Latest publications from Biomedical Instrumentation

Electro-oculography signals are corneo-retinal potentials that carry informationpertaining to eye movements. This information can be used to estimate drowsinesslevel of the subject which could provide interesting insights into research of acci-dent prevention. Of all features present, blink duration has been proved to be aneffective measure of drowsiness. The aim of this thesis work is to build a portablesystem to acquire and analyze electro-oculographic (EOG) signals in real-time.The system contains two sub-systems; a hardware sub-system that consists of thefilters, amplifiers, data acquisition card and isolation and the software sub-systemthat contains the program to acquire and analyze the signal and present the resultsto the observer. The filters were designed starting with simulation, implementa-tion on the prototype board, culminating in the design of a printed circuit board(PCB) and packaging. The complete software was written in PythonTMusing sev-eral relevant libraries for data processing. A text-based user interface was createdto enable easy user interaction. The results are graphically displayed in real-time.

Ex-situ tests were done with two volunteers while in-situ test was done onone subject. The data from the in-situ tests showed "good signal quality" in a"noisy" environment concurring with the design specifications. To motivate theimportance of calibration, two calibration paradigms were used during ex-situtests, where one paradigm records only normal blinks while the other records longblinks and the results showed differences in detection and error rates. The obser-vations made from performance tests at various levels gave "satisfactory results"and proved the usefulness of the system for experimental purposes in-situ.

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.

OBJECTIVES:

We have developed a method using transthoracic echocardiography in establishing optimal visualization of the aortic root, to reduce the amount of contrast medium used in each patient.

BACKGROUND:

During transcatheter aortic valve implantation, it is necessary to obtain an optimal fluoroscopic projection for deployment of the valve showing the aortic ostium with the three cusps aligned in the beam direction. This may require repeat aortic root angiograms at this stage of the procedure with a high amount of contrast medium with a risk of detrimental influence on renal function.

METHODS:

We studied the conventional way and an echo guided way to optimize visualisation of the aortic root. Echocardiography was used initially allowing easier alignment of the image intensifier with the transducer's direction.

RESULTS:

Contrast volumes, radiation/fluoroscopy exposure times, and postoperative creatinine levels were significantly less in patients having the echo-guided orientation of the optimal fluoroscopic angles compared with patients treated with the conventional approach.

CONCLUSION:

We present a user-friendly echo-guided method to facilitate fluoroscopy adjustment during transcatheter aortic valve implantation. In our series, the amounts of contrast medium and radiation have been significantly reduced, with a concomitant reduction in detrimental effects on renal function in the early postoperative phase.

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.

Deep brain stimulation (DBS) is an effective surgical treatment for neurological diseases such as essential tremor, Parkinsonʹs disease (PD) and dystonia. DBS has so far been used in more than 70 000 patients with movement disorders, and is currently in trial for intractable Gilles de la Tourette’s syndrome, obsessive compulsive disorders, depression, and epilepsy. DBS electrodes are implanted with stereotactic neurosurgical techniques in the deep regions of the brain. Chronic electrical stimulation is delivered to the electrodes from battery-operated pulse generators that are implanted below the clavicle.

The clinical benefit of DBS is largely dependent on the spatial distribution of the electric field in relation to brain anatomy. To maximize therapeutic benefits while avoiding unwanted side-effects, knowledge of the distribution of the electric field in relation anatomy is essential. Due to difficulties in measuring electric fields in vivo, computerized analysis with finite element models have emerged as an alternative.

The aim of the thesis was to investigate technical and clinical aspects of DBS by means of finite element models, simulations, and visualizations of the electric field and tissue anatomy. More specifically the effects of dilated perivascular spaces filled with cerebrospinal fluid on the electrical field generated by DBS was evaluated. A method for patient-specific finite element modelling and simulation of DBS was developed and used to investigate the anatomical distribution of the electric field in relation to clinical effects and side effects. Patient-specific models were later used to investigate the electric field in relation to effects on speech and movement during DBS in patients with PD (n=10). Patient-specific models and simulations were also used to evaluate the influence of heterogeneous isotropic and heterogeneous anisotropic tissue on the electric field during DBS. In addition, methods were developed for visualization of atlas-based and patient-specific anatomy in 3D for interpretation of anatomy, visualization of neural activation with the activating function, and visualization of tissue micro structure. 3D visualization of anatomy was used to assess electrode contact locations in relation to stimulation-induced side-effects (n=331) during DBS for patients with essential tremor (n=28). The modelling, simulation, and visualization of DBS provided detailed information about the distribution of the electric field and its connection to clinical effects and side-effects of stimulation. In conclusion, the results of this thesis provided insights that may help to improve DBS as a treatment for movement disorders as well as for other neurological diseases in the future.

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.