Background: Laser Doppler flowmetry (LDF) can be used to measure cerebral microcirculation in relation to stereotactic deep brain stimulation (DBS) implantations. Objective: To investigate the microcirculation and total light intensity (TLI) corresponding to tissue grayness in DBS target regions with high-resolution LDF recordings, and to define a resolution which enables detection of small vessels. Methods: Stereotactic LDF measurements were made prior to DBS implantation with 0.5-mm steps in the vicinity to 4 deep brain targets (STN, GPi, Vim, Zi) along 20 trajectories. The Mann-Whitney U test was used to compare the microcirculation and TLI between targets, and the measurement resolution (0.5 vs. 1 mm). The numbers of high blood flow spots along the trajectories were calculated. Results: There was a significant difference (p < 0.05) in microcirculation between the targets. High blood flow spots were present at 15 out of 510 positions, 7 along Vim and GPi trajectories, respectively. There was no statistical difference between resolutions even though both local blood flow and TLI peaks could appear at 0.5-mm steps. Conclusions: LDF can be used for online tracking of critical regions presenting blood flow and TLI peaks, possibly relating to vessel structures and thin laminas along stereotactic trajectories.

The aim of this study was to adapt and evaluate laser Doppler perfusion monitoring (LDPM) together with custom designed brain probes and software for continuous recording of cerebral microcirculation in patients undergoing neurosurgery. The LDPM system was used to record perfusion and backscattered light (TLI). These parameters were displayed together with the extracted heart rate (HR), pulsatility index (PI) and signal trends from adjustable time intervals. Technical evaluation was done on skin during thermal provocation. Clinical measurements were performed on ten patients undergoing brain tumour surgery. Data from 76 tissue sites were captured with a length varying between 10 s to 15 min. Statistical comparisons were done using Mann-Whitney tests. Grey and tumour tissue could be separated from white matter using the TLI-signal (p < 0.05). The perfusion was significantly higher in grey and tumour tissue compared to white matter (p < 0.005). LDPM was successfully used as an intraoperative tool for monitoring local blood flow and additional parameters linked to cerebral microcirculation (perfusion, TLI, heart rate and PI) during tumour resection. The systems stability opens up for studies in the postoperative care of patients with e.g. traumatic brain injury or subarachnoid haemorrhage.

Diffuse reflectance spectroscopy (DRS) can be used to estimate oxygen saturation (SO₂) of hemoglobin and blood fraction (f_B) in brain tissue. The aim of the study was to investigate the SO₂ and f_B in different positions along deep brain stimulation (DBS) trajectories and in specific target regions using DRS and a novel algorithm. DRS measurements were done at 166 well-defined anatomical positions in relation to stereotactic DBS-implantation along 20 trajectories toward 4 DBS targets (STN, Vim, GPi and Zi). The measurements were dived into groups (gray, white and light gray matter) related to anatomical position, and DBS targets, before comparison and statistical analysis. The median SO₂ in gray, white and light gray matter were 52%, 24% and 20%, respectively. Median f_B in gray matter (3.9%) was different from values in white (1.0%, p < 0.05) and light gray (0.9%, p < 0.001) matter. No significant difference in median SO₂ and f_B was found between DBS target regions. The novel algorithm allows for quick and reliable estimation of SO₂ and f_B in human brain tissue.

Continuous measurement of local brain oxygen saturation (SO ) can be used to monitor the status of brain trauma patients in the neurocritical care unit. Currently, micro-oxygen-electrodes are considered as the "gold standard" in measuring cerebral oxygen pressure (pO ), which is closely related to SO through the oxygen dissociation curve (ODC) of hemoglobin, but with the drawback of slow in response time. The present study suggests estimation of SO in brain tissue using diffuse reflectance spectroscopy (DRS) for finding an analytical relation between measured spectra and the SO for different blood concentrations. The P diffusion approximation is used to generate a set of spectra simulating brain tissue for various levels of blood concentrations in order to estimate SO . The algorithm is evaluated on optical phantoms mimicking white brain matter (blood volume of 0.5-2%) where pO and temperature is controlled and on clinical data collected during brain surgery. The suggested method is capable of estimating the blood fraction and oxygen saturation changes from the spectroscopic signal and the hemoglobin absorption profile.

