Deep brain stimulation in the ALIC-BNST region targeting the bed nucleus of stria terminalis in patients with obsessive-compulsive disorder: effects on cognition after 12 months.

PURPOSE: The aim of this study was to evaluate cognitive effects 12 months after Deep Brain Stimulation (DBS) of the Bed Nucleus of Stria Terminalis (BNST) in patients with refractory Obsessive-Compulsive Disorder (OCD). METHODS: Eight patients (5 female; mean ± SD age 36 ± 15) with OCD were included. A neuropsychological test battery covering verbal and spatial episodic memory, executive function, and attention was administered preoperatively and 12 months after surgery. Medical records were used as a source for descriptive data to probe for any changes not covered by standardized checklists and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the primary outcome measure. RESULTS: At 12 months, seven patients showed response to DBS: three were full responders (i.e., Y-BOCS ≥ 35% improvement), and four were partial responders (Y-BOCS 25-34% improvement). Relative to baseline, there was a slight decline on visuo-spatial learning (p = 0.027), and improved performance on the Color-Word Interference inhibition/switching subtest (p = 0.041), suggesting improvement in cognitive flexibility. CONCLUSIONS: DBS in the BNST for treatment refractory OCD generates very few adverse cognitive effects and improves cognitive flexibility after 12 months of stimulation. The improvement in Y-BOCS and the absence of major cognitive side effects support the BNST as a potential target for DBS in severe OCD.

Influence of optical aberrations on depth-specific spatial frequency domain techniques.

Significance: Spatial frequency domain imaging (SFDI) and spatial frequency domain spectroscopy (SFDS) are emerging tools to non-invasively assess tissues. However, the presence of aberrations can complicate processing and interpretation. Aim: This study develops a method to characterize optical aberrations when performing SFDI/S measurements. Additionally, we propose a post-processing method to compensate for these aberrations and recover arbitrary subsurface optical properties. Approach: Using a custom SFDS system, we extract absorption and scattering coefficients from a reference phantom at 0 to 15 mm distances from the ideal focus. In post-processing, we characterize aberrations in terms of errors in absorption and scattering relative to the expected in-focus values. We subsequently evaluate a compensation approach in multi-distance measurements of phantoms with different optical properties and in multi-layer phantom constructs to mimic subsurface targets. Results: Characterizing depth-specific aberrations revealed a strong power law such as wavelength dependence from ∼40 to ∼10 % error in both scattering and absorption. When applying the compensation method, scattering remained within 1.3% (root-mean-square) of the ideal values, independent of depth or top layer thickness, and absorption remained within 3.8%. Conclusions: We have developed a protocol that allows for instrument-specific characterization and compensation for the effects of defocus and chromatic aberrations on spatial frequency domain measurements.

A suggested climate service for cyanobacteria blooms in the Baltic Sea - Comparing three monitoring methods.

Dense blooms of filamentous cyanobacteria are recurrent phenomena in the Baltic Sea, with occasional negative effects on the surrounding ecosystem, as well as on tourism, human health, aquaculture, and fisheries. Establishing a climate service is therefore suggested; including multi-method observations of cyanobacteria biomass, biodiversity, and biogeography, in correspondence to biotic and abiotic factors. Three different approaches were compared for determination of spatial and temporal variability and trends of the blooms; 1) microscopy-based long-term data, 2) satellite remote sensing, and 3) phycocyanin fluorescence mounted on a merchant vessel. Firstly, microscopy-based data on cyanobacteria biomass from the period 2000-2020 showed that the toxin producing genus Nodularia and non-toxic Aphanizomenon both had summer means of 15 µg C L-1, while Dolichospermum was less dominant with a mean of 8 µg C L-1. Some years also the Kattegat was affected by cyanobacteria blooms, likely transported here by ocean currents. Secondly, the satellite remote sensing time series for the period 2002-2020 indicated that near surface blooms were most frequent in the Northern Baltic Proper and that near surface blooms have increased in the Bothnian Sea, starting later in the season than in the Baltic Proper. The largest extents (i.e., total area covered) were observed in 2005, 2008, and 2018. Thirdly, phycocyanin fluorescence from a flow through sensor mounted on a merchant vessel was used as a proxy for cyanobacteria biomass and correlated to cyanobacteria biomass estimated by microscopy. However, the satellite remote sensing data on surface accumulations showed little resemblance to the data on cyanobacteria biomass based on water sampling and microscopy, interpreted as an effect of methods. Sensors on satellites mainly detect surface accumulations of cyanobacteria while the microscopy data was based on samples 0-10 m, thereby comprising a larger community. Data from satellite remote sensing of cyanobacteria was correlated to the phycocyanin fluorescence indicating that similar bio-optical properties are observed. Finally, results from a downscaled ocean climate model (NEMONordic) were used to produce future scenarios for temperature and salinity, which directly affects cyanobacteria blooms in the Baltic Sea, supposedly by increasing in abundance and change in species composition. Short-term forecasts can be used together with observations for early warning of cyanobacteria blooms, and we suggest an internationally coordinated cyanobacteria observation and warning system for the Baltic Sea area.

