Biomedical Instrumentation publications

The aim was to quantify the influence of heterogeneous isotropic and heterogeneous anisotropic tissue on the spatial distribution of the electric field during deep brain stimulation (DBS). Three finite element tissue models were created of one patient treated with DBS. Tissue conductivity was modelled as I) homogeneous isotropic, II) heterogeneous isotropic based on MRI, and III) heterogeneous anisotropic based on diffusion tensor MRI. Modelled DBS electrodes were positioned in the subthalamic area, the pallidum, and the internal capsule in each tissue model. Electric fields generated during DBS were simulated for each model and target-combination and visualized in 3D with isolevels at 0.20 (inner), and 0.05 V m^-1 (outer). F-test and vector analysis was used for statistical evaluation of the distribution of the electric field. Heterogeneous isotropic tissue altered the spatial distribution of the electric field by up to 4% at inner, and up to 10% at outer isolevel. Heterogeneous anisotropic tissue had a larger impact on the distribution of the electric field with an influence of up to 18% and 15% at each isolevel, respectively. The influence of heterogeneous and anisotropic tissue on the electric field may be clinically relevant in anatomic regions that are functionally subdivided and surrounded by multiple fibres of passage.

Microdialysis can be used in parallel to deep brain stimulation (DBS) to relate biochemical changes to the clinical outcome. The aim of the study was to use the finite element method to predict the tissue volume of influence (TVI(max)) and its cross-sectional radius (r (TVImax)) when using brain microdialysis, and visualize the TVI(max) in relation to patient anatomy. An equation based on Fick's law was used to simulate the TVI(max). Factorial design and regression analysis were used to investigate the impact of the diffusion coefficient, tortuosity and loss rate on the r (TVImax). A calf brain tissue experiment was performed to further evaluate these parameters. The model was implemented with pre-(MRI) and post-(CT) operative patient images for simulation of the TVI(max) for four patients undergoing microdialysis in parallel to DBS. Using physiologically relevant parameter values, the r (TVImax) for analytes with a diffusion coefficient D = 7.5 × 10(-6) cm(2)/s was estimated to 0.85 ± 0.25 mm. The simulations showed agreement with experimental data. Due to an implanted gold thread, the catheter positions were visible in the post-operative images. The TVI(max) was visualized for each catheter. The biochemical changes could thereby be related to their anatomical origin, facilitating interpretation of results.

In this paper, we investigate the possibility of using accurate prediction models for the prediction of protoporphyrin bleaching dynamics to achieve photobleaching-insensitive methods to improve the evaluation of data in an existing clinical fluorescence-guided resection technique. To simulate the scenario, measurements were carried out in vivo on skin of healthy volunteers using a compact fiber-based fluorescence spectroscopy system. We have developed an effective method for the parameterization of sequences of bleaching spectra. We analyze convergence and decay rates with respect to initial conditions and excitation irradiance. We also discuss the consequences and the potential for bleaching-insensitive measurements and their applicability in a few examples from in vivo open brain surgery.

In routine clinical phototesting and in basic research, naked eye dermatological assessment is the "gold standard" for determining the patient's minimal erythemal dose (MED). In UV-B testing with a divergent, radially attenuating beam of characterised dosimetry, laser Doppler perfusion imaging has been previously used to give quantitative description of reactivity to doses above the MED in addition to a "single-dose" objective determination of the MED itself. In the present paper, the recently developed tissue viability imaging (TiVi) technology is presented for the first time as a reliable, easily applicable, high-resolution alternative to LDPI in the divergent beam testing concept. Data obtained after provocation with a range of doses was analysed in order to determine the reaction diameter, which can be related to the MED using field dosimetry. The dose-response features of exposure above the MED and the relationship between naked eye readings and the diameter were determined from the image data. TiVi data were obtained faster than LDPI data and at a higher spatial resolution of 100 μm instead of 1 mm. A tool was developed to centre over the erythema area of the acquired image. Response data could be plotted continuously against dose. Thresholding of processed images compared to naked eye "gold standard" readings showed that the normal skin value +4 standard deviations produced a good fit between both methods. A linear fitting method for the dose-response data provided a further method of determination of the reaction diameter (MED). Erythemal "volume under the surface (VUS)" for the reaction provided a new concept for visualising information. TiVi offers advantages over LDPI in the acquisition and analysis of data collected during divergent beam testing. An increased amount of data compared to traditional phototesting is easily and more objectively obtained which increases applicability in the clinical and research environment.

Background and Objective: Glioblastoma multiforme is a highly malignant primary brain tumor. It has no border but at best a marginal zone, however, invisible to the surgeon. An optical touch pointer (OTP) enabling differentiation of healthy and tumor tissue by means of fiber-optic fluorescence spectroscopy has been developed. In combination with an ultrasonic navigation system, the OTP may be used for demarcation of resectable tumor tissue. The aim of the study was to evaluate the clinical performance of OTP during surgery of malignant brain tumors. 

Study Design/Materials and Methods: Nine patients were operated on with the standard surgical procedure, including white light microscopy and navigation. A total of 5 mg/kg bodyweight of 5-amino-levulin acid was orally administrated before surgery. The OTP was calibrated into the ultrasound-based navigation system and measurements were performed in tumor core and along the tumor border. The ratio between the protoporphyrin IX fluorescence at 635 nm and the autofluorescence was used for quantifications of data. Biopsies (n =20), ultrasound images (n = 30), and visual inspection (n =180) were compared to the fluorescence ratio. 

Results/Conclusion : Healthy and tumor tissue could be identified and differentiated with the OTP(P < 0.001). The fluorescence ratio in average was 0 outside the tumor and low in the gliotic edema zone around the tumor. It increased in the marginal zone and was highest in the solid tumor tissue. In the necrotic tissue, in the center of the tumor, the ratio in average was 0. The OTP can be used in combination with ultrasound-based navigation and may help to determine whether to resect otherwise not identifiable tissue.

In fiber-optical based fluorescence spectroscopy during brain tumor resection, blood interference is frequently observed. Usually a considerable amount of data is discarded as the corresponding spectrum cannot be reliably quantified. In this study, a fiber-optical based fluorescence spectroscopy system with a laser excitation light of 405 nm was used during fluorescence guided brain tumor resection using 5-aminolevulinic acid (5-ALA). The blood interference pattern in the fluorescence spectrum was studied in 15 patients and compared to the operation situation modeled in the laboratory. The blood, when not blocking the optical signal totally, weakens the collected fluorescence intensity and leaves traces of oxy and de-oxy hemoglobin in addition to some other chromophores in the brain fluorescence spectrum.

Otitis media diagnosis can be assisted by measuring the shape of the tympanic membrane. We have developed an ear speculum for an otoscope, including spatially distributed source and detector optical fibers, to generate source-detector intensity matrices (SDIMs), representing the curvature of surfaces. The surfaces measured were a model ear with a latex membrane and harvested temporal bones including intact tympanic membranes. The position of the tympanic membrane was shifted from retracted to bulging by air pressure and that of the latex membrane by water displacement. The SDIM was normalized utilizing both external (a sheared flat plastic cylinder) and internal references (neutral position of the membrane). Data was fitted to a two-dimensional Gaussian surface representing the shape by its amplitude and offset. Retracted and bulging surfaces were discriminated for the model ear by the sign of the Gaussian amplitude for both internal and external reference normalization. Tympanic membranes were separated after a two-step normalization: first to an external reference, adjusted for the distance between speculum and the surfaces, and second by comparison with an average normally positioned SDIM from tympanic membranes. In conclusion, we have shown that the modified otoscope can discriminate between bulging and retracted tympanic membranes in a single measurement, given a two-step normalization. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3622486]

Implantable mechanical left ventricular assist devices (LVADs) are used as a bridge or alternative to heart transplantation. Peroperative transesophageal echocardiography is commonly applied during implantation. Significant air embolism may occur as a result of air leakage at connections and anastomoses when LV filling becomes inadequate, and this must be prevented. Early suspicion and detection of air is mandatory to avoid negative circulatory effects. We hypothesized that monitoring of heart chamber size and occurrence of single air bubbles using second harmonic imaging (SHI) echocardiography may prevent risk for significant air embolism. After implantation of the LVAD in 10 calves, invasive hemodynamic monitoring and epicardial SHI were performed while increasing pump speed. Air bubbles in the ascending aorta were monitored and the left heart visualized for off-line dimensional analysis. Detection of air bubbles in the ascending aorta preceded their appearance in the left ventricle. They occurred exclusively but not always after a decrease in left atrial (LA) size. Decrease in LA pressure did not predict bubble detection or reduction in LA size. We conclude that SHI detects spontaneous ultrasound contrast during implantation of a LVAD and that a decrease in LA size is a warning that air embolism is imminent.

