Stimulation-induced side effects in the posterior subthalamic area: distribution, characteristics and visualization.

OBJECTIVE: The posterior subthalamic area (PSA) is an emerging but relatively unexplored target for DBS treatment of tremor. The aim of the study was to explore the area further by evaluating the spatial distribution and the characteristics of stimulation-induced side effects in this area. METHODS: Twenty-eight patients with essential tremor (ET) implanted with 33 DBS electrodes were evaluated concerning stimulation-induced side effects by testing each contact separately one year after surgery. The location of the side effects were plotted on axial slides of the Morel Stereotactic Atlas and a 3-dimensional model of the area for visualization was created. RESULTS: Visualization of the contacts eliciting stimulation-induced side effects demonstrated that identical responses can be elicited from various points in the PSA and its vicinity. The majority of contacts inducing muscular affection and cerebellar symptoms, including dysarthria, could not be attributed to an effect on the internal capsule. Paresthesias, affecting various body parts were elicited throughout the area without a clear somatotopic pattern. CONCLUSION: Stimulation-induced side effects in the PSA and its vicinity were difficult to attribute to certain anatomical areas as the same response was induced from various locations. Therefore, this study could not provide a meaningful somatotopic map with regard to stimulation-induced side effects in the PSA.

Polarized laser Doppler perfusion imaging--reduction of movement-induced artifacts.

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.

Myocardial perfusion monitoring during coronary artery bypass using an electrocardiogram-triggered laser Doppler technique.

Electrocardiogram (ECG)-triggered laser Doppler perfusion monitoring (LDPM) was used to assess myocardial perfusion, with minimum myocardial tissue motion influence, during coronary artery bypass grafting (CABG). Thirteen subjects were investigated at six phases: pre- and post-CABG; post aorta cross-clamping; pre and post left internal mammary artery (LIMA) graft declamping; and post aorta declamping. The perfusion signal was calculated in late systole and late diastole, with expected minimum tissue motion, and compared with arrested heart measurements. Patient conditions or artifacts caused by surgical activity made it impossible to perform and analyse data in all six phases for some patients. No significant (n = 5) difference between perfusion signals pre- and post-CABG was found. Diastolic perfusion signal levels were significantly (p < 0.02) lower compared with systolic levels. After aorta cross-clamping, the signal level was almost zero. A distinct perfusion signal increase after LIMA and aorta declamping, compared with pre-LIMA declamping, was found in ten cases out of 13. A significantly (p < 0.04) lower perfusion signal in the arrested heart compared with in the beating heart was registered. Influence from mechanical ventilation was observed in 14 measurements out of 17. In conclusion, ECG-triggered LDPM can be used to assess myocardial perfusion during CABG. Perfusion signals were lower in the arrested heart compared with in the beating heart and in late diastole compared with late systole. No significant difference between pre- and post-CABG was found.

In vitro measurements of optical properties of porcine brain using a novel compact device.

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 microa and 1% for micro'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.

Myocardial tissue motion influence on laser Doppler perfusion monitoring using tissue Doppler imaging.

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.

Non-invasive monitoring of gingival crevicular fluid for estimation of blood glucose level.

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.

Assessment of pigmented skin lesions in terms of blood perfusion estimates.

BACKGROUND/AIMS: Cutaneous malignant melanoma is a disease of increasing clinical and economical importance. The prognosis is good with early diagnosis. The chief differential diagnosis is benign melanocytic naevus, a common lesion in Caucasians. Attempts have been made to use bioengineering techniques to aid in the initial diagnosis. The present study proposes a method of extracting possibly discriminative blood perfusion properties in pigmented skin lesions by combining information on the lesions' blood perfusion with optical or visual information of their spatial extent. METHODS: A total of 46 blood perfusion measurements were performed on 22 pigmented skin lesions, the ultimate diagnosis of which was three histologically proven malignant melanomas, four histologically proven benign naevi and fifteen naevi assessed by two specialist dermatologists as being benign. Laser Doppler perfusion imaging gave two different types of two-dimensional data sets (64x64 pixels), one representing the total backscattered light intensity at each measurement point (TLI image) and the second corresponding to perfusion values. The boundaries of each examined lesion were derived from the TLI image employing greyscale thresholding, thus resulting in an estimated region of interest (ROI) approximating the optical extent of the lesion. The ROI was superimposed on the perfusion image and extraction of perfusion features was then performed. RESULTS: The processing of the TLI images was successful in delineating the lesions' boundaries. The first hypothesis that the mean perfusion quotients in MM and benign naevi are equal could not be rejected at the chosen 5% level of significance. The second hypothesis that the mean percent-age of elevated perfusion values (image pixels) within the ROI shows no difference between MM and benign naevi could be rejected at a 5% level of significance. CONCLUSIONS: This study has presented a method of extracting blood perfusion parameters of pigmented skin lesions by combining blood perfusion information with information on the lesion's optical extent. The proposed method of presenting data could prove to be a useful discriminative adjunct in the assessment of pigmented skin lesions.

