on the preference and skills of the surgeon

Infection following neurosurgery is all too common. One possible source of infection is the transportation of dust and other contaminates into the open wound by airflow within the operating theatre. While many modern operating theatres have a filtered, uniform and gentle flow of air cascading down over the operating table from a large area fan in the ceiling, many obstacles might introduce turbulence into the laminar flow including lights, equipment and personal. Schlieren imaging - which is sensitive to small disturbances in the laminar flow such as breathing and turbulence caused by air warmed by a hand at body temperature – was used to image the air flow due to activities in an operating theatre. Color intensity projections (CIPs) were employed to reduce the workload of analyzing the large amount of video data. CIPs – which has been applied to images in angiography, 4D CT, nuclear medicine and astronomy – summarizes the changes over many gray scale images in a single color image in a way which most interpreters find intuitive. CIPs uses the hue, saturation and brightness of the color image to encode the summary. Imaging in an operating theatre showed substantial disruptions to the airflow due to equipment such as the lighting. When these disruptions are combined with such minor factors as heat from the hand, reversal of the preferred airflow patterns can occur. These reversals of preferred airflow patterns have the potential to transport contaminates into the open wound. Further study is required to understand both the frequency of the reversed airflow patterns and the impact they may have on infection rates.

Clinical interventions can cause changes in tissue perfusion, oxygenation or temperature. Real-time imaging of these phenomena could be useful for surgical strategy or understanding of physiological regulation mechanisms. Two noncontact imaging techniques were applied for imaging of large tissue areas: LED based multispectral imaging (MSI, 17 different wavelengths 370 nm-880 nm) and thermal imaging (7.5 to 13.5 μm). Oxygenation concentration changes were calculated using different analyzing methods. The advantages of these methods are presented for stationary and dynamic applications. Concentration calculations of chromophores in tissue require right choices of wavelengths The effects of different wavelength choices for hemoglobin concentration calculations were studied in laboratory conditions and consequently applied in clinical studies. Corrections for interferences during the clinical registrations (ambient light fluctuations, tissue movements) were performed. The wavelength dependency of the algorithms were studied and wavelength sets with the best results will be presented. The multispectral and thermal imaging systems were applied during clinical intervention studies: reperfusion of tissue flap transplantation (ENT), effectiveness of local anesthetic block and during open brain surgery in patients with epileptic seizures. The LED multispectral imaging system successfully imaged the perfusion and oxygenation changes during clinical interventions. The thermal images show local heat distributions over tissue areas as a result of changes in tissue perfusion. Multispectral imaging and thermal imaging provide complementary information and are promising techniques for real-time diagnostics of physiological processes in medicine.

Color intensity projections (CIPs) has been employed to improve the accuracy and reduce the workload of interpreting a series of grayscale images by summarizing the grayscale images in a single color image. CIPs – which has been applied to grayscale images in angiography, 4D CT, nuclear medicine and astronomy – uses the hue, saturation and brightness of the color image to encode the summary information. In CIPs, when a pixel has the same value over the grayscale images, the corresponding pixel in the color image has the identical grayscale color. The arrival time of a signal at each pixel, such as the arrival time of contrast in angiography, is often encoded in the hue (red-yellow-green-light blue-blue-purple) of the corresponding pixel in the color image. In addition, the saturation and brightness of each pixel in the color image encodes the amplitude range and amplitude maximum of the corresponding pixel in the grayscale images. In previous applications of CIPs the hue has been limited to less than one cycle over the color image to avoid the aliasing due to a hue corresponding to more than one arrival time. However, sometimes in applications such as angiography and astronomy, in some instances the aliasing due to increasing the number of cycles of hue over the color image is tolerable as it increases the resolution of arrival time. Key to applying hue cycling effectively is interpolating several grayscale images between each pair of grayscale images. Ideally, the interpreter is allowed to adjust the amount of hue cycling in realtime to find the best setting for each particular CIPs image. CIPs with hue cycling should be a valuable tool in many fields where interpreting a series of grayscale images is required.

Optical parametric oscillators (OPOs) are attractive tools for research on tissue ablation upon infrared irradiation. Here, we report on the performance of several mid-infrared nonlinear crystals, namely type I and type II AgGaS2 (AGS) and type I CdSiP2 (CSP), used in synchronously-pumped OPOs tuned to a wavelength of 6.45 µm, coinciding with the amide II absorption band of proteins. CSP-based OPOs clearly exhibit better performance in comparison to AGS: First, the oscillation threshold with CSP is three (five) times lower than type II (type I) AGS. Second, the idler conversion efficiency is more favourable for CSP and allows reaching 27.5 mW of idler average power, while 13 and 6 mW are obtained with type II and type I AGS, respectively. Such performance makes CSP suitable for high power 6.45 µm surgical applications. Preliminary ablation experiments on liver tissues with our CSP-based OPO highlight the promising future of CSP in medical applications.