OBJECTIVE-To compare the microcirculatory velocity distribution in type 2 diabetic patients and nondiabetic control subjects at baseline and after local heating. RESEARCH DESIGN AND METHODS-The skin blood flow response to local heating (44 degrees C for 20 mm) was assessed in 28 diabetic patients and 29 control subjects using a new velocity-resolved quantitative laser Doppler flowmetry technique (qLDF). The qLDF estimates erythrocyte (RBC) perfusion (velocity X concentration), in a physiologically relevant unit (grams RBC per 100 g tissue X millimeters per second) in a fixed output volume, separated into three velocity regions: v less than1 mm/s, v 1-10 mm/s, and v greater than10 mm/s. RESULTS-The increased blood flow occurs in vessels with a velocity greater than1 mm/s. A significantly lower response in qLDF total perfusion was found in diabetic patients than in control subjects after heat provocation because of less high-velocity blood flow (v greater than10 mm/s). The RBC concentration in diabetic patients increased sevenfold for v between 1 and 10 mm/s, and 15-fold for v greater than10 mm/s, whereas no significant increase was found for v less than1 mm/s. The mean velocity increased from 0.94 to 7.3 mm/s in diabetic patients and from 0.83 to 9.7 mm/s in control subjects. CONCLUSIONS-The perfusion increase occurs in larger shunting vessels and not as an increase in capillary flow. Baseline diabetic patient data indicated a redistribution of flow to higher velocity regions, associated with longer duration of diabetes. A lower perfusion was associated with a higher BMI and a lower toe-to-brachial systolic blood pressure ratio.

Deep brain stimulation (DBS) has become increasingly important for the treatment and relief of neurological disorders such as Parkinson's disease, tremor, dystonia and psychiatric illness. As DBS implantations and any other stereotactic and functional surgical procedure require accurate, precise and safe targeting of the brain structure, the technical aids for preoperative planning, intervention and postoperative follow-up have become increasingly important. The aim of this paper was to give and overview, from a biomedical engineering perspective, of a typical implantation procedure and current supporting techniques. Furthermore, emerging technical aids not yet clinically established are presented. This includes the state-of-the-art of neuroimaging and navigation, patient-specific simulation of DBS electric field, optical methods for intracerebral guidance, movement pattern analysis, intraoperative data visualisation and trends related to new stimulation devices. As DBS surgery already today is an important technology intensive domain, an "intuitive visualisation" interface for improving management of these data in relation to surgery is suggested.

Tissue Viability (TiVi) imaging is a promising new technology for the assessment of microcirculation in the upper human dermis. Although the technique is easily implemented and develops large amounts of observational data, its role in the clinical workplace awaits the development of standardised protocols required for routine clinical practice. The present study investigates the use of TiVi technology in a human, in vivo, localized, skin blood flow occlusion protocol. In this feasibility study, the response of the cutaneous microcirculation after provocation on the volar surface of the forearm was evaluated using a high temporal-low spatial resolution TiVi camera. 19 healthy subjects - 10 female and 9 male - were studied after a localized pressure was applied for 5 different time periods ranging from 5 to 25 seconds. Areas corresponding to 100 x 100 pixels (2.89 cm(2)) were monitored for 60 seconds prior to, during and after each occlusion period. Our results demonstrated the removal of blood from the local area and a hyperaemic response supporting the suitability of TiVi imaging for the generation of detailed provocation response data of relevance for the physiological function of the skin microcirculation in health and disease.

Intramyocardial oxygen transport was assessed during open-chest surgery in calves by diffuse reflectance spectroscopy using a small intramuscular fiber-optic probe. The sum of hemo- and myoglobin tissue fraction and oxygen saturation, the tissue fraction and oxidation of cytochrome aa3, and the tissue fraction of methemoglobin, were estimated using a calibrated empirical light transport model. Increasing the oxygen content in the inhaled gas; 21%-50%-100%, in five calves (group A) gave an oxygen saturation of 19+/-4%, 24+/-5% and 28+/-8%, and mean tissue fractions of 1.6% (cytochrome aa3), and 1.1% (hemo- and myoglobin). Cardiac arrest in two calves gave an oxygen saturation lower than 5%. In two calves (group B) a left ventricular assistive device (LVAD pump) was implanted. Group B animals displayed similar trends in hemo- and myoglobin oxygen saturation as in group A, but at higher levels (maxima of 38% (B1) and 44% (B2)). The cytochrome aa3 oxidation level was above 96% in both group A and B calves, including the two cases involving cardiac arrest.

In conclusion, the estimated tissue fractions and oxygenation/oxidation levels of the myocardial chromophores during respiratory and hemodynamic provocations where in agreement with previously presented results, demonstrating the potential of the method.

Introduction The colour of tissue is often of clinicaluse in the diagnosis of tissue homeostasis andphysiological responses to various stimuli.Determining tissue colour changes and borders,however, often poses an intricate problem and visualexamination, constituting clinical praxis, does notallow them to be objectively characterized orquantified. Demands for increased inter- and intraobserverreproducibility have been incentives for theintroduction of objective methods and techniques fortissue colour (e.g. erythema) evaluation. The aim ofthe present paper was to study the border zone of anUVB provoked erythematous response of humanskin in terms of blood volume and oxygenationmeasured by means of diffuse reflectancespectroscopy using a commercial probe.

Material and Methods A provocation model, basedon partial masking of irradiated skin areas, definestwo erythema edges at every skin site responding tothe UV irradiation. In every subject, 5 test sites wereexposed with a constant UV light irradiance (14mW/cm2), but with different exposures times (0, 3,6, 9, 12 seconds). An analysis of the spectral datameasured across the two edges was performed for every scan line. The oxygenized and deoxygenizedhemoglobin contents were estimated in everymeasurement point, using a modified Beer-Lambertmodel.

Results The fit of the experimental data to the model derived by the modified Beer-Lambert law was excellent (R2>0.95). Analyzing data for the chromophore content showed that the erythematous response in provoked areas is dominated by the increase in oxyhemoglobin. The width for the left and right border zone was estimated to 1.81±0.93 mm and 1.90±0.88 mm respectively (M±SD). The unprovoked area between the two edges was estimated to 0.77±0.68 mm.

Conclusion While the chosen data analysis performed satisfactory, the ability of the probe design to differentiate spatial aspects of a reaction with abrupt borders was found to be suboptimal resulting in a probable overestimation of the erythematous edge slope. Probe modification or imaging are possible solutions.

A new method for estimating the measurement depth and volume in laser Doppler flowmetry (LDF) is presented. The method is based on Monte Carlo simulations of light propagation in tissue. The contribution from each individual Doppler shift is calculated and thereby multiple Doppler shifts are handled correctly. Different LDF setups for both probe based (0.0, 0.25, 0.5, and 1.2 mm source-detector separation) and imaging systems (0.5 and 2.0 mm beam diameter) are considered, at the wavelengths 543 nm, 633 nm, and 780 nm. Non-linear speckle pattern effects are accounted for in the imaging system setups. The effects of tissue optical properties, blood concentration, and blood oxygen saturation are evaluated using both homogeneous tissue models and a layered skin model. The results show that the effect on the measurement depth of changing tissue properties is comparable to the effect of changing the system setup, e.g. source-detector separation and wavelength. Skin pigmentation was found to have a negligible effect on the measurement depth. Examples of measurement depths are (values are given for a probe based system with 0.25 mm source-detector separation and an imaging system with a 0.5 mm beam diameter, respectively, both operating at 780 nm): muscle - 0.55/0.79 mm; liver - 0.40/0.53 mm; gray matter - 0.48/0.68 mm; white matter - 0.20/0.20 mm; index finger pulp - 0.41/0.53 mm; forearm skin - 0.53/0.56 mm; heat provoked forearm skin - 0.66/0.67 mm.