A system for on-line laser Doppler monitoring of ECG-traced myocardial perfusion.

Laser Doppler perfusion monitoring (LDPM) is an established method for microvascular measurements. When applied to the beating heart, however, movement artifact contributions will result in an overestimation of the perfusion. In order to overcome this problem, the perfusion signal may be processed in relation to intervals in the cardiac cycle with minimal tissue motion, e.g., in late systole and late diastole. The aim of this study was to develop an electrocardiogram (ECG) tracing algorithm for R, T and P wave detection and to use these peaks to process the perfusion in intervals with minimal motion. The algorithm, evaluated in three subjects, detected the peaks correctly to 99.9% under ideal conditions. Used on a heart patient in postoperative care this was reduced to 93.2%. However, since the overall goal is to monitor changes in the myocardial perfusion over hours or even days, it is not necessary to capture perfusion values in every single heartbeat. Time traces of perfusion captured in relation to the T and P waves showed a periodical behavior. In order to tune the processing and presentation of the perfusion signal, future studies will focus on long term monitoring of myocardial perfusion during heart surgery and in the postoperative care.

Analysis and processing of laser Doppler perfusion monitoring signals recorded from the beating heart.

Laser Doppler perfusion monitoring (LDPM) can be used for monitoring myocardial perfusion in the non-beating heart. However, the movement of the beating heart generates large artifacts. Therefore the aim of the study was to develop an LDPM system capable of correlating the laser Doppler signals to the cardiac cycle and to process the signals to reduce the movement artifacts. Measurements were performed on three calves, both on the normal beating heart and during occlusion of the left anterior descending coronary artery (LAD). The recorded LDPM signals were digitally processed and correlated to the sampled ECG. Large variations in the output (perfusion) and DC signals during the cardiac cycle were found, with average coefficients of variation of 0.36 and 0.14 (n = 14), respectively. However, sections with a relatively low, stable output signal were found in late diastole, where the movement of the heart is at a minimum. Occlusion of the LAD showed the importance of recording the laser Doppler signals at an appropriate point in the cardiac cycle, in this case late systole, to minimise movement artifacts. It is possible to further reduce movement artifacts by increasing the lower cutoff frequency when calculating the output signal.

Guidelines for visualization of cutaneous blood flow by laser Doppler perfusion imaging. A report from the Standardization Group of the European Society of Contact Dermatitis based upon the HIRELADO European community project.

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.

Phototesting based on a divergent beam--a study on normal subjects.

In a previous publication from our group, phototesting based on a single exposure to a divergent UVB beam with radially decreasing irradiance values was suggested. The aim of the present study was to evaluate technical, practical and biological aspects of the suggested method in normal subjects. Twenty healthy volunteers were provoked on the back with both a collimated beam (four fixed doses, in circular areas with a diameter of 1.5 cm) and the divergent beam (a continuous, radially attenuating dose spectrum covering an area with a diameter of 4.5 cm). Eleven of the subjects were subjected to double provocation with the divergent beam. Assessment was carried out at 6 and 24 h after exposure by measuring the diameter of the reactions both visually and by mapping the skin blood flow change with laser Doppler perfusion imaging (LDPI). Minimal erythemal dose (MED) was determined for both the collimated and the divergent provocation. The reaction diameters were used to decide MED by combination to a mm for mm mapped dose spectrum of the divergent beam profile. Dose-response curves were plotted using the quantitative response data of the LDPI-images against the corresponding dosimetry data. No systematic difference could be proven between LDPI and visual diameters and a 95% confidence interval for the mean difference was calculated to (-0.8, 2.0). Slightly greater diameters were found at the visual assessment performed at 6 h compared to 24 h (95% confidence interval (-0.1, 2.8)). Double provocation showed a good reproducibility both for the visual and the LDPI assessment (P<0.05). The divergent beam provocation allowed a more detailed discrimination of MED compared to the collimated beam provocation. The MED values determined with the divergent beam were, however, generally higher, especially in the lower range of MED values. Technical factors related to the beam divergence and the correct measurement of erythemal effective irradiance are believed to be the explanation for this phenomenon, which is thus correctable. In conclusion, the results from this study support our belief that the phototesting protocol based on a divergent beam constitutes a good opportunity for improved phototesting, since MED and dose-response characteristics may be extracted in more detail from a single UV exposure.