An objective method to measure the effectiveness of regional anesthesia can reduce time and unintended pain inflicted to the patient. A prospective observational study was performed on 22 patients during a local anesthesia before undergoing hand surgery. Two non-invasive techniques thermal and oxygenation imaging were applied to observe the region affected by the peripheral block and the results were compared to the standard cold sensation test. The supraclavicular block was placed under ultrasound guidance around the brachial plexus by injecting 20 cc Ropivacaine. The sedation causes a relaxation of the muscles around the blood vessels resulting in dilatation and hence an increase of blood perfusion, skin temperature and skin oxygenation in the lower arm and hand. Temperatures were acquired with an IR thermal camera (FLIR ThermoCam SC640). The data were recorded and analyzed with the ThermaCam TM Researcher and Matlab software. Narrow band spectral images were acquired at selected wavelengths with a CCD camera either combined with a Liquid Crystal Tunable Filter (420-730 nm) or a tunable hyper-wavelength LED light source (450-880nm). Concentration changes of oxygenated and deoxygenated hemoglobin in the dermis of the skin were calculated using the modified Lambert Beer equation. Both imaging methods showed distinct oxygenation and temperature differences at the surface of the skin of the hand with a good correlation to the anesthetized areas. A temperature response was visible within 5 minutes compared to the standard of 30 minutes. Both non-contact methods show to be more objective and can have an earlier prediction for the effectiveness of the anesthetic block.

Visualisation of the thermo dynamics of surgical coagulation devices like laser, diathermy and RFA devices in tissue are essential to get better understanding about the principles of operation of these devices. Thermo cameras have the ability to measure absolute temperatures. However, the visualization of temperature fields using thermal imaging has always been limited to the surface of a medium. We have developed a new strategy to look below the surface of biological tissue by viewing through a ZincSelenide window positioned alongside a block of tissue. When exposed from above with an energy source, the temperature distribution below the surface can be observed through the window. To obtain a close-up view, the thermo camera is enhanced with special macro optics. The thermo dynamics during tissue interaction of various electro surgery modes was studied in biological tissues to obtain a better understanding of the working mechanism. Simultaneously with thermal imaging, normal close-up video footage was obtained to support the interpretation of the thermal imaging. For comparison, temperature gradients were imaged inside a transparent tissue model using color Schlieren imaging. The new subsurface thermal imaging method gives a better understanding of interaction of thermal energy of surgical devices and contributes to the safety and the optimal settings for various medical applications. However, the technique has some limitations that have to be considered. The three imaging modalities showed to be both compatible and complementary showing the pro- and cons- of each modality.

The outcome of stapedotomy depends on several surgical steps. Using laser light, the ossicular chain can be handled and the oval window can be punctured with a non-touch method. Various lasers are being used or considered, however, it is not clear which settings and characteristics will contribute to optimal or adverse effects (vestibule damage and loss hearing frequencies). Using a unique high speed thermal imaging setup based on Schlieren techniques, the mechanical and thermal effects during laser stapedotomy were studied in an inner ear model consisting of human, fresh frozen stapes positioned on a liquid filled cavity in a gel cast. The cw KTP (532 nm), cw CO 2 (10.6 μm), cw Thulium (2.0 μm), pulsed Er,Cr;YSGG (2.78 μm) coupled to special fiber delivery systems were applied at typical clinical settings for comparison. The imaging techniques provided a good insight in the extent of heat conduction beneath the footplate and (explosive) vapour formation on both sides. For the pulsed laser modes, explosive vapour expansion can to be controlled with optimized pulse energies while for continuous wave lasers the thermal effects can be controlled with the pulse length and repetition rate. The fluence at the tip of the delivery system and the distance to the footplate has a major impact on the ablation effect. The pulsed IR lasers with fiber delivery show to be promising for a controlled stapedotomy.