A method for determining a two-parametric Gegenbauer-kernel phase function that accurately describes the diffuse reflectance from a polydispersive scattering media at small source-detector separations (0.23 to 1.2 mm), is presented. The method involves spectral collimated transmission measurements, spatially resolved spectral diffuse reflectance (SRDR) measurements, and inverse Monte Carlo technique. Both absolute calibration (using a monodispersive polystyrene microsphere suspension) and relative calibration (eliminating differences between fibers) of SRDR spectra yielded comparable results. When applied to water dilutions of milk, simulated and measured spectra deviated less than 6.5% and 2.5% for the absolute and relative calibration case, respectively, even for the closest fiber separation. Corresponding values for milk including ink as an absorber, were 13.4% and 7.3%.

Deep brain stimulation (DBS) is an established treatment for Parkinsons disease. Success of DBS is highly dependent on electrode location and electrical parameter settings. The aim of this study was to develop a general method for setting up patient-specific 3D computer models of DBS, based on magnetic resonance images, and to demonstrate the use of such models for assessing the position of the electrode contacts and the distribution of the electric field in relation to individual patient anatomy. A software tool was developed for creating finite element DBS-models. The electric field generated by DBS was simulated in one patient and the result was visualized with isolevels and glyphs. The result was evaluated and it corresponded well with reported effects and side effects of stimulation. It was demonstrated that patient-specific finite element models and simulations of DBS can be useful for increasing the understanding of the clinical outcome of DBS.

Tissue Viability Imaging (TiVi) is an emerging bioengineering technology intended for two-dimensional mapping of skin erythema and blanching. Before TiVi can be effectively used in studies of diseased or damaged skin, the variability in normal skin red blood cell concentration (RBCconc) requires evaluation.

To demonstrate how TiVi maps spatial and temporal variations in normal skin RBCconc at the dorsal side of the hand at rest and during post-occlusive hyperemia.

Short-term and day-to-day variations in skin RBCconc were quantified at the dorsal side of the hand in four healthy volunteers at rest. In a separate study, the increase in skin RBCconc was recorded during post-occlusive hyperemia.

A lower skin RBCconc (179-184 TiVi units) was observed at the back of the hand and base of the thumb compared with areas adjacent to the nailfoldfold region of the fingers (190-213 TiVi units). The short-term variation (within 70 s) was < 2% in all areas of the dorsal side of the hand, while day-to-day variations were in the range 5-7% in the back of the hand and up to 10% in areas adjacent to the nailfold region. In the post-occlusive hyperemia phase, up to a 60% increase in skin RBCconc was observed in the early part of the reactive hyperemia phase. This increase in skin RBCconc successively decreased but remained about 18% above the pre-occlusion level after 30 min.

Establishment of healthy skin RBCconc reference values is important for the design of versatile test procedures for assessment of skin damage caused by vibration tools, chemical exposure or peripheral vascular disease.

Purpose: To validate the performance of an analysis method for fMRI data based on restricted canonical correlation analysis (rCCA) and adaptive filtering, and to increase the usability of the method by introducing a new technique for significance estimation of rCCA maps.

Materials and Methods: Activation data from a language task and also a resting state fMRI data were collected from eight volunteers. Data was analyzed using both the rCCA method and the General Linear Model (GLM). A modified Receiver Operating Characteristic (ROC) method was used to evaluate the performance of the different analysis methods. The area under a fraction of the ROC curve was used as a measure of performance. On resting state data the fraction of voxels above certain significance thresholds were used to evaluate the significance estimation method.

Results: The rCCA method scored significantly higher on the area under the ROC curve than the GLM. The fraction of activated voxels determined by thresholding according to the introduced significance estimation technique showed good agreement with the thresholds selected.

Conclusion: The rCCA method is an effective analysis tool for fMRI data and its usability is increased with the introduced significance estimation method.

Aim: The aim of this study is to investigate reflected light intensity combined with impedance for navigation aid during stereotactic neurosurgery.

Methods: During creation of 21 trajectories for stereotactic implantation of deep brain stimulation electrodes in the globus pallidus internus or subthalamus (zona incerta or subthalamic nucleus), impedance at 512 kHz and reflected light intensity at 780 nm were measured continuously and simultaneously with a radio frequency electrode containing optical fibres. The signals were compared with anatomy determined from pre- and postoperative MRI and CT. The measurements were performed within minutes and signal analysis was done post-operatively.

Results: Reflected light intensity was low from cortex, lateral ventricle, caudate nucleus and putamen. It was intermediate from globus pallidus and thalamus while it was high from subcortical white matter, internal capsule and the subthalamus. The electric impedance was less consistent but generally low in the cortex, intermediate in subcortical white matter, the putamen, the globus pallidus and the thalamus and high in the internal capsule and the subthalamus.

Conclusion: Reflected light intensity and electric impedance give complementary information about passed tissue and the combination seems promising for navigation aid during stereotactic neurosurgery.

A new and versatile method for tissue viability imaging based on polarization spectroscopy of blood in superficial tissue structures such as the skin is presented in this paper. Linearly polarized light in the visible wavelength region is partly reflected directly by the skin surface and partly diffusely backscattered from the dermal tissue matrix. Most of the directly reflected light preserves its polarization state while the light returning from the deeper tissue layers is depolarized. By the use of a polarization filter positioned in front of a sensitive CCD-array, the light directly reflected from the tissue surface is blocked, while the depolarized light returning from the deeper tissue layers reaches the detector array. By separating the colour planes of the detected image, spectroscopic information about the amount of red blood cells (RBCs) in the microvascular network of the tissue under investigation can be derived. A theory that utilizes the differences in light absorption of RBCs and bloodless tissue in the red and green wavelength region forms the basis of an algorithm for displaying a colour coded map of the RBC distribution in a tissue. Using a fluid model, a linear relationship (cc. = 0.99) between RBC concentration and the output signal was demonstrated within the physiological range 0–4%. In-vivo evaluation using transepidermal application of acetylcholine by the way of iontophoresis displayed the heterogeneity pattern of the vasodilatation produced by the vasoactive agent. Applications of this novel technology are likely to be found in drug and skin care product development as well as in the assessment of skin irritation and tissue repair processes and even ultimately in a clinic case situation.

An optical microvascular skin model, valid at 780 nm, was developed. The model consisted of six layers with individual optical properties, and variable thicknesses and blood concentrations at three different blood flow velocities. Monte Carlo simulations were used to evaluate the impact of various model parameters on the traditional Laser Doppler flowmetry (LDF) measures. A set of reference Doppler power spectra was generated by simulating 7,000 configurations, varying the thickness and blood concentrations. Simulated spectra, at two different source detector separations, were compared with in vivo recorded spectra, using a non-linear search algorithm for minimizing the deviation between simulated and measured spectra. The model was validated by inspecting the thickness and blood concentrations which generated the best fit. These four parameters followed a priori expectations for the measurement situations, and the simulated spectra agreed well with the measured spectra for both detector separations. Average estimated dermal blood concentration was 0.08% at rest and 0.63% during heat provocation (44°C) on the volar side of the forearm, and 1.2% at rest on the finger pulp. The model is crucial for developing a technique for velocity-resolved absolute LDF measurements with known sampling volume, and can also be useful for other bio-optical modalities.

Diffuse reflectance spectroscopy as a method for improving intracerebral guidance during functional neurosurgery has been investigated. An optical probe was developed for measurements during stereotactic and functional neurosurgery in man. The aim of the study was to investigate the spectral differences between white and grey matter and between white matter and functional targets. Diffuse reflectance spectroscopy measurements in ten patients were recorded at incremental steps towards and in three different functional targets (STN, GPi and Zi). The recorded spectra along the trajectory were sorted into white or grey matter, based on preoperative MRI images or the recorded spectral shape and intensity. The difference between tissue types was calculated as a quotient. Significant intensity differences between white and grey matter were found to be at least 14% (p < 0.05) and 20% (p < 0.0001) for MRI and spectral-sorted data respectively. The reflectance difference between white matter and the functional targets of GPi was higher than for STN and Zi. The results indicate that diffuse reflectance spectroscopy has a potential to be developed to a suitable complement to other intracerebral guidance methods.

