Karin Wårdell

Laser Doppler perfusion imaging by dynamic light scattering

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.<<ETX>>

The cutaneous vascular axon reflex in humans characterized by laser Doppler perfusion imaging.

1. Laser Doppler perfusion imaging was used to map the cutaneous vascular axon response induced by trains of electrical skin stimuli (1 ms, 2 Hz) on the dorsum of the hand, finger and foot in twenty‐four healthy subjects. Conduction anaesthesia was applied to nerves supplying the stimulated skin areas. Subtraction of images recorded before and after stimulation was used for data analysis of the intensity and area of the response. 2. The stimulation evoked a localized perfusion increase around the stimulating electrode which lasted approximately 30 min and increased in intensity and area with increasing stimulation strength to a maximum at 20 pulses and 20 mA. The intensity and area of the response was greater on the hand than on the foot. 3. Approximating the response area as a circle, the maximal perfusion increase in the hand extended 9 +/‐ 3 mm (mean +/‐ S.D.) outside the perimeter of the stimulating electrode. When stimulating within skin which had been subjected to surface anaesthesia, no response occurred, but when stimulating at the border of surface‐anaesthetized skin, the perfusion increase extended 2 +/‐ 1 mm (mean +/‐ S.D.) into anaesthetized skin. 4. The results show that the perfusion increase must have been due in part to impulse conduction to, and release of transmitters from, axon endings terminating in skin outside the contact area of the probe. It is concluded that the area of perfusion increase corresponds to the size of the receptive fields of afferent polymodal C fibres.

A Physical Action Potential Generator : Design, Implementation and Evaluation

The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxons action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1–40 in incremental steps of 1) and the node drive potential (0–2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxons programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems.

Guidelines for visualization of cutaneous blood flow by laser Doppler perfusion imaging

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.

The effect of cystic cavities on deep brain stimulation in the basal ganglia: a simulation-based study

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.

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.

Patient-Specific Model-Based Investigation of Speech Intelligibility and Movement during Deep Brain Stimulation

Background/Aims: Deep brain stimulation (DBS) is widely used to treat motor symptoms in patients with advanced Parkinson’s disease. The aim of this study was to investigate the anatomical aspects of the electric field in relation to effects on speech and movement during DBS in the subthalamic nucleus. Methods: Patient-specific finite element models of DBS were developed for simulation of the electric field in 10 patients. In each patient, speech intelligibility and movement were assessed during 2 electrical settings, i.e. 4 V (high) and 2 V (low). The electric field was simulated for each electrical setting. Results: Movement was improved in all patients for both high and low electrical settings. In general, high-amplitude stimulation was more consistent in improving the motor scores than low-amplitude stimulation. In 6 cases, speech intelligibility was impaired during high-amplitude electrical settings. Stimulation of part of the fasciculus cerebellothalamicus from electrodes positioned medial and/or posterior to the center of the subthalamic nucleus was recognized as a possible cause of the stimulation-induced dysarthria. Conclusion: Special attention to stimulation-induced speech impairments should be taken in cases when active electrodes are positioned medial and/or posterior to the center of the subthalamic nucleus.

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 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.

Optical Touch Pointer for Fluorescence Guided Glioblastoma Resection Using 5-Aminolevulinic Acid

Total tumor resection in patients with glioblastoma multiforme (GBM) is difficult to achieve due to the tumors infiltrative way of growing and morphological similarity to the surrounding functioning brain tissue. The diagnosis is usually subjectively performed using a surgical microscope. The objective of this study was to develop and evaluate a hand‐held optical touch pointer using a fluorescence spectroscopy system to quantitatively distinguish healthy from malignant brain tissue intraoperatively.

Method for patient-specific finite element modeling and simulation of deep brain stimulation

Deep brain stimulation (DBS) is an established treatment for Parkinson’s 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.