To observe local variations in temperature, oxygenation and blood perfusion over time, four imaging systems were developed and compared: Two systems consisting of white broadband light source and a CCD camera in combination with a Liquid Crystal Tunable Filter, one in the visual domain, 420-730 nm, and one in the infrared domain, 650-1100 nm. Thirdly, a CCD camera in combination with a software controlled hyper-spectral light source consisting of a panel with 600 LEDs divided in 17 spectral groups in the range from 370 to 880 nm so that specific spectral distributions can be generated at high repetition rate (>1000 Hz) and, fourthly a standard IR thermal camera for comparison. From the acquired images at the selected wavelengths chromophores concentration images of oxy and deoxy hemoglobin can be calculated applying different algorithms. These imaging techniques were applied and compared for various clinical applications: Tumor demarcation, early inflammation, effectiveness of peripheral nerve block anesthesia, and localization of epileptic seizure. The relative changes in oxygenation and temperature could be clearly observed in good correlation with the physiological condition. The algorithms and data collection/processing can be optimized to enable a real-time diagnostic technique.

Multi-infusion systems are used frequently at intensive care units to administer several liquid therapeutic agents to patients simultaneously. By passively combining the separate infusion lines in one central line, the number of punctures needed to access the patient's body, is reduced. So far, the mutual influence between the different infusion lines is unknown. Although the flow properties of single infusion systems have been investigated extensively, only a few research groups have investigated the flow properties of multi-infusion systems. We showed in a previous study that applying multi-infusion can lead to fluctuations in syringe pump infusions, resulting in uncontrolled and inaccurate drug administration. This study presents a performance analysis of multi-infusion systems as used in the Neonatology Intensive Care Unit. The dynamics between multiple infusion lines in multi-infusion systems were investigated by simulation experiments of clinical conditions. A newly developed real-time spectral-photometric method was used for the quantitative determination of concentration and outflow volume using a deconvolution method of absorption spectra of mixed fluids. The effects for common clinical interventions were studied in detail. Results showed mutual influence between the different infusion lines following these interventions. This mutual influence led to significant volume fluctuations up to 50%. These deviations could result in clinically dangerous situations. A complete analysis of the multiinfusion system characteristics is recommended in further research to estimate both the presence and severity of potential risks in clinical use.

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.

A practical near-IR blood vessel imaging system, the 'VascuLuminator', was developed to facilitate the puncturing of blood vessels for different procedures. Technical solutions were found for certain difficulties, such as obtaining a maximum image contrast by reducing the interference of IR light present in the surroundings. In phantom studies it was shown that the device is able to visualize blood vessels of different sizes to a clinically relevant maximum depth. In a preliminary clinical study, the use of the VascuLuminator resulted in decrease of the failure rate in blood withdrawal in young children from 13% to 2% and the laboratory technicians were satisfied with the practical application of the device. After this study, the effectiveness of the VascuLuminator was investigated to facilitate arterial cannulation in a group of children undergoing cardiac surgery. In an ongoing study, 71 children up to 3 years of age were included and time of arterial cannulation, number of punctures and puncture site were recorded. In 38 patients, cannulation was performed without the VascuLuminator and in 33 patients with VascuLuminator by pediatric anesthesiologists. The initial results do not show significant differences in time and in number of punctures with and without the use of the VascuLuminator. However, the VascuLuminator was able to visualize the arteries in most cases. In 11 of the 33 cases, the artery was located by using only the near-infrared image was used, without palpating for a pulse or knowledge of anatomical landmarks. Further clinical studies are needed to identify the patients groups that will benefit the most from VascuLuminator-assisted vessel punctures.

Tissue oxygenation imaging is a promising diagnostics tool to study the changes and dynamics of tissue perfusion reflecting pathologic and/or physiologic conditions of tissue. In clinical settings, imaging of local oxygenation or blood perfusion variations can be useful for e.g. detection of skin cancer, detection of early inflammation, effectiveness of peripheral nerve block anesthesia, study of the process of wound healing or localization of the cerebral area causing an epileptic attack. In this study, two oxygenation imaging methods based on multi-spectral techniques were evaluated: one system consisting of a CCD camera in combination with a Liquid Crystal Tunable Filter (420 - 730 nm or 650-1100 nm) and a broad band (white) light source, while the second system was a CCD camera in combination with a tunable multispectral LED light source (450-890nm). By collecting narrowband images at selected wavelengths, concentration changes of the different chromophores at the surface of the tissue (e.g. dO2Hb, dHHb and dtHb) can be calculated using the modified Lambert Beer equation. Two analyzing methods were used to calculate the concentration changes this to reduce the errors caused by movement of the tissue. In vivo measurements were obtained during skin oxygen changes induced by temporary arm clamping to validate the methods and algorithms. Functional information from the tissue surface was collected, in non-contact mode, by imaging the hemodynamic and oxygenation changes just below that surface. Both multi-spectral imaging techniques show promising results for detecting dynamic changes in the hemoglobin concentrations. The algorithms need to be optimized and image acquisition and processing needs to be developed top real time for practical clinical applications.