Visible and near-infrared light, particularly in the wavelength region of 600-1100 nm, offer a window into human and animal tissues due to reduced scattering and absorption. We review the main biophotonic methods applied to visualisation and assessment of the microcirculation and document the progress made over the past 10 years in particular. Applications, particularly in human skin, are of special topical importance due to an improved knowledge of its role and its value as a surrogate for other organs in drug testing at a time when drug development is under severe pressure. © 2007.

Clothing with conductive textiles for health care applications has in the last decade been of an upcoming research interest. An advantage with the technique is its suitability in distributed and home health care. The present study investigates the electrical properties of conductive yarns and textile electrodes in contact with human skin, thus representing a real ECG-registration situation. The yarn measurements showed a pure resistive characteristic proportional to the length. The electrodes made of pure stainless steel (electrode A) and 20% stainless steel/80% polyester (electrode B) showed acceptable stability of electrode potentials, the stability of A was better than that of B. The electrode made of silver plated copper (electrode C) was less stable. The electrode impedance was lower for electrodes A and B than that for electrode C. From an electrical properties point of view we recommend to use electrodes of type A to be used in intelligent textile medical applications. © International Federation for Medical and Biological Engineering 2007.

Laser Doppler flowmetry (LDF) is a non invasive method enabling the monitoring of microvascular blood flow, a very important marker of tissue health. This article gives an overview on the concept of LDF for microvascular perfusion monitoring and imaging. It first describes the theoretical background of the technique. Then, the benefits of LDF signal processing are shown through clinical examples: use of time-frequency representations and wavelets. Afterwards, the paper introduces novel approaches of velocity components. For that purpose, a work providing the determination of the velocities relative contribution in physiologically relevant units (mm/s) is presented. Imaging perfusion is also reviewed through methods based on laser speckle. The most prominent disadvantage of the latter devices being the time needed to produce a perfusion image, solutions are proposed in the last part of the paper. © International Federation for Medical and Biological Engineering 2007.

Radiofrequency lesioning of nuclei in the thalamus or the basal ganglia can be used to reduce symptoms caused by e.g. movement disorders such as Parkinson's disease. Enlarged cavities containing cerebrospinal fluid (CSF) are commonly present in the basal ganglia and tend to increase in size and number with age. Since the cavities have different electrical and thermal properties compared with brain tissue, it is likely that they can affect the lesioning process and thereby the treatment outcome. Computer simulations using the finite element method and in vitro experiments have been used to investigate the impact of cysts on lesions' size and shape. Simulations of the electric current and temperature distributions as well as convective movements have been conducted for various sizes, shapes and locations of the cysts as well as different target temperatures. Circulation of the CSF caused by the heating was found to spread heat effectively and the higher electric conductivity of the CSF increased heating of the cyst. These two effects were together able to greatly alter the resulting lesion size and shape when the cyst was in contact with the electrode tip. Similar results were obtained for the experiments.

Current knowledge about vascular function stems mainly from pharmacological in vitro studies using mounted vascular strips on a strain gauge. We know of no paper that has systematically examined the possibility of assessing the conventional dose–response effects of iontophoresis and laser Doppler investigation of vasoactive substances and compared those relations to data obtained from strips mounted on a strain gauge.

We used the vasoactive substances acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent) and an antagonist (atropine) to enable further investigations in the receptor physiology of iontophoresis.

Dose–response curves from the iontophoresis experiments showed close similarity to those obtained by vascular strips mounted on a strain gauge. The coefficient of variation (CV) of the dose–response factors found in iontophoresis (both inter and intra experimental variability) was low. The iontophoretic effective dose of 50% (ED50) for acetylcholine and nitroprusside had only CVs of 25% and 26%, respectively, compared with 71% and 77% for the vascular strips. Acetylcholine-induced response was antagonized by iontophoresis of atropine. Contrary to expectations, this antagonism was not competitive.

The results show that iontophoresis in combination with laser Doppler technology produces reproducible and reliable dose–response curves that picture the vascular effects of vasoactive drugs.

Although the therapeutic effect of deep brain stimulation (DBS) is well recognized, a fundamental understanding of the mechanisms responsible is still not known. In this study finite element method (FEM) modelling and simulation was used in order to study relative changes of the electrical field extension surrounding a monopolar DBS electrode positioned in grey matter. Due to the frequently appearing cystic cavities in the DBS-target globus pallidus internus, a nucleus of grey matter with and without a cerebrospinal fluid filled cystic cavity was modelled. The position, size and shape of the cyst were altered in relation to the electrode. The simulations demonstrated an electrical field around the active element with decreasing values in the radial direction. A stepwise change was present at the edge between grey and white matters. The cyst increased the radial extension and changed the shape of the electrical field substantially. The position, size and shape of the cyst were the main influencing factors. We suggest that cystic cavities in the DBS-target may result in closely related unexpected structures or neural fibre bundles being stimulated and could be one of the reasons for suboptimal clinical effects or stimulation-induced side effects. © 2006 IOP Publishing Ltd.

A method to separate a Doppler power spectrum into a number of flow velocity components, measured in absolute units (mm/s), is presented. A Monte Carlo software was developed to track each individual Doppler shift, to determine the probability, p(n), for a photon to undergo n Doppler shifts. Given this shift distribution, a mathematical relationship was developed and used to calculate a Doppler power spectrum originating from a certain combination of velocity components. The non linear Levenberg-Marquardt optimization method could thus be used to fit the calculated and measured Doppler power spectra, giving the true set of velocity components in the measured sample. The method was evaluated using a multi tube flow phantom perfused with either polystyrene microspheres or undiluted/diluted human blood (hct = 0.45). It estimated the velocity components in the flow phantom well, during both low and high concentrations of moving scatterers (microspheres or blood). Thus, further development of the method could prove to be a valuable clinical tool to differentiate capillary blood flow.

Laser Doppler perfusion monitoring (LDPM) is a

method to assess microvascular perfusion. A modified,

ECG-triggered LDPM system has been developed to

measure myocardial perfusion with minimum influence

from heart motion. With this method, one systolic (PLS)

and one diastolic (PLD) perfusion value is obtained.

The aim of this study was to analyse breathing-related

variations in PLS and PLD measured during open-heart

surgery. The phase delays between PLS, PLD, mean

arterial blood pressure (MAP), heart rate and, indirectly,

the respiration were determined.

MAP tended to be in phase with or precede the

variations in PLD, i.e., PLD was at a maximum at the end

of inspiration or at the beginning of expiration. No clear

relation between PLS and any of the other signals could

be found.

Laser Doppler perfusion imaging (LDPI) enables superficial tissue perfusion assessment, but is sensitive to tissue motion not related to blood cells. The aim was to investigate if a polarization technique could reduce movement-induced artifacts. A linearly polarized laser and a cross-polarized filter, placed in front of the detectors, were used to block specular reflection. Measurements were performed with, and without, the polarization filter, at a single site during horizontal and vertical movement of skin tissue (index finger, twelve subjects, n=112) and of a flow model (n=432), with varying surface structures. Measurements were repeated during different flow conditions and at increased skin specular reflection. Statistical analysis was performed using ANOVA models. The perfusion signal was lower (p <0.001, skin and p<0.05, flow model) using the polarization filter, due to movement artifact reduction. No significant influence from surface structure was found when using the polarization filter. Movement artifacts were lower (p<0.05) in the vertical movement direction, however, depending on flow conditions for skin measurements. Increased skin specular reflection gave rise to large movement artifacts without the polarization filter. In conclusion, the polarized LDPI technique reduces movement artifacts and is particularly appropriate when, assessing, e.g., ulcers and burns, where specular reflection is high. © 2005 Society of Photo-Optical Instrumentation Engineers.

Knowledge of the optical properties of tissues can be applied in numerous medical and scientific fields, including cancer diagnostics and therapy. There are many different ways of determining the optical properties of turbid media. The paper describes measurements of the optical properties of porcine brain tissue using novel instrumentation for simultaneous absorption and scattering characterisation of small turbid samples. Integrating sphere measurements are widely used as a reference method for determination of the optical properties of relatively thin turbid samples. However, this technique is associated with bulky equipment, complicated measuring techniques, interference compensation techniques and inconvenient sample handling. It is believed that the sphere for some applications can be replaced by a new, compact device, called the combined angular and spatially resolved head sensor, to measure the optical properties of thin turbid samples. The results compare very well with data obtained with an integrating sphere for well-defined samples. The instrument was shown to be accurate to within 12% for μ_a and 1% for μ _s ^′ in measurements of intralipid-ink samples. The corresponding variations of data were 17% and 2%, respectively. The reduced scattering coefficient for porcine white matter was measured to be 100 cm⁻¹ at 633 nm, and the value for coagulated brain tissue was 65 cm⁻¹. The corresponding absorption coefficients were 2 and 3 cm⁻¹, respectively.