Analysis of temperature measurement for monitoring radio-frequency brain lesioning.

During ablative neurosurgery of movement disorders, for instance therapy of Parkinson's disease, temperature monitoring is crucial. This study aims at a quantitative comparison of measurement deviations between the maximum temperature located outside the lesioning electrode and two possible thermocouple locations inside the electrode. In order to obtain the detailed temperature field necessary for the analysis, four finite element models associated with different surroundings and with different power supplies are studied. The results from the simulations show that both the power level and the power density as well as the surrounding medium affect the temperature measurement and the temperature field in general. Since the maximum temperature is located outside the electrode there will always be a deviation in time and level between the measured and the maximum temperature. The deviation is usually 2-7 s and 3-12 degrees C, depending on, for example, the thermocouple location and surrounding medium. Therefore, not only the measured temperature but also the relation between measured and maximum temperature must be accounted for during therapy and device design.

In vitro evaluation of brain lesioning electrodes (Leksell) using a computer-assisted video system.

Radiofrequency (RF) generated thermal brain lesions are widely used in functional neurosurgery. The size, shape and development of the lesions depends on system parameter settings and the electrode configuration. Difficulties in studying the effect of these factors in vivo stimulated us to develop an in vitro system for standardized comparison between different electrodes and physical parameters. A computer-assisted video system was set-up allowing continuous video recording of RF-generated coagulations in either a standard albumin solution or in the fresh white of a hen's egg as transparent test substrates. Ten lesions were made with each test electrode (two bipolar and three monopolar) in each of the two substrates at 70 degrees, 80 degrees and 90 degrees C (t = 60 sec). Due to the better homogeneity the lesions in the albumin solution were much more regular and reproducible. This made it possible to calculate the size (width 2.2 +/- 0.1 to 5.3 +/- 0.1 mm and length 3.0 +/- 0.1 to 8.7 +/- 0.3 mm) as well as the volume (8.5 +/- 1.4 mm3 to 133.5 +/- 26.8 mm3). It is concluded that this in vitro system offers a reproducible way to study and document the effect of different electrode configurations and RF-generator settings on the formation of a heat lesion. Even if the results are not directly applicable to the living human brain they give an estimate of the form and size of a coagulation lesion and can be of value for standardized comparisons between different electrodes.

A comparison between in vitro studies of protein lesions generated by brain electrodes and finite element model simulations.

The aim of this study was to develop a finite element model for simulation of the thermal characteristics of brain electrodes and to compare its performances with an in vitro experimental albumin model. Ten lesions were created in albumin using a monopolar electrode connected to a Leksell Neuro Generator and a computer-assisted video system was used to determine the size of the generated lesions. A finite element model was set up of the in vitro experiments using the same thermal properties. With a very simple heat source applied to the finite element model in the proximity of the upper part of the tip, a good agreement (no deviations in width and distance from tip but a deviation in length of -1.6 mm) with the in vitro experiments (width 4.6 +/- 0.1 mm and length 7.4 +/- 0.1 mm) was achieved when comparing the outline of the lesion. In addition, a gelatinous albumin-model was set up and compared to computer simulations resulting in deviations in width of -0.4 mm, length of -2.2 mm and distance from the tip of -0.1 mm. Hence, the utilisation of finite element model simulations may be a useful complement to in-vitro experiments.

Differential effect on vasodilatation and pain after intradermal capsaicin in humans during decay of intravenous regional anesthesia with mepivacaine.

BACKGROUND AND OBJECTIVES: When given intracutaneously, capsaicin can cause burning pain by central propagation in thin afferents, as well as neurogenic vasodilatation, reflecting antidromic conduction in the same fibers. We wanted to test the hypothesis that an intravenous regional block (IVRA) inhibits these two phenomena to a similar degree. METHODS: Sixteen healthy volunteers participated. A bilateral IVRA was performed by simultaneously injecting mepivacaine in one arm and normal saline in the other in a randomized, double-blind manner. Ten minutes after release of the tourniquet, neurogenic inflammation was inflicted in each forearm by intracutaneous capsaicin. Microvascular skin blood flow was measured with a laser Doppler perfusion imager. The area of the flare and the flow therein were measured, taking into account the change in baseline caused by mepivacaine treatment and the postischemic hyperemia. Pain was repeatedly evaluated by visual analog scale. RESULTS: The reactive hyperemia following arterial occlusion was less in the mepivacaine-treated arm 10 minutes after tourniquet release (P=.026). Intracutaneous capsaicin elicited a flare in both arms. The area of the flare was smaller 10 minutes after capsaicin (P=.009) in the mepivacaine-treated arm. There was no difference between the arms concerning the mean blood flow within the flare or in ischemic or capsaicin-induced pain. CONCLUSIONS: Mepivacaine, given as an IVRA, had no effect on the post-IVRA sensory function of thin afferents but differentially decreased the spread of the capsaicin-induced flare.