This study describes noninvasive noncontact methods to acquire and analyze functional information from the skin. Multispectral images at several selected wavelengths in the visible and near infrared region are collected and used in mathematical methods to calculate concentrations of different chromophores in the epidermis and dermis of the skin. This is based on the continuous wave Near Infrared Spectroscopy method, which is a well known non-invasive technique for measuring oxygenation changes in the brain and in muscle tissue. Concentration changes of hemoglobin (dO 2 Hb, dHHb and dtHb) can be calculated from light attenuations using the modified Lambert Beer equation. We applied this technique on multi-spectral images taken from the skin surface using different algorithms for calculating changes in O 2 Hb, HHb and tHb. In clinical settings, the imaging of local oxygenation variations and/or blood perfusion in the skin can be useful for e.g. detection of skin cancer, detection of early inflammation, checking the level of peripheral nerve block anesthesia, study of wound healing and tissue viability by skin flap transplantations. Images from the skin are obtained with a multi-spectral imaging system consisting of a 12-bit CCD camera in combination with a Liquid Crystal Tunable Filter. The skin is illuminated with either a broad band light source or a tunable multi wavelength LED light source. A polarization filter is used to block the direct reflected light. The collected multi-spectral imaging data are images of the skin surface radiance; each pixel contains either the full spectrum (420 - 730 nm) or a set of selected wavelengths. These images were converted to reflectance spectra. The algorithms were validated during skin oxygen saturation changes induced by temporary arm clamping and applied to some clinical examples. The initial results with the multi-spectral skin imaging system show good results for detecting dynamic changes in oxygen concentration. However, the optimal algorithm needs to be determined. Multi-spectral skin imaging shows to be a promising technique for various clinical applications were the local distribution of oxygenation is of major importance.

Processing large images files or real-time video streams requires intense computational power. Driven by the gaming industry, the processing power of graphic process units (GPUs) has increased significantly. With the pixel shader model 4.0 the GPU can be used for image processing 10x faster than the CPU. Dedicated software was developed to deform 3D MR and CT image sets for real-time brain shift correction during navigated neurosurgery using landmarks or cortical surface traces defined by the navigation pointer. Feedback was given using orthogonal slices and an interactively raytraced 3D brain image. GPU based programming enables real-time processing of high definition image datasets and various applications can be developed in medicine, optics and image sciences.

A multi-spectral dermatoscope was used to investigate the effect of laser hair removal. Ten volunteers underwent three laser treatments, 6 weeks apart. In a subsequent trial, three volunteers received one laser treatment after which the skin region was imaged at short intervals. Practical solutions were developed to re-locate the investigated skin area. After exact matching using rigid and elastic registration software, the images showed acute and delayed effects on the hairs, pigment and vasculature after laser hair removal and subsequent healing response. The multi-spectral dermatoscope provides a perfect tool to study the efficacy and side effects of laser hair removal procedures and can be used to optimize the treatment plan.

Multi-infusion setups for medication administration in Intensive Care Units seem uncontrolled due to flow and pressure differences between syringe pumps. To investigate the dynamics and interaction of multi-infusion, a dedicated set-up was developed to measure the concentrations of fluids dynamically in multiple lines using absorption spectral-photometry. For feasibility testing and calibration, various dyes and concentrations were investigated to find the optimal settings. The developed method was validated and showed satisfactory results for determining mixtures of up to three different dyes in different ratios, with average recoveries of 105.0% (±11.01) for two dyes and 99.6% (±6.26) for three dyes. The method was applied in initial simulation experiments for measuring effects of manipulations in a multi-infusion set-up simulating a clinical situation. Results showed evidence for mutual influencing of separate infusion lines. The method developed for measuring the fluid dynamics of multi-infusion will contribute to a better insight and controlled administration of medications.

A practical system to visualize vessels underneath the skin has been developed, based on near-infrared (NIR) transillumination. A study in the clinical setting proved the system to be useful as a support in blood withdrawal in young children. During clinical application it was found that performance varied depending on vessel size, depth of vessels and surrounding lighting conditions. To gain more insight on the different variables that determine functioning of the system, we performed phantom studies. A combined liquid/solid phantom was fabricated with similar optical properties as the tissue layers of skin reported in literature at 850 nm. This phantom was used to estimate the depth of visibility in the relation to vessel size and darkness of the skin. Vessel contrast was determined analytically from images and evaluated by 3 independent observers. The knowledge gained from these experiments will be helpful to improve the imaging system and develop a solid phantom to be used as a gold standard to test the system under various clinical lighting conditions. The working range of the system was found to be appropriate to visualize the vessels used for the most procedures, such as blood withdrawal and placement of intravenous lines.