DBSim and ELMA - Freeware for Simulations of Deep Brain Stimulation.

Finite Element Method (FEM) simulations of the electric field is a useful tool to estimate the activated tissue around Deep Brain Stimulation (DBS) electrodes. Based on our previous research, a two-part software package named DBSim and ELMA is presented. ELMA is used to classify brain tissue into grey matter, white matter, blood, and cerebrospinal fluid and assign electric conductivities accordingly. This data is then used in DBSim to generate patient-specific simulations of the electric field around currently implemented leads Medtronic 3387 and 3389, and Abbott 6180 and 6181. The software is available for free download at https://liu.se/en/article/ne-downloads Clinical Relevance- This is a tool meant for research and educational purposes for e.g. studies on optimal target areas for DBS.

Probabilistic maps for deep brain stimulation - Impact of methodological differences.

BACKGROUND: Group analysis of patients with deep brain stimulation (DBS) has the potential to help understand and optimize the treatment of patients with movement disorders. Probabilistic stimulation maps (PSM) are commonly used to analyze the correlation between tissue stimulation and symptomatic effect but are applied with different methodological variations. OBJECTIVE: To compute a group-specific MRI template and PSMs for investigating the impact of PSM model parameters. METHODS: Improvement and occurrence of dizziness in 68 essential tremor patients implanted in caudal zona incerta were analyzed. The input data includes the best parameters for each electrode contact (screening), and the clinically used settings. Patient-specific electric field simulations (n = 488) were computed for all DBS settings. The electric fields were transformed to a group-specific MRI template for analysis and visualization. The different comparisons were based on PSMs representing occurrence (N-map), mean improvement (M-map), weighted mean improvement (wM-map), and voxel-wise t-statistics (p-map). These maps were used to investigate the impact from input data (clinical/screening settings), clustering methods, sampling resolution, and weighting function. RESULTS: Screening or clinical settings showed the largest impacts on the PSMs. The average differences of wM-maps were 12.4 and 18.2% points for the left and right sides respectively. Extracting clusters based on wM-map or p-map showed notable variation in volumes, while positioning was similar. The impact on the PSMs was small from weighting functions, except for a clear shift in the positioning of the wM-map clusters. CONCLUSION: The distribution of the input data and the clustering method are most important to consider when creating PSMs for studying the relationship between anatomy and DBS outcome.

Effect of the ABCA1 agonist CS-6253 on amyloid-ß and lipoprotein metabolism in cynomolgus monkeys.

