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In the routine of stereotactic biopsy on suspected tumors located deep in the brain or patients with multiple lesions, tissue samples are harvested to determine the type of malignancy. Biopsies are taken from pre-calculated positions based on the preoperative radiologic images susceptible to brain shift. In such cases the biopsy procedure may need to be repeated leading to a longer operation time. To provide guidance for targeting diagnostic tumor tissue and to avoid vessel rupture on the insertion path of the tumor, an application specific fiber optic probe was developed. The setup incorporated spectroscopy for 5-aminolevulinic acid induced protopophyrin IX (PpIX) fluorescence in the tumor and laser Doppler for measuring microvascular blood flow which recorded backscattered light (TLI) at 780 nm and blood perfusion. The recorded signals were compared to the histopathologic diagnosis of the tissue samples (n=16) and to the preoperative radiologic images. All together 146 fluorescence and 276 laser Doppler signals were recorded along 5 trajectories in 4 patients. On all occasions strong PpIX fluorescence peaks were visible during real-time guidance. Comparing the gliotic tumor marginal zone with the tumor, the PpIX (51 vs. 528 a.u., [0-1790], p 0.05) and blood perfusion (8.3 vs. 17 a.u., [0-254], p > 0.05) were not significantly different. In conclusion, the optical guidance probe made real-time tumor detection and vessel tracking possible during the stereotactic biopsy procedures. Moreover, the fluorescence and blood perfusion in the tumor could be studied at controlled positions in the brain and the tumor.

Image processing algorithms in pathology commonly include automated decision points such as classifications. While this enables efficient automation, there is also a risk that errors are induced. A different paradigm is to use image processing for enhancements without introducing explicit classifications. Such enhancements can help pathologists to increase efficiency without sacrificing accuracy. In our work, this paradigm has been applied to Ki-67 hot spot detection. Ki-67 scoring is a routine analysis to quantify the proliferation rate of tumor cells. Cell counting in the hot spot, the region of highest concentration of positive tumor cells, is a method increasingly used in clinical routine. An obstacle for this method is that while hot spot selection is a task suitable for low magnification, high magnification is needed to discern positive nuclei, thus the pathologist must perform many zooming operations. We propose to address this issue by an image processing method that increases the visibility of the positive nuclei at low magnification levels. This tool displays the modified version at low magnification, while gradually blending into the original image at high magnification. The tool was evaluated in a feasibility study with four pathologists targeting routine clinical use. In a task to compare hot spot concentrations, the average accuracy was 75±4.1% using the tool and 69±4.6% without it (n=4). Feedback on the system, gathered from an observer study, indicate that the pathologists found the tool useful and fitting in their existing diagnostic process. The pathologists judged the tool to be feasible for implementation in clinical routine.

The principles of cancer treatment has for years been radical resection of the primary tumor. In the oncologic surgeries where the affected cancer site is close to the lymphatic system, it is as important to detect the draining lymph nodes for metastasis (lymph node mapping). As a replacement for conventional radioactive labeling, indocyanine green (ICG) has shown successful results in lymph node mapping; however, most of the ICG fluorescence detection techniques developed are based on camera imaging. In this work, fluorescence spectroscopy using a fiber-optical probe was evaluated on a tissue-like ICG phantom with ICG concentrations of 6-64 μM and on breast tissue from five patients. Fiber-optical based spectroscopy was able to detect ICG fluorescence at low intensities; therefore, it is expected to increase the detection threshold of the conventional imaging systems when used intraoperatively. The probe allows spectral characterization of the fluorescence and navigation in the tissue as opposed to camera imaging which is limited to the view on the surface of the tissue

Fluorescence guidance in brain tumor resection is performed intra-operatively where bleeding is included. When using fiber-optical probes, the transmission of light to and from the tissue is totall ...

Radiofrequency (RF) lesioning in the human brain is a commonsurgical therapy for relieving severe pain as well as formovement disorders such as Parkinsonia. During the procedure a smallelectrode is ...