An interactive image matching program has been developed to help ophthalmologists in perceiving subtle differences between sequential images obtained during fluorescein angiography. In a pilot experiment, it appeared that the image matching program could effectively correct camera alignment errors. By offering simple tools like image overlay, blinking and image subtraction, differences between angiograms can be greatly enhanced and interpreted. It appeared that newly formed, leaking blood vessels could be detected at an earlier stage of the disease process using these tools. Treatment can be initiated right away, thereby preventing the patient from having additional visual loss. The matching program seems to improve the quality of fundus diagnostics but needs to be validated in future studies.

Continuous wave Near Infrared Spectroscopy is a well known non invasive technique for measuring changes in tissue oxygenation. Absorption changes (DO2Hb and DHHb) are calculated from the light attenuations using the modified Lambert Beer equation. Generally, the concentration changes are calculated relative to the concentration at a starting point in time (delta time method). It is also possible, under certain assumptions, to calculate the concentrations by subtracting the equations at different wavelengths (delta wavelength method). We derived a new algorithm and will show the possibilities and limitations. In the delta wavelength method, the assumption is that the oxygen independent attenuation term will be eliminated from the formula even if its value changes in time, we verified the results with the classical delta time method using extinction coefficients from different literature sources for the wavelengths 767nm, 850nm and 905nm. The different methods of calculating concentration changes were applied to the data collected from animal experiments. The animals (lambs) were in a stable normoxic condition; stepwise they were made hypoxic and thereafter they returned to normoxic condition. The two algorithms were also applied for measuring two dimensional blood oxygen saturation changes in human skin tissue. The different oxygen saturation levels were induced by alterations in the respiration and by temporary arm clamping. The new delta wavelength method yielded in a steady state measurement the same changes in oxy and deoxy hemoglobin as the classical delta time method. The advantage of the new method is the independence of eventual variation of the oxygen independent attenuations in time.

Venipunctures to draw blood for diagnostics can be cumbersome. Multiple puncture attempts are distressing, painful and traumatic, especially for small children. Drawing blood from babies, in particular, is a problem, due to the cutaneous baby fat, tiny veins and, worst case, a pigmented skin. We developed a practical vein viewing system based on IR translumination that, contrary to commercial systems available, has the advantage of: a) low cost, b) easily implemented in routine practice, c) normal and IR image simultaneously available, d) small add-on, e) child friendly IR illuminator and f) efficient IR light coupling. Before introducing the vessel viewer for clinical application in the children's department, parameters were measured in 194 patients (age 0-17 yrs): time to draw blood, number of attempts, skin characteristics, discomfort of patient, and experience of nurse. In this control group, time to draw blood increases significantly with decreasing age of the children. The instant feedback from the nurses has been valuable for the improvements of especially the illumination sources. A clinical trial has been performed in 125 patients (age 0-6 yrs) to prove effectivity of the system in the blood withdrawal procedure. There was a significant decrease from 13% to 2% in failure rate. Also time needed to search for a vein was significantly decreased. A practical and accessible vein viewing system has been developed and is being introduced for clinical application. Although the concept of patient friendliness is already accepted, measurements need to show the effectiveness for particular groups of patients.

There can be a large variation in response between laser treatments of vascular malformations like port-wine stains even in one patient. This could be ascribed to variations in the skin properties like tint (melanin) and perfusion (redness) which will influence the effectiveness of the laser dosimetry. To obtain a better understanding of the relation between skin properties just before treatment, laser dosimetry and clinical response, a multi-spectral dermatoscope is applied. A sequence of calibrated images is captured from 400 to 720 nm. Images at the treatment laser wavelength (532 nm) show the absorbing structures during laser exposure. Images of different treatment sessions of one patient were matched with dedicated registration software to quantify the results of the laser treatment (change in blood vessels structure, effect on pigment). For feasibility, images were collected from 5 patients and used to determine the optimal wavelength combination strategies. The image matching software gives an objective impression of the improvement, e.g. the clearing of the port-wine stain over time or pigment reactions, which will facilitate the discussion with the patient about the end point of treatment. The multi-spectral dermatoscope and software developed enables the evaluation of large patient series which will result in objective data to advise the dermatologist on the optimal laser dosimetry in future in relation to the skin properties