A new technique for respiratory rate measurement in the neonatal intensive care unit, fiberoptic respirometry (FORE), was tested using a specially designed nasal adapter. The aim was to investigate the system's accuracy and compare it to the transthoracic impedance (TTI) method and manual counting (MC). Further, the relationship between accuracy and degree of body movement was investigated. Seventeen neonates of median gestational age 35 weeks were included in the study. Video recordings (synchronized with data recordings) were used for classification of body movement. Breaths per minute data were obtained for 23-32-min periods per child, and a subset of these included MC performed by experienced nurses. A Bland-Altman analysis showed low accuracy of both FORE and TTI. A >20% deviation from MC was found in 22.7% and 23.8% of observations for the two methods, respectively. Both methods had accuracy problems during body movement. FORE tended to underestimate respiratory rate due to probe displacement, while TTI overestimated due to motion artefacts. The accuracy was also strongly subject-dependent. The neonates were undisturbed by the FORE device. In some cases, though, it was difficult to keep the adapter positioned in the airway. Further development should, therefore, focus on FORE adapter improvements to maintain probe position over time.

Development of a non-invasive method for measuring the blood glucose level is an urgent necessity, and putting such a method into practical use will enable some of the physical and mental stress that patients with diabetes have to endure to be removed. To realise a non-invasive blood glucose monitor, the gingival crevicular fluid (GCF) was measured. A GCF-collecting device was developed that was designed to be disposable, biocompatible and small enough to be inserted in the gingival crevice for collection of a sub-microlitre sample of GCF. Also, a high-sensitivity glucose testing tape incorporated in the device was developed. Red laser light in a portable optical device measured the colour density of the testing tape. Standard glucose solutions were used to investigate the measurement accuracy of the GCF glucose monitor and showed a correlation coefficient of R=0.99 (n=20) between the optical density and the glucose levels. The GCF glucose monitor was evaluated on healthy Swedish and Japanese adults (n=10) and both GCF glucose levels (GCFLs) and blood glucose levels (BGLs) were measured in conjunction with meal loads. The GCFLs were about 1/10-1/560 lower than the BGLs. No difference in the range of GCFLs between the Swedish and the Japanese subjects was observed. Therefore it was concluded that physique, body mass index and life-style, such as dietary habit, did not significantly influence the GCFLs. Further, the correlation coefficients of all the subjects were 0.70 and 0.88 with each group. It was suggested that GCF could be used as a method of non-invasive blood glucose measurement.

Tissue motion of the beating heart generates large movement artifacts in the laser Doppler perfusion monitoring (LDPM) signal. The aim of the study was to use tissue Doppler imaging (TDI) to localise intervals during the cardiac cycle where the influence of movement artifacts on the LDPM signal is minimum. TDI velocities and LDPM signals were investigated on three calves, for normal heartbeat and during occlusion of the left anterior descending coronary artery. Intervals of low tissue velocity (TDIint, < 1 cm s-1) during the cardiac cycle were identified. During occlusion, these intervals were compared with low LDPM signal intervals (LDPMint, < 50% compared with baseline). Low-velocity intervals were found in late systole (normal and occlusion) and late diastole (normal). Systolic intervals were longer and less sensitive to heart rate variation compared with diastolic ones. The overlap between LDPMint and TDIint in relation to TDIint length was 84 ± 27% (n = 14). The LDPM signal was significantly (p < 0.001, n = 14) lower during occlusion if calculated during minimum tissue motion (inside TDIint), compared with averaging over the entire cardiac cycle without taking tissue motion into consideration. In conclusion, movement artifacts are reduced if the LDPM signal is correlated to the ECG and investigated during minimum wall motion. The optimum interval depends on the application, late systole and late diastole can be used.

We have investigated if features in the diffuse reflectance spectra from in vivo spectroscopic measurements of the tympanic membrane could aid the diagnosis of otitis media in children. Diffuse reflectance spectroscopy, in the visible wavelength range, was used in 15 ears from children with otitis media with effusion before and after myringotomy and in 15 healthy ears as a reference. Two previously published erythema detection algorithms yielded numerical quantities of haemoglobin content. With a combination of the algorithms, induced erythema (after myringotomy) was distinguished from healthy ears using Student's t-test (p < 0.01). Otitis media with mucous effusion was distinguished from (1) otitis media with serous effusion, (2) induced erythema and (3) healthy ears, (p < 0.05) using Student's t-test for independent groups and the paired t-test for dependent groups. Our results imply that reflectance spectroscopy is a promising technique to be used for the diagnosis of otitis media.

Iontophoresis of vasoactive substances is a promising tool for studying pharmacological aspects of the (patho)physiology of the microvasculature. However, nonspecific microvascular responses are a common problem in most protocols used. We studied the effect of current density (mA/cm²), charge density (mC/cm²), drug concentration (mass %) and vehicle concentration (M) on the nonspecific vasodilatation during iontophoresis of sodium chloride, acetylcholine (ACh) and sodium nitroprusside (SNP).

We found that nonspecific vasodilatation depended on current density and charge density in both anodal and cathodal iontophoresis. The responses to ACh and SNP were dependent on current density, charge density and drug concentration. We found that by limiting current density (<0.01 mA/cm²) and charge density (<7.8 mC/cm²) and with adjusted concentrations for drugs and vehicles, it is possible to prevent nonspecific effects during iontophoresis of ACh and SNP, while maximum drug effects (plateaus in the dose–response curves) are still obtained. These new findings are important for future iontophoresis studies in which vasoactive drugs are used to assess microvascular function because the presented approach has advantages compared to older techniques, which mainly have attempted to suppress or compensate for the nonspecific responses during iontophoresis by the use of local anaesthetics or the measurement of drug-minus-vehicle responses, both of which present well-known experimental shortcomings.

The depth of light penetration is an interesting issue in various tissue optics experiments. The measurements of remitted light distribution was shown to allow for estimation of optical properties. However, in case of measurements with a short distance between the emitter and the detector, the diffusion equation fails, and the proposed methods cannot be applied. The aim of this study was to develop a simple method for estimation of the light penetration depth for short-distance measurements of remitted light. The idea is based on the analysis of the diffusely back-scattered light distribution adjacent to the emitter for the assessment of the scattering volume. The Monte Carlo method was used for theoretical estimation of the relationship between the light distribution around emitting fiber and the depth of light scattering volume. Two series of Monte Carlo simulations were performed: the first one with limited and the second one with unlimited scattering volume. In both series the values of absorption and scattering coefficients were altered within ranges typical of human tissues. The results of this study show that: the diffuse reflectance is strongly dependent on the absorption and scattering properties of the tissue and it is possible to estimate the depth of the scattering volume by use of the short distance profile of diffusely back-scattered light as measured at the surface of the tissue.

Methods for local photon pathlength and optical properties estimation, based on measured and simulated diffuse reflectance within 2mm from the light source, are proposed and evaluated in vivo on Caucasian human skin. The accuracy of the methods was good (2-7%) for pathlength and reduced scattering but poor for absorption estimation. Reduced scattering and absorption were systematically lower in the fingertip than in the forearm skin (633 nm). A maximum intra-site and inter-individual variation of ~35% in the average photon pathlength was found. The methodology was applied in laser Doppler flowmetry (LDF), where pathlength normalization of the estimated perfusion removed the optical property dependency.

This report reviews how to set up a laser Doppler perfusion imaging system intended for visualization of skin blood perfusion, capture images and evaluate the results obtained. A brief summary of related papers published in the literature within the areas of skin irritant and allergy patch testing, microdialysis and skin tumour circulation is presented, as well as early applications within other fields such as diabetology, wound healing and microvascular research.