BACKGROUND: Inducing brain ATP-binding cassette 1 (ABCA1) activity in Alzheimer's disease (AD) mouse models is associated with improvement in AD pathology. The purpose of this study was to investigate the effects of the ABCA1 agonist peptide CS-6253 on amyloid-ß peptides (Aß) and lipoproteins in plasma and cerebrospinal fluid (CSF) of cynomolgus monkeys, a species with amyloid and lipoprotein metabolism similar to humans. METHODS: CS-6253 peptide was injected intravenously into cynomolgus monkeys at various doses in three different studies. Plasma and CSF samples were collected at several time points before and after treatment. Levels of cholesterol, triglyceride (TG), lipoprotein particles, apolipoproteins, and Aß were measured using ELISA, ion-mobility analysis, and asymmetric-flow field-flow fractionation (AF4). The relationship between the change in levels of these biomarkers was analyzed using multiple linear regression models and linear mixed-effects models. RESULTS: Following CS-6253 intravenous injection, within minutes, small plasma high-density lipoprotein (HDL) particles were increased. In two independent experiments, plasma TG, apolipoprotein E (apoE), and Aß42/40 ratio were transiently increased following CS-6253 intravenous injection. This change was associated with a non-significant decrease in CSF Aß42. Both plasma total cholesterol and HDL-cholesterol levels were reduced following treatment. AF4 fractionation revealed that CS-6253 treatment displaced apoE from HDL to intermediate-density- and low density-lipoprotein (IDL/LDL)-sized particles in plasma. In contrast to plasma, CS-6253 had no effect on the assessed CSF apolipoproteins or lipids. CONCLUSIONS: Treatment with the ABCA1 agonist CS-6253 appears to favor Aß clearance from the brain.

Distribution of electric field in patients with obsessive compulsive disorder treated with deep brain stimulation of the bed nucleus of stria terminalis.

BACKGROUND: Deep brain stimulation (DBS) is being investigated as a treatment for therapy-refractory obsessive compulsive disorder (OCD). Many different brain targets are being trialled. Several of these targets such as the ventral striatum (including the nucleus accumbens (NAc)), the ventral capsule, the inferior thalamic peduncle, and the bed nucleus of stria terminalis (BNST)) belong to the same network, are anatomically very close to one another, or even overlap. Data is still missing on how various stimulation parameters in a given target will affect surrounding anatomical areas and impact the clinical outcome of DBS. METHODS: In a pilot study of eleven participants with DBS of the BNST, we investigate through patient-specific simulation of electric field, which anatomical areas are affected by the electric field, and if this can be related to the clinical results. Our study combined individual patient's stimulation parameters at 12- and 24-month follow-up with image data from the preoperative MRI and postoperative CT. These data were used to calculate the distribution of electric field and create individual anatomical models of the field of stimulation. RESULTS: The individual electric stimulation fields by stimulation in the BNST were similar at both the 12- and 24-month follow-up, involving mainly anterior limb of the internal capsule (ALIC), genu of the internal capsule (IC), BNST, fornix, anteromedial globus pallidus externa (GPe), and the anterior commissure. A statistical significant correlation (p < 0.05) between clinical effect measured by the Yale-Brown Obsessive Compulsive Scale and stimulation was found at the 12-month follow-up in the ventral ALIC and anteromedial GPe. CONCLUSIONS: Many of the targets under investigation for OCD are in anatomical proximity. As seen in our study, off-target effects are overlapping. Therefore, DBS in the region of ALIC, NAc, and BNST may perhaps be considered to be stimulation of the same target.

Estimation of electric field impact in deep brain stimulation from axon diameter distribution in the human brain.

Objective.Finite element method (FEM) simulations of the electric field magnitude (EF) are commonly used to estimate the affected tissue surrounding the active contact of deep brain stimulation (DBS) leads. Previous studies have found that DBS starts to noticeably activate axons at approximately 0.2 V mm-1, corresponding to activation of 3.4µm axons in simulations of individual axon triggering. Most axons in the brain are considerably smaller however, and the effect of the electric field is thus expected to be stronger with increasing EF as more and more axons become activated. The objective of this study is to estimate the fraction of activated axons as a function of electric field magnitude.Approach. The EF thresholds required for axon stimulation of myelinated axon diameters between 1 and 5µm were obtained from a combined cable and Hodgkin-Huxley model in a FEM-simulated electric field from a Medtronic 3389 lead. These thresholds were compared with the average axon diameter distribution from literature from several structures in the human brain to obtain an estimate of the fraction of axons activated at EF levels between 0.1 and 1.8 V mm-1.Main results. The effect of DBS is estimated to be 47·EF-8.8% starting at a threshold levelEFt0 = 0.19 V mm-1.Significance. The fraction of activated axons from DBS in a voxel is estimated to increase linearly with EF above the threshold level of 0.19 V mm-1. This means linear regression between EF above 0.19 V mm-1and clinical outcome is a suitable statistical method when doing improvement maps for DBS.