Superficial blood flow following photodynamic therapy of malignant non-melanoma skin tumours measured by laser Doppler perfusion imaging.

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 non-melanoma skin tumours and the surrounding normal skin was measured in conjunction with photodynamic therapy (PDT) using topical delta-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 similar 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.

High resolution laser Doppler perfusion imaging for the investigation of blood circulatory changes after microdialysis probe insertion.

BACKGROUND/AIM: Cutaneous microdialysis enables in vivo sampling of substances in the extracellular space in human skin. It is usual to allow an equilibration time to elapse after tissue trauma caused by probe insertion. One of the prerequisites for correct interpretation of data is detailed knowledge of the effect of insertion and presence of the probe in the skin, especially in the tissue closest to the membrane. METHODS: Laser Doppler perfusion imaging was used to investigate the time required for blood perfusion to return to near normal levels after probe insertion. The standard system was used in parallel with a high resolution system. The latter gave 3600 measurement sites in an area of 2 cm × 2 cm and thus enabled a detailed study of circulatory changes immediately around the membrane. Perfusion levels prior to probe insertion as well as the perfusion response to probe insertion were recorded by both systems. RESULTS: In agreement with previous findings, the perfusion levels were found to return to near normal levels within 60 min. Individual variations were, however, seen. High resolution laser Doppler perfusion imaging provided detailed visualisation of these variations both spatially and over time. CONCLUSIONS: High resolution laser Doppler perfusion imaging is superior to standard laser Doppler perfusion imaging in detailed visualisation of the variations in skin blood perfusion after microdialysis probe insertion. The individual variations seen can be of importance in the interpretation of microdialysis data.

Does low power laser light used in laser Doppler systems affect the sensory nerves?

BACKGROUND/AIMS: Many subjects have stated that they can sense the laser light during cutaneous laser Doppler recordings. The aim of the study was therefore to investigate if low power laser light used in laser Doppler systems affects the sensory nerves. METHODS: Single point recording as well as imaging was performed with the laser Doppler perfusion imager at the finger pulp, dorsal and ventral side of the hand and the forearm skin in 12 healthy volunteers. The hypothesis "the subject can not sense the laser beam" was tested by double blind random control of the on-off pattern of the laser light reaching the skin. In total, 96 trials (each including 12 recordings) were performed. Furthermore, it was investigated if the blood flow level was influenced by the subjects "sense" of being measured. RESULTS: The hypothesis was rejected in 92 out of 96 trials. Three of the trials that could not be rejected were recorded from the same subject. In further trials no reproducibility was found. The blood flow level was not influenced by the subjects "sense" of being measured. CONCLUSIONS: In general, the laser light used in laser Doppler imaging systems does not influence the sensory nerves. However, it can not be excluded that the laser light used in laser Soppier perfusion imaging (LDPI) affects sensory nerves under unknown circumstances and at specific spots in cutaneous tissue.

Laser Doppler perfusion imaging of eyelid skin.

We report an initial laser Doppler perfusion study of the eyelids and compare the results with those of other cutaneous regions. Eleven healthy subjects with no prior medical or surgical history, or eyelid malposition underwent laser Doppler perfusion scanning of six skin locations: right forearm, right middle fingertip, right upper eyelid, right lower eyelid, left upper eyelid, and left lower eyelid. Cutaneous perfusion in the four eyelid locations and right middle fingertip were statistically similar to each other but significantly higher than that in the right forearm (p = 0.002). Also, mean perfusion in pretarsal skin was > 50% than that in preseptal skin (p = 0.002). In addition, in an eyelid with histopathologically documented basal cell carcinoma, cutaneous perfusion was significantly higher than the mean of the normal eyelids (p = 0.002). Eyelids are perfused at the same high rate as are other regions of the head, and significantly higher than low flow regions, such as the extremities. Future application of this laser Doppler perfusion scanning include assessing burn depth, postoperative monitoring of periorbital tissue transfer, distinguishing benign and malignant adnexal skin lesions, and establishing the pathologic margins of lid tumors.