OBJECTIVE: This study describes the production, under strictly standardized and controlled conditions, of radiofrequency lesions with identical neurogenerator settings: in vitro in two different albumin solutions (nongelatinous and gelatinous) and in vivo in the thalamus of the pig. METHODS: The radiofrequency lesions were investigated in vitro by the use of a specially designed video system and in vivo by magnetic resonance imaging. Moreover, the size of the in vivo lesions was estimated with the use of histological sectioning. The statistical analysis included the calculation of a correlation coefficient for the length, width, and volume for each lesion estimation. RESULTS: A high correlation (R = 0.96, P < 0.005, n = 14) was found between clot sizes in the two albumin solutions. Albumin clots generated in gelatinous albumin showed systematically larger volumes. In the pig, two concentric zones were seen in all magnetic resonance images and all histological preparations. The width correlation of the completely coagulated brain tissue (inner zones) was R = 0.94, P < 0.005, and n = 7. The corresponding correlation between magnetic resonance images and gelatinous albumin was R = 0.93, P < 0.005, and n = 7. As a rule, the in vitro clots were smaller than the outer zone but larger than the inner zone of the magnetic resonance imaging-recorded lesions for all of the electrode and temperature combinations tested. In vivo lesions generated with the same electrode and parameter settings showed high reproducibility. CONCLUSION: The value of presurgical electrode tests to validate the electrode function and lesion size in vitro has become evident in this study, which shows a high correlation between the in vitro albumin clots and the in vivo lesions observed on magnetic resonance images.

Overall inhomogeneity of ventilation distribution, as measured by single-breath vital capacity (VC) washout (SBW) is known to be greater supine vs. standing. To establish the underlying mechanisms 13 healthy males performed VC SBW of 4% SF6 and He, standing and supine, with or without a 10 sec breathhold (BH). Overall inhomogeneity, as indicated by normalized phase III slopes, was > 50% greater supine (SF6 13.1 ╫ 10-3, He 10.7 ╫ 10-3 L-1) than standing (SF6 8.6 ╫ 10-3, He 6.4 ╫ 10-3 L-1, P < 0.001). The (SF6-He) slope, an index of intraacinar inhomogeneity, did not change with posture. Breathholding, assumed to eliminate convective dependent inhomogeneity within and/or between small lung units, produced twice as great reduction of inhomogeneity when supine vs. standing. After BH inhomogeneity remained significantly greater supine vs. standing. In conclusion, at least two events seem to underlie the increased inhomogeneity when supine: (1) a substantially increased convection dependent non-uniformity between well-separated lung regions, and (2) a somewhat increased convection dependent non-uniformity within and/or between peripherally located lung units. ⌐ 2002 Elsevier Science B.V. All rights reserved.

A method for the prediction of the average photon pathlength in turbid media has been developed. The method is based on spatially resolved diffuse reflectance with discrete source detector distances up to 2 mm. Light reflectance was simulated using a Monte Carlo technique with a one-layer model utilizing a wide range of optical properties, relevant to human skin. At a source detector separation of 2 mm, the pathlength can vary sixfold due to differences in optical properties. By applying various preprocessing and prediction techniques, the pathlength can be predicted with a root-mean-square error of approximately 5%. Estimation of the photon pathlength can be used, e.g., to remove the influence of optical properties on laser Doppler flowmetry perfusion readings, which are almost linearly related to the average photon pathlength.

Rapidly repeated imaging of the left middle fingertip skin blood perfusion was performed in 51 healthy volunteers (mean age ▒ SD: 25.3 ▒ 7.6 years) prior to, immediately after and in the early reperfusion phase following introduction of an acupuncture needle at the Neiguan point (Pe. 6) and at a placebo point respectively, using a Laser Doppler Perfusion Imager (LDPI). The average skin perfusion of the fingertip was calculated for each image and used as an indicator of the microvascular response to the acupuncture needle introduction. The results of this randomised, placebo-controlled, cross-over study showed significant differences (p = 0.001) in the immediate skin blood perfusion response when needling is performed in an acupuncture point (Neiguan) and a placebo point, with a more pronounced reduction in skin blood perfusion when needling the acupuncture point. In the early reperfusion phase, however, a substantial increase in skin perfusion was observed that amounted to about 18% of the level prior to needle introduction, irrespective of the site of needle application. In a single individual it was demonstrated that the vasodilatation following needling in the acupuncture point persisted for a more extended time period. These results suggest that the LDPI technology may be useful in visualising and quantifying the peripheral vascular effects of acupuncture on the microcirculation.

Laser Doppler perfusion monitoring and imaging technologies generate time traces and two-dimensional flow maps of the microcirculation. With the goal of reaching different tissue depths, these technologies are equipped with lasers operating at different wavelengths ?. The fact that the average scattering angle, at a single scattering event, between a photon and a red blood cell increases with ? is compensated for by a 1/? effect in the scattering vector, rendering the average frequency shift virtually independent of the choice of wavelength. Monte Carlo simulations showed that the corresponding spectral signature of the Doppler signals for ? = 632.8 nm and 780 nm were close to identical. The theoretical predictions were verified by calculating the centre-of-gravity (COG) frequency of the laser Doppler power spectral density for the two wavelengths from forearm and finger skin, representing a low and high perfusion area, respectively (forearm COG = 123 against 121 Hz, finger COG = 220 against 212 Hz). When the wavelength changes from 632.8 nm to 780 nm, the heterodyne efficiency of the detector and, thereby, the inherent system amplification increase. For tissues with identical microvascular flow conditions, the output signal therefore tends to increase in magnitude when shifting to longer wavelengths.

Diaphragmatic activity is the standard assessment of respiratory neural output but is difficult to measure and cannot be used for long-term clinical monitoring. The tidal breathing minute ventilation (V»') and mean inspiratory flow (VT/tI) reflect respiratory drive and can be monitored non-invasively using respiratory inductive plethysmography (RIP). Recent findings indicate that peak inspiratory acceleration (PIA) correlates to diaphragmatic activity during CO2 rebreathing in piglets. The aim of the present study was to assess whether tidal breathing peak inspiratory acceleration reflects respiratory drive during carbachol challenge. Aerosolized carbachol was administered to 15 allergic sheep until pulmonary resistance increased by at least 400%. After threshold dose, slight increases in V»' and VT/tI were seen (8 and 5%, respectively, P = NS), while PIA increased by 30% (P<0.05). The change in PIA was closely correlated to changes in V»' and VT/tI (r = 0.73, P<0.01 and r = 0.88, P<0.001, respectively). In conclusion, peak inspiratory acceleration reflected respiratory drive during bronchoprovocation. Further, this new measure of drive has the potential to accurately estimate drive in chronic obstructive lung disease where intrinsic positive end expiratory pressure prevents accurate selection of beginning inspiration necessary for computation of, e.g. VT/tI.

Respiratory volumes are measured non-invasively by recording rib cage and abdominal motions using respiratory inductive plethysmography (RIP). Qualitative diagnostic calibration (QDC) of RIP is based on the natural variability in the relative rib-cage-to-abdomen contribution during tidal breathing. QDC does not require subject cooperation but it has previously been shown that accuracy may deteriorate when breathing pattern changes. The aim of this study was to investigate the causes and situations where QDC accuracy deteriorates. The QDC method was compared to PRA (calibration during voluntarily preferential rib cage or abdomen breathing) in ten adults. A reference RIP calibration was obtained from all validation data (REF). The PRA method had better accuracy than the QDC method (p<0.01). The volumetric error ranged between 10% and 136% with QDC and between 5% and 33% with PRA. The PRA calibration factors were within 6% of those from REF, while the QDC rib-cage factor was underestimated by 15% and the abdominal factor was overestimated by 38%. Small natural variability in the relative rib-cage-to-abdomen contribution was related to poor accuracy. Each compartment's variability depended on its magnitude, which is a violation of the QDC assumptions.

Analgesized skin, when subjected to heat stimuli, responds by increasing skin perfusion. This response does not originate from increased perfusion in superficial capillaries, but rather in the deeper lying vessels. The aim of this study was to assess changes in blood chromophore content, measured by reflection spectroscopy, in relation to the perfusion increase, especially regarding the chromophores oxyhemoglobin and deoxyhemoglobin. Eleven normal subjects were treated with analgesic cream (EMLA) and placebo for 20, 40, 60, 120, and 180 min. Individual reactions to local heating were classified as responses if the change in reflection data or the change in perfusion, as measured by laser Doppler blood flowmetry, exceeded 2 standard deviations of normal variation. The increase in blood perfusion or in blood content gave rise to an increased absorption, interpreted as an increase due mainly to the chromophore oxyhemoglobin. The number of responses increased with increased treatment time for EMLA-treated areas. In general, there was a good agreement between both methods; 44 of 55 classifications coincided for the two methods used. In conclusion, analgesized forearm skin, which had been exposed to local heating, responded with an elevated perfusion consisting of oxygenated blood. This strengthens the hypothesis that the flow increase occurs through dilatation of larger deeper lying skin vessels and not in the capillaries.