Comparison between patient-specific deep brain stimulation simulations and commercial system SureTune3.

Objective. Software to visualize estimated volume of tissue activated (VTA) in deep brain stimulation assuming a homogeneous tissue surrounding such as SureTune3 has recently become available for clinical use. The objective of this study is to compare SureTune3 with homogeneous and heterogeneous patient-specific finite element method (FEM) simulations of the VTA to elucidate how well they coincide in their estimates.Approach. FEM simulations of the VTA were performed in COMSOL Multiphysics and compared with VTA from SureTune3 with variation of voltage and current amplitude, pulse width, axon diameter, number of active contacts, and surrounding homogeneous grey or white matter. Patient-specific simulations with heterogeneous tissue were also performed.Main results. The VTAs corresponded well for voltage control in homogeneous tissue, though with the smallest VTAs being slightly larger in SureTune3 and the largest VTAs being slightly larger in the FEM simulations. In current control, FEM estimated larger VTAs in white matter and smaller VTAs in grey matter compared to SureTune3 as grey matter has higher electric conductivity than white matter and requires less voltage to reach the same current. The VTAs also corresponded well in the patient-specific cases except for one case with a cyst of highly conductive cerebrospinal fluid (CSF) near the active contacts.Significance. The VTA estimates without taking the surrounding tissue into account in SureTune3 are in good agreement with patient-specific FEM simulations when using voltage control in the absence of CSF-filled cyst. In current control or when CSF is present near the active contacts, the tissue characteristics are important for the VTA and needs consideration.Clinical. trial ethical approval: Local ethics committee at Linköping University (2012/434-31).

Postoperative Lead Movement after Deep Brain Stimulation Surgery and the Change of Stimulation Volume.

INTRODUCTION: Lead movement after deep brain stimulation may occur and influence the affected volume of stimulation. The aim of the study was to investigate differences in lead position between the day after surgery and approximately 1 month postoperatively and also simulate the electric field (EF) around the active contacts in order to investigate the impact of displacement on affected volume. METHODS: Twenty-three patients with movement disorders underwent deep brain stimulation surgery (37 leads). Computed tomography at the 2 time points were co-fused respectively with the stereotactic images in Surgiplan. The coordinates (x, y, and z) of the lead tips were compared between the 2 dates. Eleven of these patients were selected for the EF simulation in Comsol Multiphysics. Postoperative changes of EF spread in the tissue due to conductivity changes in perielectrode space and due to displacement were evaluated by calculating the coverage coefficient and the Sørensen-Dice coefficient. RESULTS: There was a significant displacement (mean ± SD) on the left lead: x (0.44 ± 0.72, p < 0.01), y (0.64 ± 0.54, p < 0.001), and z (0.62 ± 0.71, p < 0.001). On the right lead, corresponding values were: x (-0.11 ± 0.61, ns), y (0.71 ± 0.54, p < 0.001), and z (0.49 ± 0.81, p < 0.05). The anchoring technique was a statistically significant variable associated with displacement. No correlation was found between bilateral (n = 14) versus unilateral deep brain stimulation, gender (n = 17 male), age <60 years (n = 8), and calculated air volume. The simulated stimulation volume was reduced after 1 month because of the perielectrode space. When considering perielectrode space and displacement, the volumes calculated the day after surgery and approximately 1 month later were partly overlapped. CONCLUSION: The left lead tip displayed a tendency to move lateral, anterior, and inferior and the right a tendency to move anterior and inferior. The anchoring technique was associated to displacement. New brain territory was affected due to the displacement despite considering the reduced stimulated volume after 1 month. Postoperative changes in perielectrode space and small lead movements are reasons for delaying programming to 4 weeks following surgery.

A multipixel diffuse correlation spectroscopy system based on a single photon avalanche diode array.