The treatment of partial nefrectomies is usually performed under a warm ischemic period. Recently, various treatment modalities have become available to perform a partial nefrectomy without clamping off the blood circulation. We have studied three devices in laboratory setting, investigating the thermal and high speed imaging techniques in tissue models and consequently, applying the instruments in the clinic during open procedures especially looking at efficacy and blood loss. The continuous wave 2.0 micron laser of 70 W (Revolix, LISA laser) is used as a fiber delivered knife cutting through circulated tissue with controlled hemostasis for vessels up to 3 mm diameter. The 2 μm wavelength effectively vaporizes tissue water and coagulates the smaller vessels. The Hydro-Jet (ERBE, Germany) uses high pressure (20-80 bar) to ejects a water jet of 40 um diameter at high velocity (10-30 m/s). The parenchyma is resected while vessels are preserved. Consequently, the exposed vessels can be coagulated in a controlled way with minimal blood loss. The water jet showed to induce cavitation bubbles that resect the soft tissue from the matrix leaving the elastic microvessels intact. Various systems are based on bipolar RF technology. We are using the Habib device (Rita 1500X RF generator) to create a coagulation zone around the tumor. Subsequently, the tumor can be resected along the coagulation zone with minimal bleeding. The treatment modalities investigated, have their own advantages and, stand-alone or in combination, can facilitate laparoscopic partial nephrectomies without an ischemic period.

A compact multi-spectral imaging system is presented as diagnostic tool in dermatology and neurosurgery. Using an electronically tunable filter, a sensitive high resolution digital camera, 140 spect ral images from 400 nm up to 720 nm are acquired in 40 s. Advanced image processing algorithms ar e used to enable interactiv e acquisition, viewing, image registration and image analysis. Experiments in the department of dermatology and neurosurgery show that multi-spectral imaging reveals much more detail than conventional medical photography or a surgical microscope, as images can be reprocessed to enhance the view on e.g. tumor boundaries. Using a hardware-based interactive registration algorithm, multi-spectral images can be aligned to correct for motion occurred during image acquisition or to compare acquisitions from different moments in time. The system shows to be a powerful diagnostics tool for medical imaging in the visual and near IR range. Keywords: Tumor demarcation, diagnostics, multi-spectral imaging, optical biopsy.

Multi-spectral images of human tissue taken in-vivo often contain image alignment problems as patients have difficulty in retaining their posture during the acquisition time of 20 seconds. Previously, it has been attempted to correct motion errors with image registration software developed for MR or CT data but these algorithms have been proven to be too slow and erroneous for practical use with multi-spectral images. A new software package has been developed which allows the user to play a decisive role in the registration process as the user can monitor the progress of the registration continuously and force it in the right direction when it starts to fail. The software efficiently exploits videocard hardware to gain speed and to provide a perfect subvoxel correspondence between registration field and display. An 8 bit graphic card was used to efficiently register and resample 12 bit images using the hardware interpolation modes present on the graphic card. To show the feasibility of this new registration process, the software was applied in clinical practice evaluating the dosimetry for psoriasis and KTP laser treatment. The microscopic differences between images of normal skin and skin exposed to UV light proved that an affine registration step including zooming and slanting is critical for a subsequent elastic match to have success. The combination of user interactive registration software with optimal addressing the potentials of PC video card hardware greatly improves the speed of multi spectral image registration.

Multi-spectral images of human tissue taken in-vivo often contain image alignment problems as patients have difficulty in retaining their posture during the acquisition time of 20 seconds. Previously, it has been attempted to correct motion errors with image registration software developed for MR or CT data but these algorithms have been proven to be too slow and erroneous for practical use with multi-spectral images. A new software package has been developed which allows the user to play a decisive role in the registration process as the user can monitor the progress of the registration continuously and force it in the right direction when it starts to fail. The software efficiently exploits videocard hardware to gain speed and to provide a perfect subvoxel correspondence between registration field and display. An 8 bit graphic card was used to efficiently register and resample 12 bit images using the hardware interpolation modes present on the graphic card. To show the feasibility of this new registration process, the software was applied in clinical practice evaluating the dosimetry for psoriasis and KTP laser treatment. The microscopic differences between images of normal skin and skin exposed to UV light proved that an affine registration step including zooming and slanting is critical for a subsequent elastic match to have success. The combination of user interactive registration software with optimal addressing the potentials of PC video card hardware greatly improves the speed of multi spectral image registration.