Objective. The present study was aimed at determining the relative influences of tidal volume and thoraco-abdominal separation (relative thoracic and abdominal contribution to the tidal volume) on the respiratory induced intensity variation (RIIV) of the photoplethysmographic signal. The effects were studied in two body positions. Methods. Respiratory inductive plethysmography was used or quantifying thoraco-abdominal separation and for assessing tidal volumes. 10 subjects were trained to perform widely varying degrees of thoraco-abdominal separation at different tidal volumes. The relationship between the RIIV signal peak-to-peak value (measured at the forearm), and the tidal volume and thoraco-abdominal separation was investigated in two body positions with the use of multiple linear regression. Results. Larger tidal volume and more thoracic contribution to respiration were found to increase the RIIV peak-to-peak value (p < 0.0005). In the supine position, the tidal volume influence was stronger than that of thoraco-abdominal separation, and in the sitting position, the opposite was seen. Conclusions. The effects on the RIIV signal following changes in thoraco-abdominal separation and tidal volume are of the same order of magnitude. In the supine position, the influence of thoracic versus abdominal contribution to the tidal volume is not as significant as in the sitting position. Photoplethysmography is a promising technique for combined monitoring of several respiratory parameters, including tidal volume. In situations where the relative thoracic and abdominal contribution are likely to vary, the tidal volume information becomes less reliable.

Background/aims: The capillary bed is recognized as the site where metabolic and nutrient processes occur for living tissues at all levels. The evaluation of this vital process is a major concern in microcirculation. Unlike traditional approaches that concentrated on the extreme local properties of this process, a more global analysis toward capillary ensembles is employed here, since capillaries work as a cooperative entirely. As a first step toward ensemble analysis, the static and planar geometric parameters are investigated. Parameters such as the capillary adjacency and size information are very important in predicting and analysing certain malfunctions in the microvascular bed. Methods/results: In order to achieve an objective and accurate analysis of these vital parameters, a computerized imaging system is proposed. Not only the number of capillaries and the capillary cross-sectional areas are important in describing the microvascular bed but the planar distribution pattern of the capillaries also carries valid information. This information, unique to the ensemble analysis, can be used to reveal, visualise and quantify the clustering of capillaries, and this information, according to the Krogh model, is fundamental in estimating the tissue oxygen supply. Two spatial models, the closest neighbor and triangulation methods, have been applied to the captured images of capillary ensembles. The closest neighbor technique generates a minimal distance map or displays a distribution, which depicts the local clustering of capillaries. The triangulation technique, on the other hand, generates a mutual distance map, which is a global description of the capillary positions. Triangulation methods have been evaluated but all except the Greedy triangulation method have been rejected due to lack of robustness and model weakness. Therefore, the capillaries are triangulated by the Greedy triangulation method, and the capillary distribution uniformity is defined as one minus the coefficient of variance of the edge lengths of the mutual distance map. Conclusions: A series of advanced image processing methods have been developed that efficiently extract the capillary position, size and distribution information from the images. These results facilitate the automatic counting of capillaries and the capillary size-related pathological analysis.

Although topical analgesia cream has been used for several years, little is known about its effects on the microcirculation. Previous studies have shown a vasoconstrictive effect after short application times and a vasodilatation after longer application. It has also been shown that vasomotion does not occur in the analgesized skin. The present study was undertaken to investigate the alterations in skin blood perfusion following local cooling, local heating and pin-pricking after the establishment of analgesia. In 11 healthy volunteers, skin analgesia was attained by use of a eutectic mixture of lidocaine and prilocaine (EMLA, Astra Pain Control AB, Sweden) applied to the skin three hours prior to provocation. The changes in skin blood perfusion, after applying three different provocation methods, were studied using the laser Doppler technique. Local cooling and heating to temperatures of +10 and +45░C, respectively, were applied for 9 s by use of a copper probe (F12 mm). In the pin-prick provocation method, a combined effect of deflection and penetration of the skin to in total 3 mm was attained. Identical provocation methods were applied to placebo treated and untreated skin areas. After heat provocation, significant differences in the perfusion response between the treatments were seen (P < 0.0001). Skin areas treated with analgesia cream responded with a slow increase in perfusion that persisted beyond the four minute measurement period. Placebo and untreated areas decreased their perfusion over time. After cooling a significant reduction in skin perfusion was seen, irrespective of the treatment. Similarly, after pin-pricking a perfusion increase was seen for all treatments. The findings indicate that topical analgesia influences the myogenic control of the blood flow in those vascular plexa measured by laser Doppler following heat provocation. No differences could be seen in the response to pin-pricking and cooling for the different treatments. (C) 2000 Academic Press.

Background: In biomedical research and clinical medicine there is a demand for potent sensors to measure the components that make up blood gas analyses. Today, as when the electrochemical PO2, PCO2 and pH electrodes were first introduced, these measurements are usually made with the same type of sensor technology. The aims of the present study were, firstly, to find out whether the platinum cathode in the Clark electrode can be replaced by antimony for oxygen measurements (amperometry (A)), secondly, whether, during oxygen measurements, the inherent corrosion potential of the antimony metal can be used for measurement of pH in the same measurement area (potentiometry (P)). Methods: An electrode of purified, crystallographically orientated monocrystalline antimony (COMA) connected to a reference electrode (silver- silver chloride) was used for the P measurements. Measurements of A (at -900 mV) and P were made in an aqueous environment regulated for oxygen, pH, and temperature. Results: Reproducible oxygen sensitivities of 0.925 nA/% oxygen (2% CV (coefficient of variation)) (A), 10.7 mV/% (P), and 0.7mV/% (P) were found in the oxygen range: 0-21%, <5%, and above 5%, respectively. The pH sensitivity was 57 mV/pH unit (P). Oxygen and pH measurements were less accurate at oxygen concentrations close to 0%. Conclusions: Both the oxygen and pH part of the composite electrode signal can be identified by this dual mode technique (A and P). The sensor seems to be promising as it provides measurements of two separate variables (oxygen and pH) and also has the desirable characteristics of a solid state sensor.

Laser Doppler perfusion imaging offers a new modality for in vivo monitoring of the superficial blood perfusion in biological tissue. In this study, the superficial blood perfusion of malignant nonmelanoma skin tumours and the surrounding normal skin was measured in conjunction with photodynamic therapy (PDT) using topical ò–aminolaevulinic acid (ALA)–induced protoporphyrin IX as a photosensitizer. The results clearly show that, in contradiction to PDT with the intravenously administered photosensitizer photofrin. no direct vascular damage can be seen. With the topical sensitization the blood perfusion is increased immediately after the treatment irradiation. The increased blood flow is seen up to a week after treatment, in a similiar way as for an inflammatory reaction. Despite this, all basal cell carcinoma and squamous cell carcinoma in situ lesions in this study healed without any sign of residual tumour after the treatment, suggesting an efficient direct tumour cell destruction induced by PDT.

Spatial and temporal variations in forearm skin perfusion captured by laser Doppler perfusion imaging (LDI) have been compared with topographic maps recorded by laser Doppler flowmetry. In order to determine the shortest LDI sampling time required at each measurement site, with an adequate signal-to-noise ratio and with the ability to display the heterogeneity in skin perfusion, the noise-limited resolution of the LDI system as well as various sampling times were tested. The noise-limited resolution for medium and high light intensities were less than 0.5% (temporal) and 0.3% (spatial) of full scale. A sampling time of 1 sec was selected and image presentation was made by performing bilinear interpolation between perfusion values. The same area (10 x 10 mm) was mapped with LDI and topographic mapping at seven different sites. In addition, a larger area covering the surrounding skin was recorded with LDI. The small area recordings with LDI and topographic mapping could be identified in the larger LDI image. High-and low-perfusion spots coincided between the two systems. Temporal variations were studied by repeated LDI recordings of the same areas as above. Small spots were selected in the areas and plotted versus time. Without provocation, the total perfusion changes at each spot showed large variations, but the relative perfusion levels between neighboring spots persisted. Provocation with heat increased the perfusion in all spots.