The autocorrelation of laser speckles from coherent near infrared light is used for noninvasive estimates of relative changes in blood perfusion in techniques such as laser Doppler flowmetry (LDF) and diffuse correlation spectroscopy (DCS). In this study, a 2D array of single photon avalanche diodes (SPADs) was used to combine the strengths of multiple detectors in LDF with high light sensitivity in DCS. The system was tested on milk phantoms with varying detector fiber diameter (200 and 600 µm), source-detector fiber separation (4.6-10.2 mm), fiber-SPAD distance (2.5-36.5 mm), contiguous measurement time per repetition for the autocorrelation (1-33 ms) and temperature (15.6-46.7°C). An in vivo blood occlusion test was also performed. The multipixel approach improved signal-to-noise ratio (SNR) and, in our setup, the use of a multimode detector fiber was beneficial for SNR. In conclusion, the multipixel system works, but improvements and further studies regarding, for example, the data acquisition and optimal settings are still needed.

Non-invasive and quantitative in vivo monitoring of gold nanoparticle concentration and tissue hemodynamics by hybrid optical spectroscopies.

Owing to their unique combination of chemical and physical properties, inorganic nanoparticles show a great deal of potential as suitable agents for early diagnostics and less invasive therapies. Yet, their translation to the clinic has been hindered, in part, by the lack of non-invasive methods to quantify their concentration in vivo while also assessing their effect on the tissue physiology. In this work, we demonstrate that diffuse optical techniques, employing near-infrared light, have the potential to address this need in the case of gold nanoparticles which support localized surface plasmons. An orthoxenograft mouse model of clear cell renal cell carcinoma was non-invasively assessed by diffuse reflectance and correlation spectroscopies before and over several days following a single intravenous tail vein injection of polyethylene glycol-coated gold nanorods (AuNRs-PEG). Our platform enables to resolve the kinetics of the AuNR-PEG uptake by the tumor in quantitative agreement with ex vivo inductively coupled plasma mass spectroscopy. Furthermore, it allows for the simultaneous monitoring of local tissue hemodynamics, enabling us to conclude that AuNRs-PEG do not significantly alter the animal physiology. We note that the penetration depth of this current probe was a few millimeters but can readily be extended to centimeters, hence gaining clinical relevance. This study and the methodology presented here complement the nanomedicine toolbox by providing a flexible platform, extendable to other absorbing agents that can potentially be translated to human trials.

Patient-Specific Simulations of Deep Brain Stimulation Electric Field with Aid of In-house Software ELMA.

Deep brain stimulation (DBS) is an established technique for reduction of symptoms in movement disorders. Finite element method (FEM) simulations of the electric field magnitude (EF) are useful for estimating the affected tissue around the DBS lead and this can help optimize the therapy. This paper describes how patient-specific FEM models can be set up with the aid of the Matlab-based in-house software tool ELMA. Electrode placement is determined from two coordinates in postoperative medical imaging and electric conductivity is assigned from preoperative magnetic resonance imaging (MRI) and patient-specific DBS data. Simulations are performed using the equation for steady currents in Comsol Multiphysics (CM). The simulated EF is superimposed on the preoperative MRI for evaluation of affected structures. The method is demonstrated with patient-specific simulations in the zona incerta and a globus pallidus example containing cysts with higher conductive which causes considerable distortion of the EF. The improved software modules and precise lead positioning simplifies and reduces the time for DBS EF modelling and simulation.

Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems-A Simulation Study.

The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome.

Refining the Deep Brain Stimulation Target within the Limbic Globus Pallidus Internus for Tourette Syndrome.

BACKGROUND: Deep brain stimulation (DBS) in patients with severe, refractory Tourette syndrome (TS) has demonstrated promising but variable results thus far. The thalamus and anteromedial globus pallidus internus (amGPi) have been the most commonly stimulated sites within the cortico-striato thalamic circuit, but an optimal target is yet to be elucidated. OBJECTIVES: This study of 15 patients with long-term amGPi DBS for severe TS investigated whether a specific anatomical site within the amGPi correlated with optimal clinical outcome for the measures of tics, obsessive compulsive behaviour (OCB), and mood. METHODS: Validated clinical assessments were used to measure tics, OCB, quality of life, anxiety, and depression before DBS and at the latest follow-up (17-82 months). Electric field simulations were created for each patient using information on electrode location and individual stimulation parameters. A subsequent regression analysis correlated these patient-specific simulations to percentage changes in outcome measures in order to identify any significant voxels related to clinical improvement. RESULTS: A region within the ventral limbic GPi, specifically on the medial medullary lamina in the pallidum at the level of the AC-PC, was significantly associated with improved tics but not mood or OCB outcome. CONCLUSIONS: This study adds further support to the application of DBS in a tic-related network, though factors such as patient sample size and clinical heterogeneity remain as limitations and replication is required.