The microvascular perfusion can be measured using laser Doppler blood flowmetry (LDF), a technique sensitive to the concentration of moving blood cells and their velocity. However, movements of the tissue itself can cause artifacts in the perfusion readings. In a clinical situation, these movement induced artifacts may arise from patient movements or from movements of internal organs e.g. the intestines or the beating heart. Therefore, we have studied how a well-controlled tissue movement affects the LDF signals during different flow conditions and for different surface structures. Tissue perfusion was recorded non-touch in one point using a laser Doppler perfusion imager. During the measurements the object was placed on a shaker that generated the movement (both horizontal and vertical). Measurements were carried out both on DELRIN (polyacetal plastic) and the fingertip, for a wide range of velocities (0-3 cm/s). The influence of the microvascular perfusion was evaluated by occluding the brachial artery as well as blood emptying the finger and by using a flow model. The LDF signals were correlated to the movement. In vivo measurements showed that velocities above 0.8 cm/s gave a significant contribution to the perfusion signal. Corresponding velocities for the DELRIN piece were higher (1.4 - 2.6 cm/s), and dependent on the surface structures and reflecting properties. By reducing the amount of specular reflection the movement influence was substantially lowered.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Laser Doppler perfusion imaging (LDPI) has successfully been used to map the myocardial perfusion on patients undergoing coronary bypass surgery on the arrested heart. The need for intra-operative evaluation of graft function is obvious in routine surgery but even more imperative when adapting new surgical techniques where the procedure is performed on the beating heart. When using LDPI on the beating heart, artifacts originating from the movement of the heart are superimposed on the Doppler signal. We have investigated a method to reduce these artifacts by controlling the sampling sequence with ECG-triggering. The method has been assessed in an animal model on the beating calf heart. After sternotomy, an area covering 1 cm2 was imaged at the anterior wall of the left ventricle. In this area, six perfusion images were captured each of them recorded at fixed, but different time intervals in the cardiac cycle. In addition continuous measurements at one spot was done during 1 - 2 minutes. The signal recorded during pumping action was high compared to measurements performed in the same muscle area during infusion of blood with a syringe pump. Repeated measurements captured at a fixed delay time from the R-peak in the same areas at the same heart frequency showed reproducibility. ECG-triggering of the laser Doppler signal is the first step in our attempts to adapt LDPI to enabling assessment of myocardial perfusion on the beating heart. Further technical achievements and in-vivo investigations are, however, needed and will be performed by our research team in future studies.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Laser Doppler perfusion imaging has been used to assess the myocardium perfusion on the arrested heart during bypass surgery. Twenty-two patients undergoing coronary artery bypass grafting, including usage of the left internal thoracic artery, were included in the study. The anticipated perfusion increase following declamping of the internal thoracic artery was investigated by mapping areas at the size of 10 cm X 11 cm, (n equals 11) and 7 cm X 5 cm (n equals 11). The larger images allowed quantification of blood flow in different regions of the myocardium. The size of the affected area was 32.2 +/- 12.9 cm2 with a total increase of 3.17 +/- 0.75 a.u. (range 0 - 10 a.u.). Corresponding values for areas surrounding the vessels and areas defined as the larger vessels in the myocardium were 29.0 +/- 10.9 cm2 (2.85 +/- 0.57 a.u.) and 3.5 +/- 2.8 cm2 (6.78 +/- 0.18 a.u.). All subjects but two showed a substantial blood flow increase (> 2 a.u.) after release of the clamp. Six subjects had a total increase of at least 4 a.u. Correlation analysis between areas including various number of sites showed an r equals 0.91 (p < 0,0001) or better. In conclusion, laser Doppler perfusion imaging can easily be used intraoperatively in conjunction with bypass surgery. It enables immediate assessment of both the increase and spatial distribution of myocardial perfusion following declamping of an arterial graft.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Laser Doppler Perfusion Imaging (LDPI) is a method for visualization of tissue blood perfusion. A low power laser beam is used to step-wise scan a tissue area of interest and a perfusion estimate b ...