A laser Doppler perfusion imaging technique based on dynamic light scattering in tissue is reported. When a laser beam sequentially scans the tissue (maximal area approximately 12 cm*12 cm), moving blood cells generate Doppler components in the backscattered light. A fraction of this light is detected by a remote photodiode and converted into an electrical signal. In the signal processor, a signal proportional to the tissue perfusion at each measurement point is calculated and stored. When the scanning procedure is completed, the system generates a color-coded perfusion image on a monitor. A perfusion image is typically built up of data from 4096 measurement sites, recorded during a time period of 4 min. This image has a spatial resolution of about 2 mm. A theory for the system inherent amplification factor dependence on the distance between individual measurement points and detector is proposed and correction measures are presented. Performance results for the laser Doppler perfusion imager obtained with a flow simulator are presented. The advantages of the method are discussed.

Thirteen patients with port wine stains (PWS) were treated with argon laser therapy. Before and at different points in time following treatment, skin blood perfusion and temperature were mapped with laser Doppler imaging and thermography. In nine patients no elevation in blood perfusion was observed in the PWS in comparison with the surrounding normal skin before treatment. In the remaining four patients a significantly (p less than 0.01) higher blood flow was recorded within the PWS. Immediately after treatment nine patients showed elevated perfusion within the PWS. During the first two days following treatment, all patients showed a gradually decreasing hyperperfusion in the borderline between the PWS lesion and surrounding skin. Immediately after treatment 10 patients had a significantly (p less than 0.01) higher temperature in the PWS than in normal skin. During the first 24 h following treatment, an elevated perfusion was in general accompanied by a tissue temperature increase. Three and a half months after argon laser treatment, three patients showed excellent clinical results with no remaining PWS spots or scarring. Two of these patients had had both elevated perfusion and temperature in the PWS prior to treatment.

Deep brain stimulation (DBS) is widely used for reduction of symptoms caused by movement disorders. In this chapter a patient-specific finite element method for modeling and simulation of DBS electric parameters is presented. The individual’s stereotactic preoperative MR-batch of images is used as input to the model in order to classify tissue type and allot electrical conductivity for cerebrospinal fluid, blood and grey as well as white matter. With patient-specific positioning of the DBS electrodes the method allows for investigation of the relative electric field changes in relation to anatomy and DBS-settings. Examples of visualization of the patient-specific electric entities together with the surrounding anatomy are given. The use of the method is exemplified on patients with Parkinson’s disease. Future applications including multiphysics simulations and applicability for new DBS targets and symptoms are discussed.

The concept that the time to onset of erythema after the application of the rubefacient and urticant substance methyl nicotinate (MN) indicates skin barrier competence was introduced 30 years ago. MN produces a dose-dependent erythema on topical application to intact skin, the nature of which is known to be fast moving (in the order of minutes) and variable. Using tissue viability imaging (TiVi) the time course and degree of the reaction can be conveniently followed and analysed. Inter-individual variability can be quite marked but intra-individual variability is less pronounced. At the upper end of provocation (higher doses, more sensitive individuals) urtication can occur, which decreases blood flow by increasing pressure on and thus emptying capillaries. The TiVi system can quantitate urtication and inherent (blanched) skin colour. The utility of MN application in the study of individual barrier function and microvascular reactivity is increased by the use of the TiVi system for collection and analysis of data.

Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease (PD). The success of DBS is highly dependent on electrode location and electrical parameter settings. In this study patient-specific computer models of DBS were used for postoperative follow-up in three PD patients who suffered from stimulation induced hypomania, dysarthria, and uncontrollable laughter respectively. The overall aim of the study was to relate the anatomical aspect of the electric field to the effects and side effects of stimulation. The simulations showed the anatomical distribution of the electric field for all the patients and the results were in agreement with previous reports regarding these side effects of stimulation. It was demonstrated that patient-specific models and simulations of DBS may be useful for postoperative follow-up of DBS.

Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease and related movement disorders. The success of DBS is highly dependent on electrode location, electrical parameter settings and the surgical procedure. In this paper an overview of the current status of optical measurements for intracerebral guidance performed during DBS implantation is presented. Laser Doppler perfusion monitoring and/or reflection spectroscopy measurements have been done in relation to more than 70 DBS lead implantations to wards targets in the deep brain structures. The techniques have also been compared with impedance monitoring, and simulation of the measurement depth has been done with Monte Carlo technique. These studies show that grey-white matter boundaries can be determined with a resolution higher than for both impedance measurements and magnetic resonance imaging.

The aim of the study was to investigate the spectral changes during heating and to estimate threshold temperatures for initiation of the thermal coagulation. A brain electrode with optical fibers was used to generate lesions in ex-vivo porcine white and gray matter as well as in fat and meat from pork chop. Radio frequency ablation (60 s, 48–90 °C, steps of 2-10 °C) was performed while simultaneous spectroscopy measurements were made in the range 490–900 nm.

The optical signal recorded from porcine gray and white brain matter was unstable with the reflected light intensity fluctuating a lot. Nevertheless an abrupt increase in light intensity during coagulation in gray matter was found at 48 ± 6 °C (n = 21), probably indicating onset of coagulation. The reflected light intensity from white matter showed no consistent behavior during coagulation.

The results for pork chop meat and fat were considerably more consistent. The reflected light intensity from pork chop meat stayed stable up to a mean temperature of 42.5 ± 3.5 °C (n = 11). Above this temperature it abruptly increased for all wavelengths. The reflected light intensity from pork chop fat dropped over all wavelengths immediately as the temperature increased and remained low as the fat cooled (n = 8).

In conclusion diffuse reflectance spectroscopy appears to be suitable to detect onset of coagulation in muscle tissue and gray matter. The estimated initiation temperature of coagulation varied and was dependent on tissue type.

In a previous study, we presented a new technique for representation of the shape of a scattering surface. A sensor based on two parallel fiber arrays yielded a source-detector intensity matrix (SDIM). In that study, it was shown that convex and concave polyacetal plastic (Delrin) surfaces could be accurately distinguished using the proposed technique. A simplified simulation model for calculating the SDIM was used, assuming that backscattered light was generated by Lambertian sources in the illuminated surface. These simulations showed discrepancies compared to measurements, probably due to the absence of light scattering in the model.Here, we will present an improved model, based on the Monte Carlo technique for light transport in turbid media. The optical properties of the Delrin phantoms were estimated by means of different measurement techniques. The optical properties and the geometry of the Delrin phantoms were implemented in the model along with the spatial distribution of the source and detector fibers of the sensor. The SDIM was extracted from backscattered photons exiting the turbid medium from the curved surface. The SDIM:s obtained with the Monte Carlo model, showed a much closer agreement with the measurements than those obtained with the Lambertian model. The small discrepancies observed are probably due to spatially varying optical properties of the plastic phantoms. Measurements, using the previously described sensor, of the SDIM from Delrin pieces with convex and concave surfaces, are compared to the SDIM extracted from simulations using the Monte Carlo model.

Deep brain stimulation (DBS) is an effective method for managing movement disorders. A small electrode is implanted in the basal ganglia and an electric potential is applied to one or more active elements of the electrode in order to simulate the neurons in the surrounding tissue. The fundamental understanding of the mechanisms responsible for the therapeutic DBS effects is unknown. A method to increase the knowledge is to use computer simulations. In this study the finite element method has been used for investigation of relative changes of the electrical field extension surrounding a monopolar DBS-electrode positioned in gray matter. Due to the frequently appearing cystic cavities in globus pallidus and putamen a nucleus of gray matter with and without a cerebrospinal fluid filled cystic cavity was modeled. The simulations demonstrated an electrical field around the active element with decreasing values in the radial direction. A stepwise change was present at the edge between gray and white matter. The cyst increased the radial extension and changed the shape of the field. This may result in closely related unexpected structures being stimulated and could be one of the reasons of reported postoperative complications.

A detailed and a simplified model of a lesioning electrode was made using the finite element method. 15 simulations of the lesioning procedure were performed for each model and the resulting lesion volumes were compared in order to investigate if the simplified model is adequate. The simplified model resulted in a very slight overestimation of the volume compared to the detailed model. It was thus concluded that the simplified model is adequate for simulations.