Invading tumors like basal cell carcinoma have usually no distinct demarcation for the human eye. Therefore, during resection, an additional rim around the tumor is removed. However, extending sprouts can be missed since most lesions are not uniform. To improve the visualization of the tumor demarcation, we developed a multi-spectral imaging system especially adapted for dermatological applications based on tunable liquid crystal spectral tunable filter technology and LED illumination. Enhanced visualization of skin tumor demarcation was achieved using three strategies. The first strategy is based on creating false color images by combining narrow band spectral filtered images by placing them into the red, green and blue image components of a color image at three specific wavelengths. These specific wavelengths were determined using a trial on error tool to achieve the highest contrast between malignant and healthy tissue. The second strategy is to make ratio images of narrow band spectral filtered images at specific wavelengths. A trail on error tool was created which enables the user to try multiple wavelengths to obtain optimal contrast. This method could be applied in realtime. For the third strategy, on pixel spectral segmentation is applied by selecting the pixel spectra in the center of a tumor, surrounding tissue and healthy tissue far away from the tumor. The correlation between these specific spectra and all image pixels is calculated using a fast algorithm. The degree is correlation is graded by color coding and presented in a false color images showing a detailed demarcation of suspicious regions in the tissue. Although this strategy is expected to provide a higher specificity, it takes more time to calculate than the first strategy.

Recently, 2 mm cw laser systems have been introduced for surgery. The 2 mm wavelength is predominantly absorbed by water and enables effective cutting and ablation of tissue similar to the cw CO 2 laser. In contrast to the CO 2 laser, the 2 mm wavelength is delivered through fiber optics and available for endoscopic procedures. After many years of experience with the 1.06 mm Nd:YAG laser, we started to use the 2 mm cw laser as alternative for various urological treatments. The treatments strategies and optimal settings were examined in the lab comparing the two 1.06 and 2 mm wavelengths performing thermal measurements. Consequently, the laser was applied for various urological cases. Penile tumors were resected with haemostatic effects and good aesthetic healing comparable with the Nd:YAG laser. Although the Nd:YAG has initially a deeper penetration, the blackening of the fiber during tissue cutting, provides a more superficial effect like the 2 mm laser. Bladder (pre)malignancies were ablated after biopsy. Only with higher stage tumors, coagulation depth of the Nd:YAG might be preferable for adequate treatment. Strictures in the urethra were incised and stents were effectively desobstructed: one patient with a stent implanted after a pelvic trauma, and one patient with catheterizable apedico stoma stenoses. The thermal damage during incision to deeper layers is minimal so recurrence due to scarring is not expected. Also hair grow in patients who underwent urethroplasty was effectively treated and scrotal atheromata cysts were effectively resected without recurrence. Laparoscopic nefrectomies are being considered using the 2 mm cw laser. The 2 mm cw laser has shown to be a versatile instrument for effective treatment of various urological indications. More patients and long term results are needed to prove the clinical significance compared to other treatment modalities

Laser systems of various wavelengths and pulse characteristics have been introduced in dentistry. At present, the range of applications for the different systems is being investigated mainly differentiating between soft and hard tissue applications. For the preparation of root canals both hard and soft tissues are involved. Ideally, one would like to use one laser system for the whole treatment. In this study, we studied the characteristics of the pulsed 2,78 Er,Cr:YSGG laser (Biolase, Waterlase Millenium), in view of root canal cleaning and desinfection. The laser energy was fiber delivered with fiber tip diameters from 400 mm down to 200 mm. Special thermal and high speed imaging techniques were applied in a transparent model of a tapered root canal and slices cut from human teeth. High speed imaging revealed the dynamics of an explosive vapor bubble at the tip of the Er laser in water and the root canal model. Typically for Erbium lasers, within a time span of several hundred ms, a longitudinal bubble expanded to maximum size of 5 mm length and 2 mm diameter at 100 mJ and imploded afterwards. In the root canal, the explosive bubble created turbulent high speed water streaming which resects soft tissue from the hard tissue. Thermal imaging showed the dynamics of all lasers heating of the canal wall up to several mm depending on the wavelength and energy settings. The mechanism of smear layer removal and sterilization in the root canal, is attributed to cavitation effects induced by the pulsed laser. The heat generation into the dentine wall was minimal.