By the introduction of the laser Doppler perfusion imager (LDPI) the microvascular blood flow in a tissue area can be mapped by sequentially moving a laser beam over the tissue. The measurement is performed without touching the tissue and the captured perfusion values in the peripheral circulation are presented as a color-coded image. In the ordinary LDPI-set-up, 64 X 64 measurement sites cover an area in the range of about 10 - 150 cm2 depending on system settings. With a high resolution modification, recordings can be done on tissue areas as small as 1 cm2. This high resolution option has been assessed in animal models for the mapping of small vessels. To be able to record not only spatial but also temporal perfusion components of tissue blood flow, different local area scans (LAS) have been developed. These include single point recording as well as integration of either 2 X 2, 3 X 3, or 4 X 4 measurement sites. The laser beam is repeatedly moved in a quadratic pattern over the small tissue area of interest and the output value constitutes the average perfusion of all captured values within the actual region. For the evaluation, recordings were performed on healthy volunteers before and after application of a vasodilatating cream on the dorsal side of the hand.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Laser Doppler perfusion monitoring is a method of assessing tissue perfusion based on measurements performed using Doppler broadening of monochromatic light scattered in moving blood cells. Ever since laser Doppler perfusion monitors became available about 15 years ago they have been used in numerous applications in both clinical and laboratory settings. The high spatial resolution has in practice manifested itself as one of the main limitations of the method. The reason for this is the difficulty in attaining reproducible values at successive measurement sites because most skin tissue possesses a substantial variation in blood flow even at adjacent measurement sites. In order to overcome this difficulty the laser Doppler perfusion imager was developed. In this camera-like device, the laser beam successively scans the tissue and the Doppler components of the backscattered light are detected by a remote photodiode. After a scanning procedure is complete, a color-coded perfusion map showing the spatial variation of skin blood flow is displayed on a monitor. The operating principle and early applications of this emerging technology are addressed in further detail.

A laser Doppler perfusion imager has been developed that makes possible mapping of tissue blood flow over surfaces with extensions up to about 12 cm X 12 cm. The He-Ne laser beam scans the tissue under study throughout 4096 measurement sites. A fraction of the backscattered and Doppler broadened light is detected by a photo diode positioned about 20 cm above the tissue surface. After processing, a signal that scales linearly with perfusion is stored in a computer and a color coded image of the spatial tissue perfusion is shown on a monitor. A full format scan is completed in about 4.5 minutes. Algorithms for calculating perfusion profiles and averages as well as substraction of one image from another, form an integral part of the system data analysis software. The perfusion images can also be exported to other software packages for further processing and analysis.

Quasielastic scattering of coherent light in tissue can be utilized to probe the superficial blood flow of the skin and other organs. This fundamental principle has been employed in the construction of laser Doppler tissue perfusion monitors and imagers, intended for experimental and clinical investigations of tissue blood flow. In this paper, the theory of laser Doppler equipment is discussed. The measuring depth can be estimated by Monte Carlo simulation, while the dynamic light scattering (light scattering including Doppler effects) can be modeled by autocorrelation techniques. Based on these techniques estimators for tissue perfusion and tissue blood cell concentration are derived. The operating principle of the laser Doppler monitor is described in detail, with special reference to the design of probes. This monitor is useful for tracking temporal changes in tissue perfusion at a single point. The principle of a recently developed laser Doppler perfusion imager is reviewed. This imager is useful in mapping the spatial variations in tissue perfusion. Different ways of evaluating the performances of the monitor and imager in both mechanical flow simulators and in-vivo studies are discussed. Finally a brief overview is made of some fields of application in which the laser Doppler technique for measurement of tissue perfusion has been successfully used.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.