Continuous optical monitoring of local cerebral microcirculation could benefit neurointensive care patients treated for subarachnoid hemorrhage (SAH). The aim of the study was to evaluate laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) for long-term monitoring of brain microcirculation and oxygen saturation (SO2) in the neurointensive care unit (NICU). A fiber optic probe was designed for intraparenchymal use and connected to LDF and DRS for assessment of the local blood flow (perfusion and tissue reflectance (TLI)) and SO2 in the brain. The optically monitored parameters were compared with conventional NICU monitors and Xe-CT. The LDF signals were low with median and 25 to 75% interquartiles of perfusion = 70 (59 to 83) a.u. and TLI = 2.0 (1.0 to 2.4) a.u. and showed correlation with the NICU monitors in terms of heart rate. Median and interquartiles of SO2 were 17.4 (15.7 to 19.8) %. The lack of correlation between local perfusion and cerebral perfusion pressure indicated intact cerebral autoregulation. The systems were capable of monitoring both local perfusion and SO2 with stable signals in the NICU over 4 days. Further clinical studies are required to evaluate the optical systems’ potential for assessing the onset of secondary brain injury.

A two-channel standard laser Doppler perfusion monitor has been adapted for intracerebral measurements. Software developed in Labview makes it possible to present the microvascular perfusion, total light intensity (TLI), heart rate and trend curves in real-time during surgery. A custom-made optical probe was designed in order to enable easy fixation during brain surgery. The constructed brain probe was evaluated and compared to a standard probe. Both probes presented similar feasibility when used for the skin recordings. In addition, evaluation was done in one patient in relation to tumor resection. Stable perfusion and TLI signals were immediately recorded when the probe was positioned in cerebral tissue. Movement artifacts were clearly seen when the probe was moved to a new site. Recordings in cortex and tumor border showed higher perfusion and lower TLI compared to measurements in subcortical white matter. The calculated heart rate estimate agreed well with the noted value from the electrocardiographic patient monitoring system.

The cerebral microcirculation consists of a complex network of small blood vessels that support nerve cells with oxygen and nutrition. The blood flow and oxygen delivery in the microcirculatory blood vessels are regulated through mechanisms which may be influenced or impaired by disease or brain damage resulting from conditions such as brain tumors, traumatic brain injury or subarachnoid hemorrhage (SAH). Monitoring of parameters relating to the microvascular circulation is therefore needed in the clinical setting. Optical techniques such as diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) are capable of estimating the oxygen saturation (SO2) and tracking the microvascular blood flow (perfusion) using a fiber optic probe. This thesis presents the work carried out to adapt DRS and LDF for monitoring cerebral microcirculation in the human brain.A method for real-time estimation of SO2 in brain tissue was developed based on the P3 approximation of diffuse light transport and quadratic polynomial fit to the measured DRS signal. A custom-made fiberoptic probe was constructed for measurements during tumor surgery and in neurointensive care. Software modules with specific user interface for LDF and DRS were programmed to process, record and present parameters such as perfusion, total backscattered light, heart rate, pulsatility index, blood fraction and SO2 from acquired signals.The systems were evaluated on skin, and experimentally by using optical phantoms with properties mimicking brain tissue. The oxygen pressure (pO2) in the phantoms was regulated to track spectroscopic changes coupled with the level of SO2. Clinical evaluation was performed during intraoperative measurements during tumor surgery (n = 10) and stereotactic deep brain stimulation implantations (n = 20). The LDF and DRS systems were also successfully assessed in the neurointensive care unit for a patient treated for SAH. The cerebral autoregulation was studied by relating the parameters from the optical systems to signals from the standard monitoring equipment in neurointensive care.In summary, the presented work takes DRS and LDF one step further toward clinical use for optical monitoring of cerebral microcirculation. SammanfattningHjärnans mikrocirkulation består av ett komplext nätverk av små blodkärl som försörjer nervceller med syre och näring. Blodflödet och syretransporten i mikrocirkulationen regleras via olika mekanismer som kan påverkas eller försämras vid sjukdom eller hjärnskada som till exempel vid hjärntumörer, traumatisk hjärnskada eller subaraknoidalblödning (SAH). Diffus reflektansspektroskopi (DRS) och laserdopplerteknik (LDF) kan användas för att uppskatta syremättnaden (SO2) och övervaka det mikrocirkulatoriska blodflödet, också kallat perfusion, med hjälp av en fiberoptisk prob. Den här avhandlingen beskriver arbetet med att anpassa DRS och LDF för att övervaka den cerebrala mikrocirkulationen.En metod för realtidsuppskattning av SO2 i hjärnvävnad utvecklades baserat på P3 approximationen av diffus...