Devices delivering energy to biological tissues (eg lasers, RF and ultrasound) can induce surgical smoke consisting of particles, vapor, gasses and aerosols. Besides interfering with the view of the surgeon, the smoke is a risk for the health of both the users and patients. In literature, it has been shown that surgical smoke can contain carcinogenic and harmful biological agents. However, the impact on health of the users and patients is widely debated. The use of smoke evacuation systems in the OR is usually governed by economical reason instead of safety issues. A special image enhancement technique is used to study the behavior of smoke and aerosols and the effectiveness of smoke evacuation systems. A back scatter illumination technique using 1 ms light flashes at video rate was applied to image the smoke production of various surgical devices without and with smoke evacuation while ablating biological tissues. The effectiveness of various smoke evacuation devices and strategies were compared. The ablative thermal devices produced smoke but also aerosols. If the thermal energy was delivered in high peak pulses, the presence of aerosols was more significant. Ultrasound based devices produce mainly aerosols. The distance to the target, the opening of the evacuation nozzle and the dimension of aerosols were leading for the effectiveness of the smoke evacuation. The smoke visualization technique has proven an effective tool for study the effectiveness of smoke and aerosols evacuation. The results can contribute to the necessity to use evacuation systems in the OR.

A larger percentage of small tumors in the breast are being detected due to effective screening programs and improved radiological diagnostic methods. For treatment, less invasive methods are preferred which are still radical but also provide a better aesthetic result. Recently, several ablation techniques have become available to locally ablate tumors in situ. In this study, the effectiveness of three ablation techniques was compared by imaging the thermal distribution and temperature mapping in vitro. The first system (KLS Martin, Trumpf, Germany) uses Nd:YAG laser light delivered through a single diffusing fiber tip which is positioned direct into the tissue or in a water-cooled needle. The second system (Olympus-Celon, Germany) uses bipolar Radio Frequency currents between electrodes in a water-cooled needle. The RF system has a temperature feedback based on tissue impedance to prevent tissue charring. The third system is a focused ultrasound system developed in the Hospital. For all three the techniques, the dynamics of temperature gradients around the probe or focus point are visualized using color Schlieren techniques in a transparent tissue model and recorded using thermocouples. The effective lesion size and tissue temperatures were determined in in vitro bovine mamma tissue. All systems were capable to heat tissue volumes up to 3 cm in diameter. The lesion growth dependent on the power input, temperature gradient around the initial power source and treatment time. Although the three systems are capable to ablate small mamma carcinoma in situ, they differ in precision, MR compatibility, invasiveness, practical use and treatment time. The real clinical effectiveness has to be proven in large patient studies with long term follow up.

In this study, the efficacy and optimal settings of the CO 2 , Diode and cw Thulium laser systems were compared for various clinical applications in ENT, Lung and Neurosurgery. The experiments were performed using a specially developed setup, based on color Schlieren techniques, which enable real-time imaging of dynamic temperature gradients complimented with thermocouple measurements in a transparent tissue model in air and water. The CO 2 and cw Thulium laser are both efficient in superficial tissue ablation with minimal coagulation depth. The cw Thulium laser, however, is fiber delivered and can also be used in a water. The Diode laser has a relatively deep coagulation effect. The ablation efficacy was enhanced by coating the fiber tip with carbon particles. Our thermal imaging technique was useful to develop new strategies making use of the advantages and overcoming the drawbacks of laser systems. The CO 2 , Diode and cw Thulium laser can be applied for similar clinical procedures using the optimal strategy and settings for each laser type. The cw 2 μm Thulium laser shows to be a versatile laser system for a broad range of applications both in air and water.

In-vivo image-based multi-spectral images have typical problems in image acquisition, registration, visualization and analysis. As its spatial and spectral axes do not have the same unit, standard image algorithms often do not apply. The image size is often so large that it is hard to analyze them interactively. In a clinical setting, image motion will always occur during the acquisition times up to 30 seconds, since most (elderly) patients often have difficulty to retain their poses. In this paper, we discuss how the acquisition, registration, display and analysis can be optimized for in-vivo multi-spectral images.

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Surgical treatments, including hepatic resection and liver transplantation are considered as the most effective treatment of HCC. However, less than 20% of HCC patients can be treated surgically because of: multi-focal diseases, proximity of tumor to key vascular or biliary structures and inadequate functional hepatic reserve related coexistent cirrhosis. In this unfortunate groups of patients various palliative treatments modalities are being performed to extend the time of survival and quality of life. These techniques include trans-catheter arterial chemoembolization (TACE), percutaneous ethanol injection (PEI) and Interstitial Thermal Therapy: laser-induced interstitial thermotherapy (LITT) and radio-frequency ablation (RFA).

A multi-spectral imaging system is presented consisting of a spatially and spectrally uniform light source, an electronically tuneable bandpass filter and a sensitive digital camera. When properly calibrated with a white reference, it can reproducibly grab the reflection spectrum of any accessible tissue surface. After a description of technical challenges, some examples are given for the application in dermatology.