Pre-clinical longitudinal monitoring of hemodynamic response to anti-vascular chemotherapy by hybrid diffuse optics.

The longitudinal effect of an anti-vascular endothelial growth factor receptor 2 (VEGFR-2) antibody (DC 101) therapy on a xenografted renal cell carcinoma (RCC) mouse model was monitored using hybrid diffuse optics. Two groups of immunosuppressed male nude mice (seven treated, seven controls) were measured. Tumor microvascular blood flow, total hemoglobin concentration and blood oxygenation were investigated as potential biomarkers for the monitoring of the therapy effect twice a week and were related to the final treatment outcome. These hemodynamic biomarkers have shown a clear differentiation between two groups by day four. Moreover, we have observed that pre-treatment values and early changes in hemodynamics are highly correlated with the therapeutic outcome demonstrating the potential of diffuse optics to predict the therapy response at an early time point.

A method for monitoring of oxygen saturation changes in brain tissue using diffuse reflectance spectroscopy.

Continuous measurement of local brain oxygen saturation (SO2 ) 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 (pO2 ), which is closely related to SO2 through the oxygen dissociation curve (ODC) of hemoglobin, but with the drawback of slow in response time. The present study suggests estimation of SO2 in brain tissue using diffuse reflectance spectroscopy (DRS) for finding an analytical relation between measured spectra and the SO2 for different blood concentrations. The P3 diffusion approximation is used to generate a set of spectra simulating brain tissue for various levels of blood concentrations in order to estimate SO2 . The algorithm is evaluated on optical phantoms mimicking white brain matter (blood volume of 0.5-2%) where pO2 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.

Scanning, non-contact, hybrid broadband diffuse optical spectroscopy and diffuse correlation spectroscopy system.

A scanning system for small animal imaging using non-contact, hybrid broadband diffuse optical spectroscopy (ncDOS) and diffuse correlation spectroscopy (ncDCS) is presented. The ncDOS uses a two-dimensional spectrophotometer retrieving broadband (610-900 nm) spectral information from up to fifty-seven source-detector distances between 2 and 5 mm. The ncDCS data is simultaneously acquired from four source-detector pairs. The sample is scanned in two dimensions while tracking variations in height. The system has been validated with liquid phantoms, demonstrated in vivo on a human fingertip during an arm cuff occlusion and on a group of mice with xenoimplanted renal cell carcinoma.

Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies.

The in vivo optical and hemodynamic properties of the healthy (n = 22) and pathological (n = 2) human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS) and diffuse correlation spectroscopy (DCS) system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (µa, µs') at three wavelengths (690, 785 and 830 nm) to derive total hemoglobin concentration (THC) and oxygen saturation (StO2). DCS measured the microvascular blood flow index (BFI). Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 µM to 144.8 µM, showing a 25-44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s) compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s), while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%), yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 µM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening.

Non-contact scanning diffuse correlation tomography system for three-dimensional blood flow imaging in a murine bone graft model.

A non-contact galvanometer-based optical scanning system for diffuse correlation tomography was developed for monitoring bone graft healing in a murine femur model. A linear image reconstruction algorithm for diffuse correlation tomography was tested using finite-element method based simulated data and experimental data from a femur or a tube suspended in a homogeneous liquid phantom. Finally, the non-contact system was utilized to monitor in vivo blood flow changes prior to and one week after bone graft transplantation within murine femurs. Localized blood flow changes were observed in three mice, demonstrating a potential for quantification of longitudinal blood flow associated with bone graft healing.